art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 63 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 64 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 65 correlation relationship of immune-metabolic parameters in arterial hypertension navruzova shakar istamovna – head of the pediatrics department of bukhara state medical institute, shadmanova nargis kurbanovna – scientific researcher at the pediatrics department of bukhara state medical institute, soliev alisher urakovich assistant of the internal medicine department of bukhara state medical institute abstract. the authors conducted a study on the study of immuno-metabolic parameters in the regulation of blood pressure and the assessment of their diagnostic significance for optimizing the methods of diagnosis and prevention of complications of arterial hypertension. a correlation analysis of the parameters of carbohydrate, lipid metabolism and the immune system, an assessment of the significance of each parameter in the regulation of blood pressure was carried out. it was found that an increase in the level of igg in the blood confirms the risk of developing atherosclerosis in hypertension of the 1st degree, and a decrease in the level of igg in the blood shows the development of secondary immunodeficiency. each result obtained determines the further tactics of management of patients with hypertension of the 1st degree. keywords: arterial hypertension, metabolic syndrome, immune system, carbohydrate metabolism. introduction arterial hypertension (ah) is the leading risk factor for premature death. according to who experts, hypertension is the cause of 54% of cardiovascular deaths. the incidence of hypertension as the most important indicator of the state of art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 66 public health is of an epidemiological nature. the prevalence of hypertension in the russian federation is 39.2 % among men, and 41.1% in women. while in the united states, depending on age and gender, if a person lives to 70 years, then 50% of all people are hypertensive [1]. in recent years, data have been accumulating indicating the role of the immune system in the regulation of blood pressure (bp) and cardiovascular risk associated with hypertension. the first line of defense of the immune system involves an innate reaction and occurs very quickly. the second line of defense, namely adaptive immunity, is characterized by a belated, but very purposeful reaction. from the point of view of the development of hypertension, the interaction between these two components of the immune system seems to be significant [2,3]. t-cell cytokines play a central role in the pathophysiology of cardiovascular diseases and hypertension and contribute to damage to end organs [4,5]. cytokines often have overlapping functions, which is a problem in studies targeting individual cytokines to assess their role in hypertension and tissue damage. all these circumstances are responsible for the variability in the improvement of hypertension due to the suppression of specific cytokines [6]. while proinflammatory cytokines such as il-2, il-17, ifn-γ and tnf-α have a detrimental effect in the pathogenesis of hypertension, the role of anti-inflammatory il-10 is protective. adaptive immune responses mediated by both t-cells and b-cells play a key role in the development of hypertension and mediating damage to target organs. correlations are probabilistic changes that can be studied only on representative samples by methods of mathematical statistics. correlations indicate that changes in one trait, as a rule, are accompanied by certain changes in another. the aim of the study is to study the correlation between the immune status and the parameters of carbohydrate metabolism to optimize the methods of diagnosing hypertension. materials and methods of research. the study included 64 patients with idegree hypertension aged from 30 to 70 years (average age 54.0±1.0), hospitalized in art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 67 the bukhara regional cardiology dispensary. ah was verified according to the requirements of the world health organization( who), classified according to the international classification of diseases (icd-10). the exclusion criteria from the study were grade 2 hypertension, isolated systolic arterial hypertension, myocardial infarction, type 1 diabetes mellitus, unstable angina, pheochromocytoma, atrial fibrillation, chronic heart failure, acute cerebral circulatory disorder, dyscirculatory encephalopathy, urolithiasis, cholelithiasis, bronchial asthma. at the same time, adhered to the acc/aha hypertension guidelines classification (2017). all patients underwent clinical and immunological, biochemical, laboratory, functional (doechocg, ecg) and anthropometric (measurement of weight and height) researches. results and their discussion. the connection of the complement system with the components of blood pressure is established. the complement components involved in the regulation of the inflammatory response, in particular c3, have a noticeable positive relationship with systolic blood pressure (systolic bp) -r=0.42 and diastolic blood pressure (diastolic bp)r=0,55. consequently, the established correlation noticeable positive relationships in the study confirm the participation of serum proteins in the regulation of blood bp. the study of carbohydrate metabolism in patients with hypertension showed a high positive relationship of blood glucose with insulin-r=0.68, with the homa-ir index (homeostasis model assessment insulin resistance) r=0.78, with c-peptide r=0.72, hba1c (glycated hemoglobin) r=0.68 and a noticeable positive relationship with lactate dehydrogenase (ldh) r=0.45. at the same time, insulin in the blood has a high positive relationship with the homa-ir r=0.98 and hba1c r=0.73 index, the relationship between insulin and c-peptide was average positive-r=0.57. the relationship between insulin and ldh was weakly positive-r=0.26, as well as between insulin and high-density lipoproteins (hdl)r=0.24.at the same time, insulin had a negative weak association with diastolic bp r= -0.28. the homa-ir index also has a high positive relationship with hba1c r=0.78 and an average art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 68 positive relationship with c-peptide r=0.63, and with ldh it has a noticeable positive relationship-r=0.35. the correlation relationship between the homa-ir index and hdl was weak and positive-r=0.24, while the relationship with ldl was negative and weak r= -0.23 (fig. 1). fig1. correlation dependence of indicators of carbohydrate metabolism in hypertension of the 1st degree c-peptide, in turn, has an average positive relationship with hba1c r=0.63, ldh r=0.43 and a weak positive relationship with hdl r=0.29. there is no relationship between the indicators of carbohydrate metabolism and the studied immunological parameters of blood (cic, c3, crp, il-2, tnf-a) in grade 1 hypertension. the established positive correlations of blood glucose with the studied indicators of carbohydrate metabolism in hypertension of the 1st degree allows predicting the development of prediabetes, or rather the formation of type 2 diabetes mellitus in hypertension. the obtained data dictate the need for preventive measures to prevent the formation of hypertension by regularly studying the indicators of carbohydrate metabolism in people starting from the age of 30. by studying the relationship between the parameters of the lipid spectrum, a high negative relationship between hdl and low-density lipoproteins (ldl)was 0,68 0,78 0,72 0,68 0,45 0,98 0,63 0,78 0,35 0,24 -0,23 0,57 0,63 0,43 0,29 0,73 0,24 -0,4 -0,2 0 0,2 0,4 0,6 0,8 1 1,2 glucose homa-ir c-peptide gli-hb ldh hdl diastolic bp art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 69 establishedr= -0.92 and between hdl and the atherogenicity index (ia) r=-0.83. at the same time, ia has a high positive association with ldl r=0.81. at the same time, a noticeable negative relationship was also established between hdl and il-2 (r=-0.46), between hdl and igg (r=-0.43). total cholesterol in grade 1 hypertension has an average positive relationship with il-2-r=0.49 (fig.2). fig. 2. correlation relationship between the parameters of the lipid spectrum and the immunological parameters of blood in hypertension of the 1st degree thus, the established relationships between the parameters of the lipid spectrum and cytokines serve as indicators of the prevention of atherosclerosis in patients with hypertension. at the same time, an increase in the level of hdl in the blood confirms a decrease in ia and, in order to avoid financial costs, it is possible to limit ourselves only to determining the level of hdl or ldl in the blood in patients with established risk factors for the formation of hypertension. it is necessary to indicate the fact that in the study of grade 1 hypertension, significant correlations were established between the indicators of lipid and carbohydrate metabolism and the studied indicators of immunity. thus, the study revealed a high positive relationship of ldl 0,2 0,27 -0,43 0,45 0,37 -0,16 0,19 0,27 -0,23 0,61 0,49 -0,46 0,38 0,35 0,1 0,21 -0,23 -0,2 -0,22 -0,6 -0,4 -0,2 0 0,2 0,4 0,6 0,8 igm igg cic il-2 tnfa art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 70 with ia r=0.81, an average positive relationship with il-2-r=0.38, with igg-r=0.45. at the same time, ldl has a negative weak relationship with tnf-α r=-0.23, and ia has a noticeable positive relationship with igg r=0.37. this leads to the conclusion that, taking into account the established relationships between the studied blood parameters, it is necessary to study the level of blood igg, which allows early diagnosis of both secondary immunodeficiency in hypertension and early diagnosis of atherosclerosis due to its established connection with ia r=0.37. this means that an increase in the level of igg in the blood confirms the risk of developing atherosclerosis in hypertension, and a decrease-the development of secondary immunodeficiency. each result obtained determines the further tactics of management of patients with hypertension of the 1st degree. therefore, everything established confirms the dependence of immunological parameters on the degree of hypertension and the severity of the metabolic syndrome (ms). by studying the relationship between the indicators of circulating immune complexes (cic) and complement c3 in the study in patients with grade 1 hypertension, a high positive relationship was established r=0.61. the obtained result allows predicting the cic level by the c3 complement level and vice versa and indicates the participation of the cic in the regulation of blood pressure components. this conclusion confirms the still established high positive associations of complement c3 with systolic bp and diastolic bp (fig. 3.). art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 71 fig. 3. correlation relationship of complement c3 with the components of blood pressure and bmi in 1st degree hypertension cytokines in hypertension showed an average positive relationship-r = 0.39 between il-2 and tnfa in the blood. therefore, the il-2 level can predict the process of cell apoptosis and the formation of coronary heart disease (chd) in patients with grade 1 hypertension. conclusion: the established correlations between carbohydrate, lipid and immunological parameters of blood allow predicting the development of coronary heart disease and other organ changes in patients with grade 1 hypertension and dictate the need to organize and conduct early preventive measures to prevent the development of complications of hypertension, starting from the age of 30. 0,42 0,55 0,28 0 0,1 0,2 0,3 0,4 0,5 0,6 systolic bp diastolic bp bmi art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140491 72 references 1. shamukhamedova n. sh .. arterial hypertension: long-term stress, pathogenesis and drug therapy / / colloquium-journal. 2019. №3-2 (27). url: https://cyberleninka.ru/article/n/arterialnaya-gipertenziya-dolgovremennyy-stresspatogenez-i-medikamentoznaya-terapiya. 2. drummond g. r., vinh a., guzik t. j., sobey k. g. immune mechanisms of hypertension. nat rev immunol. 2019. a modern review of the mechanisms of innate and adaptive immunity in hypertension. 3. norlander a. e., madhur m. s., harrison d. g. immunology of hypertension. j. exp. med. 2018;215(1):21-33. [pmcfree rticle] [pubmed] [google scholar]. 4. amador k. a., barrientos v., pena j. et al. spironolactone reduces organ damage caused by doca-salt by blocking the activation of t-helper cells 17 and suppressing the regulation of regulatory t-lymphocytes. // hypertension. 2014;63(4):797–803. [pubmed] [googlescholar]. 5. guzik t. j., skiba d. s., tuiz r. m., harrison d. g. the role of infiltrating immune cells in dysfunctional adipose tissue. cardiovasc res. 2017;113(9):1009-23. https://doi.org/10.1093/cvr/cvx108 6. rodriguez-iturbe b, pons h., johnson r. j. (2017) the role of the immune system in hypertension. physiol. rev 97: 1127-1164. volume-1 issue-1 art of medicine international medical scientific journal 1 art of medicine international medical scientific journal volume-1 issue-1 2 art of medicine international medical scientific journal volume 1, issue 1, may 2021 volume-1 issue-1 art of medicine international medical scientific journal 3 founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine international medical scientific journal chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen art of medicine international medical scientific journal volume-1 issue-1 4 content tursunova l. d., jabbarov o. o. application of sakabutril/valsartan in patients with chronic kidney disease with type 2 diabetes mellitus...............................5 l.s. khamraeva., d.u. narzullaeva features of calculating the optical power of an intraocular lens in children with congenital cataracts at the risk of developing pseudomyopic myopia.....................10 kasimova m. s., iminova m. m., ashurov o. m. ophthalmologic complications in the structure of the clinical features of novel coronavirus infection (covid-19)......................................................................................................14 fattayeva d.r., rizayev j.a., rakhimova d.a. improvement of methods for correction of clinical and immunological disorders in comorbid state of chronic gaymoritis after covid-19....................................................................17 polatova d.sh., abdukarimov kh.g., davletov r.r., savkin a.v., sultanov b.b features of immunobiological heterogeneity in patients with osteosarcoma.................................................................................25 art of medicine international medical scientific journal volume-1 issue-1 10 features of calculating the optical power of an intraocular lens in children with congenital cataracts at the risk of developing pseudomyopic myopia. l.s. khamraeva., d.u. narzullaeva tashkent pediatric medical institute of the ministry of health of the republic of uzbekistan, tashkent. abstract the article presents the results of the clinical efficacy of the calculation formula with the correction factor of the optical force of the intraocular lens in children with congenital cataracts at risk of development of pseudophakic myopia. personalized rm corrective coefficient in the formula for calculating the force of iol in children with risk of development of pseudophakic myopia makes it possible to achieve target refraction in 83.3% cases and reduce the development of reduce myopic refraction. keywords: congenital cataract, pseudophakic myopia, intraocular lens power calculation introduction. to date, congenital cataracts (cc) occupy a significant place in the structure of blindness and weakness and are one of the main causes of disabilities in vision from childhood [1-5]. the modern and optimal method of treating cc is its extraction with an implantation of an intraocular lens (iol). there are a large number of formulas for calculating the optical force of iol to adult patients. in pediatrics, the formulas srk ii, srk \ t, taking into account the sagittal size of the eyeball, refracting the power of the cornea and the individual constants of the selected model of iol are used. when calculating the optical force of implanable iol, children of the first year of life determine the magnitude of hypocorrection (from (+) 4.0 to (+14.0 d)) refraction, taking into account the refraction of the cornea, the difference in the original and predicted axial length (al) after the completion of the physiological growth of the eye [6-8]. however, it is not known which of the formulas used are more predictable when calculating the strength of the lens in children with the risk of the development of myopic refraction. one of the most complex and important points remains the calculation of target refraction with the continued growth of the eyes during the formation of a child's visual analyzer with the risk of myopia after iol implantation. purpose. evaluation of the clinical efficacy of the recommended calculation of the optical force of iol in children with congenital cataracts at risk of the development of pseudophakic myopia. material and methods. under our observation in the eye department of the clinic of the tashkent pediatric medical institute, there were 24 (43 eyes) of the child with cc. all patients underwent extracapsular cc extraction with implantation of soft iols at the age of 1 to 5 years. children were distributed to 2 groups. in i (basic), the group includes 11 (21 eyes), in ii (control) 13 (22 eyes) of patients. all children had a risk of developing pseudophakic myopia. the optical power of the iol in the control group was calculated according to the traditional srk ii formula with the age-related refractive hypocorrection [9], in the main and also according to the srk ii formula with the agerelated refraction, but with the rm correction factor recommended by us. the results of refractive indicators were studied in 3-12 months after surgery. volume-1 issue-1 art of medicine international medical scientific journal 11 results and discussion. the srk ii formula with an introduced correction factor has the form: p = [(a2.5 x l 0.9 x k) r] rm p optical power of iol (dptr) a constant determined by the manufacturer of iol l axial length (mm), is measured by each child individually k keratometry refractive power of the cornea (dptr), is measured by each child individually r is an indicator of age residual refraction (dptr) rm correction factor (dptr) is determined by the original own formula based on clinical studies. the correction factor (rm) was determined by formula 1. the formula of a certain correction factor: r m = al p x 0.82, where the al is an indicator of the average physiological growth of the al p of the child by the time the physiological growth of the eyeball (15 years) is preached on the basis of indicators of ultrasonic biometrics of healthy eyes in children under 15 m.d. agatova [10]. constant 0.82 (dptr / mm) -mixed as a result of our statistical analysis using linear approximation of experimental data the dynamics of refraction and the increase in the al of children with pseudophakic aged 1 to 5 years with abnormal refractogenesis, 3 years after extraction cc and iol implantation. the refractive force of iol varied in the i group from (+) 16.0 to (+) 21,5 dptr, in group ii from (+) 19.0 to (+) 24,0,2 dptr. the magnitude of the age hypocorrection was +3.0 +8.0 dptr. keratometric indicators were in the range from 39.94 to 45.75 dptr. the magnitude of the al of the eyeball from 18.5 to 24.25 mm. analysis of indicators of children's refraction, conducted 3 months after extraction cc with implantation iol made it possible to reveal the deviation from the planned target refraction in the main group of 9.6%, in the control in 41% cases. in the control group, myopia is registered with a light degree of 4.6% and emmetropy, disproportionate age (reinforcement of refractive) in 36.4% of cases, respectively (table 1). table 1 dynamics of children refraction (n the number of eyes) refraction groups emmetropia, disproportionate to age hypermetropia age-appropriate (target refraction) mild myopi total abs. (%) abs. (%) abs. (%) abs.. (%) basic (n= 21) 2 9,6 19 90,4 21 100 control (n= 22) 8 36,4 13 59 1 4,6 22 100 refractometry 12 months after ñc extraction with iol implantation revealed a deviation from the target refraction in the main group in 16.6%, in the control group-in 54.5% of cases. in the control group, mild myopia was registered in 13.6% and emmetropia, art of medicine international medical scientific journal volume-1 issue-1 12 disproportionate to age, in 40.9% of cases, respectively. target refraction was achieved in the main group in 83.3%, in the control group-in 45.4% of cases (table 2.). table 2 dynamics of children refraction (n the number of eyes) refraction groups emmetropia, disproportionate to age hypermetropia age-appropriate (target refraction) mild myopi total abs. (%) abs. (%) abs.. (%) abs.. (%) basic n=18 3 16,6 15 83,3 18 100 control n=22 9 40,9 10 45,4 3 13,6 22 100 in the patients of the main group, visual functions reached an average of 0.5±0.001, in the control group 0.2±0.001 (table 3). table 3. indicators of visual acuity before and after surgery in children (m±m). after the operation before the opera tion after 3 months через 1 год вasic group 0,03±0,00 1 (n=21) 0,27±0,0015 (n=21) 0,5±0,001 (n=18) student's t-test t=133,3(p≤0,05) t=226,27(p≤0,05) control group 0,03±0,00 1 (n=22) 0,15±0,002 (n=22) 0,2±0,001 (n=22) student's t-test t= 53.67(p≤0,05) t= 155,56(p≤0,05) nnumber of eyes conclusion. based on the results obtained, it can be concluded that the personalized correction factor rm in the formula for calculating the strength of iol in children at risk of developing pseudophakic myopia allows achieving the target refraction in 83.3% of cases (vs. 54.5% of cases in the control group) and reducing the development of strong refraction by 37.9%, as well as increasing visual acuity to 0.5±0.001 (vs. 0.2±0.001 in the control group). volume-1 issue-1 art of medicine international medical scientific journal 13 references 1.libman, e. s. condition and dynamics of disability due to violation of vision in russia / e. s. libman, e. v. kaleva // ix congress of ophthalmologists of russia: moscow, 2010. p. 73. 2.katarina, l. a., mikhailova l. a., state of children's ophthalmological service in the russian federation // russian pediatric ophthalmology. 2015. no 1. p. 5-10. 3.khamraeva l.s., narzullaeva d.u., katargin l.a., kruglov t.b. lndices of refraction in children with pseudophakia predisposed to abnormal refractive error changes after congenital cataract extraction. russian ophthalmological magazine. 2020; 13 (3): 51-55. 4.khamraeva l.s., narzullaeva d.u. about risk factors and forecast of the development of pseudophacisic myopia in children. herald of ophthalmology. 2020; (3): 93-99. (in russ.). https://doi.org/10.17116/oftalma202013603193 5.chandramouli s.g.,shilpa g.r., farhadul.a. pediatric intraocular lens power calculation. journal of ophthalmic science and research.2018;4:232-236 . 6.lambert s. r. / [et al.] comparison of contact lens and intraocular lens correction of monocular aphakia during infancy: a randomized clinical trial of hotv optotype acuity at age 4.5 years and clinical finding at age 5 years // jama ophthalmol. 2014. no 6. p. 676-682 . 7.ledoux d. m. [et al.] pediatric cataract extraction with intraocular lens implantation: visual acuity outcome when measured at age four years and older / // j. aapos. 2007. no 3. ð. 218224 . 8.katarina l.a. children's ophthalmology federal clinical recommendations. moscow. sentiss. 2016. 9.trivedi rh, wilson me, et al. selecting intraocular lens power in children. ophthalmic pearls pediatrics. 2006; 35-36 . 10. kruglova t.b., kononov l.b. features of the calculation of the optchsecine forces of the intraocular lenses implanted by the first year of life with congenital cataracts. herald of ophthalmology. 2013; (4): 66-69. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 58 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 59 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 60 periodontal state and optimization of prosthodontic dental care in hiv-infected patients anvar alimov center for the development of professional qualifications of medical workers, assistant at the department of dentistry sunatullo gaffarov center for the development of professional qualifications of medical workers, professor, head of the department of dentistry, pediatric dentistry and orthodontics alisher alimov center for the development of professional qualifications of medical workers, professor, head of the department of dentistry the republic of uzbekistan abstract due to the fact that the provision of dental care to hiv-infected patients should be carried out with minimal invasive interventions, due to the high risk of transmission of the pathogen during manipulations, it seems very relevant to consider the issues of providing prosthetic dental therapy using modern materials that do not provide irritating, toxic and allergic effects on the mucous membrane of the oral cavity, and also do not require additional preparation during the manufacture of prostheses, as well as overloading the abutment teeth. in this regard, based on the results of our research, preference was given to the manufacture of removable structures. to replace dentition defects, «ftorax» base plastic and «vertex thermo sens» thermoplastic base material were used. when choosing the design of dentures in hiv-infected patients, the endurance of the periodontal teeth to loads was taken into accounts, which were determined using gnatodynamometric studies. when carrying out complex therapy, coupled with dental orthopedic therapy, there was a significant clinical improvement accompanied by normalization of both the general condition of patients and positive shifts in the dynamics of periodontal endurance to pressure. keywords: hiv infection, periodontal condition, gnatodynamometry, orthopedic dental therapy. introduction. diseases of the oral cavity against the background of hiv infection have vivid manifestations, sometimes with an atypical nature of the course [2,3]. in patients with a reduced immune status, which include hiv-infected, there is a high probability of the simultaneous existence of several infections, including in the maxillofacial region, which significantly complicates the diagnosis of diseases. at the same time, periodontal diseases are one of the typical manifestations in patients infected with hiv, and one of the main reasons for premature tooth loss and destruction of the dentition [4]. dental therapy of oral diseases in hiv-infected patients is complicated by the state of progressive immunodeficiency caused by hiv carriage against the background of art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 61 pressure from concomitant infections, massive use of antibiotics and other chemotherapeutic agents and has its own characteristics. hiv-associated patients are prescribed large doses of drugs, increase the duration of their use, and carry out targeted prophylactic administration [6, 7]. the success of dental treatment and prevention of secondary adentia, which is a consequence of caries and periodontal diseases, by replacing dentition defects with removable and fixed structures of dentures, depends on the correct preparation of the orthopedic treatment plan, on the choice of an adequate design of dentures and materials, on their hygienic state [1] however, analysis of the literature shows that the issues of providing prosthetic dental care to people living with hiv continue to remain little or almost unexplored. meanwhile, scientific research in this area would make it possible to develop a tactic of approach to assessing the state of the oral cavity in hiv-infected patients and the peculiarities of the provision of dental, including orthopedic, care, starting with the solution of the issues of indications and contraindications to dental prosthetics, the timing of treatment, the choice methods, designs, materials for the manufacture of dentures, as well as the features of oral care, dentures and tissues of the prosthetic bed [5]. objective of the study: optimization of orthopedic dental care in hiv-infected patients. the object of the study was hiv-infected patients. the study included 67 patients aged 20 to 50 years and 14 volunteers aged 30 to 50 years, not infected with hiv. we examined hiv-infected patients with iii and iv stages of hiv who were registered and inpatient treatment at the republican center for the fight against aids and at the research institute of virology of the anruz. the examined 81 patients were divided into 3 groups: 1-group of 14 patients not infected with hiv; 2-group of 31 patients, hiv-infected with iii stage of the disease; 3-group of 36 patients, hiv-infected with stage iv disease. results. in hiv-infected patients in group 2, the following inflammatory periodontal diseases were revealed: gingivitis, including catarrhal – in 56.8% of patients. periodontitis was observed in 18% of patients. mild periodontal inflammation in patients with hiv in group 2 was detected in 30.4% of patients, pi being 0.93 ± 0.25. periodontitis of moderate severity (pi 1.89 ± 0.21) with pronounced destruction, confirmed by x-ray, was observed in 52.2% of patients. severe periodontitis was noted in 17.4% of the total number of patients with periodontitis. pi in these cases was 2.41 ± 0.26. the average value of the periodontal index in this group of patients was 1.74 ± 0.29. the depth of clinical pockets averaged 5.8 mm, which corresponds to 3 points on the cpitn scale. inflammatory periodontal diseases in patients with hiv in group 3 were presented as follows: gingivitis, including catarrhal, was observed in 61.4% of patients, necrotizing ulcers – in 6.3% of those examined. a mild form of periodontal art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 62 inflammation was observed in 27.5% of patients, with a pi of 0.98 ± 0.27. moderate periodontitis (pi 2.1 ± 0.24) was observed in 52.3% of the examined patients. severe periodontitis was noted by us in 20.2% of cases, when the pi value was 2.8 ± 0.24. the average value of the periodontal index was recorded at the level of 1.96 ± 0.23. the intensity of inflammatory periodontal diseases in the groups of hiv-infected patients was high compared to group i, which is primarily due to severe immunodeficiency. against the background of immunosuppression, destructive changes in the hard tissues of the teeth were also noted, which led to the formation of a large number of missing and destroyed teeth as a result of complicated caries, and this, in turn, contributed to the overload and disruption of periodontal trophism. the results of determining the endurance of the periodontium to loads (by the method of gnatodynamometry) showed that in patients with hiv infection in group 2, the difference in vertical stability between incisors and molars was 1.04 kg; between incisors and canines and incisors and premolars – 1.99 and 1.49 kg, respectively (p≤0.05 compared with intact periodontium). against the background of severe immunodeficiency in patients with hiv in group 3, significant disturbances in periodontal endurance were observed: the difference in vertical stability between incisors and molars was 0.82 kg; between incisors and canines and incisors and premolars 1.73 and 1.13 kg, respectively (p≤0.05 compared with intact periodontium). when studying the resistance of teeth to horizontal loads, a similar trend was found. in patients of group 1 in intact periodontium, the resistance of molars to horizontal loads exceeded that of incisors by 2.25 kg; the corresponding excess in patients with hiv infection in group 2 was 0.3 kg, in patients in group 3 – 0.27 kg. the difference in horizontal stability between incisors and canines and incisors and premolars is 1.0 and 0.95 kg in the intact periodontium, respectively; a similar difference in patients in group 2 was 0.08 and 0.18 kg, in patients with hiv in group 3 – 0.06 and 0.16 kg (p≤0.05 compared with intact periodontium). it is obvious that hiv infection leads to severe changes in the functional state of the periodontal complex, which is manifested by a sharp drop in the periodontal endurance to stress and loss of stress differentiation in different groups of teeth. the leveling of gnathodynamometry indices in different groups of teeth indicates a decrease in the functional state of the periodontium. due to the significant number of teeth destroyed as a result of the carious process and extracted teeth in hiv patients; there was an increase in the proportion of people with secondary edentulousness and needing prosthetics. moreover, in both groups of hiv-infected patients, the provision with prostheses was extremely low. the quality of the prostheses was at the same level. on the day of examination, 21.2% of hiv-infected patients needed fixed dental prosthetics (bridging). in accordance with the size and localization of the dentition defect, 26 (78.8%) patients with hiv needed partial removable and removable dentures. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 63 so, after treatment, which included both pathogenetic and symptomatic therapy, including orthopedic treatment, the periodontal pi index was 0.87 ± 0.18 in the control group; in hiv-infected patients whose dentition defects were replaced with prostheses based on thermoplastic material «ftorax» and «vertex termo sens», pi was equal to 0.54 ± 0.15 (p≤0.01 compared with the data before treatment; p ≤0.05 between groups). the obtained clinical and laboratory data on the state of the tissues of the prosthetic bed make it possible to recommend, for replacing defects in the dentition in people living with hiv, prostheses made of thermoplastic material «vertex termo sens», as a method of choice, according to the results of our research, their use significantly increases the efficiency of performed activities. thus, the planning of treatment for hiv-infected patients should be based on the joint work of all medical services, i.e. improvement of dental care should be carried out along the way of improving the quality of treatment of major dental diseases against the background of path genetically and symptomatically justified therapy. it should be noted that due to the fact that the provision of dental care to hivinfected patients should be carried out with minimal invasive interventions, due to the high risk of transmission of the pathogen during manipulations, it seems very relevant to consider the issue of providing orthopedic treatment using modern materials that do not provide irritation. toxic and allergic effects on the oral mucosa, as well as additional preparation and overloading of supporting teeth that do not require additional preparation during the manufacture of prostheses. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 64 references 1. arutyunov a.s., tsarev v.n., kravtsov d.v., komov e.v. comparative analysis of the adhesion of microbial flora to the base materials of jaw prostheses based on polyurethane and acrylic plastics // russian dental journal.moscow, 2011.-№1.-с.1923. 2. atabekov ns situation on hiv infection in uzbekistan // modern approaches in the diagnosis, prevention and treatment of hiv infection: abstracts. report scientific. – practical. conf. 1-2 december 2010.tashkent, 2010.s. 12-13. 3. alimov a.s., alimov a.a. the choicejf the optimum basis material for the manufacture of tooth prosthesis in hiv-infected patiets //european scienc review journal, 2018, № 5-6. p.130-131. 4. alimov a.s., rizaev j.a., alimov a.a. construction depending choice of dental prosthesis on status of stomach of the teeth periodont to loadsin hiv-infected patients // «international scientefic review of the problems of natural sciences and medicine» (boston. usa, july 2-3, 2018. pp. 21-24. 5. alisher alimov, anvar alimov, fakhriddin shamsiev, alisher azizov. using of protective coating of the contact surface of plastic dentures by using an adhesive system for prevention and treatment of hiv-infected patients with intolerance to acrylic dental prostheses. international journal of advanced science and technology.vol. 29, no. 5, (2020), pp. 1449-1452. 6. boy s.c., van heerden m.b., wolfaardt m., cockeran r. an investigation of the role of oral epithelial cells and langerhans cells as possible hiv viral reservoirs // j oral pathol med.-2009.-№38(1)-р.114-119. 7. pokrovsky v.v. clinical guidelines. hiv infection and aids. m.:geotarmedia, 2010.-192 p. http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22boy%20sc%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22van%20heerden%20mb%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22wolfaardt%20m%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=%22cockeran%20r%22%5bauthor%5d&itool=entrezsystem2.pentrez.pubmed.pubmed_resultspanel.pubmed_discoverypanel.pubmed_rvabstractplus javascript:al_get(this,%20'jour',%20'j%20oral%20pathol%20med.'); javascript:al_get(this,%20'jour',%20'j%20oral%20pathol%20med.'); art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5848882 6 art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5848882 7 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5848882 8 characteristics of the cardiovascular system dynamics in women working at the navoi silkworm plant and the risk of developing pre-patholic conditions iskandarov aziz bakhromovich doctor of philosophy (ph.d.) in medical sciences, senior researcher of the scientific research institute of sanitation, hygiene and occupational diseases of the ministry of health of the republic of uzbekistan abstract: working conditions and the character of labor processes in the silkworm industry cause unfavorable changes in the parameters of the cardiovascular system in female workers; the most expressed negative effect on the functional state of the cardiovascular system is produced by the temperature factor (coefficient of determination 96.1% average in all indexes of hemodynamics, coefficient of elasticity 0.065-0.2%). calculation of correlation, determination and elasticity coefficients makes it possible to predict the risk of pre-pathological conditions, which allows substantiating measures to reduce the adverse effects of production factors on the body of workers. keywords: silkworm production, working conditions, cardiovascular system. in uzbekistan, the output of natural silk increases from year to year, which is associated with the development of mulberry silkworm production, where breeding caterpillars of mulberry silkworms are grown and get a highly productive elite green. over the past few years, more than 2 times increased the volume of production of domestic productive breeds of mulberry silkworms, from which grow cocoons. uzbekistan ranks 4th in the world after china, vietnam, and india's production of live cocoons. increased production of mulberry silkworm cocoons is directly related to the development of silkworm industries. currently, 17 silkworm plants and 3 breeding silk stations are operating in uzbekistan. mainly women work in the silkworm industry. one of the largest silkworm productions in uzbekistan is the navoi silkworm plant, where within the grant project atss-24.6 "development of new methodology of forecasting and prevention of professionally caused prepathological conditions at women working at agricultural silkworm productions of uzbekistan," the studies on working conditions and their influence on the functional condition of different systems of the organism, including the cardiovascular system, were conducted. the research aimed to reveal the influence of working conditions of female workers of the silkworm production on the functional state of the cardiovascular system. research methods. working conditions were studied by traditional methods, using an aspirator, psychrometer, anemometer, noise meter, luxmeter according to the art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5848882 9 requirements of sanitary rules, norms and hygienic norms of the republic of uzbekistan №№ 0294-11 [2], 0325-16 [3], 0141-03 [4], 0324-16 [5], building norms and rules 2.01.05-96 [8], and a technique "labour conditions assessment technique and the certification of work places by working conditions" [7]. hemodynamic indices studied the functional state of the cardiovascular system: pulse rate was counted by the palpatory method on the radial artery, and arterial pressure level was measured by korotkoff's sonic method. the heart's systolic and minute volumes (sb and mos) were determined using calculation methods according to the stahr formula. the hickam formula calculated the mean dynamic pressure and peripheral resistance in capillaries [6]. all measurements were made directly at the workplaces before the beginning of work (baseline values), before the lunch break and at the end of the working day. research results. studies have shown that one of grenade production's leading adverse production factors is papilionage dust, which has allergenic properties [1]. papilionage dust is formed during papilionage (mating of butterflies) when scales are separated from the wings of many moths, which fly around in the air. dust from moths consists of 75-80% of organic substances of animal origin (the smallest chitinous scales) and contains a small amount (about 0.01%) of protein substances. dimensions of 90-95% of the dust particles are up to 10 microns. they have an irregular shape with pointed edges and long spikes. research materials showed that the dustiness of papillary dust during different technological operations varies from 3.43±0.13 to 12.05±0.57mg/m3. in addition, the air of the working area of the silkworm plant is polluted by products of activity of pupae and butterflies of mulberry silkworm: ammonia (nh3), hydrogen sulfide (h2s) and carbon monoxide (co). average ammonia concentrations exceeded mpc by 1.06-1.07 times, hydrogen sulfide by 1.12-1.31 times, carbon oxide by 1.11 times. air temperature at the working places of papilionazhnits fluctuated in the dynamics of a working day from 28,8±0,45 to 32,04±0,23ос on the average, relative humidity from 33,0 to 62,4%, air speed was insignificant -0,12±0,002 m/s. illumination of working surfaces in the papilion workshop during the dynamics of the working day ranged from 5.6 to 180 lux, the coefficient of natural light was 0.19±0.09 0.45±0.1%, i.e. there was not enough light at the working places. the labor process of the workers in the papillary plant is characterized by limited general mobility, the monotony of work operations (cutting cocoons to release pupae, separating pupae by floor, working with butterflies), forced, uncomfortable working posture. production operations are performed when working with pupae. more than 25% of working time is performed in a forced working posture (squatting, kneeling), when mating and separating butterflies more than 80% art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5848882 10 of working time is performed standing, accompanied by the same type of hand movements. conditions of work of women working in the silkworm industry refer to the 3rd class of the 3rd degree of harmfulness. the research was carried out to study the dynamics of indexes of the functional state of the cardiovascular system. practically healthy women workers of navoi silkworm plant., aged 19 to 58 with 1 to 33 years of work experience, were examined. sixty man-days of working observations were carried out. the materials of the researches show that the women workers with 1-10 years of work experience have a reliable reduction of heart rate and increase of both systolic and diastolic pressure in the dynamics of work. the heart rate slows down from 82.2±0.9 to 77.6±0.7 bpm. (p<0.05), systolic blood pressure increases from 134.8±1.3 to 141.0±1.9 mm hg. (p<0.05), diastolic pressure increased from 82.0±2.9 to 93.0±1.3 mm hg. (p <0,05). apparently, such a reaction is connected with the complex influence of unfavorable production factors in combination with the character of the work performed: intensive monotonous work. this was accompanied by an unfavorable tendency of hemodynamic indexes changes: pulse pressure reduced from 52,0±1,2 to 48,0±0,9 mm hg (p<0,05). (p <0.05), increase of mean dynamic pressure from 99.3±2.1 to 109.0±1.3 mm hg (p <0.05). (p <0,05). in addition, there was a decrease in systolic and cardiac minute volumes from 45.6±1.6 to 37.0±1.1 ml (p<0.01) and from 3.7±2.4 to 2.8±2.0 l (p<0.05), respectively, from beginning to end of work. the hypertensive orientation of changes in cardiovascular system indices is confirmed by the reliable increase of peripheral resistance in capillaries in the dynamics of work (p<0,05). female workers with 11 to 20 years of work experience also show significant hypertensive changes in the maximum, minimum and mean-dynamic blood pressure. moreover, the severity of changes in the indices increases with the length of service. thus if at the work experience up to 10 years the maximal arterial pressure in the dynamics of work increased by 4,5% from the background to the operational level, then at the work experience up to 20 years this index increased by 7,5%. the minimum arterial pressure increased respectively by 13,4 and 14,5%, and mean dynamic pressure by 9,7 and 11,3%. consequently, the severity of adverse shifts of cardiovascular system indices increased with the increase of work experience. this is confirmed by hemodynamic indexes of women with more than 20 years of work experience. the maximum arterial pressure in this group of examinees increases in the dynamics of work already by 8,6% from the background level, other parameters change the same way as in women with up to 20 years of work experience. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5848882 11 the analysis of the obtained data shows that the labor process of the female papillomaniacs causes the development of unfavorable changes of hemodynamic indices in the dynamics of work, which indicates the weakening of functional reserves of the cardiovascular system [9]. to substantiate the dependence of changes in indicators in the dynamics of the shift on the levels of adverse production factors, a mathematical analysis of the dynamics of changes with the calculation of correlation, determination and elasticity coefficients was performed. the regularity of the dependence of changes in the indices on the levels of factors of working conditions has been established. a high correlation dependence on both air temperature (r -0.93-1.0) and relative air humidity (r -0.62-0.91) has been established for all the changes of cardiovascular system indices. the regularity of dependence of the dynamics of pulse rate, minimum, meandynamic blood pressure, systolic and minute volumes of the heart on microclimatic conditions has been proved. it has been found out that the temperature factor has the most negative influence on the functional state of the cardiovascular system (the determination coefficient is 96.1% on average by all hemodynamic indices, the elasticity coefficient is 0.065-0.2%). the method of predicting pre-pathological conditions was developed, which allowed substantiating measures to reduce the adverse effects of production factors on the body of workers. conclusions: 1. at women working at navoi silkworm plant in dynamics of the working day, there are observed changes of hemodynamic indexes testifying about compensatory tension of processes of regulation of functional condition of the cardiovascular system, manifested in pulse increase and increase of arterial pressure, and also in the tendency to decrease of systolic blood volume that testifies to some weakening of functional reserves of the cardiovascular system. 2. expression of changes in cardiovascular system indexes increases with working experience. 3. calculation of correlation, determination and elasticity indexes allows to prognose physiological shifts and prepathological conditions and to substantiate measures on the decrease of the unfavorable influence of production factors on the functional condition of different systems of the organism. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5848882 12 reference. 1. andriesh l.p., kozlyuk a.s. sensitizing properties of some silk production ingredients // immunodiagnostics and specific prophylaxis of infectious diseases. kishinev. -2004. -pp.159-162. 2. iskandarov t.i., ibragimova g.z., iskandarova g.t., feofanov v.n., shamansurova h.sh., tazieva l.d. sanitary rules, norms and hygienic standards of the republic of uzbekistan №0294-11 "maximum allowable concentrations (mac) of harmful substances in the air of the working area". -tashkent, 2004. -p.53. 3. iskandarov t.i., magay m.p., tashpulatova g.a., iskandarova g.t, adylov u.h. sanitary rules, norms and hygienic norms of the republic of uzbekistan №0325-16 "sanitary norms of acceptable noise levels in working places". -tashkent, 2001. p.17. 4. iskandarov t.i., ibragimova g.z., shamsurova h.sh., slavinskaya n.v., iskandarova m.s., demidenko n.m., iskandarova g.t., parsegova l.g, feofanov v.n. sanitary rules, norms and hygienic normative documents of the republic of uzbekistan n 0141-03 'hygienic classification of working conditions according to the harmfulness and hazard of factors of the industrial environment, the severity and intensity of the labour process'. -tashkent, 2004. -p.53. 5. iskandarov t.i., slavinskaya n.v. sanitary rules, norms and hygienic standards of the republic of uzbekistan № 0324-16 "sanitary and hygienic norms of the microclimate of industrial premises. -tashkent, 2016. -p.10. 6. likhnitskaya i.i. assessment of the state of functional systems in determining the ability to work. leningrad, 1962, 237p. 7. v.m. nichkasov, t.i. iskandarov, g.z. ibragimova, n.v. slavinskaya, g.t. iskandarova, "methods of assessing working conditions and workplace certification by working conditions. -tashkent, 1996. – p.21. 8. construction norms and rules 2.01.05-98 'natural and artificial lighting'. tashkent, 1998. – p.48. 9. umidova zi, glezer ga, yanbaeva hi, korol gp essays of cardiology of the hot climate. tashkent, 1975. – p.394. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533529 134 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533529 135 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533529 136 study of the application of magnetotherapy in complex with ganoderma lucidum extract on the state of the immunocompetent system in the treatment of patients with dual ultra disease with dysbiosis. kadirova s.r. khamrabaeva f.i. center for the development of professional development of medical workers of the ministry of health of the republic of uzbekistan abstract purpose of the study: to study and scientifically substantiate the use of magnetotherapy in combination with synbiotics in the rehabilitation treatment of patients with intestinal dysbiosis. research methods: 90 patients with colonic dysbiosis, 53 women and 25 men, aged 18-65 years, were studied. treatment methods. in accordance with the objectives of the study, all patients were divided into groups comparable in terms of the main clinical and physiological characteristics. patients of the first group (30 patients) were treated with magnetic therapy (mt) from the "olymp-1" apparatus. the impact was carried out by 4 pairs of inductors solenoids on the area of projection of the organs of the large intestine; exposure parameters: intensity 30% 100%, frequency 10 hz, magnetic induction value 5 mt. the procedures were carried out daily, lasting 15-20 minutes. the course of treatment is 10-12 procedures. patients of the second group (30 patients) underwent complex treatment: mt according to the above method, as well as a synbiotic consisting of an extract of ganoderma lucidum 1 capsule 2 times a day with meals for 21 days in the third comparison group (30 patients), the effect of mt from the “olymp-1” apparatus (placebo) was imitated. the course of treatment consisted of 10-12 procedures. ganoderma lucidum extract was included in the treatment complex according to the above scheme. the results of the studies conducted suggest that the proposed complex treatment potentiates and prolongs the analgesic and anti-inflammatory effects, has an immunocorrective effect, promotes the growth of saccharolytic microflora, restores the dynamic balance of the intestinal microflora and biotope, improves the functional state of the intestine, and has a positive effect on the psycho-emotional state of patients with du. with accompanying dc. keywords du, dc, frequency, the development of physiotherapeutic and biocorrective technologies of restorative medicine for diseases accompanied by the involvement in the pathological process of systems that provide adaptive reactions in the body, especially immune, metabolic, antitoxic, enzymatic, cytoprotective, etc., is one of the urgent tasks of modern medicine. (krasnopolsky v.i. et al., 1999; savelyeva g.m., 1999; yaglov v.v., 2001; vikhlyaeva em, 2012). one of the components of the pathological symptom complex in duodenal ulcer disease is the development of dysbiotic conditions, which is associated, among other things, with the use of antibacterial therapy according to the recommendations art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533529 137 of all the protocols of the maastricht consensus. in the scientific literature there are data indicating a 100% combination of some diseases with intestinal dysbiosis (dc) (strizhova n.v. et al., 2001; pasman n.m. et al., 2006), which leads to the formation of a syndrome of mutual burden , and thus complicates the treatment of this category of patients. the experience of using synbiotics (sg) in gastroenterological practice is widely presented in the literature (gusakova e.v., 2005; efendieva m.t. et al., 2006; ushkalova e.a., 2007; gionchetti p. et. al, 2006; mcfarland lv, 2006). the results of recent studies give reason to consider the methods of physical therapy as one of the most promising, given the possibility of their differentiated and targeted impact on various links of the pathogenesis of the disease, an increase in the adaptive and reserve capabilities of the body with a minimum risk of developing side and allergic reactions (strugatsky v.m. et al. , 1999; razumov a.n., 2002). various methods of physiotherapy are successfully used in gastroenterological practice. at the same time, the experience of using magnetotherapy in the treatment of intestinal diseases (serdyuk v.v., 2004, eremina a.a., 2007) is limited. the theoretical prerequisite for the use of magnetic therapy (mt) in patients with intestinal dysbiosis is the data of previous studies, indicating its beneficial effect on the state of the body's regulatory systems, an increase in adaptive reactions, an improvement in regional hemodynamics in patients with various pathologies (bogo lyubov v.m. . et al., 1998; berkutova am et al., 2000), which is important in the treatment of this category of patients. immunity disorders play one of the central places in the pathogenesis of du and dc. savelyeva g.m. et al., 1997; v. i. kulakov et al., 1998), in connection with which it was given attention to the study of the mechanism of action of mt as a method of monotherapy for localinfluence, as well as in combination with the extract of ganoderma lucidum on the state of the immune system. objective: to study the use of magnetic therapy in combination with ganoderma lucidum extract on the state of the immune system in the treatment of patients with duodenal ulcer disease with intestinal dysbiosis. research methods: 90 patients with colonic dysbiosis, 53 women and 25 men, aged 18-65 years, were studied. in addition to general clinical studies, laboratory diagnostics of dc were carried out according to the method developed by f.l. vilypanskoy (1970), endoscopic examination of the colon using the olympus apparatus, histological examination of biopsy specimens of the colon mucosa, assessment of the immune status using tests that give an idea of the quantitative indicators of cellular and humoral immunity: tand b-lymphocytes, immunoglobulins class g, a, m in peripheral blood (methods of mjondal al., 1972; i. morettaetal., 1975; g. mancini, 1965), assessment of psychological status using a computer version of the smol (abbreviated multifactorial questionnaire for personality research) according to the hare method v.p. (1981), assessment of the psychosomatic state using the san test (well-being, activity, mood). the data obtained were processed by the methods of variation statistics using the microsoft excel (2007) software package on an ibm pc with the calculation of student's t-criterion (as modified by fisher). in the presence of art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533529 138 related samples, the student's difference test was used. to assess the difference in shares (change in the presence of the sign as a percentage), the alternative f-test was used. differences between mean values were considered significant at treatment methods. in accordance with the objectives of the study, all patients were divided into groups comparable in terms of the main clinical and physiological characteristics. patients of the first group (30 patients) were treated with magnetic therapy (mt) from the "olymp-1" apparatus. the impact was carried out by 4 pairs of inductors solenoids on the area of projection of the organs of the large intestine; exposure parameters: intensity 30% 100%, frequency 10 hz, magnetic induction value 5 mt. the procedures were carried out daily, lasting 15-20 minutes. the course of treatment is 10-12 procedures. patients of the second group (30 patients) underwent complex treatment: mt according to the above method, as well as a synbiotic consisting of an extract of ganoderma lucidum 1 capsule 2 times a day with meals for 21 days in the third comparison group (30 patients), the effect of mt from the “olymp-1” apparatus (placebo) was imitated. the course of treatment consisted of 10-12 procedures. ganoderma lucidum extract was included in the treatment complex according to the above scheme. research results: analysis of the dynamics of the immune status showed the benefits of complex treatment. this was characterized by the restoration of the balance of the immunoregulatory t-cell subpopulations тƴ and тµ and an improvement in their ratio due to a clearer differentiation of t-lymphocytes in the thymus, as well as a significant increase (p <0.05) of the immunoregulatory index. the study of the immunological parameters of the patients of the 1st and 3rd groups revealed the restoration of only the immunoregulatory subpopulation of tµ-lymphocytes. at the immunoregulatory index did not change significantly. the final assessment of the effectiveness of the treatment showed the benefits complex therapy. so, at the end of the course of treatment, a significant improvement was noted 10% of patients in the 1st, 40% in the 2nd group; improvement in 46.7% of patients 1st, 43.3% 2nd and 43.3% 3rd group. 43.3% of patients in 1st, 16.7% 2nd and 56.6 ° finished without treatment effect. 3rd group. the values of the pearson criterion in the distribution of treatment results in the two main groups versus the comparison group were, respectively, x2 = 10.2; p = 0.038 x2 = 16.2; p = 0.014. long-term results of treatment showed that, on average, the achieved positive treatment effects persisted for 3 months in 40% in group 1, in 66.7% in group 2 th group. exacerbation of the disease after 3 months was noted in 28.6% of patients with 1st and 33.3% 3rd group. in the 2nd group for the specified period of exacerbation of the inflammatory process was not observed. after 6 months, the positive effect persisted in 23.3% of patients 1 th; 46.7% 2nd group. exacerbation of the disease after 6 months occurred in 47.6% of pain1st, 13.3% 2nd and 57.1% 3rd groups. after 12 months, the positive effect persisted. it was found in 13.3% of patients in the 1st and 35% in the 2nd groups. exacerbation of the inflammatory process res 12 months was observed in 66.7% of patients in the art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533529 139 1st, and 66.7% in the 3rd and 20% in the 2nd groups. bole high efficiency of treatment based on long-term results is verified reliably by the values of the pearson x2 criterion for two main groups versus the control with were set integrally over 12 months of observation (respectively for groups 1 and 2 x2 = 23.8 p = 0.026 and x2 = 28.5; p = 0.011). thus, the results of the studies carried out made it possible to identify a number of positions. the positive effects of magnetotherapy in combination with the extract of ganoderma lucidum in the influence on various links in the pathogenesis of the studied pathology. the vasotropic effect plays an important role in the realization of the therapeutic effect of magnetotherapy. the result of the improvement in regional hemodynamics, which was observed in the majority of the surveyed, was a decrease in inflammation in the gastric mucosa, which, to a certain extent, contributed to the improvement of digestion. the most pronounced effect was observed in patients with initial intestinal dysbiosis. complex treatment potentiates and prolongs the analgesic and anti-inflammatory effects, has an immunocorrective effect, promotes the growth of saccharolytic microflora, restores the dynamic balance of the intestinal microflora and biotope, improves the functional state of the intestine, positively affects the psycho-emotional state of patients with du with concomitant dc. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533529 140 references 1. yarustovskaya o.v., efendieva m.t., gusakova e.v., ondzhu n. normoflorins in complex restorative treatment of patients with chronic nonspecific saline ingoophoritis and concomitant intestinal dysbiosis. // act. recovery problems honey., kuort. and physioter., 2005. p. 237. 2. gusakova ev, efendieva mt, ondzhu n. experience in correction of dysbiosis echnika in patients with chronic nonspecific salpingo-oophoritis. // polyclinic, 005, no. 3.-p. 36-37. 3. yarustovskaya o.v., efendieva m.t., gusakova e.v., ondzhu n. eriosis in patients with chronic nonspecific salpingo-oophoritis and concomitant intestinal isbiosis. // abstracts of the plenum of the scientific society of gastroenterologists of russia. believe, november 10-11, 2005 p. 96-98. 4. razumov a.n., gusakova e.v., efendieva m.t., molina l.p., ondzhu n., doroshev .n. the possibilities of synbiotics in the correction of disorders of the intestinal microflora in practice for doctors of different specialties. // sat. tr. "new diagnostic and health-improving rehabilitation technologies of restorative medicine2005 "moscow, 2005. p. 8-69. 5. razumov a.n., efendieva m.t., gusakova e.v., molina l.p., zemlyanskaya i.v., ndzhu n. modern approaches to the rehabilitation of patients with irritable of the intestine with the help of functional nutrition. // symposium new diagnostic and health and rehabilitation technologies of restorative medicine. moscow, 005.-p. 67-68. 6. razumov a.n., gusakova e.v., efendieva m.t., molina l.p., ondzhu n. new technologies of medical rehabilitation of patients with functional disorders of the oi gut. // materials of the international conference "modern technologies for restoring ovative medicine., rehabilitation and balneology "baden-baden, 2006. p. 41-426. 7. ondzhu n.z. running pulsed magnetic field and liquid synbiotics in treatment and patients with chronic nonspecific salpingo-oophoritis. // international coness "practical gynecology: from new opportunities to a new strategy" march 27-31 006, moscow.-p. 137. 8.gusakova e.v., efendieva m.t., ondzhu n., molina l.p., zemlyanskaya i.v. physiotherapy in combination with synbiotics in the treatment of patients with irritable bowel syndrome shechnik. // gastroenterology of st. petersburg. materials of the 8th slavic-baltic forum "st. petersburg gastro-2006" 2006, №1-2. p. 41. 9. efendieva m.t., gusakova e.v., ondzhu n. intestinal dysbiosis and methods of its cortex reactions in patients with chronic salpingo-oophoritis.//vopr. resort., physiotherapy. and exercise therapy 2007, no. 1.-p. 29-31. 10. yarustovskaya o.v., efendieva m.t., gusakova e.v., derevnina n.a., ondzhu n. experience of using low-frequency traveling pulsed magnetic field and normoflo rins in the complex treatment of patients with chronic nonspecific salpingo-oophoria volume and concomitant intestinal dysbiosis.//vopr. resort., physiotherapy. and zhf. – 2008 no. 1.-p. 27-29. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 96 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 97 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 98 carbon metal disorders in cushing syndrome kholmatova. yu.a. ph.d., narimova g.d. tashkent pediatric medical institute republic of uzbekistan abstract: the article analyzes the specificity of carbohydrate metabolism in cushing's syndrome from a scientific point of view. thus, the article draws conclusions about carbohydrate metabolism in cushing's syndrome. keywords: cushing's syndrome, steroid diabetes mellitus, hyperglycemia, carbohydrate metabolism, hypercortisolism. the relevance of studying carbohydrate metabolism in patients with itsenkocushing's disease is explained by the frequent occurrence of glucose metabolism disorders, on the one hand, and difficulties in the selection of antihyperglycemic therapy in these categories of patients, on the other. the effectiveness of the treatment of hyperglycemia in such patients may be reduced due to the difficulty of achieving remission / cure of the underlying disease, as well as due to the use of specific therapy that promotes the development of hyperglycemia. recently, there has been growing interest in studies aimed at studying the role of the incretin system in the pathogenesis of secondary hyperglycemia associated with neuroendocrine diseases[1]. 1 itsenko-cushing's disease (bik) is a severely symptomatic disease of hypothalamic-pituitary genesis, occurring with a clinical picture of hypercortisolism, caused by the presence of a pituitary tumor (85%) or pituitary hyperplasia and characterized by increased secretion of adrenocorticotropic hormone (acth) and an increase in adrenocorticotropic hormone (acth). epidemiology this is the most common cause of endogenous itsenko-cushing syndrome (about 68%). the disease is more common in women than in men. women are more likely to get sick between the ages of 20 and 40, there is an addiction to pregnancy and childbirth, as well as from brain injuries and neuroinfections (in particular, herpes infection). in adolescents, the disease often begins during puberty [2]. in childhood and old age, itsenko-cushing's disease is rarely diagnosed. classification there are several degrees of severity of nik: mild form (moderately severe symptoms of the disease); moderate form (pronounced symptoms in the absence of complications); severe form (severe symptoms in combination with complications, including cardiopulmonary failure, steroid diabetes, progressive myopathy, pathological fractures, severe mental disorders). ticism is distinguished by a rapidly progressive (3-6 months) and torpid course of the disease (> one year). there are four main reasons for the state of excess glucocorticoids of any origin: art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 99 1. exogenous glucocorticoids. cushing's syndrome develops over time in patients who receive glucocorticoids for inflammatory or autoimmune diseases (including bronchial asthma, rheumatoid arthritis, systemic lupus erythematosus, skin diseases). 2. pituitary cushing's syndrome. this pathology, called itsenko-cushing's disease, develops with benign pituitary adenomas, which secrete excess acth. 3. ectopic acth products. of the two variants of ectopic production, acth of the first type is caused by malignant tumors, most often of the lungs. patients have clear signs metastatic tumor: weight loss, hypertension, hypokalemia, and hyperpigmentation. the second variety is due to slowly growing tumors referred to as carcinoids. patients with acth-producing carcinoid tumors may have the same clinical symptoms. phenomena and biochemical shifts, as well as patients with pituitary disease itsenkocushing. thus, the differential diagnosis between a pituitary tumor and a carcinoid tumor in a patient with cushing's syndrome is difficult [3] 4. adrenal causes of cushing's syndrome. both benign and malignant adrenal tumors can produce excess glucocorticoids and be accompanied by cushing's syndrome. benign adrenal adenomas are clinically similar to other varieties of this syndrome; hirsutism, however, is absent, as the tumor only secretes cocortisol and not androgens. malignant adrenal carcinomas with manifestations of cushing's syndrome are usually large tumors in the abdominal cavity and have poor forecast [4]. etiology and pathogenesis the reason for the bik has not been precisely established. most of the patients are diagnosed with a pituitary adenoma, which, according to modern concepts, is the cause of the disease. in recent years, using the methods of molecular biology, the pathogenesis of pituitary adenomas, and corticotropin in particular, has been clarified. it has been shown that most of these adenomas are monoclonal, as evidenced by the presence of the same gene mutations in adenoma cells. a potential mechanism for the development of corticotropin may be spontaneous mutation of the receptors of the corticotropin-releasing hormone (crh) or vasopressin genes. in the absence of obvious signs of a pituitary adenoma, we can talk about damage or dysfunction of higher structures, for example, the limbic region [5]. clinical signs and symptoms cortisol and other glucocorticoids have multifaceted effects as physiological regulators. they increase glucose production, inhibit protein synthesis and increase protein breakdown, stimulate lipolysis and affect immunological and inflammatory processes. glucocorticoids contribute to the maintenance of blood pressure and largely determine the body's response to stress. the production of cortisol by the adrenal glands is stimulated by acth. the secretion of acth, in turn, depends on the crh produced in the hypothalamus art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 100 and vasopressin. cortisol, acting on the pituitary gland, hypothalamus, suppresses the production of acth and crh. in normal (non-stress) conditions, the products of cor tizole is carried out in accordance with certain biological rhythms: with a higher activity in the morning and a lower activity late in the morning. black. under stressful conditions, the secretion of crh, acth and cortisol increases, and biological rhythms are disrupted. since cortisol levels can vary widely throughout the day and increase in a certain way under stress, it can be difficult to distinguish between normal and impaired secretion of this hormone.many biochemical tests are used to diagnose pathological hypercortisolemia, but none of them is absolutely reliable. therefore, the examination of a patient with suspected nik is often difficult and can give conflicting results [6]. the clinical picture of nik is caused by excessive secretion of corticosteroids, and primarily corticosteroids. characterized by the defeat of almost all organs and systems with the development of a symptom complex inherent in hypercortisolism [7]. dysplastic obesity (the earliest and most common symptom). characterized by the redistribution of subcutaneous adipose tissue (cushingoid type of obesity) with the deposition of fat in the shoulder girdle, supraclavicular spaces, above the cervical vertebrae ("climacteric hump") and on the abdomen with relatively thin limbs. the face becomes round (moon-shaped), the cheeks become purple-red (matronism) [8]. trophic changes in the skin. the skin is thinned, dry, with a tendency to hyperkeratosis, purple-cyanotic color. stretch stripes (striae) of red-violet color appear on the hips, chest, shoulders, abdomen, due to increased protein catabolism and thinning of the skin. characterized by the formation of hematomas of minor injuries due to increased fragility of capillaries and thinning of the skin, hyperpigmentation of the skin in places of friction (neck, elbow joints, armpits) due to increased secretion of acth. often women have hirsutism (mustache, beard, sideburns), breast hypertrichosis. secondary hypogonadism (early symptom). in women, the menstrual cycle is disrupted in the form of opsomenorrhea and amenorrhea, which leads to primary or secondary infertility. in men, potency decreases and gynecomastia often develops. at puberty, boys have underdevelopment of the testicles and penis, and girls have underdevelopment of the mammary glands and primary amenorrhea. these changes are accompanied by a decrease in plasma gonadotropins, testosterone and estrogens [9]. arterial hypertension (ah). develops in the majority of patients. subsequently, violations of myocardial metabolism and the appearance of symptoms are possible. ptomes of heart failure. signs of left ventricular hypertrophy can often be seen on electrocardiography (ecg). myopathy. muscle hypotrophy affecting the striated and muscular systems, benno of the upper and lower extremities (thinning of the arms and legs), atrophy of the muscles of the anterior abdominal wall with an increase in the abdomen [10]. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 101 disorders of carbohydrate metabolism. manifested by impaired glucose tolerance (in 70-80% of patients) or type 2 diabetes mellitus (dm). diabetes mellitus is characterized by hyperinsulinemia, insulin resistance, lack of tendency to ketoacidosis, and a favorable course (usually, to compensate for carbohydrate metabolism, it is sufficient to prescribe a diet and oral hypoglycemic drugs) [11]. secondary immunodeficiency. manifested by pustular (acne) or fungal lesions of the skin and nail plates, trophic ulcers shins, a long period of healing of postoperative wounds, chronic pyelonephritis. characteristic is the inhibition of all links of cellular immunity (a decrease in the number of t and b lymphocytes), a decrease in the activity of phagocytes and a decrease in humoral immunity. vegetative changes nervous system are pronounced and diverse, they form the syndrome of vegetative dystonia, which manifests itself in emotional and personal shifts from mood and sleep disorders to severe psychosis [12]. changes in the skeletal system. in children and adolescents, early symptoms of hypercortisolism are growth retardation or complete cessation, as well as a delay in skeletal differentiation; there is a difference between passport and bone age of 1–5 years. steroid osteoporosis with bone demineralization and suppression of protein matrix synthesis at any age is one of the most severe manifestations of hypercortisolism. the severity of the process depends on the degree and duration of hypercortisolism. frequent symptoms of osteoporosis are pain in the spine, often a decrease in the height of the vertebral bodies and spontaneous fractures of the ribs and vertebrae. disorders of carbohydrate metabolism are a frequent symptom of itsenko-cushing's disease patients with this pathology may experience en precrinologists, family doctors diagnosed with type 2 diabetes, hypertension, dyslipidemia, osteoporosis. at the same time, the secondary genesis of the clinical symptoms of the disease often remains unrecognized for a long time, which contributes to the progression of the disease and the development of complications. a cohort of patients with itsenko-cushing's disease has a high risk of atherosclerotic cardiovascular disease, which can continue despite remission of the disease and normalization of cortisol levels [13]. we have presented the patient's case history, which was observed by primary care specialists for type 2 diabetes and hypertension. a thorough examination of the patient, in which attention was drawn to the rapid weight gain, dysplastic structure, matronism, made it possible to suspect the secondary nature of the disorders and establish the correct diagnosis of itsenko-cushing's disease. the performed surgical treatment made it possible to eliminate the clinical manifestations of hypercortisolism, namely, secondary diabetes mellitus, dysplastic obesity, hypertension. we draw the attention of various specialists to the problem of hypercortisolism and the possibility of developing atypical, erased forms of this pathology, without characteristic skin symptoms of the disease. endogenous hypercortisolism, in our opinion, should be inappropriate in patients control of art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 102 diabetes in combination with hypertension, dysplastic obesity or rapid weight gain. such patients require a comprehensive endocrinological examination, including a study of cortisol, a small dexamethasone test, an assessment of the content of thyroidstimulating hormone, lipid profile, as well as the state of bone tissue [14]. steroid diabetes mellitus is an endocrine pathology that develops as a result of a high content of adrenal cortex hormones in the blood plasma and a violation of carbohydrate metabolism. it is manifested by symptoms of hyperglycemia: rapid fatigue, increased thirst, increased profuse urination, dehydration, increased appetite. specific diagnosis is based on laboratory detection of hyperglycemia, assessment of the level of steroids and their metabolites (urine, blood). treatment for steroidal diabetes includes withdrawal or reduction of glucocorticoid dosage, surgery to reduce the production of corticosteroid hormones, and antidiabetic therapy. steroid diabetes mellitus (sd) can be triggered by a prolonged increase in the secretion of corticosteroids or by taking them in the form of drugs. in the second case, the disease has a synonymous name drug diabetes. initially, it is not associated with the functional state of the pancreas, develops against the background of hormonal treatment and can go away on its own after drug withdrawal. sjs, provoked by an increase in natural hormones, is most often observed in itsenko-cushing's disease. in this group of patients, epidemiological indicators reach 10-12%. there is no exact information on the prevalence of sjs in the general population. causes etiologically, steroidal diabetes mellitus is subdivided into endogenous and exogenous. in the endogenous form, pancreatic dysfunction is caused by primary or secondary hypercortisolism. the reasons for this group include: secondary hypercortisolism. cushing's syndrome occurs when the level of acth, a hormone produced by the pituitary gland and regulating the activity of the adrenal glands, rises. the secretion of corticoids increases, there is a high risk of dysfunction of the pancreas. adrenal neoplasms. in primary hypercortisolism, corticosteroid production is stimulated by the growing tumor of the adrenal gland. sjs is often diagnosed with corticosteroma, aldosteroma, corticoestroma, androsteroma. the second variant of the origin of steroidal diabetes is exogenous. the highrisk group includes patients with autoimmune pathologies, chronic renal failure, and arterial hypertension. diabetes develops with prolonged therapy with drugs that inhibit the secretion of insulin by beta cells in the pancreas. these drugs are glucocorticoids, thiazide diuretics, hormonal contraceptives [15]. the level of incretins can act as a possible marker of specific disorders of carbohydrate metabolism in patients with itsenko-cushing's disease and, presumably, can help in the differential diagnosis of steroidal diabetes and type 2 diabetes mellitus. further research is needed to confirm these assumptions. itsenko-cushing's disease and type 2 diabetes sometimes have a similar clinical picture, which complicates the timely diagnosis of endogenous hypercortisolism. the presence of disorders of carbohydrate metabolism, especially in combination with art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 103 other manifestations of this neuroendocrine disease, such as dysplastic obesity, poorly controlled arterial hypertension, etc., dictates the need to exclude its secondary nature. in turn, the achievement of a satisfactory postoperative result in relation to corticotropinoma does not always lead to a regression of the formed complications. the lack of normalization of glycemic parameters, lipid metabolism, and blood pressure puts patients at high risk for the development of cardiovascular complications in the future and dictates the need for careful dynamic monitoring by specialists. to achieve compensation for dm in comorbid patients, it is worth considering therapy with new generation drugs (inhibitors of dipeptidyl peptidase-4, inhibitors of sodium glucose transporter type 2), if necessary, in combination with other drugs. references: 1.(иванов п.с., петров с.и., сидоров и.п.) том 62, № 5 (2016) https://www.probl-endojournals.ru/jour/article/view/8108/ru_ru 2.панькив в.и. украинский научно-практический центр эндокринной хирургии, трансплантации эндокринных органови тканей мз украины, г. киев№ 5(37) • (2020) 3.удк 616.453-008.61-021.3:612.122 doi: 10.22141/2224-0721.16.2.2020.201292 перцеван.о. ,чурсинова т.в.гу ≪днепропетровская медицинская академия мз украины≫, г. днепр, украина 1https://cyberleninka.ru/article/n/narusheniyauglevodnogo-obmena-v-debyute-bolezni-itsenko-kushinga/viewer 4.hirsch d, shimon i, manisterski y, et al. cushing’s syndrome: comparison between cushing’s disease and adrenal cushing’s. endocrine. 2018;62(3):712–720. doi:10.1007/s12020-018-1709-y. 5. bertagna x. management of endocrine disease: can we cure cushing’s disease? a personal view. eur j endocrinol. 2018;178(5):r183–r200. doi:10.1530/eje-180062. 6. pankiv vi. cushing’s disease: diagnosis, clinic, treatment. mìžnarodnijendokrinologìčnijžurnal. 2011;(37):159-167. (in ukrainian). 7. catargi b, rigalleau v, poussin a, et al. occult cushvol. 16, no. 2, 2020 http://iej.zaslavsky.com.ua 97оригінальнідослідження/original researches/ ing’s syndrome in type-2 diabetes. j clin endocrinol metab. 2003;88(12):5808–5813. doi:10.1210/jc.2003-030254. 8. clayton rn, jones pw, reulen rc, et al. mortality in patients with cushing’s disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study. lancet diabetes endocrinol. 2016;4(7):569–576. doi:10.1016/s22138587(16)30005-5. 9. faggiano a, pivonello r, spiezia s, et al. cardiovascular risk factors and common carotid artery caliber and stiffness in patients with cushing’s disease during active disease and 1 year after disease remission. j clin endocrinol metab. 2003;88(6):2527–2533. doi:10.1210/jc.2002-021558. https://www.probl-endojournals.ru/jour/article/view/8108/ru_ru https://cyberleninka.ru/article/n/narusheniya-uglevodnogo-obmena-v-debyute-bolezni-itsenko-kushinga/viewer https://cyberleninka.ru/article/n/narusheniya-uglevodnogo-obmena-v-debyute-bolezni-itsenko-kushinga/viewer art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5761836 104 10. feelders ra, pulgar sj, kempel a, pereira am. the burden of cushing’s disease: clinical and health-related quality of life aspects. eur j endocrinol. 2012;167(3):311–326. doi:10.1530/eje-111095. 11.https://www.krasotaimedicina.ru/diseases/zabolevanija_endocrinology/steroiddiabetes 12. стероид-индуцированный сахарный диабет/ триголосова и.в.// медицинское обозрение. – 2016 №1. 13. сахарный диабет, индуцированный экзогенным введением глюкокортикостероидов/ никитюк л.а.// международный эндокринологический журнал. – 2016. 14. клинический случай применения пиоглитазона при стероидном диабете у пациента с болезнью иценко-кушинга/ пигарова е.а., дзеранова л.к., галстян г.р. // ожирение и метаболизм. 2005.источник: https://www.krasotaimedicina.ru/diseases/zabolevanija_endocrinolo gy/steroid-diabetes 15.https://cyberleninka.ru/article/n/differentsialnaya-diagnostika-i-lecheniesaharnogo-diabeta-na-fone-bolezni-itsenko-kushinga/viewer https://www.krasotaimedicina.ru/diseases/zabolevanija_endocrinology/steroid-diabetes https://www.krasotaimedicina.ru/diseases/zabolevanija_endocrinology/steroid-diabetes https://www.krasotaimedicina.ru/diseases/zabolevanija_endocrinology/steroid-diabetes https://www.krasotaimedicina.ru/diseases/zabolevanija_endocrinology/steroid-diabetes art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 73 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 74 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 75 statistical analysis of the structure of the birth rate of underweight children in the bukhara region yuldasheva gulnoz giyasovna – assistant of the pediatrics department of bukhara state medical institute bakhranova nasiba ramazanovna director of the bukhara regional perinatal center baratov sunnat samiyevich – phd student of the pediatrics department of bukhara state medical institute abstract: the authors conducted a retrospective analysis of the frequency and structure of the birth rate of underweight children in the bukhara region for 20182020, studied the medical and social aspects and perinatal features of preterm birth. the possibility of predicting perinatal outcomes and optimizing preventive measures for pregnant women at risk has been established. keywords: small children, premature birth, pregnancy, fetus, gestation. relevance the situation of premature birth and the birth of a small child is the most acute crisis situation in a woman's life and requires timely psychological assistance to a woman in labor in the dyad "mother-small child" [1]. one of the most urgent problems of obstetrics and neonatology is the miscarriage of pregnancy and the birth of children with a low body weight (less than 2500 g) as a result of premature birth or intrauterine fetal development delay. according to who, the proportion of such children among newborns ranges from 5 to 16 %. in developed western countries, the birth of small children is registered in 4-12% of all births, and 20,000 small children are born annually in kazakhstan. perinatal mortality of underweight children is 6-10 times higher than art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 76 that of newborns with normal body weight, and perinatal morbidity is from 70 to 80% and is an important social and economic problem for the state due to the high costs of nursing, rehabilitation and social adaptation of such children [2]. the study of this problem has become especially relevant in connection with the improvement of nursing methods and the transition to new criteria for live birth, when the chance of survival appeared in newborns with a gestational age of 22 weeks [3]. despite the well-known successes achieved in perinatology, the frequency of preterm births does not have a steady downward trend and is 5-9% in developed countries, from 4 to 15% in the regions of russia. the highest rate of premature births is registered in malawi (18.1 per 100 births; 2010), pakistan (15.8), indonesia (15.5), mongolia (13.5). in the central asian region, the preterm birth rates are slightly reduced and amount to 100 cases of childbirth: in tajikistan (10.7), kyrgyzstan (10.4), kazakhstan (8.8), uzbekistan (8.7). the lowest indicator is in latvia (5.3), belarus (4.0) [4.5]. the main criterion for prematurity is the period of pregnancy at the time of delivery and the child's body weight at birth. children born before 38 weeks of pregnancy are considered premature. with a weight of 500 g to 1000 g-such children are considered to be underweight or born with extremely low body weight (elbw). with a body weight from 1001g to 1500g – low-weight or children with low body weight (lbw). if the child's weight is from 1501 g to 2000 g or more than 2000 g, then the child is premature [1]. deeply premature babies cause not only high neonatal morbidity and disability, but are also the main component of reproductive losses [6]. the issues of antenatal differential diagnosis of fetuses with low gestation weight and intrauterine growth retardation syndrome are still controversial. various perinatal outcomes in fetuses that are underweight by the gestation period dictate the need to search for additional diagnostic criteria to identify the causes of low fetal art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 77 body weight (placental, fetal and constitutional) and determine the tactics of managing such a pregnancy [7]. the purpose of research: to study the regional structure and perinatal features of the birth rate of underweight children in the bukhara region. materials and methods. a retrospective analysis of 1,181 medical records of pregnant women hospitalized in the bukhara regional perinatal center from 2018 to 2020 for premature birth was carried out. results and their discussion. the results of the study showed that the highest frequency of birth of small children was in 2018, which was 559 (47.3%), in 2019 – 436 (36.9%) and the lowest indicator was in 2020 – 186 (15.8%), which indicates a tendency to reduce the frequency of premature births over 3 years (fig.1). figure 1. birth rate of small children depending on the age, women in labor were divided into 3 age categories: 17-25 years – 582 (49.2%), 25-35 years – 496 (42.0%), 35 years and more – 104 (8.8%), who made up the smallest number of women in labor (fig.2). 2018 2019 2020 0 100 200 300 400 500 600 2018 2019 2020 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 78 figure 2. distribution of women by age categories the analysis of data on the place of residence revealed the frequent hospitalization of pregnant women living in rural conditions, which amounted to 970 (82%). among all the hospitalized patients, 61 (5.1%) had a related marriage. the study of the level of education of women showed that out of all hospitalized pregnant women 113(9.5%) were with higher education, 1007(85.2%) with secondary education. the level of enlightenment of mothers was of significant importance in postpartum adaptation and maternal-fetal relationships with an underweight child. according to the distribution by gestation period, 34 (2.9%) newborns with extremely low body weight (elbw) were born at 22-27 weeks, the highest frequency of premature births occurred at 28-34 weeks 590 (49.9%) and at 35-37 weeks – 557 (47.2%) births, respectively (fig.3). 17-25 y 25-35 y more than 35 y art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 79 figure 3. the frequency of childbirth by gestation period in the structure of extragenital diseases (egd), the following were predominant: anemia-1114 (94.3%), hypertension of pregnant women – 439 (37.2%), diffuse goiter 361 (30.6%), preeclampsia – 347 (29.3%), pyelonephritis – 75 (6.4%) (fig.4). there were no significant differences between the other nosological forms, which is consistent with the results of other researchers. figure 4. structure of extragenital pathology of women 0 100 200 300 400 500 600 gestational age 22-27 weeks 28-34 weeks 35-37 weeks 0 200 400 600 800 1000 1200 anemia hypertension preeclampsia diffuse goiter pyelonephritis anemia hypertension preeclampsia diffuse goiter pyelonephritis art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 80 in the structure of obstetric pathology, premature detachment of the normally located placenta (pdnlp) was more common 65, prenatal rupture of the fetal membranes (prfm) 189, abnormal fetal location 60, chorionamnionitis 43, failure of the scar on the uterus 93, polyhydramnios 6 and fetal disorders (fetal development delay syndrome of the 2nd degree (fdds)) 27 (fig.5). figure 5. structure of obstetric pathology of women conclusion. thus, based on the results of the study and statistical analysis of the birth histories of small children, it was revealed that premature births occur more often in women who permanently live in rural areas, aged 17 to 25 years, who have mainly secondary education. deficient conditions of pregnant women, such as anemia and diffuse goiter, as well as arterial hypertension and preeclampsia, prevail among egd, which is directly related to the risk of developing obstetric pathology. it is established that the control and prevention of the most common egd depends on the preventive measures of the primary health care system, and the choice of further delivery tactics plays an important role in the formation of a healthy generation and support for the reproductive potential of women in the future. 0 20 40 60 80 100 120 140 160 180 200 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5155178 81 references 1. karpenko a. a. (2015). the specifics of the relationship in the dyad "mothersmall child". bulletin of the bryansk state university, (3), 61-63. 2. ivakhnishina n. m., suprun s. v., s. g. dudukalov, v. p. kargin. results of diagnostics of intrauterine and perinatal infections in premature infants / / bulletin journal-2014. no. 54. pp. 88-97. 3. alyamovskaya g. a., keshishyan e. s., sakharova e. s. (2015). features of the physical development of preterm infants. russian bulletin of perinatology and pediatrics, 60 (4), 11-18. 4. "about global actions regarding preterm birth. born too soon" / / who report. 2014. p. 8-16. 5. g. b. altynbayeva, n. s. bozhbanbayeva, i. m. adilbekova, & s. s. zheksengul (2017). modern ideas about the birth of children with low weight, assessment of their development. bulletin of the kazakh national medical university, (1), 185-188. 6. stasova, yu. v., & tereshchenko, v. a. (2015). health indicators of premature babies born with the help of assisted reproductive technologies. bulletin of medical internet conferences, 5 (5), 367-370. 7. fomina m. p. (2012). cytokine status of amniotic fluid and umbilical cord blood at birth of small children. medical news, (8), 77-80. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080427 3 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080427 4 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080427 5 coronavirus infection and cardiovascular diseases abdukodirova n.m., tulaboeva g.m., saidov kh.kh., fazilbekova z.n. development center of professional qualifications of medical workers under the ministry of health of the republic of uzbekistan abstract: coronavirus pandemic the recently emerged ongoing coronavirus infection (covid-19) pandemic has spread to almost the entire world. with all the severity of the covid-19 problem, mortality rates from this disease cannot be compared with mortality rates from cardiovascular diseases (cvd), which remain the main cause of death of the population. keywords: covid-19, various cc3, chf, ah. literary review covid-19 is especially difficult for older people, most likely because it is they who, as a rule, suffer from various cc3: arterial hypertension (ah), coronary heart disease (ihd), chronic heart failure (chf). therefore, there is reason to believe that the covid-19 pandemic may further increase mortality from cc3. coronary virus infection vascular diseases it has now become apparent that the so-called severe acute respiratory syndrome (sars acute respiratory syndrome), cardiovascular pneumonia associated with it, is the main complication of covid-19, and they are believed to be the cause of death of such patients. this feature has been noted for other viral diseases as well. pneumonia itself can cause a number of cardiovascular complications, even in individuals without cvd [2]. it should be emphasized that in patients with pre-existing cvd, this risk will be significantly higher. unfortunately, to date, there is no clear statistical data on what kind of sick causes covid-19 die, but individual clinical observations indicate that the immediate cause of death may be not only acute respiratory failure, but cardiovascular complications. a meta-analysis of eight studies and> 46,000 patients in china showed that hypertension, diabetes and cardiovascular disease were the most common comorbidities. underlying cardiovascular disease gave the highest chances of any comorbidity to develop severe versus moderate covid-19. hypertension and respiratory illness also increased the risk of developing severe covid-19. patients with cvd had high preexisting mortality rates. mortality rates of covid-19 patients by selected comorbidities. patients with cardiovascular disease are at increased risk of developing covid-19 and should take extra precautions. acute heart damage in covid-19 is manifested by left ventricular (lv) dysfunction, heart failure, ventricular arrhythmias, ecg, increased changes in b-type natriuretic peptide (bnp) and troponin (2,21-23). in the first 41 cases with confirmed covid-19 in chinese patients, acute heart damage, art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080427 6 defined as elevated heart biomarkers with altered dysfunction, was observed in 12% of patients. in a later ecg and left ventricular study, the study found acute heart damage in 19.7% of patients, while in the usa, conducted in 21 as an intensive care patient study; cardiomyopathy was described in 33%. acute heart injury has been independently associated with mortality in hospitalized covid-19 patients in china. pathophysiological theories for heart damage include direct myocardial infection with sars-co-2, myocardial inflammation, takotsubo syndrome, or overwhelming multiple organ disease. while direct transmission of the virus via ace-2 receptors has been postulated, covid-19 myocardium has been histopathological examination of an associated direct infection with sars-cov-2. instead, cardiomyopathies have not been observed, infiltrates with lv dysfunction ace-1 / arb and beta-blockers are shown as the putative pathophysiology of renin-covid-19 imbalance, inflammatory myocardium. for patients of the angiotensin system, indicating their potential therapeutic role. however, much more research is needed to determine the underlying pathophysiology and optimal treatment. the increase in troponin is reflective (mi). the diagnostic value is unclear, as it may be associated with non-coronary conditions, a prognostic marker and may be myocarditis or myocardial infarction, respiratory infections and myocardial infarction type 2. myocardial injury in including acute covid-19 patients may present with st elevations in the absence of obstructive coronary artery disease (cad). whether this is due to microvascular injury or myocarditis is unclear. to avoid unnecessary coronary angiography of the disease, during the acute period, hemodynamically stable patients with covid-19 and possible mi of the patient are best managed conservatively, with invasive procedures delayed until recovery from covid-19. previously, it was shown that viral diseases can destabilize the course of тнес, in particular, in patients with ihd and chf, ruptures of atherosclerotic plaques are observed under the influence of systemic inflammation caused by the virus [3]. that is why it has long been proposed to stabilize drugs capable of atherosclerotic plaques in the complex treatment of patients with a viral infection complicated by sars. these drugs included aspirin, statins, beta-blockers, angiotensin-converting enzyme (ace inhibitor) [3]. systemic inhibitors of inflammation caused by a viral infection also have a procoagulant effect, increasing the likelihood of thrombosis; therefore, treatment with antiplatelet agents was also considered necessary, especially in those patients with coronary artery disease who had previously undergone angioplasty with stenting [4]). all of the above theoretically creates the prerequisites for active cardiovascular drugs in patients with sars caused by a viral infection. however, scientific data on the effectiveness of such treatment is extremely limited. however, it should be mentioned that in 2014, during africa, there was an outbreak of ebola, an attempt was made to treat sars with angiotensin i receptor antagonists (ara) and statins. generics were sent to the epidemic focus of sierra leone. about 100 patients with ebola fever received a art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080427 7 combination of these drugs, after which the doctors of the above drugs were given. noted a significant improvement in their condition. despite the fact that a rigorous controlled study has not been conducted, these data have been published as clinical observations [5]. it has been suggested that blockers of the aldosterone system (paas) may be very promising in the treatment of the current covid-19 pandemic [6]. therefore, the publication of the medical journal, which appeared at the end of february 2020, the authors of which, turning the obvious data on the increased mortality of patients with covid-19 in patients with concomitant drugs, renin-angiotensin-unexpected british attention to cvd, concluded that one of the reasons for this may be taking an ace inhibitor and ara [7]. the cause of the coronavirus is angiotensin-converting enzyme 2 (ace2) to enter the cell. since it has been shown that the use of both ace inhibitors and arbs can significantly increase the production of ace2, these drugs can contribute to a more severe course of covid-19. the authors, however, were rather cautious in the named use, it was concluded that the conclusions recognized that their the assumption about the relationship of coronavirus infection with the intake of ace inhibitors and arbs is only a hypothesis that needs to be confirmed by specially planned studies, and only after that it can be recommended to limit ace inhibitors and arbs for the period of covid-19 disease and replace them with drugs of a different mechanism of action [7]. soon, another publication appeared ј. diaz [8], in which the author, based on the results of a small study of 1099 patients conducted in china [9], indicates that the most severe outcomes of covid-19 were observed in patients with hypertension, coronary artery disease, diabetes mellitus and chronic kidney disease. it is these patients, as ј points out. diaz, have indications for the appointment of acei and ara. note that the original publication does not contain the therapy received with an ace inhibitor and arb. however, ј. diaz concludes that taking ace inhibitors and arbs is one of the risk factors for severe outcomes of covid-19 [8]. unfortunately, the above publications received a wide response both in the media and among practitioners. we already have separate (so far, however, not documented) reports of cancellation of ace inhibitors and arbs in elderly patients with cc3. it is surprising that some communities that, according to evidence, the center for evidencebased oxford medicine, university medicine, hastened to adopt very ambiguous documents, on the one hand, recognizing that there is no real evidence of the harm of ace inhibitors and arbs in patients at risk of getting covid-19, but on the other calling for the abolition of these drugs where cc3 is not very difficult [10]. even a special algorithm has been proposed that determines when and in which patients should be canceled an ace inhibitor or ara in covid-19. if the application is to objectively assess the degree of evidence of the proposed algorithm from the standpoint of evidence-based medicine, then it should be classified as recommendation class i (the proposed algorithm can do more harm than good), and its level of evidence should be art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080427 8 regarded as "c" (expert opinion). ironically, the position expressed by the university of oxford center for evidence-based medicine has just been endorsed in an editorial that appeared in the british medical journal [11]. this article has re-published the algorithm for applying or canceling ara in covid-19. it should be noted by the acei that the above position has just been criticized by the well-known expert in evidence-based medicine g. fitzgerald in an interview with the president of the european society of cardiology v. casadei, where the recommendations were called contradictory. it should also be noted that the publications mentioned above and their positions are a serious criticism of published works. r. sarzani expressed the opinion that "hasty speculations can be dangerous" | 12 |, believing that the binding of the virus to ace2 will result in hyper activation of the raas and an increase in the damaging effect of coronavirus, respectively, on the lungs. drugs that reduce the activity of the raas will weaken this effect. therefore, according to r. sarzani, there is no reason to restrict the use of the above drugs in patients with covid-19. d. gurwitz believes that the competition for receptors between coronavirus and ara has no clinical significance at all lags behind the tactics of using ara in covid-19 as one attempt to improve the condition of patients [13]. the european journal of cardiology has just dedicated a special publication to the topic of whether iz covid-19 inhibitors are needed [14). the main conclusion of the article: based on the existing data, as well as on the proven effect of ace inhibitors and arbs in patients with cvd, including those with comorbid pathology, on mortality rates, therapy with these drugs should be continued in chf, ah, myocardial infarction in modern recommendations, regardless from the presence of covid-19. cancellation of drugs blocking the raas or transfer of patients to drugs of other groups in accordance with clinical requirements is undesirable, since this can increase cardiovascular mortality in patients with severe covid-19. the most fully and objectively, from our point of view, the discussed problem is estimated in the publication of m. vaduganathan et al. [15]. the article notes that the hypothesis on the relationship between the activation of raas by ace inhibitors and ara and the increased risk of covid-19 disease and its complicated course has no clinical evidence. the paper also states that clinical safety effects of drugs affecting the raas in patients with covid-19 are currently underway. cancellation of ace inhibitors and arbs in cvd patients with covid-19, according to the authors, can destabilize their studies. to assess, lead to an unfavorable outcome. the main conclusion of the article: based on the existing data, as well as on the proven effect of ace inhibitors and arbs in patients with cvd, including those with comorbid pathology, on mortality rates, therapy with these drugs should be continued in chf, ah, myocardial infarction in modern recommendations, regardless from the presence of covid-19. cancellation of drugs blocking the raas or transfer of patients to drugs of other groups in accordance with clinical requirements is undesirable, since this can increase cardiovascular mortality in patients with severe covid-19. the most art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080427 9 fully and objectively, from our point of view, the discussed problem is estimated in the publication of m. vaduganathan et al. [15]. the article notes that the hypothesis on the relationship between the activation of raas by ace inhibitors and ara and the increased risk of covid-19 disease and its complicated course has no clinical evidence. the paper also states that clinical safety effects of drugs affecting the raas in patients with covid-19 are currently underway. cancellation of ace inhibitors and arbs in cvd patients with covid-19, according to the authors, can destabilize their studies. to assess, lead to an unfavorable outcome until reliable clinical status and clinical data are obtained, the authors believe, there is no reason to change cvd therapy in patients with covid-19, and even more so in commas in patients at risk of this disease. the professional communities did not remain aloof from the discussed problem. thus, the council of the european society of certain medical cardiologists on hypertension issued a special statement in which it noted that hypertensive patients are strongly advised to continue taking their usual antihypertensive therapy, since there is no clinical evidence, an ace inhibitor or that ara treatment should be discontinued due to covid 19 [15). thus, we note that medicine has more than once encountered the fact that hypotheses based on pathophysiological data, speculating on separate, not always wellstudied mechanisms of action that do not have strict clinical confirmation, lead to erroneous conclusions. attempts to introduce unproven hypotheses into medical practice can have unpredictable consequences. all this may fully be related to calls to cancel ace inhibitors and aras when they show signs of covid-19, drugs that have saved the lives of millions of people with cvd. cancellation of these drugs in patients with severe cc3 under conditions of increased load on the heart caused by infectious diseases, from our point of view, can lead to catastrophic consequences. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080427 10 references 1. russian statistical yearbook. moscow: rosstat; 2019 (in russ.) [russian statistical yearbook. m: rosstat; 2019]. 2. yu c.m. cardiovascular complications of severe аcute respiratory syndrome. postgrad med j. 2006; 82: 140-4. doi: 10.1136 / pgmj.2005.037515. 3. xiong t.y., redwood s., prendergast b., chen m. coronaviruses and cardiovascular system: acute and long-term complications. eur doi: 10.1093 / eurheartjehaa231. 4. libby p., simon d.l. inflammation and thrombosis: the clot thickens. circulation. 2001; 103: 1718-20. heart j. 2020; doi: 10.1161 / 01.cir.103.13.1718. 5. fedson d.s., rordam o.m. testing ebola patients: a "bottom up" approach using generic statins and angiotensin receptor blockers. int j infect dis. 2015: 36: 80-4. 6. fedson d.s., opal s., rordam o.m. hiding in plain sight: an approach to treating patients with severe covid-10 infection. mbio. 11: e00398-20. doi: 10.1128 / mbio.00398-20. 7. sommerstein r., grani c. rapid response: re: preventing a covid-19 pandemic: ace inhibitors as a potential risk factor for fatal covid-19. vm. 2020; 368: m810. 8. diaz j.h. hurothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe covid-19. j travel med. 2020 mar 18.pi: taaa041. doi: 10.1093 / jtm / taaa041. 9. guan w., ni z., liang w., et al. clinical characteristics of coronavirus disease in china. n engl med. 2020, february 28. doi: 10.1056 / meјmoa2002032. 10. aronson j.k., ferner r.e. angiotensin converting enzyme inhibitors and angiotensin receptor blockers in covid19 [cited by april 14, 2020]. available from: https://www.cebm.net/covid19/angiotensin-converting-enzyme-ace-inhibitors-and-angiotensin-receptor-blockers-incovid-19 /. 11. aronson j.a., ferner r.e. drugs and the renin-angiotensin 2020; 369: m1313. doi: 10.1136 / bmj.m1313. 12. sarzani r. relationship between covid-19 and rennin-angiotensinaldosterone-system blockers: hasty speculations may be dangerous. bmj. 2020; 368: m810. 13. gurwitz d. angiotensin receptor blockers as tentative sars-cov-2 therapeutics. drug disc res. system in covid-19. 2020. doi: 10.1002 / ddr.21656. 14. kuster g., pfister o., burkard t., et al. sarscov2: should inhibitors of the renin-angiotensin system be withdrawn in patients with covid-19? eur 20. нeart 2020 mar pi: ehaa235. doi: 10.1093 / eurheartj / ehaa235. 15. vaduganathan m., vardeny o., michel t., et al. renin-angiotensin-aldosterone system inhibitors in patients with covid-19. n engl j med. 2020 mar 30. doi: 10.1056 / nejmsi2005760. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5843266 1 art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5843266 2 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5843266 3 view of the quality of the life in ankylosing spondiloarthritis pulatova shakhnoza bakhtiyarovna tashkent medical academy abstract: ankylosing spondylitis (as) is a chronic systemic inflammation of the joints, mainly of the spine, with limitation of its mobility due to ankylosis of the apophysal (synovial intervertebral) joints, the formation of syndesmophytes (bridges between the vertebrae) and calcification of the spinal ligaments. the study of the quality of life of patients with as is especially relevant, since the main features of rheumatic diseases are a chronic progressive course leading to dysfunction of the musculoskeletal system and disability. all these factors give them the character of social diseases, which reduce the biological, physiological and psychological activity of members of society. keywords: spondyloarthritis; ankylosing spondylitis; the quality of life. the quality of life is the most important social category that characterizes the structure of human needs and the possibility of meeting them [1]. with regard to medicine, the quality of life is an integral characteristic of the physical, psychological, social and emotional state of a patient, assessed based on his subjective perception. according to the who definition, the quality of life is the perception by individuals of their position in life in the context of the culture and the system of values in which they live, in accordance with goals, expectations, norms and concerns [2]. the quality of life is determined by the physical, social and emotional factors of a person's life that are important to him and affect him. the quality of life is the degree of a person's comfort both within himself and within his society. the quality of life of patients with as is primarily due to the degree of functional impairment, which is associated with the nature and level of spinal lesions [3]. as is characterized by late diagnosis, which, according to literature data, is 510 years late, which leads to early disability. according to a number of authors, from art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5843266 4 34 to 81% of patients are partially or completely disabled [4]. components of quality of life health-related quality of life is based on 3 main components: physical sphere: rest and sleep; feeling of physical pain and discomfort; vitality, energy and fatigue; the ability to carry out daily activities; ability to work study, work, etc .; mobility; dependence on drugs in treatment. social sphere: personal relationships; practical social support; sexual activity, financial resources; medical and social assistance; opportunities to acquire new information and skills; opportunities for good rest and entertainment; climate; transport. psychological sphere: positive and negative emotions; thinking, learning, memory and concentration; self-esteem; appearance, religious beliefs [5]. the physical sphere in as is characterized by pronounced medical and socio-economic consequences. the onset of the disease at a young age, its steady progression with ankylosis of the spine and large joints, loss of the ability to carry out important activities for the patient and loss of professional independence, significant difficulties in performing simple everyday motor skills all these are severe consequences of the disease [6]. pain is the main symptom of this disease along with deformity joints and impaired mobility. it is the severity of pain the syndrome has a significant impact on the quality of life of patients with joint pathology, and can cause various emotional disorders, sleep disorders and pain behavior. majority as patients, first of all, expect from treatment a decrease in pain syndrome in comparison with other manifestations of the disease. vital activity changes also occur in patients with as. they become less active due to the present pain and stiffness in the joints, they quickly get tired when doing everyday activities. therefore, after the detection of this disease, patients have to significantly change their usual way of life. sometimes you even have to change the place of work, profession [7]. as the disease progresses, the affected joints become all less mobile up to complete ankylosis, which is also essential changes the patient's lifestyle and art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5843266 5 significantly affects his emotional and the physical state. as is quite common all over the world. it is characterized by chronic inflammation, which, without appropriate treatment, leads a person to disability, a significant reduction in life expectancy and a significant deterioration in its quality. as is among the most expensive in the treatment of diseases. in the absence of timely diagnosis and active therapy, the patient becomes disabled within the first 5 years from the onset of the disease. this disease is of high social importance [8]. as can affect up to half a million russians. and given that it is mainly young active people who suffer from it, that is, the future of the country, the problem is acquiring a more general, socio-economic character. as the disease progresses, the appearance of a person with as begins to change: the patient's spine becomes either even, devoid of physiological bends, or resembles a question mark due to increased cervical lordosis and thoracic kyphosis. because of this, isolation and self-doubt may appear, which in the future can lead to impaired socialization and the development of healthy interpersonal relationships [9]. uncertainty leads to a deterioration in the quality of life of patients with as and significant psychosocial problems etiopathogenesis of the disease, frequent inconsistency of clinical manifestations diseases of the severity of as, the need for constant intake of drugs, insufficient therapeutic efficacy of the drugs used [10]. in this case, the patient's personality changes both as a result of the direct effect of the disease and as a result of the patient's psychological experience of his condition, which is reflected in a decrease in self-esteem and self-confidence, dissatisfaction with his lifestyle, the development of anxiety, hostility, anger and depression. it is the personal aspect of the reaction to the disease that underlies the formation of a specific internal picture of the disease, which can significantly transform the clinical picture of the disease and have a significant negative impact on the effectiveness of therapeutic measures [11]. these problems are central to the phenomenon of the so-called "internal picture of the disease." a long-term disease can lead to various restructuring of the internal art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5843266 6 picture of the disease associated with the characteristics of the course of the disease and with complex processes of adaptation and maladjustment [12]. inadequate internal picture of the disease is mediated negatively affects the course and outcome of the disease, promotes destructive changes in the patient's personality, the development of internal conflicts of various plan, severe neurotic disorders, maladaptive types of reactions to illness that aggravate the picture of organic suffering, its course and duration, and, as a rule, worsen the behavior of patients in relation to ongoing therapy [13]. thus, as has a significant effect on all spheres of the patient's life, leads to a significant decrease in the patient's quality of life, limiting not only the functional, but also the psychological component, contributes to the formation of social maladjustment [14]. references 1. erdes sh.f., badokin v.v., bochkova a.g. and others. on the terminology of spondyloarthritis. scientific and practical rheumatology. 2015; 53 (6): 657-60. 2. smolen j.s., schöls m, braun j, et al. treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. ann rheum dis. 2018 jan; 77 (1): 317. doi: 10.1136 / annrheumdis-2017-211734. 3. van der heijde d, ramiro s, landew o r, et al. 2016 update of the asseular management recommendations for axial spondyloarthritis. ann rheum dis. 2017 jun; 76 (6): 978-991. doi: 10.1136 / annrheumdis-2016-210770. 4. amirjanova v.n., koylubaeva g.m. methodology for assessing the quality of life in practice of a rheumatologist. scientific and practical rheumatology. 2003; 41 (2): 72-6. 5. jani m, dixon w.g., chinoy h. drug safety and immunogenicity of tumor necrosis factor inhibitors: the story so far. rheumatology (oxford). 2018 nov 1; 57 (11): 1896-1907. doi: 10.1093 / rheumatology / kex434. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5843266 7 6. lapshina s.a., dubinina t.v., badokin v.v., et al. tumor necrosis factor α inhibitors in the treatment of axial spondyloarthritis, including ankylosing spondylitis. scientific and practical rheumatology. 2016; 54 (1s): 75-9. 7. rudwaleit m, van der heijde d, landewe r, et al. the development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part ii): validation and final selection. ann rheum dis. 2009 jun; 68 (6): 777-83. doi: 10.1136 / ard.2009. 108233. epub 2009 mar 17. 8. rudwaleit m, van der heijde d, landewe r, et al. the assessment of spondyloarthritis international society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. ann rheum dis. 2011 jan; 70 (1): 25-31. doi: 10.1136 / ard.2010. 133645. epub 2010 nov 24. 9. van der linden s, valkenburg ha, cats a. evaluation of diagnostic criteria for ankylosing spondylitis. a proposal for modification of the new york criteria. arthritis rheum. 1984 apr; 27 (4): 361-8. 10. taylor w, gladman d, helliwell p, et al. classification criteria for psoriatic arthritis: development of new criteria from a large international study. arthritis rheum. 2006 aug; 54 (8): 2665-73. 11. garrett s, jenkinson t, kennedy lg, et al. a new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. j rheumatol. 1994 dec; 21 (12): 2286-91. 12. lukas c, lendew r, sieper j, et al. development of an ass-endorsed disease activity score (asdas) in patient with ankylosing spondylitis. ann rheum dis. 2009 jan; 68 (1): 18-24. doi: 10.1136 / ard.2008.094870. 13. calin a, garrett s, whitelock h, et al. a new approach to defining functional ability in ankylosing spondylitis: the development of the bath ankylosing spondylitis functional index. j rheumatol. 1994 dec; 21 (12): 2281-5. 14. akulova ai, gaidukova iz, rebrov ap. validation of the 5l version of the eq-5d questionnaire in russia. scientific and practical rheumatology. 2018; 56 (3): 351-5. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 125 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 126 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 127 clinical and radiological assessment of the dental implantation technique in patients with complete absence of teeth using the dicom program. dustmatov j.e. 1 , makhkamova f.t. 2 , gulyamov s.s. 2 1tashkent state dental institute 2tashkent pediatric medical institute corresponding author: pulatabilov1985@mail.ru abstract. according to data from various regions of uzbekistan, patients with a complete absence of teeth (pod) are encountered for the first time in the 45-49 age group. by 2020, the number of patients with poi in uzbekistan will exceed 15 million people, and then among our adult fellow citizens every five years, this number is expected to increase by 3-5%.during follow-up (6-18 months) after prosthetics, signs of peri-implant mucositis in the form of hyperemia, edema were observed in the area of 4 out of 100 (4.00%). such patients were prescribed traumeel s. during the study of suppuration, the presence of ulcerations, fistulas, pain was not noticed, and complaints of these manifestations were absent, the phenomena of mucositis could be quickly stopped. no cases of peri-implantitis were diagnosed. radiographically vertical bone atrophy, i.e. the appearance of peri-implant pockets was not detected. insignificant horizontal atrophy was observed in 2 implants by the end of 18 months (2.00%) and averaged 0.62 ± 0.13 mm. in the control group (39 patients), 39 complete removable prostheses were made, supported by 98 implants. during follow-up (6-18 months after prosthetics), signs of peri-implant mucositis in the form of hyperemia and edema were observed in the area of 8 implants (8.10%). at the same time, loosening was determined in 4 of them (4.08%). during the study, no suppuration, the presence of fistulas, or pain was detected. there were no complaints about these manifestations. the phenomena of mucositis could be quickly stopped. but it should be added that 1 case of peri-implantitis was diagnosed in this group. conclusions. the loss of bone tissue in the main group was at the level of 0.54 ± 0.21 mm, while in the control group it was 0.74 ± 0.32 mm. moreover, foreign studies have shown that in the presence of 3 implants, bone loss ranged from 0.5 ± 0.46 mm to 0.7 ± 0.76 mm. keywords: dicom program; complete absence of teeth; peri-implantitis; mucositis; implants; dental computed tomography introduction. according to data from various regions of uzbekistan, patients with a complete absence of teeth (cat) are encountered for the first time in the 4549 age group. at the age of 55-59 years, every fourth surveyed has the named pathology, and for the age of 65-69 years this figure is already 42.8%. the overall prevalence of complete absence of teeth for different regions of our country ranges from 8.2 ± 0.46 to 9.3 ± 0.67. by 2020, the number of patients with cat in uzbekistan will exceed 15 million people, and then among our adult fellow citizens every five years, this number is expected to increase by 3-5%. abroad, the number of patients with cat in the united states is 27 million, and although the reduction in the prevalence of cat is declared a major medical goal mailto:pulatabilov1985@mail.ru art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 128 in the united states, according to forecasts for the first 3-5 decades of the 21st century, this prevalence will grow steadily [5, 12, 23, 27, 30 , 38]. according to some foreign authors, cat occurs already in patients aged 34 years [1, 2, 4, 8, 14, 25, 31]. in modern conditions, patients with cat have every opportunity to abandon conventional removable prostheses in favor of non-removable prosthetic structures supported by implants. the manufacture of implant-supported dentures can significantly improve the chewing function and improve the quality of life of patients with pop. the use of complete removable dentures with implant fixation in comparison with conventional removable prosthetics increases patient satisfaction with the results of treatment by more than 2 times. satisfaction of patients with cat also significantly increases after conditionally removable and fixed prosthetics [6, 11, 13, 17, 20-22, 28, 33, 34, 36,35]. thus, dental implantation can be considered not only one of the most promising options for orthopedic treatment of patients with pop, but also considered as the basis for effective orthopedic treatment and improving the quality of life of this category of patients [3, 7, 15, 19, 24, 29, 32, 39]. as you know, the installation of any implants requires increased attention and absolute accuracy from the implantologist. the lack of a clear planning of the placement of implants in the bone tissue, their installation depending only on the clinical situation, which is assessed only visually on the basis of our own clinical experience and x-ray data, can lead to incorrect implant placement. however, in dental implantation, ct examination itself without specialized software and 3-d modeling is not informative enough [9,10,16,18,26,37,40]. there are various computer programs that allow the planning and placement of implants with a predetermined result with the presence of parallel suprastructures. one of these programs is dicom (implant-assistant). the low quality of life of patients, especially those with complete loss of teeth, against the background of a relatively high frequency of complications that occur after the installation of dental implants, confirms the postulate that there is still a shortage of methods with a high efficiency of choice of tactics and sequence of orthopedic treatment of this pathology, indicating on the relevance of this study. purpose of the study. to evaluate the effectiveness of using the dicom program in patients with complete absence of teeth according to the data of dental computed tomography at the stage of the dental implantation technique. materials and research methods. in total, we examined 80 patients with complete loss of teeth, of which 29 were men, 51 were women. the age of the patients was 51-66 years (mean age 58.5 ± 4.5 years). implant prosthetics was carried out at the department of advanced training of prosthetic dentistry tgsi. implants from osstem implant (south korea) were used. all patients were divided into 2 groups: group 1 (main) 41 patients, of whom 14 were men, 27 women (mean age 56.7 ± 4.2 years), group 2 (control) 39 patients were included 15 men, 24 women (mean age 59.5 ± 4.7 years). patients were separated by simple randomization. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 129 all patients signed written consent to participate in the study. research methods. 1. clinical included a standard technique, which consisted of examination, examination of the oral cavity. clinical evaluation included determination of the severity of gingival recession, the severity of the implant, bleeding of the periimplant cuff, inflammation, the level of oral hygiene and prostheses. 2. x-ray performed using a dental computed tomograph planmeca promax 3d. her data were used using the dicom program to assess anatomical and topographic landmarks, the risks of surgical intervention and planning for implant insertion. x-ray examination was performed before implantation, 6 months after the prosthetics 1. statistical carried out using the methods of variation statistics of the student-fisher test. research results. in the main group (41 patients), 41 complete fixed prostheses were made, supported by 100 implants. before the operation, plaster models of the jaws were obtained and fixed in an asa dental articulator using a facial arch. in the dental laboratory, a wax composition with artificial polymer teeth (before the surgical template) was prepared, an individual template-spoon made of transparent plastic for the subsequent impression of the prosthetic bed during the operation with simultaneous registration of the central ratio. fig. 1. planning dental implantation using the dicom program. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 130 according to the obtained x-ray template, a surgical template was made using the dicom program (fig. 2). fig. 2. carrying out an operation using a surgical template fig. 3. template fixed with a screw to the implants art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 131 fig. 3. template fixed with a screw k during observation (6-18 months) after prosthetics, signs of peri-implant mucositis in the form of hyperemia, edema were observed in the area of 4 out of 100 (4.00%). such patients were prescribed traumeel s. during the study of suppuration, the presence of ulcerations, fistulas, pain was not noticed, and complaints of these manifestations were absent, the phenomena of mucositis could be quickly stopped. no cases of peri-implantitis were diagnosed. radiographically vertical bone atrophy, i.e. the appearance of peri-implant pockets was not detected. insignificant horizontal atrophy was observed in 2 implants by the end of 18 months (2.00%) and averaged 0.62 ± 0.13 mm. in the control group (39 patients), 39 complete removable prostheses were made, supported by 98 implants. the preliminary prosthesis was fixed on the day of taking the impression using transitional elements temporary support heads made of titanium alloy, having been carefully previously carefully finished, ground and polished implants. fig. 4. temporary support heads fixed to implants. since these patients did not undergo dental computed tomography using the dicom program, and the results were assessed only using an orthopantomogram, the patients were prescribed antibiotic therapy for 5-7 days (ampiox 250 mg, 1 table 3 times a day), nsaids (ketorol pro ) to reduce soft tissue edema. the sutures were removed on day 14 by removing the prosthesis and washing the implant shafts with antiseptic solutions. during follow-up (6-18 months after prosthetics), signs of peri-implant mucositis in the form of hyperemia and edema were observed in the area of 8 implants (8.10%). at the same time, loosening was determined in 4 of them (4.08%). during the study, no suppuration, the presence of fistulas, or pain was detected. there were no complaints about these manifestations. the phenomena of mucositis could art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 132 be quickly stopped. but it should be added that 1 case of peri-implantitis was diagnosed in this group. conclusions. the loss of bone tissue in the main group was at the level of 0.54 ± 0.21 mm, while in the control group it was 0.74 ± 0.32 mm. moreover, foreign studies have shown that in the presence of 3 implants, bone loss ranged from 0.5 ± 0.46 mm to 0.7 ± 0.76 mm. these values are comparable to those obtained by us in the main group. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5533441 133 references. 1. a method of quantifying overall satisfaction of complete denture patients / y. sato [et al.] // j oral rehabil. – 2000. – № 27. – р. 952-957. 2. a new treatment concept for rehabilitation of the edentulons mandible. preliminary results from a prospective clinical follow-up study / p.-i. 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616. 39. patient satisfaction versus retention of implant overdentures with two attachment systems: a randomized trial / r. f. de albuquerque [et al.] // clin. implant dent. relat. res. – 2018. – № 21. – р. 21-31. 40. patient-reported outcome measures of edentulous patients restored with implant-supported removable and fixed prostheses: a systematic review / c. j. yao [et. al.] // clin. oral implants res. – 2018. – № 29(16). – p. 241-254. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 103 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 104 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 105 comparative characteristics of healing of afthous stomatitis in experiment akbarov a.n., ziyadullaeva n.s., irismetova b.d. tashkent state dental institute republic of uzbekistan abstract. the work is based on the results of experimental studies on the usage of a new form of heprocel medication. the experiment has used outbred white rats, which were divided into 2 groups: control and experimental. in the experimental group of animals, heprocel powder was applied to the surface of an artificially induced traumatic ulcer. the developed method for local protection of traumatic lesions of the oral mucosa with heprocel made it possible to shorten the regeneration time of the erosive process and the period of complete regression of inflammatory changes. keywords: heprocel, treatment of aphthous stomatitis, regeneration of the oral mucosa. introduction. aphtha is a focal deep fibrinous inflammation of the oral mucosa, proceeding according to the artyus phenomenon, resulting in more or less pronounced destruction of the epithelium, and sometimes the underlying connective tissue part of the mucous membrane [6, 7]. the application of new treatment regimens for local inflammatory appears to be interesting, innovative and promising. it practices manifestations in the oral cavity through the development of differentiated principles of therapy, taking into account the pathogenetic and morphological mechanisms of the erosive process of the oral mucosa, the characteristics of the course and development of recurrence of hras [1, 2, 8, 9, 10]. however, the use of most drugs gives a short-term effect with the manifestation of discomfort in the form of a burning sensation and side effects, such as exacerbation of gastric ulcer and duodenal ulcer, leukopenia, anemia, and skin rash [3, 4, 5]. objective of the study: experimental and morphological substantiation of the effectiveness of a new local method for the treatment of aphthous stomatitis. material and methods. in the experiments were used 61 outbred white rats of different sex weighing 220-290 grams. the control group of rats included 32 individuals, experimental 29. the animals were kept in clean, spacious cages. rooms for animals are equipped with ventilation and air conditioning, constant lighting. the nutrition was balanced with the inclusion of a sufficient amount of proteins, carbohydrates, vitamins. after the ulcer formation, the animals were provided with a diet of non-coarse food to reduce pain. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 106 daily monitoring of the condition of the animals consisted of examining the oral cavity, washing the area of the formed ulcer in the control group with water (2.0 ml), and in the experimental group, after washing with water, an implant in the form of heprocel powder was applied with the formation of a gel on the surface of the ulcer. the animals were weighed. general condition, mobility, nutrition and physiological functions were assessed. all operations were carried out in accordance with the rules adopted by the european convention for the protection of vertebrate animals used for experiments or other scientific purposes (ets n 123), strasbourg, 03/18/1986. removal from the experiment was carried out by inhalation of an increased dose of halothane vapor. terms of withdrawal from the experiment: 1 hour, 12 hours, 1 day, 3, 5, 7, 14, 21, 30 days. the proposed method for the formation of a chronic ulcer is as follows: a chronic ulcer of the oral mucosa is formed by applying filter paper circles moistened with 50% acetic acid to the oral mucosa, characterized in that standard 3x3 mm circles are applied from the side of the lower lip mucosa and fixed with a special holder a clip of the appropriate size, allowing for fixation in a certain place with a force of 50-100 kpa, and also to prevent dilution of the concentration of the active agent by the separating saliva. the model of such a formation of an ulcer in the oral cavity in a rat makes it possible to cause a lesion with the development of a local aphthous lesion of the mucous membrane, which provides a more comprehensive study to assess the effectiveness of topical application of various agents. in the experimental group of animals, starting from 3 days after exposure to the surface of the aphthous ulcer, the powder "heprocel" (finely dispersed) was applied with the formation of a gel due to the secretion of the salivary glands. the gel has good adhesion to necrotic tissues, therefore, application is sufficient for 1 minute. treatment of the ulcer with a wound dressing with the formation of a gel was carried out daily at the same time. heprocel is a bio-soluble, biodegradable polymer implant with hemostatic properties, manufactured by turon silk. release form powder. physicochemical characteristics of the finished product "нeprocel": at t 20°c solubility in water 10 g/l, soluble in water, insoluble in most organic solvents. melting point 220°c. stable at ph 5-7. it hydrolyzes quickly in an alkaline environment, more stable in an acidic environment. the next stage of the study was a morphological assessment of changes in the oral mucosa in experimental animals during the formation of an aphthous ulcer and the dynamic processes of its reparation. tissue samples were fixed in 10% formalin solution in phosphate buffer. paraffin sections were stained with hematoxylin and art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 107 eosin. light-optical micrographs were obtained with an axioscop 40-zeiss microscope, coupled with a digital camera. all micrographs were processed and data saved on a computer using microsoft-windows xp-professional software. to assess the adhesion of the cover for use in the oral cavity, we took into account the following circumstances: to determine the optimal type and consistency of the coating for better adhesion to the wound surface of the oral mucosa; to study the adhesion and durability of the coating depending on the phases of wound healing; to study the rate of dissolution of the coating under the conditions of washing with liquid or enzyme solutions. results. the results of treatment in the experimental group of rats showed that on the 3rd day after exposure, an aphthous ulcer was detected, formed on the mucous membrane of the lower lip with indistinct contours, undermined edges. on the 5th day, treatment was started, the heprocel powder was applied to the area of aphthous ulcer of the mucous membrane of the lower lip to form a gel on the surface of the ulcer (fig. 1). on the 7th day of the experiment, the ulcer is covered with a fibrin film, has a fairly clear border, signs of inflammation with subsiding, granulation tissue is visible under the fibrin film (fig. 2). fig. 1. the experimental rats on the 5th day of the experiment. field mucosa of the lower lip aphthous ulcers coated powder "нeproсel" to form a gel on the fig. 2. the experimental rats on the 7th day of the experiment. ulcer is covered with a fibrin film has enough clear boundary. signs of inflammation from subsiding. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 108 ulcer surface. granulation tissue viewed under a fibrin film. at the same time, a finely dispersed powder "heprocel" was again applied to the area of the formed aphthous ulcer with the formation of a gel on the surface of the ulcer (fig. 3). on the 14th day, complete healing of the oral mucosa was determined after the formation of an acetate ulcer and treatment with a gel coating of cellulose derivatives (fig. 4). fig. 3. experienced rat on the 7th day. on the region formed aphthous ulcer re-applied fine powder "нeproсel" to form a gel on the ulcer surface. fig. 4. experienced rat on the 14th day of treatment. complete healing of the mucosa of the oral cavity after formation of ulcers acetate and treatment with the gel coating of cellulose derivatives. thus, experimental studies on the formation of chronic aphthous ulcers in the oral cavity showed that, in the absence of specific treatment, regression of the inflammatory process begins only by 10-14 days of observation with complete epithelialization by 30 days, in turn, the local application of the powder form of the drug "heprocel" with the subsequent formation of a gel on the surface of the ulcer already 2 days after the start of therapy (on the 7th day of the experiment) leads to the activation of the reparative process with the formation of granulation tissue under the fibrin film and complete healing of the mucous membrane by 14 days. analysis of histological changes during the formation and healing of experimental aphthous ulcers in rats showed that 12 hours after the start of the art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 109 experiment, it was determined that the stratified squamous epithelium was thinned, the mucous membrane was degraded, the lamina propria was edematous with elements of necrosis, the muscle layer was edematous with degradation, the glands were numerous (fig. 5). after 36 hours, degradation of the epidermis and stratified squamous epithelium was already noted, the lamina propria was with necrotic masses, the glands were degraded, the striated muscles were edematous and dissociated (fig. 6). on the third day, the same pattern persisted (fig. 7). further, in the control group of animals, the healing process was characterized by the following picture on the 5th day. the stratified squamous epithelium was eroded in places, the epidermis was altered, the papillae were smoothed, the mucous membrane with elements of degradation and necrosis, the lamina propria is edematous with elements of necrosis, the muscle layer is edematous with degradation, and few glands are degraded. in dynamics, on the 7th day, an actually equivalent picture was determined (fig. 8). fig. 5. micrograph of an aphthous ulcer of the oral mucosa in rats 12 hours fig. 6. micrograph of aphthous ulcer of the oral mucosa in rats, 36 hours art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 110 fig. 7. micrograph of aphthous ulcer of the oral mucosa in rats on the 3rd day of the experiment. fig. 8. micrograph of the rat lip mucosa in the control group of animals: the beginning of the healing process on the 7th day on the 14th day, signs of the onset of regression of the inflammatory process were determined, the epidermis was modified, the papillae were high, the stratified squamous epithelium was edematous, the mucous membrane with elements of degradation and necrosis, the lamina propria edematous with elements of necrosis, the muscle layer was edematous with degradation, the glands were numerous degraded (fig. 9). on the 21st day, cleansing of necrotic masses was noted, but signs of edema of the epithelium, fibroelastic and muscle tissue, and the glands were partially degraded (fig. 10). by the 30th day, complete restoration of the structure of the tissues of the mucous membrane, the absence of signs of degradation, the glands are numerous, the vessels with blood filling. fig. 9. micrograph of the rat lip mucosa in the control group: the healing process on the 14th day. fig. 10. micrograph of the mucous membrane of the lip of a rat in the control group of animals: the healing process on day 21 in the main group of animals in the study of the morphology of the proposed interaction with the coating surface of the wound in the space between them is marked formation of thrombotic masses. in the experimental group animals 1 day after exposure of the powder surface aphthous ulcers "нeproсel" formed film adheres to the wound surface. the epithelial layer is composed of stratified squamous epithelium, which places thinned, the epidermis is modified, papillae smoothed art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 111 mucosa with elements degradation and necrosis, lamina propria of the mucosa with edematous necrosis elements muscular layer edematous with degradation few gland degraded (fig. 11). subsequently on day 7 of the experiment and 2 hours after application of the powder "нeproсel" morphological pattern of interaction with the surface of the ulcer gprs characterized in that the formed film is subjected to fragmentation in the abutment zone defined clusters of blood cells. high epithelium, lamina propria mucosa forms a high papillae, striated muscle slightly swollen in the submucosa mucosal side lips are numerous glands, ducts their associated with the mucosal surface. there was a significant reduction in signs of inflammation, necrotic changes actually determined (fig. 12). fig. 11. micrograph of the mucous lip of the rat in the experimental group of animals: 1 day after exposure to the surface of the aphthous ulcer of the powder "нeprocel" fig. 12. micrograph of the mucous lip of the rat in the experimental group of animals: on the 7th day after exposure to the surface of the aphthous ulcer of the powder "heprocel" art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 112 fig. 13. micrograph of the mucous lip of the rat in the experimental group of animals: on the 14th day after exposure to the surface of the aphthous ulcer of the powder "heprocel" fig. 14. micrograph of the mucous membrane of the rat lip in the experimental group of animals: on the 21st day after exposure to the surface of the aphthous ulcer of the powder "heprocel" on the 14th day after exposure to the surface of the aphthous ulcer of the powder "heprocel", only small areas were determined after the fragmentation of the applied coating. the epithelial layer consists of stratified squamous epithelium, the lamina propria forms papillae, the striated muscles are slightly edematous, numerous glands are located in the submucosa of the mucous part of the lip, their excretory ducts are lined with stratified squamous epithelium and are connected to the mucosal surface. there are no phenomena of degradation, necrosis and inflammation, complete repair of the ulcer. (fig. 13). on the 21st day after exposure to the surface of the aphthous ulcer of the "heprocel" powder, only unchanged tissue was determined. complete repair of the ulcer (fig. 14). аnalyzes and discussions. thus, the model of the formation of an aphthous ulcer of the oral mucosa in rats according to our modified method allows the formation of a chronic ulcer of the mucous membrane in the area of the lower lip and gums. already 20 minutes after exposure, you can trace visual changes in the mucous membrane in the form of darkening of tissue color and edema. after 3 hours, the affected area has a dark color and clearly differs from the surrounding healthy tissue. after 12 hours, an ulcerative necrotic crater forms on the surface of the mucosa with necrotic tissues and detritus along the periphery of the ulcer. after 1 day, the formed mucosal defect has undermined edges with necrotic plaque and tissue edema. starting from 3 days after exposure, the ulcer looks like a chronic one, covered with fibrin, the edges are edematous, distinct. there are no signs of granulation. in the control group of animals, the healing process is delayed up to 3 weeks with a gradual rejection of necrotic masses, the formation of a fibrin film and epithelialization starting from the edges of the ulcer. complete healing of the ulcer can be traced to 30 days after exposure. in the experimental group of animals, the research results showed that the gel on the surface of the ulcer visually lasts for 2-3 hours, then covers the ulcer in the form of a transparent, barely perceptible thin film tightly adhered to the surface of the ulcer, a faster relief of the inflammatory process with epithelization of the surface is noted ulcers within 2 weeks of exposure. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 113 conclusions. comparative studies of various forms of the domestic drug "нeprocel" with the formation of a gel coating on the surface of a chronic aphthous ulcer of the oral mucosa in rats showed that, depending on the phase of the wound process, the fixation resistance and the strength of the gel structure change, with the best performance achieved when using fine powder in phase of necrotic changes. the study of the morphological features of the interaction of the proposed coating with the wound surface of the oral mucosa showed that the heprocel powder has a good adhesive ability, adheres tightly to the wound surface, a decrease in the inflammatory process and the beginning of repair is noted already from the second day after application with complete restoration of signs of degradation of cell structures and regression their edema and necrosis by 14 days of the experiment and, accordingly, 7 days of treatment. the developed method of local protection of aphthous lesions of the oral mucosa in conjunction with a systemic approach to the treatment of stomatitis made it possible to shorten the regeneration time of the erosive process and the period of complete regression of inflammatory changes. references. 1. akbarov a.n., ziyadullaeva n.s., irismetova b.d. chronic recurrent aphthous stomatitis: modern approaches to treatment (literature review). rehealth journal. 2021; 2(10): р. 196-203. 2. akbarov a.n., ziyadullaeva n.s., irismetova b.d. chronic recurrent afthous stomatitis. modern treatment approaches (review article). european science 2021. no 4 (60): р: 35-41 3. marco a peres and al. oral diseases: a global public health challenge. lancet. 2019 https://doi.org/10.1016/s0140-6736(19)31146-8 4. queiroz siml, silva mvad, medeiros amc, oliveira pt, gurgel bcv, silveira éjdd. recurrent aphthous ulceration: an epidemiological study of etiological factors, treatment and differential diagnosis. an bras dermatol. 2018;93(3):341-346. doi:10.1590/abd1806-4841.20186228. 5. fitzpatrick sg, cohen dm, clark an. ulcerated lesions of the oral mucosa: clinical and histologic review. head neck pathol. 2019;13(1):91-102. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5762446 114 6. shah k, guarderas j, krishnaswamy g. aphthous stomatitis. ann allergy asthma immunol. 2016;117:341-343. 7. hamedi s, sadeghpour o, shamsardekani mr, amin g, hajighasemali d, feyzabadi z. the most common herbs to cure the most common oral disease: stomatitis recurrent aphthous ulcer (rau). iran red crescent med j. 2016;18:e21694. 8. edgar nr, saleh d, miller ra. recurrent aphthous stomatitis. j clin aesthet dermatol. 2017;10(3):26-36 9. esma kürklü gürleyen, kadriye peker, gülsüm ak. the evaluation of oral health related quality of life in patients with recurrent aphthous stomatitis. yeditepe dental journal. 2018; 14(3):91-96. 10. cardoso ja, et. al. salivary alpha-amylase enzyme. рsychological disorders, and life quality in patients with recurrent aphthous stomatitis. int j dent 2017; 2017:5269856. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 9 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 10 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 11 comparative analysis of separate results of arthroplasty for aseptic necrosis of the femoral head akramov vohid rustamovich bukhara state medical institute, bukhara, uzbekistan abstract. objective: improving the results of arthroplasty in aseptic necrosis of the femoral head (anfh). materials and methods: we studied the quality of life of patients according to the scale developed by us; we examined patients before and after treatment in 172 patients. the patients were of working age from 20 to 65 years old. in this system, 6 clinical parameters were used on a 5-point scale, the clinical result was assessed by the analysis of the sum of points. results: analysis of the results of surgical treatment of patients with anfh showed the prevalence of the proportion of good results in patients of the main group in 45 (82.6%) cases versus the control group 40 (73%) and a decrease in unsatisfactory results to 1 (1%) case in patients of the main group against the control 2 (3%). keywords: separate results, endoprosthetics, aseptic necrosis of the femoral head. introduction. aseptic necrosis of the femoral head is one of the most pressing problems of modern orthopedics, which leads to severe pain syndromes, limited joint function, significant economic costs and increased mortality [1, 2, 8, 9, 10, 12]. clinical and radiological signs of degenerative-dystrophic diseases of large joints are found in 55 65% of cases in people over 60 years old and in about 80% of people over 75 years old. many authors have proven that early diagnosis, complex and specific treatment of anfh, depending on the stage of the disease, are the key to successful treatment and reduce complications [3, 4, 5, 6, 7, 11]. as studies of recent years show, anfh is a polietiologic disease, with a large role playing, general and local factors of them: trauma, alcohol intoxication and those taking steroid drug therapy [13, 15, 16, 17, 18, 19, 21]. the authors describe in patients who have suffered fractures of the femoral neck and traumatic dislocation of the femoral head in the near and long-term, anfh art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 12 develops. these patients have obstruction of the blood vessels feeding the femoral head, which leads to degenerative-dystrophic changes characteristic of anfh [14, 20, 22, 23, 24, 25, 26]. materials and methods. we studied the quality of life of patients according to the scale developed by us; we examined patients before and after treatment in 172 patients. the patients were of working age from 20 to 65 years old. in this system, 6 clinical parameters were used on a 5-point scale, the clinical result was assessed by the analysis of the sum of points. results. according to our assessment of the quality of life, good results were in the range from 15 to 22 points, satisfactory from 8 to 14; unsatisfactory was assessed by the sum from 0 to 7 points. summarizing the scores obtained, we evaluated the effectiveness of the treatment and presented them as a percentage, which reflected the difference between the post-treatment increase in the score. we took the initial state of the patient as 100%. after surgery, an increase in the score of up to 30% of the initial patient scores before surgery was noted (table 1). table 1 criteria for assessing the quality of life of patients with anfh pain function emotion al percepti on necessity of means of rehabilitatio n and support, (orthoses, cane) ability to walk / perform an action with the upper limb gait disorder / ability to lift and carry weights poin ts no no restrictio ns enthusias m no no restriction s norm 5 transient weak transient weak transient weak transient weak transient weak transient weak 4 weak restrictio n in precise moveme nts satisfacti on brace limited minimal cosmetic disturbance s 3 transient transient transient transient transient transient 2 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 13 moderate moderate moderate moderate moderate moderate moderate partial incapacit y acceptabl e one cane or crutch a housewife maximum cosmetic, minimum physical difficulties 1 significa nt complete inability unaccept able two canes or crutches need for outside help absent 0 to study the results of treatment, comparative immediate results of treatment were carried out in patients with anfh before and after 1 month. after surgical treatment. comparative results of treatment in patients with anfh before and 1 month after surgical treatment (table 2). table 2 criteria for assessing the quality of life of patients with anfh criteria for evaluation before treatment (n = 110) patients after treatment, one month later (n = 110) patients the main control the main control pain 1 1,0 2,5 2,0 function 1,5 1,5 2,5 2,0 emotional perception 1,5 1 1,5 1,5 the need for rehabilitation and support (orthoses, cane) 1,0 1,0 2,5 2,5 the ability to walk / perform an action with the lower limb 1,5 1,5 2,5 2,0 gait disorder / ability to lift and carry weights 1,5 1 2,5 2 points total 8 7 14 12 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 14 from table 2 it can be seen that before the operation, that in anfh patients before the operation, pain was noted in the main group, 1 points, in the control group, 1 points. after the operation, one month later, it became 2.5 points in the main and 2 points in the control. before the operation, the patients had impaired mobility function of varying severity after the operation, the dysfunction recovered before the operation in the main group, 1.5 points and the control group were also 1.5 points. after the operation, one month later, it became 2.5 points in the main group and 2 points in the control group. before the operation, the patients had emotional perception in the main group, it was 1.5 and the control group was also 1.0 points. after the operation, one month later, it became 1.5 points in the main group and 1.5 points in the control group. before the operation, the patients had a need for means of rehabilitation and support, (orthoses, canes) in the main group, 1.5 points were noted, and in the control group, they were also 1.0 points. after the operation, one month later, it became 2.5 points in the main group and 2.5 points in the control group. before the operation, the patients had an insignificant ability to walk, to perform the action with the upper limb before the operation in the main group, 1.5 points were noted and in the control group, also 1.5 points. after the operation, one month later, it became 2.5 points in the main group and 2 points in the control group. before the operation in patients, the ability to lift and carry weights before the operation in the main group was 1.5 and the control group was also 1.0 points. after the operation, one month later, it became 2.5 points in the main group and 2 points in the control group. the average score before treatment in the main group was 8, in the control group. after the treatment, it became the main group of 14, and in the control group 12 points. the presence of persistent pain was the main indication for surgery in both groups; after surgical treatment, pain decreased most in the main group compared to the control group, which shows a good efficacy of surgical treatment of hip joint. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 15 we present the comparative results of treatment in patients with anfh after treatment at 3.6 months and one, two years (table 3). table 3 comparative results of treatment in patients with anfh after surgical treatment criteria for evaluation 3 months 6 months 1 year 2 year the main cont rol the main cont rol the main cont rol the main cont rol pain 3 2,5 3,5 3 4 3 4,0 4,0 function 3 2,5 4 3,0 4,0 3 4 4,0 emotional perception 3 3 3 3 3 4,0 4 3 the need for rehabilitation and support (orthoses, cane) 3,0 3 3,5 3,0 4 4 4 4 the ability to walk / perform an action with the lower limb 2,5 2 3 3 3 2,5 3,0 3,0 gait disorder / ability to lift and carry weights 2,5 2 3 2,0 3 2,5 3,0 3,0 points total 17 15 20 17 21 19 22 21 table 3 shows that in patients after surgery, pain was noted in the main group: after 3 months 3, 6 months 3.5, 1 year 4 and 2 years 4 points. in the control group: after 3 months 2.5, 6 months 3.0, 1 year 3 and 2 years 4 points. after the operation, dysfunction was observed in the main group: after 3 months 3, 6 months 3.5, 1 year 4 and 2 years 4 points. in the control group: after 3 months 2.5, 6 months 3.0, 1 year 3 and 2 years 4 points. after the operation, the patients had emotional perception in the main group: after 3 months 3, 6 months 3.0, 1 year 3 and 2 years 4 points. in the control group: after 3 months 3.0, 6 months 3.0, 1 year 4 and 2 years 3 points. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 16 after the operation, the patients noted the need for rehabilitation means and support (orthoses, canes) in the main group: after 3 months 3.6 months 3.5, 1 year 4 and 2 years 4 points. in the control group: after 3 months 3.0, 6 months 3.0, 1 year 4 and 2 years 4 points. after the operation, the patients had the ability to walk, perform an action with the upper limb, emotional perception in the main group: after 3 months 2.5, 6 months 3.0, 1 year 3 and 2 years 3 points. in the control group: after 3 months 2.0, 6 months 3.0, 1 year 2.5 and 2 years 3 points. after the operation, the patients had a gait disorder, the ability to lift and carry weights in the main group: after 3 months 2.5, 6 months 3.0, 1 year 3 and 2 years 3 points. in the control group: after 3 months 2.0, 6 months 2.0, 1 year 2.5 and 2 years 3 points. the average score before treatment in the main group: after 3 months 17, 6 months 20.0, 1 year 21 and 2 years 22 points. in the control group: after 3 months 15.0, 6 months 17, 1 year 19 and 2 years 21 points. from these data, we can say that in patients in the postoperative period after 6 and 12 months, there is an improvement in the results of treatment: a decrease in pain, deformity and an increase in the amplitude of joint movement and an improvement in limb function (table 4). table 4 results according to the scale developed by us scale score основная группа контрольная группа количество больных good 45 (82,6%) 40 (73%) 85 (77%) satisfactory 9 (16,4%) 13 (24%) 22 (20%) unsatisfactory 1 (1%) 2 (3%) 3 (3%) total 55 (100%) 55 (100%) 110 (100%) table 4 shows that in patients with anfh, good results were obtained in the main group in 45 (82.6%), in the control group in 40 (73%). satisfactory in the main group in 9 (16.4%), in the control group in 13 (24%). unsatisfactory in the main art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 17 group in 1 (1%), in the control group in 2 (3%). compared to the main and control groups, the results of treatment after arthroplasty in the main group are good results 82.6%, in the control group 73%, these data show the effectiveness of surgical treatment in the main group. conclusion. the use of the developed method of hip arthroplasty in anfh against the background of severe osteoporosis promoted good integration of the prosthesis with the bone, leading to an improvement in the functional capacity of the joint and lengthening the life of the endoprosthesis. analysis of the results of surgical treatment of patients with anfh showed the prevalence of the proportion of good results in patients of the main group in 45 (82.6%) cases versus the control group 40 (73%) and a decrease in unsatisfactory results to 1 (1%) case in patients of the main group against the control 2 (3%). references: 1. akramov v.r. features of hip arthroplasty in case of anatomical disorders of the acetabulum // "bulletin of the association of doctors of uzbekistan" uzbekistan, tashkent № 3 2011, pages 94-97. [in russian] 2. akramov v.r. some problems of hip joint replacement previously operated on. // “bulletin of the association of doctors of uzbekistan” uzbekistan tashkent № 2 2011, pp. 110-113. [in russian] 3. akramov v.r.,akhmedov sh.sh., khamraev b.u.(hip replacement in femoral neck fractures) // "problems of biology and medicine" uzbekistan, samarkand no. 3 2017 (96), pp.23-26 [in russian] 4. akramov v.r., sh.sh., khamraev a.sh., khamraev b.u. – (total hip replacement and prevention of possible complications) // "a new day in medicine” uzbekistan. tashkent, no.4 (20) 2017, pp.56-58. [in russian] 5. akramov v.r., akhmedov sh.sh., khamraev a.sh., khamraev b.u. (hip replacement in degenerative-dystrophic diseases in adults) // "bulletin of the association of doctors of uzbekistan” uzbekistan, tashkent no. 2 2018, pp.42-44. [in russian] art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5634147 18 6. sh.sh.akhmedov, a.sh.khamraev, v.r.akramov, b.u.khamraev, a.a.teshaev, a.u. gaffarov the arthroplasty of the hip at fracture of a neck of a femur // “a new day in medicine "uzbekistan.tashkent, no. 1 (25) 2019, pp. 5-7. 7. v.r.akramov,b. a.sh.khamraev, sh.sh.akhmedov, b.u.khamraev the arthroplasty of the hip at fracture of a neck of a femur // european journal of business & social sciences., issn: 2235-767x.,volume 07 issue 05., may 2019. 8. v.r.akramov, b.a.sh.khamraev, sh.sh.akhmedov, b.u.khamraev // prevention of possible complications before and after total endoprotesization of the combin) european journal of business & social sciences., issn: 2235767x.,volume 07 issue 05., may 2019. 9. bu khamraev, bp akramov. program for expressing the method of treatment by the method of blocking intramedullary osteosynthesis for a fracture of the femur // certificate of official registration of a computer program. agency for intellectual property of the republic of uzbekistan. 2019. 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s. vaidyanathan, y. murugan, k. paulraj// case rep. orthop. – 2013. – vol. 2013. – p. 313289. 26. vascularized fibular grafts in patients with avascular necrosis of femoral head: a systematic review and meta-analysis/ t. fang, e.w. zhang, f.c. sailes// arch orthop trauma surg. – 2013. – vol. 133(1). – p. 1–10. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 168 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 169 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 170 histological structure of the rat spleen in early postnatal ontogenesis dilnoza akhrorovna khasanova phd, associate professor of the department of anatomy, clinical anatomy (osta) of bukhara state medical institute named after abu ali ibn sino, bukhara, uzbekistan e-mail: akwamarin80@gmail.com abstract: on total sections of the spleen by the 21st day, the area occupied by the white pulp also increases, the absolute number of lymphoid nodules with reproduction centers increases to 31.4 ± 2.1 and the marginal zone of periarterial lymphoid couplings thickens. in the centers of reproduction of lymphoid nodules on an area of 2500 sq. during this period, the number of blasts increases 15.0 ± 1.1 and average lymphocytes to 16.9± 2.3. on total sections of the spleen, white pulp occupies 49.1± 1.5% of the total area of the histological section. the proportion of lymphoid nodules with breeding centers increases 2.1 times, equal to 34.3 ±1.9 in absolute numbers compared to the control. keywords: histology, spleen, early postnatal ontogenesis, lymphoid nodes. 1. introduction 1.1. the relevance of the problem. the spleen is an organ of immunogenesis and lymphopoiesis, in which antigen-dependent differentiation of immunocompetent cells occurs, the formation of effector cells and memory cells, as well as the elimination of obsolete and damaged hematopoietic cells [10]. it has a complex anatomical structure of immunocompetent white pulp, including periarterial lymphoid couplings, lymphoid nodules with germinative centers, periarterial, mantle and marginal zones. this structure creates favorable conditions for effective cooperative interaction of cells involved in the immune response [1,2]. a population of immunocompetent cells usually has distribution mechanisms in specific functional areas of the spleen. understanding the immunomorphological properties of this organ can be used in the diagnosis of pathological processes of immune genesis [6,8]. mailto:akwamarin80@gmail.com art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 171 white and red pulp form reticular tissue, which plays an important role in the stratification of each functional zone [7]. dendritic cells of the spleen can contribute to the escape of the tumor from immune surveillance [7,9]. the organs of the immune system are the main homeostatic and regulatory organs for the internal environment of the body. the spleen is an important and the largest peripheral organ of the immune system [3,4]. the spleen is the largest secondary lymphoid organ, at the fetal stage it also performs the role of hematopoiesis. it acts as a blood filter, and also acts as a storage place for iron, erythrocytes and platelets [5]. knowledge of prenatal ontogenesis of the spleen will help to understand the mechanisms of pathology in the organ and create methods of diagnosis and prevention [7,9,10]. 2. the results of the study. outside, the spleen of newborn baby rats is covered with a capsule consisting of thin connective tissue. trabeculae containing arteries and veins extend from the capsule deep into the spleen. the study of the cellular composition of the white pulp of newborn baby rats showed the following picture: the width of the germinal center averaged -55.6 ± 0.74 microns. the width of the periarterial zone is on average 27.8 ± 0.18 microns. fig. 1.the spleen of a newborn rat. ihc. 10 x 20. 1white pulp, 2lymph node, 3trabeculae, 4 spleen capsule. in a third of the total number of nodules, mantle and marginal zones can be distinguished. the width of the mantle zone averaged 69.6±1.09 microns. the width of the marginal zone is on average 38.2 ± 1.65 microns. 1 2 3 4 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 172 the white pulp is formed mainly from lymphocytes at various stages of maturation. there are small, medium and large lymphocytes. the thickness of the capsule at the gate averaged -4.70±0.34, at the front end it averaged 6.2±1.15 microns, at the rear end it averaged 5.5±0.14 microns. the diameter of the trabecula in the proximal part averaged 11.8±0.12, and in the distal part it averaged 8.7 microns. the depth of the trabecula averaged 12.1±0.17 microns. the relative area of the white pulp is on average -24.6 ± 0.6%. the relative area of the red pulp averaged 75.4±0.1%. fig.2. the spleen of a newborn rat. hematoxylin-eosin staining. 10x10. 1lymphoid follicle, 2red pulp, 3spleen capsule the number of lymphoid follicles (lf) without breeding centers averaged 2.3± 0.37, and with a breeding center averaged 7.3± 0.1. the size of the lf is on average 40.4± 0.2 microns. the distance between the marginal zone of the lf was on average 24.6 ± 0.15 microns, the distance between the germinal centers is on average 42.1 ± 0.19 microns the study of the trabecular vessels of newborn rats in the proximal part showed that the thickness of the venous wall averaged 3.13±0.37 microns, the inner diameter of the vein was on average 5.8±0.1 microns, the thickness of the artery wall averaged 4.3±0.07, the inner diameter of the artery was on average -5.0±0.12. the thickness of the venous wall of the trabecular vessel in the distal part was on average 2.5±0.32, the inner diameter of the vein averaged 4.7±0.2 microns, the thickness of the arterial wall averaged 3.4± 0.02, the internal diameter of the artery is on average 3.87 ± 0.04. the wall thickness of the venule of the pulpary vessel was on average 2 ± 0.12 microns, the inner diameter of the venule was on average 3.6 ± 0.7, the wall thickness of the arteriole was on average 2.6± 0.42, and its inner diameter was on average 2.7± 2 1 3 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 173 0.02 microns. the wall thickness of the lymphoid follicle venule is on average 1.4 ± 0.08, the inner diameter is on average 3.5 ± 0.12. the wall thickness of the lymphoid follicle arteriole was on average 1.3 ± 0.1, and the inner diameter of the lf arteriole is on average 2.7± 0.31 microns. the study of the cellular composition of the white pulp of 6-day-old baby rats showed the following picture: the width of the germinal center averaged 64.1 ± 0.6 microns. the width of the periarterial zone is on average 32.3 ±0.12 microns. the width of the mantle zone averages 71.9±1.12 microns. the width of the marginal zone was on average 43.6±1.2 microns. the thickness of the capsule at the gate was on average -5.54± 0.31, at the front end on average this value was equal to 6.7± 0.12 microns, at the rear end it averaged 5.8± 0.37. the diameter of the trabecula in the proximal part is on average 13.1 ± 0.33, and in the distal part on average 9.7 ± 0.52 microns. the depth of the trabecula averages 15.4±0.72 microns. the relative area of the white pulp is on average 22.8 ± 0.41%. the relative area of the red pulp averaged 76.81±0.15%. the number of lymphoid follicles (lf) without breeding centers averaged 3.2 ±0.1, and with a breeding center averaged 8.73. the lf dimensions were equal to an average of 50.0 microns. the distance between the marginal zone of the lf averaged 25.1 microns, the distance between the germinal centers averaged 48.3 microns. the study of the trabecular vessels in the proximal part showed that the thickness of the venous wall averaged 3.7 microns, the inner diameter of the vein was 6.4 microns on average, the thickness of the artery wall averaged 4.81, and the inner diameter of the artery averaged -5.44. the trabecular vessel in the distal part had the following values: the thickness of the venous wall was on average 2.75, the inner diameter of the vein was on average 4.9 microns, the thickness of the arterial wall was on average 3.7, the inner diameter of the artery was on average 4.1. the wall thickness of the venule of the pulpary vessel is on average 2.38 microns, the inner diameter of the venule was on average 4.1, the wall thickness of the arteriole was on average 2.7, and its inner diameter was on average 2.9 microns. the wall thickness of the lymphoid follicle venule is on average 1.5, the inner diameter is on average 3.4. the wall thickness of the lymphoid follicle arteriole was on average 1.4, and the inner diameter of the lf arteriole is on average 2.8 microns. the width of the germinal center of 11-day-old rats was on average 68.1±0.2 microns, and the periarterial zone was on average 35.8±0.4 microns. the width of the mantle zone averages 77.3±2.2 microns. the width of the marginal zone is on average 46.6 ± 1.21 microns. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 174 the thickness of the capsule at the gate was on average -6.28 ± 0.14, at the anterior end on average this value was equal to 8.84 microns, at the posterior end it averaged 7.21. the diameter of the trabecula in the proximal part is on average 13.4, and in the distal part on average 10.01 microns. the depth of the trabecula averaged 21.0 microns. the relative area of the white pulp was on average 22.5±0.2%. the relative area of the red pulp averaged 77.4±0.13%. the number of lymphoid follicles (lf) without breeding centers averaged 2.5, and with a breeding center averaged 9.2. the size of the lf is 57.6 microns on average. the distance between the marginal zone of the lf averaged 24.3 microns, the distance between the germinal centers was 55.8 microns on average. the study of the trabecular vessels in the proximal part showed that the thickness of the venous wall averaged 4.3 microns, the inner diameter of the vein was 6.6 microns on average, the thickness of the artery wall averaged 5.1, and the inner diameter of the artery averaged -5.7. the trabecular vessel in the distal part had the following values: the thickness of the venous wall was on average 3.1, the inner diameter of the vein was on average 5.5 microns, the thickness of the arterial wall was on average 4.0, the inner diameter of the artery was on average 4.9. the wall thickness of the venule of the pulp vessel averaged 2.5 microns, the inner diameter of the venule averaged 4.61, the wall thickness of the arteriole was on average 3.1, and its inner diameter was on average 3.3 microns. the wall thickness of the lymphoid follicle venule is on average 1.6, the inner diameter is on average 4.1. the wall thickness of the lymphoid follicle arteriole was on average 1.7, and the inner diameter of the lf arteriole was on average 3.1 microns. the study of the cellular composition of the white pulp of 16-day-old baby rats showed the following picture: the width of the germinal center is on average 77.0 ± 0.3 microns. the width of the periarterial zone averaged 40.6±0.7 microns. the width of the mantle zone averages 82.4±4.2 microns. the width of the marginal zone is on average 52.6 ± 1.3 microns. the thickness of the capsule at the gate was on average -5.9 ± 0.2, at the anterior end on average this value was 11.5 microns, at the posterior end it averaged 9.7. the diameter of the trabecula in the proximal part is on average 14.0, and in the distal part on average 10.6 microns. the depth of the trabecula averaged 21.4 microns. the relative area of the white pulp is on average 22.8 ± 0.4%. the relative area of the red pulp averaged 77.3±0.2%. the number of lymphoid follicles (lf) without breeding centers averaged 2.5, and with a breeding center averaged 8.12. the lf dimensions were equal to an art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 175 average of 63.9 microns. the distance between the marginal zone of the lf averaged 24.3 microns, the distance between the germinative centers averaged 63.5 microns. the study of the trabecular vessels in the proximal part showed that the thickness of the venous wall averaged 5.2 microns, the inner diameter of the vein was on average 6.8 microns, the thickness of the artery wall was on average 5.5, the inner diameter of the artery was on average -6.4. the trabecular vessel in the distal part had the following values: the thickness of the venous wall was on average 3.4, the inner diameter of the vein was on average 5.8 microns, the thickness of the arterial wall was on average 4.2, the inner diameter of the artery was on average 5.3. the wall thickness of the venule of the pulpary vessel averaged 2.5 microns, the inner diameter of the venule averaged 5.12, the wall thickness of the arteriole is on average 3.1, and its inner diameter was on average 3.7 microns. the wall thickness of the lymphoid follicle venule is on average 1.7, the inner diameter is on average 4.3. the wall thickness of the lymphoid follicle arteriole was on average 1.82, and the inner diameter of the lf arteriole is on average 3.12 microns. the study of the cellular composition of the white pulp of 21-day-old baby rats showed the following picture: the width of the germinal center was on average 80.4 ± 0.4 microns. the width of the periarterial zone averaged 41.8±0.7 microns. the width of the mantle zone averaged 85.6±2.7 microns. the width of the marginal zone was on average 54.8±1.4 microns. the thickness of the capsule at the gate was on average -7.14±0.17, at the front end on average this value was equal to 13.9 microns, at the rear end it averaged 13.2. the diameter of the trabecula in the proximal part is on average 15.5, and in the distal part on average 11.4 microns. the depth of the trabecula averaged 21.8 microns. the relative area of the white pulp was on average 24.9±0.52%. the relative area of the red pulp averaged 75.2±0.23%. the number of lymphoid follicles (lf) without breeding centers averaged 2.13, and with a breeding center averaged 8.8. the size of the lf was 77.6 microns on average. the distance between the marginal zone of the lf was on average 24.6 microns, the distance between the germinative centers was on average 66.4 microns the study of the trabecular vessels in the proximal part showed that the thickness of the venous wall averaged 5.73 microns, the inner diameter of the vein was on average 7.33 microns, the thickness of the artery wall averaged 6.33, and the inner diameter of the artery averaged -7.12. the trabecular vessel in the distal part had the following values: the thickness of the venous wall averaged 3.7, the inner diameter of the vein averaged 6.3 microns, the thickness of the arterial wall averaged 4.6, the inner diameter of the artery averaged 5.6. the wall thickness of the venule art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 176 of the pulpary vessel averaged 2.9 microns, the inner diameter of the venule averaged 5.13, the wall thickness of the arteriole averaged 3.5, and its inner diameter averaged 4.5 microns. the wall thickness of the lymphoid follicle venule is on average 1.9, the inner diameter is on average 4.3. the wall thickness of the lymphoid follicle arteriole was on average 2.1, and the inner diameter of the arteriole is on average 3.4 microns. 3. discussion and conlcusions. in the early postnatal ontogenesis of the rat spleen, the surface layers develop faster, then the ratio changes and subsequently the growth of the middle and deep layers is observed. the greatest rate of increase in the thickness of trabeculae was observed up to the 21st day of age by 1.3 times. the decrease in the thickness of the capsule and the trabecula of the thymus depends on age. the greatest decrease in the thickness of the capsule is observed on the 11th day, trabeculae on the 21st day. on total sections of the spleen by the 21st day, the area occupied by the white pulp also increases, the absolute number of lymphoid nodules with reproduction centers increases to 31.4 ± 2.1 and the marginal zone of periarterial lymphoid couplings thickens. in the centers of reproduction of lymphoid nodules on an area of 2500 sq. during this period, the number of blasts increases 15.0 ± 1.1 and average lymphocytes to 16.9± 2.3. on total sections of the spleen, white pulp occupies 49.1± 1.5% of the total area of the histological section. the proportion of lymphoid nodules with breeding centers increases 2.1 times, equal to 34.3 ±1.9 in absolute numbers compared to the control. in the centers of reproduction of lymphoid nodules on an area of 2500 microns, the number of blasts reaches up to 19.6 ± 0.8, the number of macrophages is 3.4 ± 0.4. in the deep part of the periarterial lymphoid couplings, the number of plasmocytes and small lymphocytes reaches maximum figures. in the splenic cords, the maximum number of plasmocytes, small lymphocytes and macrophages is noted, compared with the control. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558698 177 references [1] ahrorova, k. d. (2021). morphofunctional properties of the lymphoid structures of the spleen in norm and under the influence of various factors. academicia: an international multidisciplinary research journal, 11(1), 459465. [2] ahrorovna, k. d., &jumaevich, t. s. (2018). topografic-anatomical features of lymphoid structures of the small intestine of rats in norm and against the backround of chronic radiation diseases. european science review, (9-10-2). [3] akhrorovna, k. d. medical field morphological features of human and mammalian spleen in postnatal ontogeny. journalnx, 7(1), 252-256. [4]ahrorovna, k. d. (2020). effect of a genetically modified product on the morphological parameters of the rat’s spleen and thymus.european journal of molecular and clinical medicine, 7(1), 3364-3370. retrieved from www.scopus.com [5] ahrorovna, k. d. (2021). evaluation of the effect of a genetically modified product on the morphological parameters of the spleen of experimental animals. academicia: an international multidisciplinary research journal, 11(1), 885888. [6] balogh p., horvath g., szakal a.k. immunoarhitecture of distinct reticular fibroblastic domains in the white pulp of mouse spleen. j. histochem. cytochem. 2004; 52 (1287): 98. [7] khasanova, d. a. (2021). morphofunctional changes in thymus gland of rats effected by genetically engineered crops. in advanced research: problems and new approaches (pp. 120-125). [8] khasanova, d. (2020). wirkung eines gen-modifizierten produkts auf die morphologischen parameter der strukturen der milz weißer ratten. interconf. [9] khasanova, d. a., &asadova, n. k. (2021). morpho functional changes in thymus of white rats in acute stress. academicia: an international multidisciplinary research journal, 11(1), 685-691. [10] khasanova, d. a., &teshaev, s. j. (2018). topografic-anatomical features of lymphoid structures of the small intestine of rats in norm and against the backround of chronic radiation diseases. european science review, (9-10-2), 197-198. volume-1 issue-1 art of medicine international medical scientific journal 1 art of medicine international medical scientific journal volume-1 issue-1 2 art of medicine international medical scientific journal volume 1, issue 1, may 2021 volume-1 issue-1 art of medicine international medical scientific journal 3 founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine international medical scientific journal chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen art of medicine international medical scientific journal volume-1 issue-1 4 content tursunova l. d., jabbarov o. o. application of sakabutril/valsartan in patients with chronic kidney disease with type 2 diabetes mellitus...............................5 l.s. khamraeva., d.u. narzullaeva features of calculating the optical power of an intraocular lens in children with congenital cataracts at the risk of developing pseudomyopic myopia.....................10 kasimova m. s., iminova m. m., ashurov o. m. ophthalmologic complications in the structure of the clinical features of novel coronavirus infection (covid-19)......................................................................................................14 fattayeva d.r., rizayev j.a., rakhimova d.a. improvement of methods for correction of clinical and immunological disorders in comorbid state of chronic gaymoritis after covid-19....................................................................17 polatova d.sh., abdukarimov kh.g., davletov r.r., savkin a.v., sultanov b.b features of immunobiological heterogeneity in patients with osteosarcoma.................................................................................25 volume-1 issue-1 art of medicine international medical scientific journal 5 application of sakabutril/valsartan in patients with chronic kidney disease with type 2 diabetes mellitus tursunova laylo dilshatovna, jabbarov ozimbay otaxonovich tashkent medical academy, tashkent, uzbekistan abstract chronic kidney disease (ckd) is a generalized term that indicates damage to the renal tissue, regardless of the etiology of the underlying disease. ckd develops in every second patient with diabetes mellitus (dm) and significantly limits the duration and quality of life. ckd is diagnosed by the level of glomerular filtration rate (gfr), which is recognized as the most fully reflecting the number and total volume of nephrons. the article presents data on disturbances of the excretory and filtration functions of the kidneys, as well as lipid metabolism in patients with chronic kidney disease. the experience of the clinical use of sacubitril / valsartan in patients of this category is presented in order to study their functional state of the kidneys. the patients were divided into two groups. the first group of patients during the treatment took sacubitril / valsartan 200 mg / day, the second group valsartan 160 mg / day. the functional state of the kidneys and heart was assessed on the basis of clinical and laboratory parameters. on the 30th day of treatment, these parameters were monitored. the positive effect of this combination on some biochemical parameters, blood lipid spectrum and renal function was noted. key words: сhronic kidney disease, diabetes mellitus, diabetic nephropathy, glomerular filtration rate, natriuretic peptide. introduction in 2002, the national kidney foundation, in order to unify approaches to the diagnosis and treatment of kidney diseases, proposed calling chronic kidney disease (ckd) structural and functional changes in the kidneys lasting 3 months or more, regardless of what diseases caused them. [15]. ckd also includes a decrease in the glomerular filtration rate (gfr) of less than 60 ml / min per 1.73 m2, which persists for 3 months or more, even if there are no other markers of kidney damage [13]. the fundamental difference between the concept of chronic kidney disease and chronic renal failure is the inclusion in this category of patients, including those with a normal functional state of the kidneys. the concept was quickly recognized in the world [5]. the prevalence of ckd in romania (60 969 people aged 18 and over were examined) is 7% [8], in the united states among the population aged 20 and over 12% [14]; higher figures are also given, in particular for the united states, which largely depends on the assessment methodology [16]. overall, it is likely that about 10% of the world's adult population has ckd. in patients with arterial hypertension, the prevalence of ckd is significantly higher and amounts to 27.5% [11]. ckd occurs in different age groups, and the frequency naturally increases with age. thus, in the united states, among the population over the age of 65, the frequency of only stage iii ckd (gfr 30-59 ml / min per 1.73 m2) is 36.1%; while 38.6% of them have a serum creatinine level less than 1.2 mg / dl (<106 μmol / l) [12], which confirms the opinion about the need to focus not on the serum creatinine level, but on gfr [9]. the leading causes of end-stage renal failure requiring replacement therapy are diabetes mellitus, arterial hypertension and glomerulonephritis [10]. the frequency of development of dn closely depends on the duration of the disease, with a maximum peak in the period from 15 to 20 years of the course of diabetes. according to the state register of dm, the prevalence of dn is on average about 30% in type 1 diabetes (t1dm) and type 2 dm (t2dm) [1,2]. according to the literature, the earliest laboratory marker of renal dysfunction is hyperfiltration, i.e. increased glomerular filtration rate (gfr). it develops in the first months after the onset of diabetes and can persist for several years. in subsequent years, art of medicine international medical scientific journal volume-1 issue-1 6 with persisting hyperglycemia, structural restructuring of the kidneys begins: the basement membrane of the glomeruli (bmc) thickens, the volume of the mesangium increases. scientific studies have shown that the first changes in the mesangium appear in the area of the glomerulus knob, where the maximum gradient of intraglomerular hydrostatic pressure is formed [6]. as a result, the integrity of the bmc is disrupted and microalbuminuria (mau) occurs the first laboratory marker of diabetic nephropathy. in the future, the accumulation of remarkable structural changes leads to the formation diffuse glomerulosclerosis, which is usually accompanied by the development of proteinuria and a decrease in gfr. at the final stage of structural changes, nodular glomerulosclerosis is formed, the clinical equivalent of which is decreased gfr, azotemia [7]. gfr takes on a progressive course 4-5 years after the onset of chronic kidney disease (ckd) with a decrease in gfr to 5.9-6.2 ml / min / year. during the first 3 years, the rate of gfr decline remains significantly lower (gfr 2.8-3.4 ml / min / year, p <0.05). in patients with ckd, direct correlations were established between indicators of tubular dysfunction and the main parameters of disease progression gfr, daily proteinuria, and serum creatinine levels. correlation analysis revealed a high inverse degree of correlation between creatinine and total protein (p <0.05), urea and total protein; as well as creatinine, urea and serum albumin [3]. diabetic nephropathy develops for a wide variety of reasons. but of all the variety of mechanisms of development of dn, the most studied and proven are: metabolic (hyperglycemia, hyperlipidemia) and hemodynamic (activation of the renin-angiotensin-aldosterone system, renal arterial hypertension). according to the literature and numerous studies, it was found that blockers of the renin-angiotensin-aldosterone system are more effective in reducing albuminuria compared to placebo or other antihypertensive drugs in patients with diabetic and nondiabetic nephropathy, cvd, and are also effective in preventing microalbuminuria. in recent years, natriuretic peptides have also been used in experimental studies to achieve the same results. they play an important role in the activation response of the renin-angiotensin-aldosterone system. natriuretic peptides are physiological antagonists of angiotensin ii in relation to stimulating the secretion of aldosterone, enhancing sodium reabsorption and increasing vascular tone. besides, atrial natriuretic peptide (anp) enhances venous permeability, causing the liquid portion of plasma to move into the extravascular space (reduced preload) and reduce the tone of the sympathetic nervous system (effect on afterload). the main stimulus for increased anp secretion is atrial volume overload and increased myocardial tension. among the new drugs actively developed by pharmaceutical companies that affect the kidneys by normalizing cardiac activity is the combined drug sacubitril / valsartan (uperio). the use of this drug is positioned with an increase in natriuresis, followed by a moderate decrease in blood pressure as a consequence of the effect on the natriuretic peptide and the renin-angiotensin aldosterone system. normally, atrial natriuretic peptide binds to a specific set of receptors: a, b, and c (anp receptors). aand b-receptors are responsible for the main actions of the hormone, and c-receptors are located inside cells, where, by binding to anp, they reduce its effect. the attachment of an agonist to these receptors causes a decrease in circulating blood volume and systemic arterial pressure. in this case, activation of lipolysis and a decrease in sodium reabsorption in the renal tubules are observed. the effect of atrial natriuretic peptide is opposite to that of the renin-angiotensin system. according to the literature, this drug also has a nephroprotective effect [4]. thus, the most important point that determines the tactics of managing patients with ckd is the recognition of diabetes as an independent risk factor for the development of this complication. patients with diabetes are classified as high / very high risk ckd. accordingly, patients with ckd should receive full treatment in accordance with national and international guidelines, unless contraindicated. determination of the role of natriuretic peptides in preventing or slowing down the progress of renal dysfunction in patients with diabetes mellitus will make it possible to scientifically substantiate their use in the treatment of patients with chronic kidney disease of diabetic etiology. volume-1 issue-1 art of medicine international medical scientific journal 7 the aim: to study, in a comparative aspect, the functional state of the kidneys in patients with chronic kidney disease of the ii-iii stages of diabetic etiology during treatment with the combined drug sacubitril/valsartan. material and methods: the study included 68 patients (36 men and 32 women) who were hospitalized at the republican scientific and practical center of nephrology on the basis of the iii clinic of tma, with a clinically established diagnosis of type 2 diabetes with diabetic nephropathy. the average age of the patients was 56.0 ± 0.4 years, the duration of type 2 diabetes was 11.8 ± 0.3 years. these patients received traditional basic therapy. patients (n = 68) were divided into two groups that did not differ in age, sex and duration of the disease, and clinical and laboratory parameters. the studied patients of the 1st (n = 35) and the 2nd group (n = 33) underwent general clinical and biochemical analyzes, echocardiography in b-modes. echocardiographic examination was performed on a sonoscape s20 ultrasound machine using a 3.5 mhz cardiac transducer in modes according to the standard simson technique. glomerular filtration rate (gfr) was determined using the ckd-epi formula (ml / min / 1.73 m2). results and discussion: to compensate for renocardiac syndrome, patients of group i received a combined drug sacubitril / valsartan in a daily dose of 200 mg. patients of the second group were prescribed an angiotensin receptor antagonist valsartan in a daily dose of 160 mg. the control points of the study were the first and thirtieth day of treatment. the results of therapy were evaluated by comparison (table 1). table 1. dynamics of blood biochemical parameters in patients with chronic kidney disease on the background of type 2 diabetes № indicators group i group ii 1st day 30th day 1st day 30th day 1 urea, mmol/l 12,4±0,51 9,03±0,71** 11,6±0,83 9,6±1,56* 2 creatinine, mmol/l 163,4±12,3 1 142,6±8,5** 159,6±7,81 150,8±6,04 * 3 total cholesterol, mmol/l 6,38±0,43 5,71±0,13* 6,29±0,39 5,91±0,18* 4 tg mmol/l 2,32±0,45 1,65±0,23** 2,29±0,31 1,78±0,27* 5 ldl mmol/l 4,1±1,12 3,18±0,32** 4,22±1,24 3,32±0,31* 6 hdl mmol/l 1,09±0,25 1,22±0,32 1,07±0,31 1,18±0,26 note: delivery * р<0.05. ** р<0.01. according to the data given in the first table, we can say that, in both groups, the biochemical parameters of blood have changed with positive dynamics. in particular, in patients of the first group, urea decreased by 24.2%, and in the second group by 17.25% compared with the initial indicator, respectively. if in the first group the concentration of creatinine in the blood decreased by 12.7%, then in the second group this indicator changed by 5.51% with positive dynamics. thus, on the background of treatment in both groups, the blood urea and creatine levels significantly improved, but more significantly in the first group (p <0.01) than in the second group (p <0.05). when determining the lipid profile in the studied patients, an increased level of tg, cholesterol and ldl was observed in 44 (63.63%), 68 (100%) and 59 (86.36%) patients, respectively, and a low hdl level was detected in 34 ( 48.4%) of patients. after 30 days of treatment, positive dynamics was determined from the side of the blood lipid profile in patients of both groups. however, the most pronounced effect was observed in the main group of patients receiving the combined drug (sacubitril / valsartan) (table 1). on the table 1. dynamics of blood biochemical parameters in patients with chronic kidney disease on the background of type 2 diabetes № indicators group i group ii 1st day 30th day 1st day 30th day 1 urea, mmol/l 12,4±0,51 9,03±0,71** 11,6±0,83 9,6±1,56* 2 creatinine, mmol/l 163,4±12,3 1 142,6±8,5** 159,6±7,81 150,8±6,04 * 3 total cholesterol, mmol/l 6,38±0,43 5,71±0,13* 6,29±0,39 5,91±0,18* 4 tg mmol/l 2,32±0,45 1,65±0,23** 2,29±0,31 1,78±0,27* 5 ldl mmol/l 4,1±1,12 3,18±0,32** 4,22±1,24 3,32±0,31* 6 hdl mmol/l 1,09±0,25 1,22±0,32 1,07±0,31 1,18±0,26 art of medicine international medical scientific journal volume-1 issue-1 8 background of treatment with sacubitril / valsartan in the first group, the level of cholesterol, ldl, tg decreased by 10.5% (p <0.05), 22.4% and 28.87%, respectively, compared with their initial levels (p <0 , 01). in the 2nd group, receiving valsartan, similar indicators were: 6.04%, 21.3% and 22.27% (p <0.05) (table 1). the data obtained indicate a more reliable change in the lipid spectrum in the 1st group, who took the combined drug sacubitril / valsartan, in relation to the parameters of cholesterol, ldl and tg in the blood serum compared with valsartan therapy (table 1). based on the biochemical parameters of the blood, the gfr of both groups was calculated. before treatment, in group i patients, this indicator was 45.4 ± 8.5 ml / min / 1.73 m2, and in group ii, 43.4 ± 7.5 ml / min / 1.73 m2, respectively. on the 30th day of treatment, there was a significant change in these indicators with positive dynamics with a significant difference between the groups. in patients receiving sacubitril / valsartan, gfr improved by 65.4 ± 7.5 ml / min / 1.73 m2 (p <0.01), and in the group of patients taking valsartan by 60.6 ± 5.2 ml / min / 1.73 m2 (p <0.05). the 30-day course of treatment showed that in the first group the gfr increased by 44.05%, and in the second group by 39.6% compared with the initial values, respectively. correlation analysis revealed a close proportional relationship between gfr and the levels of tc, ldl, tg, respectively (r=0,68, r=0,26). the above mentioned gfr changes are provided in the form of this diagram: diagram 1. gfr indices in patients with chronic kidney disease with type 2 diabetes note: delivery * р<0.05. ** р<0.01 thus, the study of the functional state of the kidneys and the blood lipid spectrum in type 2 diabetes mellitus with chronic kidney disease, there was an improvement in renal dysfunction and blood dyslipidemia in patients taking sacubitrile / valsartan compared with valsartan. conclusion: 1. in all groups of examined patients, an improvement in the functional state of the kidneys was noted, however, the nephroprotective effect was more pronounced in the group of patients taking sacubitril / valsartan, in comparison with the group receiving valsartan with a comparable effect of equivalent doses of these drugs. 0 10 20 30 40 50 60 70 80 1st day 30th day 45,4 65,4 43,4 60,6 group i group ii volume-1 issue-1 art of medicine international medical scientific journal 9 2. through justified pharmacotherapy with sacubitril / valsartan, it is possible to influence not only the mechanisms of renal dysfunction in ckd, but also to improve the dyslipidemic process in the body, thereby improving the functional state of the kidneys in this category of patients. references: 1.bikbov b.t., tomilina n.a. the state of substitution therapy in patients with chronic renal failure in the russian federation in 1998-2007. (analytical report on the data of the russian register of renal replacement therapy) // nephrology and dialysis. 2009. no. 3. ð. 144-233. 2.bikbov b.t., tomilina n.a. replacement therapy for patients with chronic renal failure in the russian federation in 1998-2011. // nephrology and dialysis. 2014.16 (1). p. 11-117. 3.vyalkova a.a. chronic kidney disease // orenburg medical bulletin. 2015. t. 3. no. 2 (10). p. 42-51. 4.kuzmin ob et al. double blockade of neprilysin and at1-angiotensin receptors: a new approach to antihypertensive and nephroprotective therapy in patients with arterial hypertension // arterial hypertension. 2017. t. 23. no. 6. p. 498-506. 5.national recommendations. chronic kidney disease: basic principles of screening, diagnosis, prevention and treatment approaches // st. petersburg: publishing house "levsha". 2012. 6.shestakova m.v., neverov i.i., dedov i.i. the role of intraglomerular hypertension and lipids in the development of diabetic nephropathy // therapeutic archive. 1993. no. 6. p. 61-65. 7.shestakova m.v., dedov i.i. diabetes mellitus and chronic kidney disease // m.: medical information agency. 2009 .-p. 482. 8.cepoi v., onofriescu m., segall l., covic a. the prevalence of chronic kidney disease in the general population in romania: a study on 60,000 persons // int. urol. nephrol. 2012. v. 44. p. 213. 9.cockcroft d.w., gault m.n. prediction of clearance creatinine from serum creatinine // nephron. 1976. ¹16. p. 31-41. 10.collins a.j., foley r.n., herzog c. et al. united states renal data system 2008. annual data report // american journal of kidney disease. 2009. ¹53. p. 1-374. (12) 11.crews d.c., plantinga l.c., miller e.r. et al. prevalence of chronic kidney disease in persons with undiagnosed or prehypertension in the united states // hypertension. 2010. v. 55. p. 1102 12.duru o.k., vargas r.b., kermah d. et al. high prevalence of stage 3 chronic kidney disease in older adults despite normal serum creatinine // journal of internal medicine. 2009. v. 24. p. 86-92. 13.kdigo 2012 clinical practice guideline for the evaluation and management of chronic kidney disease // kidney int. suppl. 2013. -v. 3. p.1-150. 14.levey a.s., stevens l.a., schmid c.h. et al. a new equation to estimate glomerular filtration rate // ann. internal medicine. 2009. v.150. p. 604-12. 15.national kidney foundation. k/doqi clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification // american journal of kidney disease. 2002. s. 39. p. 1-266. 16.shahinian v.b., hedgeman e., gillespie b.w. cdc ckd surveillance system. estimating prevalence of ckd stages 3-5 using health system data. american journal of kidney disease. 2013. v. 61. p. 930. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 176 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 177 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 178 the importance of the criteria of systemic inflammatory responce syndrome of early diagnostics and detection of bloodstream infections 1 akhmedova d.r., 1 abdukhalilova g.k., 1 otamuratova n.kh., 2 tadjieva n.u., 1 bektimirov a.mt., 1 akhmedov i.f., tadjiev b.m. 1 republican specialized scientific and practical medical center of epidemiology, microbiology infectious and parasitic diseases, 2 tashkent medical academy ministry of health of republic of uzbekistan, tashkent. for corresponding 1. akhmedova dilshoda rakhmanberdievna, junior researcher, phd student, rspmcemipd. tashkent, uchtepa district, zakovat st.,2. 100133. dilyaahmedova85@mail.ru *corresponding author 2. abdukhalilova gulnora kudratullaevna, doctor of medical sciences, head of the center of antimicrobial resistance at rspmcemipd, tashkent, uchtepa district, zakovat st., 2. 100133. gula-abd@yandex.ru 3. otamuratova nargiza khasandjanovna, ph.d., senior researcher, epidemiologist of the center of antimicrobial resistance at rspmcemipd, tashkent city, uchtepa district, zakovat street, 2. 100133. nargiza.otamuratova@gmail.com 4. tadjieva nigora ubaidullaevna, md, dsc, associate professor of the department of infectious and children's infectious diseases of the tashkent medical academy, olmazor distr ict, st. farobi, 2. nigora1973@list.ru 5. bektimirov amir mangu-temirovich, ph.d., senior researcher, bacteriologist at the center of antimicrobial resistance at rspmcemipd, tashkent city, uchtepa district, zakovat st., 2. 100133. amtbektimirov@gmail.com 6. akhmedov ildar farrukovich, junior researcher, bacteriologist of the center of antimicrobial resistance at rspmcemipd, tashkent, uchtepa district, zakovat str., 2. 100133. a978da@yandex.com 7. tadjiev batyr mirkhashimovich, director of 1 republican specialized scientific and practical medical center of epidemiology, microbiology infectious and parasitic diseases. tashkent, uchtepa district, zakovat str., 2. 100133.. infoniiemiz@minzdrav.uz mailto:dilyaahmedova85@mail.ru mailto:gula-abd@yandex.ru mailto:nargiza.otamuratova@gmail.com mailto:nigora1973@list.ru mailto:amtbektimirov@gmail.com mailto:a978da@yandex.com mailto:infoniiemiz@minzdrav.uz art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 179 summary purpose of study determine the frequency of detection of patients with bloodstream infections (bsi) with applying systemic inflammatory response syndrome (sirs) criteria, and analyze the clinical characteristics of patients with suspected bsi. methods in the study were included 1,463 patients hospitalized in various departments according to their primary diagnosis. indication for study inclusion and hemoculture collection of patients was the detection of at least 2 or more criteria of sirs (accp/sccm, atlanta, 1992), in accordance with the protocol of the pop project "proof-of-principle routine diagnostic project for a antimicrobial resistance surveillance", with technical support from who, during the period from 2019-2020. the obtained results the largest number of patients (376) was admitted to the intensive care unit, 293 patients each admitted to the pediatric and infectious disease units and 183 patients admitted to the diagnostic units. all characteristic clinical symptoms of sirs occurred in the examined patients. hyperthermia was the most common in all age groups in 47 patients in 74.60±1.08% of cases in the group of patients under one year of age, significantly more frequent in the group of 1 -5 years (594), 5-12 years (166), 12-18 and over 18 years (60; 486, respectively p<0.05). tachycardia was also frequently observed in all age groups almost in all patients (91.9±0.99%) in the group less than 1 year old, almost equally often in 75±0.66% and 73.90±0.38% of cases in the group 5 -12 and over 18 years old, respectively. this symptom was noted in more than 50% of cases in patients in the 1-5 (65%) and 12-18 (84%) age group. tachypnea and leukocytosis were most frequently observed in patients under 1 year of age (47.62±0.87% and 71.43±1.06%, respectively), whereas in the remaining groups (1-5, 5-12, 12-18, and over 18 years of age), leukocytosis was noted in 63%, 50%, 59%, and 58% of cases, respectively, and tachypnea in 23%, 10%, 19%, and 25%, respectively. a combination of 2 symptoms (hyperthermia and tachycardia), a combination of hyperthermia and leukocytosis in 18.1% of cases, a triad of symptoms tachycardia, hyperthermia and leukocytosis in 23.9% of cases was the most common (41.5%) of the criteria for ssris. also often enough (6.8%) were observed 4 symptoms hyperthermia, tachycardia, tachypnoea and leukocytosis. conclusions the most frequent localization of infection in bsi was the upper respiratory tract, lower respiratory tract infections were detected twice as often. predominantly, regardless of the art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 180 localization of infection, a combination of the criteria for sirs of two symptoms was observed. irrespective of the localization of infection, all patients had fever in various combinations, most frequently with tachycardia (26.8%) and leukocytosis (26.2%). keywords bloodstream infections, systemic inflammatory response syndrome, sepsis, hyperthermia, tachycardia, tachypnea, leukocytosis, neutrophilia. introduction bloodstream infections (bsis) are defined as the presence of bacteria in the blood detected by hemoculture testing. this definition includes all clinical manifestations of bsi, including systemic inflammatory response syndrome (sirs/sirs, the initial manifestation of bsi), sepsis (life-threatening illness accompanied by organ dysfunction due to dysregulated host response to infection) and septic shock (sepsis accompanied by persistent pressure drop despite rehydration, plus impaired cellular metabolism) 1. bloodstream infections are among the most common diagnoses treated in intensive care units. according to some author reports, 1.7 million patients develop bsis each year in the united states, most of whom are over 65 years of age 2. mortality, which reaches 10% in patients with sepsis and 40% in patients with septic shock, is usually the result of multiple organ dysfunction syndrome (mods) 3. the introduction of the use of the sirs criteria proposed at the consensus conference of the american college of thoracic surgeons and society of emergency physicians would be an indication for hemoculture testing and would allow identification of patients at risk for sepsis and mods, and would facilitate early intervention and appropriate management tactics . sirss are characterized by a wide range of conditions and may have a severe clinical course. the main clinical and laboratory indicators for the diagnosis of sirs are body temperature above 38.3°c (fever) or below 36°c (hypothermia), heart rate more than 90 beats per minute (tachycardia), respiratory rate more than 20 breaths per minute (tachypnea), white blood cell count more than 12 × 109/l or less than 4 × 109/l or more than 10% immature neutrophils (stabial forms). sirs criteria for children are presented in table 1 according to the age of the child. table 1. specific age criteria for sirs age group body temperature (°c) heart rate (beats per minute) respiratory rate (breaths per minute) white blood cell count (in 10 9 /l) fever hypothermia tachycardia bradycardia newborn (0 days to 1 week) >38,3 <36,0 180 100 50 34 newborn (1 week to 1 month) >38,3 <36,0 180 100 40 19,5 or 5 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 181 infant (1 month to 1 year) >38,3 <36,0 180 90 34 17,5 or 5 pre-school age (from 1 to 5 years) >38,3 <36,0 140 нп 22 15,5 or 6 school age (5 to 12 years old) >38,3 <36,0 130 нп 18 13,5 or 4,5 teenagers (12 to 18 years old) >38,3 <36,0 110 нп 14 11 or 4,5 the presence of two or more of the above signs against the background of infection and bacteremia is interpreted as a systemic inflammatory response to the infection, i.e., sirs 4,5,6. the purpose of our study is to determine the frequency of detection of patients with bloodstream infections when applying the criteria of systemic inflammatory response syndrome, and to analyze the clinical characteristics of patients with suspected bloodstream infections. materials and methods in the study were included 1,463 patients hospitalized in various departments according to their primary diagnosis. indication for study inclusion and hemoculture collection of patients was the detection of at least 2 or more criteria of sirs (accp/sccm, atlanta, 1992), in accordance with the protocol of the pop project "proof-of-principle routine diagnostic project for a antimicrobial resistance surveillance", with technical support from who, during the period from 2019-2020. from the total number of patients, 42% were female (615) and 58% male (848). the age of the patients ranged from a few months to 90 years (up to 1 year 5%, 1-5 years 45%, 5-12 years 12%, 12-18 years 4%, and over 18 years 34%). in the selected patients we analyzed medical history data, clinical parameters in accordance with sirs criteria, the fact of taking antibiotics at the time of blood sampling, empirical therapy before the bacteriological test result of hemoculture, and the tactics of antibiotic therapy after a positive result from the bacteriological laboratory. obtained results all patients were hospitalized in different departments of huge multidisciplinary hospitals of tashkent, uzbekistan (table 2). table 2. distribution of patients according to departments departments n % 1. adults icu 376 25,7±0,13 2. pediatric/newborn 296 20,23±0,12 3. infectious diseases 293 20,03±0,12 4. diagnostic 183 12,51±0,09 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 182 5. pediatric/newborn icu 95 6,49±0,07 6. therapeutic 92 6,29±0,07 7. surgical 91 6,22±0,07 8. urologic 34 2,32±0,07 9. rehabilitation 3 0,21±0,04 comparative analysis of the obtained data showed that the largest number of patients (376) were hospitalized in the intensive care unit (p 0.05)/ between the number of patients hospitalized in pediatric (293), infectious diseases (293) and diagnostic (183) departments significance was not noted. hospitalization of the examined patients in the neonatal intensive care unit, therapeutic and surgical departments was equally frequent (p0.05). hospitalization of patients at the urologic department and rehabilitation department was significantly less frequent, and showed only in 2.32±0.07%, 0.21±0.04% cases, respectively (p0.05). the distribution of patients according to sirs clinical criteria at the time of hospitalization is shown in table 3. table 3. clinical parameters of the whole group of patients according to age clinical parameters under 1 year old 1 5 years old 6-12 years old 13 – 18 years old older than 18 years old hyperthermia 74,60±1,08 90,69±0,37* 96,51±0,75*° 80,00±1,03*°˄ 97,597±0,44*° hypothermia 3,17±0,22 2,9±0,07 3,49±0,14° 1,20±0,05*°˄ tachycardia 91,9±0,99 50,84±0,28* 75±0,66*° 61,33±0,90°˄ 73,90±0,38*° bradycardia 0,46±0,03* 0,58±0,06* 1,41±1,08*°˄ tachypnea 47,62±0,87 20,15±0,18* 8,72±0,23*° 16,00±0,46*°˄ 21,08±0,21*°˄ leukocytosis 71,43±1,06 59,69±0,30* 46,51±0,52*° 49,33±0,81*°˄ 55,02±0,33*°˄ leukopenia 4,76±0,27 1,37±0,05* 1,74±0,10*° 1,33±0,13* 1,20±0,05* neutrophilia 3,17±0,22 0,76±0,03* 1,16±0,08*° 0,80±0,04*˄ note: * comparison of indicators with the group of patients under 1 year of age (p0.05) ° comparison of indicators with the group of 1-5 years, (p0.05) ˄ comparison of indicators with the group of 5-12 years, (p0.05) comparison of indicators with the group of 12-18 years, (p0.05) the examined patients had all clinical symptoms of sirs. the most common in all age groups was hyperthermia: in the 1-5 years group and in over 18 year’s group it amounted significantly more frequent 594 (p<0.05) and 486 of cases (p<0.05), respectively. in the 6-12 years group – in 166 of cases, in the 13-18 – in 60 of cases, and in the group of patients under one year of age it amounted 47 patients (74.60±1.08% of cases), which shows that it was not had significant difference. tachycardia were also frequently observed in all age groups nearly all patients (91.9±0.99%, p0.05) in the group less than 1 year old, almost equally often in 75±0.66% and art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 183 73.90±0.38% of cases in the group 5-12 and over 18 years old, respectively. in more than 50% of cases this symptom was observed in patients in the age group of 1-5 (65%) and 12-18 (84%) years old. such symptoms as tachypnoea and leukocytosis were most frequently observed in patients under 1 year of age (47.62±0.87% and 71.43±1.06%, respectively), whereas in the remaining groups (1-5, 5-12, 12-18 and over 18 years old), leukocytosis was noted in 63%, 50%, 59% and 58%, respectively, and tachypnoea in 23%, 10%, 19% and 25%, respectively. we divided all the examined patients into groups according to combinations of symptom occurrence. the results showed that the most common combination of 2 characteristic clinical symptoms was registered in 758 patients (51.8%), in 590 patients (40.3%) of 3 symptoms, and in 115 cases (7.9%) 4 symptoms were encountered. but there was no statistical reliability in the distribution of patients into groups. (p0.05). table 4. distribution of patients into groups according to combinations of sirs criteria groups combinations of sirs criteria quantity (n, %) 1 group 2 symptoms 758 (51,8%) 2 group 3 symptoms 590 (40,3%) 3 group 4 symptoms 115 (7,9%) table 5. combination of sirs criteria combination of sirs criteria quantity (%) quantity (n) hyperthermia + tachycardia 26,8% 392 hyperthermia + tachycardia + leucocytosis 26,2% 384 hyperthermia+leukocytosis 20,6% 301 hyperthermia+tachycardia+tachypnoea 9,0% 132 hyperthermia+tachycardia+tachypnoea+leukocytosis 6,7% 98 tachycardia+tachypnoea+leukocytosis 3,3% 48 hyperthermia+tachycardia+leukocytosis+neutrophilia 1,0% 15 hyperthermia+tachypnoea 1,0% 15 tachycardia+tachypnea 0,6% 9 leukocytosis+tachypnea 0,5% 8 tachycardia+tachypnoea+hypothermia 0,5% 7 combinations of sirs criteria depending on the presumed localization of infection are shown in fig.1a, and fig.1b art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 184 analysis of the occurrence of various combinations of sirs criteria in the surveyed group of patients showed that the most frequent was a combination of two symptoms: in 62.2% for localization on the skin and soft tissues, in 61.7% in the upper respiratory tract, and in 52.5% for a source of infection in the gastrointestinal tract. the greatest combination of three ssri criteria was observed in the lower respiratory tract (53.1%) and gastrointestinal tract (42.4%). combinations of ssrs criteria of hyperthermia, tachycardia and tachypnoea were observed in 26.6% of cases with localization of infection in the lower respiratory tract (301), 22.6% of hyperthermia, tachycardia and leucocytosis, 9.6% of hyperthermia, tachypnoea and leucocytosis, in 20.3% of cases there was a combination of 2 symptoms hyperthermia and leucocytosis, and in 14.3% of hyperthermia and tachycardia. figure 1a combinations of sirs figure 1b combinations of sirs when we analyzed the localization of infection in our patients with suspected bsi, the most frequent was in the upper respiratory tract (703), accounting for 48.1%; in the lower respiratory tract 301 patients, accounting for 20.6%. gastrointestinal diseases accounted for 10.8% (158) of the cases (p≥0,05) fig.2a, 2b, 2c. 0,0% 50,0% 100,0% 6,8% 3,8% 4,2% 20,0% 3,5% 5,7% 9,3% 33,3% 5,3% 5,0% 4,4% 3,2% 1,8% 11,4% 25,6% 3,2% 23,5% 9,5% 28,4% 66,7% 50,9% 8,6% 22,6% 100,0% 69,5% 0,4% 22,2% 1,1% 2,3% 0,3% 4,4% 1,8% 2,9% 1,3% hyperthermia, tachycardia, leukocytosis, neutrophilia hyperthermia, tachycardia tachypnoea, leukocytosis hyperthermia, tachycardia tachypnoea hyperthermia, tachycardia, leucocytosis 0,0% 50,0% 100,0% 42,1% 8,9% 25,3% 6,7% 8,8% 28,6% 14,0% 33,3% 9,5% 17,6% 30,4% 34,7% 28,1% 31,4% 19,6% 33,3% 7,4% 0,3% 3,8% 1,1% 1,8% 8,6% 2,0% 0,0% 2,1% 0,1% 4,4% 2,9% hyperthermia + tachycardia hyperthermia+leukocytosis hyperthermia+tachypnoea art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 185 fig. 2a, 2b, 2c combinations of sirs criteria depending on the presumed localization of infection in this group of patients, a combination of 2 symptoms (hyperthermia and tachycardia), in 18.1% of cases a combination of hyperthermia and leukocytosis, and in 23.9% of cases a triad of symptoms tachycardia, hyperthermia and leukocytosis was observed most frequently. the 4 symptoms of hyperthermia, tachycardia, tachypnoea and leucocytosis were also common (6.8%). in the gastrointestinal tract, a combination of hyperthermia and leucocytosis (30.4%) was more frequent, hyperthermia, tachycardia with leucocytosis was shown in 9.5% of cases, and less frequent were the criteria of sirs such as hyperthermia with tachycardia, in 8.9% (p≤0.05). art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 186 fig.3a, 3b, 3c. combinations of sirs criteria depending on the presumed localization of infection more than half of the cases (51.8%) showed a combination of three symptoms: hyperthermia, tachycardia and leucocytosis, and 28.6% showed a combination of 2 symptoms: hyperthermia and leucocytosis, if the infection was localized in the urogenital tract (fig. 3b). a comparative analysis of the results showed that irrespective of the localisation of infection, all patients had fever in various combinations, most frequently with tachycardia (26.8%) and leucocytosis (26.2%). thus, all the characteristic clinical symptoms of sirs were mostly present. hyperthermia was the most common in all age groups. the most frequent localization of infection in bsi was in the upper respiratory tract (702), accounting for 48.1%, (p0.05); almost half as many were in the lower respiratory tract, 301 patients, accounting for 20.6%, (p0.05). in 10.8% (158) of cases, the development of septic conditions was observed in gastrointestinal diseases. analysis of the occurrence of various combinations of sirs criteria in the examined group of patients showed that the most frequent was a combination of two symptoms: in 62.2% for localization in the skin and soft tissues, in 61.7% in the upper respiratory tract, and in 52.5% for a source of infection in the gastrointestinal tract (p<0.05). the most frequent combination of three sirs criteria was observed in the lower respiratory tract (53.1%) and gastrointestinal tract (42.4%). a comparative analysis of the findings showed that irrespective of the localisation of infection, all patients had fever in varying combinations, most frequently with tachycardia (26.8%) and leucocytosis (26.2%), p0.05. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 187 conclusions. 1. the upper respiratory tract, lower respiratory tract infections was the most frequent localization of infection in bsi. 2. predominantly, irrespective of the localization of infection, a combination of the criteria for sirss of two symptoms was observed. 3. irrespective of the localization of infection, all patients present with fever in varying combinations, most commonly with tachycardia (26.8%) and leucocytosis (26.2%). conflict of interest the authors declare no conflict of interest. financial support the study was conducted by the "proof-of-principle routine diagnostic project for a antimicrobial resistance surveillance" with technical and financial support of who. who was involved in the development of the pop-project protocol. who was not involved in the conduct of the study; data collection, management, analysis and interpretation, or in the preparation, review or approval of the manuscript. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558714 188 references 1. singer m., deutchman c.s., seymour c.w., shankar-hari m., annane d., bauer m. the third international consensus definitions for sepsis and septic shock (sepsis-3). jama. 2016 315 (8):801-10 2. patel r., vetera e.a., harmsen w.s., schlek c.d., fadel j.h.., cockeril f.r. 3 rd . 2011; 49 (12): 4047-51 3. bone r.c., balk r.a., cerra f.b., dellinger r.p., fein a.m., knaus w.a. definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. the accp/sccm consensus conference committee. american college of chest physicians/society og critical care medicine. chest. 1992; 101 (6): 1644-55 4. pronoza a.v., presnetcov d.m. osobennosti techeniya pon u pacientov s hronicheskoy postgemorragicheskoy anemiyey. metodicheskie recomendacii. omsk, 2000. – 20 s. 5. baue а.е. multiple, progressive or sequential systems failure: a syndrome of the 1970's//arh. surg. -1975. v. 110. p.779-781. 6. bone r.c. immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (sirs) and the multiple organ dysfunction syndrome (mods)//ann. intern. med. -1996. v.125. n8. -p.680-687). art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 1 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 2 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 3 analysis of reparative after surgical treatment of diaphyseal fractures of the shin bones 1 gafforov a.u., 2 asilova s.u., 3 teshaev a.a. 1, 3 department of traumatology and orthopedics and pediatric surgery, bsmi, bukhara, uzbekistan 2 department of traumatology and orthopedics, tma, tashkent, uzbekistan abstract. complications of reparative osteogenesis in long bone fractures remain a major problem in traumatology, despite significant advances in their treatment. as shown by numerous observations, the disability rate of patients with fractures is still high, amounting to 19–37.9%, so it is obvious that it is necessary to study the causes of such conditions. based on the analysis of radiographs of 122 patients with diaphyseal fractures of the leg bones at the age of 18 to 60 years with dynamic observation for 8 months. up to 3 years, the timing of fusion, types of callus and the frequency of complications of reparative osteogenesis were established. complications during fracture healing were noted in 46 (37.7%) injured patients. key words: bones, shin, diaphyseal fractures, callus, radiography, reparative ostegenesis, complications. introduction reparative osteogenesis in fractures is a complex, multi-stage process, the course of which is influenced by many factors, including local, peripheral circulation, immune status, and so on [1]. its essence is the restoration of damaged tissues, anatomical shape, function of the damaged bone and the segment of the limb as a whole [2]. fracture healing can take different paths. it largely depends on the quality of bone fragments immobilization (complete immobility and good reduction) [3, 4]. morphologically, the following types of callus are distinguished: endosteal, periosteal, intermediate, and paraossal [5]. intermediate callus forms between the cortical layers, while the periosteal and endosteal layers are almost absent. with such fusion, the absence of periosteal callus is not a sign of poor regeneration [6]. the presence of a large periosteal callus indicates not so much the favorable processes of art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 4 regeneration as the mobility of bone fragments during the formation of the regenerate [7]. in addition, the size of the callus is influenced by the volume of the hematoma and the nature of soft tissue damage. in healing fractures, they describe mainly the periosteal callus, since the endosteal and intermediate calluses, as a rule, are not visible behind the general shadow [5]. standard radiography in two projections is the main method for diagnosing fractures at the present time, since, according to many authors, up to 85% of primary diagnoses are made with its help [8]. however, the assessment of the course of the reparative process during the primary healing of fractures (which often occurs during transosseous osteosynthesis) may not always be objective [2]. complications of reparative osteogenesis in long bone fractures remain a major problem in traumatology, despite significant advances in their treatment [3, 6]. as shown by numerous observations, the disability rate of patients with fractures is still high, amounting to 19–37.9%, so it is obvious that it is necessary to study the causes of such conditions. purpose of the study to study the features of reparative osteogenesis in diaphyseal fractures of the leg bones in young and middle-aged patients. materials and methods the analysis of radiographs of 122 patients with diaphyseal fractures of the leg bones aged 18 to 60 years (men 54.2%; women 45.8%) in standard projections with dynamic observation for 8 months. up to 3 years old. all patients were divided into 2 groups in terms of age: group 1 age from 18 to 35 years (44 patients 36.1%, average age 28.4 ± 4.3 years); group 2 from 35 to 60 years old (78 patients 63.9%; average age 48.7 ± 9.4 years). according to vi gongalsky (1987), the timing of the fusion of diaphyseal fractures of the tibial bones is the longest among all fractures of the long bones and is 2.5–3.5 months for fractures of the tibial diaphysis; with fractures of the diaphysis of the fibula 1.0–1.5 months; with fractures of the diaphysis of both bones of the lower art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 5 leg 3.0-4.0 months [9]. it was these terms that were taken into account in the analysis; an increase in the duration of fusion up to 2 weeks was not considered a delay in regeneration. when conducting statistical analysis, the data obtained were expressed in absolute values and percentages, to compare the indicators in the groups, the χ2 criterion was used; discrepancies in the values of individual signs were considered reliable if the level of significance was less than 0.05 (p <0.05). research results in the study, combined damage to the tibia and fibula was found in 85.2 ± 3.2% of cases. in 61.5 ± 4.4% of cases, patients were treated with external fixation devices; in 22.9 ± 3.8% by the method of external osteosynthesis, in 15.6 ± 3.3% with plaster casts. complete union of fractures within 4 months was noted only in 28.7 ± 4.1% of cases (35 patients), within 6 months in 33.6 ± 4.3% (41 patients), up to 8 months in another 16.4 ± 3.3% (20 patients). in 26 patients (21.3 ± 3.7%), the fusion of diaphyseal fractures of the tibia was formed over 1.5–2 years, among them, in 9 patients (7.3 ± 2.4%), the formation of callus took place over 6 months was completely absent. the most common (p <0.001) when fractures were healed was periosteal callus 102 (83.6 ± 3.4%) patients (fig. 1), less often intermediate 14 (11.4 ± 2.9%) (fig. . 2) and paraossal 6 (4.9 ± 1.9%). x-ray signs of endosteal callus (sclerosis at the level of the bone marrow cavity) were determined only in combination with periosteal and paraosseal bone formations. intermediate fusion was observed in isolated oblique fractures of the middle and distal third of the tibial diaphysis at 2.5–3 months. paraosseous fusion was observed during long-term formation of callus in patients with complications of comminuted fractures of the tibia. the formation of periosteal callus did not depend on the type and location of the fracture. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 6 fig. 1. patient i., 32 years old: a on radiographs of the lower leg in frontal and lateral projections with the presence of wire splints, a helical fracture of the distal third of the tibial diaphysis is determined with a transverse displacement by ½ of the diaphysis outward, fragments overlapping up to 1.5 cm and angular displacement, open to the inside; oblique fracture of the middle third of the diaphysis of the fibula; b on control radiographs of the lower leg after 7 months. from the start of treatment healed fracture of the tibia due to the formation of circular periosteal and endosteal callus fig. 2. formation of intermediate bone callus in patient k., 24 years old at a control study 2.5 months after surgical treatment complications during fracture healing were noted in 46 (37.7 ± 7.2%) injured, among them delayed fracture union 60.9 ± 7.2% (p <0.01), pseudarthrosis formation 21.7 ± 6 ,1 %; the development of post-traumatic osteomyelitis in 26.1 ± 6.5%; fused fractures with preserved deformation of the bone axis 13.0 ± 5.0%; non-union art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 7 of a fracture with the presence of a bone defect 6.5 ± 3.6%. several complications were observed in 18 patients (39.1 ± 7.2%). slowing down of the fusion of diaphyseal tibial fractures up to 6 months was not included in the group of patients with complications. in 43.4 ± 7.3% of patients with complications, their radiological signs were determined from 2 to 3 months; in 21.7 ± 6.1% from 3 to 5 months from the start of treatment, that is, in 65.1 ± 7.0% of patients, the treatment tactics could be changed at an earlier stage of impaired development of the reparative process. the proportion of complications in the groups was: in the 1st group 25.0 ± 6.5% (11 patients); in group 2 44.9 ± 5.6% (35 patients) (p <0.01). discussion of research results according to [3], during the initial examination of patients of working age with diaphyseal fractures of long bones, their localization at the level of the lower leg was the highest frequency 54.6%; all the rest (thigh, shoulder, forearm) are only 46.4%. the authors noted that the most frequent complication of diaphyseal fractures of the shin was slow-healing fractures (62.7%), which coincides with the data obtained in the study. slowly healing fractures according to the msec characteristics were those when, after 4 months. and more after it, the persisting clinical and radiological indicators did not allow predicting the patient's recovery in the next 2–4 months, at the same time, the existing signs did not give grounds to raise the question of changing the treatment tactics. the diagnosis of a pseudarthrosis was made after 6–8 months. from the start of treatment and was considered as a variant of non-union of fragments [3]. at the same time, the term “nonunited fracture” was used to describe a condition when, after 4 months of treatment, there were clear clinical and radiological signs of the absence of regenerative osteogenesis, indicating the need for a radical change in treatment tactics [3]. such disagreements in the assessment of fracture fusion in terms of callus formation, as well as in terms of diagnosis of complications of reparative osteogenesis, their interpretation and related changes in treatment tactics art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 8 require additional research. until now, the methods of directed drug management of reparative osteogenesis have been insufficiently studied, although there are publications on the use, for example, of growth factors for its stimulation [10]. according to [6], it is possible to determine the timing of dismantling the external fixation apparatus, as well as to plan the nature and duration of rehabilitation measures for closed diaphyseal fractures of the tibial bones, based on a complex of modern methods of radiation diagnostics (including x-ray, computed and magnetic resonance imaging), with the help of which it is possible to evaluate the features of the formation of contact regenerate and bone remodeling with their quantitative assessment. in our opinion, in all patients 2-4 months after the start of treatment, on the basis of x-ray indicators (type of fracture, formation of callus, degree of its severity), it is possible to predict the duration of maturation of a full-fledged bone regenerate, and the use of magnetic resonance imaging in the presence of metal structures in such patients are not indicated. the reasons for the high frequency of delayed formation of reparative osteogenesis in diaphyseal fractures of the lower leg bones in young and middle age require further study. conclusions 1. in most cases, diaphyseal fractures of the leg bones healed for more than 4 months, with complications in every third patient. 2. it was found that the incidence of complications of reparative osteogenesis in diaphyseal fractures of the shin bones increases with age. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 9 references 1. mamaev, v. i. transosseous osteosynthesis and the possibility of predicting the outcomes of treatment of the consequences of bone fractures [text] / v. i. mamaev // bulletin of traumatology and orthopedics them. n.n. priorova. 2008. no. 3. p. 27-29. [in russian] 2. litvishko, v. o. functional treatment of diaphragmatic fractures of the gomilka's cysts from the dressing of the abdominal device [text] / v. o. litvishko, o. k. popsuyshapka // orthopedics, traumatology. 2015. no. 4. p. 91–102. [in ukrainian] 3. popsuishapka, ak frequency of nonunion of fragments in isolated diaphyseal fractures of the long bones of the extremities [text] / ak popsuishapka, oe uzhigova, va litvishko // orthopedics, traumatology and prosthetics. 2013. no. 1. p. 39–43. [in russian] 4. korzh, n. a. prevalence of bone fractures and the results of their treatment in ukraine (clinical and epidemiological study) [text] / n. a. korzh, s. i. gerasimenko, v. g. klimovitsky, a. e. loskutov et al. // orthopedics, traumatology and prosthetics. 2010. no. 3. p. 26–35. [in russian] 5. semizorov, an radiography in the diagnosis and treatment of bone fractures [text]: pos. / a. n. semizorov. m .: vidar-m, 2007 .-176 p. [in russian] 6. stepanov, rv complex beam diagnostics in the assessment of the reparative process in the treatment of patients with closed diaphyseal fractures of the shin bones [text]: author. dis. ... cand. med. sciences / r. v. stepanov. 2011 .-21 p. [in russian] 7. claes, l. monitoring and healing analysis of 100 tibial shaft fractures [text] / l. claes, r. grass, t. schmickal, b. kisse, c. eggers, h. gerngro et. al. // langenbeck's archives of surgery. 2002. vol. 387, issue 3-4. p. 146-152. doi: 10.1007 / s00423-002-0306-x 8. kessler, t. follow-up of fracture healing –indications and clinical relevance of direct radiographic magnification in comparison with conventional roentgen art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5633974 10 imaging [text] / t. kessler et. al. // unfallchirurg. 1994. vol. 97, issue 12. p. 619-624. 9. gongalsky, v. i. the volume of research and treatment and preventive care for orthopedic and traumatological patients in polyclinics [text] / v. i. gongalsky, g. f. martynenko, g. t. likhvar and others departmental instructions of the ministry of health of the ukrainian ssr , 1987. [in russian] 10. dedukh, n. v. new technologies in bone regeneration: the use of growth factors [text] / n. v. dedukh, s. a. khmyzov, a. a. tikhonenko // orthopedics, traumatology and prosthetics. 2008. no. 4. p. 129–133. [in russian] art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 63 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 64 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 65 prosthetic hiatoplasty in surgical treatment of hiatal hernias khashimov sh.kh., sadikov n.s., ligai r.e., tsoi a.o., tashkenbaev f.r., zaripov a.a. republican specialized scientific and practical medical center of surgery named after academician v. vakhidov. tashkent, uzbekistan abstract. the article describes the experience of surgical treatment of hiatal hernias of types ii and iii. the authors proposed an original technique of prosthetic hiatoplasty aimed at the prevention of general and specific postoperative complications. the article presents an analysis of the immediate results of the proposed operation, as well as long-term results. key words: hiatal hernia, prosthetic hiatoplasty, laser therapy, postoperative complications. introduction in recent years, interest in the problem of hiatal hernias and gastroesophageal reflux disease has increased, since today they occupy a leading position in gastroenterology in frequency after gastric ulcer and duodenal ulcer and cholecystitis [2,3,9]. hernias of the esophageal opening of the diaphragm account for 98% of all hernias of the diaphragm. it is important to note that in 50% of patients, it does not cause any clinical manifestations and, therefore, is not diagnosed [1,5,6,10,12]. the urgency and need to address the issues of effective treatment of hh is primarily due to the frequency of the spread of this disease in 44% of the population, at least once a month symptoms of heartburn appear; 7% experience it daily; 18% are forced to resort to self-medication to eliminate the symptom [1,7,11]. thus, approximately 1% of the population suffers from gerd symptoms, and 40% of the diagnostic examination reveals a hiatal hernia [8,11]. the need for further study of various aspects of this problem does not raise doubts, since the issues of choosing the optimal method of treatment have not been fully determined [5,9,12]. this has become especially important in recent years in art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 66 connection with the widespread introduction of endovideosurgical technologies in the treatment of hh [2,7,10]. purpose of the study to study the results of a new method of surgical treatment of hh using prosthetic hiatoplasty. materials and methods department of endovisual surgery of the republican specialized scientific and practical medical center of surgery named after academician v. vakhidov for the period from 2006 to 2019 has experience in the surgical treatment of 105 patients operated on for hernia of the esophageal opening of the diaphragm. when distributing patients, the comparison group consisted of 61 patients, where the choice of surgery was carried out based on the preferences and experience of the operating surgeon, some of which are currently not used due to frequent relapses of the disease. when choosing the operation, such indicators as the hiatal surface area (hsa) and the degree of atrophy of the legs of the diaphragm were not taken into account, and it is these indicators that determine the long-term results. the main group consisted of 44 patients, in whom a differentiated approach to the choice of surgical intervention depending on the hsa was used, as well as prosthetic hiatoplasty according to the original technique, both from the open and from the laparoscopic approach. after a comprehensive examination, including endoscopy, x-ray contrast study, and computed tomography, the distribution of patients by the type of hh was carried out according to the classification recommended in 2013 by the american association of gastroenterological and endoscopic surgeons (sages) for the treatment of hh [6], which includes 3 types of hh (fig. 1). art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 67 fig. 1. types of hiatal hernia (sages, 2013) according to the classification, when examining patients, type ii hh was diagnosed in 10 (9.5%), of which 7 (11.4%) patients in the comparison group and in 3 (6.8%) patients in the main group. hh type iii were diagnosed in 95 (90.4%) patients, of which 54 (88.5%) patients in the comparison group and 41 (93.1%) patients in the main group. the distribution of patients depending on the type of hh is presented in table 1. table 1 distribution of patients by types of hiatal hernia size of hernia comparison group main group total type ii 7(11,4%) 3(6,8%) 10(9,5%) type iii 54(88,5%) 41(93,1%) 95(90,4%) total: 61(100%) 44(100%) 105(100%) reliability χ 2 =0.64, p=0.42 if with hernias of type ii, the contents are the stomach, then with hernias of type iii, in addition to the stomach, the hernial contents can be a loop of the small or large intestine, as well as a strand of the greater omentum. hh of type iii was established in 95 (90.4%) patients, with subtotal gastric hh in 78 (74.2%) and total gastric hh in 17 (16.2%) patients. in this group, 15 (14.2%) of 105 patients had a art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 68 mixed nature of the hh content: small intestine in 1 (1%), omental in 6 (5.7%), colonic in 5 (4.7%). %) and mixed (colonic + omental) in 3 (2.8%) patients. the distribution of patients depending on the type of surgery is presented in table 2. table 2 types of surgical interventions surgical intervention comparison group main group total allison's operation 4(6,5%) 4(3,8%) hill's operation 23(37,7%) 23(22%) collis's operation 1(1,6%) 1(1%) cruroraphy 33(54%) 18(41%) 51(48,5%) cruroraphy with prosthetic hiatoplasty 22(50%) 22(21%) laparoscopic cruroraphy with prosthetic hiatoplasty 4(9%) 4(3,8%) total 61(100%) 44(100%) 105(100%) in the comparison group, the largest number was cruroraphy, performed in 33 patients and amounted to 54%. hill's operation was performed in 23 (37.7%) patients, allison's operation in 4 (6.5%) patients and collis's operation in 1 (1.6%) patient. all of the above operations, the execution technique of which is widely known and described in detail in the available literature, therefore we do not consider it necessary to dwell on their description in detail. as mentioned earlier, in the comparison group, the choice of surgical aid was based on the experience of the surgeon and his preferences. in the main group, the choice of surgical intervention was based on hsa and the presence of atrophy of the legs of the diaphragm. the technique for measuring the size of a hernial defect is not standardized, and the measurement of such an indicator as diameter is incorrect, since in most cases the hh has the shape of a triangle or, more precisely, an inverted drop. granderath f.a. et al. in 2007 [4] was published article based on the intraoperative measurement of the indicator they proposed hsa (fig. 2). it is calculated using the equation: art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 69 hsa = arcsin (td / 2 / vd) x vd 2 vd vertical dimension; td transverse dimension. fig. 2. measurement of hiatal surface area (hsa). based on the method of measuring the indicator "hiatal surface area" granderath f.a. et al. and the results of a retrospective analysis of 787 operations, created the classification of the hh: small – hh <10 cm 2 ; large – hh 10-20 cm 2 ; giant – hh > 20 cm 2 . the applied value of this classification consists in a clear definition of the indications for the plastic technique (for small hernias, cruroraphy is indicated, for large and giant ones alloplasty), which is evidence-based on the dependence of an increase in the frequency of relapses on the value of hh. according to the proposed indicators and classification, in the main group, when choosing a surgical aid, we analyzed the following parameters: f.a. granderath, as well as the degree of atrophy of the legs of the diaphragm in large and giant hiatal hernia. hsa was measured intraoperatively according to the proposed equation. at the same time, in the main group, we obtained the following results: small hh was established in 18 (41%) patients, large in 17 (38.6%) patients and gigantic in 9 (20.4%) patients. vd vd td art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 70 in addition to hsa, the degree of atrophy of the pedicles of the diaphragm was assessed, which was also important in determining the indications in favor of prosthetic hiatus. the severity of atrophy of one or both legs of the diaphragm depended on the size of the hernial sac and the location of the latter relative to the median axis. atrophy of the legs of the diaphragm is the result of compression by the hernial sac and ischimization in the pressure zone, followed by atrophy of one or both legs. the degree of atrophy of the pedicles of the diaphragm, as well as the hh, was assessed intraoperatively. when assessing this indicator, we obtained the following results: no changes were found in both diaphragm legs in 18 (41%) patients with small hh, atrophy of the left leg was detected in 18 (41%) patients, while the hernial sac was located to the right of the median axis. the right leg was, on the contrary, pronounced in 8 (18.1%) patients. after the analysis of the results obtained, in 18 (41%) patients, given the small size of the hh, the hsa is less than 10 cm 2 and the absence of changes in the side of the diaphragm legs, there were no indications for prosthetic hiatoplasty. in 26 (59%) patients, in addition to the large size of hh, hsa was from 10 cm2 or more, and there was also atrophy of both one and both legs of the diaphragm. the totality of these indicators was an indication for performing prosthetic hiatoplasty. the original technique of prosthetic hiatoplasty used in the main group included two stages: operational and postoperative. we named it "a method of surgical treatment of hiatal hernia" for which a patent was received for the invention of ipa ruz iap23124. surgical stage: the method of surgical treatment of hiatal hernia includes, in addition to the conventional stages of surgery, selective proximal vagotomy, pyloroplasty according to heinecke-mikulich, the formation of a fundoplication cuff, behind the esophageal cruraphy, and the imposition of a u-shaped mesh implant on the suture area. at the same time, when the fundoplication cuff is formed, the anterior wall of the abdominal esophagus is captured, a u-shaped mesh prosthesis made of polytetrafluoroethylene (ptfe) is used, while the horizontal part of the prosthesis is art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 71 fixed to the diaphragm legs with interrupted (stapling) sutures, 3-4 mm away from the edges esophageal opening of the diaphragm, the free floors of the specified prosthesis are fixed to the diaphragm also with interrupted (stapling) sutures (fig. 3). fig.3. cutting out the prosthesis and fixing it to the diaphragm. postoperative stage. starting from the first day after the operation, 5 sessions of percutaneous laser therapy are performed using the sogdiana apparatus (fig. 4). with mild pain syndrome, the pulse frequency was 80 hz, with intense pain syndrome, 1500 hz, exposure time 256 s per 1 zone, daily during one session, 3 zones are affected the lower third of the sternum, the epigastric region and the area of the pain point. fig. 4. laser machine "sogdiana" art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 72 research results when assessing the results, we assessed the frequency and nature of postoperative complications, the length of the patient's stay in the hospital, and also studied long-term results in terms of 1 month to 2 years. postoperative complications. complications that developed in the postoperative period were conditionally divided into general and specific. general complications developed in 20 patients, which amounted to 19%, and specific complications in 17 patients, which amounted to 16.2%. all postoperative complications were eliminated by conservative measures and only in one case required relaparotomy. no lethal outcomes were observed. when analyzing the postoperative period, it was found that in 85 patients, which amounted to 81%, the latter proceeded without any postoperative complications. in 20 patients, which amounted to 19%, general postoperative complications were observed in the postoperative period (table 3.) table 3 general postoperative complications. general complications. comparison group main group total without complications 43(70,5%) 42(95,4%) 85(81%) postoperative complications 18(29,5%) 2(4,5%) 20(19%) reliability χ 2 =10.33, p=0.0013 postoperative complications suppuration of the wound 5(8,2%) 5(4,7%) bleeding from a wound 3(5%) 3(2,8%) pneumonia 2(3,2%) 2(2%) pleurisy 3(5%) 1(2,2%) 4(3,8%) intra-abdominal bleeding 1(1,6%) 1(1%) cardiovascular complications 4(6,5%) 1(2,2%) 5(4,7%) total 61(100%) 44(100%) 105(100%) in the main group, it was possible to reliably (χ 2 = 10.33, p = 0.0013) reduce the number of postoperative complications from 29.5% to 4.5%. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 73 the total number of specific complications observed in the immediate postoperative period was 83.8%. at the same time, thanks to a new method of surgical treatment of hh, in the main group it was possible to reduce the number of patients without specific complications from 73.7% in the comparison group to 97.7% in the main group. specific complications developed in 17 patients, which amounted to 16.2%. analysis of specific complications is presented in table 4. table 4. specific complications specific complications comparison group main group total without specific complications 45(73,7%) 43(97,7%) 88(83,8%) specific complications 16(26%) 1(2,2%) 17(16,2%) reliability χ 2 =10.8, p=0.001 specific complications dysphagia 7(11,4%) 1(2,2%) 8(7,6%) reflux esophagitis 4(6,5%) 4(3,8%) gastrostasis 5(8,2%) 5(8,5%) total 61(100%) 44(100%) 105(100%) in the main group, thanks to the proposed method, it was possible to reliably (χ 2 = 10.8, p = 0.001) reduce the number of specific complications from 26% in the comparison group to 2.2% in the main group. among the specific complications in the immediate postoperative period, we noted the following: dysphagia was observed in 8 (7.6%) patients, of which in 7 (11.4%) patients in the comparison group and in 1 (2.2%) patients in the main group; reflux esophagitis was observed in 4 (6.5%) patients, only in the comparison group; gastrostasis was diagnosed in 5 (8.2%) patients also only in the comparison group. the duration of the postoperative period. as the analysis of the duration of the postoperative period has shown, the number of patients with the shortest period of the postoperative period "up to 5 days" was observed in 4 (3.8%) patients. the largest number of patients were discharged within 5 to 7 days 70 patients, which amounted to 66.6%. in terms of 7 to 10 days, 25 (23.8%) patients were discharged, and the art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 74 longest postoperative period of 10 or more days was observed in 6 (5.7%) patients (table 5). table 5 duration of the postoperative period bed days comparison group main group total up to 5 4(9%) 4(3,8%) 5-7 30(49,1%) 40(91%) 70(66,6%) 7-10 25(41%) 25(23,8%) 10 and more 6(9,8%) 6(5,7%) total 61(100%) 44(100%) 105(100%) reliability χ 2 =20,03, p=0.000008 as follows from the table, thanks to the introduction of a new method of surgical treatment of hh, the stages of which are aimed at the prevention of postoperative complications, as well as the possibility of laparoscopic execution, in the main group, 91% of patients were discharged on the 5th day after the operation, and patients after laparoscopic operations were discharged on the 3rd and 4 days after surgery, which amounted to 9%. in the comparison group, there were no patients discharged within 5 days. with a favorable course, in the comparison group, patients were discharged within 5 to 7 days and amounted to 49.1%. in terms of 7 to 10 days, 41% of patients were discharged with general or specific complications. the longest postoperative period was also observed only in the comparison group in 6 patients and amounted to 9.8%. long-term results. after undergoing operations, out of 105 patients, in the long-term period from 1 month to 2 years, 93 patients were examined, which amounted to 88.5%, and 12 (11.4%) patients did not appear on time for the control examination. in the comparison group, out of 61 operated patients, 49 (80.3%) were examined, and 12 (19.6%) were not examined. in the main group, at various times after the operation, all 44 (100%) patients were examined (table 6). table 6 long-term observation art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 75 terms of observation cg n=61 mg n=44 total n=105 not observed 12(19,6%) 12(11,4%) 1 to 3 months 28(46%) 27(61,3%) 55(52,3%) 4 to 6 months 17(27,8%) 11(25%) 28(26,6%) 1 year 4(6,5%) 4(9%) 8(7,6%) 2 years 2(4,5%) 2(2%) total 49(80,3%) 44(100%) 93(88,5%) in terms of 1 to 3 months, 55 (52.3%) patients underwent control examination, of which 28 (46%) were patients in the comparison group and 27 (61.3%) were patients in the main group. in the period from 4 to 6 months after the operation, 28 (26.6%) patients, 17 (27.8%) patients in the comparison group and 11 (25%) patients in the main group were examined. a year after the operation, 8 (7.6%) patients, 4 (6.5%) patients from the comparison group and 4 (9%) patients from the main group were examined. the longest follow-up period was 2 years after the surgery. during this period, 2 (4.5%) patients of the main group were examined. after examining 93 patients, we found that 77 patients had no specific complications, which amounted to 82.8%. in 16 patients, which amounted to 17.2%, various specific complications were revealed. analysis of specific complications in the long-term period is presented in table 7. table 7 long-term specific complications complications comparison group main group total without specific complications 37(75,5%) 40(91%) 77(82,8%) specific complications 12(24,4%) 4(9%) 16(17,2%) reliability χ 2 =3,86, p=0.049 specific complications dysphagia 4(8,1%) 2(4,5%) 6(6,4%) recurrent reflux esophagitis 3(6,1%) 1(2,2%) 4(4,3%) gastrostasis 2(4%) 1(2,2%) 3(3,2%) recurrent hh (clinically significant) 2(4%) 2(2,1%) recurrent hh (clinically insignificant) 1(2%) 1(1%) total: 49(100%) 44(100%) 93(100%) art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 76 in the main group in the long-term period, the number of specific complications was significantly (χ 2 = 3.86, p = 0.049) lower than in the comparison group. discussion of research results as follows from the table, dysphagia was established in 6 (6.4%) patients, while in 4 (8.1%) patients in the comparison group and in 2 (4.5%) patients in the main group. recurrent reflux esophagitis was established in 4 (4.3%) patients, of which 3 (6.1%) patients in the comparison group and 1 (2.2%) patients in the main group. gastrostasis was observed in 3 patients, which amounted to 3.2%. of these, in the comparison group in 2 (4%) patients and in 1 (2.2%) in the main group. relapse of hh was observed only in the comparison group in 3 (6.1%) patients. at the same time, a clinically significant relapse, accompanied by a relapse of preoperative complaints of heartburn, belching and feeling of a "lump" behind the breastbone after a meal, was observed in 2 patients, which amounted to 4%. clinically insignificant recurrence of hh, not accompanied by any complaints, was observed in 1 patient, which was 2%. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 77 conclusions partial or total necrosis of the hernial contents, which occurs during infringement in type ii and iii hh, determines the absolute indications for surgical treatment in the diagnosis of the latter; measurement of the apf and assessment of the severity of atrophy of the legs of the diaphragm, with hh of the ii and iii types, is considered mandatory when choosing a surgical aid; if the sfa is more than 10 cm², as well as in the presence of atrophy of one or both legs of the diaphragm, prosthetic hiatus is indicated; the stages of the proposed method of surgical treatment of hiatal hernia are aimed at preventing the development of both general and specific complications in the immediate postoperative and long-term periods. the use of prosthetic hiatoplasty made it possible to reliably (χ 2 = 10.33, p = 0.0013) reduce the number of general postoperative complications from 29.5% to 4.5%. thanks to the proposed method, it was also possible to reliably (χ 2 = 10.8, p = 0.001) reduce the number of specific complications from 26% in the comparison group to 2.2% in the main group. in the main group in the long-term period, the number of specific complications was significantly (χ 2 = 3.86, p = 0.049) lower than in the comparison group. references 1. abu-seida a. diagnostic and treatment challenges for diaphragmatic hernia in equids: a concise review of literature. j equine vet sci. 2021 nov;106:103746. 2. dallemagne b, quero g, lapergola a. treatment of giant paraesophageal hernia: pro laparoscopic approach. hernia. 2018 dec;22(6):909-919. 3. dreifuss nh, schlottmann f, molena d. management of paraesophageal hernia review of clinical studies: timing to surgery, mesh use, fundoplication, gastropexy and other controversies. dis esophagus. 2020 aug 3;33(8):doaa045. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5701370 78 4. granderath fa, schweiger um, pointner r. laparoscopic antireflux surgery: tailoring the hiatal closure to the size of hiatal surface area. surg endosc. 2007 apr;21(4):542-8. 5. karatay e, gok ma, javadov m. measurement of hiatal surface area and other hiatus oesophageal diameters at computed tomography imaging in patients with gastroesophageal reflux disease and its relationship with hiatal hernia. j minim access surg. 2021 oct-dec;17(4):537-541. 6. kohn gp, price rr, demeester sr, zehetner j, muensterer oj, awad z, mittal sk, richardson ws.; sages guidelines committee. guidelines for the management of hiatal hernia. surg endosc. 2013 dec;27(12):4409-28. 7. lovece a, sironi a, asti e, milito p, boveri s, bonavina l. laparoscopic surgery for recurrent hiatal hernia: clinical outcomes and quality of life. j gastrointest surg. 2021 oct 19. doi: 10.1007/s11605-021-05165-0. 8. maret-ouda j, wahlin k. association between laparoscopic antireflux surgery and recurrence of gastroesophageal reflux. jama 2017;318(10): 939-946. 9. mazer l, telem da. paraesophageal hernia: current management. adv surg. 2021 sep;55:109-122. 10. pham m, cohen-hallaleh r. laparoscopic repair of para-esophageal hernia using absorbable biosynthetic mesh. j vis exp. 2021 sep 11;(175). 11. rodríguez de santiago e, albéniz e, estremera-arevalo f. endoscopic anti-reflux therapy for gastroesophageal reflux disease. world j gastroenterol. 2021 oct 21;27(39):6601-6614. 12. suppiah a, sirimanna p, vivian sj, o’donnell h, lee g, falk gl. temporal patterns of hiatus hernia recurrence and hiatal failure: quality of life and recurrence after revision surgery. dis esophagus. 2017;30(4):1–8. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 11 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 12 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 13 dynamics of markers of bone metabolism in the oral fluid in patients with diseases of the cardiovascular system in preparation for dental implantation a.a. khadjimetov, a.a. yuldashev. tashkent state dental institute abstract. the purpose of this study was to study the dynamics of markers of bone metabolism in the oral fluid in patients with diseases of the cardiovascular system in preparation for dental implantation. a total of 74 patients with chronic generalized periodontitis and concomitant diseases of the cardiovascular system and with partial secondary adentia (absence of 1-2 teeth, duration of dentition defect up to 1 year) were examined before dental implantation. oral fluid in patients with chronic periodontal pathology and combined disease of the cardiovascular system during the preparation of dental implantation is statistically significant, indicating the state of the alveolar bone and hard tissues of the teeth on the contact and cervical surfaces. keywords: alkaline phosphatase, osteocalcin, hydroxyproline, calcium, phosphorus, oral fluid, urine introduction. as you know, the success of dental implantation is associated primarily with the osseointegration of implants, their survival and long-term functional constancy. meanwhile, a very important condition for bone restoration and osseointegration of dental implants is the normal functioning of the bone tissue, which is ensured by the balance between the interrelated processes of bone resorption and its formation. the noticeable influence of osteocytes and immune cells has recently been widely discussed as a key regulatory moment in the osseointegration of a dental implant. changes in homeostasis that occur during the development of inflammatory and destructive processes in the maxillofacial region can affect the biochemical parameters of the oral fluid, which, along with other compounds, contains a system of enzymes that activate various osteogenesis processes. according to the literature, based on the dynamics of the parameters of the oral fluid (oc), one can judge the activity and completeness of the processes of bone tissue regeneration, and the analysis of specific components in the oc reflects the state of the periodontium around the implant, including the development of the inflammatory process in soft tissues. alkaline and acid phosphatase levels are one of the markers that allow assessing the processes of bone tissue regeneration. alkaline phosphatase plays a key role in mineralization by breaking down inorganic pyrophosphate and releasing free inorganic phosphate. it is believed that this enzyme can also be used as a biochemical marker to determine the activity of osteoblasts, since it is present on fragments of their plasma membranes. one of the important markers of bone metabolism is osteocalcin, which is a non-covalent calcium-ion binding protein, also known as yart of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 14 carboxyglutamic acid protein, produced by both osteoblasts and odontoblasts. osteocalcin binds hydroxyapatite and calcium during the mineralization of the organic matrix. it is one of the serological markers in the process of bone formation. found that osteocalcin plays an important role in the formation and metabolism of bone tissue. it should be noted that in many studies, blood was the material for studying the processes of reparative bone regeneration, and very little information is available on the determination of the above parameters in gastric cancer. to date, there are limited studies examining bone metabolism around dental implants, the consequences and complications of dental implantation, and most of these studies are experimental in nature. most researchers believe that the use of alkaline phosphatase and osteocalcin as potential indicators of the activity of reparative and destructive inflammatory processes requires more detailed study. based on the foregoing, the purpose of this study was to study the dynamics of markers of bone metabolism in the oral fluid in patients with diseases of the cardiovascular system in preparation for dental implantation. material and research methods we examined 109 people aged 40 to 60 years, all patients showed signs of chronic generalized periodontitis (cgp). in accordance with the objectives of the study, 3 groups were formed: group i 50 patients (39 men and 11 women) with chronic generalized periodontitis against the background of ah and ihd: exertional angina pectoris ii-iv functional class (according to the canadian classification), aged 43 to 60 years. group ii 34 patients (22 men and 12 women) with cgp on the background of ah and coronary artery disease combined with adentia who are at the stages of treatment for cvd, group iii 25 patients (15 men and 10 women) with periodontal pathology (cgp), without diseases of the cardiovascular system (cvs) at the age of 40 to 60 years. it was mandatory for all study participants to read and sign an informed consent approved by the local ethics committee of the ministry of health of the republic of uzbekistan. it should be noted that all patients included in the groups were examined by a cardiologist. to clarify the diagnosis of coronary artery disease, all patients underwent physical and instrumental examination: ecg at rest in 12 conventional leads, twodimensional echocardiography, coronary angiography, 24-hour blood pressure monitoring, 24-hour holter monitoring and laboratory studies. all patients were examined by a dentist. a standard clinical dental examination was carried out: assessment of patient complaints, medical history and life, objective status, assessment of periodontal indices. the level of individual hygiene and the condition of periodontal tissues were assessed in all patients. the hygienic state of the oral cavity was determined by the green-vermillion (ohi-s) method (simplified oral hygiene index). the depth of the periodontal pocket (pc) and the art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 15 loss of the periodontal attachment (pzp) were measured. gingival bleeding was assessed using h.r. muhleman. tooth mobility was determined using the miller scale (modified by t.j. fleszar). to identify the developed forms of periodontal pathology, the periodontal index was used (pi, rüssel, 1956); the degree of gingival recession according to p.d. miller (1985). oral fluid (or), which was collected on an empty stomach, from 8.00 to 9.30 was used as a biological material. the activity of alkaline phosphatase and the content of osteocalcin in the gastric fluid were measured by elisa using diagnostic test kits from hoffmann-laroche (switzerland). to study calciumphosphorus metabolism, the daily excretion of calcium and phosphorus in the urine was determined. the calcium content was determined in daily urine by the greenblatt and hartman method. determination of inorganic phosphorus in daily urine was carried out according to the method of o.a. bodansky (1978). the excretion of free hydroxyproline in daily urine was carried out according to the method of neumann and logan modified by p.n. sharaeva (2002). statistical processing of the obtained data was carried out using standard software packages statisticaversion7.0 (usa). differences in comparison of mean values in paired comparisons were considered significant when _p <0.05. research results and their discussion when analyzing the dental status of patients, more pronounced changes in the periodontal index were found, which indicates inflammatory processes in the periodontium of patients of the first and second observation groups. the average value of the pma index in the observation group was 63% (in the comparison group 34%), the periodontal index russel-pi = 4.9 ± 0.3 (in the comparison group 1.4 ± 0.1). the pbi bleeding index in the observation group is almost three times higher than in the comparison group (3.1 and 1.1, respectively), although the mean values of the ohi-s hygiene index in patients of the observation group and the comparison group differ insignificantly: 2.5 and 2.3 ... the main factor affecting the state of the periodontium in patients without concomitant pathology is the hygienic state of the oral cavity. the values of hygiene indices in the observation group were statistically significantly higher than in the comparison group, which indicated a deterioration in the state of oral hygiene. based on the complaints identified, it should be assumed that the majority of patients with coronary heart disease have bleeding gums; they art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 16 associate this with the intake of antiplatelet agents and anticoagulants, and not with unsatisfactory hygienic care. the analysis of the obtained research results showed that the majority of patients of group i complained of gum bleeding (spontaneous, when eating and brushing teeth) 57.9%. in group ii patients, bleeding of the gums was observed only in 68.7%. pain sensations when chewing food and brushing teeth were more often observed in patients of group ii 69.4%, in group ii 20%. no less characteristic complaint in generalized periodontitis is the mobility of the teeth, so. group i patients noted this symptom in 65.1% of cases, versus 72% of group ii patients. table 1 patient complaints group i patients n = 50 group ii patients n = 34 comparison group n = 25 bleeding gums 31 (61%) 28 (83%) 6 ( 25%) painful sensations (when experiencing food, brushing teeth) 26 (52%) 24 (71%) 4 (17%) tooth mobility 27 (54%) 23 (67%) 5 (18%) dry mouth 31 (62%) 27 (78%) 10 (39%) burning tongue 15 (29%) 12 (34%) 5 (18%) smell from the mouth 38 (76%) 28 (84%) 11 (42%) thus, all patients of groups i and ii presented complaints. associated with periodontal damage. the study of periodontal pockets revealed that in patients of group i, the average value of the pocket depth was 3.7 ± 1.5 mm. in patients of group ii 4.1 ± 0.3. to assess the state of the periodontium, the cpitn index was calculated. these tables show that more severe periodontal damage is observed in the second group than in the first group of patients, this is shown by the high values of the cpitn index. analysis of the ohi-s hygiene index (g&v) shows that higher values are noted in both the first and second groups. the pi index, which reflects the severity of periodontal lesions, is 3.9 ± 0.5 in the first group, and 4.1 ± 0.3 in the second group. at the same time, the maximum value of the pi index was noted in cgp against the background of coronary artery disease with art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 17 combined adentia. it is 4.1, which corresponds to a moderate-severe degree of chronic generalized periodontitis. alkaline phosphatase levels are one of the indicators that allow assessing the processes of bone tissue regeneration. it was found that this enzyme is involved in the regulation of phosphorus-calcium metabolism. alkaline phosphatase plays a key role in mineralization by breaking down inorganic pyrophosphate and releasing free inorganic phosphate. it is believed that this enzyme can also be used as a biochemical marker to determine the activity of osteoblasts, since it is present on fragments of their plasma membranes. alkaline phosphatase is directly involved in the implementation of the phagocytic function and its level changes depending on the severity of the inflammatory and necrotic process of the tissue. the data we obtained, presented in table 2, indicate the inhibition of the enzyme activity in the examined persons of groups 1 and 2 relative to the indicators of the comparison group. as you know, one of the important markers of bone metabolism is osteocalcin, which is a non-covalent calcium-ion binding protein produced by both osteoblasts and odontoblasts. osteocalcin binds hydroxyapatite and calcium during the mineralization of the organic matrix. the analysis of the obtained research results showed that in patients of the 1st group the content of osteocalcin in the oral fluid increased insignificantly, while in the patients of the 2nd group the increase in osteocalcin was significantly higher on average by 26% relative to the indicators of the comparison group. the increase in the levels of osteocalcin in the oral fluid in the examined persons with concomitant pathology indicated the formation and metabolism of bone bone tissue. a comparative analysis of the study results regarding the excretion of oxyproline in daily urine revealed an increase in this indicator in the main group compared with the comparison group. so the indicators of hydroxyproline in urine in patients of group 1 exceeded the initial level by 14%, while this indicator in patients of group 2 averaged 81.63 ± 5.33 μmol / l, which is 38% higher than the indicators of the comparison group. table 2 indicators of markers of bone metabolism in patients with the disease cardiovascular system in preparation for dental implantation indicators group iii comparisons n = 25 the patients i-groups n = 50 the patients ii-groups n = 34 alkaline phosphatase in the oral fluid u / l 28,98 ± 1,21 27,17 ± 1,14 25,02 ± 1,03* art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 18 osteocalcin in the oral fluid u / l 0,73 ± 0,05 0,81 ± 0,07 0,92 ± 0,08* free hydroxyproline in urine, μmol / l 59,17 ± 4,03 67,24 ± 4,89 81,63 ± 5,33* calcium content in urine, μmol / l 2,28 ± 0,19 2,59 ± 0,17 3,34 ± 0,21* phosphorus content in urine, μmol / l 21,03 ± 1,42 23,58 ± 2,07 27,12 ± 1,62* note: *reliability of differences p <0.05 relative to the group comparisons when analyzing the elemental composition of urine in the examined individuals, it was found that the average indicators of calcium concentration in the urine in patients of group 1 relative to the indicators of the comparison group increased by 14% and amounted to 2.59 ± 0.17 μmol / l versus 2.28 ± 0.19 μmol / l. in the group of patients with concomitant pathology against the background of adentia, the average was 3.34 ± 0.21 μmol / l, which is 46% higher than the initial values. the average indicator of the level of phosphorus in urine in patients of group 1 increases to 23.58 ± 2.07 μmol / l, which is 12% more than in the comparison group. in patients with chronic periodontal pathology and combined disease of the cardiovascular system against the background of adentia, the studied indicator was 27.12 ± 1.62 μmol / l , which is 29% higher than the initial indicators. thus, the results of a comprehensive assessment of the metabolic state of bone tissue in patients with chronic periodontal disease and combined cardiovascular pathology indicate a systemic impairment of the remodeling of the alveolar bone of the jaw, depending on the severity of the underlying and concomitant pathology. the pathological changes are based on increased resorption of bone tissue and suppression of the processes of its formation. at the same time, the biochemical parameters of the oral fluid and urine of the examined patients allow us to assess the intensity of damage to soft tissues, alveolar bone and hard tissues of teeth on the contact and cervical surfaces. conclusions 1. a decrease in alkaline phosphatase activity and an increase in osteocalcin in the oral fluid in patients with chronic periodontal pathology and combined disease of the cardiovascular system during the preparation of dental implantation is statistically significant, indicating the state of the alveolar bone and hard tissues of the teeth on the contact and cervical surfaces. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080522 19 2. the content of hydroxyproline, calcium and phosphorus in urine was increased relative to the comparison group. the revealed features of mineral mineral metabolism in patients with combined pathology confirm the possibility of the development of osteopenic 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(7): 2075-2089. volume-1 issue-1 art of medicine international medical scientific journal 1 art of medicine international medical scientific journal volume-1 issue-1 2 art of medicine international medical scientific journal volume 1, issue 1, may 2021 volume-1 issue-1 art of medicine international medical scientific journal 3 founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine international medical scientific journal chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen art of medicine international medical scientific journal volume-1 issue-1 4 content tursunova l. d., jabbarov o. o. application of sakabutril/valsartan in patients with chronic kidney disease with type 2 diabetes mellitus...............................5 l.s. khamraeva., d.u. narzullaeva features of calculating the optical power of an intraocular lens in children with congenital cataracts at the risk of developing pseudomyopic myopia.....................10 kasimova m. s., iminova m. m., ashurov o. m. ophthalmologic complications in the structure of the clinical features of novel coronavirus infection (covid-19)......................................................................................................14 fattayeva d.r., rizayev j.a., rakhimova d.a. improvement of methods for correction of clinical and immunological disorders in comorbid state of chronic gaymoritis after covid-19....................................................................17 polatova d.sh., abdukarimov kh.g., davletov r.r., savkin a.v., sultanov b.b features of immunobiological heterogeneity in patients with osteosarcoma.................................................................................25 art of medicine international medical scientific journal volume-1 issue-1 14 ophthalmologic complications in the structure of the clinical features of novel coronavirus infection (covid-19) kasimova munirakhon sadikjanovna, iminova mufazzal muzaffarovna ashurov olimjon mirzazhanovich center for development of professional qualifications of medical workers republican clinical ophthalmology hospital tashkent emergency hospital abstract. the data from 26 patients suffering from covid-19 during the manifestation of the disease served as the material for the research. the features of pathological processes in various parts of the organ of vision have been demonstrated with the help of ophthalmologic and standard examination methods. the data received, together with information from the reference materials, allow us to draw conclusions about the damage to the structures of the organ of vision under covid-19, depending on the concomitant somatic pathology and the state of homeostasis in the body. emphasis is placed on mutiltifactory lesion of both the front segment and the vitreoretinal interface. today, the variability of ophthalmic complications is demonstrated in the form of catarrhal conjunctivitis, vascular and inflammatory lesions, in the flesh to the phlegmon of the orbit and thrombosis of the carotid-cavernous sinus, which is a frightful and life-threatening condition. in the light of the foregoing, it can be concluded that today the organ of vision is a target organ under covid-19. thus, ophthalmologists are required to develop a unified classification for ophthalmic complications under covid-19, which facilitates the effective management and pathogenetic targeted correct therapy. key words: organ of vision, papilophlebitis, hemophthalmos, caratid-cavernous sinus, retrobulbar neuritis relevance of the topic. after severe respiratory syndrome and middle east respiratory syndrome in 2004, the 2019 global pandemic caused by a novel β-coronavirus virus, called sars-cov-2, was the third coronavirus pandemic in 2019. the source of sars-cov-2 has not yet been identified, but there are suggestions about the zoonotic type of infection. human-tohuman transmission occurs through close contact with an infected person, due to airbornedroplets, air-dust transmission path. also, recorded and described the contact-household and fecal-oral transmission routes. the average infected age is 51. the most severe course develops in patients 60 years and older, with concomitant diseases such as diabetes mellitus (20%), arterial hypertension (15%), and other cardiovascular diseases (15%) [1]. the clinical picture can vary from acute respiratory viral infection (mild course) 80%, to pneumonia with symptoms of respiratory failure, ards, respiratory distress syndrome, sepsis and septic (infectious toxic) shock (severe course). it gives negative impacts, with lesions of target organs such as heart, brain, kidneys and eyes to multiple organ failure. hypoxemia develops in more than 30% of those infected (spo² less than 88%) [2]. the disease can be attributed to generalized vasculitis, and the developing lung pathology is a variant of angiogenic pulmonary edema. the pathogenesis of covid-19 fits not only into the picture of catarrhal phenomena in the upper and lower respiratory tract. one of the main damaging factors is a violation of blood coagulability with the start of intravascular disseminated coagulation. volume-1 issue-1 art of medicine international medical scientific journal 15 at an early stage of the epidemic, ophthalmic symptoms manifested themselves in the form of follicular conjunctivitis. with the passage of time, and the clinical symptoms were studied in more depth, the sources report increasingly of damage to the posterior segment of the eyeball and the adnexa of the organ of vision. patients with confirmed sars-cov-2 manifested central retinal vein thrombosis in combination with thrombosis of the lower extremities [3]. a case of papilophlebitis was registered it is a variety of occlusion of the central retinal vein. in both cases the authors indicate that the cause was hypercoagulation [4]. in addition, there is data on the registration of vitriitis and other diseases of the choroid of an inflammatory nature. the authors suggest this can be caused by the autoimmune genesis of the disease [5]. as of today, the sources do not portray the variations of ophthalmic complications and specific management tactics for patients with severe forms of damage to the organ of vision under covid-19. aim of the study. develop generalization and summary of the variability of ophthalmic complications under (when infected with) covid-19. materials and methods used. the findings from clinical and functional studies were based upon the analysis of data from 26 (52 eyes) patients with a confirmed diagnosis of covid-19 during the period of manifestation of the disease, with ophthalmological complications. they were hospitalized in the emergency ophthalmology department of the tashkent clinical emergency hospital in the period from 09.10.20 20.11.2020. among them, there were 13 males, 11 females, aged 18 to 81. the sars-cov-2 virus was detected through pcr testing in 18 (69%) patients. all patients were diagnosed with polysegmental viral pneumonia with the 1-3rd degree of severity of lung lesions, according to computed tomography (ct) and through arf (acute respiratory failure) testing 1-2nd degree severities. in the medical history of somatic diseases, hypertension was recorded in 5 (19%) patients, type ii diabetes mellitus was recorded in 9 (34.6%) patients, 5 (19%) patients had mild and moderate iron deficiency anemia, 5 (19%) patients had rhinosinusitis, sinusitis was recorded in 2 (7.6%). 2 patients suffered from ophthalmic complications in the form of moderate myopia, open-angle glaucoma was found in 1 patient, cataracts was found in 3 patients, diabetic retinopathy in the paired eye was found in 4 patients, and 2 patients had hypertensive angiopathy. the research involves: collection of anamnestic data and complaints about the presence of changes in taste and smell; clarification of the degree of severity ct according to medical records. in compliance with the temporary methodological recommendations developed by the ministry of health of uzbekistan, with purpose of prevention, diagnosis and treatment of new coronavirus infection, patients with covid-19 received symptomatic, immune-modulatory, antiviral, anticoagulant, prophylactic antibacterial therapy. all patients received traditional ophthalmological examinations, such as: visometry with determination of the maximum corrected visual acuity, according to the table (hcp 700, huvitz, korea), auto-refractometry, tonometry (maklakov), non-contact ophthalmotonometry (trk-1p, topcon, japan), b-scanning, statistical perimetry (hfa 745 i, carl zeiss, germany), direct and reverse ophthalmoscopy (with a 90.0d noncontact lens, in addition to the standards, optical coherence tomography (oct) was performed on the rtvue 100 apparatus (optovue, usa). the patients also received mri of the brain as well as consultation based on indications from ent specialists, neurosurgeons, hematologists and endocrinologists. analysis of the statistical data. details are presented for continuous values as average and standard deviation; for an overview of the presence of signs, the absolute number of patients and the percentage of the total group size are presented. fisher's exact test art of medicine international medical scientific journal volume-1 issue-1 16 was used to compare the data. p < 0.05 was considered a statistically significant difference. statistical data processing was carried out on a personal computer using microsoft excel 2016 software. results bacterial conjunctivitis encountered in 2 (7.5%) cases, and acute catarrhal conjunctivitis in 2x (7.5%) cases. all patients with id (iron deficiency) anemia of varying degrees suffered from acute herpetic keratitis 4 (15%); acute iridocyclitis was observed in one patient with type ii diabetes mellitus and in 2 patients with rhinosinust (11.5%); posterior uveitis in 4 (15%) patients with type ii diabetes mellitus; in 3 patients with hypertension of various degrees and type ii diabetes mellitus and in one patient isolated with hypertension, hemophthalmus was recorded in total 4 (15%); acute circulatory disorders in the central retinal artery in 2 (7.6%) patients with hypertension; neurovasculitis was observed in the 1 (3.8%) patient with id anemia; the patient with retrobulbar neuritis had no concomitant pathology -1 (3.8%); phlegmon of the orbit, followed by thrombosis of the cavernous sinus was observed in 3 patients (11.5%) with rhinosinusitis and sinusitis. findings the cited arguments justify the cause of multifocal damage to the organ of vision when infected with covid-19. the degree and nature of disorders in the tissues of the organ of vision depends on the individual characteristics of the organism. provided we consider id anemia as a factor influencing immunodeficiency, then the level of id anemia under covid-19 can contribute to the development of other viral infections (in our cases herpes simplex). metabolic syndrome have brought vascular complications such as ischemic (in nature), and complications of an inflammatory nature. the latter was complicated ent pathologies up to cavernous sinus thrombosis. based on the afore-mentioned, it can be concluded that today the organ of vision is a target organ under covid-19, and ophthalmologists need to develop a unified classification concerning ophthalmic complications under covid-19. this facilitates the management and pathogenetic targeted correct therapy. references: 1.îíóôðèé÷óê î.í., ãàçèçîâà è.ð., ìàëþãèí á.ý., êóðîåäîâ à.â. êîðîíàâèðóñíàÿ èíôåêöèÿ (covid-19) îôòàëüìîëîãè÷åñêèé ïðîáëåìû. îáçîð ëèòåðàòóðû /015/ îôòàëüìîõèðóðãèÿ. 2020. ¹3. ñ. 115-125 2.hoffman m., kleine-weber h., schroeder s. et al. sars-cov-2 cell entry depends on ace2 and tmprss2 find is blocked by a clinically proven protease inhibitor // cell. 2020. vol. 181. p. 1-10. 3.insausti-garcia a., reche-sainz j.a., ruiz-arranz c. et al. papillophlebitis in a covid-19 patient: inflammation and hypercoagulable state // europ. j. ophthalmol. 2020. vol. 30. p.55-59 https://doi.org/10.1177/1120672120947591 4.marinho p., marcos a., romano a. et al. retinal findings in patients with covid19 // lancet. 2020. vol. 395 (10237). p. 1610. 5.sadjoro de figereyredo k., raoni o., gestal-de-araujo e. sara-cov2, ïîðàæàþùèé ñåò÷àòêó: âçàèìîäåéñòâèå õîçÿèíà ñ âèðóñîì è âîçìîæíûå ìåõàíèçìû âèðóñíîãî òðîïèçìà // ocul. immunol. inflamm. 2020. vol. 28, ¹8. p. 1301-1304. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5847906 11 art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5847906 12 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5847906 13 influence of working conditions in uzbek silkworm plants on the functional state of the body of women iskandarov aziz bakhromovich doctor of philosophy (ph.d.) in medical sciences, senior researcher of the scientific research institute of sanitation, hygiene and occupational diseases of the ministry of health of the republic of uzbekistan abstract: workers' working conditions in producing silkworm grapes do not comply with hygienic regulations. analysis of the dynamics of the indicators of the functional state of their bodies showed that from the beginning to the end of the working day, physiological reactions are indicating pronounced industrial fatigue. the introduction of preventive measures is necessary to reduce the fatigue of the labor process. keywords: silkworm production, working conditions, functional state of the body, fatigue, prevention. the production of natural silk is increasing year by year in uzbekistan. the government's investment policy of the republic has allowed in recent years to more than 2 times increase the volume of production of domestic productive breeds of mulberry silkworms, than which cocoons are grown. uzbekistan ranks 4th in the world after china, vietnam, and india production of live cocoons. currently, there are 17 silkworm plants and 3 breeding silk stations producing elite and super elite grennas in uzbekistan. the peculiarity of the technological process of grenache production, increasing from year to year volumes of grenache production, cause the employment of a large contingent of working women in this agricultural branch of the national economy of the republic. the technological process of grenade production (mulberry silkworm eggs) is divided into two stages. the first stage is the fattening of caterpillars (april-may), which is carried out on farms. the second stage is acceptance of cocoons at mulberry silkworm plants, papilionage operations (leaving cocoons, laying them on frames for mating, steaming moths and collecting deposited larvae), processing, washing and hanging larvae (june); storage of larvae in cold storage chambers in winter conditions (novemberfebruary). the main sanitary and hygienic factors during the feeding period of silkworm caterpillars, which lasts up to 30 days, are heating, humid microclimate of wormhouses, abundant microflora, high content of carbon monoxide vapor, hydrogen sulfide and ammonia, dusty air, irregular, intensive work with considerable physical exertion. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5847906 14 the duties of worm breeders include collecting and preparing silkworm leaves, stacking them in the worm houses, and working with mulberry silkworm caterpillars. women mostly perform all production operations. work involving the collection and preparation of mulberry leaves takes up to 50% of worm breeders' daily time, i.e. up to 12 hours. in the breathing zone during this period, they determine dust, the source of which is dusty silkworm branches. concentration of dust varies from 5,8 to 7,4 mg/m3, average level is 6,7 mg/m3 (mac-6,0 mg/m3) [2]. during this period, the severity of the labor process is associated with the need to lift and carry mulberry leaves to worm-houses at a distance of more than 5 meters. the physical dynamic load during this labor operation (involving arm, trunk and leg muscles) is more than 40000 kgm. worm breeders systematically put mulberry leaves to caterpillars during the day, every day they come into contact with mulberry silkworm caterpillars and products of their life activity for an average of 4 hours. while in worm-houses, working women are exposed to a warming, humid, convectional microclimate. the air temperature in worm-houses during the fattening period varies from 24 to 36°c and averages 29.8°c, the relative humidity is 26-55% (the average is 38.8%), and the air is low-moving. it was found that total insemination characterizes the air in the worm-houses with sanitary-positive microorganisms, the level of insemination is within hygienic norms. sanitary-positive microorganisms were also detected on clothes and exposed body parts of working women. the presence of hydrogen sulfide, ammonia and carbon monoxide vapors was also detected in the air in the worm-houses. the content of ammonia in the air of worm-houses in the breathing zone of fatteners exceeded mpc 1.1 times, the average concentration being 22,2±0,7 mg/m3. the content of hydrogen sulfide (a substance with an acute effect) in the breathing zone of fatteners exceeds the mpc 1.3 times, the average concentration is 13.0±0.56 mg/m3. carbon monoxide content in the breathing zone of worm breeders did not exceed on average the sanitary norms, it was equal to 14,3±1,4 mg/m3. illumination of working surfaces in worm-houses is natural, artificial light is turned on only in the dark time of day. the level of illumination is uneven and varies from 5 to 800 lux, the average level is 111.6±9.8 lux, the coefficient of natural illumination (cei) ranges from 0.45 to 5.79%, on average cei is 2.04%. working conditions of women engaged in feeding silkworm caterpillars belong to the 3rd class of the 3rd degree of hazard [3,6]. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5847906 15 a study of the functional state of women engaged in feeding silkworm caterpillars showed that 57.3% of those examined had elevated blood pressure. more often, elevated blood pressure was in low-salary women. with increasing length of service associated with feeding silkworm caterpillars in women increases the difference between proper and actual biological age: with the length of service of 1 year biological age is higher than the proper biological age on average of 2.3 years, with up to 10 years of service this figure increases to 5 years, with experience over 15 years biological age is 12.5 years above the proper biological age [biol.oz]. besides, with the increased length of service, the indicators characterizing subjective estimation of their psycho-emotional state worsen in working women. the obtained data indicate the necessity to develop and implement measures to improve the working conditions of worm breeders. the second stage reception of live cocoons and carrying out papilionage work is carried out at silkworm plants. cocoons are received at the silkworm factories within about 20 days. cocoons are accepted from 6 to 8 a.m., while there is no heat, so as not to damage the pupa inside the cocoon. the agronomist-grener accepts the breeding cocoons and evaluates their quality. accepted by the plant breeding cocoons that are not sorted by sex are transferred to the workshop, where they cut the shell with a blade, released pupa, sorted by sex pupae. one worker cuts off 3-4 kg of cocoons (1 kg 290-300 cocoons). after 3-4 days, the chrysalis turns into a butterfly (usually at 6-7 a.m.) and work with them begins (papillonage). the worker by hand on a frame, the bottom of which is lined with lavsan cloth, throws a certain number of butterflies (50 to 100 pieces) females, then adds a larger number of male butterflies there. after one-hour, free male butterflies (not involved in mating) are manually removed from the frame, the frame is left for another 2 hours. then the frames are placed on racks in workshops with high humidity (more than 80%), which is achieved by watering the floor of the workshop. in 4 hours, the frames are dropped from the butterflies (frame weight 2.5 kg) and the fabric is left on the elite grenade, which is stored until november in conditions of low temperature and high humidity. a complex of adverse factors characterizes working conditions for women working with cocoons, pupae and butterflies: the dustiness of the working area with fine dust during the emergence of butterflies from cocoons; limitation of general mobility, the monotony of work operations (cutting cocoons to release pupae, division of pupae by floor, work with butterflies), performing not very complex production operations, but which require stress of attention and vision, forced, uncomfortable working posture, static muscle tension when lifting the art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5847906 16 during the papilionage period (mating of butterflies) scales are detached from the wings of many butterflies, which fly around in the air. they are irregularly shaped with pointed edges and long spikes. dust from mating plants consists of 75-80% of organic substances of animal origin (the smallest chitinous scales) and contains a small amount (about 0.01%) of protein substances. the size of 90-95% of the dust particles is up to 10 microns. the concentration of dust in the breathing zone of papilionadiers ranges from 5.3 to 12.5 mg/m3 (mpc 4 mg/m3). the organic composition of industrial dust, the presence of a protein of animal origin, shape and size of dust particles have a pronounced allergenic and local irritant effect. during work with cocoons, pupae and butterflies, the air of the working area is polluted with ammonia, hydrogen sulfide and carbon monoxide products of life activity of pupae and butterflies. an excess of ammonia in the breathing zone of women was observed during production operations of separating pupae by sex and removing free male butterflies from the frames. the mean concentrations of ammonia were 21.45±0.7 and 21.3±1.26 mg/m3 (1.06-1.07 times excess of mpc), respectively. content of dihydrosulfide (hydrogen sulfide) in the air of the working area exceeded mpc when free male moths were removed from frames, when moths were steamed and when male moths were removed from frames. mean concentrations of dihydrosulfide at these sites were 11.3±1.26, 13.1±0.69 and 11.2±0.96 mg/m3, respectively (exceeding mpc by 1.12-1.31 times). the excess of carbon monoxide content was detected in the breathing zone of women during the production operation, "cutting the head of a cocoon". the average concentration of carbon monoxide was 22.3±0.43 mg/m3 (exceeding mpc by 1.11 times). in the process of gyre production, a certain temperature-humidity regime is maintained, in which silkworm moths are most viable. meteorological conditions in the silkworm workshops are discomforting: the temperature ranges from 28.8 to 32o c from the beginning to the end of work, humidity is 40-50%. this is achieved by primitive means: darkening the windows from direct sunlight and moistening the rooms' floor. most of the production operations in the silkworm plant are carried out under visual control. the lighting of working surfaces is natural. the level of illumination in different production areas is significantly lower than the hygienic regulations [8], fluctuates on average from 25 to 53 lux, the coefficient of natural lighting is 0.3% on average. all labor processes of silkworm production are characterized by repeated repetition of the same working operations, i.e. refer to monotonous labor. production operations performed when working with pupae more than 25% of working time are art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5847906 17 performed in a forced working posture (squatting, kneeling), when mating and separating butterflies, more than 80% of working time are performed standing, accompanied by the same type of hand movements and associated with the strain of vision. working conditions of women working at the silkworm plants are referred to as the 3rd class of the 3rd degree of harmfulness [3,6]. the study of functional condition of an organism of women working at silkworm works has revealed unfavorable changes from the beginning to the end of a working day in a condition of the higher nervous activity and attention function, deterioration of parameters of the neuromuscular system, not sharply expressed changes of the cardiovascular system, and also premature aging of an organism. specific working conditions in the silkworm industry affect health: some workers suffer from respiratory diseases. to eliminate the adverse effects of the working conditions of silkworm production on the body of working women, it is necessary to use the following recommendations: 1. in order to prevent occupational diseases of female workers in silkworm plants, it is necessary to follow the list of medical contraindications when hiring strictly. persons with severe atrophic rhinitis, laryngitis, tracheitis, chronic bronchitis, bronchial asthma, pulmonary emphysema, pneumosclerosis, bronchiectatic disease, chronic eye diseases (eyelids, conjunctivae, cornea, tear-exhaust), persistent decrease in visual acuity [7] should not be employed at the silkworm plants. 2. an important measure to prevent occupational diseases of silkworms and reduce overall morbidity is to conduct periodic medical examinations. general blood test, chest radiography is mandatory. workers of the silkworm industry must be examined once a year by a therapist, eye doctor, dermatovenerologist and otolaryngologist. 3. in order to prevent occupational diseases to work on feeding silkworms, should be allowed to persons after a preliminary medical examination. in addition, periodic examinations of workers (especially adolescent girls) should be conducted for early detection of diseases of the musculoskeletal system, initial changes in posture and other disorders. arterial hypotension, all forms of anemia and metabolic disorders are contraindications to work in silkworm fattening. 4. artificial local exhaust and supply ventilation with air conditioning should be installed in all production shops. 5. in order to avoid the dust entering the papillary rooms, the silkworm plants must have a set of amenity rooms isolated from production and equipped with a separate entrance: rooms for eating, dressing rooms, showers and toilets. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.5847906 18 6. in the period of papilionage one should use dust-proof respirators such as rh 19 or "lepestok". 7. dry cleaning of rooms by hand is prohibited. it should be done with the help of a vacuum cleaner.. 8. it is recommended to provide the workers of silkworm plants with hot and cooled green and black tea, carbonated water (it should be taken into account that due to the content of caffeine, tannin and vitamins, green tea has a pronounced tonic effect). great importance should be given to a rational and balanced diet. 9. it is forbidden to use the labor of girls under 18 years of age at the silkworm plants according to the "list of jobs with hard and hazardous working conditions, which prohibit the use of the labor of persons under 18 years of age".) 10. weight of lifting and carrying weights for women must not exceed 9 kg, and manual transportation on carts or wheelbarrows 50-60 kg[5]. reference. 1. voytenko v.p., polyukhov a.m., barbaruk l.g. et al. / / biological age, heredity and aging. kiev, 1984. pp. 5-15. 2. iskandarov ty, ibragimova gz, iskandarova gt, feofanov vn, shamansurova hs, tazieva ld. sanitary rules, norms and hygienic standards of the republic of uzbekistan №0294-11 "maximum allowable concentrations (mac) of harmful substances in the air of the working area". -tashkent, 2004. – p.53. 3. iskandarov t.i., ibragimova g.z., shamsurova h.sh., slavinskaya n.v., iskandarova m.s., demidenko n.m., iskandarova g.t., parsegova l.g, feofanov v.n. sanitary rules, norms and hygienic regulations of the republic of uzbekistan #0141-03 'hygienic classification of working conditions according to the indicators of harm and danger of factors of the industrial environment, the severity and intensity of the work process'. tashkent, 2004. -p. 53. 4. iskandarov t.i., slavinskaya n.v. sanitary rules, norms and hygienic standards of the republic of uzbekistan № 0324-16 "sanitary and hygienic norms of the microclimate of production premises. -tashkent, 2016. – p.10. 5. iskandarov t.i., slavinskaya n.v. sanitary rules, norms and hygienic norms of the republic of uzbekistan № 0364-18 "norms of acceptable loads for girls under 18 years old and women when lifting and moving weights manually". -tashkent.2018. – p.9. 6. nichkasov v.m., iskandarov t.i., ibragimova g.z., slavinskaya n.v., iskandarova g.t. "methodology of evaluation of working conditions and certification of workplaces by working conditions". -tashkent, 1996. -p.21. 7. order no. 200 of the ministry of health of the republic of uzbekistan, dated 10 july 2012, "on approval of the provisions on medical inspections of employees". 8.8. 8. construction norms and regulations 2.01.05-98 "natural and artificial lighting". tashkent, 1998. -p.48. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5495417 91 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5495417 92 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5495417 93 the functional state of the women’s body working in the drainage industry iskandarov aziz bakhromovich doctor of philosophy (phd) in medical sciences, senior researcher at the institute of sanitary, hygiene and occupational diseases, ministry of health. tashkent, uzbekistan e-mail: a.iskandarov@yahoo.com abstract: the study of the functional state of women’s bodies working in the drainage industry has revealed unfavorable changes from the beginning to the end of the working day in the state of the higher nervous activity and attention function, the deterioration of the neuromuscular system, not sharply expressed changes in the cardiovascular system and premature aging. the introduction of preventive measures is necessary to reduce the fatigue of the work process. keywords: grinding production, working conditions, functional state of the organism, fatigue, prevention. uzbekistan ranks 4th in the world after china, vietnam and india in the production of live cocoons. currently, there are 17 gerna factories producing gerna and 3 breeding silk stations producing elite and super elite gerna in uzbekistan. investment policy of the government of the republic in recent years has allowed more than a 2-fold increase in the volume of production of domestic productive breeds of mulberry silkworm grennas, from which the cocoons are grown. the peculiarity of the technological process of mulberry production, increasing from year to year volumes of mulberry production, cause the employment of a large contingent of working women in this agricultural sector of the national economy of the republic. the technological process of grenade production (mulberry silkworm eggs) is divided into two stages. the first stage is the fattening of caterpillars (april-may), which is carried out on farms. the second stage is acceptance of cocoons at mulberry silkworm breeding plants, papilionage operations (leaving cocoons, laying them on frames for mating, steaming moths and collecting deposited larvae), processing, washing and hanging larvae (june); storage of larvae in cold storage chambers in winter conditions (november-february). the main sanitary and hygienic factors during the feeding period of silkworm caterpillars, which lasts up to 30 days, are heating, the humid microclimate of wormhouses, abundant microflora, high content of carbon monoxide vapor, hydrogen sulfide and ammonia, dusty air, irregular, intensive work with considerable physical exertion. the duties of worm breeders include collecting and preparing silkworm leaves, stacking them in the worm houses, and working with mulberry silkworm caterpillars. all production operations are performed mainly by women. mailto:a.iskandarov@yahoo.com art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5495417 94 work involving the collection and preparation of mulberry leaves takes up to 50% of worm breeders’ daily time, i.e. up to 12 hours. in the breathing zone during this period, they determine dust, the source of which is dusty silkworm branches. concentration of dust varies from 5,8 to 7,4 mg/m 3 , average level is 6,7 mg/m 3 (mac-6,0 mg/m 3 ) [2]. during this period, the severity of the labor process is associated with the need to lift and carry mulberry leaves to worm-houses at a distance of more than 5 meters. during this labor operation, the physical dynamic load (involving arm, trunk and leg muscles) is more than 40000 kgm. worm breeders systematically put mulberry leaves to caterpillars during the day. every day, they contact mulberry silkworm caterpillars and products of their life activity for an average of 4 hours. while in worm-houses, working women are exposed to a warming, humid, convectional microclimate. during the fattening period, the air temperature in wormhouses varies from 24 to 36°c and averages 29.8°c, the relative humidity is 26-55% (the average level is 38.8%), and the air is low-moving. it was found that the total insemination characterizes the air in the wormhouses with sanitary-positive microorganisms, the level of insemination is within the hygienic standards. sanitary-positive microorganisms were also detected on clothes and exposed body parts of working women. the presence of hydrogen sulfide, ammonia and carbon monoxide vapors was also detected in the air in the wormhouses. the content of ammonia in the air of worm-houses in the breathing zone of fatteners exceeded mpc 1.1 times, the average concentration being 22,2±0,7 mg/m 3 . the content of hydrogen sulfide (a substance with an acute effect) in the breathing zone of fatteners exceeds the mpc 1.3 times, the average concentration is 13.0±0.56 mg/m 3 . carbon monoxide content in the breathing zone of worm breeders did not exceed, on average the sanitary norms, it was equal to 14,3±1,4 mg/m 3. illumination of working surfaces in worm-houses is natural, artificial light is turned on only in the dark time of day. the illumination level is uneven and varies from 5 to 800 lux. the average level is 111.6±9.8 lux, the coefficient of natural illumination (cei) ranges from 0.45 to 5.79%, on average cei is 2.04%. working conditions of women engaged in feeding silkworm caterpillars belong to the 3rd class of the 3rd degree of hazard [3,6]. a study of the functional state of women engaged in feeding silkworm caterpillars showed that 57.3% of those examined had elevated blood pressure. more often, elevated blood pressure was in low-salary women. with increasing length of service associated with feeding silkworm caterpillars in women increases the difference between proper and actual biological age: with the length of service of 1 year biological age is higher than the proper biological age on average of 2.3 years, with up to 10 years of service this figure increases to 5 years, with experience over 15 years biological age is 12.5 years above the proper biological age [biol. age]. besides, with the increased length of service, the indicators characterizing subjective estimation of their psycho-emotional state worsen in working women. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5495417 95 the obtained data indicate the necessity to develop and implement measures to improve the working conditions of worm breeders. the second stage reception of live cocoons and carrying out papilionage work is carried out at grenadier plants. cocoons are received at the drainage factories within about 20 days. cocoons are accepted from 6 to 8 a.m., while there is no heat not to damage the pupa inside the cocoon. the agronomist-grener accepts the breeding cocoons and evaluates their quality. accepted by the plant breeding cocoons that are not sorted by sex are transferred to the workshop, where they cut the shell with a blade, released pupa, sorted by sex pupae. one worker cuts off 3-4 kg of cocoons (1 kg 290-300 cocoons). after 3-4 days, the chrysalis turns into a butterfly (usually at 6-7 a.m.) and work with them begins (papillonage). the worker by hand on a frame, the bottom of which is lined with lavsan cloth, throws a certain number of butterflies (50 to 100 pieces) female, then adds a larger number of male butterflies there. after one hour, free male butterflies (not involved in mating) are manually removed from the frame, the frame is left for another 2 hours. then the frames are placed on racks in workshops with high humidity (more than 80%), which is achieved by watering the workshop’s floor. in 4 hours, the frames are dropped from the butterflies (frame weight 2.5 kg) and the fabric is left on the elite grenade, which is stored until november in low temperature and high humidity. a complex of adverse factors characterizes working conditions for women working with cocoons, pupae and butterflies: the dustiness of the working area with fine dust during the emergence of butterflies from cocoons; limitation of general mobility, the monotony of work operations (cutting cocoons to release pupae, division of pupae by floor, work with butterflies), performing not very complex production operations, but requiring stress of attention and vision, forced, uncomfortable working posture, static muscle tension while dressing the during the papilionage period (mating of butterflies), scales are detached from the wings of many butterflies, which fly around in the air. they are irregularly shaped with pointed edges and long spikes. dust from mating plants consists of 75-80% of organic substances of animal origin (the smallest chitinous scales) and contains a small amount (about 0.01%) of protein substances. the size of 90-95% of the dust particles is up to 10 microns. the concentration of dust in the breathing zone of papilionadiers ranges from 5.3 to 12.5 mg/m3 (mac 4 mg/m3). the organic composition of industrial dust, the presence of a protein of animal origin, shape and size of dust particles have a pronounced allergenic and local irritant effect. during work with cocoons, pupae and butterflies, the air of the working area is polluted with ammonia, hydrogen sulfide and carbon monoxide products of life activity of pupae and butterflies. an excess of ammonia in the breathing zone of women was observed during production operations of separating pupae by sex and removing free male butterflies from the frames. the mean concentrations of ammonia were 21.45±0.7 and 21.3±1.26 mg/m3 (1.06-1.07 times excess of mpc), respectively. content of dihydrosulfide (hydrogen sulfide) in the air of the working area exceeded art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5495417 96 mpc when free male moths were removed from frames, when moths were steamed and when male moths were removed from frames. mean concentrations of dihydrosulfide at these sites were 11.3±1.26, 13.1±0.69 and 11.2±0.96 mg/m3 respectively (exceeding mpc by 1.12-1.31 times). the excess of carbon monoxide content was detected in the breathing zone of women during the production operation, “cutting the head of a cocoon”. the average concentration of carbon monoxide was 22.3±0.43 mg/m3 (exceeding mpc by 1.11 times). in the process of gyre production, a certain temperature-humidity regime is maintained, in which silkworm moths are most viable. meteorological conditions in the silkworm workshops are discomforting: the temperature ranges from 28.8 to 32o c from the beginning to the end of work, the humidity is 40-50%. this is achieved by primitive means: darkening the windows from direct sunlight and moistening the rooms’ floor. most of the production operations in the dredging plant are carried out under visual control. the lighting of working surfaces is natural. the level of illumination in different production areas is significantly lower than the hygienic regulations [8], fluctuates on average from 25 to 53 lux, the coefficient of natural lighting is 0.3% on average. all labor processes of drainage production are characterized by repeated repetition of the same working operations, i.e. refer to monotonous labor. production operations performed when working with pupae more than 25% of working time are performed in a forced working posture (squatting, kneeling) when mating and separating butterflies more than 80% of working time are performed standing, accompanied by the same type of hand movements and associated with strain of vision. working conditions of women working at the mating plants are referred to as the 3rd class of the 3rd degree of harmfulness [3,6]. the study of functional condition of an organism of women working at drainage works has revealed unfavorable changes from the beginning to the end of a working day in a condition of the higher nervous activity and attention function, deterioration of parameters of the neuromuscular system, not sharply expressed changes of the cardiovascular system, and also premature aging of an organism. specific working conditions in the drainage industry affect health: some workers suffer from respiratory diseases. to eliminate the adverse effects of the working conditions of drainage production on the body of working women, it is necessary to use the following recommendations: 1. to prevent occupational diseases of female workers of dredge plants, it is necessary to strictly follow the list of medical contraindications when hiring. persons with severe atrophic rhinitis, laryngitis, tracheitis, chronic bronchitis, bronchial asthma, pulmonary emphysema, pneumosclerosis, bronchiectatic disease, chronic eye diseases (eyelids, conjunctiva, cornea, tear-exhaust), persistent decrease in visual acuity [7] should not be employed at the drainage plants. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5495417 97 2. an important measure to prevent occupational diseases of silkworms and reduce overall morbidity is to conduct periodic medical examinations. workers of the drainage industry must be examined once a year by a therapist, eye doctor, dermatovenerologist and otolaryngologist. general blood tests, chest radiography are mandatory. 3. in order to prevent occupational diseases to work on feeding silkworms, should be allowed to persons after a preliminary medical examination. in addition, periodic examinations of workers (especially adolescent girls) should be conducted for early detection of diseases of the musculoskeletal system, initial changes in posture and other disorders. arterial hypotension, all forms of anemia and metabolic disorders are contraindications to work in silkworm fattening. 4. artificial local exhaust and supply ventilation with air conditioning should be installed in all production shops. 5. in order to avoid the entry of dust papillary rooms, grapes plants should have a set of household rooms isolated from production and equipped with a separate entrance: rooms for eating, dressing rooms, showers and toilets. 6. in the period of papilionage one should use dust-proof respirators such as rh 19 or “lepestok”. 7. dry cleaning of rooms by hand is prohibited. it should be done with the help of a vacuum cleaner. 8. it is recommended to provide the workers of drainage plants with hot and cooled green and black tea, carbonated water (it should be taken into account that due to caffeine content, tannin and vitamins, green tea has a pronounced tonic effect). rational and balanced nutrition is of great importance. 9. it is forbidden to use the labor of girls under 18 years of age at the milling plants according to the “list of jobs with hard and hazardous working conditions, which prohibit the use of the labor of persons under 18 years of age”.) 10. weight of lifting and carrying weights for women must not exceed 9 kg, and in manual transportation on carts or wheelbarrows 50-60 kg [5]. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5495417 98 reference 1. voytenko v.p., polyukhov a.m., barbaruk l.g. et al. / / biological age, heredity and aging. kiev, 1984. pp. 5-15. 2 iskandarov ty, ibragimova gz, iskandarova gt, feofanov vn, shamansurova hs, tazieva ld. sanitary rules, norms and hygienic standards of the republic of uzbekistan №0294-11 “maximum allowable concentrations (mac) of harmful substances in the air of the working area”. -tashkent, 2004. -p.53. 3. iskandarov t.i., ibragimova g.z., shamsurova h.sh., slavinskaya n.v., iskandarova m.s., demidenko n.m., iskandarova g.t., parsegova l.g, feofanov v.n. sanitary rules, norms and hygienic regulations of the republic of uzbekistan #0141-03 ‘hygienic classification of working conditions according to the indicators of harm and danger of factors of the industrial environment, the severity and intensity of the work process’. -tashkent, 2004. -p.53. 4. iskandarov t.i., slavinskaya n.v. sanitary rules, norms and hygienic standards of the republic of uzbekistan № 0324-16 “sanitary and hygienic norms of the microclimate of production premises. -tashkent, 2016. -p.10. 5. iskandarov t.i., slavinskaya n.v. sanitary rules, norms and hygienic standards of the republic of uzbekistan no. 0364-18 “norms of acceptable loads for girls under 18 years old and women when lifting and moving weights manually.” tashkent.2018. – p.9. 6. nichkasov v.m., iskandarov t.i., ibragimova g.z.,.slavinskaya n.v., iskandarova g.t. “methodology of evaluation of working conditions and attestation of working places according to working conditions”. -tashkent, 1996. – p.21. 7. order of the ministry of health of the republic of uzbekistan, #200 of 10.07.2012 “on approval of the provision of medical examination of employees”. 8. construction norms and regulations 2.01.05-98 “natural and artificial lighting”. -tashkent, 1998. – p.48. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 139 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 140 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 141 hygienic assessment of leading harmful factors in pharmaceutical enterprises iskandarova g.t. professor, tashpulatova m.n. assistant, samigova n.r. associate professor, kurbanova sh.i. associate professor, sherkuzieva g.f. associate professor, yusupkhujaeva a.m. senior teacher guzal iskandarova, munisa tashpulatova, nargiz samigova, shakhnoza kurbanova, guzal sherkuzieva, aziza yusupkhujaeva tashkent medical academy tashkent, uzbekistan abstract. the article discusses the development of science-based preventive measures to identify leading dangerous variables in the main workplaces of pharmaceutical companies' injectable medications production shops, as well as how to mitigate the bad effects of noise and chemical factors on workers' bodies. keywords: pharmaceutical companies, injectable medications, technological process, harmful factors, noise, chemical factor, permissible norms, preventive measures. the relevance of the topic. scientific and technological advancements, as well as socioeconomic shifts, have resulted in significant changes in workers' working circumstances in a variety of industries, including the pharmaceutical business. reorganization and the introduction of new technologies and equipment have been carried out and continue to be carried out, taking into consideration recent scientific discoveries and achievements [1, 4]. in addition to the positive aspects, highefficiency equipment and conveyor lines lead to changes in the working conditions of workers, the formation of various factors that negatively affect their health [2, 5]. on the one hand, the introduction of new techniques and technologies, machines and equipment into the modern production enterprises studied leads to an increase in labor productivity and its facilitation, while on the other hand, it leads to the formation of previously little-studied or unexplored factors of production. however, it persists, even aggravates, and adverse working conditions adversely affect the body of the worker [3, 6, 9]. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 142 it is well known that production conveyors are employed in the manufacture of modern medications, as a result of which workers are exposed to a variety of elements, the most prominent of which are noise and chemical factors in the manufacturing environment [7, 12]. however, the complex effects of these factors have not been sufficiently studied, and only data on operations and processes performed in separate hot climates are available [10]. all of the above once again confirms the relevance of this study. aim. identification of the leading harmful factors in the production of injectable medications of pharmaceutical companies and the development of preventive measures. tasks. to achieve this goal, the following should be addressed: hygienic assessment of noise and chemical factors leading to harmful factors in production and development of health measures to prevent their impact. object and method of research. research was held in the injection shop of uzkimyofarm jsc named after s.k.islombekov. commonly used, tested sanitary-hygienic, laboratory-instrumental and statistical methods were used. the injection molding plant's principal workplaces had their noise levels measured. sanitary rules and norms no0325-16 “permissible sanitary norm of noise level in workplaces” [8] analyzed the acquired data [8]. air dust is determined by the method of gravity, the concentration of dust in the air of the workplace was assessed in accordance with state standard 12.1.005-88 “general sanitary and hygienic requirements for air in the workplace”. the level of gassing was measured and determined by sanitary rules and norms №0294-11 “permissible standards of harmful substances (permissible standard) in workplace air”. the summation coefficient was calculated and the class of working conditions was determined according to sanitary rules and norms no0141-03 "hygienic classification of the severity and severity of the work process, harmful and hazardous art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 143 working conditions in the production environment," taking into account the formation of several types of chemicals in the production process. one-way exposure to several harmful substances in the air of workplaces at the same time, the actual amount (k1, k2, ...,), the permissible standard (ps1, ps 2, ... ps n) of each substance in the air should not exceed one. calculation of the summation coefficient ≤1 the results obtained. after tablets, the preparation of injectable medications in ampoules is the second most popular product [11]. the injection shop of uzkimyofarm jsc named after s.k. islambekov employs 132 people, 97 of whom are women. ampoules are used to produce liquid and powder pharmaceuticals in this business. dissolving the beginning components, filtering the solutions, preparing the ampoules, preparing them for collection (washing and other procedures), filling, sealing, sterilization, and labeling are all part of the technological process. workers from 17 different professional groups operate at the injection plant. the chemical factor is one of the most harmful things here. the chemical component outperformed permissible standard in the workplaces of four different groups (shop technologist, master, ampoule filler, and ampoule welder) (table 1). table 1 assessment of chemical factors in the air of the workplace of the injection molding shop of a pharmaceutical company № occupatio nal groups the average amount of chemical factors class of workin g conditi ons benzene (class 2) nitrogen dioxide (class 3) carbon monoxide (class 4) ammonia (class 4) obtain ed result rem мg/м 3 obtain ed result rem мg/м 3 obtaine d result rem мg/м 3 obtain ed result rem мg/м 3 1. production engineer 5,2 5,0 2,0 2,0 19,6 20,0 2 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 144 2. master 5,2 5,0 2,2 2,0 21,3 20,0 3.1 3. ampule filler 4,8 5,0 19,8 20,0 2 4. ampoule welder 1,89 2,0 17,2 20,0 2 the results showed that in the workplace of production engineer benzene was 0.2 times higher than permissible standard, in the workplace of master benzene and nitrogen dioxide was 0.2 times higher than permissible standard and ammonia was found to be 1.3 times higher than permissible standard. although the chemicals in the ampoule filling and ampoule welding workplaces did not exceed permissible standard, the study found that the summation coefficient of the chemical factors was higher than ≤1. noise is another harmful component that is one of the physical aspects. mechanical origin, high frequency in terms of frequency composition, broad spectrum in terms of spectral features, and steady in terms of noise time stable and constant noise levels measured per unit of time are all characteristics of noise in many workplaces, according to studies. the following results were obtained when measured the noise level in the workplaces of workers of the main professional group operating in the injectable medications production shop (table 2). table 2 results of noise assessment in the workplace of the injection shop of a pharmaceutical company № occupational groups noise volume, average equivalent level of sound, dba class of working conditions obtained results red 1. production engineer 84 80 3.1 2. master 81 80 3.1 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 145 3. ampoule filler 82 80 3.1 4. ampoule welder 81 80 3.1 5. plumber-repairman 81 80 3.1 6. sterile solution maker 84 80 3.1 7. chemical water purifier 82 80 3.1 8. ampoule and dish washer 83 80 3.1 9. production room cleaner 82 80 3.1 the acceptable level of noise during work for 17 groups of workers in the main occupational group was assumed to be 80 dba based on the preceding data. during the inspection, it was found that the noise level in the workplaces did not exceed 80 dba in the workplaces of sterilizers of materials and medications, packers, cutters of tubes and ampoules, repair and commissioning of gas appliances, medical product inspector, auxiliary worker, ampoule controller with injection solution and shop manager. therefore, it was determined that the working conditions of the workers in this group corresponded to the permitted 2nd class. the noise level in the workplace of production engineer, master, ampoule filler, ampoule welder, plumber-repairman, sterile solution maker, dry cleaner, ampoule and dish washer, production room cleaner increased by 80 dba. therefore, the working conditions was classified as 3rd harmful 1st class (table 2). conclusions. based on the results of a study conducted in the injection molding shop of jsc “uzkimyofarm” named after s.k.islombekov, the following conclusions were developed: art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 146 1. it was found that in the production engineer and master workplaces of the shop the chemical factor is higher than permissible standard. 2. it was found that the summation coefficient of chemical factors is higher than <1.0 in all workplaces and this leads to an early manifestation of production fatigue. 3. it was found in the shop that noise levels are higher than permissible degree in the workplaces of production engineer, master, ampoule filler and ampoule welder, plumber repairman, sterile solution maker, dry cleaner, ampoule and dish washer, and production rooms cleaner. 4. the study of leading harmful factors allowed to determine the class of harmfulness and hazard according to sanitary rules and norms 0141-03. it was found that the shop production engineer, which fills ampoules and seals ampoules, belongs to the 2nd permissible class, and the master workplace to the 3rd harmful 1st class. the results from the noise measurement showed that the main workplaces above permissible degree were classified as 3rd harmful 1st class. proposals. 1. in improving the working conditions in the injection shop of the pharmaceutical company the main focus should be the improvement of technology and equipment. 2. to reduce dust and gassing of workplace air, it is necessary to ensure continuous operation and control of the efficiency of the existing ventilation system in production rooms, if necessary, once a year prophylactic inspection and maintenance is required. 3. in order to reduce the noise intensity of noise-generating devices, noise protection enclosures and noise-absorbing devices should be installed. in addition, it is advisable to acoustically treat the walls and ceilings of rooms where such a source is located. 4. it is necessary to rationalize work and rest to prevent fatigue. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 147 5. workers should be fully equipped with modern personal protective equipment. 6. according to the order no. 200 of the ministry of health of the republic of uzbekistan (dated 29.08.2012), before commencement with the work, initial medical examinations and periodic medical examinations should be carried out in full. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537045 148 references: 1. alisherov t.a., tashpulatova m.n. problems of occupational hygiene in modern pharmaceutical enterprises // proceedings of the 10th republican online scientific conference "prospects for the development of science in the xxi century and the role of innovation in them." 2019. № 10. 45-46 p. 2. behbutova m.d. hygienic aspects of working conditions of workers in pharmaceutical industries // young scientist. 2017. no. 1.2 (135.2). p. 21-22. 3. veliyeva m.n., atakishizade sa innovative approaches to pharmaceutical and medical support in azerbaijan // modern achievements of medicine in azerbaijan. baku. 2015. no. 1. p. 3542. 4. zambrzhitsky o.n., batsukova n. l. occupational hygiene in pharmacy organizations and at pharmaceutical industry enterprises // teaching aid. 2014.52 p. 5. iskandarova g.t., tashpulatova m.n., samigova n.r. the importance of studying the labor process and the organization of working conditions in the pharmaceutical industry // association of physicians of uzbekistan: scientific-practical medical journal. 2020. № 2. 59-62 p. 6. petrov a.g. the development and implementation of pharmaceutical care is the most important aspect of the professional activity of a pharmaceutical worker // mvk. 2014. no. 3. p.1016. 7. sanitary rules and norms no. 0141-03 hygienic classification of working conditions by indicators of hazard and hazard of factors of the working environment, the severity and intensity of the labor process. tashkent-2004. 53 p. 8. sanitary rules and norms ruz no. 0325-16 sanitary norms of permissible noise levels at workplaces. tashkent-2016. 10 p. 9. tashpulatova m.n. issues of studying the hygienic features of working conditions at modern pharmaceutical enterprises // international scientific review of the problems of natural sciences and medicine. 2019. p. 47-52. 10. tashpulatova m.n., dzhuraeva d.a. nanotechnology is a new direction of development in the industry of uzbekistan. // young scientist. 2016.no. 8.3 (112.3) p. 18-19. 11. tashpulatova m.n., iskandarova g.t. legislation in the pharmaceutical industry // bulletin of the tashkent medical academy. 2020. №2. 215 p. 12. khashirbaeva d.m., tashpulatova m.n. evaluation of the chemical factor in the working conditions of pharmaceutical workers // collection of articles of abu ali ibn sino and the iv international scientific-practical conference on innovations in modern pharmacy. 2021. 365-366 p. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 188 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 189 medieval metalworking crafts of khorezm in the sources. turganov baxit qurbanbaevich nukus state pedagogical institute named after ajiniyaz associate professor of history teaching methods, candidate of historical sciences. e-mail: turganovbaxit@gmail.com reimbayev rustem sarsenbayevich nukus state pedagogical institute named after ajiniyaz. senior lecturer of the department of methods of teaching history. keranova aigul kuandykovna. student of the historical faculty of the nukus state pedagogical institute named after ajiniyaz. abstract: the article studies the history of the medieval metalworking craft of khorezm on the basis of information from written sources. iron products were widely used in the economic and social life of khorezm. metal raw materials and certain types of weapons were imported from neighboring countries, some of the metal products were used for foreign trade. the process of specialization of some branches of metalworking in khorezm has began since the x century. the analysis of the sources indicates to the consistent development of metalworking in khorezm during the ix-xiv centuries. keywords: khorezm, written sources, cities of the middle age, metal things, trade relationship, handicraft centers, blacksmith trade, arm equipment trade. introduction. medieval khorezm was famous for its trade and the products of artisans. in the ix-x centuries, the number of settlements and rural settlements increased, the process of development of crafts and trade began in them. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 190 according to the sources of the viii x centuries, there is a sharp increase in the number of cities in khorezm. during the arab conquest (712) there were only three cities in khorezm: kat (al-fir), hazarasp and urgench, at the beginning of the ix century the number of cities is ten, and by the end of the x century it reaches thirty-three [14,180,202]. valuable information on the handicrafts of khorezm is contained in sources dating back to the early middle ages. according to al-maqdisi (x century), there were handicraft workshops in the cities of zarduh, sadvar, kat (kiyat) [14,187]. during this period, there is an intensive growth in the production of handicrafts for the market, due to the increase in the number and development of cities. as a result, a wide volume of handicrafts begins to enter the foreign market as a commodity. in the early middle ages, the cities of urgench and kat played an important role in trade relations with central asia, eastern europe and nomads. trade was conducted in about 160 bazaars of urgench. in particular, the appearance of outpost cities on the outskirts for the nomads of khorezm from the x-xi centuries had a positive impact on the development of trade and economic relations and crafts. at that time, trade and craft quarters operated around dozens of outposts of cities, such as the city of shamakhi (30 ha), shehrlik (15 ha), bolshoy aybuyir (10 ha), bugrakhan (60 ha), puljay (60 ha). archaeological materials in the monuments prove the increase in the number of ceramic, metal, glass and bone objects, as well as the appearance of their new types. the works of the authors ibn rust (x century), al-maqdisi (x century), azzamakhshari (xii century), al-qurashi (early xiii century), zakariya al-qazwini (xiii century), muhammad an-nasawi (early xiii century) ibn battuta (xiv century) contain some information about the khorezm metalworking crafts. in khorezm since the x century there have been specialized branches of metalworking craft, some metal products were exported. it is reported by al-maqdisi (985) that in khorezm "... castles, intricate bows were made and exhibited for foreign trade, boats were built and equipped" [14,202]. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 191 in the 10th century, 42 types of goods were exported from khorezm to the countries of the east, of which 27 types were brought from bulgaria. at that time, metallurgy and metalworking were developed in volga bulgaria. swords, bows, daggers, armor and copper were brought to khorezm from bulgaria [14,202]. in particular, bulgarian swords and armor were exported to the countries of the east through khorezm. ambassador ibn fadlan (921-922), who traveled to bulgaria along the volga, also noted that iron raw materials came to khorezm through trade with the turkic peoples [10,55,57]. according to his report, there was a khorezm blacksmith named takin al-turki in khorezm. he was engaged in the iron trade in the country of the infidels (volga bulgaria t.k.b.). the information of ibn fadlan (922) and al-maqdisi (985) confirm that iron, copper raw materials and weapons came to khorezm from volga bulgaria as a result of trade and economic ties. iron objects were widely used in the medieval economic life of khorezm. the gates of the castles were covered with iron, and stone-throwing machines stood above the gates. there was a suspension bridge "ramp" in front of the castle gate, which was raised at night and lowered again during the day. sources note that in the early medieval settlements of aykhan there was a stone machine "manjanak" above the gate, and in nuzvar and zamakhshar there were iron gates and suspension bridges [14, 187-188]. in khorezm since the x century, metal products such as locks, saddles and horse harnesses were made in specialized industries and exported during the mongol period for foreign trade [21,3]. according to the arab authors of an nuweiri, ibn abda-zahra, and such products continued to be produced in khorezm in the xiii-xiv centuries. khorezm saddles and bridles with gold and silver notches were especially famous in the art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 192 golden horde period. such products were sold in muslim countries and were highly valued in foreign trade [16,60,100,152]. especially during the reign of the anushtakins (1097-1231), the economy, trade and craft were highly developed in khorezm. at that time, about 400 cities of khorezm had mutual trade and economic integration. urgench has become a major trade and craft center of the east. the area of the city occupied an area of 1000 hectares and numbered thousands of trade and craft workshops. the development of crafts is also observed in other cities of khorezm, the process of craft specialization has been strengthened. during this period, as a result of close trade and economic ties with the states of the east, there is an increase in the range of metal products made by khorezm craftsmen and an increase in their quality. in the work "mukaddimat ul-adab" by the khorezm scholar az-zamakhshari (1075-1144), a number of terms concerning tools, weapons, household utensils, as well as the names of individual specialized crafts are noted: jewelers (oltunchi), coppersmiths (kulachi), lock makers (kulfchi) and terms of some tools of craftsmen [11,93]. the listed indirect data allow us to assume that in addition to the manufacture of various products from copper, bronze, iron, metalworking artisans at that time produced steel products and used steel swords, scissors, which were complex metals. among the authors, al-qurashi (beginning of the xiii century) notes that there are about 50 specialized crafts in khorezm, and zakaria al-qazwini (xiii century) writes that the inhabitants of gurganj (kunya-urgench) are "skilled artisans", especially blacksmiths, carpenters, etc., who have achieved perfection in their craft [1,520]. according to the manuscript of the "tariff of shahru khorezm", before the mongols (beginning of the xiii century) there were three thousand and thirteen caravanserais in khorezm, and each had a thousand cells. there were seventeen art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 193 hundred bazaars. if someone needed a kumach or silk fabric, then he could satisfy all his needs. there were one thousand three hundred blacksmiths, one thousand five hundred shoe shops, one thousand three hundred shoe shops, one thousand three hundred salt shops, one thousand two hundred coppersmiths' shops, one thousand three hundred grocery stores [5,151-153]. sources indicate that the blacksmith and copper workshops in khorezm at that time were not inferior to other industries. products made of precious metals, such as gold and silver, were brought to khorezm mainly from the countries of the east by trade and embassy caravans. for example, among the gifts and gifts sent to khorezm shah by genghis khan in 1216, there were chinese goods. among them was pure gold, which looked like a camel's hump, brought on a separate chariot. the caravan of 500 camels sent by genghis khan in 1218 under the leadership of bahauddin ar-razi also contained gold, silver, precious metals and many other goods [4,164-165]. during the anushtakin period, gunsmithing was one of the most developed industries. the number of troops of khorezm at that time, their military achievementsa logical basis for the development of the arms industry. in 1218, khorezm shah organized a general review of the troops, which was attended by "about 150 thousand mounted soldiers in addition to foot soldiers, which numbered up to 100 thousand more." this is confirmed by the registers of the khorezm shah's military divan, in which 400 thousand horsemen on horses and camels participated in the campaign to baghdad [4.89]. in the state of anushtakinov, “divan al-ard" was in charge of military ribbons (iqta'), all types of salaries and payments to soldiers of all ranks, as well as control and registration of troops and their weapons. in the state of anushtakins, blacksmiths produced military equipment in addition to conventional weapons. muhammad an-nasawi (beginning of the xiii century) noted that in the army of the khorezmshahs, in addition to conventional weapons swords, spears, bows and arrows, maces and pikes – the khorezmshahs' troops were art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 194 armed with catapults (mandanjik), siege engines (dabbabat), crossbow (tir-charkh), turtle (turtle), i.e. movable towers (mataris), battering rams (jamalukat), siege ladder (salalim) and other military vehicles [2,156,231]. according to the reports of al-khorezmi, al-maqdisi (x century), the persian poet al-lohuri (xi century), metal parts were widely used in the construction of military equipment [6,218]. in particular, al-maqdisi (x century) notes that manjanak uses metal structures called "halka" or "al-halka" [6,215-221]. it should be noted that metal structures in the construction of suspension bridges, iron gates, mandrels and military equipment were made by specialized blacksmiths. active participation of gunsmiths and blacksmiths in national military companies lasted until the late middle ages. according to the documents of the khiva khans, the army was followed by riflemen, carpenters, blacksmiths, infantrymen, cleaners and boatmen [7,91]. the armies had gunsmiths and blacksmiths who repaired and supplied the army with weapons and equipment like swords, daggers, bows, spears, shields, armor, chain mail, helmets, horse equipment. in khorezm, the production of bows and arrows, swords, spears and other weapons in the traditional style continued in the late middle ages [8,178]. gunsmiths have long been a specialized industry, and the sale of weapons in the markets of khorezm was organized until the last quarter of the xix century [9,304]. during the anushtakin period, trade and crafts were highly developed in the cities of khorezm. yakut al-hamawi (1219) states: "... i was here in 616 (12191220). almost all cities of khorezm have markets rich in goods and shops, and villages without markets are rare " [12,2021; 14,419]. in mirza ulugbek's work "tarikh arba ulus" he wrote that "the mongol army killed 100 thousand people after the conquest of urgench, and 100 thousand artisans were expelled to mongolia" [3,329]. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 195 a similar message was sent to muhammad al-nasawi, secretary of jalaladdin manguberdi. according to the work, after the mongol conquest of khorezm, the captives were divided into separate groups. one hundred thousand artisans were separated from them and taken to their lands.... [19,129]. perhaps the figures in the sources are exaggerated, but these data show that at that time urgench (the beginning of the xiii century) was a major center of crafts in the east, among which the metalworking crafts industry is undoubtedly developed. despite the fact that the mongol invasion caused great damage to cities, in the second half of the xiii century a new center of agricultural and urban culture was formed in the west of khorezm. economic and cultural life in cities has been revived in a new way. as part of the golden horde, the lands of northwestern khorezm became one of the strong economic bases, and then the politically influential region of the golden horde. in khorezm, from the middle of the xiii century, such settlements as urgench, mizdakhkan, sharlik, shamakhi, janik-kala were restored. this is due to the fact that "urgench, which was necessary as a source of invaluable wealth for the khans of the golden horde, rose again from the ashes and became a major center of trade and crafts" [17,309]. the traveler plano carpini stopped in khorezm in 1246 on a trip to mongolia. in his memoirs, he talks about the wealth of the markets of the city of ornas (urgench), which is rich and has a large population [15,46,209]. the arab cosmographer shamsiddin ad-dimishki (1256-1327) wrote that "the khorezm region covers sixty thousand villages", which indicates the revival of economic and cultural life in khorezm shortly after the mongol invasion [18,30]. and in the information of the traveler ibn battut (1333) khorezm and its capital the city of urgench at that time as a major economic and cultural center [12,47]. according to his work, it is mentioned that the urgench market was so crowded that “he could not move back or forward”" ibn battuta writes about urgench: "it is the largest, most significant and beautiful city of the turks, having art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 196 glorious markets, spacious streets, numerous buildings (mosques, madrasahs, khanaks). in the city, life boils from a large number of people, it looks like an undulating sea” [12,48]. during this period in khorezm, gold and silver vessels were used in the decoration of palaces and houses of officials, as well as in hospitality [12, 48]. ibn battuta (1333) describing the house of abu hafs umar, the judge of urgench, said: "this is a beautiful and spacious room, ... silver vessels filled with gilding were placed on each of the rows of shelves. this is how the residents of the country usually decorate their homes" [12,59-60]. continuing, he writes: "they brought other trays. the peeled pomegranate fruits were served in gold and silver dishes, with golden spoons." silver and bronze spoons with gilding are also known according to local archaeological data of the xii-xiv centuries. the tradition of covering jewelry, various dishes, weapons and other objects with gold and silver by khorezm craftsmen continued in the xiii and xiv centuries. according to an-nuweiri and ibn abd-zahr (xiii-xiv centuries), the following items exported from khorezm are noted: "locks, saddles, horse harness, etc." [16,60,100,152]. these authors noted that the products of khorezm coiners, for example saddles and horse harness, using gold and silver, were exported from khorezm to the countries of the east. in the second half of the xiv century, according to ibn arabshah, khorezm (urgench) was "... one of the largest cities in the region" [18,102]. the rich bazaars of the city attracted many trade caravans. various handicrafts were sold in the bazaars, in particular, weapons for war and hunting, jewelry, ceramics and stonecutting products, carpets and fabrics. sources also describe khorezm as a silver-rich state. according to ibn arabshah, during timur's second campaign in khorezm, a merchant named hassan surij left the city to meet temur and ask him to stop the war and give him loot in return. timur asks him to give two hundred mules (donkeys) as a burden of silver and art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 197 hand them over to his treasury as a coin. however, hussein surij persuaded timur to persuade him to ask for a quarter of what he asked for (silver). hassan surij separates the necessary wealth from his property and then weighs (silver) [13,88]. for comparison, when the sassanid ruler feruz (459-484) was captured by the ephthalites, it was decided to release him in exchange for 30 mules of silver coins, but there were only 20 mules in the sassanid treasury (a mixed type of donkey and horse). blog daria foreign trade that in the middle ages khorezm had sufficient reserves of silver. this is due to the fact that from the early middle ages to the late middle ages, silver coins and ingots, silver vessels of eastern countries such as central asia, china, india, iran, were among the goods exported to the markets of eastern europe through khorezm merchants. in particular, in 1749, merchants of khiva and bukhara exported 3 batches of silver products weighing 15 pounds 10 pounds through orenburg to astrakhan [20,118]. in the middle ages in khorezm there was a profession of "kumushchi" working with silver. this is evidenced by the export of silver products from khorezm (vi-viii centuries), seats covered with a layer of silver, horse harness (ix-xiv centuries), silver processing of weapons and household utensils. these sources indicate that in the middle ages, the metalworking industry developed in khorezm, some metal products were exported. in the ix-x centuries, there were industries specializing in the metalworking craft industry. this proves that the tools, weapons and equipment, coppersmith, jewelry, necessary for the national economy, were mainly made by local craftsmen. the production of weapons and equipment by artisans continued until the late middle ages. in general, the active participation of khorezm in foreign trade in the ix-xiv centuries was one of the factors that influenced the growth of urbanization and the development of the crafts industry. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5558733 198 references 1. al-qazwini zakariya. asar al-bilad wa akhbar alibad. -beirut, 1960. 2. an-nasawi muhammad. biography of sultan jala ad-din mankburny / translated from the arabic by z.m. buniyatov. baku, 1973. 3. amеdmedov b. tarikhdan saboklar. -toshkent, shkituvchi, 1994. 4. buniyatov z.m. the state of khorazmshakhov anushteginidov. -m.: nauka, 1986. -248 p. 5. buniyatov z.m. selected compositions in three volumes. the states of the khorezmshahs of the anushteginids 1097-1231 -boku. elm, 1999. 6. belinitsky a.m., marshak b.i. the oldest image of a siege engine in central asia // culture of the east. antiquity and the early middle ages. -l.: 1978. -pp.215-221 . 7. gulboev n.n. khiva honligi кучarbiy kuchlari tashkent tuzilmasi //khorazm tarikhi zamonaviy tadkikotlarda. -toshkent-urgench. 2018. -p.89-93 8. jenkinson a. travel in central asia in 1558-1560. // english travelers in the moscow state in the xvi century. m.: 1937. 9. zhelyabuzhsky e. essays on the conquest of khiva. m.: 1875. 10. ibn fadlan ibn fadlan's journey to the volga/ trans. and comment. edited by i.y.krachkovsky. -m.-l.: publishing house of the ussr academy of sciences, 1939. 11. ibroимimov s. fargona shevalaring kasb-унаunar lexikasi. -toshkent, 1958. gild. ii-iii. 12. ibroимimov n. ibn battuta va uning srta osiega saeатиati. -toshkent, 1993. 13. ibn arabshoҳ. ajoib al-makdur fi tarihi taimur (temur tarikhida taqdir ajoibotlari). 1 whale. toshkent. meнnat. 1992. 14. materials on the history of turkmens and turkmenistan. m.-l., 1939. t.i. 519 p. 15. plano carpini giovanni. the history of the mongols / per. a.i. maleina. v. book: plano karpina j. the history of the mongols. rubruk g. journey to the eastern countries. -m.: 1957. 16. tiesenhausen v.g. collection of materials related to the history of the golden horde. -st. petersburg: 1884. 17. tolstov s.p. in the footsteps of the ancient khorezm civilization. m.: ussr academy of sciences, 1948. -378 p. 18. uvatov u. donolardan saboklar. toshkent. abdullah kodiriy. 1994. 19. khrapachevsky r.p. the golden horde in the sources. volume i. arabic and persian sources. m.: 2003. 20. yukht a.i. trade of khiva and bukhara with russia through astrakhan (20-40s of the xviii century)// late feudal city of central asia. -tashkent. 1990.-pp.115-122. 21. yakubovsky a.yu. feudal society of central asia and its trade with eastern europe in the x-xv centuries. // materials on the history of the uzbek, tajik, turkmen ssr. part i. -m-l., 1932. pp. 1-60. 1 volume 1, ¹4 art of medicine international medical scientific journal 2 art of medicine international medical scientific journal volume 1, ¹4 december 2021 3 volume 1, ¹4 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen 17 volume 1, ¹4 clinical and instrumental peculiarities of the postoperative period in children with tetralogy of fallot akhmedova n.r., matkarimova a.a., kazakbaeva t.t., seitbaeva a.m. republican children's multidisciplinary medical center, nukus city tashkent pediatric medical institute karakalpak medical institute abstract.the article presents the results of an examination of 20 patients with tetralogy of fallot who underwent surgery for the correction of the defect. the research results showed that in children with tf, the postoperative period proceeds with various complications, the course of which directly depends on the severity of the defect, the volume, complexity, duration of surgery, as well as the presence of concomitant diseases in the form of hypoxicischemic encephalopathy and eating disorders. key words: òetralogy of fallot, postoperative complications, course features relevance. (tof) is diagnosed in 8-13% of all patients with congenital heart disease [1,3]. among malformations requiring surgical treatment in early childhood, fallo's tetrad (ft) accounts for 15%. the incidence in newborns varies from 4% to 7%. the average life expectancy of patients with ft is 12-13 years and depends on the degree of pulmonary artery stenosis. mortality during the first year of life is 25%, by the age of 3 years 40%, by the age of 10 years -70%. typically, severe unoperated patients die from thromboembolism in the brain vessels with the formation of abscesses, heart failure and infectious endocarditis. considering the current results on elimination of this malformation, the majority of patients will undergo surgery and reach adulthood [1, 2, 6, 9]. despite significant achievements of cardiovascular surgery in the radical correction of ft, the issues of studying the development of postoperative complications and the development of rehabilitation methods for these children still remain relevant, since the prevention of complications after successfully performed ft correction directly depends on the immunity status, the presence of concomitant diseases and the quality of care for these patients [4, 5, 8]. based on the above, the study of the peculiarities of the postoperative period course in children with ft is urgent. objective: to study clinical and instrumental peculiarities of the course of postoperative period in children with ft. materials and methods. we examined 20 patients with ft hospitalized in the department of cardiorheumatology and cardiosurgery at the clinic of tashkent pediatric medical institute, republican children's multidisciplinary medical center in the postoperative period. all patients underwent clinical-anamnestic, laboratory and instrumental investigations (chest x-ray, ecg and echo). results of the study. analysis of the findings showed that the postoperative period in children with ft is characterized by the presence of various complications. the chief complaints on admission were fever (25%), shortness of breath (95%), cough (95%), lividity of lips and fingertips weakness (95%), lethargy (95%), restlessness (95%), and rapid fatigue (100%). dyspnea-cyanotic attacks occurred more frequently in children with a history of birth trauma or with a hypertensive-hydrocephalic syndrome and were characterized by an abrupt worsening of condition with forced positioning. art of medicine international medical scientific journal 18 the study of the obstetric history of the mothers of children with tf showed that most children were born from 1-2 pregnancies (90%). the course of pregnancy in 95% of the mothers was aggravated by pre-eclampsia and anemia of varying severity. most of the women had a respiratory viral infection (65%). 75% of children with tf were born asphyxiated. the severity of clinical manifestations of the malformation depended on the premorbid background of the child. according to our data, 40% of children with ft showed hypoxic-ischemic encephalopathy in the form of hypertension syndrome, hyperexcitability syndrome, seizure and hydrocephalus syndromes. 70% of children suffered from grade i-ii anemia. from the first days of life, children suffered from malnutrition and retarded physical development (45%). the study of anamnestic data of children revealed a high percentage of morbidity in children. thus, by the time of surgical correction, almost all children with ft had frequent recurrent respiratory diseases in the form of vri, bronchitis, and pneumonia, which allowed us to classify them as frequently ill children. clinically, all patients had a typical picture of malformation manifested as cyanosis, intensifying with crying and child restlessness (75%), dyspnea (95%), tachycardia (45%), widening of the borders of relative cardiac dullness. frequent symptoms of malformation in older children were thickening and changes in the shape of "watch glasses" nails and "drumstick" nail phalanges (85%), chest deformity in 25% of children (heart hump). the severity of the condition was due to frequent respiratory infections, retarded physical development and phenomena of heart failure. percussionly, in children with ft the boundaries of relative cardiac dullness were dilated on both sides, more to the right, the apical thrust was intensified and pervasive. systolic tremor was palpated in the 3rd-4th intercostal space. on auscultation in children with ft a coarse systolic murmur was heard over the heart area with maximum in 3-4 intercostal space on the left side of the sternum, weakening of ii tone over the pulmonary artery. the electrocardiogram recorded pronounced tachycardia, signs of right ventricular hypertrophy (75%), both ventricles (25%), metabolic changes of myocardium. the radiological picture was characterized by cardiomegaly, due to enlargement of the right ventricle. other radiological signs were pulmonary artery retreatment and impoverishment of the pulmonary pattern. fig.1. chest radiograph of patient l., 3 years old. fallo's tetrad. a segment of the pulmonary artery trunk is sunken. the apex is elevated due to rv hypertrophy. 19 volume 1, ¹4 echo revealed pulmonary artery stenosis, large vsd, mitral-aortic extension and rightward displacement of the aorta. the study of laboratory data showed that leukocytosis and lymphopenia predominated in blood tests. almost all children had degree ii circulatory disorders (dc). the course of the postoperative period was characterized by various complications. they manifested as postoperative pneumonia (20%), postcardiac syndrome (15%), rhythm disturbances (25%), acute heart failure (5%) and bacterial endocarditis (5%) (fig. 2). fig.2.structure of postoperative complications in children with ft. according to ecg monitoring in the postoperative period, ventricular arrhythmias occurred in children with fallo's tetrada, which accounted for 60% of all rhythm disturbances. atrial rhythm disturbances were registered in 20% of cases and av nodal tachycardia in 25% of cases. echo revealed the following changes: right heart dilatation. the occurrence of these complications depended on the nature as well as the extensiveness, duration of surgical intervention, premorbid background of the body and age of children. the occurrence of pneumonia and postcardiac syndrome in this period is also facilitated by complications directly related and caused by the surgical trauma itself. fig.3. ellectrocardiogram of child k., 13 years old. fallot's tetrad. accelerated ab rhythm hr 100 bpm. normal eos. complete blockade of the right giss bundle leg. left ventricular extrasystole. hypertrophy of both ventricles. art of medicine international medical scientific journal 20 clinical manifestations were characterized by increased body temperature and worsened physical findings (percussion sound blunting, moist rales with crepitations. according to literature data, impaired drainage function of bronchi creating favorable conditions for infection development, congestion in pulmonary artery system, decreased immune protective forces of the organism are of great importance for pneumonia development in postoperative period. conclusions. thus, in children with tf the postoperative period proceeds with various complications, the course of which depends directly on the severity of the defect, the volume, complexity, duration of surgical intervention, as well as the presence of concomitant diseases such as hypoxic-ischemic encephalopathy and feeding disorders. 21 volume 1, ¹4 used literature. 1.bokeria l.a. morbidity and congenital circulatory system defects in children (prevalence and correction)/l.a. bokeria, i.n. stupakov, r.g. gudkova // pediatric heart and vascular diseases.-2016.-#1.p.z-10. 2.cardiac rhythm disturbances during surgical correction of acquired heart defects in artificial circulation / v.v. plechev, i.a. nagaev, n.g. sibagatullin et al // health care of bashkortostan,-2016.-#1.-p.82-84. 3.predictors of rhythm disturbances in young children in the early period after surgery for radical correction of fallo's tetrad / li.a. bokeria, e.z. golukhova, a.i. kim et al. // annals of arrhythmology.-2016.-#5.-p.66-73. 4.cherepenin l.p., ivanov a.s., buravikhina t.a., baloyan g.m., kudryashov v.e., kulagina t.i., dobrovolskaya t.n. results of radical correction of tetradafallo in patients over 16 years // chest and heart-vascular surgery. -2014.-#2.-p. 15-19. 5.prilepko l.p. physical development of patients with fallo's tetrad // med. aid.2012.-sh.-p.40-45. 6.nikitin ye.s., tskhovrebov s.v., zatevakhina m.v., makrumin km, suvorova g.yu., safonova e.m. mechanical properties of lungs in patients with fallo tetrad after radical correction of malformation // chest and heart and vascular surgery. -2017.#1.-p.27-30. 7.weissman,c.pulmonary complication after cardiac surgery./c.weissman// sem. in cardiathorac. and vasc. anesth. 2018. vol. 8, n3-p.185-211. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 113 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 114 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 115 anthropometric, metabolic and bone changes in women with premature ovarian failure when using estradiol analogues 1 khaidarova feruza alimovna, 2 fakhrutdinova sevara srajitdinovna, 3 azizov bakhodir sadikovich 1,2 republican specialized scientific practical medical center of endocrinology, tashkent, uzbekistan 3 tashkent state dental institute, tashkent, uzbekistan abstract. goal. to compare changes in bone, metabolic and anthropometric parameters in young women with hypergonadotropic amenorrhea (premature ovarian failure [pof], complete androgen insensitivity syndrome [cais] with removed gonads), undergoing various ht (transdermal estradiol [te], oral estradiol valerate [oev], oral ethinyl estradiol [oee] with or without progestin) or without therapy. methods. a pilot cohort study based on prospectively collected data. bone density, body composition and anthropometric parameters were assessed in 40 young women. results. at time t0, only 5% of patients had normal bone mineral density (bmd) in all bone regions, while 75% and 20% had osteopenia or osteoporosis, respectively, in at least one bone region. control densitometry (t1) was performed 22.1 ± 9.2 months later. lumbar and femoral bmd increased over time in the treatment groups with a significant time-treatment interaction effect (p = 0.004 and p = 0.025, respectively). conclusions. these preliminary data suggest that estradiol is administered both transdermally and orally in young women with hypergonadotropic amenorrhea. keywords: bones; hypergonadotropic hypogonadism; amenorrhea; estradiols; oral estradiol; transdermal estradiol. introduction. premature ovarian failure (pof) is a clinical syndrome characterized by loss of ovarian activity before the age of 40; this is due to hypoestradiolism and oligoor amenorrhea [1]. pof can have different etiopathogenic causes: it can be iatrogenic, as after chemotherapy, radiation therapy, or surgery, but it can also be associated with chromosomal / genetic defects (turner syndrome or fragile x syndrome) and with autoimmune disorders, or it may be idiopathic [2]. hypergonadotropic amenorrhea also occurs in women with complete androgen insensitivity syndrome (cais) who have undergone gonadectomy. cais is the most common sexual development disorder 46, xy, caused by mutations in the androgen receptor, causing complete resistance to the action of androgens [3]. both pof and cais after gonadectomy are conditions associated with a high risk of bone health problems. pof is known to be associated with lower bone density than in healthy people [1,4–6] and with an increased risk of fractures at a later age [7]. in adolescents and adults with cais and remote gonads, there is a decrease in bone mineral density (bmd), mainly in the lumbar region; [8-13] however, adequate hormone therapy (ht) appears to be able to improve bmd, at least at the lumbar level [6,9,11]. ht is strongly recommended for women with pof and patients with cais gonadectomy because it plays an important role in bone protection, as well as in the art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 116 prevention of cardiovascular disease and mortality [1]. there is still little data on the optimal dose, regimen and type of ht in young women with no ovarian estradiol production [6,14-17], and, in particular, there are still no data on oral administration of estradiol valerate. the main objective of this retrospective pilot study was to assess the effect of various estradiolic molecules and routes of administration (oral estradiol valerate, transdermal estradiol, oral ethinyl estradiol) on bone health in young women with hypergonadotropic amenorrhea (idiopathic or iatrogenic pof, women with pof and terner syndrome) and compare them with the results in untreated women. a secondary goal of our study was to evaluate the effect of these treatments on the biochemical and clinical characteristics of these patients. material and methods study design and population. in this retrospective pilot study, we evaluated young adults with secondary hypergonadotropic amenorrhea. the women were selected from among the patients who attended the republican specialized scientific and practical medical center of endocrinology named after v.i. j.h. turakulova. in this study, we included women with normal karyotype 46, xx with pof, gonadectomized women with spna, and women with turner syndrome. all spna patients had a 46, xy karyotype with a confirmed androgen receptor mutation and previous bilateral gonadectomy, while turner syndrome patients had a 45, x0 karyotype. for all groups of patients, the following data were recorded: age of onset of amenorrhea, age of onset of estradiol intake, type and dose of estradiol, and route of administration (oral or transdermal). age at gonadectomy was also recorded for cais subjects. patients were divided into four study groups depending on treatment: transdermal estradiol in gel (te), oral estradiol valerate (ev), oral ethinylestradiol (oe) with or without progestin or without treatment (femur delta bmds varied significantly between groups (p = 0.004), with a significant increase in both te and ev groups compared to oe or e). we compared bmd of the spine and hip in these four groups. all patients underwent clinical, laboratory and radiological examinations in accordance with clinical practice. anthropometric measurements were carried out on all subjects: height was measured with a stadiometer as the distance from the top of the head to the floor, when the subject was asked to stand straight, barefoot, touching the walls with his shoulders. body mass index (bmi) was calculated as weight in kilograms divided by the square of height in meters (kg / m2). bone parameters were recorded in patient records. bmd was measured using dual x-ray absorptiometry. the bmd of the spine was obtained between the lumbar levels [1–4] (l1 l4) and the total bmd of the femur in the femoral neck, trochanteric and intertrochanteric regions. the results of measuring the mic were recorded in g / cm2. for bmd, the t-score indicates the extent to which bmd measured at a site of bone differs from bmd in a control sample of healthy subjects aged [25–30] years (age at which peak bone mass is achieved) ... the world health organization (who) criteria divide bmd t-scores as follows: normal: +2.5 to 1.0 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 117 standard deviation compared to the mean maximum bone mass in a young person; osteopenia: –1 to –2.5 sd and osteoporosis: below –2.5 sd. bmd z-scores, on the other hand, refer to the number of standard deviations of values measured at sites of bone and how they deviate from values measured in a healthy control population of subjects of the same age and sex as the study patients. bmd changes were also expressed as deltas (the difference between the two bmd scans. the following laboratory test results have been reported: estradiol, lh, fsh, fasting glucose, total cholesterol (tc), high and low density lipoproteins (hdl and ldl), triglycerides (tg), aspartate and alanine aminotransferase, prothrombin time, and activated partial thromboplastin time. all patients were over 18 years of age at the time of enrollment. results clinical characteristics of the enrolled women, sixty-two women with amenorrhea were potentially eligible and screened. according to our inclusionexclusion criteria, 22 women were excluded due to lack of densitometry data. thus, 40 women were included in the data analysis. their average age at the time of the first available densitometry assessment (t0) was 23.8 ± 5.5 years (range: 15–35 years). the etiopathogenetic factors of amenorrhea were distributed as follows: 22 women with pof, 10 women with turner syndrome and eight with idiopathic (five patients) or iatrogenic pof (three patients after chemotherapy and / or radiation therapy for cancer treatment), the latter 46, xx karyotype. the average duration of amenorrhea before the onset of ht was 13.2 ± 4.1 months. the clinical characteristics of patients at the time of their first densitometry are presented in tables 1 and 2. at t0 (first densitometry)), 30 patients (75%) did not receive hormones, while 10 patients (25%) underwent the first densitometry after starting treatment. smoking rates did not differ between groups. liver enzymes were within the normal range for all included subjects (data not shown). the groups were homogeneous, with no significant differences in assessed anthropometric and metabolic parameters, with the exception of ldl cholesterol, which showed significantly higher levels in ee compared with the ev group (133 ± 41 mg versus 88 ± 22 mg, p = 0.01) (table 1, 2). table 1 baseline anthropometric and clinical parameters of patients included during their first dxa scan. parameters gt (n = 34) bt (n = 6) p increase (years) in t0 24.2 ± 5.4 20.0 ± 6.2 0.093 gt in t0 (years) (for non-accepting gt, n) 2.6 ± 1.8 (10/34) n.a. height (cm) 58.6 ± 13.6 57.0 ± 13.5 0.792 weight, kg) 1.64 ± 0.11 1.61 ± 0.12 0.547 bmi 21.5 ± 3.8 20.9 ± 3.0 0.719 smoking 3 (8.8%) 0 0.999 values are expressed as mean ± standard deviation, unless otherwise indicated. bmi, body mass index; ht, hormone therapy art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 118 table 2 baseline anthropometric, clinical and bone parameters of the included patients undergoing various hormonal regimens. parameters te (n = 12) ev (n = 15) ev (n = 7) bt (n = 6) r age (years) in t0 24.3 ± 4.4 24.7 ± 5.3 23.0 ± 7.3 20.0 ± 6.2 0.247 duration of gt in t0 (years) (for non-accepting gt, n) 2.3 ± 1.9 (5/12) 2.8 ± 1.4 (3/15) 3.4 ± 2.8 (2/7) n.a. 0.248 height (cm) 59.8 ± 15.6 57.9 ± 12.6 57.7 ± 12.5 57.0 ± 13.5 0.925 weight, kg) 1.63 ± 0.11 1.66 ± 0.11 1.63 ± 0.13 1.61 ± 0.12 0.739 bmi 21.9 ± 4.0 21.3 ± 4.0 21.1 ± 2.7 20.9 ± 3.0 0.944 smoking 3 (23%) 0 0 0 0.999 δ bmd of the lower back (g / cm2) (t1-t0) 0.037 ± 0.041 0.064 ± 0.084 * -0.003 ± 0.073 -0.078 ± 0.116 0.008 δ bmd of the femur (g / cm2) (t1-t0) 0.026 ± 0.035 * 0.026 ± 0.034 * § -0.06 ± 0.06 -0.048 ± 0.046 0.004 values are expressed as mean ± standard deviation, unless otherwise indicated. bmi, body mass index; te, transdermal estradiol; ev, oral estradiol; ee, oral ethinyl estradiol; no, no hormonal treatment. * = p <0.01 compared with bt; § = p <0.01 compared to ee. bone parameters bone parameters during baseline densitometry (t0) in the entire cohort, the bmd of the lumbar spine at the first densitometry was 0.913 ± 0.131 with a t-score of -1.92 ± 1.04 and a z-score of -1.81 ± 0.98. femur mineral density was 0.865 ± 0.125 with a t-score of -1.06 ± 0.99 and a z-score of 1.02 ± 0.90. taking the entire cohort into account, 30/40 patients (75%) had osteopenia and 8/40 (20%) osteoporosis in at least one site of the bone. no osteoporotic fractures were found in the study groups. at time t0, the bmd of the lower back and hip did not differ significantly between the four groups. in addition, most of 10 women already using ht during their first densitometry had bmd abnormalities, three patients had osteoporosis (two in the te group and one in the ev group) and six had osteopenia (three in the te group, one in the ev and one in the ee group) in at least one site of the bone. two had normal bmd in all areas of the bone. variations in bone tissue parameters in women receiving different hormonal regimens. the time interval between the two estimates of bone mineral density (t1 t0) was 22.1 ± 9.2 months, with no significant differences between the four groups (the time interval of densitometry was 20.6 ± 8.9 months for te, 22.9 ± 9 , 3 months for ev, 20.3 ± 8.8 months for ee and 25.0 ± 9.5 months for bt). all ht patients reported correct and consistent use of their treatment between the two bmd scores. lumbar bmd showed a significant interaction of time and treatment (p = 0.004]. the changes in bmd from t0 to t1 (delta) varied significantly between treatment groups ( p = 0.008) .a posteriori analysis revealed a significant increase in lumbar bmd in the ev group compared to the bt group (p = 0.006) and in the te group compared to art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 119 bt (p = 0.036). in addition, the bmd of the femur showed a significant effect of time interaction and treatment (p = 0.025). changes in bmd from t0 to t1 (delta) significantly differed between groups (p = 0.004), with a significant change (increase) in bmd of the femur both in the te and ev groups compared to bt or with ee. anthropometric and metabolic parameters bmi at baseline was within normal limits and the same in all groups. bmi and metabolic parameters (glucose, total cholesterol, hdl and ldl cholesterol, triglycerides and liver enzymes) did not show significant changes in patients receiving and not receiving therapy. blood pressure was within normal limits and did not change during the study period. discussion. in this pilot study, we compared changes in bone, metabolic, and anthropometric parameters in very young women with hypergonadotropic hypogonadism, pof, and cais receiving different hormonal regimens (oral estradiol valerate, transdermal estradiol, oral ethinyl estradiol, or no hormonal therapy). although our results should be validated in a larger sample, both transdermal and oral estradiol appeared to be associated with large short-term improvements in bone bmd compared with ethinyl estradiol or no therapy. during their first densitometry, the entire cohort presented t-scores indicative of osteopenia, in particular for the lumbar region, but also for the femur, with only five percent of patients having normal bmd in all areas of the bone. the second bmd study was performed 22.1 ± 9.2 months after the first. both oral estradiol valerate and transdermal estradiol were associated with significant increases in lumbar bmd and changes in femur bmd, significantly different from those obtained with oral ethinyl estradiol or no treatment. in women who received oral ethinylestradiol or did not receive treatment, there was a slight decrease or no significant changes in bmd. no significant changes in anthropometric and metabolic parameters were observed during the treatment period, even though the small sample size may have limited the detection of differences. pof and cais are known risk factors for bone health. several studies have shown that women with pof have lower bmd and a significantly increased risk of fractures [7,18,19]. long-term ht can reduce the increased risk of fractures [4,17,2022]. in particular, a major health concern for very young women with pof is that potentially long-term estradiol deficiency at a young age can lead to a decrease in peak bone accumulation in the event of delayed or inadequate ht [4]. likewise, it is known that women living with cais have low bmd both before and after gonadectomy due to a combination of estradiol deficiency and bone resistance to androgens, and in some cases due to inadequate ht after gonadectomy [9,11, 12]. the lumbar spine is more prone to bmd deficiency, as it is characterized by a predominance of trabecular bone. recently, it was confirmed that ht-containing estradiols are able to increase bmd in this area, but not on the femoral neck [6, 20] research on optimal hormonal treatment for women with pof and cais is still limited. in our cohort, the transdermal route was confirmed to be superior to oral ethinyl estradiol in improving bmd in the lumbar and femoral regions. transdermal art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 120 estradiol administration has already been associated with better bmd in women with pof compared to both conjugated oral estradiols and oral ethinylestradiol [15,21]. in the cais population, the transdermal route of estradiol administration appears to be superior to oral administration in terms of increasing total body mineral density [6]. although the sample size is limited, our study appears to show that oral estradiol valerate is superior to oral ethinyl estradiol in increasing bmd in the lumbar and femoral regions. this is the first study to show the ability of oral administration of 2 mg estradiol valerate with or without progestin to increase bmd more than oral administration of ethinyl estradiol plus progestin: the increase in bmd in the lumbar spine was the same as with transdermal estradiol. and even more than that obtained transdermally in the femoral neck. there are limited but consistent data on estradiol in this population: cartwright et al. in a two-year, open-label, randomized trial reported the superiority of estradiol 2 mg (plus 5 mcg levonorgestrel for 12 days per month) over 30 mcg ethinyl estradiol (plus levonorgestrel). 150 mcg taken daily for 21 days a month) to increase bmd of the lumbar spine in women with spontaneous pof [17]. some limitations of this study should be noted. first of all, pof at this young age and cais are rare conditions; for this reason, a small cohort was analyzed in this pilot study, and this could lead to a statistical error of type ii. in addition, various etiologies of amenorrhea were included in the analysis. in addition, some statistically significant associations should be interpreted with caution given the small number of subjects in each group. another limitation is the retrospective nature of the study. the two bmd evaluations were performed on the same machine for each patient, but the cohort as a whole used different machines. in conclusion, these preliminary data suggest a superiority of oral estradiol valerate over oral ethinyl estradiol in improving lumbar and femoral bmd in young women with hypergonadotropic hypogonadism. in accordance with previous literature, our cohort of women with pof and cais was characterized by some violation of the bmd, in particular, at the level of the lower back. after 22.1 ± 9.2 months, treatment with oral estradiol valerate or transdermal estradiol showed the ability to induce positive changes in the lumbar and femoral regions, while women who received oral ethinyl estradiol or did not receive any treatment showed little or no significant changes in bmd. further research in larger cohorts is imperative to understand which hormone treatment is best for bone health in young women with pof or cais, as there is little data available on optimal molecules, regimen, and dosages. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 121 references 1. european society for human reproduction and embryology (eshre) guideline group on poi, webber l, davies m, anderson r, et al. eshre guideline: management of women with premature ovarian insufficiency. hum reprod. 2016;31:926-37. 2. maclaran k, panay n. current concepts in premature ovarian insufficiency. womens health (lond). 2015;11:169-82. 3. berglund a, johannsen th, stochholm k, et al. incidence, prevalence, diagnostic delay, and clinical presentation of female 46, xy disorders of sex development. j clin endocrinol metab. 2016;101: 4532-40. 4. popat vb, calis ka, vanderhoof vh, et al. bone mineral density in estradioldeficient young women. j clin endocrinol metab. 2009;94:2277-83. 5. uygur d, sengül o, bayar d, erdinç s, batioğlu s, mollamahmutoglu l. bone loss in young women with premature ovarian failure. arch gynecol obstet. 2005;273:17-9. 6. gava g, mancini i, orsili i, et al. bone mineral density, body composition and metabolic profiles in adult women with complete androgen insensitivity syndrome and removed gonads using oral or transdermal estradiols. eur j endocrinol. 2019;181:711-8. 7. van der voort dj, van der weijer ph, barentsen r. early menopause: increased fracture risk at older age. osteoporos int. 2003;14:525-30. 8. bertelloni s, baroncelli gi, federico g, cappa m, lala r, saggese g. altered bone mineral density in patients with complete androgen insensitivity syndrome. horm res. 1998;50:309-14. 9. danilovic dl, correa ph, costa em, melo kf, mendonca bb, arnhold ij. height and bone mineral density in androgen insensitivity syndrome with mutations in the androgen receptor gene. osteoporos int. 2007;18:369-74. 10. sobel v, schwartz b, zhu y-s, cordero jj, imperato-mcginley j. bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes. j clin endocrinol metab. 2006;91:3017-23. 11. han ts, goswami d, trikudanathan s, creighton sm, conway gs. comparison of bone mineral density and body proportions between women with complete androgen insensitivity syndrome and women with gonadal dysgenesis. eur j endocrinol. 2008;159:179-85. 12. soule sg, conway g, prelevic gm, prentice m, ginsburg j, jacobs hs. osteopenia as a feature of the androgen insensitivity syndrome. clin endocrinol (oxf). 1995;43:671-5. 13. marcus r, leary d, schneider dl, shane e, favus m, quigley ca. the contribution of testosterone to skeletal development and maintenance: lessons from the androgen insensitivity syndrome. j clin endocrinol metab. 2000;85:1032-7. 14. webber l, anderson ra, davies m, janse f, vermeulen n. hrt for women with premature ovarian insufficiency: a comprehensive review. hum reprod open. 2017;2017:hox007. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5772964 122 15. guttmann h, weiner z, nikolski e, et al. choosing an oestradiol replacement therapy in young adult women with turner syndrome. clin endocrinol (oxf). 2001;54:159-64. 16. sullivan sd, sarrel pm, nelson lm. hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. fertil steril. 2016;106:1588-99. 17. cartwright b, robinson j, seed pt, fogelman i, rymer j. hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: a randomized controlled trial of the effects on bone mineral density. j clin endocrinol metab. 2016;101:3497-505. 18. abdullaeva u.k. predicting the risk of atrophic transformation in chronic gastritis using serum pepsinogen // world journal of pharmaceutical research, faculty of pharmacy medical university, bulgaria, vol. 8, iss. 13, 2019, p. 219-228. 19. abdullaeva u.k., sobirova g.n., karimov m.m., aslonova i.j. the prevalence and possibilities of prevention of noncardial gastric cancer in the bukhara region // american journal of medicine and medical sciences, 2020, 10(9), р. 679-681. 20. abdullaeva u.k., shadjanova n.s. using the olga system in chronic atrophic gastritis // new day in medicine, 2020, №2, p. 9-12. 21. abdullaeva u.k. the value of interactive teaching methods in improving the level of clinical knowledge of students // medical education and professional development. 2019, №1 (33), p. 29-32. [in russian] 22. abdullaeva u.k. predicting the risk of atrophic transformation in gastritis associated with chronic helicobacter pylori // abstract of phd dissertation on medical sciences. tashkent. 2021. 46-p. https://elibrary.ru/item.asp?id=43137990 https://elibrary.ru/item.asp?id=43137990 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 22 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 23 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 24 clinical manifestation of irritable bowel syndrome makhmudova l.i., akhmedova n.sh., ergashov b.b. bukhara state medical institute, bukhara, uzbekistan e-mail address: makhmudova.lola.89@mail.ru abstract. irritable bowel syndrome (ibs) is a biopsychosocial disease consisting of a set of functional disorders not explained by organic changes in the intestine. patients with ibs were divided into two groups: with non-refractory (ibsn 35 people) and refractory (ibsr 47 people) the course of the ibs. of these, taking into account the leading clinical syndrome, patients with ibsn-d (diarrhea) 21 people were identified (25.6%), ibsn-c – (constipation) 14 people (17%), ibsr-d 28 people (34.2% ), ibsr-c 19 people (23.2%). more abdominal pain syndrome was noted in patients with a clinical form of ibs with a predominance of diarrhea. the ordinal assessment of the severity of ibs symptoms allows to objectify the severity of clinical manifestation of intestinal dysfunction in patients, identify the clinical features of the course of this pathology. key words: irritable bowel syndrome, clinical symptoms, bristol scale introduction. functional bowel diseases (fbd) make up the majority of functional gastrointestinal (gi) pathology, characterized by a variable combination of chronic or recurrent symptoms related to different parts of the gi tract that cannot be explained by morphological or biochemical abnormalities. these disorders are diagnosed by excluding a number of organic gastrointestinal diseases that have similar manifestations, after a thorough examination of the patient. in may 2016, the world gastroenterological community at the american gastroenterology week got acquainted with the rome iv criteria, the main provisions of the consensus have already been published [1,2,3,4]. table 1. rome criteria iv. section c. "functional bowel disorders" c1. irritable bowel syndrome mailto:makhmudova.lola.89@mail.ru art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 25 c2. functional constipation c3. functional diarrhea c4. functional bloating c5. nonspecific functional intestinal disorder c6. opioid-induced constipation irritable bowel syndrome (ibs) is a biopsychosocial disease that is a complex of functional disorders that cannot be explained by the organic changes in the intestine in the patient [5,6,7,8]. according to the metaanalysis published in 2012, in which, according to quite strict selection criteria, 80 clinical studies with a total number of patients 260,960, the prevalence of ibs in the world is 11.2% [9]. only 12-15% of patients seek medical care. in southeast asia, its frequency is 7%, in europe 20%, 21% in south america. according to literature, the number of patients with functional disorders of the gastrointestinal tract, including the ibs, in a specialized gastroenterological hospital reaches 41-45% [10,11,12]. the massage of the ibs among women remains higher than among men. young people are more susceptible to the development of the disease, rather than 50 years old. any case of the manifestation of the clinical picture of the ibs in patients of an older age category should alarm in relation to the elimination of organic pathology. the purpose of the study. a study of the clinical symptoms of patients with different forms of ibs. material and research methods. the article summarizes the data of surveys 82 patients with the ibs on the examination and treatment in the gastroenterology bombing department from 2017 to 2019. the average age of patients was 33,2 ± 0.8 years. patients with ibs were divided into two groups: with non-refractory (ibsn 35 people) and refractory (ibsr 47 people) the course of the ibs. of these, taking into account the leading clinical syndrome, patients with ibsn-d (diarrhea) 21 people art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 26 were identified (25.6%), ibsn-c – (constipation) 14 people (17%), ibsr-d 28 people (34.2% ), ibsr-c 19 people (23.2%). the control group included 20 healthy volunteers (6 males and 14 females) who underwent prophylactic screening as part of the examination of gastrointestinal tract pathology at brmmc (bukhara regional multidisciplinary medical center). the mean age of the control group was 27,8 ± 4,1 years. the diagnosis of ibs was established taking into account the roman criteria iv (2016), recommendations of the bomb. when determining the clinical version of the ibs used the bristol cala's forms [blake m.r., raker j.m., whelan k., 2016]. patients were examined according to standards: general blood test, biochemical blood test with assessment of liver and kidney function, general urine analysis, electrocardiogram, coprogram, test for hidden blood, ultrasound examination of abdominal organs (vivid s-60,2014, norway), esophagogastroduodenoscopy fuginon. fugi film epx-2500, 2014, japan; fugi film-eg-530pf, 2014, japan), fibrocolonoscopy (fugi film-eg-530fl, 2014, japan), contrast x-ray. in 82 patients with crc, microelements were performed (mass-spectrometry of usuli, perkinelmer inc., shelton, ct 06484, usa) on her hair. in 42 patients with ibs, bacteriological examination of feces on dysbacteriosis. results and discussion. the non-refractory ibs was determined taking into account the anamnesis data. in case of non-refractory ibs, the total length of symptoms over the past year to the present appeal to the doctor was an average of 11.14 ± 0.29 weeks, a positive effect was observed from the therapy appointed in accordance with the clinical recommendations of the bomb. the overall duration of the disease at a non-refractory ibs was 4.3 ± 0.39 years. with refractory ibs, the total duration of symptoms over the past year to the present appeal to the doctor was an average of 29.81 ± 0.27 weeks, there was a low effectiveness of the therapy appointed in accordance with the clinical recommendations of brmmc, with a confirmed diagnosis of ibs and sufficient adherence to treatment. the total duration of the disease in the refractory ibs was 4.7 ± 0.27 years. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 27 data on the age of debut of the ibs are presented in table. 2. table 2. the debut of the disease is the debut of the disease in various types of ibs index sex ibsn-d (n =21) ibsn-c (n=14) ibsr-d (n = 28) ibsr-c (n=19) 1 2 3 4 5 6 medium debut age м±m male 21,2 ± 0,4 26,2 ± 0,6 19,3 ± 0.3* 24,0 ± 0,2 female 22,0 ± 0,4 28,6 ± 0,5* 24, ± 0.3 20,1 ± 0,3* regardless of the sex 21,9 ± 0,3 27,6 ± 0,5* 21,6 ± 0.5 21,9 ± 0,5 notes: ibsn-d non-refractory ibs with diarrhea; ibsn-c non-refractory ibs with constipation; ibsr-d refractory ibs with diarrhea; ibsr-c refractory ibs with constipation; * differences with an average of the middle-aged debut in the entire sample of patients with ibs (p <0.05) the age of the debut with an non-refractory version of the ibs 24,14 ± 0.54 years: with ibsn-d 21.9 ± 0.3 years, with ibsn-c 27.6 ± 0.5. later, the very beginning of the disease was noted in women with ibsn-c (28.6 ± 0.5) in comparison with the overall sample of patients with ibs (p <0.05). the age of debut of the disease in patients with a refractory variant of the flow of the ibs was 21.6 ± 0, years, which is significantly lower (p <0.05) than with the irrefractive course of the disease. in men earlier, the ibsr-d (19.3 ± 0.3) was debuted, in women – ibsr-c (20.1 ± 0.3). to determine the clinical severity of the ibs flow, we accepted a ballroom system of assessment of symptoms: the lack of a sign was evaluated as 0 points, from weak severity to moderate manifestations 1 point, expressed manifestations 2 points. summing the number of points for each patient is carried out in eight signs (the presence of abdominal pain, diarrhea, constipation, flatulence, feelings of incomplete intestinal emptying, false urges, secretion of mucus, long-term outline art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 28 during defecation). patients who scored 11-16 points were attributed to a group with severe / pronounced manifestations that scored 6-10 points in a group with moderate / mid-severity, and received 1-5 points to a group with light manifestations (table 3). table 3. palk scale to determine the severity of the flow of the ibs basic symptom 0 балла 1 балла 2 балла abdominal pain "not very serious", rarely "not very serious", rarely very strong, "terrible" diarrhea less than 3 times a day less than 3 times a day over 5 times a day constipation 1 time less than 2 days 1 time less than 2 days 1 time in 5-7 days metiorism + ++ +++ feelings of incomplete emptying of the intestine + ++ +++ false urges seldom seldom always selection of mucus seldom seldom always long strain during defecation seldom seldom always the distribution of patients depending on the severity of the clinical manifestations of the ibs, obtained as a result of the use of a ball assessment of the severity of symptoms as follows (table 4). table 4. clinical severity of flow and signs of illness during the period of exacerbation in various clinical versions of the ibs art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 29 clinical symptoms вариант течения срк ibsn-d (n =21) abs.num. (%) ibsn-c (n=14) abs.num. (%) ibsr-d (n = 28) abs.num. (%) ibsr-c (n=19) abs.num. (%) abdominal pain 21 (100) 14 (100) 28 (100) 19 (100) diarrhea 21 (100) 0 (0) 28 (100) 0 (0) constipation 0 (0) 14 (100) 0 (0) 19 (100) flatulence 15 (71,4) 9 (64,2) 11 (39,3) 15 (78,9) feelings of incomplete emptying of the intestine 8 (38,2) 11 (78,5) 13 (46,4) 16 (84,2) false urges 8 (38,2) 2 (14,2) 12 (42,8) 9 (47,4) selection of mucus 9 (42,8) 3 (21,4) 17 (60,7) 10 (52,6) long strain during defecation 9 (42,8) 7 (50) 9 (32,1) 13 (68,4) frequency chaul 1-4 times a day 12 (57,1%±11,1)* 0 (0) 6 (21,4%±7,9)* # 0 (0) 5 or more than a day 9 (42,9%±11,1)* 0 (0) 22 (78,6%±7,9)* # 0 (0) 1 time in 3-4 days 0 (0) 8 (57,1%±13,7) 0 (0) 6 (31,6%±11,0) 1 time in 5-7 days 0 (0) 6 (42,9%±13,7) 0 (0) 13 (68,4%±11,0) # clinical severity of the flow of the ibs easy 10 (47,6) 9 (64,3) 6 (21,4) 4 (21,1) average 8 (38,2) 5 (35,7) 9 (32,2) 6 (31,6) heavy 3 (14,2) 0 (0) 13 (46,4 9 (47,3) notes: ibsn-d non-refractory ibs with diarrhea; ibsn-c non-refractory ibs with constipation; ibsr-d refractory ibs with diarrhea; ibsr-c refractory ibs with constipation; * differences with indicators of a group of non-refractory patients (p <0.05); *# differences with indicators of a group of refractory patients (p <0.05) art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 30 the "intestinal" symptomatics in the refractory current of the ibs was more pronounced than with a non-refractory: at the ibsr-d, the chair was rapid up to 5 or more than a day (p = 0.0011), in the morning hours, with an admixture of mucus, tensies were more often marked (p = 0.0341) and a sense of incomplete emptying of the intestine after defecation (p = 0.0314). most patients with ibsr-c presented complaints to constipation up to 5-7 days (p = 0.0000), admixture of mucus in feces (p = 0.0087). tenses (p = 0.0007) and a sense of incomplete emptying of the intestine (p = 0.0263) were noted more often than with the non-refractory course of the ibsn-c. ibs with constipation prevailed the types of chaul 1st (ibsr-c) and 2nd (ibsnz) on a bristol scale. for the ibs with diarrhea, the types of chaul 5th (ibsn-d), 6th (ibsr-d) were characterized. the type of chaul 7th was noted in 8 (28.6%) patients with ibsr-d. the normal forms of chaul (3rd and 4th in a bristol scale) with a change in the multiplicity of defecation and a sense of incomplete emptying of the intestine in 10 (24.4%) patients with a non-refractory version of the ibs and 8 (7.5%) of patients with refractory variant of the disease (table 5). table 5. forms of a chaul in a bristol scale типы стула option of the flow of ibs ibsn-d (n =21) abs.num. (%) ibsn-c (n=14) abs.num. (%) ibsr-d (n = 28) abs.num. (%) ibsr-c (n=19) abs.num. (%) 1 0 (0) 2 (14,2) 0 (0) 13 (68,4) *# 2 0 (0) 8 (57,1) 0 (0) 4 (21,1) *# 3 2 (9,5) 2 (14,2) 0 (0) 2 (10,5) 4 3 (14,2) 2 (14,2) 3 (10,7) # 0 (0) 5 6 (28,5) 0 (0) 6 (21,4) *# 0 (0) 6 10 (47,6) 0 (0) 11 (39,3) # 0 (0) 7 0 (0) 0 (0) 8 (28,6) *# 0 (0) notes: ibsn-d non-refractory ibs with diarrhea; ibsn-c non-refractory ibs with constipation; ibsr-d refractory ibs with diarrhea; ibsr-c refractory ibs with constipation; * differences with art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 31 indicators of a group of non-refractory patients (p <0.05); *# differences with indicators of a group of refractory patients (p <0.05) when estimating the intensity of abdominal pain on a visual analog scale (vas), a moderate (p = 0.0082) and an intense (p = 0.0001) abdominal pain syndrome (table 6) was more often recorded during the refractory flow. table 6. the intensity of abdominal pain (vas) pain intensity ibsn-d (n =21) abs.num. (%) ibsn-c (n=14) abs.num. (%) ibsr-d (n = 28) abs.num. (%) ibsr-c (n=19) abs.num. (%) weak 12 (57,1%±11,1) 8 (67,1%±13,0) 3 (10,7%±5,9)* 2 (10,5%±7,2)* average 9 (42,9%±11,1) 6 (42,8%±13,7) 14(50%±9,6)* 9 (47,5%±11,8)* # strong 0 (0) 0 (0) 11(19,3%±7,6)* # 8 (42,2%±11,7)* notes: ibsn-d non-refractory ibs with diarrhea; ibsn-c non-refractory ibs with constipation; ibsr-d refractory ibs with diarrhea; ibsr-c refractory ibs with constipation; * differences with indicators of a group of non-refractory patients (p <0.05); *# differences with indicators of a group of refractory patients (p <0.05) the index of abdominal pain according to your refractory ibs was estimated as moderate pain syndrome and was significantly higher than with an non-refractive ibs (3.6 ± 0.2 points, p = 0.0000). the intensity of abdominal pain at the ibsr-d (5.7 ± 0.3) was lower than when ibsr-c (6.0 ± 0.4, p = 0.0000). conclusion 1. more abdominal pain syndrome was noted in patients with a clinical form of ibs with a predominance of diarrhea. 2. the ordinal assessment of the severity of ibs symptoms allows to objectify the severity of clinical manifestation of intestinal dysfunction in patients, identify the clinical features of the course of this pathology. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 32 references 1. maev i.v., cheremushkin s.v., kucheryavy yu.a. an irritable bowel syndrome. roman criteria iv. on the role of visceral hypersensitivity and methods for its correction. toolkit. m., 2016. 2. makhmudova l.i., shazhanova n.s., akhmedova n.sh., (2021). clinical features of irritable intestinal syndrome. the american journal of medical sciences and pharmaceutical research, 3(04), 154-159. 3. abdullayev r.b., makhmudova l.i., (2021). assessment of clinical and psychological status and quality of life of patients in different forms of irritable bowel syndrome. the american journal of medical sciences and pharmaceutical research, 3(02), 127-134 4. makhmudova l.i, akhmedova n.sh. irritable bowel syndrome: a new look at the problem // academicia. 10.5958/2249-7137.2020.00983.0. 433-38 5. abdullayev r. b., makhmudova l.i. features of chemical elements in various forms of irritable bowel syndrome // annals of r.s.c.b., issn:1583-6258, vol. 25, issue 2, 2021, pages. 2993 – 3000 6. abdullayev r.b., makhmudova l.i. micro elemental imbalance in irritable bowel syndrome and its correction. academicia. vol. 11, issue 5, may 2021:655-662 7. abdullaeva u.k., shadjanova n.s. using the olga system in chronic atrophic gastritis // new day in medicine, № 2 (30) 2020, bukhara, uzbekistan, р. 9-12. 8. abdullaeva u.k., sobirova g.n., karimov m.m., aslonova i.j. the prevalence and possibilities of prevention of noncardial gastric cancer in the bukhara region // american journal of medicine and medical sciences, 2020, 10(9), р. 679-681. 9. sobirova g.n., abdullaeva u.k., nosirova m.s., aslonova i.j. evaluation of the gastrointestinal mucosa by the olga system in chronic atrophic gastritis // journal of critical reviews, kuala lumpur, malaysia, vol. 7, iss. 2, 2020, p. 409-413. 10. karimov m.m., sobirova g.n., abdullaeva u.k., aslonova i.zh., tulyaganova f.m. possibilities of serological diagnosis of atrophic processes of the gastric mucosa art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080550 33 // european journal of molecular & clinical medicine vol. 7, iss. 11, 2020, p. 29552960. 11. sobirova g.n., abdullaeva u.k., mirzaeva d.b., ismitdinova n.s. immunopatogenesis of chronic gastritis and its role in carcino genesis // academicia an international multidisciplinary research journal, affliated to kurukshetra university, kurukshetra, india. vol.8, iss.12, 2018, p. 32-40. 12. abdullaeva u.k. predicting the risk of atrophic transformation in chronic gastritis using serum pepsinogen // world journal of pharmaceutical research, faculty of pharmacy medical university, bulgaria, vol. 8, iss. 13, 2019, p. 219-228. 13. sobirova g.n., abdullaeva u.k. chronic gastritis and carcinogenesis issues // electronic journal of actual problems of modern science, education and training, urganch, uzbekistan, 2019-i, p. 159-172. art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.6034654 18 art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.6034654 19 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.6034654 20 features of the episodic process in the territory of natural focuses of the plague of the cis countries dmitriev a.n. 1 , nematov a.s. 2 , rakhmanova d.a. 2 1 uchkuduk anti-plague station" si "nmmc foundation", uchkuduk, republic of uzbekistan, 2 tashkent institute of postgraduate medical education."" tashkent medical academy” of the ministry of health of the republic of uzbekistan, tashkent, republic of uzbekistan abstract: aepizootological manifestations of the plague in 2011-2020 were registered on the territory of 11 states. data on the central part of the kyzylkum natural desert plague outbreak indicate a reduction in major and minor plague carriers. in the conditions of mountainous and high-altitude landscapes, the impact of modern climate warming on the state of parasitic systems of the mountain and highaltitude natural plague foci is less pronounced. the epizootic potential of many autonomous biological principles of the gopher and sandy type has significantly decreased in the current century. keywords: epizootic activity, natural plague focus, central kyzylkum, giant gerbil, y. pestis. in 2011-2020, the total number of plague cases was 6743, of which 906 (13.4%) were fatal. a high incidence of the population was observed in africa: in the republic of madagascar (5451), the democratic republic of the congo (608), the republic of uganda (74) and the united republic of tanzania (61). in south and north america, cases of infection have been reported in the republic of peru (67), bolivia (4), and the usa (51). sporadic morbidity was recorded in asia in the people's republic of china (14), mongolia (16), the russian federation (3), and the kyrgyz republic (1). the most difficult epidemiological situation in 2011-2020 was on the territory of the republic of madagascar, where a significant outbreak of pneumonic plague took place in 2017. in 2020, 535 cases were registered in four countries of the world (148 patients in six countries in 2019), of which 37 were fatal. epidemiological problems were noted in the territories of the democratic republic of the congo (520 cases; 31 deaths), the people's republic of china (4 cases; 2 deaths), mongolia (6 cases; 3 fatal), and the usa (5 cases of the disease; 1 terminal). in total, epizootological manifestations of the plague in 2011-2020 were registered on the territory of 11 states; on the territory of the russian federation and other cis countries, the presence of 45 natural plague foci of various biocenosis structures has been confirmed to date, the functioning of which is associated with the circulation of yersiniapestispestis strains of medieval and ancient biovars, caucasian and central asian subspecies. the total area of the plague-enzootic territory of the cis countries art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.6034654 21 is 2101288 km2. the total area of the historical range of y. pestis strains of the medieval biovar 2.med1 is 1959965 km2 93.3% of the entire enzootic plague territory of the cis countries. epizootic manifestations were registered on an area of 352731 km2 (18.0%), the epidemic – on a site of 47241 km2 (2.4%). within the boundaries of the historical range of y. pestispestis of the phylogenetic branch 2.med1, 33 autonomous natural foci are currently located on the territory of the caspian and turanian lowlands, as well as the caucasus and transcaucasia, including sandy (25), gopher (6), marmot (2) types. the natural foci of the gopher type with the circulation of y. pestispestis strains of the medieval bioware2.med1 is 221347 km2; gerbil type 1728676 km2; marmot type 18442 km2. the pulsations of epizootic activity observed in the xx century of individual autonomous natural foci of y. pestispestis of the medieval biovar 2. climatic and anthropogenic factors entirely determined med1. it should be assumed that it was the high ecological plasticity of y. pestispestis strains of the medieval biovar 2.med1 decided the possibility of their distribution in populations of a broad species spectrum of rodents living in the territories of the caspian and turanian lowlands. in the current century, due to the influence of modern climate warming, the epizootic potential of many autonomous natural foci of the gopher and sandy type with the circulation of y. pestispestis strains of the medieval biovar has significantly decreased. in 2011-2020 years in the russian federation, songs of this branch were isolated only in 2013-2015 years on the territory of the caspian gerbil natural hearth. on the republic of kazakhstan territory at the beginning of this century in the desert, autonomous natural foci with the circulation of y. pestispestis of the medieval biovar, the last finds of infected animals took place in the volga-ural interfluve. until now, in the northern subzone of the desert zone of the republic of kazakhstan, only the north-aral and aral-karakum desert natural foci have retained epizootic activity. in the central part of the desert zone of kazakhstan, the last manifestations of epizootic activity also took place on the territory of the betpakdalinsky desert hearth – in 2014. a sharp decrease in epizootic activity occurred on the territory of the republic of turkmenistan (kopetdag desert hearth – since 1969, kara-kum desert hearth – since 2005) and the republic of uzbekistan (the southern part of the kyzylkum desert hearth – since 2012). in the southern and southeastern regions of the republic of kazakhstan, high epizootic activity was recorded only in the balkhash, moynkum, taukum desert, and ili intermountain natural foci of y. pestispestis of the medieval bioware. in the western part of the pamir-alai mountain system, within the boundaries of the hissar natural focus of the vole type with an area of 400 km2 (0.2% of the total area of the plague-enzootic territory of the cis countries), the circulation of y. pestis strains of the hissar biovar of the central asian subspecies 0.pe4h was registered. the last findings of infected animals were recorded here in 1991. in the last decade, the activation of the epizootic process in mountainous and high-altitude natural foci of y. pestispestis of the ancient biovar of phylogenetic branches 0.ant5 (kyrgyz republic), 4. ant (russian federation) has been noted. on the territory of the russian federation in 2011-2020 years in the tuva mountain art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.6034654 22 and gorno-altai high-mountain natural foci with the circulation of y. pestispestis strains of the ancient biovar of the phylogenetic branch 4. ant, the preservation of a tense epizootic and epidemiological situation was noted. in 2020 on the territory of the russian federation, local plague epizootics have been registered on the altai republic, as well as the republic of tyva. plague epizootics were detected on the territory of two (gorno-altaisk highland and tuva mountain) of 11 natural plague foci of the russian federation. in the course of further expansion of the range of y. pestispestis of the ancient biovar of the phylogenetic branch 4. ant in the western direction, it is impossible to exclude the possibility of forming a new cross-border focal territory within the boundaries of the southern altai ridge, located at the junction of the borders of four states russia, mongolia, china, and kazakhstan. in the conditions of climate warming in the current decade, it is expected to maintain a multidirectional trend in the dynamics of epizootic activity of natural foci with the circulation of y. pestispestis strains of the medieval biovar of the phylogenetic branch 2. med1 and the ancient biovar of the phylogenetic branches 0.ant5, 4. ant. on the territory of the russian federation, the parasitic systems of lowland natural foci of gopher and sandy-type plague with the spread of y. pestispestis of the medieval biovar branch 2.med1 will continue to remain in a state of deep depression. an increase in the temperature of the winter months is accompanied by frequent thaws icy phenomena, which increase the risks of death of rodents, including a wide species spectrum of gerbils of the genus meriones. an increase in temperatures in january-february leads to an early, undulating exit from the hibernation of ground squirrels of the genus spermophilus, which disrupts the rut, leads to the death of animals from starvation, delays the breeding period. high temperatures insufficient precipitation in the spring and summer months provoke dry winds vegetation burnout, which negatively affects the state of the rodent food supply and the generative potential of their populations. in the conditions of mountain and high-altitude landscapes, the impact of modern climate warming on the state of parasitic systems of the mountain and high-altitude natural plague foci due to the high mosaic of landscapes is less pronounced. in the plague-enzootic territory of the russian federation, following the longterm epizootological forecast, the preservation of a tense epidemiological situation is expected in the gorno-altai highland and tuva mountain natural foci of the plague. the favorable epizootological prognosis also extends to the biological principles of y. pestispestis of the medieval biovar of the phylogenetic branch 2.med1 transcaucasian plain-foothill, priaraxin low-mountain, and y. pestis of the caucasian subspecies of the phylogenetic branch 0.pe2 is a transcaucasian highland located in the republic of azerbaijan, georgia, and the republic of armenia. on the territory of the republic of kazakhstan, the preservation of high epizootic activity is predicted in the north aral, aral-karakum, balkhash, moyinkum, taukum desert, and ili intermountain natural foci with the circulation of y. pestispestis strains of the medieval biovar of the phylogenetic branch 2.med1. in the kyrgyz republic, the development of plague epizootics was caused by y strains. pestispestis of the antichnogobiovar of the phylogenetic branch 0.ant5 is expected on the territory of art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.6034654 23 the saryjaz and verkhnenarynsky high-altitude natural foci. there are no data on the state of natural plague foci in the republic of turkmenistan, the republic of uzbekistan, and the republic of tajikistan [1]. the kyzylkum natural foci of the plague, according to 2020, covers an area of 385,000 km2 is the most significant in epidemic terms; the territory with epidemic manifestations occupies 6700 km2. the most important part of the stationary objects of supervision of the anti-plague station of the state institution "navoi mining and metallurgical combine fund" of the republic of uzbekistan is located on the territory of the kyzylkum natural meso-plague outbreak, in its central part. the kyzylkum natural plague center is localized on the physical and geographical district of the same name, almost in the very center of the flat part of central asia, which is associated with its truly desert landscape. it includes the western part (belonging to uzbekistan) of the kyzylkum desert (its northern and eastern parts are located on the territory of kazakhstan). in the north, the district borders with kazakhstan, in the southwest with turkmenistan, in the east is the mirzachul district, in the southeast zarafshan and in the west — the lower reaches of the amu darya. the surface of the area decreases slightly in the direction from the southeast to the northwest. the average height is 200-300 m; in the southeast, the size reaches 350-400 m, in the northwest only 100 m. the lowest point is the mingbulak depression at 12 m below sea level. the highest point is the aktau peak (height 922 m) of tamdytau mountain. the relief of the kyzylkum district is diverse. there are plains, remnant mountains, and depressions located between the mountains. but most of kyzylkum is made up of tables with an absolute height of up to 200 m. the central part of the plain is occupied by sand ridges, sandhills, dunes, takyrs. dunes are found mainly along the banks of the amu darya and around wells. plants anchor sand ridges and hills. takyrs occupy the inter-row depressions. the mountains bukantau (764 m), auminzatau (695 m), etymtau (571 m), tamdytau (922 m), kuljuktau (785 m), sultan-uwais (473 m) are located mainly in the central part of kyzylkum.between these mountains are the depressions of mingbulak, karakata, mullali, ayakagitma. the lowered areas of these depressions are occupied by salt marshes, takyrs, sand massifs. [2,3]. the vegetation cover is dominated by perennial and sagebrush phytocenoses, psammophilic and halophilic communities are widespread, fragments of tugai vegetation are found. ephemera and ephemerides with a short spring growing season prevail among them: bulbous bluegrass, sedge, dantonia bonfire, tulips, snowdrops, ixiolirion, small-fruited cousins. juzgun, white saxaul, celine, sandy acacia, kandym grow on the fixed sands. wormwood and weeds are common on gray-brown soils. black saxaul, tamarisk, fleshy solyanka, sarisazan grow on saline, saline-marsh soils, and sheep's cleavage grows on takyrs. tugai plants grow in the amu darya valley. on the territory of the central section of the kyzylkums, it is noted that the threshold for experiencing rodent depression caused by internal mechanisms of selfregulation was passed in 2016-2017. 2018-2020 indicates a decrease in the number of art of medicine volume-2 international medical scientific journal issue-1 10.5281/zenodo.6034654 24 significant and minor plague carriers after the positive dynamics that appeared in 2016-2017, concerning both reproduction and the numerical composition of rodents. references: 1. n.v. popov, g.a. eroshenko,i.g. karnaukhov, a.a. kuznetsov , a.n. matrosov, a.v. ivanova, e.g. ogoldin, k.a. nikiforof, v.m. korzun, d.b. verzhutsky, e.v. chipanin, t.z. ayazbaev, a.k. dzhaparova, s.k. berdiev, a.a. lopatin, v.m. dubyansky, s.a. shcherbakova, s.v. balakhonov, a.n. kulinichenko, v.v,. kutirev. [epidemiolokal situation on plauge in 2020. forecast of episootic activity of natural plauge foci in the russian federation and other cis countries for 2021]. problemy osobo opasnikh infektsii [problems of partikulary dangerous infektions]. 2021; 1:52-62. 2. [physical and geographical zoning of uzbekistan]. training manual.t.: university, 2010. 3. k.g. tojibaev, n.y. beshko, v.a. popov. [botanical and geographical zoning of uzbekistan]. botanical journal. 2016;1. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 27 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 28 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 29 methods and principles of excision of perforated duodenal ulcers 1 botirov a.k., 2 izatullaev i.r., 3 nosirov m.m., 4 botirov j.a. 1,2,4 department of surgery and urology andijan state medical institute. andijan, uzbekistan 3 department of endosurgery andijan state medical institute. andijan, uzbekistan abstract. the authors have developed and implemented techniques and techniques for excision of perforated duodenal ulcers (pdu) with pylorus-preserving pyloroduodenoplasty (pdp) by preserving the integrity of the multifaceted function of the pyloric pulp (patents no. 2262 and no. 0128 ipa ruz were obtained). the subject of the study was patients who underwent excision pdu with pylorus-sparing pdp (main group) and 98 (20.5%) patients who underwent excision of pdu with pdp accompanied by destruction of the pyloric pulp (comparison group). by optimizing the surgical tactics, along with improved techniques and techniques for excision of pdu with pylorus-sparing pdp, the authors improved excellent and good results by 23.1% (in the control group 64.4%, in the main group 87.7%), reduced the frequency of satisfactory results by 16.0% (in the control group 24.4%, in the main group 8.4%) and unsatisfactory by 7.1% (in the control group 11.0%, in the main group 3.9%) keywords. perforated duodenal ulcer, duodenoplasty, pyloroduodenoplasty, gastric motor evacuation function, duodenogastric reflux, selective proximal vagotomy. introduction perforated duodenal ulcer (pdu) continues to occupy a leading place in the structure of frequency (10-20%) and mortality (2.0-20%) to this day. at the same time, the results of surgical treatment are not completely satisfactory [3; 4; 5; 9; 10]. the main integral link of the gastroduodenal complex is the pyloric pulp and the art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 30 mechanisms that control its activity [6; 7]. clinicians are more and more convinced that the destruction of the pyloric pulp by draining operation due to the perversion of the mechanisms of evacuation and secretion, sharply increases the frequency of duodenogastric reflux (dgr), dumping syndrome, diarrhea, alkaline reflux gastritis, non-healing or recurrence of ulcers, gastric ulcers and cancer [1; 2; 6; 8; 13]. most surgeons refrain from isolated low-traumatic operations, in particular from excision of the pdu with pylorus-sparing duodenoplasty (pdp), fearing a high risk of recurrent duodenal ulcer (du), despite the high efficiency of antisecretory and antihelicobacter pylori therapy, which was the subject of this study. purpose of the study improving the results of surgical treatment through the development and widespread use of improved techniques and techniques for excision of pdu with pylorus-sparing ppd. materials and methods the subject of our study were 381 (79.5%) patients who underwent excision of the pdu with pylorus-sparing pdp (main group) and 98 (20.5%) patients who underwent excision of the pdu with pdp accompanied by the destruction of the pyloric pulp (comparison group). all patients with pdu, upon admission to the admission department of the clinic, underwent general clinical blood and urine tests, coagulogram, blood tests for the presence of hepatitis viruses, syphilis, ecg, fluorography, plain radiography of the abdominal cavity, ultrasound, and, if indicated, diagnostic laparoscopy. in the postoperative period, up to 1 year or more, the functional state of the gastroduodenal complex was studied using conventional research methods. research results when choosing the method of surgery, we take into account many factors, the most important of which is: localization of the pdu and its complications; the time elapsed from the moment of perforation, the degree of risk of surgery, which depends on the age, concomitant therapeutic and concomitant surgical diseases, the general art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 31 condition of the patient and the type of surgery, especially the pathological changes detected during the operation. despite the success of the surgical treatment of pdu, the incidence of postoperative complications and mortality in the immediate postoperative period remain high. all patients underwent excision of the pdu, however, pyloric and duodenoplasty after excision of the pdu was performed in various modifications. it is known that gastric drainage operations improve the motor-evacuation function of the stomach (mefs) and reduce the contact of food with the mucous membrane of the antrum, which leads to a decrease in the gastrin mechanism. in the initial period of our work, during excision of duodenal ulcers, we used pdp according to finney, heineck-mikulich and judd-tanaka. type of the surgical interventions performed by us for pdu is presented in table 1. table 1. type of the performed surgical interventions for pdu. operation type – excision of pdu with: number of patients difference statistics by t criterion (p) abs % pdp for judd-tanaka 64 13,4 p<0,05 pdp for geineke-mikulich 14 2,9 p>0,05 pdp for finney 20 4,2 p>0,05 duodenoplasty 387 79,5 p<0,001 total 479 100 as can be seen from table no. 1, in the case of pdp by geyneke-mikulich 14 (2.9%), a longitudinal incision was used along the axis of the stomach and duodenum, i.e. a wide pyloroduodenotomy was performed. the wound was sutured with a two-row suture after excision of the perforated ulcer. in this type of draining stomach of the operation, the integrity of the pylorus sphincter is completely violated, which is often the cause of dgr, dumping syndrome and other disorders of the mefs. when the pdu was excised and an ulcer was diagnosed on the posterior wall of the duodenum, finney pyloroduodenoplasty was performed on 20 (4.2%). in this art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 32 case, a wider outlet from the stomach is formed, adequate drainage and elimination of the pathological substrate is ensured, i.e. pdu. but this is due to the destruction of the integrity of the pylorus sphincter. at the same time, pronounced cicatricial changes in the pyloric canal and the presence of a large inflammatory infiltrate around the ulcer often make it difficult to perform this type of plastic surgery and conditions arise for the occurrence of dgr, dumping syndrome and other disorders of the mefs. performing an operation directly in the area of scar tissue can, in addition, lead to secondary scarring, deformity in the area of pyloroplasty and disruption of the mefs, as a result of the destruction of the multifaceted function of the pyloric sphincter. in addition, this type of plasty is feasible in the absence of obstacles to the free mobilization of the descending duodenum and comparing it with the pyloric sphincter. during excision of the pdu with pdp by judd-tanaka 64 (13.4%), the ulcer of the anterior wall of the duodenum was excised with a rhomboid incision. in this case, along with the ulcer, the anterior semicircle of the pyloric sphincter was excised (hemipilorectomy). plastic surgery was performed by stitching the stomach wall and duodenum with double-row sutures. with this method of excision, along with a violation of the integrity of the pyloric sphincter, the circular muscles of the duodenum are destroyed to a greater extent, which also leads to the development of dgr, dumping syndrome and other disorders of the mefs. however, in the process of further work and studying the immediate and distant results, we abandoned these operations. the goal of radical gastric surgery for ulcer is to influence 3 factors: a decrease in gastric secretion (acidity and pepsin) at a sufficient level; removal of an ulcer as a source of complications and a focus of pathological impulses, as well as a pathomorphologically altered section of the duodenal wall; normalization of mefs and duodenum, as well as influence on the second art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 33 phase gastric secretion (a decrease in the contact of food with the mucous membrane of the antrum, removal of the last section leads to a sharp decrease in gastric secretion in the ii phase). with vagotomy, the 1st phase of gastric secretion decreases. in our practice, we used the classification of v.i. onopriev [6], which, although to some extent conventional, nevertheless, as a working scheme, it is simple and convenient for a practical surgeon to use. with regard to our material and using this classification by the localization of the du, we distinguish between ulcers located on the anterior, posterior, lateral lesser curvature, lateral greater curvature; "mirror" or "kissing" ulcers. in recent years, during surgery for pdu, we have widely used an improved method of excision of pdu with pdp (patent no. 2262 ipa ruz, 2017) [11]. a method of forming a double-row intestinal suture. after performing the upper midline laparotomy, an intraoperative study of the surgical macromorphology of the pdu is performed. thorough toilet and abdominal sanitation. the adhesive "mantle" covering the contours of the gastroduodenal complex is removed, the level and size of the perforated ulcer of the anterior wall of the duodenal bulb is specified. within the limits of healthy tissues, the edges of the ulcerative infiltrate are taken on holders from the lateral edges. distal and proximal to the ulcerative infiltrate, two semicircular bordering incisions are made in the transverse direction with a sharp scalpel, cutting only the serous membrane. in the future, using an electric knife, the distal edge of the ulcer is first dissected. through the defect, the ulcer is additionally lifted with a dissector and after finger checking of the intactness of the pyloric sphincter, a perforated ulcer is excised with a proximal incision with an electric knife within healthy tissues. by this, the circular muscles of the duodenum are injured to a lesser extent, the integrity of the pyloric sphincter and the lateral walls of the duodenal bulb is preserved. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 34 an additional revision of the posterior wall, proximal and distal parts of the duodenum is performed. when diagnosing an ulcer of the posterior wall of the duodenum, the edges of the ulcer of the posterior wall are excised through the duodenal defect to the bottom of its crater (often penetrating into the head of the pancreas), retreating 5 mm. this technique avoids injury to the pancreas. the defect on the posterior wall of the bulb is sutured with muco-submucosomuscular interrupted sutures using silk threads, the edges of the posterior intestinal wall are aligned and adapted. at the same time, the sutures are tied after their complete imposition, having previously tightened and brought together the edges of the intestine. thus, the bottom of the ulcer crater remains outside the intestinal tube, i.e. extraduodenization is performed without using a strand of the gland. v.i. onopriev [6] recommends: to apply the method of "tunneling", in which there is a high probability of damage to the gastroduodenal artery, terminal sections of the common bile duct and pancreatoduodenal arteries. the defect of the posterior intestinal wall is sutured with single-row interrupted sutures. by a similar technique, penetrating and bleeding "mirror" ulcers are excised. when suturing a defect in the posterior intestinal wall according to the method of v.i. onopriev, the edge of the omentum strand on the vascular pedicle is drawn into the suture line. the area of duodenoplasty looks like a broken curve. in cases of detection of functional stenosis before the operation, expressed during the operation in the form of spasm of the pyloric pulp due to perifocal inflammation, pylorodilation is performed, while the diameter of the pyloric pulp is brought to 22-24 mm. after pylorodilation, the pyloric pulp remains in an expanded state, which is associated with the atony of its muscles. in all cases, leave the nasoesophago-gastruodenal tube from the single-use system for intravenous drip transfusions of blood and other fluids. before surgery, a thick gastric tube is inserted into the stomach. before plastic surgery of the anterior wall, the distal end of the sterile probe with lateral holes up to 20 cm in length is held art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 35 in the direction of treitz's ligament, and the proximal end is tied to a gastric tube previously inserted into the stomach. the gastric tube is removed together with the proximal end of the decompression tube at the desired distance for us and fixed to the patient's nose for 2-3 days with the expectation that the microperforated holes are located simultaneously in the lumen of the stomach and duodenum. duodenoplasty. in the initial period of our work, the defect on the anterior wall of the duodenum was sutured with separate intra-nodular catgut sutures in the transverse direction, over which "p" -shaped nylon sutures were applied. control of the tightness and patency of duodenoplasty is carried out by introducing and subsequent aspiration of 400 ml of furacillin solution through a nasogastroduodenal tube. in recent years, with the localization of pdj on the anterior-lateral walls of the duodenal bulb, we began to use the methods of excision of the pdj with pyloruspreserving pd (patent no. 0128. ipa ruz, 2021) [12]. method for surgical treatment of pdu. usage: medicine, namely surgical gastroenterology, and can be used in urgent surgery of du. objective: to reduce trauma and increase the efficiency of the operation by preserving the integrity of the "multifaceted" function of the pyloric sphincter of the stomach, as well as maximizing the conservation of the circular muscles and crypts of the duodenal mucosa. the essence of the invention: with the method of pylorus-preserving duodenoplasty, there is no need to mobilize the duodenum according to kocher, but only in an acute way a limited thorough dissection of the periulcerous adhesive "mantle" is performed, which excludes traumatization of its walls. in addition, damage to the right gastroepiploic and pancreatoduodenal arteries is excluded, depending on the localization of the ulcer. the integrity and intactness of the pylorus sphincter with its "multifaceted" functions is preserved and the circular duodenal muscles and crypts of the mucous membrane are preserved as much as possible. this art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 36 is achieved by bordering cuts parallel to the gastric axis around the perforated ulcer. after, the ulcer of the anterior lateral wall of the duodenum is excised with an electric knife within healthy tissues, then a gastric tube is removed through the duodenal defect, to which a nasogastroduodenal probe is fixed for decompression; its proximal end is removed through the patient's nose. the integrity of the intestinal wall is restored by duodenoplasty with single-row, pre-licensed, adapting sero-muscularsubmucosal interrupted sutures with nodules outward. in this case, the distance between the stitches should be 0.5 cm, and the indentation from the edge of the incision should be 0.5 cm from the proximal side of the wound without grasping the tissues of the pyloric pulp and up to 0.8-1.0 cm from the distal edge of the wound, which ensures the density of contact fabrics. when tightening the knots of single-row serous-muscular submucosal sutures above the decompression probe, the physiological tightness and mechanical strength of duodenoplasty are ensured. so, the method allows you to radically excise the pdu of the anterior and anterior-lateral walls and excise the edges of the ulcer of the posterior wall (i.e., the pathological focus is removed) with subsequent extraduodenization (the bottom of the ulcerative crater is removed outside the intestinal tube) while maintaining the continuity of the side walls and the integrity of the sphincter gatekeeper. the operation is low-traumatic, the neurovascular connections are preserved, ensuring the vital activity of the preserved parts of the stomach with its multifaceted relationships with other organs of the digestive system. preservation of the integrity of the pylorus sphincter provides portioned evacuation of gastric contents and prevents an increase in the number of dgr, and is also the prevention of dumping syndrome. leaving the pvc probe provides decompression, thereby preventing suture failure, and the intestinal suture technique allows you to restore the duodenum lumen without disturbing its drainage function. thus, the developed techniques ensured the safety of the surgical intervention. in no case, after the operation, such complications as anastomotic suture failure, art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 37 peritonitis, traumatic pancreatitis, damage to adjacent organs (liver, bile ducts, pancreas) were not observed. discussion of research results in recent years, pdp has been completed with separate serous-muscularsubmucosal silk sutures in the transverse direction with nodules outward. in this case, the injection of the needle is carried out at a distance of 6-7 mm from the upper edge of the intestinal incision, and the injection is carried out at a distance of 4-5 mm from the lower edge of the incision. the distance between the nodes should be 6-8 mm. this method of surgery, being a type of bridging dp, has the following advantages: 1) allows you to preserve the integrity of the stomach and the pyloric sphincter as a whole, with their neurovascular interrelationships, which ensures portioned evacuation of food while maintaining the natural passage through the gastrointestinal tract; 2) after excision of the ulcer with dp without vagotomy, digestion is restored early after the operation, however, there is a high risk of ulcer recurrence, which in the studied patients requires planned spv. we, however, successfully applied the method of "drug vagotomy" according to the scheme; 3) pylorodilation leads to expansion of the inner wall and restoration of the lumen of the pyloric sphincter, which expands the indications for this technique; 4) the abandonment of the pvc probe ensures the decompression of the area and dp, thereby being a measure for the prevention of inconsistency of the seams; 5) the technique of imposing an intestinal suture allows you to restore the lumen of the duodenum without disturbing its drainage function. due to the high risk of complications associated with trauma to the pancreas and terminal sections of the common bile duct, we, in contrast to v.i. onopriev [6], segmental dp was not used. conclusions improved techniques and techniques for excision of pdu with pyloruspreserving pdp (patents no. 2262 and no. 0128 ipa ruz were obtained), by preserving the integrity of the multifaceted function of the pyloric pulp, reduce the art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 38 frequency of dgr and dumping syndrome. optimization of surgical tactics, along with the techniques and techniques for excision of pdu with pylorus-sparing pdp, made it possible to improve excellent and good results by 23.1% (in the control group 64.4%, in the main group 87.7%), to reduce the frequency of satisfactory results by 16.0% (in the control group 24.4%, in the main group 8.4%) and unsatisfactory by 7.1% (in the control group 11.0%, in the main group 3.9%). references 1. bondarev v.i. immediate and long-term results of the use of pyloric and pyloric operations in the complex of surgical treatment of perforated pyloroduodenal ulcer // klin. surgery. 2004. no. 2. p. 39-42. [in russian] 2. vasilenko l.i. improved technique of pyloroduodeno and duodenoplasty for perforated and stenosing pyloroduodenal ulcers // materials of the xii congress of russian surgeons rostov-on-don, 2015. pp. 365 366. [in russian] 3. heinrich, s.r. possibilities of preservation and surgical correction of the pylorus in ulcerative damage to the gastroduodenal junction: dis. ... cand. honey. sciences krasnodar, 1995 .120 p. [in russian] 4. gostishchev, v.k. radical surgical interventions in the treatment of patients with perforated gastroduodenal ulcers // surgery. 2009. no. 3. p. 10-16. [in russian] 5. the incidence of the entire population of russia in 2019. statistical materials of the ministry of health of russia. m., 2020.140 p. [in russian] 6. onopriev v.i. sketches of functional surgery of peptic ulcer / krasnodar., 1995.-296 p. [in russian] 7. onopriev v.i., karipidi g.k., voskanyan s.e., balyan a.s. surgical pathomorphology (histotopography) of sutured duodenal ulcers. types and types of art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639587 39 radical pyloroduodenoplasty // kuban scientific medical bulletin. 2006. -no. 7-8 (88-89). -p. 78-87. [in russian] 8. rakhmetov n.r., khrebtov v.a., aimagambetov m.zh. features of duodenoplasty in different localizations of duodenal ulcers // surgery 2004. no. 12. p. 35-37. [in russian] 9. nikitin, v.n. duodenoplasty for a giant perforated duodenal ulcer penetrating into the hepatoduodenal ligament // surgery news. 2019. t. 27. no. 5. – p. 67-72. [in russian] 10. nikitin, v.n. to excise or suture a perforated duodenal ulcer? // medical review. 2020. t. 4. no. 2. p. 78-82. [in russian] 11. method for the formation of a two-row intestinal suture // rasmiy akhborotnoma (patent no. 2262 ipa ruz). -1995. -no. 1 (7). -p.23 (nishanov f.n., botirov a.k., khakimov d.m., etc.). [in uzbek] 12. method of surgical treatment of perforated duodenal ulcer // rasmiy akhborotnoma (patent no. 0128 ipa ruz). -2021. -no. 4 (240). -p.23 (botirov a.k., izatullaev i.r., nosirov m.m. botirov j.a.). [in uzbek] 13. chernov, v.n. the results of the treatment of peptic ulcer disease by the method of radical duodenoplasty // surgery. journal them. n.i. pirogov. 2013. no. 4. p. 48-54. [in russian] art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5563473 197 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5563473 198 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5563473 199 obesity and uterine fibroids i.m. tojieva 1 , z.yu. khalimova 1 , sh.a. zufarova 2 republican specialized scientific and practical medical center of endocrinology named after y. h. turakulova republican center for reproductive health of the population abstract: the review is devoted to the role of metabolic syndrome in the development of good-quality hyperplastic myometrial lesion. obesity is a potent potentiating endocrine factor in uterine diseases. modern correction of endocrinemetabolic disorders is a key component of complex treatment and prevention of hyperplastic diseases of the uterus. keywords: uterine fibroids; dyslipidemia; metabolic endocrine diseases; metabolic syndrome uterine fibroids (uf) is a benign monoclonal tumor made up of smooth muscle cells and connective tissue that develops in the wall of the uterus. also known as uterine leiomyoma, uf is one of the most coufon pelvic tumors, affecting over 70% of women of reproductive and premenopausal age [1]. leiomyoma can be asymptomatic, but at the same time it is the main reason for hospitalization. because most patients with ufs remain asymptomatic, the actual incidence of ufs is assumed to be much higher than that reported. based on the ultrasound screening, the incidence for ufs is reported to be 1.278% in asia and 3.745% in africanamerican women per year [2]. ufs may be responsible for a wide range of severe and chronic symptoms (heavy menstrual bleeding, anemia, pelvic pressure, bladder/bowel dysfunction, pelvic non-cyclic pain, dyspareunia, infertility, pregnancy complications) [3] with a deep impact on patients quality-of-life [4]. many risk factors have been identified, such as a positive family history for ufs, combined oral contraceptive use or the use of an intrauterine device, low parity, early onset of menarche, unhealthy lifestyle and, more recently, obesity [3]. although the etiology is largely unknown, leiomyomas are estrogenand progesterone-dependent tumors characterized by an increased and disorganized proliferation of smooth muscle cells with an over-production of extracellular matrix (ecm). a study showed that obesity leads to changes in endocrine system function, affects the levels of blood sex hormones and alters the secrete modes and metabolic pathways of hormones and their roles in target organs [5]. furthermore, some current studies have proved that obesity is one of the risk factors for uterine fibroids. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5563473 200 however, studies on the risk of uterine fibroids in women with central obesity, especially those with relatively large visceral fat area (vfa), are rare. obesity is able to cause metabolic disorders, making local tissues to form an abnormally high estrogen environment. the mechanism includes: 1) androstenedione secreted by adrenal glands can be converted into estrone by aromatase in adipose tissues, and the level of estrone in plasma is increased with elevated adipose tissues and strengthened conversion ability, thus leading to persistent estrogen effect; 2) obesity leads to the lack of periodic regulation of progesterone, so that the endometrium is in an environment of over stimulation from no estrogen antagonistic progesterone for a long time [6,7] 3. systemic inflaufation: excessive fat accumulation is associated with increased production of adipokines and inflaufatory cytokines, which can lead to increased levels of reactive oxygen species (ros). ros are capable of stimulating cell proliferation, inhibiting cell apoptosis, and promoting the deposition of ecm, which is a key event in the emergence of uf [8]. in addition, in vitro studies have shown that uf cells have defective antioxidant enzymatic activity with reduced expression of catalase and superoxide dismutase, thus increasing the effect of ros on smooth muscle cells [9]. 4. decreased production of sex hormone binding globulin (shbg): overweight women are more likely to have decreased production of shbg by the liver, resulting in more unbound levels of circulating estrogen [10]. low shbg concentration has been shown to be associated with increased insulin resistance [11,12] there are no definitive conclusions about a possible correlation between obesity and uf. several studies have been published on this topic with conflicting results. some authors found a positive correlation [13-15] or inverse correlation [16-18], while others reported no association [19-21]. a possible explanation for the inverse correlation may be related to the fact that women with high obesity have lower levels of sex hormones due to anovulation and a decrease in the number of menstrual cycles, which are often observed in such patients. decreased physical activity, diet and weight changes can also be considered modifiable risk factors for uf. feedback has been reported between exercise and uf risk. indeed, regular physical activity is responsible for increasing shbg levels and lowering insulin and sex hormones. in addition, a diet rich in fruits, green vegetables, and fish also appears to play a protective role against leiomyomas [22]. only a few studies have examined the relationship between weight change in adulthood and the risk of uf. a study by terry et al. [19] found no association between childhood / adolescence weight and risk of uf. similar results were obtained in a recent study: data presented by lee et al. [23] show that weight gain in adulthood (starting at age art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5563473 201 18), rather than current bmi, is associated with a higher risk of developing leiomyomas. insulin resistance (ir) following hyperglycemic status is coufon in patients with metabolic syndrome, and hyperinsulinemia caused by ir may provide a possible biological link underlying the relationship between uf and metabolic syndrome. indeed, insulin appears to have a direct, specific effect on the ovaries. through insulin receptors or insulin-like growth factor-1 receptors, insulin can promote the secretion of ovarian hormones and can also reduce their binding to globulins, ultimately increasing the total level of unbound circulating sex steroid hormones [24]. in addition, insulin has been observed to enhance the proliferation and mitosis of vascular smooth cells (animal model) and promote the growth of uf cells (in vitro studies) by altering the tyrosine kinase signaling pathway [24]. however, the relationship between uf and ir is still debated, given the conflicting results obtained in various experimental studies [25-26]. regarding the relationship between dyslipidemia and uf, it is well known that estrogens affect several aspects of lipid metabolism (hdl and triglyceride levels, lipoprotein lipase expression) [27]. given the fact that uf are estrogen-dependent tumors, it seems plausible to hypothesize a link between leiomyomas and the development of metabolic diseases. however, reports on this issue differ [28,29], and further research is required. in conclusion, obesity is one of the risk factors for uterine fibroids, and increased body fat (especially abdominal visceral fat) is capable of raising the risk of uterine fibroids. meanwhile, providing nutrition guidance and changing diet and exercise habits are important measures to prevent the development of uterine fibroids. further research is needed to elucidate the biology and natural history of leiomyomas in order to identify modifiable risk factors and to identify effective prevention and treatment strategies. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5563473 202 references 1. stanoevich i.v. benign hyperplastic diseases of the uterus: from treatment tactics to prevention strategy. doctor. 2009; (2): 9-12 2. dagur g, suh y, warren k, et al. urological complications of uterine leiomyoma: a review of literature. int urol nephrol 2016;48:941–8. 3. kiselev v.i., sidorova i.s., unanyan a.l., muizhnek e.l. hyperplastic processes of the female reproductive system: theory and practice. m .: medpraktika-m; 2010.soave i, marci r. uterine leiomyomata: the snowball effect. curr med res opin 2017;33:1909–11 4. mayes js and watson gh: direct effects of sex steroid hormones on adipose tissues and obesity. obes rev 5: 197‑ 216, 2004. 5. ziufermann a, bernuit d, gerlinger c, schaefers m and geppert k: prevalence, symptoms and management of uterine fi broids: an international internet‑ based survey of 21,746 women. bmc womens health 12: 6, 2012. maruo t, ohara n, wang j, et al. sex steroidal regulation of uterine leiomyoma growth and apoptosis. hum reprod update 2004;10:207-20 6. curti ml, jacob p, borges mc, rogero uf and ferreira sr: studies of gene variants related to inflaufation, oxidative stress, dyslipidemia, and obesity: implications for a nutrigenetic approach. j obes 2011: 497401, 2011. 7. alpay z, saed gm, diamond mp. female infertility and free radicals: potential role in adhesions and endometriosis. j soc gynecol investig 2006;13:390-8 8. fletcher nm, saed mg, abu-soud hm, et al. uterine fibroids are characterized by an impaired antioxidant cellular system: potential role of hypoxia in the pathophysiology of uterine fibroids. j assist reprod genet 2013;30:969-74 9. maggio m, lauretani f, basaria s, et al. sex hormone binding globulin levels across the adult lifespan in women—the role of body mass index and fasting insulin. j endocrinol invest 2008;31:597-601 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5563473 203 10. golden sh, dobs as, vaidya d, szklo m, gapstur s, kopp p, liu k, ouyang p. endogenous sex hormones and glucose tolerance status in postmenopausal women. j clin endocrinol metab 2007;92(4):1289-95. 11. hautanen a. synthesis and regulation ofsex hormone-binding globulin in obesity. intj obes relat metab disord 2000;24(supple 2):s64-70. 12. ross rk, pike mc, vessey mp, et al. risk factors for uterine fibroids: reduced risk associated with oral contraceptives. br med j (clin res ed) 1986;293:359-62 13. sato f, nishi m, kudo r, et al. body fat distribution and uterine leiomyomas. j epidemiol 1998;8:176-80 14. wise la, laughlin-toufaso sk. epidemiology of uterine fibroids: from menarche to menopause. clin obstet gynecol 2016;59:2-24 15. marshall lm, spiegelman d, manson je, et al. risk of uterine leiomyomata among premenopausal women in relation to body size and cigarette smoking. epidemiology 1998;9:511-17 16. wise la, palmer jr, spiegelman d, et al. influence of body size and body fat distribution on risk of uterine leiomyomata in u.s. black women. epidemiology 2005;16:346-54 17. terry kl, de vivo i, hankinson se, et al. anthropometric characteristics and risk of uterine leiomyoma. epidemiology 2007;18:758-63 18. parazzini f, la vecchia c, negri e, et al. epidemiologic characteristics of women with uterine fibroids: a case-control study. obstet gynecol 1988;72:853-7 19. samadi ar, lee nc, flanders wd, et al. risk factors for selfreported uterine fibroids: a case control study. am j public health 1996;86:858-62 20. chen cr, buck gm, courey ng, et al. risk factors for uterine fibroids among women undergoing tubal sterilization. am j epidemiol 2001;153:20-6 21. pavone d, clemenza s, sorbi f, et al. epidemiology and risk factors of uterine fibroids. best pract res clin obstet gynaecol 2018;46:3-11 22. lee je, song s, cho e, et al. weight change and risk of uterine leiomyomas: korea nurses’ health study. curr med res opin 2018 may 9:1-7. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5563473 204 23. wei jj, chiriboga l, mittal k. expression profile of the tumorigenic factors associated with tumor size and sex steroid hormone status in uterine leiomyomata. fertil steril 2005;84:474-84 24. hou zm, sun q, liu y-z, et al. effects of insulin resistance on myometrial growth. int j clin exp med 2015;8:1552-7 25. sadlonova j, kostal m, smahelova a, et al. selected metabolic parameters and the risk for uterine fibroids. int j gynaecol obstet 2008;102:50-4 26. shen m, shi h. sex hormones and their receptors regulate liver energy homeostasis. int j endocrinol 2015;2015:29478 27. he y, zeng q, li x, et al. the association between subclinical atherosclerosis and uterine fibroids. plos one 2013;8:e57089 28. parazzini f, chiaffarino f, polverino g, et al. uterine fibroids risk and history of selected medical conditions linked with female hormones. eur j epidemiol 2004;19:249-53 29. ilaria soave & roberto marci (2018) from obesity to uterine fibroids: an intricate network, current medical research and opinion, 34:11, 1877-1879, doi: 10.1080/03007995.2018.1505606 30. kejuan sun1, ying xie2, na zhao3 and zengning li a case‑ control study of the relationship between visceral fat and development of uterine fibroids. experimental and therapeutic medicine 18: 404-410, 2019.404 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 34 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 35 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 36 features of change of microelemental composition in anemia of chronic diseases in elderly and old age boltaev kamol zhumaevich bukhara state medical institute, bukhara, uzbekistan abstract. the purpose of this study is to carry out a comparative analysis of hematopoietic trace elements iron, copper and zinc in apparently healthy elderly men and women, depending on the age range. for these purposes, all surveyed men and women living both in urban and rural conditions were divided into two age ranges surveyed up to and over 70 years. the results of the analysis showed that there is no statistically significant difference between the indicators of blood hemoglobin and hematopoietic microelements iron, copper and zinc in the whole group of examined elderly men and the group of examined elderly men and examined elderly women in old age. keywords: hematopoiesis, trace elements, blood serum, hemoglobin, age range. introduction. it is known that anemia of chronic diseases (acd) is the most common anemia worldwide, which ranks second after iron deficiency anemia (ida). acd accompanies infectious, rheumatic diseases, neoplasms, as well as chronic heart failure, chronic kidney disease, diabetes mellitus, liver cirrhosis and other nosological units [1, 2, 3, 4]. it was found that the presence of anemia leads to a decrease in the oxygenation of organs and tissues, a decrease in physical activity, the appearance of weakness in the body and a deterioration in the quality of life. in contrast to ida, in which the diagnosis is not difficult, acd is often art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 37 not diagnosed, since at the wound stages it proceeds as normocytic and normochromic [5, 6, 10, 11]. chronic diseases and anemia are independent factors of an unfavorable prognosis of the course of the disease in elderly and senile patients in relation to patients of a younger age [7, 8, 9]. numerous studies of domestic and foreign scientists have studied achd from the point of view of the etiopathogenesis of the disease. it has been established that with this pathology, the exchange of trace elements, primarily iron, is disturbed. in this regard, in the diagnosis of acd, it is important to determine the transferrin and ferritin in the blood serum for the completeness of early diagnosis. but so far, the features of changes in essential trace elements in this category of persons with early diagnosis of acd have not been fully studied. in this regard, the purpose of this part of the dissertation work was to determine and assess the indicators of ferrokinetics, as well as essential trace elements in elderly and senile people with ida, acd in a comparative aspect. materials and methods for this, the results of studies of elderly (n = 325) and senile (n = 65) persons with ida, acd and their combinations were analyzed. analysis of the research results shows that the combined form of ida and acd occurs most often in both study groups. results and discussion. studies have found that in elderly people the number of patients with ida and acd did not significantly differ among themselves, amounting to 23.08 + 2.13% (n = 90) and 27.18 + 2.25% (n = 106), respectively p > 0.05. as for ida + acd, the percentage of patients with a combination of these two ailments was significantly higher in relation to ida and acd art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 38 taken separately 1.43 times, respectively, in relation to ida (respectively 33.08 + 2.38% (n = 129) versus 23.08 + 2.13% (n = 90) p <0.05), as well as 1.22 times in relation to acd (respectively 33.08 + 2.38% (n = 129) versus 27 , 18 + 2.25% (n = 106) p <0.05). almost the same picture was observed in the parameters of elderly people, with the only difference that the parameters of ida and acd also differed in reliability, respectively 2.56 + 0.80% (n = 10) versus 5.64 + 1.17% (n = 22) p <0.05. the combined incidence of these pathologies was most noticeably increased, as ida + acd were 3.30 times increased in relation to persons of old age with ida (8.46 + 1.41%, n = 33 versus 2.56 + 0.80% , n = 10) p <0.001. the same trend was observed when comparing the data of acd and ida + acd, where the difference was 1.50 times (8.46 + 1.41%, n = 33 versus 5.64 + 1.17%, n = 22) p <0.001. it should be emphasized that the number of elderly patients with a combined occurrence of ida + acd was higher than ida and acd, instead of 8.46% (n = 33) versus 8.2% (n = 32). thus, the analysis of the parameters of the occurrence of various forms of anemia in elderly and senile people shows that in elderly people there is a significant difference between the indicators of the combined occurrence of ida + acd in relation to ida (1.43 times, p <0.05) and to acd (1.22 times, p <0.05). however, no significant differences were observed between the parameters of acd and ida. this indicates that acd occurs quite often in elderly people, not yielding to the detection of ida in this age group of patients, a significantly increased state of the combined occurrence of ida and acd (ida + acd) in these individuals indicates a peculiarity of the course of these diseases and allows more closely attention when diagnosing the above conditions. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 39 this tendency persisted in elderly people, with the following differences: firstly, the indicators of ida and acd significantly differed among themselves, the increase was in favor of acd; secondly, the combined occurrence of ida and acd was sharply increased in relation to individual ida and acd (3.30 and 1.50 times, respectively, p <0.001); thirdly, the number of patients with the combined occurrence of ida and acd was greater than that of ida and acd instead of those taken. these facts should also be taken into account when planning diagnostic and treatment-and-prophylactic measures in relation to elderly people. in addition, there was an interesting comparative characteristic of the occurrence of these pathologies within a separate group of elderly and senile people. the results obtained show that ida is less than 1/3 of patients in this age category 27.69%. acd makes up 32.60% of the total number of sick elderly people, most of it was the combined occurrence of ida and acd, which reached 39.69%. the data for the elderly were somewhat different respectively, ida 15.38%, acd 33.85 and ida + acd 50.77%. the true incidence of anemia in elderly and senile people differs from each other, which requires close attention when planning therapeutic and prophylactic measures for treatment and prevention of complications of this pathology. it should be emphasized that the following pathologies appeared with acd: coronary heart disease (chd), chronic heart failure (chf), arthritis of various etiologies, hepatitis of various etiologies, chronic kidney disease (ckd), chronic inflammatory diseases of the gastrointestinal tract (git). the most common among patients with coronary artery disease, chf and arthritis of various etiology (more than 60.0%). art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 40 the next stage of the research was to study the parameters of the hemogram in elderly and senile people with ida, acd and ida + acd. the results obtained show that the parameters of the hemogram in elderly and senile people practically did not differ among themselves, the difference between the obtained average figures was insignificant and not reliable, and therefore we did not consider it appropriate to provide a comparative analysis of the hemogram in this dissertation work. the obtained results show that in patients with ida, the blood hemoglobin content was significantly reduced in relation to the reference values to 76.8 + 7.3x1012 / l (p <0.001). in addition, the same parameters were significantly reduced in relation to the selected standard in patients with acd (on average, up to 94.6 + 8.4x1012 / l, p <0.001) and with acd + ida (on average, up to 82.1 + 6.8x1012 / l, p <0.001). comparative analysis between the study groups shows that there is a significant difference between the hemoglobin data in patients with ida and acd, which is 1.23 times more in favor of acd. a slight increase was also noted in patients with ida + acd, but the results between them were not reliable (p> 0.05). the number of erythrocytes was slightly increased in patients with ida in relation to the compared groups, but if in patients with acd the decrease in the number of erythrocytes was not significant (p <0.05), then with the combined occurrence of ida and acd, the decrease in relation to data with ida was significant (p <0.05). the mean erythrocyte volume (mcv) also differed in the compared groups, the indicators of patients with acd were significantly (p <0.05), and ida + acd were not significantly (p> 0.05) increased in relation to the data of patients with ida. the average amount of hemoglobin in the erythrocyte (mch) and the average concentration of hemoglobin in the erythrocyte (mchs) in art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 41 patients with acd and ida + acd were significantly higher than the parameters of patients with ida, which has a certain diagnostic value. the level of erythrocyte anisocytosis (rdw) was significantly increased in patients with ida in relation to the data of patients with acd and ida + acd ((p <0.05). it should be emphasized that in elderly and senile people with ida, of the 6 studied parameters, all (100%) were lower than the reference values, while in acd only 2m out of 6 parameters (33.3%) significantly differed from the reference values. the counts showed. that in patients with ida + acd, the differences from the reference values concerned 5 parameters out of 6 (83.3%). this fact indicates that not only ida, but also its combination with acd will lead to an imbalance of hematological parameters concerning hemoglobin, its content, concentration, volume in erythrocytes. thus, the study of comparative hemogram parameters in elderly and senile patients of patients with different forms of anemia, indicators that all parameters in relation to the reference values (100%) were reduced in patients with ida in patients with acd, this indicator was 33.3%, and in those surveyed with ida + acd was 83.3%. significant differences between the comparison groups indicate the effect of acd on hematological parameters in the surveyed. significant differences between the compared parameters in patients with different forms of anemia indicate a different approach in planning treatment and prophylactic measures for elderly and senile patients. the next stage of the research was a comparative study of ferrokinetic indices and some parameters of the inflammatory process in elderly and senile people with different forms of anemia (ida, acd, ida + acd). art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 42 studies have established that serum iron is one of the main indicators of ferrokinetics, and therefore its determination is mandatory in research work. we found that the content of serum iron in elderly and senile persons differed from each other depending on the pathological process associated with anemia. so, if in those examined with ida, the serum iron content averaged 7.7 + 0.74, then in individuals with acd this parameter increased 2.2 times (on average, up to 16.5 + 1.06. p <0, 05). not such a significant, insignificant increase in relation to the data of patients with ida was also distinguished in patients with ida + achd (on average, up to 10.4 + 0.86, p <0.05). sharp differences between the indicators were distinguished in the determination of ferritin in the blood serum of patients. it was found that in elderly and senile patients with ida, ferritin was determined on average in the amount of 12.6 + 1.2 μg / l, which is 19.62 times and 9.02 times, respectively, less than the data of patients with acd and ida + acd ( respectively 213.2 + 2.5 μg / l and 113.7 + 2.4 μg / l. these data turned out to be increased reference values of this indicator. huge differences between the studied parameters indicate a somewhat deep pathological process that involves ferritin and leads to a large imbalance between indicators. the opposite picture was observed when studying the results of a study to determine transferrin in the blood serum of the examined. the parameters of patients with ida and ida + ahz were significantly reduced by 4.0 and 1.79 times in relation to the data of patients with ida 1.3 + 0.11 g / l, respectively; 2.9 + 0.24 g / l versus 5.2 + 0.49 g / l (p <0.001). noteworthy is the fact that in all cases cst (the ratio of serum iron to transferrin), which in all studied groups was below the reference values art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 43 (p <0.05). the lowest indices for cst were in patients with ida (1.48 + 0.4%) and ida + acd (3.6 + 0.9%). there is an increase in one of the main diagnostic markers of the inflammatory process, c-reactive protein (crp) in patients with acd and ida + acp in relation to the indicators of ida. such a 4.91 short and 4.24 short increase in crp in relation to the compared group (ida) indicates the development of the inflammatory process in patients. thus, the study and analysis of comparative indicators of ferrokinetics and some parameters of inflammation in elderly and senile people with ida and achd indicators are the following features; firstly, the parameters of serum iron in patients with acd and ida + acd were significantly increased in relation to patients with ida; secondly, the content of ferritin and transferrin in blood serum changed in different directions in patients also in relation to patients with ida; thirdly, cst was significantly reduced in all study groups, especially this one concerned elderly and senile patients with ida and ida + acd; fourthly, the marker of inflammation crp was significantly increased in patients with chronic diseases (acd and ida + acd) in relation to patients with ida without signs of inflammation; fifth, the crp content directly, closely positively correlates with the concentration of serum iron, serum ferritin, and also has a negative strong, close relationship with the content of transferrin and tibc. studies have shown that in the pathogenesis of chronic inflammatory diseases, an important place is occupied by the deficiency of trace elements, especially essential trace elements iron, zinc and copper. conclusions art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 44 based on the above, at the next stage of the research, the content of essential trace elements in the blood serum of elderly and senile patients was determined. the obtained results show that no significant differences were observed in the iron content in elderly and senile people respectively 12.9 + 0.7 in elderly people and 13.4 + 0.7 in elderly people (p> 0.05) ... almost the same picture is observed in the content of zinc in the blood serum (respectively 6.7 + 0.5 in the elderly and 5.5 + 0.7 in the elderly, p> 0.05), although a slight increase differs in individuals old age in relation to the data of elderly people. in terms of the content of copper in the blood serum, the opposite picture is observed, that is, a significant increase differs in elderly people respectively, on average, 13.2 + 0.6 in elderly people versus 11.7 + 0.7 in elderly people, p> 0 , 05). thus, the study of the content of essential trace elements (iron, zinc and copper) in the blood serum of elderly and senile patients with acd showed that the tendency of a comparative increase was distinguished in the elderly in iron and copper, the opposite tendency was observed in the content of zinc. this pattern of change is typical for elderly and senile patients with acd. references 1. boltaev k.zh., akhmedova n.sh. characteristics of the phenomenon of the development of polydeficiency states during aging // problems of biology and medicine. 2020. no. 1. issue 116. p. 24-26. 2. buglanov a.a., mamatkhonov o.a. exchange of hematopoietic nutrients in healthy women of fertile age in uzbekistan // problems of hematology and blood transfusion, 2005.-n 3.-p.25-27 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 45 3. fofanova i.yu., prilepskaya v.n. the content of folic acid, zinc and copper in blood serum in pregnant women with urogenital mycoplasma infection. medical advice. 2015; (xx): 39-45. 4. skalnaya, m. involvement of macroand trace elements in dysregulatory mechanisms of obesity and type ii diabetes pathogenesis in preand postmenopausal women // cell biology and toxicology. — 2008. — vol. 24 (suppl. 1). — p. 39. — issn 07422091. 5. abdullaeva u.k., shadjanova n.s. using the olga system in chronic atrophic gastritis // new day in medicine, № 2 (30) 2020, bukhara, uzbekistan, р. 9-12. 6. abdullaeva u.k., sobirova g.n., karimov m.m., aslonova i.j. the prevalence and possibilities of prevention of noncardial gastric cancer in the bukhara region // american journal of medicine and medical sciences, 2020, 10(9), р. 679-681. 7. sobirova g.n., abdullaeva u.k., nosirova m.s., aslonova i.j. evaluation of the gastrointestinal mucosa by the olga system in chronic atrophic gastritis // journal of critical reviews, kuala lumpur, malaysia, vol. 7, iss. 2, 2020, p. 409-413. 8. karimov m.m., sobirova g.n., abdullaeva u.k., aslonova i.zh., tulyaganova f.m. possibilities of serological diagnosis of atrophic processes of the gastric mucosa // european journal of molecular & clinical medicine vol. 7, iss. 11, 2020, p. 2955-2960. 9. sobirova g.n., abdullaeva u.k., mirzaeva d.b., ismitdinova n.s. immunopatogenesis of chronic gastritis and its role in carcino genesis // academicia an international multidisciplinary research journal, affliated to kurukshetra university, kurukshetra, india. vol.8, iss.12, 2018, p. 32-40. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5080556 46 10. abdullaeva u.k. predicting the risk of atrophic transformation in chronic gastritis using serum pepsinogen // world journal of pharmaceutical research, faculty of pharmacy medical university, bulgaria, vol. 8, iss. 13, 2019, p. 219-228. 11. sobirova g.n., abdullaeva u.k. chronic gastritis and carcinogenesis issues // electronic journal of actual problems of modern science, education and training, urganch, uzbekistan, 2019i, p. 159-172. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 77 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 78 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 79 compleks pregravid preparation in the prevention of miscarriage in women with hyperandrogenism sidikova nigora marifovna tashkent pediatric medical institute, tashkent, uzbekistan sidikovanigora88@gmail.com abstract: hyperandrogenism is diagnosed in almost 10% of women worldwide and impairs the reproductive system: menstrual disorders are diagnosed in 50-70% of patients, infertility in 60-80% of cases and miscarriage in 20-30% of cases. comprehensive corrective pre-pregnancy treatment was used in these patients, and its efficacy was confirmed by the onset of pregnancy and normalization of the hormonal background. keywords: hyperandrogenism, hormonal background, pregravidarial preparation. miscarriage (mc) and infertility in women of fertile age is a very urgent medical and social problem. hyperandrogenism (ha) is rightfully recognized as one of the causes of these conditions and a common risk factor for pathology of the reproductive system. ga is quite widespread in women of reproductive age. violation of the secretion of androgens by the adrenal glands and ovaries, impaired metabolism of the hormones produced and leads to ha [4]. in almost ¾ women, ha causes disorders of menstrual and reproductive functions, which leads to infertility [1]. during pregnancy, women with ha often experience complications: the threat of termination of pregnancy, ischemic-cervical insufficiency (ici), placental dysfunction, and the threat of premature birth. one or more of these complications cause miscarriage (fb) or premature birth [4]. russian scientists cite some figures: spb is noted in 20% of women, and in 80% in the first trimester. endocrine pathology, in particular ha, is the cause of habitual miscarriages in every fifth pregnant woman [2]. pregnant women with ga have a proven high risk of perinatal complications; therefore, at the stage of pregnancy planning, pregravid preparation is mandatory in order to minimize the negative effects of an excess of androgens on pregnancy and reduce the incidence of complications [11]. ha in women also disrupts the reproductive system: menstrual irregularities (mc) are noted in 50-70% of patients, infertility in 60-80%, nb in 20-30%. consequently, ga is not only a medical, but also a social problem, since against the background of internal and external changes occurring in a woman's body, the psychoemotional state changes and the quality of life decreases [9]. the most common pathology leading to ha in women is pcos; it is diagnosed in three out of 4-5 women [5, 6, 7, 10]. clinical symptoms of pcos are well diagnosed: mc disorders, infertility, hirsutism. pregnancy is possible only after mailto:sidikovanigora88@gmail.com art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 80 effective medical correction of the condition (treatment of infertility by stimulating ovulation) or surgical treatment [3]. diagnosis of pcos is based on the results of clinical, hormonal and ultrasound studies. the history should focus on oligomenorrhea with menarche, anovulation, primary infertility, early multiple spd [3]. these facts involuntarily suggest that the attitude of the female population to such a formidable pathology as ga is not serious, which is most likely explained by the lack of knowledge of women about this pathology and the lack of active educational work at the level of primary health care, the media and the state as a whole. correction and prevention of ha should be carried out starting with pregravid preparation and continued in early pregnancy. the duration of correction for each patient is individual and depends on the severity of the obstetric and gynecological history, the severity of clinical and biochemical symptoms of ha and concomitant somatic pathology. in women with infertility and / or with the usual spd, correction implies the restoration of reproductive function and the preservation of the subsequent pregnancy with the minimization of androgen-dependent complications. correction of ga and treatment of necj is extremely necessary both from the point of view of the health of each individual woman and the female population as a whole, and therefore the composition of the population and fertility in it. objective: to develop and evaluate the effectiveness of diagnostic markers of complex corrective pregravid preparation in terms of the relationship between hormonal status and biochemical markers of the endometrium in women with hyperandrogenism. material and research methods: we examined 146 women of reproductive age 21-35 years (the average age of the examined patients was 27.8 ± 2.89) with reproductive disorders (primary / secondary infertility, early spd) against the background of clinical and / or biochemical symptoms of ga in history. group i included 62 patients with pcos with pre-obesity and degree i obesity (bmi within 25-34.9 points) aged 21 to 35 years, the average age was 28.2 ± 1.34 years. group ii included 64 patients with pcos and normal body weight (bmi in the range of 18.5-24.9 points) aged 23 to 35 years, the average age was 29.8 ± 1.25 years. the control group (cg) included 20 pregnant women 22-34 years old without ga and with physiological hormone levels, with normal bmi, identical with the studied patients in terms of age and presence of extragenital pathology (mean age 29.1 ± 1.16 years). we studied the prevailing nature of the distribution of subcutaneous fat (sfa) along the waist circumference (ot), with ot less than 80cm, the female (gynoid) type of sss distribution was ascertained, and with ot over 80cm, the visceral (android) type. the severity of hirsutism was assessed according to the ferriman-gallwey scale [8], calculating the "hirsut number" in points, the norm was taken as a sum of 7art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 81 12 points, moderate hirsutism was stated with a hirsut number of 20-25 points, pronounced hirsutism more than 25 points. laboratory studies of the condition of the patients of all groups, including the control group, were carried out in parallel with the clinical examination for the first time upon treatment, then again 2 weeks after the completion of the course of pregravid preparation. the laboratory examination consisted of standard and specific tests, based on the purpose and objectives of the study, its specificity and design: general clinical analysis of blood and urine, biochemical blood test, indicators of various links of hemostasis, levels of steroid hormones in serum and saliva, determination of infectious markers, which meant taking venous and peripheral blood and urine strictly on an empty stomach, excluding fatty and salty foods and spices the day before. the study of hormones in the blood serum and saliva in all patients of the main and cg implied the determination of gonadotropic hormones (lh, fsh), total testosterone, estradiol, progesterone, 17-onp, dhea-s, glycodelin (pp14) and ipfr-1. the results obtained for the patients of the main group were compared with the results for women in the cg. the hormonal background was studied in the first phase of mc, in dynamics after corrective therapy before pregnancy. the main groups of patients were divided by us according to the type of pregravid corrective therapy, each into 2 subgroups a and b. pregravid preparation of patients a of subgroups i and ii of groups consisted of standard conservative treatment, including biguanides (metformin 500 mg), stimulation of ovulation with agonists and antagonists of gonadotropin-releasing hormones, anti-estrogen drugs (clomiphene citrate) at 50-100 mg / day. under the control of ultrasound. we performed ultrasound to monitor the dynamics of follicle growth. starting from the 14th day of the menstrual cycle, the patients took gestagens (dydrogesterone 10/20 mg or micronized progesterone 100 mg (daily dose 200-300 mg), continuing their intake with the onset of pregnancy. micronized progesterone was extended to 36 weeks to reduce the risk of complications at various gestational times. pregravid preparation of patients in subgroups i and ii of groups consisted of standard conservative treatment, adherence to a healthy lifestyle, exclusion from the diet of foods from fast-dissolving glucose and with a high index of insulin resistance. in order to increase the sensitization of cells to insulin, myoinositol 750 mg (daily dose up to 4000 mg) was included in the standard treatment. stimulation of ovulation was carried out by agonists and antagonists of gonadotropin-releasing hormones, anti-estrogen drugs (clomiphene citrate) at 50-100 mg / day. under the control of ultrasound. with the onset of biochemical pregnancy, metformin was canceled, while myoinositol was continued. results of our own research at the initial visit, all patients had complaints of primary or secondary infertility, mc, violations of mc disorders. when analyzing morphograms in pregnant women of groups i and ii, an insignificant difference in body type was art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 82 noted. most patients of group i were diagnosed with male type of hair growth, visceral type of obesity was diagnosed in 22.58% (n = 14) from puberty, in the remaining 77.42% (n = 48) in the post-pubertal period (table 1). in group ii, the picture was similar 81.25% (n = 52) had a female type of body structure. table 1. data of anamnesis and examination of patients of groups i and ii and cg the diagnosis of pcos was made taking into account the history, complaints and results of laboratory and instrumental research methods. we studied the hormonal background on days 2-3 with natural or induced mc an increase in total testosterone up to 4.12 ± 0.26 ng / ml, dhea-s 9.83 ± 0.35 μmol / l, lh 13.51 ± 1.79 iu / l, fsh 5.34 ± 0.55 iu / l, growth of 17-onp no more than 1.85 ± 0.75 ng / ml, lh / fsh ratio 2.78 ± 0.75, those. exceeding more than 2, which is a diagnostic criterion for pcos, was typical for all women in the main groups. signs of pcos by ultrasound on the 3-7th day of the mc (an increase in the volume of the ovaries by more than 10 cm3 due to a hyperechoic stroma with many (more than 10-12) diffusely and / or along the periphery in the form of a necklace of follicles, up to 8-10 mm in size, compaction ovarian capsules) were found in the majority of women in the main groups. visualization of such a picture is typical for women with ga. the hormonal background in ga differs sharply from the cg indicators, so all indicators differ significantly (p <0.05), with the exception of fsh and 17-snp, the differences of which are not statistically significant (p≥0.05), which, apparently, associated with the nature of the ga skpj. also, some vitamin d deficiency was noted in patients of the main groups. the levels of thyroid-stimulating hormone in the patients of the main groups were almost twice as high as those in the cg, and the indicators of prolactin were one and a half times higher than those in the cg in the blood serum and in saliva, and the indicators of the i group were significantly higher than the levels of the ii group of patients (p <0.05). we stated that there was no difference in the lh / fsh ratios in all groups between the studies in blood serum and in saliva, which proves the consistency of the options i group (n=62) ii group (n=64) cg (n=20) primary infertility 44 (70,97%) 14 (21,88%) - secondary infertility 14 (22,58%) 47 (73,44%) - early pregnancy loss 26 (41,94%) 17 (26,56%) - mc violations 52 (83,87%) 46 (71,88%) - male body type 60 (96,77%) 52 (81,25%) - female body type 2 (3,23%) 12 (18,75%) 20 (100%) hirsutism scores 22,7±1,5 22,2±1,6 4,7±0,68 acne 10 (16,13%) 9 (14,06%) - striae 38 (61,29%) 26 (40,63%) - acanthosis nigroid 14 (22,58%) 8 (12,50%) - art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 83 study of the hormonal background of patients with ha and pcos in terms of concentration in saliva. analysis of statistical processing revealed the presence of a significant (p <0.05) average strength of the correlation between bmi and ipfr-1, in group i patients (r = 0.48), with glycodelin (r = 0.47), androstenedione (r = 0.50), free testosterone (r = 0.42), hirsutism scores (r = 0.44). we stated that there was no correlation between the above parameters in the control group of patients (r <0.23). we found strong direct correlations between bmi and the level of dihydrotestosterone (r = 0.60) and glycodelin pp14 (r = 0.58). in patients with ga, a significant (p <0.05) direct relationship was found between the scores of hirsutism and the levels of the following hormones: androstenedione (r = 0.51), free testosterone (r = 0.47), glycodelin (r = 0.48 ), ipfr-1 (r = 0.46). a significant (p <0.05) average strength direct relationship was found between the level of glycodelin and the levels of ipfr-1 (r = 0.40), androstenedione (r = 0.41), free testosterone (r = 0.44). the indicators of the hormonal background of the patients of the main and control groups when measured in saliva were displayed more accurately and had many correlations identical to the blood indicators within the measurement, but at the same time, the levels of free testosterone and dhea-s in saliva were significantly higher in the patients of the main groups, it should also be taken into account that the collection of saliva and its study is much easier, therefore, the main hormones were measured by us by the level of their concentration in saliva. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 84 table 2. hormonal background of patients of groups i and ii and cg before corrective therapy note:* – statistically significant intergroup differences i and ii relative to the control group (p<0,05). options group i (n = 62) group ii (n = 64) kg (n = 20) in blood in the saliva in blood in the saliva in blood in the saliva thyroid stimulating hormone, μiu / ml 3,4±0,35* 3,2±0,32* 3,3±0,34* 3,2±0,31* 1,9±0,28 1,5±0,27* prolactin, μiu / ml 612,3±22,4* 594,9±22,9* 439,8±23,4* 499,3±22,1* 413,7±24, 2 337,6±22,5 total testosterone, ng / ml 2,17±0,15* 1,65±0,12* 2,01±0,16 1,89±0,13* 2,71±0,15 1,51±0,13 total testosterone, ng / ml 4,32±0,37* 4,09±0,35* 4,12±0,36* 3,75±0,28* 3,87±0,09 3,27±0,10 free testosterone, pg / ml 4,79±0,13* 4,4±0,15* 3,98±0,15* 3,75±0,16* 1,2±0,15 0,8±0,10 dihydrotestosterone, pg / ml 450,3±12,4* 415,6±12,3* 395,2±16,3* 327,3±12,4* 191,9±11, 4 116,7±10,3 androstenedione, nmol / l 13,5±3,9* 13,1±3,4* 11,7±3,25* 11,5±3,3* 0,89±0,25 0,90±0,20 dihydroepiandrosterone sulfate, μmol / l 13,55±0,55* 12,09±0,60* 10,82±0,63* 10,11±0,60* 6,8±0,16 5,04±0,13 17-hydroxyprogesterone, ng / ml 1,85±0,75 1,79±0,80 1,49±0,68 1,45±0,60 1,02±0,20 0,97±0,18 lh, iu / l 13,51±1,79* 12,47±1,89* 11,8±1,4* 10,09±1,25* 8,5±0,95 7,8±0,86 fsh, iu / l 5,9±0,50 5,6±0,35 5,34±0,45 5,01±0,25 5,5±0,15 5,3±0,19 lh / fsh 2,28±0,75* 2,28±0,65* 2,19±0,28* 2,02±0,55* 1,56±0,22 1,52±0,35 glycodelin pp14, μg / ml 14,81±0,91* -18,72±0,85* - 33,58±1,3 5 - ipfr-1, ng / ml 537,08±35,6* -496,23±36,2* - 367,5±26, 8 - 25-oh d3 22,63±1,65 29,57±1,79 31,89±1,8 7 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 85 during the treatment, pregnancy occurred in 88.89% (n = 56) patients: 26 (83.87%) from group ib and 30 (93.75%) from group iib. of all our patients who became pregnant, 39.42% (n = 41) became pregnant during the first 2 months, and 60.58% (n = 63) during the 3rd 4th months of corrective pregravid preparation. in the control group, this ratio was 60% (n = 12) to 40% (n = 8), respectively. there was no statistically significant difference in the timing of pregnancy between the subgroups, despite the difference in bmi and corrective pregravid preparation. after the completion of the complex corrective pregravid preparation of the patients of both groups, the level of almost all hormones in the study groups was comparable, however, within each group, the levels of hormones significantly differed between the subgroups. in ia and iia subgroups, the levels of hormones in the blood serum and saliva differ more from the norm than the indices of the ic and iic subgroups. there were statistically significant differences in the levels of total and free testosterone, dihydrotestosterone, androstenedione, dihydroepiandrosterone sulfate and glycodelin (p <0.05). attention should be paid to statistically significant differences between the two subgroups of corrective pregravid training, which indicates a clear higher efficiency of the complex training offered by us, which also has a good effect on patients in subgroup i of group with preobesity and obesity of i degree (p <0.05) , but the expected best efficacy was obtained by us in subgroup ii of group of patients with normal body weight. it should be noted that the level of vitamin d in the blood serum of patients has normalized, and we have achieved greater success in this aspect in the subgroups of the main groups, the difference is significant (p <0.05). the levels of thyroid-stimulating hormone and prolactin by the end of pregravid preparation were slightly lower in the b groups of both main groups. the lh / fsh ratio in all subgroups in serum and saliva was identical, which again confirms the possibility of monitoring the effectiveness of therapy by the concentration of hormones in saliva. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 86 table 3. hormonal background of patients of the main groups and cg after corrective pregravid therapy note: * – statistically significant differences between a and b subgroups of both groups (p<0,05). options i a group (n=31) i b group (n=31) ii a group (n=32) ii b group (n=32) in blood in the saliva in blood in the saliva in blood in the saliva in blood in the saliva thyroid stimulating hormone, μiu / ml 2,5±0,35 1,6±0,30 2,1±0,34 1,4±0,29 2,4±0,32 1,6±0,29 2,2±0,31 1,7±0,28 prolactin, μiu / ml 291,1±32,4 196,8±28,4 270,6±32,8 204,8±29,2 296,3±30,4 201,9±25,5 259,6±27,8 198,3±20,8 total testosterone, ng / ml 2,78±0,15* 2,46±0,12* 2,45±0,15* 2,09±0,10* 2,21±0,17 2,08±0,14 1,88±0,08 1,64±0,07 free testosterone, pg / ml 2,41±0,18* 2,15±0,14* 1,73±0,16* 1,62±0,14* 1,55±0,15 1,34±0,13 0,97±0,10 0,81±0,09 dihydrotestosterone, pg / ml 252,1±13,6* 224,9±12,5* 223,6±13,4* 209,4±12,9 224,7±11,8 210,1±11,5 197,6±10,4 170,9±10,1 androstenedione, nmol / l 10,04±3,9* 9,07±3,8* 8,27±3,7* 7,09±3,4* 9,4±3,35 7,13±3,25 7,44±3,15 6,81±2,95 dihydroepiandrosterone sulfate, μmol / l 9,37±1,85* 8,14±1,82* 6,02±1,78* 5,78±1,73* 6,13±1,63 5,04±1,58 4,31±1,23 4,04±1,18 17-hydroxyprogesterone, ng / ml 1,23±0,84 1,13±0,80 1,08±0,82 0,94±0,56 1,11±0,60 0,96±0,45 0,95±0,35 0,84±0,30 lh, iu / l 8,93±1,25 8,18±1,22 7,87±1,15 7,66±1,12 7,61±1,13 7,54±1,11 6,73±1,08 6,33±1,05 fsh, iu / l 5,39±0,55 5,21±0,41 5,36±0,38 5,07±0,35 5,76±0,32 5,43±0,29 5,58±0,34 5,31±0,25 lh / fsh 1,58±0,31 1,57±0,21 1,47±0,28 1,51±0,21 1,32±0,22 1,38±0,22 1,21±0,30 1,19±0,31 glycodelin pp14, μg / ml 25,31±0,82* 31,74±0,84 27,67±0,80* 33,51±0,56 ipfr-1, ng / ml 413,98±36,2 376,31±35,4 387,63±34,5 365,8±27,9 25-oh d3 42,7±2,75* 51,37±2,86 43,56±2,71* 54,87±2,65 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 87 attention should be paid to statistically significant differences between the two subgroups of corrective pregravid training, which indicates a clear higher efficiency of the complex training offered by us, which also has a good effect on patients in subgroup i of group with preobesity and obesity of i degree (p <0.05) , but the expected best efficacy was obtained by us in subgroup ii of group of patients with normal body weight. conclusion for the most part, it is advisable to measure hormonal levels by studying the saliva of patients, given the presence of strong correlations between the levels of hormones in serum and saliva. the study of free testosterone, dha-c glycodelin and ipfr-1 already at the stages of pregravid preparation as a marker of the processes occurring in the body of women, especially in the presence of pcos and ha, is of great diagnostic value. the proposed and tested by us complex corrective pregravid training of patients with ha and pcos with normal body weight, as well as with preobesity and obesity of the 1st degree, showed greater efficiency, manifested in a greater proportion of pregnant patients relative to standard pregravid training. references 1. manukhin i.b., tumilovich l.g., gevorkyan m.a. gynecological endocrinology: clinical lectures. m .: geotar-media, 2013 .-272 p. 2. mordyk a.v., novitskaya e.l., puzyreva l.v. et al. the main causes of fetal loss syndrome (literature review) // ural medical journal. 2016. no. 2 (135). p. 18-21 3. mukhtarov t.a., molchanova i.v., skvortsov v.v. congenital adrenogenital syndrome // nurse. 2017. no. 1. p. 31-34 4. sidelnikova v.m. endocrinology of pregnancy in health and disease. m., medpress-inform, 2009 .-352 p. 5. bednarska s., siejka a. the pathogenesis and treatment of polycystic ovary syndrome: what's new? // adv clin exp med. 2017. vol. 26, no. 2. p. 359-367., 6. bousmpoula a., kouskouni e., benidis e. et al. adropin levels in women with polycystic ovaries undergoing ovarian stimulation: correlation with lipoprotein lipid profiles // gynecol endocrinol. 2018. vol. 34, no. 2. p. 153-156, 7. carmona-ruiz i.o., saucedo-de la llata e., moraga-sánchez m.r. et al. polycystic ovary syndrome: is there a rise in the prevalence? // ginecol obstet mex. 2015. vol. 83, no. 12. p. 750-759, 8. ferriman d.m., gallwey j.d. сlinical assessment of body hair growth in women // the journal of clinical endocrinology & metabolism. 1961. vol.21, no. 11. p.1440-1447, https://doi.org/10.1210/jcem-21-11-1440 9. kellesarian s.v., malignaggi v.r., kellesarian t.v. et al. association between periodontal disease and polycystic ovary syndrome: a systematic review // int j impot res. 2017. vol. 29, no. 3. p. 89-95 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5713450 88 10. li d., li c., xu y. et al. differential expression of micrornas in the ovaries from letrozole-induced rat model of polycystic ovary syndrome // dna cell biol. 2016. vol. 35, no. 4. p. 177-183 11. mossa f, latham ke, ireland jj, veiga-lopez a. undernutrition and hyperandrogenism during pregnancy: role in programming of cardiovascular disease and infertility. // mol reprod dev. 2019 vol.86 (9) p1255-1264 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517016 97 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517016 98 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517016 99 the value of perimetric and electrophysiological diagnostic criteria in early primary open-angle glaucoma yusupov azamat farkhadovich, m.d, director of the state institution "republican specialized scientific and practical medical center of eye microsurgery", tashkent, 100173, uzbekistan, eye-сenter@inboх.ru karimova muyassar khamitovna, m.d, professor, deputy director for scientific work of the state institution "republican specialized scientific and practical medical center for eye microsurgery mkarimova2004@mail.ru tashkent, 100173, uzbekistan zakirkhodjaeva mastona azizkhodzhayevna, basic doctoral student, ophthalmologist, state institution "republican specialized scientific and practical medical center of eye microsurgery", mastonaz@bk.ru tashkent, 100173, uzbekistan abdushukurova asal azamat kizi, clinical resident of the state institution "republican specialized scientific and practical medical center of eye microsurgery", yusupovaasal0917@mail.ru tashkent, 100173 ,uzbekistan abstract the purpose of the study to study and analyze electrophysiological indicators in the early diagnosis of primary open-angle glaucoma. material and research methods. studies of electrophysiological characteristics were carried out in rsspmcem under photopic conditions on a neuro-erg device from neurosoft company using chess receptive fields of 0.75 arc minutes in black and white and blue-yellow versions. clinical static perimetry was performed in the rsspmcem on a tomey ap-3000 (automated perimeter) device with the ability to conduct threshold and color-opposing methods for studying the central field of view. results. when analyzing the main functional perimetric indices and the nature of the topography and depth of defects in the central field of view (md, psd, cpsd), a significant change in the light sensitivity thresholds of the blue-yellow perimetry relative to the standard research method was noted. conclusion. the complex use of erg and static perimetry makes it possible to reveal the presence of changes in the visual system at the early preclinical stages of the development of glaucomatous optic neuropathy. keywords: oscillator potentials, glaucomatous optic neuropathy, blue cone erg, retinal ganglion cells. introduction. at this time, the problem of early diagnosis of glaucoma, as well as the peculiarities of changes in certain types of erg at the early stages of the development of glaucomatous optic neuropathy remain very relevant [1, 10, 11, 12, 13, 14]. it is well known that standard static threshold perimetry reveals functional defects in the visual field with the death of 30% of retinal ganglion cells. on the other hand, standard types of erg are insensitive and nonspecific in the development of mailto:eye-сenter@inboх.ru mailto:mastonaz@bk.ru mailto:yusupovaasal0917@mail.ru https://translate.google.com/ https://translate.google.com/ art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517016 100 glaucomatous primary lesions [2, 6, 7, 19]. in the early preclinical diagnosis of glaucomatous neuropathy, a special position is occupied by disorders in the blueconical system of the visual analyzer [3, 8, 9, 20]. blue cones are distinguished by the presence of large receptive fields, pronounced color opposition to yellow, and localization in the paramacular region 7–10 ° from the center of fixation. in this regard, we used a complex of electrophysiological recording methods, in particular, electroretinography (erg) for a short-wave stimulus [4, 5, 15, 16, 17, 18]. material and research methods at the republican specialized scientific and practical medical center of eye microsurgery, 42 patients (84 eyes) were examined with a diagnosis of suspected glaucoma. the visual acuity of patients with ametropia correction was 0.9–1.0. refractive errors did not exceed 3.0 diopters; concomitant disorders of the visual analyzer were not detected. at the time of diagnosis, none of the examined patients received local drug antihypertensive therapy. the average age of the patients was 50.5 ± 2.5 years. the comparison group consisted of 20 people without changes in visual functions of the corresponding sex and age. electrophysiological and perimetric methods were used: blue-yellow threshold static perimetry, color-opposing blue-yellow electroretinography for examining the visual organ to assess the functional state of the visual system with standard methods for examining the organ of vision. clinical static perimetry was performed in the rsspmcem on a tomey ap3000 (automated perimeter) device with the ability to conduct threshold and coloropposing methods for studying the central field of view. the stimulus parameters corresponded to goldman 3 standards, the background brightness was 31.5 asb, the program for early glaucoma diagnosis was 30-2 threshold (sap), 30-2 blue-yellow (swap). the stimuli are presented on a white or yellow background using appropriate light filters in the form of blue-yellow or white-and-white (standard) perimetry. the results of the conducted perimetric studies were analyzed using statistical package data: md, ms, psd. studies of electrophysiological characteristics were carried out in rsspmcem under photopic conditions on a neuro-erg device from neurosoft company using chess receptive fields of 0.75 arc minutes in black and white and blue-yellow versions. the results of standard and color-opposing perimetry research methods, as well as electrophysiological indicators were processed using the applied package of research methods statistica 6.0. research results when analyzing the main functional perimetric indices and the nature of the topography and depth of defects in the central field of view (md, psd, cpsd), a significant change in the light sensitivity thresholds of the blue-yellow perimetry relative to the standard research method was noted. the data are shown in table 1. table 1. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517016 101 comparative analysis of perimetric parameters in patients with suspected glaucoma control group clinical group perimetric indices sap swap sap swap md, db 0,75 ± 0,25* 0,93 ± 0,5 –1,57 ± 0,45 * –1,75 ± 0,75 ms, db 21 ± 1,5 25 ± 2,75 18 ± 2,5 22 ± 3,5 psd, db 2,37 ± 0,75 3,25 ± 1,5* 3,37 ± 1,5 5,75 ± 2,5* these indicators in patients with suspected glaucoma were two times higher than those in the control group, which indicates a higher sensitivity of the swap technique in the early diagnosis of glaucoma. the topography of visual field defects during swap perimetry did not differ from that with standard, however, the depth of defects was significantly higher with swap perimetry. when conducting electrophysiological studies, the criteria were selected that are most similar in damage to the s-cone system of the retina: perg, oscillatory potentials, blue-cone electroretinography (s-con erg). the data are shown in table 2. table 2. comparative analysis of electrophysiological parameters in patients with suspected glaucoma. pattern-erg complex n95 black and white chess stimulus blue and yellow chess stimulus black and white chess stimulus blue and yellow chess stimulus amplitude, μv 5 ± 0,75 5,28 ± 0,45* 4,75 ± 1,25 3,78 ± 1,75 latency, ms 95 ± 2,5* 97 ± 2,5* 112 ± 3,0* 117 ± 3,8* oscillatory potential index 9,75 ± 1,75 10,73 ± 1,85* 14,4 ± 1,85 17,2 ± 2,5* d-wave amplitude, mv blue-conical erg 34 ± 0,75* 28 ± 1,25* in the study of the color channels of the retina in patients with suspected glaucoma in the blue-yellow variant to a stimulus of 0.75 arc minutes according to perg data, a change in the culmination time of the n95 complex to 117 ± 3.8 ms, as well as a change in the amplitude to 5 ± 2.3 mb. in patients of the "suspected glaucoma" group, the perg data for a black-and-white checkerboard pattern of 0.75 also differed from normal values and amounted to 112 ± 3.0 ms and 6.5 ± 2 ma in terms of culmination time and amplitude, respectively. in the control group, the value of the culmination time and amplitude of the n95 complex was 95 ± 2.5 ms and 5.5 ± 0.75 ma. the results obtained, presented in table 1, indicate a greater sensitivity of blue-yellow perg relative to the standard technique of glaucomatous lesions of retinal ganglion cells in early diagnosis (poag). when studying the index of oscillatory potentials for a white stimulus in patients of the "suspected glaucoma" art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517016 102 group, it was 14.4 ± 1.85 mv, and for a blue stimulus 17.2 ± 2.5 mv. in the control group, the op index was 9.75 ± 1.75 mv for the white stimulus and 10.73 ± 1.85 mv for the blue stimulus, respectively. the data reflect the presence of overexcitation processes at the level of the inner layers of the retina at the preclinical stages of development of glaucomatous optic neuropathy. the variant of the study of op neither blue stimulus showed significantly more sensitive results with respect to oscillatory potentials to a white stimulus, which suggests the presence of its better informative value in the diagnosis of primary openangle glaucoma. during studies of the blue-cone erg (s-con erg), the amplitude of the dwave generation was 28 ± 1.25 mv in the group of patients with suspected glaucoma and was characterized by a decrease in the amplitude of the off-blue cone response. in the control group, the above s-con erg index was 34 ± 0.75 mv. an increase in the latency and a decrease in the amplitudes of the d wave in the s-con erg in patients with suspected glaucoma relative to the control group indicates the likelihood of damage to the off-short-wave channels at the level of retinal ganglion cells during the development of excitotoxic glaucoma reactions. сonclusions 1. indicators md.ms.psd in patients with suspected glaucoma were 2 times higher than those in healthy subjects during swap perimetry, which makes it possible to use it for early diagnosis of ischemic changes in the retina in glaucoma. 2. oscillatory potentials (op) to a blue stimulus are significantly more sensitive, relative to (op) to a white stimulus, which is informative in the diagnosis of poag. 3. the complex use of erg and static perimetry makes it possible to reveal the presence of changes in the visual system at the early preclinical stages of the development of glaucomatous optic neuropathy. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517016 103 references 1. national guide to ophthalmology. m .: goetar, 2008 .-944 p. 2. shamshinova a.m. volkov v.v. functional research methods in ophthalmology. m .: medicine, 1999 .-414 p. 3. shamshinova a.m. clinical physiology of vision. m .: scientific medical firm mbn, 2002 .-672 p. 4. shamshinova a.m. clinical physiology of vision. m .: scientific medical firm mbn, 2002. 514 p. 5. shamshinova a.m. and other electroretinography in ophthalmology. m .: scientific medical firm mbn, 2002 .-321 p. 6. weinreb r, greve 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oftal`mologiya, 2009. 13. volkov v.v., sukhinina l.b., ustinova e.i. glaucoma, preglaucoma, ophthalmic hypertension. leningrad: meditsina; 1985. 14. volkov v. v. otkry`tougol`naya glaukoma. moskva: med. inf. ag.; 2008. 15. kasimov e. m., ibragimova s. n., e`fendieva m. e., agaeva m. a. preimushhestva perimetr xamfri v diagnostike i monitoringe glaukomy` (obzor literatury`). oftal`mologiya. zhurnal elmi-praktika 2015;(3):130-136. 16. simakova i. l., suxinin m. v., serdyukova s. a. e`ffektivnost` razlichny`x metodov komp`yuternoj perimetrii pri pervichnoj otkry`tougol`noj glaukome. chast` 1. rossijskij zhurnal glaukomy`. 2016;15(1):25-36. 17. kachorovskij k., mulak m., shumny`j d., misyuk-xojlo m. perimetr kraya gejdel`berga: novy`j metod perimetrii. adv clin exp med. 2015;24(6):1105-1112. doi: 10.17219/acem/43834. 18. dannxajm f. merczanie i oby`chnaya perimetriya v sravnenii so strukturny`mi izmeneniyami pri glaukome. oftal`molog.2013;110(2):131-140. doi: 10.1007/s00347-012-2692-u. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517016 104 19. fortuna b, demirel` s, chzhan x i dr. sravnenie mul`tifokal`noj ve`p i standartnoj avtomatizirovannoj perimetrii pri glaznoj gipertenzii vy`sokogo riska i rannej glaukome. investirujte v oftal`mol vis sci.2007;48(3):1173-1180. doi: 10.1167/iovs.06-0561. 20. kanadani fn, mello pa, dorairaj sk, kanadani tc. frequencydoubling technology perimetry and multifocal visual evoked potential in glaucoma, suspected glaucoma, and control patients. clin ophthalmol. 2014;8:1323-1330.doi:10.2147/opth.s64684. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537109 147 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537109 148 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537109 149 results of assessment of class and degree of harmfulness of working conditions of medical workers, indexed by complexity and severity of the work process sabirova g.a., sadikov a.u., khamrakulova m.a., sadikov u.a. research institute of sanitation, hygiene and occupational diseases, ministry of health of the republic of uzbekistan fiscal institute under the state tax committee republic of uzbekistan abstract the article presents the results of the study of working conditions of the workers of the gissar oil and gas field in the kashkadarya region of uzbekistan, with the definition of the complex of unfavorable production factors at the main. according to studies, it was found that the body of workers in oil and gas production is affected by a number of adverse factors: the presence in the air of the working area of chemicals, noise, vibration, adverse microclimate, especially heating in the warm period and cold in winter, insufficient and uneven lighting, increasing stressful nature of the labor process. the impact of the above-mentioned production factors on the body of workers can cause the development of occupational and occupational diseases. keywords: oil and gas industry, working conditions, meteorological conditions, chemical factors, noise and vibration. in the light of structural transformations in the economy of the republic of uzbekistan, aimed at modernization and technical re-equipment of industries and enterprises, the most complete and efficient use of the rich natural potential of the country, the formation of export-oriented and import-substituting industries, the oil and gas industry occupies a priority place. the modern level of working conditions is characterized by improvements in technology and equipment. however, we do not imagine it is possible to completely exclude the negative impact of production factors on the body of workers. in the process of labor activity persons working in the oil and gas industry come into contact with components of multisulfur oil and oil products, physical factors and heating microclimate, which has a very adverse effect on the health of workers [4, 5]. earlier studies on the health of the population employed or residing in the territory of oil refining areas revealed its negative changes at the level of neurological status and skin [1, 6, 18]. in view of this situation, the management of oil and gas refineries began to pay special attention to the problem of environmental protection and public health [3]. numerous studies indicate that the impact of adverse working conditions on workers can be manifested by an increase in general medical morbidity, reduced life expectancy, early aging, increased mortality [8, 13]. it is known that chemical factors present at oil refineries have an adverse effect on the health of workers [11]. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537109 150 the authors have studied working conditions and labor protection of oil workers in kazakhstan. they established that the number of injured at work remains quite high and it is connected with such factors as production culture, technological and production discipline, availability of individual protective equipment, availability of special clothes and special footwear, good work organization [12]. industrial injuries are still high in the industry, the main causes of which are considered to be the deterioration of production technology, weakening of departmental control, reduction of labor protection services at enterprises, depreciation of fixed assets, reduction of funding for safety [7]. in order to preserve and protect the environment it is necessary to restore natural resources, it is necessary to carry out environmental control in the oil companies for emissions of pollutants, for water discharges, for the development of fauna and flora [9]. according to some authors, acidic products of some chemical industries, penetrating by air into the body, undoubtedly affect the cell membranes of the body, primarily red blood cells. workers of these enterprises have the most significant changes, reflecting the adaptation reactions to harmful industrial factors [10]. studies on the study of hygienic assessment of working conditions of gas industry workers revealed early changes in the nervous system in workers. the author found that natural gas has a toxic effect on the central nervous system with the development of astheno-neurotic syndrome or vegetative dystonia [2, 15]. the degree of toxic damage of the nervous system, as well as in other occupational diseases, is determined by the length of service at the enterprise. of the complex of adverse production factors the chemical components prevailed: hydrogen sulfide, hydrocarbons, ethylene glycol, ammonia, monoethanolamine, which in some shops exceeded the maximum allowable concentrations (mac) on the average values, but their maximum values in some samples significantly exceeded the mac [17]. despite the improvement of oil exploration and oil production technologies and the improvement of working and living conditions of shift workers, in most cases their working and living conditions associated with exposure to climatic and production factors are harmful and dangerous [9]. temperature factor, physical loads, high air humidity are dangerous for workers' health. a group of authors proposed a developed and tested system of industrial preventive medicine, taking into account the specifics of gas industry and extreme climatic conditions of high northern latitudes, which gives an opportunity of targeted prevention of diseases and recovery of workers' health, prolongation of professional longevity [12, 16]. research objective: assessment of working conditions and levels of harmful factors at the main oil and gas production sites of gissar. research material and methods: the main unfavorable factors of the working environment in oil and gas production are chemical and physical (noise and vibration) factors, as well as unfavorable meteorological conditions. taking into account the purpose of the study, we studied the main chemical factors in the working areas as a factor determining the functional state of the digestive organs. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537109 151 study of working conditions of workers engaged in extraction, processing and transportation of natural gas was conducted according to sanpin № 0141-03 «hygienic classification of working conditions according to indicators of harmfulness and hazard of factors of industrial environment». concentration of chemical substances in the air of working zone of gissar oil and gas production fields was determined in accordance with gost 12.1.005, and the results were evaluated in accordance with the requirements of sanpin ruz №0209-06 «sanitary rules and hygienic requirements for oil industry». noise was evaluated on the basis of sanpin ruz №0325-16 «sanitary norms of permissible noise levels in workplaces», and vibration was evaluated on the basis of sanpin ruz №0326-16 «sanitary norms of general and local vibration in workplaces». results and their discussion: we studied the working conditions of workers at modern oil and gas producing branches of the republic by the example of one of the largest divisions of lukoil uzbekistan operating company, south-west gissar. the southwest gissar project includes seven fields, of which the main ones are adamtash, gumbulak and dzharkuduk-yangi kyzylcha, as well as several other areas. the fields are located in the mountainous regions of the kashkadarya region, near the border with tajikistan, and in addition to gas contain oil and condensate reserves. noise and vibration parameters at the main objects of gissar field are presented in table 1. the table shows that the objects of special noisiness (85-110dba) are the site of gas extraction and treatment adamtash (94,0±1,41 dba), oil and gas extraction shop (92,0±1,38), industrial and technological service (92,2±1,5 dba), gas extraction and complex treatment area gumbulak jarkuduk (94±1,52 dba). noise level at the above-mentioned objects exceeds mpl from 10 to 15 dba. table 1. noise level at the oil and gas production sites gissar field № measurement location maximum permissible level equivalent sound level, dba (m±m) class of working conditions 1 oil and gas production shop 80 92±1,38 3.2 2 production and technological service 80 92,2±1,50 3.2 3 chemicalization department 80 75±1,67 2 4 chemical and analytical laboratory 80 72±1,15 2 5 transportation section 80 82±2,07 3.1 6 gumbulak-jarkuduk production and 80 94±1,52 3.2 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537109 152 comprehensive gas treatment facility 7 adamtash gas production and treatment section 80 94±1,41 3.2 8 pipeline and metering units operation section 80 84±2,43 3.1 9 central dispatch service 80 75±2,88 2 10 instrumentation, control and metrology department 80 75±3,16 2 11 it and communications service 80 72±1,36 2 12 technological equipment repair unit 80 85±3,49 3.1 13 mechanical-repair shop team 80 78,2±1,39 2 at the transport section, as well as in the sections of operation of pipelines and metering units, on repair of technological equipment and repair-technological workshop brigade, a slight increase of the maximum permissible level of noise is observed, on average from 82±2,07 to 85,0±3,49 dba. at the other facilities and sites (chemicalization team, chemical-analytical laboratory, central dispatcher service, instrumentation and metrology site, communication service) the noise level is lower than the permissible level by 5-15 dba. our measurements of vibration at the main working places showed the following: the parameters of general vibration were depending on the technical features of the equipment (power, number of revolutions and shocks). the highest frequency of vibration was detected on the transport area for car drivers, in the premises of the repair-mechanical workshop on the working places of the foreman for repair of technological equipment, fitter for repair of technological installations and general machinist the level of general vibration exceeded mpl from 10 to 36 hz (tab. 2.). table 2 vibration levels at workplaces oil and gas production field gissar shop, work place type vibrati on/ catego ry direction actions maxim um permis sible level, db equivalent corrected vibration velocity level, db duration of exposure (hours %) class of worki ng condit ions 1 2 4 5 6 7 8 transport area driver of the car (passenger car) i general 107 88 80 2 local 112 104 2 operator of truck lifts and hydraulic elevator ii general 101 104 80 3.1 local 112 108 2 hydraulic crane operator ii general 101 109 80 3.1 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537109 153 in all workplaces of the transport section the level of local vibration was low by 2-8 db in relation to mpl (112 db). in the repair-mechanical workshop team the highest vibration frequency was observed in the rooms and workshop for repair of technological equipment, the fitter for repair of technological installations was lower than the mpl by 36 hz, and in the workplace of the electric welder the local vibration level was higher by 3-20 hz (mpl 115-128 hz). study of meteorological conditions during the observation period in the oil and gas production industry, which was carried out in the following areas: oil and gas production shop; production and technological service; chemistry team; chemical and analytical laboratory; tractor shop; production and comprehensive gas treatment; gas production and treatment area; pipeline operation; central control room; metrology area; it service; mechanics repair of process equipment; repair and mechanical workshop team. changing meteorological conditions were conducted 3 times during the working day: at 800, 1200 and 1600 hours at the field workplaces. at investigated sites of oil and gas extraction industry in the hot period of year (july) there were sharp changes of indicators of physical factors (temperature, relative humidity of air, speed of air movement). at the same time, in the workshops of oil and gas production and in other open sections the air temperature during the day (1600 hours) was at the level of 36,8 – 42,8 o c, at other closed sections the air temperature ranged from 25,8±0,26 to 26,8±0,22 o c. relative humidity in the above (closed) sections ranged from 15,4 to 18,2%, and air velocity from 1,1 to 1,2 m/s. the study of the microclimate of workplaces in open areas showed that the maximum air temperature during the warm season ranged from 38°c to 42°c. relative humidity, local 112 107 2 operator of mobile steam dewaxing units iii «а» general 92 104 80 3.2 local 112 105 2 operator of mobile compressor iii «а» general 92 105 80 3.2 local 112 107 2 operator of a bulldozer ii general 101 106 80 3.1 local 112 108 2 cementing machine operator iii «а» general 92 88 80 2 local 112 104 2 repair and mechanical workshop team master of repair of technological equipment ii general 101 65 20 2 technological systems fitter ii general 101 65 60 2 general machine operator iii «а» local 112 92 60 2 automotive mechanic iii «а» local 112 92 60 2 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5537109 154 the highest in the morning hours (29%). the speed of air movement was determined on average at 1,0-3,7 meters per second. we conducted a study of the chemical composition of oil and gas for the content of hydrogen sulfide, nitrogen oxide, carbon monoxide, hydrocarbon, sulfur dioxide and ammonia in the workplace in the oil and gas production industry in the study areas. the air environment in the working zone of the main facilities (oil and gas production shop, production and technological service, gas production and preparation sections, process equipment repair section) of oil and gas production industry was contaminated with a complex of chemical harmful substances. concentrations of hydrogen sulfide, nitrogen oxide, hydrogen oxide and hydrocarbon sulfide also increased at the main sites, which exceeded mpl from 1.5 to 4.32 times. at the other sites, the content of chemical substances was within less or permissible norms. conclusion: conducted studies of working conditions of workers in the oil and gas field gissar kashkadarya region of the republic of uzbekistan is characterized by a complex of unfavorable production factors: the presence in the air of the working area of chemicals, noise, vibration, unfavorable microclimate, especially heating in the warm period and cold 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[4]. oncological and cardiovascular diseases are often a comorbid pathology, the development of which is facilitated by common risk factors, such as old age, smoking, obesity, and a sedentary lifestyle [5]. the mutual influence and strengthening of a number of pathogenetic mechanisms are also important, in particular inflammation, oxidative stress, endothelial dysfunction, impaired apoptosis, dysregulation of angiogenesis, epigenetic and other factors [6]. perhaps the maximum contribution to the development of cardiovascular pathology in cancer patients is made by the toxic effects of anticancer therapy. one of the most significant cardiovascular complications (cvc) of anticancer treatment is left ventricular (lv) dysfunction a decrease in lv ejection fraction (ef) by more than 10 percentage points from the initial value and below 50% [7, 8] and heart failure ( ch). lv and hf dysfunction associated with anticancer therapy can lead to its interruption or premature withdrawal and thereby reduce the chances of cure. being a late manifestation of cardiotoxicity of anticancer therapy, hf can not only worsen the quality of life, but also significantly affect the prognosis of patients successfully treated for cancer. the overall mortality rate of patients with hf (6%) is ten times higher than the population one [9]. studies of both past and recent years indicate that patients with late onset hf associated with anticancer therapy (more than five years after its completion) have a poorer prognosis than patients with hf due to other causes. [10]. materials and methods. patients received from 6 to 12 courses of chemotherapy. 22 patients were studied (mean age 48.8 ± 10.9 years) depending on the chemotherapy option, the patients were divided into 2 groups: 1st (n = 12) art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5109227 50 treatment duration of 8 weeks or less, the cumulative dosage of doxorubicin was 360 mg / m2; 2nd (n = 10) duration of treatment 16 weeks, cumulative dosage of doxorubicin 500 mg / m2. all patients underwent echocardiography before and after chemotherapy. echocardiographic examination was performed on a vivid s70n (ge health care) using an m5sc 1,7-3,0 мhz matrix transducer. all participants in the study underwent an assessment of the longitudinal deformation of the lv myocardium using the 2d strain method. data analysis was performed off line. results. in patients who received a higher cumulative dose of doxorubicin (group 2), there was a statistically significant increase in myocardial injury, a decrease in the global longitudinal strain of the left ventricle according to two-dimensional speckle-tracking echocardiography (from -18,6±0,4 to -14,8±0,4%; p<0,05) conclusions. an increased risk of developing subclinical cardiotoxicity was associated with a higher cumulative dose of doxorubicin (500 mg / m2) in breast cancer patients. on echocardiography, a decrease in longitudinal lv deformity is observed, this indicates a high cardiotoxicity of the drug and requires corrective therapy. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 87 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 88 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 89 epileptic encephalopathy and angelman syndrome gulyamova durdona nasriddinovna dotsent at department pediatric neurology center for the development of professional qualifications of medical personnel abstract: angelman syndrome (as) is a chromosomal syndrome characterized by atypical autism with intellectual retardation, epilepsy, a gross impairment of speech, motor disorders, ataxia, as well as special the behavior (happy demeanor) of patients in combination with frequent laughter or smiling bursts. the disease is caused by mutation of the genes on the maternally inherited 15q11.2-13 locus or gene ube3apart of the ubiquitin complex. these genes regulate the functional activity of neurons in the hippocampus, olfactory bulb, the primary visual cortex, cerebellum. keywords: epilepsy, chromosome, angelman syndrome, the ube3a gene, tremor-shivering, ataxia. introduction. the establishment of a clinical diagnosis and etiology of the disease in the examination of patients with mental retardation is the basis of medical genetic counseling. the confirmed diagnosis allows to evaluate the course of the disease, to determine the possibilities of treatment, the prognosis of the offspring for relatives, and, if necessary, the prevention of the disease in the family. one of such syndromes, difficult for diagnosis and insufficiently studied in clinical practice, is angelman syndrome (as). angelman syndrome is a genetic disease characterized by intellectual and physical developmental delay, sleep disorders, seizures, sharp movements (especially applause), frequent causeless laugh or smile and, as a rule, patients with as, look very happy. as is named after the british pediatrician, dr. harry angelman, who first described the syndrome in 1965. earlier, another alternative was used to characterize the as, the alternative name is the happy puppet syndrome, but today, officially this term is no longer used, because it is considered disparaging. people with as are sometimes called "angels", because of the name of the syndrome, their youth and happy appearance. the syndrome occurs with the same frequency in representatives of both sexes. the prevalence is 1 to 10-30 thousand newborns, but a significant number of children with this disease as a result of the lack of a correct diagnosis are observed as patients with epilepsy or suffering from behavioral disorders and delayed speech development. seventy percent of cases occur as a result of a mutation of 15q11.2-13 de novo, 2% of observations disomia on the paternal line (loss of the parent locus), 2-3% defect of the imprinting center. most of the remaining cases are associated with a mutation of the ubiquitin ube3a gene. to establish the form of the disease in 7-9% is currently not possible. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 90 as is a classic example of genomic imprinting, as it usually arises from the deletion or inactivation of genes on a copy of the 15 chromosome inherited from the mother, while the activity of the parent copy (whose sequence may be normal) does not affect the functioning of the organism. karyotype 46 xx or xy, 15p-. usually, the syndrome is caused by a spontaneous chromosomal defect when there is no large adjacent region of 3-4 million base pairs of dna in the q11-q13 region of the 15th chromosome. the angelman syndrome arises from the loss of normal maternal copies of genes in a specific region of the 15 chromosome. most often this happens by deletion of the segment of this chromosome. other causes of the onset of the disease may be uniparental paternal disomia, translocation or mutation of one gene in this area. this gene (ube3a), involved in the metabolism of ubiquitin, is present on both copies of the chromosomes (on the paternal and on the maternal), but its effect differs from the process of methylation (imprinting). inactivation of the father's copy of the gene ube3a occurs in the brain (in the hippocampus and the cerebellum), whereas the maternal allele is almost always remains active. the ube3a gene produces the protein ube3a (also called e6-ap) and this protein is an important component of the pathway for ubiquitin-proteasome formation. this pathway is extremely important for all cells, especially neurons of the brain. however, it is clear that ube3a is closely related to the synaptic function of neurons. and it was the identification of four e6-ap substrates that allowed us to understand somewhat the possible molecular mechanisms underlying the onset of angelman syndrome. the disease is characterized by the absence of abnormalities during the perinatal period and pronounced malformations at birth. the main characteristic symptoms of angelman syndrome are manifested at the age of 6-12 months. the circumference of the newborn's head does not deviate from the norm. in newborns with as, you can note sluggish sucking and muscle hypotension, which may result in regurgitation, gastroesophageal reflux, and children gain weight poorly. at this age, patients can detect an obvious delay in development in the absence of a progressive loss of acquired skills. at half of children by the end of the first year of life the insufficient head growth (microcephaly) and hyperreflexia are noted. strabismus may develop. as the development of motor skills becomes noticeable tremor. at the age after a year there is a constant smile, fits of laughter. face dysmorphism becomes prominent: a wide mouth, protruding lower jaw, large interdental spaces, brachyand microcephaly, hypopigmentation, blond hair and eyes (compared to the family). there are stereotypes (repeated strokes of hands, torsion with brushes and frequent clapping), not characteristic of healthy children. in water, children with angelman's syndrome feel more comfortable, increased sensitivity to heat and fluid needs (a constant sense of thirst). the results of laboratory tests do not deviate from the norm, examination using mri or ct does not show the presence of structural changes in the brain. possible art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 91 moderate cortical atrophy and manifestation of selective damage to the myelin sheath (demyelination). at preschool and school age, a child with a as has a kind of "hard" gait, raised to the level of the chest and bent at the elbow joints with hands. disinhibited, laughable, tongue stuck out, salivation increased. there is no speech. 10% of children with as do not go and are usually observed with the diagnosis of "infantile cerebral palsy". sleep disorders (dyssomnia) are very common. typical difficulties of falling asleep and frequent awakening. characteristic hyperactive behavior, which is more correctly called hyperdynamic syndrome. often there are constipation, obesity. a child with a as is continuously engaged in something: moves from object to object, grabbing, licking and discarding toys or other objects. speech development is grossly violated. rarely developed phrase of two words. the volume of understood speech is usually larger than the active vocabulary. most older children and adults communicate with non-verbal means. the pubertal in patients with as does not differ from the norm, the fertility is preserved. the main problems: scoliosis and gastroesophageal reflux. adult patients with as are not capable of self-care, they need constant supervision. life expectancy as in the general population. epilepsy is noted in the vast majority of patients with as (80-90% of cases). epileptic seizures debut at the age of 3 months to 20 years, but more often in young children (up to 2 years), often with febrile seizures. in 50% of cases, epileptic seizures continue to be febrile provoked. in older children, even with a small subfebrile condition, there is a greater frequency of seizures; often marked by the transition of seizures to serial and the development of epileptic status. atypical absences and epileptic myoclonus are the main types of epileptic seizures in as, which in most cases are detected for the first time during video-electric-phalographic (video-eeg) monitoring and are much less frequent complaints of the parents of patients. atypical absences are manifested by a decrease in the level of consciousness, motor activity is suspended, there is a general inhibition. minimal atonic (nodding, lowering of the shoulders, torso of the trunk) and myoclonic (twitching of limbs and facial musculature) are possible. salivation may increase during seizures. consciousness often fluctuates. absences can occur so often that a clinical picture of the epileptic status develops (peak-wave stupor), especially this is characteristic in the morning, after awakening. anxiety epileptic status is noted in more than half of patients with as and can last for days, weeks and even months. myoclonic seizures may occur in isolation (usually in the limbs and facial muscles) or as a myoclonic component in the structure of atypical absences. epileptic myoclonus in the structure of arbitrary movements is difficult to differentiate from tremor. in a dream of myoclonic seizures, as a rule, no. the status of myoclonic seizures can develop in isolation or in combination with the status of atypical absence. generalized convulsive seizures and focal epileptic seizures, from the cortex of the occipital lobe, are also characteristic. in some patients with the as phenotype, mutations in the mecp2 genes (rett's syndrome), cdkl5 (x-linked early epileptic encephalopathy) and x-linked mental art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 92 retardation are revealed. in most cases, the diagnosis is made to the patient at a more adult age, about 3-7 years. by this moment, the signs of a defect are, as a rule, pronounced. the speed with which the disease progresses will depend on the nature of the damage to the 15 chromosomes. for this reason, some patients will be able to lead an independent life, while others will not be able to even speak normally. doctors in europe have drawn attention that children with this disease have much in common with patients suffering from autism. they are united by impulsiveness, problems in communication, obsessive movements, and also a tendency to use things that are not suitable for children of their age. one of the most notable features of the angelman syndrome is its pathognomonic neurophysiological characteristics. for patients with as, three different eeg results are common: very low amplitude rhythms, whose frequency is 2 -3 hz, the greatest deviations are observed in the prefrontal zone; symmetrical high-amplitude rhythm with a frequency of 4-6 hz; the presence of close-connected acute sharp waves in the occipital areas at a frequency of 3-6 hz. due to the rarity of such descriptions in the domestic literature, we give a description of the clinical case. clinical case. girl k. 4 years. complaints: delay in psycho-speech development, restless sleep, cramps, tremor. from the anamnesis of life, it is known that the child was born from the first pregnancy, which was taking place with mild toxemia. childbirth on the 38th week, immediately screamed. the score for apgar is 6/7 balls, weight-3450 kg, height 50 cm. the neonatal period proceeded smoothly. not a kindred marriage. heredity for neurological diseases is burdened by the father of the girl. after discharge from the maternity home, parents noted the increased excitability of the child. from the age of two months were observed in the neurologist about anxiety, frequent flinch. from the words of the mother until the year the girl developed according to age: crawling, sitting alone, playing toys. the first epileptic seizures appeared against the background of apparent well-being, from 1 year 2 months in the form of head bendings with lifting of the shoulders and dilution of elbows to the sides. attacks with a duration of no more than 5 seconds, without disturbance of consciousness, during waking period, 2-4 times a day. the mother began to notice the tremor first in the distal parts of the limbs, most of all the torso. we started taking convulex 50 mg / ml at 20 mg / kg per day. as the attacks increased, the child began to experience delayed psychomotor development and muscle hypotension. in the further because of frequent paroxysms, convulex was calculated from the calculation at a daily dose of 40 mg / kg. paroxysms were absent for 6 months, but there were no positive changes in psychomotor development. after the acute respiratory viral infection, the paroxysms resumed. paroxysms of atonic character (a drop of a head on a breast, a torso of a trunk), on 10-20 times a day were observed. then the therapy scheme was used convulex + lamictal in the maximum tolerated therapeutic doses. paroxysms partially decreased, insomnia art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 93 joined and tremor increased, in connection with which hormonal therapy was prescribed (prednisone in a daily dose of 1 mg per 1 kg of weight with a gradual decrease in a month). the effectiveness of the drugs was partial the number of paroxysms decreased (5-6 times a month). in general, the duration of the relatively "quiet" period was about two months. on the video eeg monitoring (daytime): background eeg slow-wave activity originating from the central-parietal divisions at a frequency of 3 hz. these epileptiform patterns are present in all stages of non-rem with different amplitudes from 50 to 150 μv, mainly in the anterolateral parts of the brain on the right. after awakening with active wakefulness in the frontal areas slow slow wave complexes and rhythmic slow wave activity of the delta range are recorded (figure 1). fig.1 based on the above data, a diagnosis was made: epileptic encephalopathy. the lennox-gastaut syndrome. then, against the background of respiratory infectious disease at the age of 2.5 years, paroxysms resumed and paroxysms joined in the form of tonic torso and limb stresses, head and eye movements, nocturnal flinches. after the deterioration of the child's condition, another therapy scheme was used convulex + levetiracetam. but this combination of the drug worsened the condition, seizures became more frequent, generalized clonic convulsions joined the paroxysms. in the future the scheme of therapy of convulex + topiramate was used. at the last hospitalization at the age of 3 years 11 months the state of the child on the disease is severe. paroxysms have become more frequent on the background of respiratory infectious disease in the form of tonic seizures of atypical absences with atonic component, frequent flinching’s with a frequency of 2-3 times a day. in objective status, physical development by age, stigma of dysembryogenesis is absent, a head of normal size, a flattened back of the head. skin, hair and eyes of light color. signs of the pathology of the respiratory and cardiovascular system are art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 94 absent. frequent constipation, increased salivation. on the lower extremities in the region of the shin there is a spot of blue color, which (according to the mother) increases with increasing temperature. in neurological status: cranial innervation movement of eyeballs in full volume, nystagmus, there is no strabismus. the face is symmetrical, the function of the chewing and facial muscles is not violated. the tongue along the middle line, the soft palate with phonation is symmetrically movable, the voice is loud. in the motor sphere: muscle tone is hypotonic. tendon reflexes are called symmetrically. pathological bone, carpal reflexes are not revealed. severe tremor of the trunk and extremities. expressed motor delay: does not walk alone, stands with support, takes objects with hands. active speech is absent, hardly understands the converted speech. the mood is increased, a constant smile on the face, periodically laughs. frequent stereotypes in the hands. video eeg monitoring (full-time): on the background recording, polymorphic activity with the predominance of theta waves of the diapason. the slow forms of activity are recorded widely, diffusely, often dominate the background, are mainly represented by fluctuations in theta of the range of 4-5 hz with an amplitude of up to 150 μv, less often in the delta range with an emphasis in the fronto-central and parieto-occipital hemispheres. against this background, on a regular basis, during wakefulness and during sleep, slow slow-wave complexes with a frequency of 1.5-3 hz and an amplitude of 150 μv are recorded in a generalized manner. sleep does not differentiate in phases and stages. the physiological patterns of sleep are mostly mixed in epileptiform activity. (figure 2 and 3) fig.2 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 95 fig.3 mri of the brain signs of moderate hypoxic ischemic encephalopathy, delayed myelination (figure 4). fig.4 ultrasound examination of internal organs: reactive changes in the liver, spleen and pancreas without pathology. blood chemistry: calcium1.95mmol/l (n 2.02-2.60); magnesium0.8mmol/l (n 0.7-1.0); iron31.4mmol/l (n 8.9-21.0); ammonia197mmol/l (n 9-33); cholesterol4.1mmol/l (n 3.7-5.2); triglycerides1.24mmol/l (n 0.1-1.1); urea 6,5mmol/l (n 1,8-6,4); glucose3.35mmol/l (n 2.5-4.7); lactate2.5mmol/l (n 0.7-2.1). the concentration of valproate acid in the blood: 152.5 μg/ml (n 50-100). art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 96 immunogram: imbalance of immunoregulatory t-lymphocytes. presence of an allergic component in the body. activation of apoptosis of lymphocytes. the presence of an inflammatory process on the mucous membranes (lga increased). tandem mass spectrometry (ms) pathological abnormalities are not revealed. genetic research: results of karyotyping 46, xx. conclusion of the exome sequencing (wes): on chromosome-15 was detected a chromosomal microdeletion, that included a total of 282 exon genes: mkrn3, magel2, ndn, pwrn1, npap1, snrpn, snord116-1, snord114, snord116-10, snord116-22, ipw, snord115-1, ube3a , atp10a, gabrb3, gabra5, gabrg3, oca2, herc2. the deletion is identified as probably pathogenic. it should be noted that the ube3a gene is entered the deletion region (omim 105830 angelman syndrome), heterozygous mutations in this gene leads to the clinical manifestations of as. clinical diagnosis: epileptic encephalopathy. angelman syndrome.based on laboratory data (elevated blood ammonia level, reactive hepatitis), the anticonvulsant therapy regimen was changed. despite the attacks, the dose of convulex was reduced to 25 mg/kg per day, lamotrigine was added at a rate of 5 mg/kg per day, topiramate was canceled. hepatoprotectors were added to the treatment. after a month, the condition of the girl improved, the attacks decreased, ammonia in the blood normalized to 40.6 mmol/l. currently, seizures 2-3 times a month, tremor and ataxia persists, night sleep restless. this clinical case seems interesting with a few poses. the clinical picture of the disease itself is of interest the impossibility of a clear syndromological diagnosis of this syndrome and unclassified form of epilepsy. by the type of seizures and according to eeg data, we can not attribute this case to classical encephalopathies of early childhood. in all cases of early epileptic encephalopathy, we can not explain a certain etiology (hypoxic-ischemic encephalopathy, developmental defects of the brain), the child needs to carry out a genetic examination, in particular comparative genomic hybridization and full genome sequencing. the most important aspect of this clinical observation is the mutation of the ube3a gene, which in some patients can be detected with a mutation in the mecp2 genes (rett syndrome), cdkl5 (xlinked early epileptic encephalopathy). but it is possible that such cases are much more common than they are. the development and accessibility of modern methods of genetic research, such as comparative genomic hybridization and full genome sequencing, will soon make it possible to clarify the genesis of a number of genetic and epileptic syndromes, and possibly help in the development of new ways of treating childhood epilepsy. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5717607 97 references. 1. bakhtin i.s, belousova e.d, shatalov p.a. severe epileptic encephalopathy of early childhood associated with a mutation in the gene scn2a journal of epilepsy 2015; №1; с .35-40; 2. voropanova e.b, bobylova m.yu, mironov m.b, kulikov a.v. acute ataxia, which occurred after acute respiratory virus infection in a 2-year-old girl, as a debut of the clinical manifestations of angelman syndrome. russian journal of pediatric neurology. volume 10 №1 2015 pages 64-69; 3. mironov m.b, mukhin k.yu, kuzina n.yu. et al. angelman syndrome. clinical case. russian journal of pediatric neurology 2009; 4 (1): 52-62; 4. mukhin k.yu, mironov m.b. angelman syndrome. in the book: mukhin k.yu, petrukhin a.s, kholin a.a. epileptic encephalopathies and similar syndromes in children. moscow: artservice ltd., 2011. s. 520-34; 5. skvortsov i.a, bashina v.m. diseases of development of communicative functions at children with autistic spectrum diseases. tula: image print, 2013. pp. 174-7. (in russ.); 6. castro-gago m, gomez-lado c, eiris-punas j, rodrigez-mugico v.m. abnormal myelination in angelman syndrome. european journal paediatric neurology 2010; 14 (3): 292; 7. peters s.u, bird l.m, kimonis v. et al. double-blind therapeutic trial in angelman yndrome using betaine and folic. american journal med genetic a 2010; 152a (8): 1994-2001. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 203 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 204 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 205 expert assessment of survival prognosis and optimization of approaches to early examination of patients with chronic obstructive pulmonary disease. liverko i.v., tashmetova g.t. republican specialized scientific and practical medical center of tuberculosis and pulmonology center for the development of professional qualifications of medical workers tashkent, uzbekistan abstract. the results of the analysis showed that among the cohort of patients with copd with a bode index of more than 5 and according to the results of the cat test, which determines a serious impact on the daily life of patients (more than 30 points), the proportion of disabling conditions is high: pulmonary hypertension (62.6% and 42, 2%, respectively), cor pulmonale (37.4% and 21.9%, respectively), confirming the need for primary examination of this category of patients, where it is expected for the first time to establish disability in every 3-4 patients from this cohort of patients. keywords. bode, copd, fev1, bmi. introduction. questions of expert early examination of patients with copd in the category of vital activity: the ability to self-service, movement, work activity and the establishment of their limitations in terms of severity has an important aspect for predicting the progression of the disease, determining the early terms of social rehabilitation measures. the steadily progressive course of copd leads to the development of early disability and a decrease in life expectancy. severe concomitant diseases in copd, advanced age of patients, progressive emphysema, the development of respiratory and heart failure are unfavorable prognostic signs [2; p. 1-36]. further evolution is a progressive restriction of air flow, increased pressure in the pulmonary artery, the development of hypertrophy of the right ventricle and cor pulmonale [4; c.1-6]. with the progression of obstruction, patients become less and less mobile, this leads to muscle and cardiovascular disorders, and an increase in disability. the growth of disability contributes to depression, social isolation, which is widespread among seriously ill copd [3]. in advanced stages of copd, severe pulmonary hypertension is a serious complication, which predicts an increased frequency of exacerbations. disability in copd is established late and is established almost immediately the second group. the life expectancy of disabled people with copd is no more than 6 years on average, which is 3.5 times less than in ba [1; c. 221-232]. the aim of this study was to conduct an expert assessment of the prognosis of survival and optimization of approaches to early examination of patients with chronic obstructive pulmonary disease.. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 206 material and research methods. a total of 340 patients with copd were examined. clinical and functional data of patients with copd were assessed, including the main parameters bmi (body mass index), mrc (dyspnea scale of the medical research council), fev1 (forced expiratory volume in the first second), 6mst (six-minute step test), which determine prognostic outcomes the survival rate of patients with copd and indicators of the effect of the disease according to the cat test (the effect of copd on the patient's daily life and health). research results. assessment of the clinical and functional data of patients with copd, including the main parameters bmi, mrc, fev1, 6-mst, which determine the prognostic survival outcomes of patients with copd and indicators of the effect of the disease according to the cat test are presented in table 1. table 1. characteristics of clinical and functional parameters in patients with copd (n = 340) factors n copd functional degree of copd i stage, n=25 ii stage, n=56 iii stage, n=100 iv stage, n=159 bmi, kg / m 2 340 23,5±2,5 24,3±1,2 22,1±2,6 20,8±1,9 18,1±2,4 mrc, points 340 3,1±1,1 0,9±0,3 1,9±0,3 2,6±0,5 3,5±0,4* fev1,% from due 340 48,4±2,1 81,4±1,1 63,8±3,1* 43,8±2,4* 33,8±1,4* 6msht, m 340 171,9±11,2 301,9±19,5 241,9±11,5 151,9±10,2* 125,8±13,8* cat test, points 340 30,5±5,5 9,3±1,2 16,1±3,6 29,8±2,5* 35,1±1,4* from the presented table it can be seen that with the severity of the functional stage, the severity of the clinical manifestations of the disease increases, in particular, the intensity of shortness of breath from 0.9 ± 0.3 to 3.5 ± 0.4 points, the 6-mst indices decrease by 58.3% and manifestations of nutritional deficiency are increasing, accompanied by a decrease in bmi by 25.5%, and the degree of influence of the disease on the patient's life increases by 4 times from a level of insignificant influence (9.3 ± 1.2 points) to a serious (35.1 ± 1, 4 points). analysis of clinical and functional parameters with the calculation of the bode index in patients with copd showed that 25% of patients with copd had a calculated bode index, which determines the 80% probability of 4-year survival (in a grading of 0-2 points); 30% of patients with copd had a 67% probability of 4-year survival with a calculated bode index of 3-4 points; in 27.6% of patients with copd 57% probability of 4-year survival with the calculated data of the bode art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 207 index of 5-6 points; 17.4% of patients with copd had a probability of 18% 4-year survival according to the bode index from 7 to 10 points. the assessment of the disease outcome by the bode index was compared with the indicators of the cat result, which determines the impact of copd on the patient's daily life and health (table 2). table 2 comparison of the results of estimates of the bode index and cat points total by bode index, score n impact of copd on the patient's daily life and health, score minor 0-10 moderate 11-20 expressed 21-30 serious 31-40 0-2 85 25(29,4±4,9) 56(65,9±5,1) 4(4,7±2,3) 3-4 102 1(1,0±1,0) 1(1,0±1,0) 74(72,5±4,4) 26(25,5±4,3) 5-6 94 1(1,1±1,1) 20(21,3±4,2) 73(77,7±4,3) 7-10 59 2(3,4±2,4) 57(96,6±2,3) according to the results of the study, a high correlation was established between the bode index and the results of cat (r = 0.83). it was noted that with a decrease in the percentage of 4-year survival, there is a tendency for the aggravation of the serious impact of copd on the daily life and health of the patient from 25.5% to 96.6%. the results of the study compared the clinical and functional parameters that determine the clinical status of the severity of copd disease, which had a previously established group of disability for respiratory diseases (table 3). table 3 frequency of scoring criteria in patients with copd with and without disabilities indicator by indicators score in points copd patients with an established invalidity, n = 82 without established disability, n = 258 b m i, k g / m 2 more than 21 0 29(35,4±5,3) 249(95,6±1,3) less than 21 1 53(64,6±5,3)* 9(4,4±1,3) f e v 1 , % d u e over 65 0 1(1,2±1,2) 114(44,2±3,1) art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 208 50-64 1 11(13,4±3,8) 86(33,3±2,9) 36-49 2 25(30,5±5,1)* 38(14,7±2,2) less than 35 3 45(54,8±5,5)* 20(7,7±1,6) 6 -m s h t , m more than 350 0 110(42,6±3,1) 250-349 1 9(11,0±3,4) 90(34,9±3,0) 150-249 2 29(35,4±5,3)* 31(12,0±2,0) less than 149 3 44(53,6±5,5)* 27(10,5±1,9) m r c , sh o rt n es s o f b re at h 0-1 0 1(1,2±1,2) 116(45,0±3,1) 2 1 4(4,9±2,4) 80(31,0±2,9) 3 2 22(26,8±4,9)* 38(14,7±2,2) 4 3 55(67,1±5,2)* 24(9,3±1,8) note: * reliability of the difference between the indicator values (p <0.05). as can be seen from the presented table, the assessment of individual functional parameters cannot accurately reflect the degree of functional disorders and objectively serve as a criterion for assessing the ability to work. so, up to 14.6% of disabled people had fev1 parameters of more than 50% of the required value, up to 11.0% had the result of 6 mst more than 250 m (more than 75% of the required value) and 6.1% of patients had an assessment of the degree of cough by mrc not more than 3 points. also, copd patients without established disability had certain disorders that determine the possible degree of disability, which were characterized by a pronounced degree of functional impairment by a decrease in fev1 of less than 50% of what should be and the results of 6 mst less than 250 m and were 45.0% in the cohort of copd patients without disability. ... the evaluated functional criteria, allowing to accentuate the degree of the functional class of the disease, were ranked according to the sum of points, where 0-3 points functional class i; 4-6 points functional class ii, 7-10 points functional class iii, and analyzed by the frequency of their occurrence in cohorts of copd patients with and without disabilities (fig. 1). art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 209 fig. 1. frequency of occurrence of functional classes of the disease in copd in the cohort of copd patients with disabilities, there was a trend towards an increase in the functional class of copd disease from 11.0% to 52.4%. assessment of the integral bode index in copd patients with an established disability group shows that only 24.4% have a 4-year survival rate of more than 57% (table 4). from the presented table it can be seen that 90% of patients with copd, with an existing iii disability group, had an 80% probability of 4-year survival; 46.1% of patients with copd in group ii and 71.4% of patients with copd in group i had an 18% probability of 4-year survival. table 4 percentage rate of 4-year survival in copd patients with various disabilities disability group 4-year survival rate 80% 67% 57% 18% iii 10 9(90,0±10,0) 1(10,0±10,0) ii 65 1(1,5±1,5) 9(13,8±4,3) 25(38,5±6,0) 30(46,2±6,2) i 7 2(28,6±18,4) 5(71,4±18,4) 82 10(12,2±3,6) 10(12,2±3,6) 27(32,9±5,2) 35(42,7±5,5) assessment of the impact of the disease on the daily life of copd patients with an established disability group shows that only 26.8% have a slight or moderate impact on the patient's life according to the results of the cat test (table 5). table 5 assessment of the impact of copd on the daily life and health of a copd patient with disabilities disability impact of copd on the patient's daily life and health, score 0 20 40 60 80 100 i fc ii fc iii fc 11 36,6 52,4 94,2 4,6 1,2 disability no disability art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 210 group n minor 0-10 moderate 11-20 expressed 21-30 serious 31-40 iii 10 6(60,0±16,3) 3(30,0±15,1) 1(10,0±10,0) ii 65 1(1,5±1,5) 12(18,5±4,8) 30(46,1±6,2) 22(33,8±5,9) i 7 1(14,3±14,3) 6(85,7±14,3) total 82 7(8,5±1,5) 15(18,3±4,3) 32(39,0±5,4) 28(34,1±5,2) the used assessment of expert examination of patients with copd is based on parameters reflecting the severity of obstruction and hemodynamic disorders, taking into account the nature of the patient's work activity and concomitant pathology, today, without taking into account and assessing the integral indicators of the bode index, which determine the probability of the percentage of 4-year survival and outcomes cats assessing the impact of copd on a patient's daily life may not reflect a valid level of expert judgment. analysis of the occurrence of functional and hemodynamic criteria that determine the assessment of expert examination of patients with copd in a cohort of individuals with a 57% probability of 4-year survival and the level of serious impact of copd on the patient's daily life is presented in table 6.. table 6 frequency of occurrence of functional and hemodynamic criteria that determine the assessment of expert examination of patients with copd copd patients with indicator values n functional and hemodynamic parameters sdla more than 25 mm hg sodi poll rice index less than 10 pii-iii more than 2 for physical activity the rise decline heart rate over 15% np more than 20% saturation by more than 3% cat more than 30 points 128 54 42,2±4, 4 31 24,2±3,8 28 21,9±3, 5 36 28,1±3,6 40 31,2±4,1 26 20,3±3,5 bode index 5 and more 91 57 62,6±5, 1 32 35,2±5,0 34 37,4±5, 1 30 33,0±4,9 42 46,1±5,2 33 36,3±5,1 the results of the analysis showed that among the cohort of patients with copd with a bode index of more than 5 and according to the results of the cat test, which determines a serious impact on the daily life of patients (more than 30 points), there is a high proportion of disabling conditions: pulmonary hypertension (62.6% and 42, 2%, respectively), cor pulmonale (37.4% and 21.9%, respectively), confirming the need for art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 211 primary examination of this category of patients, where it is expected for the first time to establish disability in every 3-4 patients from this cohort of patients. conclusions: 1. the high diagnostic significance of the integral estimates of the bode index and the results of the cat test in the issues of early examination of patients with copd was stated. 2. these integral indices have a high correlation with clinical and functional indicators that determine the severity of the disease and its functional classes, and their close correlation with the disability group has been established, which determine persistent disability.. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5564196 212 references 1. belevsky a.s., meshcheryakova n.n. rehabilitation of patients with copd. clinical guidelines. chronic obstructive pulmonary disease. russian respiratory society; ed. a.g. chuchalin. 2nd ed., [rev. and add.]. moscow. atmosphere. 2007. p. 221-232. 2. chuchalin a.g. et al. federal clinical guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease // pulmonology. 2014. no. 3. p.1-36 p. 3. pollok j, van agteren jem, carson-chahhoud kv. pharmacological interventions in the treatment of depression in patients with chronic obstructive disease. 2018.https://doi.org/10.1002/14651858.cd012346.pub2 4. robert a. wise. chronic obstructive pulmonary disease (copd) // johns hopkins university school of medicine.-2020.-p.1-10. 1 volume 2, ¹1.2 art of medicine international medical scientific journal 2 art of medicine international medical scientific journal volume 2, ¹1.2 february 2022 3 volume 2, ¹1.2 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen art of medicine international medical scientific journal 4 neonatal resuscitation in 22-week pregnancies debasis basu ph.d., harish kumar ph.d., internal, family medicine physician staten island a 20-year-old woman pregnant with her second child presents to the emergency department with premature contractions at 22 weeks’ gestation. her first child had been born by spontaneous vaginal delivery at 34 weeks’ gestation and is currently a healthy 2year-old. the woman has no chronic medical conditions and takes a prenatal vitamin daily. she has had routine prenatal care, and prenatal ultrasonography has shown no fetal or placental anomalies. her vital signs are within normal limits. physical examination is notable only for a gravid abdomen. cervical examination shows dilation to 3 cm, 40% effacement, and a fetal station of -2. she is admitted to the obstetrics ward for further management of her pregnancy. you are an administrator in the hospital. the physicians caring for this patient contact you for guidance, since you have been charged with deciding whether resuscitation should be routinely performed for all neonates born at 22 weeks’ gestation or whether selective resuscitation should be offered. which one of the following approaches would you take? base your choice on the literature, your own experience, published guidelines, and other information sources. recommend resuscitation for all neonates born at 22 weeks’ gestation. recommend selective resuscitation for neonates born at 22 weeks’ gestation. to aid in your decision making, we asked two experts in the field to summarize the evidence in favor of approaches assigned by the editors. given your knowledge of the issue and the points made by the experts, which approach would you choose? option 1: recommend resuscitation for all neonates born at 22 weeks’ gestation option 2: recommend selective resuscitation for neonates born at 22 weeks’ gestation the issue of the initial management and resuscitation of infants born at 22 completed weeks of gestation has led to substantial debate among neonatology and maternal–fetal medicine specialists. both the exact definition of and the approach to the limit of viability are major sources of anxiety for families and health care providers. that limit has changed drastically in the past 30 years, from 27 to 28 weeks of completed gestation to the current 22 to 23 weeks. it is important to note that delaying delivery as long as it is safe for the mother and the fetus is the preferred approach. now let us consider the question of resuscitation in all infants. after all, wouldn’t it be easier to take a case-by-case approach? the answer is an emphatic “no.” first, a standard approach to neonatal resuscitation and early postresuscitative care, within the so-called golden hour, is well accepted to improve outcomes.1 second, these decisions are often made quickly, as in this vignette. having a truly informed discussion is difficult given the stressors involved and the need to focus 5 volume 2, ¹1.2 on the mother’s medical care as well. third, prenatal gestational age assessments are suboptimal, which makes it difficult to be certain of a fetus’s exact gestational age.2 fourth, a case-by-case approach allows for implicit biases to potentially influence decisions and contribute to the well-documented disparities in infant mortality in the united states. data have been published that support the use of a standard approach to resuscitating the neonates in all deliveries at 22 weeks’ gestation. for example, in a study by backes et al., the mortality rate at a hospital that used selective resuscitation was worse than the rate at a hospital in which active care was provided to all infants (survival, 19% vs. 53%, p<0.05).3 a report from a hospital in iowa in which active resuscitation was offered for all infants born at 22 to 23 weeks’ gestation showed that 70% of the infants born at 22 weeks survived and 55% of these patients had no or only mild neurodevelopmental impairment at follow-up.4 a cohort study of swedish infants born at 22 to 24 weeks’ gestation showed that 52% of the infants born at 22 weeks’ gestation survived, with 50% of the survivors having no neurodevelopmental impairment at 2.5 years of age, outcomes that mirrored those in infants born at 23 to 24 weeks.5 in pediatric cardiology practices, the survival rate of 30 to 70% among patients who require extracorporeal life support is considered reasonable for initiating that form of invasive therapy, so it certainly appears from the available data that birth at 22 weeks’ gestation with resuscitation for all neonates also meets this mark.6 the earliest gestational age at birth after which survival is possible has decreased incrementally over time. such improved survival has occurred as vanguard centers challenged conventional limits and demonstrated survival of infants born at gestational ages previously considered nonsurvivable. in this case vignette, an expectant mother presents with threatened preterm delivery at 22 weeks’ gestation, the current “limit of viability.” during antenatal counseling, parents should be offered selective resuscitation for their child. what is selective resuscitation? almost all extremely preterm infants require resuscitative interventions after birth to survive. antenatal counseling for parents facing extremely preterm delivery of their baby is recommended and is typically possible, despite known challenges.7 “do not resuscitate” orders are accepted and encouraged in other medical settings when the possibility of survival is low and the burden of treatment is high. selective resuscitation represents shared decision making to ensure that plans to initiate intensive care immediately after birth respect parental autonomy and wishes. as proxy decision makers, parents may select resuscitation as the first step of providing intensive care for their extremely premature infant or they may reasonably prioritize comfort care over invasive and potentially futile interventions. predicting outcomes with certainty after extremely preterm birth is difficult, owing to imprecise statistical models and the influence of factors beyond gestational age.8 morbidity and mortality are very high among infants born at 22 weeks’ gestation, and nuanced features that influence outcomes should be acknowledged. in a 2021 metaanalysis of 2226 infants born at 22 weeks’ gestation who received active treatment, the pooled prevalence of survival was 29%, and survival without major in-hospital complications was 11%.9 furthermore, the burden of treatment is high. extremely preterm newborns who survive spend months in the neonatal intensive care unit, undergo hundreds of painful procedures, and are at high risk for subsequent neurodevelopmental impairment.10,11 isolated centers have reported survival rates higher than 50% for infants born at 23 weeks or less of gestation. it is tempting to speculate that similar outcomes would be uniform after universal resuscitation, but that conclusion would be premature. first, art of medicine international medical scientific journal 6 such accounts represent the limited experience of specific and highly resourced hospitals, a factor that reduces generalizability. survival estimates after active treatment are lower when pooled from more inclusive settings.9 second, many reports combine outcomes among infants born at 22 weeks’ gestation with those among infants born at 23 and 24 weeks’ gestation, making it difficult to ascertain the experience for infants at 22 weeks. finally, infants born at the limits of viability are poorly represented in clinical trials and receive largely experimental care extrapolated from the care given to more mature patients. ongoing scientific collaborations focused on this population may produce an evidence base for future widespread implementation, but this is not yet the current state of the field. as perinatal medicine continues to advance, there always will be a gestational age threshold at which survival is possible but unlikely. resuscitation should be offered but not universally mandated for these infants. the current limit of viability is 22 weeks’ gestation. prospective parents such as the mother in the vignette should be counseled regarding the range of possible outcomes and provided the opportunity to inform the goals of their child’s medical care. these studies call into question the notion that gestational age is itself a signal for determining the need for neonatal resuscitation. as is true for ill neonates of any gestational age who require intensive care, a universal approach to resuscitation improves overall outcomes; if severe life-limiting complications develop, a palliative approach can be offered when more prognostic information is available. the use of a standard approach for infants born at 22 weeks’ gestation results in outcomes that are as good as those among infants born at 23 to 24 weeks’ gestation; thus, at this time there seems to be no persuasive argument against offering resuscitation to all neonates born at 22 weeks. this section asks about your financial relationships with entities in the bio-medical arena that could be perceived to influence, or that give the appearance of potentially influencing, what you wrote in the submitted work. you should disclose interactions with any entity that could be considered broadly relevant to the work. for example, if your article is about testing an epidermal growth factor receptor (egfr) antagonist in lung cancer, you should report all associations with entities pursuing diagnostic or therapeutic strategies in cancer in general, not just in the area of egfr or lung cancer. report all sources of revenue paid (or promised to be paid) directly to you or your institution on your behalf over the 36 months prior to submission of the work. this should include all monies from sources with relevance to the submitted work, not just monies from the entity that sponsored the research. please note that your interactions with the work's sponsor that are outside the submitted work should also be listed here. if there is any question, it is usually better to disclose a relationship than not to do so. for grants you have received for work outside the submitted work, you should disclose support only from entities that could be perceived to be affected financially by the published work, such as drug companies, or foundations supported by entities that could be perceived to have a financial stake in the outcome. public funding sources, such as government agencies, charitable foundations or academic institutions, need not be disclosed. for example, if a government agency sponsored a study in which you have been involved and drugs were provided by a pharmaceutical company, you need only list the pharmaceutical company. this section asks for information about the work that you have submitted for publication. the time frame for this reporting is that of the work itself, from the initial conception and planning to the present. the requested information is about resources that you received, either directly or indirectly (via your institution), to enable you to complete the work. checking "no" means that you did the work without 7 volume 2, ¹1.2 receiving any financial support from any third party -that is, the work was supported by funds from the same institution that pays your salary and that institution did not receive third-party funds with which to pay you. if you or your institution received funds from a third party to support the work, such as a government granting agency, charitable foundation or commercial sponsor, check "yes". it is important to note that delaying delivery as long as it is safe for the mother and the fetus is the preferred approach. now let us consider the question of resuscitation in all infants. after all, wouldn’t it be easier to take a case-by-case approach? the answer is an emphatic “no.” first, a standard approach to neonatal resuscitation and early postresuscitative care, within the so-called golden hour, is well accepted to improve outcomes.1 second, these decisions are often made quickly, as in this vignette. having a truly informed discussion is difficult given the stressors involved and the need to focus on the mother’s medical care as well. third, prenatal gestational age assessments are suboptimal, which makes it difficult to be certain of a fetus’s exact gestational age.2 fourth, a case-by-case approach allows for implicit biases to potentially influence decisions and contribute to the well-documented disparities in infant mortality in the united states. data have been published that support the use of a standard approach to resuscitating the neonates in all deliveries at 22 weeks’ gestation. for example, in a study by backes et al., the mortality rate at a hospital that used selective resuscitation was worse than the rate at a hospital in which active care was provided to all infants (survival, 19% vs. 53%, p<0.05).3 a report from a hospital in iowa in which active resuscitation was offered for all infants born at 22 to 23 weeks’ gestation showed that 70% of the infants born at 22 weeks survived and 55% of these patients had no or only mild neurodevelopmental impairment at follow-up.4 a cohort study of swedish infants born at 22 to 24 weeks’ gestation showed that 52% of the infants born at 22 weeks’ gestation survived, with 50% of the survivors having no neurodevelopmental impairment at 2.5 years of age, outcomes that mirrored those in infants born at 23 to 24 weeks.5 in pediatric cardiology practices, the survival rate of 30 to 70% among patients who require extracorporeal life support is considered reasonable for initiating that form of invasive therapy, so it certainly appears from the available data that birth at 22 weeks’ gestation with resuscitation for all neonates also meets this mark.6. art of medicine international medical scientific journal 8 used literature. 1.wyckoff mh. initial resuscitation and stabilization of the periviable neonate: the golden-hour approach. semin perinatol 2014;38:12-16. 2.committee opinion no 700: methods for estimating the due date. obstet gynecol 2017;129:e150-e154. 3.backes ch, söderström f, ågren j, et al. outcomes following a comprehensive versus a selective approach for infants born at 22 weeks of gestation. j perinatol 2019;39:3947. 4.watkins pl, dagle jm, bell ef, colaizy tt. outcomes at 18 to 22 months of corrected age for infants born at 22 to 25 weeks of gestation in a center practicing active management. j pediatr 2020;217:52-58.e1. 5.söderström f, normann e, jonsson m, ågren j. outcomes of a uniformly active approach to infants born at 22–24 weeks of gestation. arch dis child fetal neonatal ed 2021;106:413-417. 6.di nardo m, maclaren g, marano m, cecchetti c, bernaschi p, amodeo a. ecls in pediatric cardiac patients. front pediatr 2016;4:109-109. 7.cummings j; committee on fetus and newborn. antenatal counseling regarding resuscitation and intensive care before 25 weeks of gestation. pediatrics 2015;136:588595. 8.rysavy ma, horbar jd, bell ef, et al. assessment of an updated neonatal research network extremely preterm birth outcome model in the vermont oxford network. jama pediatr 2020;174(5):e196294-e196294. volume-1 issue-1 art of medicine international medical scientific journal 1 art of medicine international medical scientific journal volume-1 issue-1 2 art of medicine international medical scientific journal volume 1, issue 1, may 2021 volume-1 issue-1 art of medicine international medical scientific journal 3 founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine international medical scientific journal chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen art of medicine international medical scientific journal volume-1 issue-1 4 content tursunova l. d., jabbarov o. o. application of sakabutril/valsartan in patients with chronic kidney disease with type 2 diabetes mellitus...............................5 l.s. khamraeva., d.u. narzullaeva features of calculating the optical power of an intraocular lens in children with congenital cataracts at the risk of developing pseudomyopic myopia.....................10 kasimova m. s., iminova m. m., ashurov o. m. ophthalmologic complications in the structure of the clinical features of novel coronavirus infection (covid-19)......................................................................................................14 fattayeva d.r., rizayev j.a., rakhimova d.a. improvement of methods for correction of clinical and immunological disorders in comorbid state of chronic gaymoritis after covid-19....................................................................17 polatova d.sh., abdukarimov kh.g., davletov r.r., savkin a.v., sultanov b.b features of immunobiological heterogeneity in patients with osteosarcoma.................................................................................25 volume-1 issue-1 art of medicine international medical scientific journal 17 improvement of methods for correction of clinical and immunological disorders in comorbid state of chronic gaymoritis after covid-19 fattayeva d.r. tashkent state dentistry institute, republic of uzbekistan, tashkent rizayev j.a. samarkand state medical institute, republic of uzbekistan, samarkand rakhimova d.a. the republican specialized scientific and practical medical center for therapy and medical rehabilitation. abstarct.each body has its own defenses, which help to neutralize and destroy various microorganisms that can cause disease. however, sometimes these defenses are weakened for whatever reason, and cannot cope with the infection penetrated. the question arises: how to boost immunity? how to prevent the occurrence of dangerous diseases? what can help strengthen the body? this article will help you understand these and other issues. keywords: immunity, kinds of immunity, gaimor sinus, herbal preparations the frequency of odontogenic inflammation of the maxillary sinus is ambiguous. odontogenic maxillary sinusitis accounts for 3 to 7% of the total number of all stomatological diseases, patients with odontogenic maxillary sinusitis account for about 25.8% among patients with inflammatory processes of the maxillary sinus and about 7.6% of all patients with maxillofacial diseases. [1-4]. according to aa timofeev [5], odontogenic sinusitis occurs in 21.3% of cases, and rhinodontogenic in 3.1% of the total number of purulent inflammatory processes in the maxillofacial region, and from all cases of sinusitis, 87% and 13%, respectively . despite the emergence of new, original and, indeed, effective methods of diagnosis and treatment of paranasal sinusitis, their number is growing every year. according to the data of domestic and foreign authors, the incidence of chronic sinusitis over the past 10 years has increased by more than 2 times, and the proportion of patients hospitalized in ent hospitals is increasing annually by 1.5 2% and has no tendency to decrease. of particular interest in this plan are the combined diseases of the periodontal, maxillary sinus and bronchi. according to some authors, a combination of chronic nonspecific lung diseases and chronic sinusitis is noted in 17.7-28.0% of cases (1,6,12). studies have revealed a relationship between foci of chronic odontogenic infection and an increased risk of developing chronic obstructive bronchitis and bronchial asthma. the foci of infection in the tissues of the periodont also serve as a reservoir for the colonization of respiratory pathogens that cause the development of infectious pneumonia, and the destruction of the periodontal inflammation-destructive nature can sensitize the course of the bronchial organisms and thus with it (3,4,13). in turn, a chronic process in the bronchi, reducing the general immunological reactivity of the body, can contribute to the progression of inflammatory diseases of the tissues of the parodontium. it is suggested that the quantitative and qualitative composition of the microbial landscape of the oral cavity is determined by the reactivity of the organism (5,7,9). in addition, chronic obstructive pulmonary diseases are accompanied by the development of systemic hypoxia, including periodontal tissues, which, according to a art of medicine international medical scientific journal volume-1 issue-1 18 number of researchers, is also a factor that aggravates the course of sinusitis (10, 14). against the background of the existing metabolic disorders, the oxygen deficiency in the tissues of the periodont further inhibits the regenerative and reparative processes in all its structural components and the mucous membrane. the importance of the combined pathology of the periodontal and bronchi is determined not only by the prevalence and severity of the disease, the negative effect on the body as a whole, but also by the low effectiveness of the treatment. in the domestic and foreign literature, there are practically no scientifically substantiated data on the possibilities of an integrated approach to systemic methods of treating sinusitis combined with chronic obstructive pulmonary disease (copd), which is due to the functional and industrial separation of dentists with other specialties. at the same time, one of the main directions of therapeutic measures is the correction of the immunological imbalance detected in such patients (2,15). at the present time, the study of the clinical and immunological features of the course of sinusitis combined with chronic obstructive pulmonary disease and the improvement of the methods of complex therapy is an urgent problem of stomatology. in our age of new technologies, every year the burden of unfavorable environmental factors on our health is increasing. first of all, the mechanisms of the protective reactions of our body are exposed to the negative influence. [2,17]. immunity is the ability of human and animal organisms to specifically react to the presence of some substance, usually foreign, in it. this reaction to foreign substances ensures the body's resistance, and therefore is extremely important for its survival. the reaction is based on the synthesis of special proteins, so-called antibodies, capable of entering into combination with foreign substances antigens. the science that studies the mechanisms of immunity is called immunology. [1,3]. the main elements of the body's immune system are white blood cells lymphocytes, existing in two forms: t-lymphocytes and b-lymphocytes. the antibodies produced by b-cells and entering the blood and other body fluids are referred to as factors of humoral immunity (from lat. humor liquid). the protection of the organism, carried out with the help of t-cells, is called cellular immunity, since it is based on the interaction of individual cells with antigens. t cells not only activate other cells by releasing lymphokines, but also attack antigens with the help of structures containing antibodies on the cell surface. damage or inadequacy of this protective system can manifest itself in the form of allergic reactions to substances that are usually harmless to the body [3,22]. congenital and acquired: congenital or hereditary. we are born with you with a certain set of antibodies, genetically laid down in us. for example, american indians are much less susceptible to syphilis than europeans. acquired or adaptive. it is formed under the influence of the external environment. that is, any infection leads to the development of antibodies in the body, which immediately become involved in the struggle when they meet again with this pathogen. vaccination is a particular case of acquired immunity. active and passive: active the production of antibodies as a result of external influences. post-infectious and post-vaccination immunity is always active. passive the introduction of antibodies from the outside. for example, serum containing donor antibodies. the composition of mother's milk includes antibodies that protect the baby, and this is also a passive immunity. specific and nonspecific: nonspecific a complex of mechanisms aimed at protecting against any external intrusion. example: saliva and tears contain antibacterial substances; interferon is present in the blood, which fights any viral particles that enter the body. specific antibodies against a very specific pathogen, some for influenza, others for plague, others for whooping cough, etc. [4,6,23]. it is a great misconception that the volume-1 issue-1 art of medicine international medical scientific journal 19 immune system fights only against microorganisms or viruses. it also protects us from cancer cells, which are defined as "alien" and are eliminated by specific and nonspecific mechanisms. therefore, one of the theories of the origin of cancer associates this disease with a malfunction in the immune system. there are several factors that negatively affect the immune system. stress and negative emotions (fear, anger, jealousy, anxiety, disappointment, regret, concern), generated by the unsuccessful attempts of many people to meet the requirements of life, cause disastrous experiences. they give rise not only to neuroses, but also to many other diseases. stress and negative emotions lead to an increase in blood levels of cortisol, a hormone that is a poison for immune cells [12,15]. the lack of sleep has the same effect on the immune blood cells. with a reduction in the time of sleep, the number of cells that defeat a viral infection is reduced by a third [7]. unfavorable ecology. the human environment is ubiquitously contaminated with various carcinogens (radioactive radiation, chemical and others). an unfavorable environment, constantly affecting the body, even in permissible concentrations, leads to "overwork" of internal organs and systems, including a decrease in immunity. so, the number of people suffering from various types of allergies at the beginning of the century was counted in units, and now more than 50% of the population suffer from it. bad habits further worsen the air environment. not only active, but also passive smoking contributes to the spread of infection. sun rays. ultraviolet rays, if exposed for too long, destroy the skin's immune cells. physical stress (work, sports), leading to overwork, reduces immunity. it is no coincidence that all peoples have at least one day of rest per week. a, if a person, in addition to five working days, still works on weekends (for example, at work), then the overload is inevitable. temperature load (overcooling, overheating), leading to overwork, also reduces immunity [4]. nutrition is, perhaps, the most important factor affecting the immune system. with a lack of food, it ceases to fulfill its protective function, the body easily, without a fight, becomes a victim of various infections. this circumstance should be borne in mind by those who often use a diet with limited calorie content. the defenders of our health immune cells need vitamins a, c, e and b, as well as trace elements such as selenium, zinc, iron. their deficiency slows down the division of these cells, reduces their activity. all the necessary substances are contained in ordinary food. self-disposal. alcohol with frequent use suppresses the activity of t-lymphocytes cells that play an important role in the destruction of pathogens. some medications (antibiotics, cortisone and pain relieversa) reduce the mobility of immune cells, their aggressiveness towards pathogens, and the ability to produce antibodies [6]. signs of weakened immunity the line between reduced and normal immune function is very thin and it is impossible to determine it independently. therefore, you should contact a doctor, an immunologist, an allergist, who will assign an immunological laboratory study to clarify the presence of immunodeficiency. indirect signs of its decline can be: frequent colds, viral infections more than 5 times a year (this is normal for preschoolers, not for older children and adults, see the difference between influenza and sars and how to treat a cold in a child). increased fatigue, general weakness, headaches, blue under the eyes, pallor of the skin. however, such symptoms can be present in case of blood diseases, therefore, in case of such symptoms, one should consult a doctor. drowsiness, insomnia (see how to fall asleep quickly). enlargement of the spleen, painless enlargement of the cervical and axillary lymph nodes. brittle nails, dull split hair (see causes of hair loss) art of medicine international medical scientific journal volume-1 issue-1 20 dryness and flaking of the skin (see treatment of cracked hands). allergy a sign of a failure in immunity (food allergies, allergies to the sun, cold allergies, allergic cough, allergic rhinitis). intestinal dysbiosis, which can be manifested by decreased appetite, flatulence, impaired stool, weight loss [7,18]. despite the fact that today in every pharmacy you can find a lot of drugs to increase immunity, natural medicine recipes and herbal medicines are still very popular. moreover, many scientific laboratories, which are engaged in the search for substances that strengthen the immune system, find inspiration in natural resources, isolating and studying the active components of plants. physiologically active substances inside plants, due to their complex, delicately balanced composition by nature itself, cause complex changes in the function of the immune system. these changes, including selective stimulation of the lagging links of the immunological response and the same selective suppression of overly active links, are called immunomodulation. accordingly, the plants used for this purpose are called immunomodulators. many known plants belong to the group of immunomodulators. significant advances in the treatment of hap in recent years are associated with the use of phytopreparations and alternative therapy, which significantly improve the survival rate and life prognosis of patients with cor pulmonale. (3) however, not all the effects of glycyrrhizic acid have been sufficiently studied. the plant world is rich in medicinal plants, among them you can distinguish naked licorice. licorice naked has been used for a long time for diseases of the bronchocellular system in the practice of oriental medicine. avicenna very often mentioned licorice in his "canons" as a means of "facilitating the work of the bronchi and lungs, removing all kinds of fluids." [7]. glycyrrhizic acid (ha) from the composition of naked licorice can have several beneficial effects at once. first of all, of course, we are talking about the presence of anti-inflammatory effects. in addition, drugs containing this substance have antiviral, antipruritic and immunostimulating effects. antiviral action is carried out mainly against the following pathogens: human papilloma virus and some others [2,6,8]. the antiviral effect is based on the ability of glycyrrhizic acid to interrupt the reactions of viral dna synthesis at various stages of this process. as a result, the assembly processes of viral particles cannot reach the stage of complete completion, and this means that the causative agent of the disease will be deprived of the opportunity to multiply. in addition, glycyrrhizic acid blocks the processes of interaction between the virus and the target cell, which greatly complicates the penetration of the pathogen, where it can have its harmful effect. in addition to the above, it should be noted the ability of glycyrrhizic acid to enhance the reactions responsible for the processes of biosynthesis of interferons. these substances significantly reduce the susceptibility of healthy cells to viral particles, which inhibits the spread of pathology. all of the above effects are manifested even with the use of drugs in non-toxic dosages, which means that the risk of developing unwanted consequences of antiviral therapy is minimized [1,2]. glycyrrhizic acid preparations are highly active against the pathogens mentioned above. unlike many other representatives of the group of antiviral drugs, addiction rarely develops to such drugs, even despite constant mutations of the causative agents of the disease. glycyrrhizic acid is a stimulant of nonspecific immunity. when exposed to this substance phagocytic reactions are activated, which are responsible for the capture and destruction of foreign agents [1,10]. on the basis of the extract of licorice glycyrrhizic acid, a number of expectorants have been created. however, due to the emergence of powerful expectorants, its use has volume-1 issue-1 art of medicine international medical scientific journal 21 receded into the background. celandine big, elecampane tall, field clover (red), representatives of the stonecrop family [2]. plants, called adaptogens, have an immunomodulatory effect. this category includes many representatives of the araliev family (eleutherococcus, aralia), chinese magnolia vine, rhodiola rosea, licorice and some others. with weakened immunity, stimulation is required. for this purpose, use means -immunostimulants, for example, aloe-agave [3]. with the advent of biologically active food additives on the russian market, immunomodulatory plants have become known that grow in south america, southeast asia and other regions of the earth. examples: gotu kola (gotu cola), cat's claw wiltsazora (uncaria tormentosa). immunomodulating plants can only increase humoral immunity [24]. preparations for enhancing immunity medicines that have a stimulating effect on immunity can be classified both by origin and by the mechanism of influence. herbal preparations o echinacea this is the name of a whole clan from the astrov family. this genus contains 10 species, of which echinacea purpurea is the most popular as a medicinal raw material. for medicinal purposes, all parts of the plant are used: stems, leaves, roots, flower baskets. echinacea contains a large amount of vitamins and essential oils, has a direct antimicrobial and antiviral effect, and also stimulates cellular immunity (increases the number of leukocytes in the blood). the most popular drug containing echinacea is immunal [12]. echinacea purpurea is used: for infectious and septic diseases, outwardly for carbuncles, abscesses, infected wounds, burns of i-iii degree (as an anesthetic) and severe bedsores; echinacea preparations are used with a prophylactic purpose at the first signs of a cold, with prolonged use of antibiotics, recovery of persons who have undergone exposure to radiation or living in areas unfavorable for radiation levels; the antiinflammatory effect of biologically active substances of echinacea is combined with its immunomodulatory properties and is used in pulmonary practice: regular prophylactic intake for 40-50 days allows you to almost 2 times reduce the likelihood of respiratory tract infection, and in case of infection, the disease occurs in a milder form; echinacea preparations are used in allergological practice, which is determined by their immunomodulatory, anti-inflammatory and antioxidant properties; echinacea preparations have a therapeutic effect in various pathological conditions by increasing the natural protective forces of the body. as a result of pharmacological studies, the stimulating effect of echinacea on the immune system has been shown. this effect is manifested not only in adults, but also in children with an unsettled immune system, as well as in elderly people, in whom the functions of this system are reduced due to general aging of the body [29]. eleutherococcus is a genus of thorny shrubs and trees from the araliev family, which includes 30 species. its roots and rhizomes are considered medicinal raw materials. it is used as an extract. contains a mass of useful substances with anti-stress action. it also contains caffeine, so it invigorates and increases performance. it was included in the composition of the drink under the name "baikal", which was also called "soviet cocacola" [13]. ginseng whole volumes have been written about its beneficial properties, so i will not repeat myself, i will only point out that the composition of this root is similar art of medicine international medical scientific journal volume-1 issue-1 22 to the composition of eleutherococcus, therefore, almost everything that is written on ginseng is fair for eleutherococcus. and do not forget about caffeine, which can cause an overdose, addiction and can be dangerous in case of hypertension and heart disease [7,14]. chinese schisandra is a perennial flowering plant. fruits are used for food, tea can be brewed from the leaves. contains a huge amount of vitamin c, and also has a powerful psychostimulating effect, increases performance and resistance to stress, in case of an overdose, causes insomnia. also, as with ginseng, it is necessary to take "hypertensive patients" and "cores" with caution. bacterial preparations a group of drugs containing components of the bacterial cell. bacterial proteins entering the body do not cause a disease, but an immune response to a given microorganism, therefore, when it encounters a real microbe, the immune system will already be "armed" with antibodies. the action of drugs from this group is similar to vaccines [6,25]. ribomunil, imudon, irs-19, lycopid, etc. contains the components of bacteria most common in infections of the upper respiratory tract and ent organs. uro-vax lysate of escherichia coli bacteria, is used for chronic urinary tract infections caused by this microbe. interferon preparations are drugs with antiviral activity, divided into two large subgroups. human interferon. in fact, there are about 20 interferons in our body, divided into 3 subgroups (alpha, beta and gamma). pharmaceutical companies can produce them both separately and in the form of mixed mixtures: laferon, viferon, velferon, gripferon, etc. produced from donated blood or using genetic engineering. stimulants of endogenous interferon production a group of drugs in the fight against viral infections, especially influenza: anaferon, arbidol, amiksin, kagocel, etc. [5]. nucleic acid preparations are stimulators of cellular and, to a lesser extent, humoral immunity, the mechanism of action of which has not been fully understood. they are mainly used for bacterial infections (including tuberculosis), to enhance the effectiveness of vaccines: sodium nucleinate, derinat. also, these drugs have a pronounced wound healing effect, which makes them very useful for purulent wounds and extensive burns. some drugs of this group are used as stimulants of interferon production in viral infections ridostin [7]. thymus preparations or other name immunoregulatory peptides: thymalin, thymosin, thymactide, thymogen, etc. the very old group of immunomodulators, known since the 1970s. they are extracts of the thymus gland of animals. they stimulate individual links of immunity, but are effective only in immunodeficiency states caused mainly by chronic infections: tuberculosis, trophic ulcers, etc. [22, 30]. biogenic stimulants. this is a group of immunostimulants, the source for which are animals or plant tissues: aloe extract, actovegin, fibs, humisol, biosed. the mechanism of action has not been fully understood, therefore, medical literature, which has not been abused by pharmaceutical cartels, is full of skepticism about the effectiveness of this group of drugs [8]. a fairly new drug polyoxidonium (1997), which is now actively used, in addition to immunostimulating, antioxidant, detoxifying and membrane stabilizing effects, has the properties of a hepatoprotector (review of tablets for the liver) hepatoprotectors. to increase its bioavailability, a drug has been created longidase (a combination of lidase and polyoxidonium) [9]. vitamins. they normalize metabolic processes in the body, including restoring the functioning of the immune system. but it is best to use natural products containing vitamins fruits, vegetables, cereals, nuts, sea fish, etc. vitamins). moreover, studies by volume-1 issue-1 art of medicine international medical scientific journal 23 doctors at the university of washington led to terrible results. for many years they have studied the evolution of the state of health of 78,000 people 50-76 years old and came to a startling conclusion. the increased use of vitamins c and e at the same time is extremely dangerous, since it leads to a significant increase in the risk of developing lung cancer. finnish scientists have come to the conclusion that the combination of e and c vitamins provokes the onset of tuberculosis. you should be aware that there are many multivitamin complexes on the russian market, the content of vitamin e in which is very high, moreover, often vitamin complexes cause allergic reactions. therefore, their use should be treated with caution, as with any drugs, drink vitamins only in a strict course of indications and appointment of a doctor, give preference to 1-2 component preparations (it is better to make sure that there is a lack of one or another vitamins in blood) [4.25]. transfer-factor. in the early 50s of the last century, special proteins were discovered that transmit information from one immune cell to another, providing a link between cellular and humoral immunity. the combination of these proteins was called the transfer factor. in the 80s of the 20th century, life research was able to develop a technology for extracting the transfer factor from cow colostrum and chicken yolks. it was found that the transfer factors of cows are identical to human ones, as a result of which the idea was born to stimulate the production of antibodies in our body with their help. for more than 30 years life research has been selling the transfer factor as a baa all over the world. the manufacturer claims that their product has no contraindications and side effects, so it can be used even for pregnant and nursing infants. doubts are raised by the fact that for all these years life research has not been able to register the transfer factor as a drug. it is believed that they do not have sufficiently convincing data on the clinical efficacy of the manufactured product [17]. medicines and preparations. 'immunal' is produced in slovenia; (immunal) 100 ml of a 20% solution of ethanol contains 80 ml of juice of flowering echinacea purpurea in 50 ml bottles. it is used to increase nonspecific immunity in case of recurrent colds, to prevent colds and flu, to prevent immunodeficiency with prolonged antibiotic therapy. drink immun-guard is a source of sambunigrin glycoside, echinacoside and vitamin c. it has anti pyretic, diaphoretic, diuretic, anti-inflammatory, expectorant, and sedative effect. it is used for colds, flu, bronchitis, pneumonia, dry cough, edema [7]. our domestic medicine produces a natural immunostimulant called immuhelp. immuhelp has a complex effect on the immune system and has an original combination of herbal components. one capsule of immuhelp contains: golden root, wild rose, valerian, marsh air, scarlet, elecampane, anise, carnation, mint, oregano. the drug is intended to maintain the function of the immune system and restore normal physiological functions of the body in asthenic conditions and also after prolonged bed rest. as an immunostimulating agent, immuhelp is prescribed: children 1 capsule 3 times a day 510 minutes before meals, adults 1-2 capsules 3 times a day 5-10 minutes before meals. the course of treatment is 15 days. in scientific research [3,4,5] examples are given: the prescription of antibiotics is inadequate: the use of two or more antibiotics in the absence of a pronounced clinic of inflammation. surgical treatment was carried out in 70% of cases: plastic fistula (7.7%); radical sinusitis (83%); cystohaymorotomy (8.2%). among the operated patients with acute sinusitis made up 1.8% of all examined and about 44% in this group. with achog, 31% of all patients and 57% with a diagnosis of achd were operated on. conservative treatment was carried out in 35 (2.4%) patients with chronic odontogenic sinusitis, 12 (0.8%) patients with a foreign body in the maxillary sinus. thus, the problem of prevention, diagnosis (including differential) and treatment of odontogenic sinusitis is an urgent task of dentistry. among the causes of art of medicine international medical scientific journal volume-1 issue-1 24 the development of the disease, a significant part is made up of pathological processes, the development of which was facilitated by inadequate medical tactics in the treatment of chronic inflammatory processes in the upper jaw molars. references. 1.aäî a.ä. "îáùaÿ aëëåðãîëîãèÿ. ðóêîâîäñòâî äëÿ âða÷åé".ìîñêâa, "ìåäèöèía", 2008. 2.áaðûøíèêîâ a.þ. "èììóíîëîãè÷åñêèå ïðîáëåìû aïîïòîça". ìîñêâa, ýäèòîðèaë óðññ, 2002. 3.áîãàòîâ à. è. àíàëèç îøèáîê è îñëîæíåíèé ïðè õèðóðãè÷åñêîì ëå÷åíèè áîëüíûõ ñ îäîíòîãåííûìè âåðõíå÷åëþñòíûìè ñèíóñèòàìè // àêòóàëüíûå âîïðîñû ñîâðåìåííîé ñòîìàòîëîãèè. ñàìàðà, 2000. ñ.102-103. 4.âèøíÿêîâ â. â. àíàòîìè÷åñêèå âàðèàíòû ñòðîåíèÿ ïîëîñòè íîñà è îêîëîíîñîâûõ ïàçóõ ïðè êîìïüþòåðíîé òîìîãðàôèè / â. â. âèøíÿêîâ // âåñòí. îòîðèíîëàðèíãîëîãèè. 2004. ¹1. ñ. 65-67. 5.åìåëüÿíåíêî ë. ì. ýôôåêòèâíîñòü ëå÷åíèÿ ãíîéíîãî ãàéìîðèòà ëàçåðîôîðåçîì ñ èçîòèîðáàìèíîì / ë. ì. åìåëüÿíåíêî, ñ. ñ. öåëóéêî, î. è. êîíîïëåâ. òð. 16 ñúåçäà îòîëàðèíãîëîãîâ ðô. ñ.-ïåòåðáóðã, 2001. ñ.56-57. 6.êëaóñ äæ. "ëèìôîöèòû. ìåòîäû". ìîñêâa, ìèð, 2000. 7.êîëëèíç ó.ï. "íîâûå ìåòîäû èììóíîaíaëèça". ìîñêâa, ìèð, 1991. 8.ëåáåäåâ ê.a. "èììóíîëîãèÿ â êëèíè÷åñêîé ïðaêòèêå". 2006. 9.ëåôêîâèòñ è. "ìåòîäû èññëåäîâaíèÿ â èììóíîëîãèè". ìîñêâa, ìèð, 2001. 10.ëîïàòèí à. ñ. õèðóðãè÷åñêîå ëå÷åíèå îäîíòîãåííîãî âåðõíå÷åëþñòíîãî ñèíóñèòà / à. ñ. ëîïàòèí, ñ. ï. ñûñîëÿòèí, ï. ã. ñûñîëÿòèí // ðîñ.ñòîìàòîë.æóðíàë, 2001. ¹3. ñ.24-28. 11.ìåäóíèöûí í.â. "îñíîâû èììóíîïðîôèëaêòèêè è èììóíîòåðaïèè èíôåêöèîííûõ áîëåçíåé". ìîñêâa, ãýîòað-ìåäèa, 2005. 12.ìåøêîâa ð.ß "ðóêîâîäñòâî ïî èììóíîïðîôèëaêòèêå äëÿ âða÷åé".ñìîëåíñê, 1998. 13.ìèíååâa í.â. "ãðóïïû êðîâè ÷åëîâåêa. îñíîâû èììóíîãåìaòîëîãèè". ñaíêòïåòåðáóðã, 2004. 14.íañîíîâ å. ë. "aíòèôîñôîëèïèäíûé ñèíäðîì". ìîñêâa, ëèòòåðða, 2004. 15.îäîíòîãåííûå ãàéìîðèòû / à. à. òèìîôååâ, ã. ï. áåðíàäñêàÿ, ë. ô. êîð÷àê, ñ.ï.êîëîìèåö êèåâ: ×åðâîíà ðóòà-òóðñ. 2002. ñ.48-50 16.ïîêðîâñêèé â.â. "êëèíè÷åñêaÿ äèaãíîñòèêa è ëå÷åíèå âè×-èíôåêöèè". ìîñêâa, ãîó âóíìö ìç ðô, 2001. 17.ñèïêèí à. ì. äèàãíîñòèêà, ëå÷åíèå è ðåàáèëèòàöèÿ áîëüíûõ îäîíòîãåííûìè âåðõíå÷åëþñòíûìè ñèíóñèòàìè, ñ ïðèìåíåíèåì ýíäîñêîïè÷åñêîé òåõíèêè: àâòîðåô.äèñ.íà çäîáóòòÿ íàóê.ñòóïåíÿ ê.ìåä.í.: ñïåö.14.00.21-ñòîìàòîëîãèÿ / à. ì. ñèïêèí. ìîñêâà, 2005. 20 ñ. 18.øàðãîðîäñêèé à. ã. âîñïàëèòåëüíûå çàáîëåâàíèÿ òêàíåé ÷åëþñòíî-ëèöåâîé îáëàñòè / à. ã. øàðãîðîäñêèé. ì., 2001. ñ.86-98. 19. øóëüìàí ô. è. èíîðîäíûå òåëà âåðõíå÷åëþñòíûõ ïàçóõ. òàêòèêà âðà÷à / â. à. êîçëîâ, ô. è. øóëüìàí. // òðóäû vii âñåðîññèéñêîãî ñúåçäà ñòîìàòîëîãîâ, 10 13 ñåíòÿáðÿ 2001 ã. ìîñêâà. 2001. ñ.98-100. 1 volume 1, ¹4 art of medicine international medical scientific journal 2 art of medicine international medical scientific journal volume 1, ¹4 december 2021 3 volume 1, ¹4 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen art of medicine international medical scientific journal 22 safety of insulin degludec/insulin aspart in patients with diabetes mellitus over a period of 1 year during routine clinical care in india: smart (study of management of diabetes with ryzodeg™ treatment) debasis basu ,rekonstruktive und ästhetische chirurgie, handchirurgie, essen, germany harish kumar jothydev’s diabetes research centre, trivandrum 695032, india abstract.this post-authorization study was conducted to evaluate the safety of insulin degludec/insulin aspart (idegasp) in adult patients with diabetes mellitus (dm) during routine clinical care under a real-world setting in india. eligible patients received idegasp for a minimum of 12 months during routine clinical management. data were collected at 0, 3, 6, and 12 months. in total, 1029 adult patients with dm were included; 65.2% (n = 671) were men; mean age was 55.0 ± 12.2 years, and the mean duration of diabetes mellitus was 10.8 ± 7.4 years. thirty adverse events were reported in 23 patients (2.2%) during the follow-up: two adverse events in two patients were serious with fatal outcomes, which were unrelated to idegasp use. at baseline, there were 176 confirmed hypoglycemic events in 67 (6.7%) patients while they were on their previous treatment options. at 12 months of treatment with idegasp, 11 confirmed hypoglycemic events were reported in 11 (1.1%) patients since the previous visit; there were no reported episodes of severe hypoglycemia. mean glycosylated hemoglobin value reduced from 9.5% ± 1.8% at baseline to 7.7% ± 1.1% at 12 months. this study showed the safety of idegasp in patients with diabetes mellitus over a period of 1 year during routine clinical care. keywords: diabetes mellitus; glycemic control; idegasp; india; insulin therapy; safety 1. introduction the burden of diabetes mellitus (dm) is on the rise globally; at 77 million, india ranks second for the number of people with dm in the age group of 20–79 years, and by 2045, this number is estimated to rise to 134.2 million [1]. insulin is the mainstay of therapy against type 1 dm (t1dm) and is also necessary for people with type 2 dm (t2dm) under certain circumstances at the diagnosis of t2dm, and particularly following the inability of oral anti-diabetic drugs (oads) to maintain glycemic control [2,3]. the joint rssdi-esi (research society for the study of diabetes in india—endocrine society of india) clinical practice recommendations 2020 suggest that insulin initiation with once-daily co-formulation/premix or basal insulin should be considered if the glycosylated hemoglobin (hba1c) value is not on target despite three oads [4]. basal insulins primarily control fasting plasma glucose (fpg), and overall hba1c values might still exceed target value owing to uncontrolled post-prandial plasma glucose (ppg) excursions [5,6]. ppg excursion is of concern among people with dm in india, owing to relatively high dietary carbohydrate intake that can lead to relatively higher contribution of ppg to hyperglycemia [7,8]. post-prandial hyperglycemia can be corrected by using prandial insulins [9]. however, introduction of an additional injection may reduce patient compliance [10]. idegasp is a coformulation of 70% insulin degludec and 30% insulin aspart, offering total control of fasting and postprandial glucose levels [11]. phase 2 and 3 studies have demonstrated safety and efficacy of the idegasp compared with basal, basal-plus, basal-bolus, and analog premix insulin regimens [11,12,13,14,15,16]. this post-marketing surveillance (pms) study of idegasp (ryzodeg™), titled “study of management of diabetes with ryzodeg™ treatment (smart)”, was conducted as part of a regulatory requirement. it aimed at assessing the safety of idegasp during routine clinical care under a real-world setting in indi 23 volume 1, ¹4 2. materials and methods 2.1. participants men and women with dm aged >18 years who were scheduled to start treatment with idegasp based on the clinical judgement of the investigator during routine care were included in this study. patients previously on idegasp therapy or those participating in another study were excluded. patients with mental incapacity, unwillingness to participate, or language barriers precluding adequate understanding or cooperation were excluded. women who were pregnant, were breast-feeding, or had the intention of becoming pregnant within 12 months were also excluded. 2.2. study design this multicenter, prospective, single-arm, observational, pms study (nct02230618; ctri/2015/12/006442) was conducted at 40 sites across india between november 2015 and june 2017. it was conducted as per the declaration of helsinki and international conference on harmonizationgood clinical practice guidelines. after obtaining approval from institutional review board/independent ethics committee of each participating center, the study was conducted in compliance with the protocol. all enrolled patients provided written informed consent. at baseline (visit 1), data on demographics, medical history (dm history, prior dm treatment, history of hypoglycemia on previous treatment, and reason to start idegasp), concomitant medications, height, and weight were recorded. idegasp, marketed as ryzodeg™ flextouch® prefilled pen injector (100 units/ml) and available in the market by prescription, was prescribed. the decision to initiate, titrate, and intensify with idegasp, its dose, its timings, and frequency were based on the investigator’s discretion in line with approved indian label. safety data, including the hypoglycemic episodes since the last visit, were collected at 3 months ± 2 weeks (visit 2), 6 months ± 2 weeks (visit 3), and finally at 12 months ± 2 weeks (visit 4). hypoglycemic events while on previous treatment were recorded based on patient recall of confirmed (blood glucose < 56 mg/dl) or severe hypoglycemic (requiring third-party assistance) events in the immediate 4-week period before starting idegasp. because this was a non-interventional study, meticulously structured self-monitoring of blood glucose was not mandatory, and hypoglycemic events during the 12-month treatment with idegasp were recorded based on patient recall of confirmed or severe hypoglycemic events during follow-up visits. 2.3. safety assessments during the 1-year study period, patients reported safety incidences were evaluated and categorized by physicians as follows: adverse events (aes), serious adverse events (saes), adverse drug reactions (adrs), serious adrs, and confirmed or severe hypoglycemia. additionally, causality (probable, possible, or unlikely), severity (mild, moderate, or severe), and outcome (recovered/resolved, recovering/resolving, recovered/resolved with sequelae, not recovered/not resolved, fatal, or unknown) of aes/adrs were recorded. 2.4. assessment of the change in hba1c, fpg, and ppg endpoints included mean change in hba1c, fpg, and ppg values from baseline at 3, 6, and 12 months in the overall population. the additional analysis included mean change in hba1c, fpg, and ppg values from baseline to 3, 6, and 12 months, stratified by previous treatment (oads or insulin). given the non-interventional nature of this study, the most recent fasting and post-prandial glucose value was captured for assessment at different time points which could either be a lab or glucometerbased measurement. 2.5. statistical analyses assuming a 20% dropout rate, a sample size of 1000 patients was determined to provide a power of 80% to detect at least one ae that occurs with an incidence of 2 in 1000 patients, or approximately 6 events with an incidence of 1 in 100 patients. the descriptive statistics for continuous variables were art of medicine international medical scientific journal 24 statistics were presented using counts and percentages. all the patients who received at least one dose of idegasp during the study were included in the safety analysis set (sas), and patients who had at least one post-baseline measurement available for hba1c, fpg, or confirmed hypoglycemic event were included in the efficacy analysis set (eas). a paired two-sided t-test at a 5% significance level was used to evaluate the changes in hba1c, fpg, ppg, and confirmed hypoglycemic events by the visit. statistical analyses were performed using statistical analysis software (version 9.4). 3. results the mean (±sd) age of the study participants was 55.0 ± 12.2 years, and majority of them were male (n = 671, 65.2%). the mean duration of dm was 10.8 ± 7.4 years. based on eas, before visit 1, 730 patients (72.8%) were on oad(s) and 273 (27.2%) were on insulin therapy ± oad(s). along with other concomitant drugs, oad(s) in use at baseline included metformin (n = 766, 74.4%), sulphonylureas (n = 599, 58.2%), alpha-glucosidase inhibitors (n = 203, 19.7%), meglitinides (n = 2, 0.2%), thiazolidinediones (n = 86, 8.4%), dipeptidyl peptidase-4 (dpp-4) inhibitors (n = 363, 35.3%), and sodium-glucose co-transporter-2 (sglt-2) inhibitors (n = 16, 1.6%) apart from glucagon-like peptide-1 receptor agonists (glp-1 ras) (n = 5, 0.5%). treatment with idegasp and its continuation over a period of 12 months resulted in a change in use of oad(s) such that at the last visit, oad(s) in use were metformin (n = 684, 66.5%), sulphonylureas (n = 456, 44.3%), alpha-glucosidase inhibitors (n = 159, 15.5%), meglitinides (n = 6, 0.6%), thiazolidinediones (n = 58, 5.6%), ddp-4 inhibitors (n = 283, 27.5%), and sglt-2 inhibitors (n = 50, 4.9%) apart from glp-1 ras (n = 5, 0.5%). other concomitant medications in use reported in ≥5% of patients are mentioned in table s1. in terms of insulin therapy, at baseline, 124 patients (12.1%) were on basal insulins, 135 (13.1%) on premix insulins, and 95 (9.2%) on bolus insulins with or without basal/premix insulins before being enrolled in this study. subsequently, 158 patients (15.4%) at visit 2 (at 3 months), 160 patients (15.5%) at visit 3 (at 6 months), and 162 patients (15.7%) at visit 4 (at 12 months) were on bolus insulin along with idegasp. 4. discussion idegasp (ryzodeg™) received its first regulatory approval by japanese ministry of health in december 2012 [17]. united states food and drug administration approved its use on 25 september 2015 [18]. it is available in the indian market since january 2015 [19]. idegasp provides total (fpg + ppg) glycemic control with simplicity and convenience [11,16,20]. the basal insulin component in idegasp, i.e., insulin degludec has a long half-life and achieves a steady state within 2–3 days [21,22]. the efficacy and safety of idegasp had already been established based on the data obtained from earlier phase 2 and 3 studies [11,12,13,14,15]. however, to ensure its safety in the indian population, central drugs standard control organization (cdsco) recommended a local post-marketing safety study. hence, this multicenter, prospective, single-arm, observational study was conducted in patients who were scheduled to start treatment with idegasp as a part of standard routine clinical care. a oneyear study duration was considered sufficient to determine any adr associated with idegasp use. 5. conclusions this prospective, non-interventional study of idegasp confirms its long-term safety and tolerability with good improvements in glycemic control when used under routine clinical practice conditions. 25 volume 1, ¹4 references 1.idf (international diabetes federation). idf diabetes atlas, 9th ed.; idf: brussels, belgium, 2019; available online: https://www.idf.org/e-library/epidemiology-research/diabetes-atlas/159-idfdiabetes-atlas-ninth-edition-2019.html (accessed on 8 july 2021). 2.american diabetes association: standards of medical care in diabetes—2021. diabetes care 2021, 44, s1–s232. available online: https://care.diabetesjournals.org/content/44/supplement_1 (accessed on 8 july 2021). 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[google scholar] [crossref] art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5552262 164 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5552262 165 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5552262 166 frequency of observation of anxiety and depression in the diagnosis of primary headaches akhmedova dilafruz bahodirovna bukhara state medical institute republic of uzbekistan abstract. nowadays, the international headache society has identified over 160 different headaches, categorizing them into primary and secondary headaches. primary headaches are independent entities that include migraines, cluster headaches, and tension headaches. in some patients, migraine is combined with tension headache keywords. headaches, frequency, zung depression. headaches are the most common complaint of patients seeking medical care and are therefore of interest to many researchers. it is noted in many foreign and russian medical publications (naprienko m.v., 2019; osipova v.v., tabeeva g.r., 2017; sergeev a.v., 2018; sadokha k.a., 2014; belimova l n., balyazin v.a., 2016; maksimova m. yu., khokhlova t. yu., piradov m.a., 2016; sanoeva m.yu., 2020). nowadays, the international headache society has identified over 160 different headaches, categorizing them into primary and secondary headaches. primary headaches are independent entities that include migraines, cluster headaches, and tension headaches. in some patients, migraine is combined with tension headache. these are patients who have suffered from migraines for many years and are accompanied by episodic tension headaches as a result of mental stress or prolonged stay in the same position. because patients know the difference between the two headaches, they can tell the difference between a migraine attack and a stressful headache. actuality of the topic: 85% of the population experience periodic headaches, 40% of them feel a decrease in social and labor activity, and this requires qualified medical care (naprienko m.v., 2019). the presence of tension headaches in a third of the population aged 30–39 years has been identified in various studies (m. yu. maksimova, 2016). according to the world health organization, three quarters of art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5552262 167 the population aged 18 to 65 experience a headache attack at least once in the last year, while chronic stress headaches occur in 2-3% of the population (belimova l.n., 2016). episodic stress headaches are not a serious medical or social problem, while chronic stress headaches are accompanied by various comorbid disorders (depression, sleep disturbances, somatoform disorders) that significantly impair the patient's daily life and quality of life. brings pain to the level of a complex socio-medical problem (sergeev a.v., 2018). the goal of the study was to examine the cognitive changes observed in stress headaches, especially levels of anxiety and depression. research method and materials: the prevalence of headaches in patients was studied on the basis of a questionnaire. the study involved a total of 117 patients who received inpatient treatment with a diagnosis of tension headache in the clinics "azizmed shifo" and "carmen" in bukhara region. the mean age of the patients was 38.53 ± 10.36. of those surveyed, 87 were female (74.5%) and 30 (25.64%) were male patients. all patients underwent clinical anamnestic and neurological examination. anxiety and depression in patients ch. d. spilberger, yu. l. xanin anxiety level detection scale concentration v. zung was assessed using a depression detection test. the results were statistically analyzed. the student criterion was used in the statistical analysis of the materials. results: out of a total of 117 patients monitored, 3 patients (2%) were diagnosed with asthenoneurotic syndrome, three patients (2%) were diagnosed with angiospastic migraine, and patients were classified as having chronic headache with tension. anxiety rate in patients ch. d. spilberger, yu. l. the results obtained when determined on the hanin scale are as follows. table.1. anxiety level in patients and their evaluation by the help of the scale spilberger ch. d. and hanin yu. l. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5552262 168 anxiety levels abs % p anxiety in low level 19 16.24* 0.05 anxiety in middle level 17 14.53 0.05 anxiety in high level 23 19.65** 0.01 as it can be seen from the table data that there is a significant anxiety among patients against the background of chronic headache. in patients, high levels of anxiety were observed in large percentages (p≥0.01). low anxiety was observed in 16.24% of patients (p≥0.05). also, the degree of depression in all patients was assessed by using v. zung depression detection test. the results are as follows: table 2. degree of depression was assessed by using zung depression detection test depression rates abs % no depression 31 26.50 mild depression of situational or neurotic genesis 19 16.23 subdepressive condition or masked depression 40 34.18 real depression 34 29.05 analyzing the results of the experiment, showed that 26.5% of patients did not have depression, 16.23% of patients had mild depression of situational or neurotic art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5552262 169 genesis, subdepressive condition, masked depression was observed in 34.18% of patients, true depression was observed in 29% of patients. conclusion: chronic stress headaches are a long-lasting pathological condition that affects patients ’behavioral and cognitive spheres. chronic observation of headaches in patients leads to an increase in the level of anxiety, long-lasting chronic headaches affect the lifestyle of patients and also increase the level of depression in the patient. as well as, proper organization of the agenda in the treatment of chronic headaches, adherence to a healthy lifestyle will have a positive impact on the treatment process and increase the effectiveness of treatment. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 156 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 157 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 158 genealogical characteristics of patients with ckd at the level of primary health care daminova k.m., sabirov m.a. tashkent pediatric medical institute, republican specialized scientific and practical medical center for nephrology and kidney transplantation, uzbekistan, tashkent abstract: the main task of the genealogical method is to study the nature of the distribution of hereditary traits in the family. genealogical analysis of pedigrees serves as the basis for medical and genetic counseling, that is, resolving the issue of the risk of having patients in a family burdened with hereditary diseases. keywords: genealogical analysis, transplantation, ckd, patients introduction. the most important method of preventing severe genetically determined diseases is medical and genetic counseling. currently, clinical genetics uses various methods of obtaining information to identify patterns inherent in hereditary diseases. in clinical therapy, genealogical, mathematical-statistical and other methods of genetic analysis are often used. the main task of the genealogical method is to study the nature of the distribution of hereditary traits in the family. genealogical analysis of pedigrees serves as the basis for medical and genetic counseling, that is, resolving the issue of the risk of having patients in a family burdened with hereditary diseases. when compiling pedigrees, special symbols are used. first of all, the so-called "legend" is drawn up, the initial collection of the family history is carried out. after drawing up the pedigree, a genealogical analysis is carried out. early diagnosis of chronic kidney disease (ckd) can help to reduce the progression of the disease, improve the clinical condition of patients and improve the prognosis of the course of the disease, reduce the number of patients with end-stage disease, reduce disability rates and reduce mortality. based on the foregoing, the goal art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 159 of our study was to study the role of genealogical analysis in patients with ckd as a method of prevention and early diagnosis of progression at the level of primary health care. materials and research methods. there were 217 ckd patients under observation in the primary health care unit, the average age of which was 46.17 ± 0.63 years, mainly of uzbek nationality. the control group consisted of 20 healthy people of uzbek nationality of the same age without signs of ckd. after drawing up the legend of 217 families, a pedigree was compiled and a genealogical analysis was carried out. in order to identify the burden of ckd, the data obtained were compared with the results of the analysis of the pedigrees of individuals (n = 20) of a healthy population. the genealogical method was used to examine 893 relatives of the 1st degree of relationship (parents, siblings) of patients with ckd for the presence of renal pathology. a detailed pedigree was compiled, which included information about diseases in 2-3 generations of the family. genetic material was collected from both parental lines by cross-examination of both parents, sometimes grandparents. a total of 1761 people were analyzed in the model population. results and its discussion. the data obtained were compared with the generalized family response of 20 practically healthy people, in the model population of which 172 people were analyzed, of which the incidence of renal pathology was 2.13%. comparative analysis of the generalized family portrait of ckd patients with a generalized family portrait of a population of practically healthy people revealed a more frequent lesion of renal pathology in relatives with ckd (11.07 %). in families of probands, renal pathology in generations in relation to the total number of patients with each concentration is iii 7.49%; ii 11.06%; i 17.43%. the burden in the population of practically healthy people was observed significantly less: iii 0%; ii 0.15%; i0%. it turned out that relatives of the 1st degree of kinship 130 (14.56 ± 2.50%) suffer from renal pathology more often, which in relation to the total number of art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 160 patients with this concentration is 7.38%. at the same time, the following distribution was observed among groups: in group 1 (n = 224) in 27 people, which amounted to 12.05 ± 0.69%, of which 16 men (59.26 ± 0.57%), 11 women (40.74 ± 0.41%); group 2 (n = 219) 28 (12.78 ± 0.75%), of which 19 men (67.86 ± 0.68%), 9 women (32.14 ± 0.38%); group 3 (n = 239) 36 (15.06 ± 0.81%), of which 23 men (63.89 ± 0.62%), 13 women (36.11 ± 0.50%); group 4 (n = 211) 39 (18.48 ± 0.76%), of which 22 men (54.41 ± 0.64%), 17 women (43.59 ± 0.51%). hereditary burden of renal pathology was observed more often on the father's side in 46 (10.60 ± 1.50%) than on the mother's side 19 (4.38 ± 1.04%) (table 1). among the 1st degree relatives of grandmothers (n = 434) with renal pathology, there were 29 (6.68 ± 1.22%) of them on the father's side 18 (62.07±0.93%), on the mother's side 11 (37,93 ± 0.73%) . table 1. the incidence of ckd in the pedigrees of ckd patients. study group prevalence of renal disease in relatives of patients all relatives n = 1761 total 195(11,07±3,14%) men 116(59,48±2,46%) women 79(40,51±1,91%) mothers n = 217 20(9,22±0,98%) fathers n = 217 28(12,90±1.13%) grannies n = 434 total 29(6,68±1,22%) from the mother's side 11(37,93±0,73%) from the father's side 18(62,07±0,94%) grandfathers n = 434 total 36(8,29±1,29%) from the mother's side 8(22,22±0,62%) from the father's side 29(77,78±1,13%) sibs n = 459 total 80(17,43±1,98%) men 51(63,75±1,67) women 29(36,25±1,15) relatives of the 1st degree of kinship n = 893 total 130(14,56±2,50%) men 80(61,54±2,08%) women 50(38,46±1,49%) let us consider their distribution into groups: in group 1 (n = 54) in 2 people, which amounted to 1.85 ± 0.19%, of them on the father's side 1 (50 ± 0.14%), on the art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 161 mother's side 1 (50 ± 0.14%); group 2 (n = 105) 5 (4.71 ± 0.30%), of which on the father's side 3 (60 ± 0.23%), on the mother's side 2 (40 ± 0.19%); group 3 (n = 116) 8 (6.90 ± 0.35%), of which 6 on the father's side (75 ± 0.31%), on the mother's side 2 (25 ± 0.18%); group 4 (n = 104) 14 (13.46 ± 0.53%), of which 8 on the father's side (57.14 ± 0.36%), on the mother's side 6 (42.86 ± 0.32 %). there were 36 grandfathers (n = 434) with renal pathology (8.29 ± 1.29%), 28 of them on the father's side (77.78 ± 1.13%), on the mother's side 8 (22.22 ± 0.62 %). let us consider their distribution into groups: in group 1 (n = 54) in 4 people, which amounted to 3.70 ± 0.26%, of which all were not observed on the part of the father on the part of the mother; group 2 (n = 105) 7 (6.60 ± 0.34%), of which 6 on the father's side (85.71 ± 0.32%), on the mother's side 1 (14.29 ± 0.14 %); group 3 (n = 116) 10 (8.62 ± 0.38%), of which 8 on the father's side (80 ± 0.35%), on the mother's side 2 (20 ± 0.18%); group 4 (n = 104) 15 (14.42 ± 0.50%), of which 10 on the father's side (66.67 ± 0.40%), on the mother's side 5 (33.33 ± 0.30 %). in a genealogical study, 459 siblings were studied, of which renal pathology was noted in 80, which amounted to 17.49 ± 1.98%. at the same time, 51 of them were men (63.75 ± 1.67%), and 29 women (36.25 ± 1.15%). when examined by groups, the following picture was observed: in group 1 (n = 116) in 19 people, which amounted to 16.38 ± 0.59%, of which 11 men (57.89 ± 0.53%), women 8 (42.11 ± 0.36%); group 2 (n = 113) 20 (17.70 ± 0.66%), of which 14 men (70 ± 0.56%), 6 women (30 ± 0.32%); group 3 (n = 123) 20 (16.26 ± 0.58%), of which 14 men (70 ± 0.47%), 6 women (30 ± 0.31%); group 4, (n = 107) 21 (19.63 ± 0.60%), including 12 men (57.15 ± 0.51%), women 9 (42.85 ± 0.43%). for illustration, we give an example: pedigree of the patient l.f., 53 years old; diagnosis: basic ischemic heart disease voltage angina, fc1. gd 2, ag 2, h 3; competed chronic glomerulonephritis, mixed form, diabet mellitinus 2 type, severe current, in the decompensation stage; complication ckd 3ast. diabetic encephalopathy, diabetic nephropathy. (fig.1) from the pedigree it can be seen that the patient has a hereditary burden on the part of the patient, the patient has a art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 162 hereditary burden on the part of the father, whose grandfather suffered from renal pathology, on the maternal side no morbidity was detected. fig. 1. fragment of l.f.'s pedigree, 53 years old. note: a patient with ckd. the more frequent lesion of ckd in the relatives of the proband than in the relatives of healthy people indicates a significant role of genetic factors in its occurrence. the results of our study indicate a significant prevalence of ckd in families of probands, but with a predominant lesion of relatives of the first degree of relationship. the analysis of the pedigree confirms the absence of a monogenously inherited disease as a simple recessive or dominant inheritance. along with this, the wide spread of renal pathology in the population suggests that only a predisposition to the development of ckd is inherited. a decrease in the incidence of ckd in relatives with a distance from the degree of relationship from the proband may indicate the multifactorial nature of the disease. such diseases are called multifactorial or polygenic, since their occurrence is due to the action of a whole complex of genes and the influence of the external environment. output. the results of the study showed that ckd can be considered as having a hereditary predisposition, which brings it closer to polygenic diseases. taking this art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 163 into account, the use of methods of clinical and genetic examination of patients in primary health care should be more widely recommended, since knowledge of the family background greatly facilitates the early diagnosis and prevention of disease progression. moreover, the hereditary burden was more on the paternal side. at the same time, nephropathy was more often registered in the relatives of the proband of the i-ii degree of kinship in comparison with other relatives. a decrease in the frequency of renal pathology in relatives with a distance from the degree of relationship from the proband may indicate the multifactorial nature of the disease. the risk of developing the disease was higher in cases when the father or mother of the proband suffered from nephropathy. thus, ckd can be considered as having a hereditary predisposition, which brings it closer to polygenic diseases. the polygenicity hypothesis explains well why in families with a large number of affected members, ckd is difficult, becomes protracted, and often progresses to the terminal stage. taking this into account, the use of methods of clinical and genetic examination of patients should be more widely recommended, since knowledge of the family background greatly facilitates the prognosis of individual cases of the disease within the family. moreover, it is more accessible precisely in the primary health care setting from family doctors. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 164 references: 1. abdulloev s.m., gulov m.k. clinical and epidemiological features and risk factors for the development of chronic kidney disease in the republic of tajikistan // healthcare of tajikistan. 2019. no. 2. s. 5-13. 2. akhmedova n.sh. features of screening of renal function in an outpatient setting // medicus. 2019. no. 2 (26). s. 17-21. 3. veltischev yu.e., ignatova m.s. preventive and preventive nephrology (genetic and ecopathogenic risk factors for the development of nephropathy): a guide for doctors. m., 1996. with. 61 4. ignatova m.s. the role of genetic research in the development of nephrology // therapeutic archives. m., 2003. no. 6. p.66-72. 5. podzolkov v.i., bragina a.e. chronic kidney disease as a multidisciplinary problem of modern medicine // therapeutic archive. 2018. t. 90, no. 6. p.121129. 6. bisi-onyemaechi ai, okafor hu, ughasoro md. profile of chronic kidney disease modifiable risk factors in a rural community of south east nigeria. // bmc public health. 2018 jul 27; 18 (1): 922. 7. connaughton dm, kennedy c, shril s, mann n, murray sl, williams pa, conlon e, nakayama m, van der ven at, ityel h, kause f, kolvenbach cm, dai r, vivante a, braun da, schneider r, kitzler tm, moloney b, moran cp, smyth js, kennedy a, benson k, stapleton c, denton m, magee c, o'seaghdha cm, plant wd, griffin md, awan a, sweeney c, mane sm, lifton rp, griffin b, leavey s, casserly l, de freitas dg, holian j, dorman a, doyle b, lavin pj, little ma, conlon pj, hildebrandt f. monogenic causes of chronic kidney disease in adults. kidney int. 2019 apr; 95 (4): 914-928. doi: 10.1016 / j.kint.2018.10.031. epub 2019 feb 14. pmid: 30773290; pmcid: pmc6431580. 8. gaitonde dy, cook dl, rivera im. chronic kidney disease: detection and evaluation. // am fam physician. 2017 dec 15; 96 (12): 776-783. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5547926 165 9. groopman ee, povysil g, goldstein db, gharavi ag. rare genetic causes of complex kidney and urological diseases. nat rev nephrol. 2020 nov; 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"family history of chronic renal failure is associated with malnutrition in korean hemodialysis patients." nutrition research and practice vol. 3.3 (2009): 247-52. doi: 10.4162 / nrp.2009.3.3.247 11. mcclellan wm, satko sg, gladstone e, krisher jo, narva as, freedman bi. individuals with a family history of esrd are a high-risk population for ckd: implications for targeted surveillance and intervention activities. am j kidney dis. 2009 mar; 53 (3 suppl 3): s100-6. doi: 10.1053 / j.ajkd.2008.07.059. pmid: 19231753. 12. malik s, syed z, naz f, rehman n, rauf a, ali r. risk factors of chronic kidney disease leading to dialysis in patients presenting at ayub teaching hospital abbottabad. // j ayub med coll abbottabad. 2019 oct-dec; 31 (suppl 1) (4): p 672-673. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 38 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 39 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 40 clinical and immunological indicators of inflammatory diseases of the nervous system m.sh. khozhimatova, n.a. nasirdinova andijan state medical institute abstract: inflammatory diseases of the central nervous system are severe processes with a wide range of pathogenetic disorders and lead to a gross deficiency in the nervous system or, in the worst cases, to the death of the patient. acute inflammatory diseases of the central nervous system represent an extremely heterogeneous group of diseases and conditions in terms of clinical manifestations and prognosis, traditionally combined according to one of the main pathomorphological signs primary demyelination. keywords: primary, demyelination, diseases, clinical. introduction: clinical manifestations of inflammatory diseases of the central nervous system in the acute period to a certain extent depend on the tropism of the pathogen, the predominant localization of lesions and the characteristics of pathogenesis, as well as on the age of the patients. despite the expansion of the diagnostic capabilities neuroimaging, immunological studies, the possibility of carrying out these methods in the shortest possible time, there remain a number of unspecified questions both in the diagnosis and in the treatment of these diseases. in this regard, the goal was set for us: to study the clinical and immunological features of inflammatory diseases of the central nervous system and to optimize the diagnosis of these processes. material and research methods: in the period from 2015 to 2020. 124 patients with acute inflammatory diseases of the central nervous system at the age from 18 to 74 years were examined. the patients were observed in the neuro-intensive care units of the clinic of the andijan medical institute. the comparison group consisted of 30 apparently healthy people. all patients were divided into 3 groups depending on the localization of organic lesions of the central nervous system and the clinical diagnosis. group 1 consisted of 34 patients with myelitis, group 2 of 58 patients with encephalitis and group 3 of 32 patients with encephalomyelitis. in all patients, the nosological forms were verified both clinically and neuroimaging (according to mri data). table no. 1 distribution of patients depending on age patient age 1st group myelitis 2 group encephalitis group 3 encephalom yelitis healthy n % n % n % n % 18-44 years 20 58,8 45 77,6 22 68,8 1 2 40 44-59 years 9 26,5 10 17,2 7 21,9 133,3 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 41 0 60-74 years 5 14,7 3 5,2 3 9,3 8 26,7 всего 34 100 58 100 32 100 3 0 100 the distribution of patients depending on age indicates the predominance of patients from 18 to 44 years old in different age categories (patients with myelitis in this interval accounted for 58.8%, encephalitis 77.6%, encephalomyelitis 68.8%) (table 1). the average age of patients at the time of examination was determined. according to statistical data, the average age of patients with myelitis was 39.2 ± 2.6 years, the average age of patients with encephalitis was 37, 4 ± 1.7, and patients with encephalomyelitis, 37 ± 2.5. studies have shown that most often inflammatory processes affect people of young and working age, which is consistent with the literature data. all patients underwent clinical neurological, laboratory, neuroimaging, immunological studies in order to determine the main mechanisms of the development of the disease. of all the examined patients with encephalitis, 39 (67.2%) people had a severe and extremely difficult disease, 16 (27.6%) patients had a moderate form, a mild form of acute encephalitis in 3 (5.2%) patients ( table 2). in patients with myelitis, 8 (23.5%) patients had a severe course of the process, 22 (64.7%) patients had a moderate course, and 4 (11.8%) patients had a mild course. encephalomyelitis, as a more common and severe process, proceeded in the following indicators: extremely severe course in 8 (25%) patients, severe in 12 (37.5%) patients and moderate in 12 (37.5%) people. table no. 2 the course of the inflammatory process depending on the disease № nosology the severity of the flow art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 42 lung average heavy heavy extremely heavy 1 myelitis 4 (11,8%) 22 (64,7%) 8 (23,5%) 2 encephalitis 3 (5,2%) 16 (27,6%) 29 (50%) 10 (17,2%) 3 encephalomyelitis 12 (37,5%) 12 (37,5%) 8 (25%) total 7 (5,6%) 50 (40,3%) 49 (39,5)% 18 (14,5%) clinical and neurological research showed that in all study groups they had signs of organic lesions of the brain and spinal cord with a number of neurological symptoms in the form of bulbar disorders (in group 2 58.6%, in group 3 84.4%), pyramidal disorders ( in group 1 100%, in group 2 74.1%, in group 3 90.7%), pelvic disorders (in group 1 85.3%, in group 3 93.8%) (table no. 3). table no. 3 comparative characteristics of the main neurological symptoms № neurological symptoms 1 group (encephalomyelitis) 2 group (encephalomyelitis) 3 group (encephalomyelitis) 1 bulbar disorders 34 (58,6%) 27 (84,4%) 2 convulsive syndrome 23 (39,7%) 10 (31,2%) 3 cranial nerve damage 17 (39,3%) 15 (46,8%) 4 pyramidal violations 34 (100%) 43 (74,1%) 29 (90,7%) 5 sensory impairment 34 (100%) 38 (65,5%) 30 (93,8%) 6 pelvic 29 (85,3%) 30 (93,8%) art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 43 disorders 7 intellectual impairment 2 (3,4%) complications after a previous illness № nosology vegeta tive (trophy ica l) violation s epi lep thi s pa resis and paralysis ex trapyra mine disorder s co ordinati ng violation s pe lvic dysfunct ion 1 myelitis 33(97%) 34(100% ) 33(97,1 %) 29(85,3 %) 2 encephalitis 23(39,7 %) 43(74,1 %) 8(13,7%) 4(6,89%) 3 encephalom yelitis 25(78,1 %) 10(31,2 %) 29(90,7 %0 10(31,2 %) 6(18,7%) 30(93,8 %) total 58(46,7 %) 33(26,6 %) 106(85,4 %) 18(14,5 %) 43(34,7 %) 59(47,5 %) complications after the previous illness among patients of all groups were observed more in the pyramidal, coordinating systems and pelvic disorders (diagram no. 1). also, among patients with encephalitis and encephalomyelitis, the disease was complicated by epilepsy and amounted to 39.7% and 31.2%, respectively. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 44 diagram no. 1 among patients with myelitis and encephalomyelitis, a large number (97% and 78.1%, respectively) were trophic disorders, which, according to literature data, is associated with damage to the lateral horns of the spinal cord in inflammatory processes of the central nervous system. here is an example: patient k., born in 1984, was admitted to the neurology department of the agmi clinic with a diagnosis of acute meningoencephalitis. complaints at admission: severe headaches, nausea, vomiting, fever up to 39 ° c, chills, pain throughout the body, weakness in the arms and legs on the left, drowsiness, general weakness. anamnesis morbi: the patient considers himself ill for 10 days, the left extremities began to weaken on the sly, then he turned to a specialist, where he was urgently hospitalized. status praesens: the general condition is more serious, is in an unconscious state. visible skin and mucous membranes were unchanged. peripheral lymph nodes are not enlarged. breathing is even through the nose. weak vesicular breathing is heard in the lungs. heartbeats are rhythmic. hell 140/90 mm hg pulse 80 beats per 0% 100% 200% 300% 400% 500% 600% 700% 800% myelitis encephalitis encephalomyelitis peat disturbances epilepsy paresis extrapyramidal disorders coordinating violations столбец1 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 45 minute. the tongue is clean, uncoated. the liver and spleen are not enlarged. urination is carried out through a urinary catheter. neurostatus: (given the serious condition of the patient) the pupils are uniformly narrow, photo reaction and corneal, conjunctival reflexes are weak. the face is symmetrical. there is no deviation. motor sphere: there is a limitation of movement in the left limbs. decreased muscle tone on the left. tendon reflexes are triggered. pathological reflexes: upper, lower rossolimo, babinsky on the left are positive. sensitivity: the reaction is weak to external stimuli (needle prick). the coordination samples could not be verified. meningeal signs: stiff neck, kernig positive. there are no trophic changes. vnd soporous state. test results: 1. general analysis: hb 108 g / l, erythrocytes-3.74, tsv.pok-0.8, leukocytes-25 g / l, esr-25 mm / h, 2. analysis of cerebrospinal fluid: quantity-2.0, color-colorless, protein-6.6, cytosis-82, pandey reaction ++++, lymphocytic pleocytosis ,. 3. ecg: sinus tachycardia, horizontal position of the electric axis of the heart. 4. biochemistry blood test: sugar -6.2 mmol, pti-105%, inr-0.94, total bilirubin -36.54, bound-8.7, unbound-27.84, total protein -64.7, ast-1.2, alt-1.5, 5. urine analysis: straw yellow color, protein abs, leukocytes 3-0-2. 6. mri of the brain: external dropsy of the brain, ventriculmegaly, hypotrophy of the cerebral cortex. infiltration of the right hemisphere. мрт расм based on the history, clinical, mri and laboratory findings, the following diagnosis was made: acute encephalitis, viral etiology. complication: left-sided hemiparesis. edema of the brain. sopor. jacksonian seizures. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 46 treatment: was carried out according to the standard of treatment of the ministry of health of the republic of uzbekistan. 1. antiviral drugs 2. decongestants 3. drugs that improve microcirculation 4. neuroprotective agents 5. hormone therapy 6. antibiotic therapy 7. plasmapheresis in order to confirm the participation of the autoimmune component in the development of demyelination in patients with inflammatory diseases of the central nervous system, we examined the indicators of the following main cytokines: il-1β, il6, tnf-alpha (table 4). table no. 4 indicators of immunological research for encephalitis (pg / ml) № nosological forms the number of patients examined il-1β il-6 tnfalpha cec lar ge c ec small a bs numbe r % 1 encephalitis 2 0 3 4,4 13, 5±0,5 *** 8,4 ±0,6** ^ 7 ,4±0,3 12 4,1±1,8* * 12 7,7±1,8* *^^ 2 myelitis 2 0 5 8,8 11, 8±06 6,9 ±0,3^ 7 ,4±0,4* * 10 2,5±1,7* * 10 1,8±1,3^ ^ 3 encephalomy elitis 2 0 6 2,5 22, 9±1,0*** 11, 0±0,4** ^ 6 ,6±0,4* * 13 2,7±2,3* * 13 0,6±3,0* *^^ 4 control 2 0 6 6,7 9,9 4 ± 1,78*** 3,4 2 ± 0,28^ 4 ,58 ± 0,81** 10 1±1,5** 10 0±1,7** *** p<0,001 between 1 and 3, 1 and 4 comparison group for il -1β ** p<0,01 between 1 and 3 comparison group according to il-6 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 47 ^ p<0,001 between 2 and 3, 1 and 4, 2 and 4, 3 and 4 comparison group according to il6 ** p<0,01 between 2 and 4, 3 and 4 comparison group for tnf-alpha *** p<0,01 between 1 and 3, 2 and 3 by the cec comparison group, large ^^ p<0,001 between 1 and 2, 2 and 3 comparison group by cec small ** p<0,01 between 1 and 3 comparison group according to the cec small in all three observation groups, the above cytokines were also examined to determine the level of the autoimmune response. as can be seen from the data presented in the first group (encephalitis), the level of il-1β was 2.5 times higher than the reference value and amounted to 13.5 ± 0.5. an increase in il-1β was also observed in the groups examined with myelitis (11.8 ± 06 pg / ml) and encephalomyelitis (22.9 ± 1.0 pg / ml), and these indicators have a significant increase both between groups 1 and 3, and with the control group. in the study of the level of cytokines in the acute period of the disease, an increase in the production of il-1β was observed in all studied groups, but it was significant in relation to the control group with encephalitis and encephalomyelitis (13.5 ± 0.5 pg / ml and 22.9 ± 1, 0 pg / ml, respectively). moreover, with encephalitis and encephalomyelitis, this indicator was significantly higher than with myelitis, which once again proves the severity of these processes. it also correlates with both the course and clinical manifestations of the disease. when determining the level of il-6, it was found that this indicator was significantly higher in all three groups compared with the control (8.4 ± 0.6 pg / ml with encephalitis, 6.9 ± 0.3 pg / ml with myelitis and 11 , 0 ± 0.4 pg / ml with encephalomyelitis). when comparing il-6 between groups with diseases, it turned out that a significant increase was also observed between patients with encephalitis and encephalomyelitis. with encephalomyelitis, this indicator exceeded those with encephalitis (8.4 ± 0.6 pg / ml and 11.0 ± 0.4 pg / ml). this ratio corresponds to the severity and prevalence of the inflammatory process. the same tendency is characteristic of the tumor necrosis factor tnf-alpha a cytokine, which usually increases during viral processes in the central nervous system, and also determines the immune response of the organism to pathogenic art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 48 processes. this indicator was significantly higher in all three groups with diseases compared to the control group (7.4 ± 0.3 with encephalitis, 7.4 ± 0.4 with myelitis, 6.6 ± 0.4 with encephalomyelitis). however, this indicator in the comparison groups did not have a significant difference in increase, although it exceeded the indicators of the control group, but at the same time did not go beyond the limits of the reference value. conclusions: 1. studies have shown that all inflammatory processes of the central nervous system are characterized by a predominance of severe (39.5%) and moderate (40.3%) forms of diseases, a high incidence of residual consequences (75%): in them, a chronic vegetative state was detected in 10% patients, symptomatic epilepsy 26.6%, psychoorganic syndrome 12.5%, coordination disorders 34.7%, paresis and paralysis 85.4% and others. 2. the level of il1-β, il6, tnfa, cec large and cec small in acute inflammatory diseases of the central nervous system directly correlates with the severity of the course of the disease and the development of demyelination in the central nervous system (according to computed and magnetic resonance imaging), although according to tnfa indicators were in the study group were not reliable and did not exceed the reference values. 3. investigation of the level of circulating immunological complexes allows to determine the severity of the course of the disease and to predict the outcome in inflammatory diseases of the central nervous system. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 49 references: 1. antsilevich lm, yagudina la practical application of enzyme immunoassay in the diagnosis of diseases [electronic resource] // practical medicine. 2014. 2. belova a.n., shalenkov i.v. differential diagnosis of focal noncompression lesions of the spinal cord of the cervicothoracic localization. practical medicine. 2013 no. 66, 31 pages 3. galaktionov. v.g. immunology. m .. academy, 2004. s. 122-123. 4. lobzin yu.v. meningitis and encephalitis / yu.v. lobzin, v.v. pilipenko, yu.n. gromyko. spb.yooo "foliant publishing house", 2003. 128 p. 5. odinak m.m. private neurology / m.m. same. spb .: lan, 2002. "446 p. 6. protas i.i. herpetic encephalitis / i.i. protas. minsk: llc "met". 2000 .- 176 p. 7. chuchalin a.g., t.v. sologub. influenza in adults: guidelines for diagnosis, treatment, specific and non-specific prevention. spb .: publishing and printing complex "np-print". 2014: 192. 8. yatsyshina s.b., tvorogova m.g., shipulin g.a., maleev v.v. laboratory diagnostics of influenza and other acute respiratory viral infections by the method of polymerase chain reaction. laboratory service. 2017; 6 (3): 238-267. https: // doi: 10.17116 / labs201763238-267. 9. borchers a.t., gershwin m.e. transverse myelitis // autoimmun. rev. 2012. v. 11. p. 231-248. 10. dinarello, c., simon, a., van der meer, j. treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. nat rev drug discov., 2012. — vol. 11(8). — p. 633-652. 11. giovannini, s., onder, g., liperoti, r. et al. interleukin-6, c-reactive protein, and tumor necrosis factor-alpha as predictors of mortality in frail, community-living elderly individuals. j am geriatr soc., 2011. — vol. 59(9). — p. 1679-1685. 12. goh c., desmond p.m., phal p.m. mri in transverse myelitis // j. magn. reson. imaging. 2014. v. 40. p. 1267-1279. 13. kamei s, sekizawa t, shiota h, et al. evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis. j neurol neurosurg psychiatry 2005;76:1544-1549. 14. malmgaard l. induction and regulation of ifns during viral infections. j interferon cytokine res 2004;24:439-454. 15. misra uk, tan ct, kalita j. viral encephalitis and epilepsy. epilepsia 2008;49(suppl. 6):13-18. 16. misra uk, kalita j, phadke rv, et al. usefulness of various mri sequences in the diagnosis of viral encephalitis. acta trop 2010;116:206-211. 17. renard d, nerrant e, lechiche c. dwi and flair imaging in herpes simplex encephalitis: a comparative and topographical analysis. j neurol 2015;262:2101-2105. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5639620 50 18. solomon t, michael bd, smith pe, et al. management of suspected viral encephalitis in adults—association of british neurologists and british infection association national guidelines. j infect 2012;64:347-373. 19. sutter r, kaplan pw, cervenka mc, et al. electroencephalography for diagnosis and prognosis of acute encephalitis. clin neurophysiol 2015;126:15241531. 20. thakur kt, motta m, asemota ao, et al. predictors of outcome in acute encephalitis. neurology 2013;81:793-800 21. venkatesan a, geocadin rg. diagnosis and management of acute encephalitis: a practical approach. neurol clin pract 2014;4:206-215. 22. venkatesan a, tunkel ar, bloch kc. case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. clin infect dis 2013;57:1114-1128. 1 volume 1, ¹4 art of medicine international medical scientific journal 2 art of medicine international medical scientific journal volume 1, ¹4 december 2021 3 volume 1, ¹4 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen art of medicine international medical scientific journal 4 effects of intensive hypoglycemic therapy from the position of their influence on the development of heart rhythm disorders mirzarahimova z. h., rakhimova g.n., mullabaeva g. u., yakubov a. a. republican specialized scientific and practical medical center of cardiology tashkent, uzbekistan abstract: it is known that dm 2-4 times increases the risk of cvd, and mortality when combined increases 4-5 times. the combination of a cluster of risk factors for the rapid development and progression of atherosclerosis, which is based on insulin resistance hyperglycemia, dyslipidemia, hypertension, allowed the expert commission of the national educational program of the united states cholesterol (ncep) to equate dm2 risk to coronary heart disease. this article reviews the literature on the relationship of diabetes and hypoglycemia with the development of cardiac arrhythmias. key words: atrial fibrillation, diabetes mellitus, hypoglycemia, prevention cvds remain the leading cause of death worldwide, they are responsible for 17.3 million deaths annually 31.5% of all deaths of the world population and 45% of all deaths from ncds, which include 4 groups of diseases, including cardiovascular, cancer, bronchopulmonary and diabetes mellitus (dm) [2]. however, the xxi century was marked by an epidemic of metabolic risk factors of cvd, such as obesity, impaired glucose tolerance, diabetes mellitus (dm). according to the international diabetes federation (idf, 2014) currently 400 million people in the world suffer from diabetes and by 2035 their number will increase to 600 million people. in russia, by 2030, the number of patients with diabetes is predicted to increase to 14 million. it is known that diabetes 2-4 times increases the risk of cvd, and mortality when combined increases by 4-5 times [3]. the combination of a cluster of risk factors for the rapid development and progression of atherosclerosis, based on insulin resistance hyperglycemia, dyslipidemia, arterial hypertension allowed the expert committee of the us national cholesterol education program (ncep) to equate type 2 diabetes with coronary heart disease. today, t2dm is considered the equivalent of having clinically significant cvd [1]. well-known prospective studies have confirmed the role of hyperglycemia in the development of cvds (decode, epic-norfolk, aric, advance). however, a number of studies have shown that despite improved glycemic control, macrovascular complications and associated cvds continue to progress in dm2 patients (ukpds, kumanato study) glycemic control studies have shown that intensive glycemic control in the two types of diabetes does not always have similar effects. the diabetes control and complications trial (dcct) has convincingly demonstrated the positive role of intensive glycemic control in reducing the risk of microand macrovascular complications in patients with type 1 diabetes. it was shown that strict and constant glycemic control (average hba1c level ~ 7% for 6.5 years) is the main prevention of the development and progression of microvascular complications and reduces the frequency of microalbuminuria by 39%, proteinuria by 54%, neuropathy by 60% [20]. 5 volume 1, ¹4 the target hba1c level, according to the current consensus of the european association for the study of diabetes and the american diabetes association, is less than 7.0% (with normal values less than 6.0%). microvascular complications are known to be the cause of early disability in patients with type 2 diabetes, whereas macrovascular complications in the form of cardiovascular disease are the cause of death in eight out of ten patients [7, 9]. according to veterans affairs diabetes trial (vadt) data, severe hypoglycemic reactions in dm 2 are one of the main predictors of myocardial infarction, cerebral stroke and death from all causes [3]. the ambiguous role of intensive glycemic control was demonstrated by a large-scale multicenter randomized two-factor accord (action to control cardiovascular risk in diabetes) study, the key point of which was to maintain diabetes compensation with glycosylated hemoglobin (hba1c) levels less than 6.5%. the study included 10251 high-risk patients with type 2 dm, randomized into intensive (hba1c less than 6%) and traditional (hba1c 7.0-7.9%) glycemic control groups with different intensity of control of blood pressure and lipid profile. the study was terminated early due to high mortality in the intensive treatment group (257 deaths, mean hba1c 6.4% versus 203 deaths, mean hba1c 7.5% in the traditional treatment group, i.e., 54 excess deaths in the intensive treatment group) [16]. as a careful review of the study results showed, episodes of hypoglycemia were significantly more frequent in the intensive glycemic control group (10.5% vs 3.5%). at the same time, a statistically significant reduction in myocardial infarction, stroke, and cv mortality was observed in the group of patients without cvd with baseline hba1c<8.0% [3]. the effect of intensive glycemic control on reducing the risk of microvascular (nephropathy and retinopathy) and macrovascular (myocardial infarction, stroke, cc mortality) complications was demonstrated in the advance (the action in diabetes and vascular disease preterax and diamicron-mr controlled evaluation) study (or 0, 9 [95% ci 0.82-0.98] p=0.01), but it should be noted that the reduction in risk of microvascular events (or 0.86 [95% ci 0.77-0.97], p=0.01) was significantly higher, whereas the reduction in risk of macrovascular events did not reach the level of statistical significance (or 0.94 [95% ci 0.84-1.06], p=0.32). however, in contrast to the accord study, no increase in total or cv mortality was observed in the intensive glycemic control group compared to the standard glycemic control group [4]. later, the results of the vadt study confirmed those of the advance study, where there were no differences in the incidence of cv events between the intensive and standard glycemic control groups (or 0.88 [95% ci 0.74-1.05], p=0.12). cvd mortality in the intensive glycemic control group was slightly higher than in the standard glycemic control group (38 versus 29, sudden death 11 versus 4), but this difference did not reach statistical significance. an in-depth analysis of the results showed the effect of the duration of diabetes disease on the incidence of endpoints. thus, when the history of diabetes was not longer than 12 years, intensive glycemic control did not demonstrate its negative effect on cv mortality. at the beginning of the 21st century nordin c. expressed an opinion about proarrhythmogenic effect of hypoglycemic reactions due to the direct effect of hypoglycemia and catecholamine reactions, causing hypokalemia and other disorders [13]. a number of studies have demonstrated an independent role of dm in the development of sudden death (sd) [5]. several mechanisms may be involved in the development of sudden death against the background of hypoglycemia. an important pathogenetic link is the development of the so-called "autonomic dysregulation disorder associated with hypoglycemia" (narsh). narsh is a form of sympathoadrenal system failure as a result of a recent episode of art of medicine international medical scientific journal 6 iatrogenic hypoglycemia, which leads to a lower blood glucose threshold level that triggers the counterinsulatory response necessary to restore normoglycemia [18]. this contributes to an almost 25-fold increase in the risk of severe hypoglycemia against the background of intensified insulin therapy and the appearance of repeated episodes of hypoglycemia. the pearson e.c. study found an association between dm and prolongation of the pq interval in patients with coronary heart disease (chd) [15]. older age and the presence of comorbidities determine the greatest risk of cardiovascular complications associated with hypoglycemic states in type 2 dm. at blood glucose levels < 3 mmol/ l for more than 30 min, increased qtc time and ventricular tachycardia occur with an increased risk of ventricular fibrillation and vs. abrupt changes of mean amplitude of glucose excursion (mage) more than 5 mmol/l contribute to greater vulnerability of electrical stability of the heart, especially in weakened patients with the presence of coronary heart disease and autonomic dysfunction. the independent role of diabetes in the development of af was assessed in the fremingham study [21]. numerous studies since then have found that af in people with diabetes is at least twice as common as in people without diabetes, and 3 times as common if, in addition to diabetes, ah is present [14]. the advance study demonstrated the role of af as a strong independent marker of total and cardiovascular mortality, as well as severe chronic chf in dm patients [7], which required more intensive control of blood pressure and other cardiovascular risk factors in the study population of patients. so what is the determining role of dm in the development of fp? cardiac muscle damage in dm2 is determined not only by atherosclerotic lesions of the coronary arteries, but also by specific changes peculiar to "late" complications of diabetes (microangiopathy, neuropathy). based on pathological anatomical studies rubler s. et al. [1972] proposed the term diabetic cardiomyopathy (dc), characterized by the clinical picture of dilated cardiomyopathy with the development of heart failure with low ejection fraction in diabetic patients in the absence of arterial hypertension and coronary artery atherosclerosis. dc is a pathology of the heart muscle, manifested by a wide range of biochemical and structural abnormalities, mediated by insulin resistance, hyperglycemia, impaired free fatty acid metabolism and increased free radicals. diastolic dysfunction of the left ventricle (lv) is considered as an early marker of myocardial damage in dm2, noting the pathogenetic relationship between lv diastolic dysfunction and lv hypertrophy (lvh) in the development and progression of chronic heart failure (chf), which in turn contributes to the formation of arrhythmogenic substrate [11]. the pathogenetic role of glycometabolic processes in the development and progression of diastolic abnormalities is associated with the formation of hypertrophy under the influence of insulin resistance and activation of fibrosis processes against the background of hyperglycemia [17]. to date, there are still discussions on the topic should diastolic dysfunction and autonomic cardiovascular neuropathy be combined into a single concept, or is there still a need to distinguish between these mechanisms? another key point explaining the high risk of af in dm is the results of studies of purely electrophysiological interest. aleksandrov a.a. et al. [2011] explain the formation of electrophysiological remodeling of ion channels of myocardiocyte sarcolemmal membrane in dm patients by the presence of a transmembrane phosphoinositol mechanism, which normally represents a kind of glucose transport mechanism that is activated when insulin binds to the cell receptor, or when sulfonylurea derivatives interact with the cellular component of phospholi pase c (flc). the resulting 7 volume 1, ¹4 diacylglycerol (dag), by stimulating pyruvate kinase c (pks), increases the availability of glucose transporters and promotes glucose diffusion inside the cardiomyocyte. at the same time, electrolyte fluxes of the cardiomyocyte are formed, providing the correct action potential of the myocardial cell, periods of its electrical refractoriness (katpdependent channels, ca-balance, na/h-exchange). electrophysiological activity of ion channels is dramatically impaired by the processes of insulin resistance and/or lack of insulin. the high risk of electrophysiological abnormalities in dm is associated with the overload of cardiomyocytes with ca2+ ions. against the background of a sharp decrease in glycolysis, the sarcoplasmic reticulum loses the ability to absorb calcium at the normal rate. this in turn leads to an imbalance between the mitochondria's need for atp to pump out protons as protection against excess calcium and its amount. thus, myocardial contracture is formed, conjugation of myocardial electrophysioo logical and contractile processes is disturbed. in the works of z.h. lu et al., high levels of hba1 were associated with increased risk of atrial fibrillation recurrence in patients with type 2 dm and paroxysmal af who underwent catheter ablation [12]. at the same time, the effect of hypoglycemia on increased risk of cardiac arrhythmias is currently not confirmed in randomized clinical trials. thus, in the accord study, where 10082 patients were selected, intensive glycemic control did not demonstrate its effect on the development of af. similar results were obtained by researchers nicolas g.a. et al. where hypoglycemia was associated with the development of af only in female patients. in later studies, it was demonstrated that dm in need of pharmacological control by 40% increased the risk of pd, as well as the risk of pd was associated with the duration and lack of adequate glycemic control. the chang sh. study found a positive role of metformin monotherapy in reducing the risk of af in patients with diabetes. the authors attribute this effect to a decrease in tachyinduced cell myolysis and oxidative stress. in a study by e. chow et al. studied the effect of hypoglycemic episodes on the incidence of various types of ldcs. the study included 25 patients with type 2 diabetes receiving insulin therapy. all patients had atherosclerotic lesions of the cardiovascular system (chd, peripheral arterial lesions or cerebrovascular disease), as well as risk factors in the form of obesity, smoking, and hypodynamia. all patients underwent longterm glucose-cardiac monitoring for 5 days. hypoglycemia was established at hba1c?3.5 mmol/l. during the observation period, 14 patients had episodes of hypoglycemia with a total duration of 134 hours. at the same time, the duration and frequency of nocturnal hypoglycemia prevailed over daytime values. a comparative analysis of hrs for euand hypoglycemia showed that bradycardia was 8 times more frequent in nocturnal episodes of hypoglycemia (or 8.42 [95% ci 1.40-51.0]). noteworthy is the fact that despite the presence of daytime episodes of hypoglycemia, bradycardia was not recorded during these hours. af was 4 times more frequently observed in hypoglycemia (3.98 [1.1014.4]), but without significant differences between its frequency in daytime and nighttime. ventricular extrasystole was recorded with equal frequency during hypoglycemia, both during the day (1.31 [1.10-1.57]) and at night (3.06 [2.11-4.44]). the analysis of the heart rhythm variability condition showed its reliable decrease, as well as a decrease in the total power of the spectrum, an increase in the strength of high-frequency components. episodes of hypoglycemia contributed to a significant increase in the corrected qt interval predominantly in the daytime. researchers have concluded that the mechanisms of ventricular tachyarrhythmias during daytime and nighttime hypoglycemia are different. thus, prolongation of the qt art of medicine international medical scientific journal 8 interval in the daytime may lead to an increase in trigger activity, a form of early postdepolarization. sympathetic activity and cytosolic calcium overflow, in turn, leads to prolongation of postdepolarization and development of ventricular extrasystole. the two mechanisms described probably explain ventricular hrv predominantly during daytime hypoglycemia. nevertheless, the vast majority of ldcs occurred during nocturnal hypoglycemia, when sympathetic system activity is not pronounced. researchers found the answer to this question in experimental hypoglycemia. in response to increased vagus system activity and decreased sinus node activity, especially in the presence of narsh, latent rhythm drivers are activated, which explains the frequent development of af and ventricular extrasystole at night. ventricular extrasystole against a background of bradycardia is highly likely to be a trigger for torsade de pointes, which has been demonstrated in previous studies in patients with hypoglycemic coma. summarizing their results, the authors emphasize that in this study, despite the lack of intensive glycemic control, episodes of hypoglycemia occurred with approximately the same frequency as in studies with intensive glycemic control and call for cardiologists and endocrinologists to more carefully perform risk-stratification of patients with a high risk of cardiac arrhythmias and, therefore, with the risk of a fatal outcome. a relatively new study on the effect of hypoglycemia on the risk of af was the work of ko s.h. et al. [9]. using a retrospective analysis of the case histories of more than 2 thousand patients with type 2 diabetes without prior af, it was found that hypoglycemia is an independent predictor of af within 5 years of follow-up in patients with type 2 diabetes even in the absence of cvd. but it should be noted that this study was retrospective and studied only cases of documented hypoglycemia, that is, when patients seek medical care, while the vast majority of episodes of hypoglycemia are asymptomatic. and the development of af was also diagnosed when it was detected during a standard ecg, that is, episodes of paroxysmal af might have been missed. the study of the role of hypoglycemia in the increased risk of cardiovascular death is complicated by the absence of specific anatomical and morphological markers of hypoglycemia and by the fact that when acute cardiac pain occurs, the patient does not always determine the glycemic level and/or fix posthypoglycemic hyperglycemia. it is these factors that limit the analysis of existing studies and make it difficult to design a study that can prove or disprove the effect of hypoglycemia on arrhythmia risk. given the growing incidence of diabetes and associated af, which in turn increase the incidence of cardiovascular complications in the form of strokes, heart failure, inevitably leading to disability and increased mortality, the problem of safe hypoglycemic therapy and the development of methods for its optimal control will only increase its relevance. the problem of interaction between antiarrhythmic, hypoglycemic and antiplatelet drugs also requires detailed coverage, which will serve as a basis for new research in the future. 9 volume 1, ¹4 used literature. 1.cardiovascular prevention 2017. russian national recommendations. 2.kronenberg, g.m. diabetes mellitus and disorders of carbohydrate metabolism: transl. from english, ed. by i.i. dedov, g.a. melnichenko / g.m. kronenberg, sh. melmed, k.s. polonski, p.r. larsen moscow: reed elsiver llc, 2010. 448 ñ. 3.action to control cardiovascular risk in diabetes study group, gerstein h.c., miller m.e., byington r.p., et al: effects of intensive glucose lowering in type 2 diabetes // n. engl. j. med. 2008. 358. p. 25452559. 4.advance collaborative group, patel a., macmahon s., chalmers j., et al: intensive blood glucose control and vascular outcomes in patients with type 2 diabetes // n. engl. j. med. 2008. 358. p. 2560-2572. 5.brown d.w., giles w.h., greenlung k.j. et al. // j. cardiovasc. risk. 2001. vol. 8. p. 227-233. 6. duckworth w., abraira c., moritz t. et al. // nejm. 2009. vol. 360, n 2. p. 129-139. 7. du h.t., de galan s., abadre e., et al. cardiovascular event risks and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the advance study // eur. heart j2009.-n 30 (9).p 112-1135 8.krolewski a.s., warram j.h., valsania p., et al. evolving natural history of coronary heart disease in diabetes mellitus // am. j. med. 1991. vol. 90. -p. 56-61. 9.ko sh park ym, yun js, cha sa, choi ek, han k, han e, lee yh, ahn yb. j severe hypoglycemia is a risk factor for atrial fibrillation in type 2 diabetes mellitus: nationwide population-based cohort study of diabetes complications. 2018 feb;32(2):157-163. 10.laakso m., lehto s. epidemiology of macrovascular disease in diabetes // diabetes rev. 1997. vol. 5. ñ. 294-315 11.lee p.w., zhang q., yip g.w. et al. left ventricular systolic and diastolic dyssynchrony in coronary artery disease with preserved ejection fraction // clin. sci. (lond.). 2009. vol. 116. p. 521-529. 12.lu z h, liu n, bai r. et al. hba levels as predictors of ablation outcome in type 2 diabetes mellitus and paroxysmal atrial fibrillation //herz.-2014.-0ct. 23.-00110 1007/ s00059-0144154-6 13.nordin c. // diabetologia. 2010. vol. 53. p. 1552-1561 14.ostgren c .j., merlo j, rastam l, lindad u. atrial fibrilation and its association with type 2 diabetes and hypertension in a swedish community // diabetes obes. metab.-2004.n 6 (5).-p. 367-374. 15.pearson e.c., woolsey r.l. // drag saf. 2005. 14. p. 747-753 16.pfeffer ma accord(ing) to a trialist // circulation. 2010. vol. 122, n 8. p. 841-843 17.phillips r.a. relationship between left ventricular mass, insulin resistance and blood pressure in non-obese subjects / r.a. phillips, l.r. krakoff, a. dunaif, d.t. finegood et al. // j clin endocrinol metab. 1998. vol.83. ð. 4284-4288 18.seaquist er, anderson j, childs b, cryer p, dagogo-jack s, fish l, et al. hypoglycemia and diabetes: a report of a workgroup of the american diabetes association and the endocrine society. diabetes care. 2013;36(5):1384-1395. 19.shang-hung chang, lung-sheng wu, meng-jiun chu et al. association of metformin with lower risk of atrial fibrillation among patients with type 2 diabetes: population-based dynamic cohort and in vitro studies // cardiovasc. drabetoi.2014.art of medicine international medical scientific journal 10 n 13(1).-p. 123 20.united kingdom prospective diabetes study (ukpds) group. intensive blood glucose control with sulfonylurea or insulin versus conventional treatment and risk of complications in patients with type 2 diabetes (ukpds). lancet. 1998. 352. ð. 837853). 21.wolf ra, abbott r.d, kannel w.w. atrial fibrillation as an independent risk factor for stroke in the framingham study // stroke.1991.n 22.p 983-988 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 49 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 50 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 51 difficulties and prospects for non-drug treatment of metabolic syndrome badritdinova matluba nazhmidinovna., nurulloeva shakhodat nurullo kizi bukhara state medical institute, bukhara, uzbekistan abstract: abdominal obesity (and the closely related metabolic syndrome) is one of the most common diseases in the world. the urgency of the problem of the progression of abdominal obesity lies not only in its widespread prevalence, but also in the formation of a high risk of developing cardiovascular diseases and type 2 diabetes mellitus. the main reasons for the rapid development of obesity are considered high-calorie nutrition (which includes not only the quantity, but also the quality of food eaten), a sedentary lifestyle and a genetic predisposition. until now, there has been a heated debate about methods for fast and high-quality weight loss. there are many studies on the treatment of the various components of metabolic syndrome. despite the many different pharmaceuticals developed for the treatment of abdominal obesity, non-drug methods of treatment and the organization of a healthy lifestyle come out on top, which is a difficult and, at times, overwhelming task for the clinician. one of the main reasons for failure in this field is the lack of time at the doctor for outpatient appointments. to address this issue, the role of the "schools of health" is considered in order to effectively reduce the body weight of patients with metabolic syndrome and maintain long-term results. a review of the prevalence and main causes of abdominal obesity is carried out, the results of existing schools in real clinical practice for the treatment of various chronic diseases are analyzed, an assessment of their effectiveness is given. keywords: metabolic syndrome, obesity, diet. introduction: metabolic syndrome (ms) is characterized by an increase in visceral fat mass, decreased sensitivity of peripheral tissues to insulin, and hyperinsulinemia, which cause the development of disorders of carbohydrate, lipid, purine metabolism and arterial hypertension (ah). the problem of ms progression is one of the most pressing problems of modern medicine, associated not only with leading an unhealthy lifestyle, excessive nutrition and physical inactivity, but also with a genetic predisposition [1]. metabolic syndrome is gaining importance in the world. the number of patients increases dramatically every year. more than 1 billion people on our planet are overweight and over 300 million are obese. according to the who, the number of patients with a high risk of developing diabetes mellitus (including insulin resistance and obesity) is 40-50 million people in europe [2]. according to various authors, in industrialized countries among the population over 30, the prevalence of ms ranges from 10 to 20% [3,4]. the prevalence of ms in western countries, according to various sources, is 25-35% of the population, increasing with age. at the age of 60 and older, ms accounts for 42-43.5%. more than 47 million people in the united states have ms [5art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 52 7]. in developing countries, including russia and belarus, about 30% of the population is overweight [8.9]. there is a high increase in the incidence of ms among adolescents [10-14]. the prevalence of ms among men and women is equal: in men 24%, among women 23.4%, with than in women, the incidence of ms increases in the postmenopausal period [14,15]. тarget. to study the role of non-drug methods of treatment of metabolic syndrome based on the results of clinical studies. results and discussions. the clinical significance of disorders and diseases united by the framework of the syndrome is that their combination greatly accelerates the development and progression of diseases associated with atherosclerosis. the latter, according to who estimates, rank first among the causes of mortality in the population of industrially developed countries [23-25]. thus, in addition to the epidemiological aspect, ms is a serious factor of cardiovascular risk and the risk of developing type 2 diabetes, affects life expectancy and its quality. in recent years, more and more information has been accumulating on the relationship of metabolic disorders with cardiovascular morbidity (cvd) and mortality [13, 26-28,35]. it has been proven that it is patients with ms who are at risk of rapid development of diabetes mellitus and various forms of coronary artery disease [25, 27, 29]. in the 21st century, for mankind, which has overcome the epidemic of lifethreatening infections over a centuries-old history, the problem of cvd has come to the fore in relevance among all causes of morbidity and mortality. a significant role in this was played by lifestyle modification associated with limiting physical activity, increasing the calorie content of food, and a steady increase in emotional stress. all this potentiates the main risk factors for cvd, namely, an increase in blood pressure (bp), dyslipidemia, diabetes mellitus and obesity [6, 30, 31]. obesity is recognized as one of the most significant risk factors for the development of cvd, early disability of patients and premature mortality [25, 32]. according to the framingham heart study, obesity was found to be an independent risk factor for all-cause mortality [33]. with obesity of 1 degree, the risk of developing diabetes increases by 2-3 times, 2 degrees 5 times, and 3 degrees 10 times [34]. to date, it has been proven that the most dangerous in relation to the development of various diseases is the visceral type of obesity [25], which is widespread in modern society and is the main and mandatory criterion for ms [8,21, 28-34]. тhe problem of ms development is directly related to lifestyle and poor nutrition. over the years, hundreds and even thousands of works devoted to mc have accumulated [20]. pharmaceutical companies have invented a huge number of drugs that affect various links in the pathogenesis of ms. but, despite the successes, in this direction there are no positive shifts in solving this problem as a whole. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 53 throughout humanity, anthropometric data have constantly changed, mainly due to an increase in height, to a lesser extent due to an increase in body weight. things have changed dramatically lately. the lifestyle of a modern person has changed dramatically and ceased to correspond to the concept of healthy. instead of national cuisines, a high-calorie diet has come: universal "mcdonaldization", "cocacolanization" of the population. in large industrial cities, most of the working-age population among the choice of places for public catering prefers various fast food cafes, where they often offer food containing large the amount of fats, carbohydrates, salt, sugar, low in fiber, vitamins and minerals. therefore, lifestyle modification and diet therapy remain the primary treatment strategies for ms. ms before the development of type 2 diabetes mellitus is a reversible condition, thus, by making a diagnosis and starting treatment, regression of the main manifestations can be achieved. the main goal of ms treatment is to reduce the risk of developing cvd and type 2 diabetes. therapeutic measures in the treatment of patients with ms should correct the main links of its pathogenesis [17]. the main tasks in the treatment of patients with ms are: weight loss, achieving good metabolic control, achieving an optimal blood pressure level, preventing acute and long-term cardiovascular complications (cvc). the main component of ms, triggering a further pathological mechanism of metabolic disorders, is abdominal obesity (ao). treatment of ao is acquiring important medical importance, since the increase in waist volume is directly associated with a number of disorders that affect life expectancy, ahead of such serious risk factors as smoking and alcohol abuse [28]. it is the normalization of body weight that causes a decrease in insulin resistance, an improvement in insulin sensitivity, a decrease in blood pressure and regression of impaired functions. according to the who, the health of the population is 70% conditioned by the lifestyle, therefore an important factor in the fight against cvd is the formation of a healthy lifestyle [19, 29, 30]. data from three large studies (da qing stady, dpp, fdp) have shown that lifestyle changes in people with ms reduce the risk of developing diabetes by more than 50% [31,34]. it has been proven that diet and moderate exercise for at least 3-6 months leads to a significant decrease in body weight by 11%, waist circumference by 9%, high-density lipoprotein cholesterol (ldl) levels by 13%, triglycerides by 24%, improvement of insulin sensitivity by 15% [12-14]. a decrease in body weight by 5.6 kg by 58% reduces the risk of further progression of carbohydrate metabolism, and a decrease in body weight by 10% leads to a decrease in overall mortality by 10%, a decrease in mortality from diabetes by 10%, a decrease in systolic and diastolic blood pressure by 10 mm hg, an increase in high-density lipoprotein (hdl) by 8%, a decrease in triglycerides (tg) by 30% [22]. for every 1 kg of weight loss, there is a decrease in total cholesterol by 0.05 mmol / l, ldl by 0.02 mmol / l, tg by 0.015 mmol / l, increase in hdl by 0.009 mmol / l [32]. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 54 diet therapy is the cornerstone of the management of ms patients, and perhaps the most difficult to manage. many nutritionists testify that changing their dietary habits for patients with ms is a difficult and sometimes daunting task [19]. despite the fact that dietetics has made great strides in studying the dietary aspects of obesity treatment, patient adherence to changes in eating behavior remains extremely low [22, 28, 30]. difficulties also arise for doctors who recommend weight loss to patients with ms. there are no clearly prescribed dietary recommendations for the treatment of patients with ms. there are developed dietary tables according to pevzner, general recommendations for hypocaloric nutrition, food pyramids, etc. however, ms is a multicomponent disease, and if a pevzner dietary table is prescribed, then all components should be taken into account. in case of obesity, dietary table no. 8 according to pevzner is prescribed, with impaired carbohydrate metabolism and type 2 diabetes dietary table no. 9 with restriction of carbohydrates, with hypertension and concomitant coronary artery disease dietary table no. 10, with dyslipidemia restriction of animal fats, with hyperuricemia and gout limiting the intake of purines, etc.). in this situation, the doctor is faced with the question: what exactly should be prescribed in dietary recommendations. most authors believe that the nutrition of patients with ms should be frequent and fractional (up to 5-6 times a day) in small portions, low in calories and low in fat and simple sugars. the optimal daily food ration includes: proteins 15%, complex carbohydrates 55%, simple carbohydrates levoda less than 10%, fats 30% (of which saturated animal fats should be less than 7%) of the daily diet [32]. given the frequent presence of hypertension in patients with ms, the consumption of sodium chloride is limited to no more than 2-5 g / day. an increase in fiber-containing foods has been recommended [31]. it is necessary to teach patients how to calculate the daily caloric intake; to create a negative energy balance, the daily caloric intake should be reduced by 500 kcal. caloric content for each patient is is read individually using special formulas, taking into account such components as gender, age, physical activity [16,19]. on the modern pharmaceutical market there is a huge number of drugs that are used in the treatment of individual links in the pathogenesis of ms: antihypertensive, hypoglycemic, hypocholesteric, antipurine [22], but non-drug methods of treatment are returning to the first place in the treatment of ms [17, 21]. increasing physical activity is the second most important non-drug weight loss method along with diet therapy. however, physical activity should be dosed and individual for each patient. other methods of non-drug effects on body weight have been described, such as herbal medicine, the use of dietary supplements, psychological effects, hypnosis, and auto-training [29]. there is no sufficient evidence base for their widespread use; their use is possible only as additional methods to the main treatment. it should be said that the majority of patients have no concept of a healthy lifestyle. everyone knows that you shouldn't take too much alcohol, smoking is harmful, but the concept of healthy eating is blurred even among educated people. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 55 the concept of a healthy food is biased towards foods with a low glycemic index, which is not always correct: people strive to choose a product free of genetically modified and transgenic products, which may be correct, but by no means the primary one in the choice of products. on the other hand, there is no information in the media, special literature for patients. it is clear that if a person has the opportunity to have access to information on healthy eating, then his eating behavior is close to the correct one. due to proper nutrition, body weight decreases, waist volume decreases, anthropometric indicators improve, and the risk of cvd and diabetes mellitus decreases [20]. an important task is not only to reduce weight to optimal indicators, but also to further maintain it at a certain level. often, patients have no idea what their weight and waist circumference should be. the key point for people motivated to reduce their excess weight is the course approach. changing the diet plan, lifestyle should be perceived by the patient relatively easily, not become burdensome, it is easy enough to be carried out for a long time. the more the doctor interferes with the patient's lifestyle and lifestyle, the less hope for success: competence and long-term fulfillment of any prescription is directly dependent on a person's motivation, personality traits, and also on the degree of lifestyle change. the number of recommendations that a doctor must give should be limited, his task is to develop a strictly limited, but most effective number of recommendations. the diet of a patient with ms should not only ensure weight loss, but also not cause metabolic disorders and not provoke an increase in blood pressure. weight loss should be gradual. a rapid and sharp decrease in body weight by 10–20 kg leads to a decrease in the hormone leptin, which leads to a compensatory, difficult to overcome feeling of hunger and an increase in food consumption [18]. one of the problems of withdrawal from priority tasks is the independent expansion of physical activity with insufficient change in the diet. for the treatment and prevention of many diseases (arterial hypertension, diabetes, bronchial asthma, etc.), health centers have been established in uzbekistan, where "health schools" are successfully carried out, each of which has developed programs to educate patients, and which have proven their effectiveness in real clinical practice [5, 28, 29, 32]. created obfor patients with alcoholism, drug addiction, but for patients with ms, overweight, there are no such schools. for the effective treatment of arterial hypertension, the “school of health for patients with arterial hypertension in primary health care” has been successfully used. on the basis of many treatment-and-prophylactic institutions, "health centers" have been created, in which lectures are given on the formation of a healthy lifestyle for patients with arterial hypertension, bronchial asthma, diseases of the musculoskeletal system [22.35] the effectiveness of programs to reduce mortality from cvd is mainly due to prevention and largely depends on the active participation of patients themselves and their immediate family [29]. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 56 according to the literature, there are practically no works devoted to the feasibility of creating "health schools for patients with ms" based on teaching proper nutrition, changing lifestyle, eating behavior, and correct calculation of physical activity. the introduction of an innovative program in a primary care setting makes it possible to improve the early detection and systematization of metabolic syndrome and its main components. this, in turn, enhances the early detection of various metabolic syndrome-related diseases. measures for non-drug prevention and treatment of metabolic syndrome expand the range of opportunities for lifestyle modification by involving family members in the treatment and prophylactic process. the practical use of an innovative prevention program creates a methodological basis for the development of individual preventive strategies for patients with metabolic syndrome and its main components. from innovative technologies in the prevention of metabolic syndrome, you can use a digital program for calculating cardiovascular risk, which takes into account the main components of metabolic syndrome; the program can run on a computer, tablet and smartphone; the program allows the patient to self-monitor the state of the ms components and the level of risk [20]. conclusion. thus, among the unorganized population, there is a high prevalence of the main components of the metabolic syndrome, which are the main risk factors for cvd. the prevention technologies that exist today do not meet modern requirements and cannot fully get the result from their use. modern prevention of metabolic syndrome and cvd requires the use of new innovative methods. the positive effect of preventive intervention increases significantly when, along with personal contact, modern information and communication technologies through the phone, instant messengers. the use of modern gadgets, diagnostic and preventive digital programs significantly increases the effectiveness of preventive measures. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5658996 57 references: 1.aneja a., el-atat f., 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art of medicine international medical scientific journal 3 founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine international medical scientific journal chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen art of medicine international medical scientific journal volume-1 issue-1 4 content tursunova l. d., jabbarov o. o. application of sakabutril/valsartan in patients with chronic kidney disease with type 2 diabetes mellitus...............................5 l.s. khamraeva., d.u. narzullaeva features of calculating the optical power of an intraocular lens in children with congenital cataracts at the risk of developing pseudomyopic myopia.....................10 kasimova m. s., iminova m. m., ashurov o. m. ophthalmologic complications in the structure of the clinical features of novel coronavirus infection (covid-19)......................................................................................................14 fattayeva d.r., rizayev j.a., rakhimova d.a. improvement of methods for correction of clinical and immunological disorders in comorbid state of chronic gaymoritis after covid-19....................................................................17 polatova d.sh., abdukarimov kh.g., davletov r.r., savkin a.v., sultanov b.b features of immunobiological heterogeneity in patients with osteosarcoma.................................................................................25 volume-1 issue-1 art of medicine international medical scientific journal 25 features of immunobiological heterogeneity in patients with osteosarcoma polatova d.sh., abdukarimov kh.g., davletov r.r., savkin a.v., sultanov b.b republican specialized scientific and practical medical center of oncology and radiology of the ministry of health of the republic of uzbekistan, tashkent tashkent state dental institute abstract the aim of the research was to study the characteristics of immune changes in patients with osteosarcoma before starting therapy. the presence of an immunodeficiency state in patients with osteosarcoma, which was expressed in deep t cellular immunodeficiency and activation of the humoral immunity, was established, which allows early immunological diagnosis of the progressive course of the malignant process. it is planned to further study the cytokine status, which plays an important role in the formation, development and progression of osteosarcoma. consequently, our results will help practitioners in understanding the molecular-immunological behavior in osteosarcoma, which will make it possible to establish the immunopathogenetic features of the course of the disease, its severity and prognosis, to differentiate periods of exacerbation and remission, which will also make it possible to assess the effectiveness of drug therapy. the immunoreactivity of patients with osteosarcoma is characterized by an increase in the total number of leukocytes, which is a sign of inflammation, cd8 + cytotoxic t lymphocytes, cd16 + lymphocytes, cd20 + lymphocytes and cd38 + lymphocytes, small and large cics against the background of suppression of cd3 + lymphocytes, cd4 + and iri. the pronounced indicators of suppression of immunity and the progression of the disease were iri and cic. on the part of humoral immunity factors, the increased serum values of igg and iga turned out to be of paramount importance. an imbalance of t-lymphocyte subpopulations was also revealed. there is a decrease in the immunoregulatory index from 0.4 to 1.1 (normally from 1.5 to 2.0), which is an indicator of an unfavorable course of the disease and immune response. key words: osteosarcoma, immunity, cellular parameters of immunity, humoral parameters of immunity, heterogeneity of immunity, oncology. topicality. osteosarcoma is referred to as the most aggressive human tumor disease, which is mainly due to the tendency of these neoplasms to early hematogenous dissemination [1,4,7,8,11]. despite the success achieved in recent years in the treatment of these diseases, a number of aspects related to the biological characteristics of osteosarcoma remain poorly understood [4,8,9,14,25]. one of the directions, the study of which can influence the results of treatment, is the study of the characteristics of immune behavior and heterogeneity in this category of patients. in recent years, a number of new techniques have been actively introduced into clinical practice to assess the immunity of patients, in particular, the study of the phenotype of peri pheral blood lymphocytes using monoclonal antibodies to their differentiating antigens [6,10,17,21,26]. at the same time, information on the state of immunity in patients with osteosarcoma was obtained using insufficiently informative research methods on a small clinical material [4,7,13,17]. the currently available information does not allow to fully describe the changes in immunity characteristic of these diseases on an equal footing of the populations and subpopulations of blood lymphocytes. we studied the immunological changes occurring against the background of combined treatment, and the true changes in osteosarcoma, especially immune art of medicine international medical scientific journal volume-1 issue-1 26 material and research methods. research had been carried out at the republican specialized scientific and practical medical center of oncology and radiology of the ministry of health of the republic of uzbekistan since 2005. there were 221 patients with verified osteosarcoma under observation. the control group consisted of 48 healthy individuals of the same age and sex. the diagnostic program included generally accepted measures, such as an objective examination, anamnesis, x-ray examination of the affected bone, x-ray examination of the chest organs, ultrasound of the tumor zone and surrounding tissues, regional lymph nodes, abdominal organs and retroperitoneal space, in order to identify distant metastases, cytological examination of the primary tumor and obligatory histological examination of biopsy and postoperative material with an assessment of the degree of therapeutic pathomorphosis. analysis of the distribution of the examined patients by sex: men 133 (60.1%), women 88 (39.8%). with the distribution of patients by age in our studies, it turned out that osteosarcoma was more common in the group of patients from 18 to 35 years old (45.3%) with the incidence of the disease among men 28.9 ± 3.0% (64) and women 16.3 ± 2.4% (36). the average age in the general group was 23.78 ± 1.52 years for women and 21.24 ± 0.80 years for men. the prevalence of the process was assessed according to the international tnm classification (classification of the international union against cancer, 2007). in accordance with this, in the studies, patients were distributed taking into account the stage of the disease: in 187 (84.6 ± 3.2%) patients, stage t2n0m0 was determined, in 26 (11.8 ± 1.7%) t2n0ml, t1n0m0 in 8 (3.6 ± 0.8%). according to the clinical classification, the patients were also divided into stages: ib 8 (3.6 ± 1.2%), iia 12 (5.4 ± 1.5%), iib 125 (56.5 ± 3.3% ), iii 62 (28.0 ± 3.0%), iva 11 (4.9 ± 1.4%), ivb 3 (1.3 ± 0.7%). immunological studies included the study of cellular and humoral parameters of the immune system of patients with osteosarcoma before treatment. immunological studies were carried out at the institute of immunology of the academy of sciences of the republic of uzbekistan, in the laboratory of immunocytokines. determination of cellular immunity (cd3 +, cd4 +, cd8 +, cd16 +, cd20 +), as well as identification of activation markers of lymphocytes (cd38 + and cd95 +) was carried out using monoclonal antibodies, sorbent, moscow. the humoral link of immunity was assessed in the serum of peripheral blood by the elisa method. for clarity of the results obtained, all the studied parameters of the state of the immune system of patients were converted into percentages in relation to 100% for the norm. the reliability of the differences revealed in the analysis of quantitative features was assessed using the student-fisher test. methods of variational parametric and nonparametric statistics with m, σ, m, relative values (frequency,%) were used, the statistical significance of the obtained measurements when comparing the mean values was determined by the student's test (t) with the calculation of the error probability (p) when checking the normal distribution (by kurtosis criterion) and equality of general variances (f fisher's criterion). the level of significance p <0.05 was taken as statistically significant changes. results of the research the study of the state of the immune system in osteosarcoma undergoes certain difficulties, which are expressed in the instability of the course of the oncological process, in the presence of various forms and morphological variants of the disease. in connection with the above, the study of the immune system of patients with osteosarcoma has not only scientific, but also practical importance for assessing the state of the immune system and predicting the disease. it is known that the leading role in the antitumor defense of the organism is given to the cellular link of immunity, where t-lymphocytes play a key role. the expression of t-cell markers of lymphocytes was determined by the relative number of cd3 + t-lymphocytes, cd4 + thelpers / inducers and cd8 + t-cytotoxic lymphocytes, as well as by the value of the cd4 + / cd8 + ratio (immunoregulatory index iri). it was found that the phenotypic markers of t-lymphocytes include cd3 +, cd4 +, cd8 + receptors. it has been shown that the triggering and regulation of the effectiveness of the immune volume-1 issue-1 art of medicine international medical scientific journal 27 response is largely determined by the specific antigen of t-lymphocytes. it is known that the degree of surface expression of cd3 + receptors on the membrane of t-lymphocytes reflects its transmissive function and makes it possible to identify the total number of t-lymphocytes [4,5,8,14,16,24,27]. analysis of the t cellular link of immunity showed that the state of the immune system of patients with osteosarcoma is manifested by an imbalance of cellular and humoral parameters of immunity. at the same time, the immune system of patients with osteosarcoma is characterized by an increase in the total number of leukocytes, which is a sign of inflammation against the background of suppression of the total number of lymphocytes, cd3 + t-lymphocytes, cd4 + tlymphocytes, iri against the background of an increase in cd8 + t-lymphocytes, cd16 + tlymphocytes , cd20 + b-lymphocytes, cd38 + tand b-lymphocytes and cd95 + marker of apoptosis, as well as an increase in cic of small and large values. the results obtained characterize the state of immunoreactivity of patients with osteosarcoma, and can serve as diagnostic and prognostic criteria for monitoring during therapy. thus, the most informative were the changes at the level of subpopulations of activation markers. as for the humoral factors of immunity, it should be noted that in patients with osteosarcoma, there is a significant increase in the concentration of igg and iga against the background of a decrease in the serum concentration of igm. thus, for the first time in uzbekistan, an attempt was made to conduct a study of immunity at the level of populations and subpopulations of lymphocytes depending on osteosarcoma. the studies were carried out in comparison with the indicators of the control group. thus, the features of the immune status of patients with osteosarcoma in comparison with healthy individuals have been established. the signs of osteosarcoma were revealed, the characteristic variability of which is reflected in the picture of immunological parameters. changes in populations and subpopulations of lymphocytes that occur before the start of specific therapy have been studied. the immunological parameters characteristic of osteosarcoma were determined. an immunodeficiency state was revealed in patients with osteosarcoma, which was expressed in deep t cellular immunodeficiency and activation of the humoral link of immunity, which allows for early immunological diagnosis of the progressive course of the malignant process. it is planned to further study the cytokine status, which plays an important role in the formation, development and progression of osteosarcoma. consequently, our results will help practitioners in understanding the molecular-immunological behavior in osteosarcoma, which will make it possible to establish the immunopathogenetic features of the course of the disease, its severity and prognosis, to differentiate periods of exacerbation and remission, which will also make it possible to assess the effectiveness of drug therapy. thus, the analysis revealed that the immunoreactivity of patients with osteosarcoma is characterized by an increase in the total number of leukocytes, which is a sign of inflammation, cd8 + cytotoxic t lymphocytes, cd16 + lymphocytes, cd20 + lymphocytes and cd38 + lymphocytes, cic of small and large values against the background of suppression of cd3 + lymphocytes , cd4 + lymphocytes and iri. the pronounced indicators of suppression of immunity and the progression of the disease were iri and cic. on the part of humoral immunity factors, the increased serum values of igg and iga turned out to be of paramount importance. an imbalance of t-lymphocyte subpopulations was also revealed. there is a decrease in the immunoregulatory index from 0.4 to 1.1 (normally from 1.5 to 2.0), which is an indicator of an unfavorable course of the disease and immune response. art of medicine international medical scientific journal volume-1 issue-1 28 references 1.adhikari a.s. cd117 and stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance // cancer res. 2010.т.70.no11. р.4602. 2.antony p., restifo n. cd4+ cd25+ t regulatory cell, immunotherapy of cancer, and interleukin-2 // j. immunother. 2005. – v.28. – p.120-128. 3.bacci g., longhi a., ferrari s. prognostic significance of serum alkaline phosphotase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: recent experience at rizzoli institute // oncol. rep.-2002.-vol.9, n.l.р.171-175. 4.barbieri f. cxc receptor and chemokine expression in human meningioma: sdf1/cxcr4 signaling activates erk1/2 and stimulates meningioma cell proliferation // ann. n. y. acad. sci.2006.-v.1090.p.332-343. 5.barlett 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2007;109:693–702. 27.linterman ma, pierson w, lee sk, kallies a, kawamoto s, rayner tf, et al. foxp3(+) follicular regulatory t cells control the germinal center response. nat med. 2011;17:975–82. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 128 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 129 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 130 comparative analysis of the results of therapy according to the protocols allbfm-95m and all-mb-2008 in uzbekistan ibragimova s.z. center for professional development of medical workers, ministry of health of the republic of uzbekistan, tashkent, uzbekistan abstract. the results of treatment of 368 primary patients with all (aged from 1 to 18 years) were analyzed. of these, 145 received treatment according to the all-bfm -95m protocol and 223 children according to the all-mb-2008 protocol in the children's department of the republican specialized scientific and practical medical center of hematology. clinical, morphological, immunological, molecular genetic research studies of bone marrow and statistical methods for processing the results. the results of therapy of 145 patients according to the all-bfm-95m protocol were analyzed. overall survival (os) was 48% ± 4% (67 patients). the 10year disease-free survival (efs) was 48% ± 4% (67 patients). the cumulative recurrence risk (cir) was 38% ± 4.1% (53 patients). there were 11.2% ± 2.6% of cases of deaths associated with therapy (trd) 16 patients. according to the results of therapy, 223 patients who received treatment according to the all_mb-2008 protocol: overall survival (os) was 75% ± 3% (162 patients). the 10-year relapsefree survival (efs) was 71% ± 3% (152 patients), the cumulative recurrence risk (cir) was 16.4% ± 2.5% (36 patients). there were 8.8% ± 1.9% of cases of deaths associated with therapy (trd) 19 patients. in a comparative analysis of the results of treatment programs with different intensities of chemotherapy, 10-year relapsefree survival (efs) according to the all-bfm-95m protocol was 48% ± 4% versus 71% ± 3% according to the all-mb-2008 protocol. the percentage of achieving remissions was higher in patients under the all-mb-2008 protocol, 95.1% (n = 213) compared to 90.3% under the all-bfm-95m protocol (n = 131, p = 0.0765). thus, it is possible to reduce the intensity and toxicity of the chemotherapy performed without reducing the final results of treatment. at the same time, the high intensity of chemotherapy according to the all-bfm-95m protocol was the reason for the high induction mortality. keywords: children, acute lymphoblastic leukemia, chemotherapy, risk groups, survival, relapse introduction. acute lymphoblastic leukemia (all) occupies a leading place in the structure of oncohematological pathology in childhood and adolescence. it accounts for up to 20% of all malignant diseases (fiel r.j. et al., 1988) and up to 75% of all leukemias (stiller c.a. et at., 1990) [1,2,9]. the high efficiency of all treatment in children is one of the most impressive achievements of modern medicine. the programs of chemotherapy, developed over the last period, all in children can achieve a cure in 80% of patients with all [3,4,6]. currently, there are opportunities for organizing effective measures for early diagnosis, treatment and art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 131 prevention of complications [11,12]. in particular, the successful experience of introducing in russia the original moscow-berlin protocol, created in cooperation with the charite clinic (berlin, germany), has shown the effectiveness of multicenter research technology in hematology/oncology to optimize the therapy of hematological malignancies in children [4,13]. earlier in uzbekistan, non-programmed treatment of all was carried out with a very low disease-free survival rate close to zero, then in 1999 it was started according to the all-bfm-95m protocol without immunophenotyping and molecular genetic analyzes, without stratification into risk groups. since 2008, the implementation of the new all-mb-2008 protocol began, which involves riskadapted therapy using new diagnostic technologies [3,8]. advances in all treatment have demonstrated the potential of modern high-dose chemotherapy, the role of concomitant therapy, and the important role of multicenter randomized clinical trials. in this all-mb-2008 protocol, stratification was carried out into 3 risk groups, which was carried out taking into account the size of the spleen, initial leukocytosis, the results of immunophenotyping and molecular genetic research [4, 2]. isolation of such prognostic factors as the age and sex of patients, initial leukocytosis, lesions of the central nervous system and mediastinum, the immunological phenotype of the tumor substrate, served as a rationale for modifying therapy programs, reducing the toxic effects of therapy for patients with a good prognosis and, conversely, for intensifying treatment protocols for patients. high risk, which significantly increased their chances of survival [4,5,6]. of all the known prognostic factors, only the factors associated with the ongoing therapy can be modified and improved as the treatment protocols are optimized [4,10,13]. material and research methods. the results of treatment of 368 primary patients with all (aged from 1 to 18 years) were analyzed. of these, 145 received treatment according to the all-bfm -95m protocol and 223 children according to the all-mb-2008 protocol in the children's department of the republican specialized scientific and practical medical center of hematology. the analysis included 368 patients, including 226 boys (61.4%) and 142 girls (38.5%) aged 1 to 18 years (median age 5.1 years). the number of boys (63.4% and 60.1%) and girls (36.6% and 39.9%), depending on the treatment protocol, is approximately the same (p = 0.5178). according to age groups, patients were distributed as follows: up to 10 years 300 (81.5%); from 10 to 18 years old 68 (18.5%). the age composition of the patients of both groups is approximately the same: <10 years 76.6% and 84.3%, >10 years 23.4% and 15.2%, respectively (p = 0.0476). there were 198 (53.8%) patients with initial leukocytosis in peripheral blood (pc) less than 10,000 / μl; more than 100,000 / μl 54 (14.7%). depending on the initial leukocytosis, the distribution of patients also does not differ: <10 thousand 51.7% and 55.2 (p = 0.5186), >10 thousand<30 thousand. 17.7% and 9.5% (p = 0.6837), >30 thousand<100 thousand. 16.6% and 13% (p = 0.3436), >100 thousand 15.9% and 13.9% (p = 0.6034). art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 132 the proportion of patients with an initial increase in the size of the spleen (more than 4 cm) was 38.3% (n = 141), did not depend on gender and was the same in different age groups. according to the size of the spleen, the distribution of patients is also the same: spleen <4 cm 56.6% and 64.6%, spleen >4 cm 43.4% and 35% (p = 0.1024). initial cns damage was registered in 5 (3.2% of patients), 2.8% and 0.4% in patients of two groups, respectively (p = 0.0614) (see table 1.). table 1. initial characteristics of patients bfm-95 mb-2008 p n % n % total 145 100 223 100 sex boys 92 63.4 134 60.1 0.5178 girls 53 36.6 89 39.9 age <10 111 76.6 189 84.3 0.0476 >=10 34 23.4 34 15.2 leukocytosis <10 75 51.7 123 55.2 0.5186 >=10 <30 23 15.9 39 17.5 0.6837 >=30 <100 24 16.6 29 13 0.3436 >=100 23 15.9 31 13.9 0.6034 spleen <4 82 56.6 145 64.6 0.1024 >=4 63 43.4 78 35 answer 8 day <1000 142 100.0 108 86.4 <0.0001 >=1000 0 0 17 13.6 неизвестно 3 98 answer 15 day <10 108 76.6 89 70.6 0.2689 >=10 <30 25 17.7 12 9.5 0.0526 >=30 7 5.0 25 19.8 0.0002 неизвестно 5 97 cns defeat 4 2.8 1 0.4 0.0614 immunophenotyping b-all 3 2.1 123 55.2 non b-all 0 0 15 6.7 unknown 142 97.9 85 38.1 cytogenetics t(4;11) 0 0 0 0 t(9;22) 0 0 4 1.8 t(12;21) 0 0 8 3.6 unknow 145 100 154 69.1 risk group srg 57 39.3 83 37.2 0.6864 art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 133 imrg 68 46.9 121 54.3 0.1672 hrg 20 13.8 19 8.5 0.1083 research methods: clinical, morphological, immunological studies of bone marrow by flow cytofluorimetry in the russian children's clinical hospital (moscow), molecular genetic research of bone marrow in the laboratory of biochip diagnostics of the federal scientific clinical center for pediatric hematology, oncology and immunology named after v.i. dmitry rogachev ”ministry of health and social development of russia (moscow) and statistical methods for processing the results. results and discussion. the results of therapy of 145 patients according to the all-bfm-95m protocol were analyzed. overall survival (os) was 48% ± 4% (67 patients). the 10year disease-free survival (efs) was 48% ± 4% (67 patients). the cumulative incidence of relapse (cir) was 38% ± 4.1% (53 patients). there were 11.2% ± 2.6% of cases of deaths associated with therapy (trd) 16 patients. (see figure 1). the results of therapy of 223 patients who received treatment according to the all-mb-2008 protocol were analyzed. overall survival (os) was 75% ± 3% (162 patients). the 10-year disease-free survival (efs) was 71% ± 3% (152 patients). the cumulative incidence of relapse (cir) was 16.4% ± 2.5% (36 patients). there were 8.8% ± 1.9% of cases of treatment-related death (trd) 19 patients. the results are presented in figure 1 and table 2. fig. 1. treatment results according to the protocols all-bfm-95m and allmb-2008 table 2. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 134 results of therapy by risk groups according to the all-bfm-95m protocol the distribution of patients by risk groups was srg 57 patients, 30 of them in ccr, efs was 56%. 68 patients were assigned to the imrg group, 30 in ppr, efs was 46%. hrg was 20 patients, 7 in pr, efs was 35%. there is also a high relapse rate in hrg of 40%. in the srg group, 37.1% (20), in the imrg group, 38% (25), the relapse rate is also high. a high percentage of relapses is possibly associated with an unknown immunophenotype and cytogenetics, the lack of the possibility of stratification into risk groups and, as a consequence, of adequate therapy, when all patients, regardless of the risk group, received the same therapy. (see figure 2.) art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 135 fig. 2. results of treatment by risk groups according to the all-bfm-95m protocol it is noteworthy that the frequency of induction deaths is quite high and amounts to 6.9% for all patients, and 9.18% in the hrg group. induction mortality rates did not differ in srg and imrg 6.9%. mortality in remission was 4.1%; it did not differ in the standard and intermediate risk groups. in 2.8% of patients were resistance (non-responder) to chemotherapy. there were no secondary tumors in the study group. in 53 patients (36.6%), the development of a relapse of all was recorded, while among srg patients more than 70% of relapses developed 6 months after the end of therapy and later, then in imrg and hrg patients, very early and early relapses prevailed. in general, and among individual risk groups, isolated bone marrow relapses prevailed. the incidence of relapses with cns involvement was 18.8% among all patients, 5.6% in srg and 11.3% in imrg. the incidence of combined bm+cns relapses is higher in imrg –3.7% (2); 5 patients lost to followup 3.4% (lfu). relapses with lesions of the testicles were registered in 2 (3.7%) patients, in 2 more patients with combined bone marrow and testicular. results of therapy by risk groups according to the all-mb-2008 protocol the distribution of patients by risk groups was srg 83 patients, 68 of them in ссr, efs was 83%. 121 patients were assigned to the imrg group, 79 in ppr, efs was 69%. hrg was 19 patients, 5 in ссr, efs was 30%, it should be noted that due to the lack of the possibility of high-dose chemotherapy according to the all-mb2008 protocol and the possibility of performing allogeneic bmt, patients in this group received treatment at an intermediate risk group. there is also a high relapse rate in hrg of 42.5%. in the srg group, 8.5% (7) relapses, in the imrg group, 18.2% (21) relapses were recorded. (see figure 3) the high relapse rate in the intermediate risk group is possibly associated with a large number of patients with unknown immunophenotype and cytogenetics. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 136 figure 3. results of treatment by risk groups according to the all-mb2008 protocol the incidence of induction deaths was 1.8% for all patients, 6.18% in the hrg group. induction mortality rates did not differ in srg and imrg. mortality in remission was 6.7%, did not differ in the groups of standard and intermediate risk and was about 5%. in 1 patient, the development of a secondary tumor was registered 15.2 months after the end of all therapy in the form of bladder cancer. in 36 patients (16.1%), the development of a relapse of all was recorded, while more than 50% of relapses were late among srg patients, more early relapses were observed in imrg and hrg patients. isolated bone marrow relapses prevailed in all risk groups. there were 5 (13.8%) isolated cns relapses among all patients, most of them were in imrg, combined (bm+cns) relapses were 2. there were only 1 relapses with testicular lesions, and 1 extramedullary relapse (emr) in the form of unilateral damage to the cervical lymph node. table 3. the number and location of relapses localization of relapse all-bfm95 all-mb2008 p bone marrow 37 (69,8%) 27 (75%) 0.2689 cns 10 (18,8%) 5 (13,8%) <0.0001 testicular 2 (3,7%) 1 (2,7%) 0.0002 combined (bm + cns) 2 (3,7%) 2 (5,5%) 0.0614 combined (bm + testicular) 2 (3,7%) _ extramedullary relapse (emr) (cervical lymph node involvement) _ 1 (2,7%) total 53 (36,6% of the total 145) 36 (16,1% of the total 223) <0.0001 in a comparative analysis of the results of treatment programs with different intensities of chemotherapy, 10-year relapse-free survival (efs) according to the allbfm-95m protocol was 48% ± 4% versus 71% ± 3% according to the all-mb2008 protocol. the percentage of achieving remissions was higher in patients in the all-mb-2008 protocol, 95.1% (n = 213) compared to 90.3% in the all-bfm-95m protocol (n = 131, p = 0.0765). it should be noted that induction mortality was high in patients of the first group (6.9%) compared with the second group (1.8%, p = 0.0121). there is also a high trd of 11.2% ± 2.6% versus 8.8% ± 1.9%. there were no significant differences in the number of non-responder patients. in a comparative analysis of the risk groups of the two protocols in the standard risk group (srg), efs in the all-bfm-95m group was 56% compared to efs in the all-mb-2008 group of 83%, which is significantly higher. art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 137 in the all-bfm-95m group, the result of therapy in the intermediate risk group (imrg) was 46% efs, compared with a similar risk group in the all-mb-2008 group of 69%, which is also significantly higher. in the hrg group under the allbfm-95m protocol, efs was 35%, which is higher than under the all-mb-2008 protocol, here efs was 30%. but given the small number of patients, the comparison is unreliable. the relapse rate was significantly higher in srg and imrg risk groups when treated with the all-bfm-95m protocol. conclusions. thus, it is possible to reduce the intensity and toxicity of the chemotherapy performed without reducing the final results of treatment. at the same time, the high intensity of chemotherapy according to the all-bfm-95m protocol was the reason for the high induction lethality. the rate of death in remission in patients under the allmb-2008 protocol was somewhat high, 6.7% compared to 4.1% (p = 0.3010), but the difference was not statistically significant. about 90% of deaths are due to infectious complications. the number of relapses is significantly higher in the first group, 36.6% (53) compared to 16.1% (36), and the difference is statistically significant (p <0.0001). perhaps this is due to the fact that patients of the first group underwent the same chemotherapy regardless of the risk group, since it was not possible to carry out a full diagnosis (lack of immunophenotyping, cytogenetic studies) and stratification into risk groups, as well as non-compliance with the timing of treatment, in more than 50% of patients with this in a group of patients, post-induction chemotherapy was performed with a delay of 10 days to 20 days, although the intensity of post-induction therapy was much higher. ccr in the first group of patients was 46.2% compared to 67.9% in the second group, that is, significantly higher (p <0.0001). references 1. "the results of treatment of adolescents and young people with acute lymphoblastic leukemia according to the therapeutic protocols all-bfm-90m and all-mb-91. materials of the 1st all-russian congress of hematologists (april 1618, 2002, moscow)," problems of hematology and blood transfusion "2002, no. 1, p. 78. syomochkin sv., triputen nz, rogacheva er, loria ss, markaryan vg, alisova am, lavrukhin d.b. (in russian) 2. gavrikova n.v. clinical and immunological characteristics of the stem cell subvariant of acute lymphoblastic leukemia in children. abstract dissertation. cand. honey. nauk, m., 2000, 24 p. (in russian) 3. ibragimova s.z., babakhanova n.n., aripova n.b., rizaeva f.a., erimbetova i.o. the results of treatment of acute lymphoblastic leukemia in children according to the mb-2008 protocol. bulletin of the association of physicians of uzbekistan. 2015. no. 1с.28-30(in russian) 4. karachunsky a.i. treatment strategy for acute lymphoblastic leukemia in children. // diss. doct. honey. sciences. m 1999. s. 53. (in russian) 5.r.f. tepaev, o.a. polyakova, a.a. basistova et al. results of treatment of acute lymphoblastic leukemia in children according to modified protocols allbfm-90m and all-bfm-95m // hematology and transfusiology. 2002. t. 47. no. 4. p. 11-14. (in russian) art of medicine volume-1 international medical scientific journal issue-3 10.5281/zenodo.5842838 138 6. therapeutic efficacy of the all-bfm-90m and all-mb-91 protocols in the treatment of adolescents and young people with acute lymphoblastic leukemia. issues of hematology / oncology and immunopathology in pediatrics, 2004; 3 (2): 64-73. loria s.s., semochkin sv., triputen n.z., rumyantsev a.g. (in russian) 7. triputen nz, efficiency of treatment of adolescents and young persons with acute lymphoblastic leukemia according to all-bfm-90m and all-mb-91 protocols. abstract dissertation. cand. honey. nauk, m., 2004, 24 p. (in russian) 8. bakhramov s.m., ibragimova s.z. t-cell acute lymphoblastic leukemia in children: the experience of the treatment protocol all-mb-2008 in uzbekistan. journal of research in health science, 2018 (2), januar-april. r.-74-78 9. borkhardt a., cazzaniga g., viehmann s. et al. incidence and clinical relevance of tel / ml1 fusion genes in children with acute lymphoblastic leukemia enrolled in the german and italian multicenter therapy trials // blood.-1997.vol. 90.p. 571-577. 10. c.h. pui, s. salan, m.v. relling et al. international childhood acute lymphoblastic leukemia workshop: sausalito, ca, 30 november-1 december 2000 // leukemia. 2001. vol. 15.p. 707-715. 11. chessells j.m., bailey c., richards s.m. intensification of treatment and survival in all children with lymphoblastic leukaemia: results of uk medical research council trial ukallx // lancet. 1995 vol. 345.p. 143-148. 12. ching-hon pui, william e. evans. acute lymphoblastic leukemia // the new england journal of medicine. 1998 vol. 339.n 9.p. 605-615. 13. d.o. harms, g.e. janka-schaub. co-operative study group for acute childhood lymphoblastic leukaemia (coall): long-term follow-up of trials 82, 85, 89 and 92 // leukemia. 2000 vol. 14.p. 2234-2239. 1 volume 1, ¹4 art of medicine international medical scientific journal 2 art of medicine international medical scientific journal volume 1, ¹4 december 2021 3 volume 1, ¹4 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa chief editor dr. pascual izquierdo-egea editorial board prof. dr. francesco albano dr. catherine j. andersen prof. dr. sandro ardizzone dr. dmitriy atochin prof. dr. antonio aversa prof. dr. tamam bakchoul prof. dr. pierre-gregoire guinot prof. dr. rainer haak prof. henner hanssen 11 volume 1, ¹4 eradication of histopathological and biochemical changes in testes and reproductive organs on exposure to organophosphate, ethion department for health services research, carl von ossietzky university of oldenburg, oldenburg, germany abstract: the question-answer centered theory is another important discovery after the three major theories of modern education (student centered theory, subject centered theory and culture centered theory), and it is also the divergence of educational models between western countries and eastern countries. problem centered teaching is a theme of quality education in recent years. its core ideas mainly include: starting from problems, carrying out innovative questions, cultivating problem awareness; taking problems as a link, running through all links of "preparation, speaking, practice, assistance and examination" in chemistry teaching; cultivating creative thinking and solving problems. key words: question-answer centered theory; creative thought; question awareness; chemistry teaching introduction the german educator f.a. diesterweg ever said: "don't be keen on teaching students knowledge.try to let students find it and get it through their own activities. the real teacher is not to let the students observe the completed science building, but to lead them to participate in the construction project until the completion. through this process, they were taught the basic methods of construction. first class teachers teach students how to find the truth. second class teachers ask students to study the truth. later, an american psychologist bruna put forward the discovery method. he believed that discovery is not limited to seeking things that human beings have not yet known, but "including all forms of knowledge obtained personally with his own mind". it is suggested that the goal of structural curriculum should be realized by discovery method.students' learning and scientists' research, their intellectual activities are only different in degree but not in nature. bruner attaches great importance to human initiative and emphasizes that students should learn actively. in order to cultivate a new generation of knowledge leaders, or in the student era, the new generation will be trained as primary school students and small scientists. this kind of teaching purpose theory, curriculum theory and methodology highly unify and complement each other, which constitutes the unique style of bruner's teaching theory. this is to guide students to actively think about, explore and develop corresponding principles and conclusions based on certain problems and materials provided by teachers and books. this kind of teaching method is discovery method.discovery teaching is called discovery teaching. the discovery method creates the situation of research problems, causes similar tasks and problems of scientific research in students' consciousness, and urges them to explore and master scientific conclusions. therefore, discovery teaching is hypothetical. most of the traditional teaching methods are to teach the ready-made knowledge to students; students only want to learn what, remember what, how to memorize it and so on, and they are in a passive state of accepting knowledge. this kind of teaching is explanatory. the author thinks that "problem" is the core and essence of the discovery method. because all of these activities are inseparable from "problems". from realizing the existence of the problem, or putting forward the problem, to exploring the problem, to solving the "problem", it can be seen as a process of seeking the answer. as early as in inge köhne art of medicine international medical scientific journal 12 the spring and autumn period of china, confucius, a great educator, put forward the idea of "questioning, thinking and asking",his wise saying "there must be my teacher for three people" has been handed down to this day.in hanyu's "persuading students to learn", he said that "teachers, so preachers and dispellers" all emphasized the importance of the problem.throughout the history of mankind, outstanding creative masters and scientists have always been able to see through the smallest, commonplace and commonplace phenomena and see problems as challenges and opportunities for success,in addition, with persistent efforts, we have finally put forward the idea of straighten to "!". problem consciousness refers to the psychological state of perplexity and exploration when people realize some practical or theoretical problems that are difficult to solve and have doubts in the cognitive activities. it is reasonable to say that problem consciousness is the innate instinct of human beings and does not need to be cultivated."life is about facing problems, and solving problems is about growing wisdom," said goldford, president of the american psychological association?creative problem solving is the core of human activities. please see that as soon as the children learn to walk, they try to get rid of the shackles of adults, leave the big road that adults think is justified and used to, and go to the road that is not the road where there are mud pools, stones and weeds. to say it is not a road is to say it from the perspective of adults; to say it is a road is to say it from the perspective of children. the children didn't have the concept of road originally, it was because of the repeated instruction and coercion of parents that the children gave up the different roads every time and walked onto the recognized road [4].but mr. lu xun said: "there is no way in the world, there are many people walking, and it will become a way." this sentence is really thought-provoking. the watershed between traditional and modern education theories lies in whether children are the starting point, while modern education theories emphasize children as the starting point. the most common thing a child says when he or she is two years old is the question: "what is this?" "what is that?". at the age of three, i began to ask, "why?" until the age of five. children of this age often ask scientific questions, such as: "why can pigeons fly to the roof? why does it have wings? " why can't geckos fall down on the roof. unfortunately, with the growth of age, problem awareness tends to be weakened, so the students' problem awareness needs to be specially trained. when primary school students are just entering school, they come into the school with questions in high spirits. they are full of fantastic ideas. every child has infinite desire for knowledge and expression,therefore, on the first day when the teacher asked them questions, 60 students raised 120 hands. everyone wanted to answer the questions too much, so they all raised their hands. in the face of such high enthusiasm, the general teacher's usual reaction was: students should learn the correct posture, raise one hand, and put the other down, so the 120 small hands were reduced to 60, but this did not hinder children's enthusiasm, a hand on a hand, the rest of the hand is still very high, not only high and shaking left and right, nothing more than to attract the attention of the teacher: "i want to say, i want to say!"in the face of the enthusiasm of the students, the teacher's response is: "raise your hands to have the right posture, arms do not leave the table". although the children are a little discouraged, they quickly adapt to this requirement. hold your little hand up as required. when the children's answers meet the standard answer, they will be affirmed and praised by the teacher. if they are unique or ask some absurd questions, they will inevitably be criticized and ridiculed. in the face of such a situation, the enthusiasm of children to ask questions is gradually reduced. we can see the following situation: the students in the lower grade of primary school are like a forest of small hands, the students in the higher grade of primary school are gradually sparse, 13 volume 1, ¹4 the students in the middle school raise their hands only like stars, and no one raises their hands in the high school. they understand the rules of answering questions, and know that if they don't answer or ask questions, there will be no trouble, but if they don't answer well, there will be unpleasant results,this is the first; the second is that all the questions of teachers have standard answers, and asking is only a means. people gradually learn to listen passively and wait for teachers to ask and answer themselves. with the development of this kind of attitude, the problem consciousness is also gradually weakened. only when college students and graduate students do knowledge will they find that the previous problem consciousness and thinking ability are quite important for scientific research and invention and creation, but "stereotype" limits their thinking ability. in the face of students' questions, we should encourage the questioners to find information, provide possible answers, and evaluate the possible answers. since the establishment of the education system, there have been special problems. the problem is the accompanying production of the education system. since we have textbooks, we have exercises. that's right and wrong. after chinese children come home from school, the first sentence of parents is: "have you finished your homework today? does the teacher still assign homework? " and another country in the world, like china, which is particularly concerned about the next generation of education, israel, when the children come home from school, the first words of parents are: "did you ask the teacher at school today?" if the child says proudly, "yes, the teacher didn't answer!" then parents will be as happy as their children.another example: at the end of 1998, an american science education delegation visited shanghai, hoping to listen to an open class of science education in high school. the receptionist arranged a very famous key middle school to give them a physics lesson in the first year of high school. the teacher is an excellent super teacher. in the teaching process, the teaching purpose is clear, the teaching content is clear, the teaching method is flexible, there is theory and experience; the teaching process is active, the teacher asks questions, the students answer questions, the teachers and students interact with each other, and the atmosphere is warm; the teacher's language is accurate and concise, and the teaching time is well arranged, when the teacher says, "this class will come here." wait, the bell for class is ringing. according to our habitual concept, this class is seamless. next, nearly 100 teachers applauded as the bell rang. but five american guests had no expression. the next day when the receptionist asked them to talk about their impressions, their answers were unexpected. they asked, "the teacher asked questions and the students answered questions in this class. since all the students can answer the teacher's questions, what else can they do in this class?"it can be seen that different countries have different educational traditions and need international exchanges and mutual reference to develop their strengths and make up for their weaknesses. in the traditional teaching process, the knowledge transfer to students is basically realized by recurring and concluding questions. but in the above two ways of asking questions, students are allowed to accept the ready-made knowledge in books, without fully considering how to teach students to create, so it is impossible to cultivate students' creativity very well. the fundamental purpose of learning is to better serve human beings. for example, according to the law of gravitation, scientists have made earth satellites. therefore, it is an urgent task for us educators to cultivate students' creativity, ask creative questions and make them have creative thinking. many scientific discoveries come from problems, such as newton's discovery of the law of gravitation: why did apple land? if you take this question to ask a person who has no scientific brain, he will definitely say: "nonsense, where does apple fall? will it fall into the sky? " but newton art of medicine international medical scientific journal 14 spread out his imagination wings. he thought, "why does the apple on the tree fall on the ground instead of fly to the sky? no matter how high the apple tree is, the apple will fall, so it has nothing to do with the height of the tree. if the tree is higher than the moon, will the apple fall from the moon? isn't the moon a big apple? why doesn't it land on earth? " after a series of in-depth and detailed research, we finally found the law of universal gravitation. the graduation project of the famous "massachusetts institute of technology" and "harvard university" needn’t write papers, but to submit physical works, which is a good method. creative questioning is to raise creative questions in teaching, and then lead to the teaching of creative thinking. first of all, we must make clear what is creative problem. in order to be creative, one of the following two conditions must be met: first, the problem should enable students to understand the actual process of previous creation. second, the problem should be able to make students try to carry out a creative activity. this is the starting point to analyze whether a problem has creativity in teaching. for a specific question, we should consider the following two aspects to judge whether it is creative: first, the relationship between the question and the existing knowledge level of students; second, the way of asking questions. that is to say, how to ask questions can make them think positively and answer enthusiastically in the direction you expect, so as to avoid students' feeling that "a dog has no place to bite a hedgehog". creative teaching questions are mainly to let students understand the ways of previous research and problem-solving, in which the knowledge of scientific history and chemical history is essential. the development of science is a model of putting forward solving putting forward again in practice solving problems. it is called "learning by doing" for researchers to study and work with problems. college students with problems to attend classes, to learn, will receive twice the result with half the effort. for example, when talking about the theory of acid and alkali, from the earliest proposal of the concept of acid and alkali to the coming out of "arrhenius's acid and alkali ionization theory", let students understand the development of the theory along the historical footprint, and understand its historical contribution and limitations. in order to solve the problems left by this theory, the "acidbase proton theory of brownstead" is introduced. when one problem is solved, another problem arises. this problem needs to be solved by another theory "acid-base solvent system theory". in this way, in the exploration of solving the old problems and generating new problems, we have comprehensively mastered the modern acid-base theoretical knowledge.suhomlinsky pointed out that "research-based learning refers to a learning method in which students obtain knowledge and apply knowledge in a similar way to scientific research under the guidance of teachers."this method follows the law that the teacher's leading role and the student's main role are opposite, unified and mutually restricted, embodies the guiding ideology of heuristic teaching, and realizes the principle of democratization and subjectivity of teaching. this educational concept is the value and goal to be established and pursued in the implementation of quality education today. through research and learning, students' questioning ability can be cultivated. the socalled research, first of all, is to detect the existence of the problem, clarify the content of the problem, and then form a hypothesis, and then verify or overturn the hypothesis through experiments, surveys, literature review and other methods, and then write the research process, data or conclusions into a report, if possible, make suggestions. participate in research questions, let students experience the actual process of invention and creation under the guidance of teachers, so as to preliminarily realize the attempt and imitation of creation activities. in fact, research is also based on problems. if there is no "problem", what should we study? and we can train students' innovation ability in one question and many questions. for example, when we talk about super-acid, we mentioned that hf 15 volume 1, ¹4 belongs to the category of super-acid, and its acidity is stronger than h2so4. some students are confused. at this time, "why hf belongs to superacid" should be put forward and answered in time. to answer this question, we may first ask a question: "what acid is the most acidic among the acids we have learned in basic inorganic chemistry?" "how does its acidity manifest?" some students answered h2so4, some said hno3, some said hci, and some said "aqua regia", so aqua regia is the strongest in terms of its solubility to metals. the reason is that in the aqua regia system with the strongest solubility, it contains not only strong oxidants such as hno3, cl2 and nocl, but also high concentration of clwhich is easy to form stable complexes with metalions. for example, [aucl4]or [ptcl6]2-, thus reducing the concentration of metal ions, which is conducive to the reaction in the direction of metal dissolution. next, we will further question the condition of hf as weak acid. under what circumstances is hf weak acid? students often have incomplete answers. in fact, hf is a weak acid when the concentration is small. when the concentration is large, the acid is very strong. the next answer is that hf is the reason for superacidity. through the analysis, we know that the root cause of not accepting hf as super acid is that their thoughts are still "immersed in aqueous solution". we can make a finishing point. the premise of discussing super acid is "in non-aqueous solution", turn this around first, and then explain the characteristics of especially strong protonation ability. after step-bystep explanation, students can master it well, i was also very impressed.another example is to give students a bottle of colorless solution or white precipitate to analyze its components. students can solve this problem better than giving them ten theoretical lessons to explain this problem. it is an excellent content to use the analysis scheme of anion and anion system in chemical analysis, but many schools have cut off this chapter because they are too troublesome and time-consuming. it's not worth the loss! therefore, it is quite reasonable for some chemistry departments of key universities to arrange the experimental class hours as well as the theoretical class hours, or even more than the theoretical class hours. stephen divides the questions in the discussion into seven types and points out that the core pillar of participating in the discussion is to master the skills of questioning, listening and answering. the students' knowledge and skills are formed between asking and being asked, answering and being answered. the ability of asking lies in the students. it depends on the teachers' level whether they can run through the teaching with questions. some problems are relatively simple, and most of them are very complex, so we need to learn the skills of finding problems. this skill is not the stars in the sky, but can be mastered by everyone through learning. the way to learn is to understand and practice. after a period of training, you will get the courage necessary to face the problem. art of medicine international medical scientific journal 16 references. 1.noecker a m, chen j-f, zhou q, et al. development of patient-specific threedimensional pediatric cardiac models. asaio j,2006;52:349–353. 2.noecker a m, cingoz f, ootaki y, et al. the cleveland clinic pedipump: anatomic modeling and virtual fitting studies in a lamb model. asaio j,2007;53:716– 719. 3.saeed d, ootaki y, noecker a. m, et al. the cleveland clinic pedipump: virtual fitting studies in children using three-dimensional reconstructions of cardiac computed tomography scans. asaio j,2008;54:133–137. 4.khalpey z, kazui t, ferng a s, et al. first north american 50 cc total artificial heart experience: conversion from a 70 cc total artificial heart. asaio j,2016;62:e43– e45. 5.carpentier a, latrémouille c, cholley b, et al. first clinical use of a bioprosthetic total artificial heart: report of two cases. lancet,2015;386:1556–1563. 6.morris, r. j. the syncardia total artificial heart: implantation technique. operative techniques in thorac cardiovasc surg,2012;17(2):154–164. 7.torregrossa, g, anyanwu a, zucchetta f, et al. syncardia: the total artificial heart. ann cardiothorac surg,2014;3(6):612–620. 8.morshuis m, schulz u. kunstherzen (tah); tah: cardiowest. in boeken u, assmann a, born f, et al. mechanische herz-kreislauf-unterstützung. springer-verlag gmbh, berlin,2013:156–182. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 116 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 117 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 118 efficacy of empagliflozin in older patients with chronic heart failure with preserved left ventricular ejection fraction tulaboeva g.m., talipova yu.sh., sagatova x.m., xusanov a.a., abdukodirova n.m. center for the development of qualifications of medical workers under the ministry of health of the republic of uzbekistan, department of cardiology and gerontology abstract: chronic heart failure (chf) is the leading cause of hospitalization in europe, the united states and asia. mortality in chf increases with each hospitalization. chf with preserved ejection fraction (ef) occurs when the heart muscle contracts ineffectively and there is reduced blood flow in the body compared to a normally functioning heart. numerous studies have shown that symptoms associated with heart failure, such as shortness of breath and fatigue, can negatively affect quality of life. keywords: chronic heart failure, introduction. despite the availability of a wide choice of medications for the treatment of chf, which can improve the survival rate of patients, the prognosis of the disease remains unfavorable [1, 2], therefore, the search for new treatment options for this pathology is an urgent task of modern cardiology. there are numerous contradictory data regarding the use of empagliflozin in chf. empagliflozin, a selective inhibitor of the sodium-dependent glucose transporter type 2 (sglt2), became the first antihyperglycemic drug to be superior to placebo in cardiovascular safety. empagliflozin, a specific inhibitor of sglt2, is a representative of a promising new class of drugs that lower glucose levels, independent of insulin. in addition to its well-proven glycemic effect, ample evidence suggests cardioprotective potential. empagliflozin is able to improve myocardial microvascular perfusion, enos activity, and endothelium-dependent relaxation. empagliflozin may have a beneficial effect by art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 119 inhibiting dm-induced mitochondrial division in a 5'amp-activated protein kinase (ampk) dependent manner. on the one hand, the action induced by this drug can slow down the aging of endothelial cells by suppressing oxidative stress, which leads to an improvement in their viability and barrier function. on the other hand, empagliflozin-induced endothelial migration as a result of f-actin homeostasis may promote angiogenesis [4]. with the progression of diabetes, endothelial damage is detected at an early stage. thanks to these mechanisms, empagliflozin improves the blood supply to the myocardium. significant data indicate the ability of empagliflozin to reduce systolic blood pressure by facilitating osmotic diuresis, influencing the microvascular diastolic response by stimulating enos phosphorylation, vascular remodeling, reducing the level of inflammatory proteins, and decreasing collagen synthesis [4]. the principle of action of type 2 sodium glucose cotransporter inhibitors is based on a decrease in glucose reabsorption in the proximal renal tubules, which leads to an increase in urinary glucose excretion and a subsequent decrease in plasma glucose levels. this mechanism of action is insulin-independent and, therefore, has a low risk of hypoglycemia [3, 4, 5]. it should be noted that earlier, within the framework of the emperor-reduced study, it was shown that the sglt2 inhibitor empagliflozin reduces the risk of death and hospitalization due to chf decompensation in patients with reduced lvef by a quarter [8]. it is important to note that the emperor-preserved and emperor-reduced projects are part of a program to study empagliflozin in patients not only with metabolic disorders, but also with pathologies of the cardiovascular system and kidneys. thus, the drug is currently being investigated in patients with chronic kidney disease (ckd), as well as in patients with acute myocardial infarction and a high risk of chf [8]. on the other hand, sglt-2 inhibitors have also shown a significant reduction in the risk of hospitalization not only for chf, but also for end-stage ckd. as a consequence of this growing body of evidence, the focus of t2dm treatment has shifted from glucose control to organ preservation. sglt-2 inhibitors have become a art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 120 key tool in the treatment of cvd and in reducing the progression of ckd. the results of large randomized controlled trials, which included patients with and without type 2 diabetes, have shown that glyflozin therapy is associated with a decrease in hospital admissions for chf and the progression of ckd. in t2dm, the positive effects of sglt-2 inhibitors appear early and do not depend on the effect on lowering the level of glycemia [6, 7, 8]. the above aspects made it possible to determine the purpose of the study. target. to assess the effect of the inhibitor empagliflozin on exercise tolerance, quality of life, on the endpoints of chf in older persons with preserved left ventricular ejection fraction. material and research methods. this study evaluated the efficacy and safety of empagliflozin in patients with chronic chf with preserved lvef. the present study included 115 patients aged from 62 to 78 years (average age 71.2 ± 3.6 years) with chf with verified data of clinical and instrumental analyzes diagnosed with chf functional class (fc) ii and iii. the new york heart association (nyha) classification by functional class was used to enroll patients in the study groups. patients, depending on the therapy performed by the method of "random" sampling, were divided into 2 groups: group 1 (n = 75, main group) of patients on the background of standard chf therapy took empagliflozin (emgalif, orville services) 10 mg / day and group 2 (control group, n = 40) who took only standard therapy. the observation period was 12 weeks. the study was carried out at the clinical base of the department of cardiology and gerontology of the center for the development of professional qualifications of medical workers at the ministry of health of the republic of uzbekistan. all patients underwent a 6-minute walk test at baseline and at the end of the study, and underwent quality of life, blood lipid composition, and resting echocardiography. the criteria for exclusion from the main study group were: art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 121 hypertrophic, restrictive, obstructive or dilated cardiomyopathy, constructive pericarditis, primary pulmonary hypertension or cor pulmonale, myocarditis; acute myocardial infarction (or less than 30 days after its development), coronary artery bypass surgery (within 6 months), unstable angina pectoris, valvular heart disease, acute cerebrovascular accident (within 6 months), renal or hepatic failure, autoimmune or endocrine diseases. the data obtained during the study were subjected to statistical processing on a pentium-iv personal computer using the microsoft office excel-2012 software package, including the use of built-in statistical processing functions. methods of variational parametric and nonparametric statistics were used with the calculation of the arithmetic mean of the studied indicator (m), standard deviation (χ2), standard error of the mean (m), relative values (frequency,%), the statistical significance of the measurements obtained when comparing the mean values was determined by the criterion student's t (t) with the calculation of the error probability (p) when checking the normal distribution (according to the kurtosis criterion) and the equality of general variances (f fisher's test). research results. the results of the assessment of the severity of the clinical condition according to the scale of the assessment of the clinical condition (sacc) showed that the patients in the general sample (n = 115) had an average of 4.4 ± 2.0 points. the average score of the 6-minute walk test (tsw) for the entire group was 329.8 ± 80 m, while the average survey result on the scale of quality of life assessment (mlhfq) was 42.3 ± 7.8 points. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 122 fig. 1. the results of assessing the main indicators of the severity of chf (score, meter) among the patients of the main group, after the therapy (after 12 weeks), 1 (1.3%) lethal outcomes and 1 (1.3%) cases of fc 2 change to fc 3 were observed. among the untrained, there were 2 (5%) deaths and 2 (5%) cases of changes in fc chf. the assessment of the number of visits of patients with chf according to the family polyclinic showed a generally satisfactory level of clinical examination in the main group on average, the indicator of planned visits was 2.3 times (3.1%) in the control group. the dynamics of the main hemodynamic parameters (the number of heartbeats (nhb), systolic blood pressure (sbp) and diastolic blood pressure (dbp) in patients in the study groups also had a positive trend. in the main group, the average heart rate decreased significantly (p> 0.05) and sbp (p> 0.05) in comparison with the indices at the beginning of the study it is noteworthy that in the patients of the control group there was an increase in the mean indices of heart rate, sbp and dbp after 12 weeks of observation. 0 50 100 150 200 250 300 350 sacc qol tsw 4,3 42,3 329 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 123 table 1. dynamics of hemodynamic parameters in the analyzed groups of patients studied indicators on the first visit after the therapy (after 12 weeks) control group (n=40) main group (n=75) nhb 75,7±10,3 76,7±10,4 70,1±8,7* sbp 142,0±15 141,0±13,9 139,1±15,7* dbp 85±11,1 86±11,0 82,2±7,9 note: * p> 0.05 reliability of differences in relation to the initial data. nhb heart rate, sbp systolic blood pressure, dbp diastolic blood pressure. indicators of the dynamics of the clinical and functional state of patients in the form of sacc and tsw within 12 weeks. from the beginning of observation in the compared groups are shown in figure 2. in the main group, significant differences were noted as tsw (p <0.01), sacc (p <0.01) and quality of life (qol) (p <0.01), whereas in the control group, no significant and reliable positive dynamics was observed. note: * p <0.05: ** p <0.01 reliability of differences in relation to the initial data 0 50 100 150 200 250 300 350 400 sacc кж tsw 4,3 42,3 329 2,6* 34* 367** 3,2 37 342 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 124 figure 2. data of qol, sacc and tsw in patients of the compared groups against the background of the therapy (score, meter). table 3. lipid composition of blood in the analyzed groups (м±m) indicators main group (n=75) control group (n=40) initial data (n=115) total cs, mg / dl 196±5,1 202±5,0 219±3,0 tg, mg / dl 185,0±4,6* 196,0±9.7 208±6,2 cs ldl, mg / dl 138±2,5* 140± 3,7 148±3,4 cs hdl, mg / dl 34,2± 1.1 33,2±1,0 33,4± 1.0 ca, rel. 4.1±0,11 4,3±0,1 4,8±0,3 note: * p <0.001-reliability of differences in relation to healthy groups, cs-cholesterol, tgtriglycerides, ldl-low-density lipoproteins, hdl-high-density lipoproteins, ca-coefficient of atherogenicity. after 12 weeks. during the course of treatment in patients in the main group, there was a significant decrease in triglycerides (p <0.01) and low-density lipoproteins (ldl) (p <0.01) in the control group, similar dynamics were not revealed. table 4. indicators of lv systolic function in middle-aged patients. initial data main group control group eds, sm 5,0±0,32 4,6±0,3 4,9±0,2 ess, sm 4,9±0,2 4,3±0,21 4,7±0,22 edv, ml 124,5±52 119,5±42* 121,3±50 esv, ml 52±18,0 43±14,0* 49±17,0 ef, % 56,5±5,0 58,3±4,3 57,2±5,5 ivs, mm 12,6±1,1 11,0±1,02 12,0±1,1 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 125 note: * p <0.05 reliability of differences in relation to the initial data, eds-end diastolic size, ess-end systolic size, edv-end diastolic volume, esv-end systolic volume, ef-ejection fraction, ivs-interventricular septum.. the analysis of echocardiographic parameters in patients in 2 study groups in patients with chf was carried out on the basis of a study of the main indicators of systolic and diastolic lv dysfunction. in the main group of patients with chf, after the therapy, a significant decrease in esv and a relative decrease in edv in relation to the initial values was revealed by 21% (p <0.05). along with this, ivs in the main group also tends to decrease. whereas in the control group, significant dynamics in terms of echocardiography indicators is not observed. thus, for patients with chronic heart failure with preserved left ventricular ejection fraction, the use of the sglt2 inhibition drug, empagliflozin for 12 weeks against the background of the main therapy, demonstrated a positive effect in relation to an increase in exercise tolerance according to the data of the 6-minute walk test with an improvement in quality parameters. life on the shoks scale. a positive trend of restoration of the contractility of the left ventricular myocardium was shown according to the end-systolic and end-diastolic volumes with a positive cardiac effect. therapy with the inclusion of empagliflozin is aimed at preventing manifestations such as chronic heart failure, which is aimed at reducing the progression of morbidity and mortality in older patients with preserved left ventricular ejection fraction. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5520856 126 references: 1. arutyunov a.g. the strategy for choosing the risk scales, prognosis and severity of patients with acute decompensated chf syndrome. // russian journal of cardiology. 2013. no. 2 (100). pg. 50-55. 2. koudstaal s., pujades-rodriguez m., denaxas s., et al. prognostic burden of heart failure recorded in primary care, acute hospital admissions, or both: a population-based linked electronic health record cohort study in 2.1 million people. eur j heart fail. 2017;19(9):1119-27. doi:10.1002/ejhf.709. 3. ferrannini e., mark m., mayoux e. cv protection in the empareg outcome trial: a “thrifty substrate” hypothesis. diabetes care 2016; 39:1108– 1114. doi: 10.2337 / dci16–0033. 4. low wang c., hess c. n., hiatt w. r., goldfine a. b. atherosclerotic cardiovascular disease and heart failure in type 2 diabetes –mechanisms, management, and clinical considerations. circulation 2016;133 (24):2459–2502. doi: 10.1161 / circulationaha. 116.022194. 5. jones n.r., roalfe a.k., adoki i., et al. survival of patients with chronic heart failure in the community: a systematic review and meta-analysis. eur j heart fail. 2019;21(11):1306-25. doi:10.1002/ejhf.1594. 6. packer m. sglt2 inhibitors produce cardiorenal benefits by promoting adaptive cellular reprogramming to induce a state of fasting mimicry: a paradigm shift in understanding their mechanism of action. diabetes care 2020;43:508-11. doi:10.2337/dci19-0074. 7. packer m., anker s.d., butler j., et al. cardiovascular and renal outcomes with empagliflozin in heart failure. n engl j med. 2020;383(15):1413-24. doi:10.1056/nejmoa2022190. 8. packer m., anker s.d., butler j., et al. effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: the emperor-reduced trial. circulation. 2020 oct 21. doi:10.1161/circulationaha.120.051783. 9. wanner c., inzucchi s.e., lachin j.m., et al. empagliflozin and progression of kidney disease in type 2 diabetes. n engl j med. 2016;375(4):323-34. doi:10.1056/nejmoa1515920. 10. zinman b., wanner c., lachin j.m., et al. empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. n engl j med. 2015;373(22):2117-28. doi:10.1056/nejmoa1504720. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 51 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 52 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 53 diagnostic role of immunological and biochemical parameters in the gastrointestinal food allergy in children 1 ganieva shakhzoda shavkatovna – assistant of the pediatrics department of bukhara state medical institute 2 juraeva firuza rakhmatovna assistant of the pediatrics department of bukhara state medical institute, 3 hamdamova gulhayo rakhmatovna assistant of the internal medicine department of bukhara state medical institute abstract. studies have shown that the gastrointestinal form of food allergy in children is often combined with diseases of the gastrointestinal tract associated with helicobacter pylori infection. the aim of the study was to study the relationship between the immunological and biochemical parameters of blood and saliva in the gastrointestinal form of food allergy in children, depending on the helicobacter pylori infection. to study the effect of concomitant pathology on the course of food allergy and non-invasive diagnostic methods, 63 patients from 3 to 10 years of age with gastrointestinal allergy were examined. for early non-invasive diagnosis and differentiation of gastrointestinal allergy in children, depending on the helicobacter pylori infection, it is advisable to determine the concentration of ige in saliva and diastasis in urine. the authors conducted a study of immunological and biochemical parameters in biological media in the gastrointestinal form of food allergy in children. the study proved an increase in the concentration of il-8, tnf-α, ige and a decrease in siga in saliva in patients with gastrointestinal allergy, regardless of the association with helicobacter pylori; it was proved that the quantitative insufficiency of cd8+ t cells in helicobacter pylori-associated gastrointestinal allergy is an informative factor in the development of chronic diseases of the gastrointestinal tract with a high risk of art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 54 developing an autoimmune mechanism. it was also revealed that ige in saliva and urine diastasis are informative indicators of early and non-invasive diagnosis, differentiation of gastrointestinal allergy in children, depending on the infection with helicobacter pylori. in patients with helicobacter pylori-associated gastrointestinal allergy, a strong positive relationship of helicobacter pylori infection with saliva ige and urine diastasis was established, which was not typical for gastrointestinal allergies without helicobacter pylori infection. keywords: allergy, helicobacter pylori, gastrointestinal food allergy, correlation, children, non-invasive diagnosis, saliva introduction food allergy (fa) is characterized by polymorphism of clinical manifestations and complex immunological mechanisms. it has a high and uneven prevalence in various regions of the world, due to specific dietary traditions and the peculiar impact of environmental factors on the child's body [1]. recent scientific works prove the importance of the microbiocenosis of the gastrointestinal tract (git) in the process of allergy formation, that the prevalence of helicobacter pylori infection significantly differed between children with and without allergies, and also revealed the role of the interaction of genetic (family history of allergies) and environmental (type of birth, breastfeeding, previous antibacterial therapy) factors in the development of allergies [2, 3, 4]. in recent years, many studies have been conducted indicating that specific microorganisms can cause diseases even away from the main focus of infection, which also proves the importance of helicobacter pylori in various extra-gastric diseases [5]. sang pyo lee's research has shown that helicobacter pylori infection has a pathogenetic link to allergic diseases. helicobacter pylori can provoke the release of art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 55 histamine from basophils and, apparently, also suppresses the allergic reaction of the immune response through t-helper cells [6]. in children with allergic pathology, due to the atopic tendency of the immune response, the synthesis of ige-antibodies to helicobacter pylori is increased, which is manifested by their increased level and high frequency of detection with an exacerbation of the allergic process against the background of a decrease in the level of ige antibodies. the production of ige-antibodies to helicobacter pylori is a kind of protective reaction of the body in conditions of chronic infection of the mucous membranes. the protective effect of ige-antibodies to helicobacter pylori is also confirmed by their detection in insignificant concentrations, but with a high frequency of cases in the sera of practically healthy children. the presence of these antibodies indicates a predisposition to the th2 response, which is characteristic of mucosal immunity, which provides asymptomatic persistence of the microorganism in the gastrointestinal tract [7]. children differ from adults regarding helicobacter pylori infection in many aspects. helicobacter pylori causes some extra-intestinal diseases along with gastrointestinal diseases. although among these diseases in children, symptoms such as recurrent abdominal pain are not specific. a reliable way to detect helicobacter pylori is a crucial issue that is still being actively discussed. the tests used to diagnose infection are grouped into invasive and non-invasive methods. non-invasive tests include a urea breath test, fecal antigen test, serological examination, and molecular diagnostic approaches. the use of the endoscopic method is a prerequisite for all invasive methods and creates difficulties in children, as it is a complex procedure and requires the participation of the patient. for this reason, non-invasive tests are widely used in children [8]. taking into account the above, it can be confidently stated that at present, it is extremely difficult to conduct a differential diagnosis between non-ige-mediated gastrointestinal allergies (gia) and functional disorders of the gastrointestinal tract [9]. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 56 although knowledge of the various characteristics of helicobacter pylori infection has been expanded since its discovery, much remains to be done to better understand its underlying mechanisms. in addition, new diagnostic methods should be better understood in order to reduce health care costs and provide patients with less invasive diagnostic alternatives [10,11]. the purpose of the study was to study the relationship of immunological and biochemical parameters of blood and saliva in the gastrointestinal form of fa in children, depending on helicobacter pylori infection. materials and methods of research. to study the effect of concomitant pathology on the course and prognosis of fa, 63 sick children from 3 to 10 years of age with gia were examined, who were undergoing inpatient examination and treatment at the bukhara regional children's multidisciplinary medical center. the patients were divided into 2 groups: 32 children with helicobacter pylori-associated gia and 31 children with gia without helicobacter pylori. all patients were examined for general, biochemical tests of blood (bilirubin, alt, ast, urea, diastasis) and urine (general analysis of urine, diastasis in urine). antibodies to helicobacter pylori in the blood were determined by elisa (human, germany). immunological studies were carried out by studying the indicators of humoral immunity (iga, igm, siga, ige) and cytokines (il-8, tnf-α) in peripheral blood serum and saliva by the elisa method (vector best jsc, russia), according to the attached instructions. statistical analysis of the obtained results was carried out using the methods of variation statistics. the reliability of the differences in the mean values was estimated on the basis of the student's test (t) with the calculation of the error probability (p) when checking the normality of the distribution and the equality of the general variances (f – fisher's test). the data was considered reliable under the condition that t ≥2, and p<0.05. the correlation analysis was performed using spearman (rs) and pearson (r) methods. the relationship criteria were evaluated on the cheddock scale: 0.1 < r < art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 57 0.3: weak; 0.3 < r < 0.5: moderate; 0.5 < r < 0.7: noticeable; 0.7 < r < 0.9: high; 0.9 < r < 1: very high; results and discussion. the study of the factors of humoral immunity of the blood in patients with gia showed a characteristic imbalance in the composition of immunoglobulins in gia, depending on the helicobacter pylori infection (table 1). table 1. the concentration of immunoglobulins in children with food allergies blood parameters control group (n=30) gia with helicobacter pylori (n=32) gia without helicobacter pylori (n=31) ig a (g/l) 3,1  0,5 8,8  1,2* 1,36±0,17* ig m (g/l) 2,2  0,5 3,5 0,8 1,91±0,19 ig g (g/l) 14,8  1,0 21,51,0* 9,54±0,43* ig e (iu/ml) 22,0  1,2 25,01,1 88,67±4,84*** note: * differences relative to the control group data are significant (* p<0,05, ** p<0,01, *** p<0,001) analysis of the results of blood tests in patients with gia associated with helicobacter pylori showed a significant increase in the concentration of ig a-8.8 ± 1.2 g/l versus 3.1 ± 0.5 g/l in the control and igg-21.5±1.0 g/l versus 14.8 ± 1.0 g/l in the control (p < 0.05). comparative characteristics of the content of immunoglobulins in the blood of patients with gia without association with helicobacter pylori revealed opposite shifts in the ratio of the studied immunoglobulins. it was characterized by a significant decrease in the concentration of iga to 1.36±0.17 g/l and igg to 9.54±0.43 g / l (p<0.05) compared with the data of the control group. the igm concentration had an unreliable tendency to increase relative to the control in gia associated with helicobacter pylori and vice versa, in gia without art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 58 association with helicobacter pylori, it tended to decrease against the background of a significant increase in the level of ig e-88.67±4.84 iu/ml versus-22.0 ± 1.2 iu/ml in the control. in the study, patients with gia without association with helicobacter pylori showed a significant 4-fold increase in ig e-88.67±4.84 µl compared to the control parameters-22.0 ± 1.2 µl (p<0.001). the study of secretory immunity in patients with gia showed a significant decrease in siga in both follow-up groups (table 2). table 2. the concentration of immunoglobulins and cytokines in the saliva of gia in children parameters of saliva control group (n=30) gia with helicobacter pylori (n=32) gia without helicobacter pylori (n=31) ig a mg% 1,1  0,04 0,3  0,02*** 0,6±0,04*** ig e mg% 1,2  0,05 21,51,29*** 27,9±1,82*** il-8 pg/ml 16,2  0,6 95,36,12*** 57,3±3,26*** tnf-α pg/ml 21,2  1,0 60,88,63** 41,6±3,2*** note: * differences relative to the control group data are significant (* p<0,05, ** p<0,01, *** p<0,001) it was noted a significant decrease in siga 3.7 times (0,3 ± 0,02 mg%) with gia associated with helicobacter pylori and 1.83 times (0,6 ± 0.04 mg%) with gia no association with helicobacter pylori against benchmarks and 1.1 ± 0.04 mg% (p<0.001). the concentration of sige is increased as in gia association with helicobacter pylori (up to 21.5 ± 1,29 mg%) , and in its absence (up to 27.9 ± 1.82 mg%) vs control 1,2 ± 0,05 mg% (p<0.001). art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 59 in order to introduce non-invasive manipulations in the practice of pediatric allergy and improve the methods of non-invasive diagnosis of fa in children, cytokines in saliva were studied. the results showed a significant increase in the level of il-8 and tnf-α in saliva in gia in children, regardless of helicobacter pylori infection. il — 8 is known to be produced by monocytes, fibroblasts, and endothelial cells. it acts as a neutrophil activator, because it is a chemokine, i.e. an endogenous chemoattractant. it stimulates the directional movement of various types of white blood cells. il-8, tnf-α, and other cytokines produced by macrophages during the early inducible response are pro-inflammatory cytokines. their action completely determines the development of the inflammatory process that develops when the antigen is introduced into the macroorganism. the study showed an increase in il-8 by 5.8 times (95.3 ± 6.12 pg/ml) in gia associated with helicobacter pylori and by 3.53 times (57.3 ± 3.26 pg/ml) in gia without association with helicobacter pylori in relation to the control 16.2 ± 0.6 pg / ml. a significant increase in the concentration of tnf–α in saliva was found in patients with gia, regardless of helicobacter pylori infection. in gia associated with helicobacter pylori, tnf-α increases to 60.8±8.63 pg / ml, and in gia without association with helicobacter pylori to 41.6±3.2 pg/ml versus control 21.2 ± 1.0 pg/ml (p<0.01). correlation analysis helps to predict the possible values of one indicator, knowing the value of the other, which is very important when performing noninvasive diagnostic manipulations with high accuracy and significance. during the exacerbation of gia in patients without helicobacter pylori, the linear correlation coefficient showed a strong positive relationship between blood and saliva ige (r=0.80) and an inverse strong relationship between saliva siga and blood ige (r=-0.78) art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 60 based on the results of the study, it can be stated that the increase in the concentration of ige in both blood and saliva is accompanied by a decrease in the level of siga in saliva in children with gia. the established relationships between salivary and blood immunoglobulins allow early and accurate non-invasive diagnosis of gia, which, due to the presence of a correlation, is sufficient to study ige in saliva. it is known that il-8 is a pro-inflammatory cytokine and plays a huge role in the innate immune system. il-8 stimulates the secretion of histamine by basophils and is one of the stimulators of angiogenesis [4]. in our studies in patients with helicobacter pylori unassociated gia, an average positive relationship was found between saliva il-8 and blood ige (r=0.49), and between saliva il-8 and saliva ige (r=0.39). there is also an average negative feedback in the saliva of il-8 with siga (r=-0.45). consequently, in saliva, an increase in ige is accompanied by an increase in il-8 and a decrease in siga. studies on helicobacter pylori infection in gia showed a weak negative association of saliva il-8 with blood helicobacter pylori (r=-0.29). of interest was the study of the relationship between blood helicobacter pylori and other blood parameters in gia. in this respect, weak positive relationships were found between the content of helicobacter pylori and white blood cells (r=0.27), and tnf-α of saliva (r=0.27). the average positive association of blood helicobacter pylori with blood ast was also revealed (r=0.39). the average positive association of urine diastase with saliva siga (r=0.40) and negative association with saliva ige (r=-0.50) was also revealed. it should be noted that there is a positive relationship between saliva and blood iga (r=0.47), while saliva siga has a strong negative relationship with blood igm (r=-0.59). the established pattern makes it possible to predict helicobacter pylori infection by the level of diastasis in the urine, which proves the possibility of limiting noninvasive diagnostics and reducing the financial costs of tests. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 61 in studies in patients with helicobacter pylori-associated gia, a strong positive relationship was established between helicobacter pylori infection and saliva silencing (p=0.83), blood ige (p=0.71), and blood idm (p=0.56), which was not typical for gia without helicobacter pylori infection. a characteristic moderate positive relationship of helicobacter pylori in the blood with blood leukocytes (r = 0.28), blood eosinophils (r = 0.38) and with blood ast (r = 0.26) was also established in the presence of a moderate negative relationship with urine diastasis (r = 0.26). in contrast to the correlations in helicobacter pylori unassociated gia, the association of gia with helicobacter pylori infection shows an average positive association of tnf-α saliva with il-8 saliva (p=0.44) and a weak positive association of tnf-α saliva with iga in the blood (p=0.20). consequently, in studies on the correlation relationships of immuno-biochemical parameters, it was found that saliva immunoglobulin and urine diastasis are more informative indicators for the urgent and non-invasive diagnosis of gia. thus, for early non-invasive diagnosis and differentiation of gia in children, depending on helicobacter pylori infection, it is advisable to determine the concentration of salivator ige and diastase in the urine. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 62 references: 1. allen j. k., coplin j. j. epidemiology of ige-mediated food allergy and anaphylaxis. allergy wedge. north am. 2012. vol. 32. p. 35-50. 2. lionetti e, leonardi s, lanzafame a, garozzo mt, filippelli m, tomarcio s, etc. helicobacter pylori infection and atopic diseases: is there a link? systematic review and meta-analysis. world j gastroenterol. 2014;20:17635-17647. 3. wang q, yu c, sun y. the relationship between asthma and helicobacter pylori: a meta-analysis. helicobacter. 2013;18:41-53. 4. zhou x, wu j, zhang g. association between helicobacter pylori and asthma: a meta-analysis. eur j gastroenterol hepatol. 2013;25:460-468. 5. rajuka-ebela d, giupponi b, franceschi f. helicobacter pylori and extragastric diseases. helicobacter. 2018; 23 supplement 1: e12520. doi: 10.1111/hel. 12520 6. sang pyo lee, * sang-young lee,* correlation between helicobacter pylori infection, ige hypersensitivity, and allergic diseases in korean adults 2014 helicobacter issn 1523-5378 doi: 10.1111/hel.12173 7. viha g. v. secretory immunoglobulin a-a marker of adaptation of the human body to external influences. special issue lab # 3, 2013. p. 15-17 8. sabbagh p, yavanyan m, coppolu v, vasigala v. r., ebrahimpur s. helicobacter pylori infection in children: a review of diagnostic methods. eur j clin microbiol infect dis. 2019; [epub before printing]. https://doi.org/10.1007/s10096-019-03502-5 9. vandenplas i. i., zakharova i. n., dmitrieva yu. a. gastrointestinal manifestations of food allergy or functional disorders of the gastrointestinal tract principles of differential diagnosis and diet therapy medical council • no. 16, 2016 p. 110-114 10. de brito bb, da silva faf, soares as, pereira va, santos mlc, sampaio mm, neves phm, de melo ff. pathogenesis and clinical treatment of gastric infection with helicobacter pylori. world j gastroenterol 2019; 25(37): 5578-5589 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5140474 63 11. den hollander wj, sonnenschein-van der voort am, holster il, et al. helicobacter pylori in children with asthmatic conditions at school age and their mothers. pharmacol alimony. 2016;43(8):933-943. doi:10.1111/apt. 13572 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 211 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 212 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 213 the role of endothelial dysfunction in the development of immune microthrombovasculitis islamova z.s., inoyatova f.kh., babadjanova sh.a., yusupkhodjaeva kh.s., kurbonova z.ch. tashkent medical academy republic of uzbekistan abstract: comparative assessment of endothelial dysfunction indicators in patients with imtv depending on the form of the disease and the characteristics of its course. material and methods. we examined 140 patients with bmi at the age of 18-62 years. all patients, depending on the clinical manifestations of the disease, were subdivided into 4 groups: 1st 32 patients with skin, 2nd 84 patients with skinarticular, 3rd 12 patients with mixed skin-articular and abdominal and 4th group 12 patients with generalized skin-articular and renal forms of imtv. the control group consisted of 20 conditionally healthy individuals. the indices of the vascularplatelet, coagulation link of hemostasis, the anticoagulant system were assessed according to generally accepted methods. endothelial dysfunction was assessed by the level of endothelin 1 (et-1), von willebrand factor (vwf), thrombomodulin and adhesion molecules (sicam-1)) by enzyme immunoassay. the digital material was processed by the method of variation statistics. results. the study of the vascularplatelet link of hemostasis in patients with imtt showed a tendency to develop moderate thrombocytosis and an increase in their thrombogenic activity. the study of three phases of the coagulation link of hemostasis indicated pronounced hypercoagulation in all groups. the dynamics of changes in hemostasiological parameters showed their relationship with the activity and severity of imtv. a pronounced endothelial dysfunction was revealed, manifested by an increase in the content of et-1, vwf, sicam-1, and thrombomodulin in the blood plasma. the severity of these changes is minimal in the cutaneous form of the disease and sharply increases in its generalized form.. output: in patients with imtv, depending on the form of the disease, dysfunction of endotheliocytes of microvessels develops with inhibition of anticoagulant and increased procoagulant components. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 214 keywords: immune microthrombovasculitis, vascular endothelium, endothelin 1, von willebrand factor, adhesion molecules, thrombomodulin, hemostasis. among the general human pathology, there is an increase in the incidence of hemorrhagic diathesis (hd). hd is characterized by widespread distribution, a variety of clinical manifestations, and a high incidence of severe hemorrhagic and thrombohemorrhagic complications, which are often fatal. in the general structure of hd, in terms of the frequency of its occurrence among all populations and age groups of the population, polymorphism and severity of the clinical course, a special place is given to pathologies of the primary hemostasis of an acquired nature, including immune microthrombovasculitis (imtv) [3, 4, 5, 7, 21] ... the annual incidence of imtv is 2 people per 10,000 population and there is an increase in the number of patients [6, 9]. the pathogenesis of the disease is associated with overproduction of low molecular weight circulating immune complexes and the deposition of granular iga deposits in the vascular wall [1, 10, 13]. this leads to the activation of the complement system, an increase in the permeability of the vessels of the microvasculature and with the involvement of the hemostatic system in the process. as a result, the rheological properties of blood are disturbed, platelet aggregation increases, and hypercoagulability syndrome with depression of the fibrinolytic system develops [1, 8, 10, 11]. according to the literature, the leading role in the development of predisposition to this pathology belongs to the polymorphism of genes of proinflammatory cytokines, genes of the angiotensin and endothelial systems [2, 16, 17]. the study of the formation mechanisms of imtv is a priority in a number of large research centers of the world [12, 14, 19]. in the development of this multifactorial disease, an important place is given to both the individual characteristics of the organism, the influence of exoand endogenous factors, the intensity of which largely determines the risk of its formation [15, 18, 20]. the expansion of innovative strategies and the introduction of high technologies in our republic allow a targeted approach to the development of the foundations of evidence-based medicine, including such important aspects as the art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 215 mechanisms of formation, the development of effective methods for predicting the development of a severe course of the disease and the risks of developing complications of imtv. the introduction of methods for determining endothelial dysfunction made it possible to decipher the main mechanisms of the development of pathological conditions, develop criteria for early and differential diagnosis and improve the tactics of treating various diseases manifested by endothelial dysfunction. however, in the literature, there are sporadic data on the presence of endothelial dysfunction with imtv. purpose of the study: comparative assessment of endothelial dysfunction indicators in patients with imtv, depending on the form of the disease and the characteristics of its course. material and research methods. the study included 140 patients with an established diagnosis of imtv. verification of the bmi diagnosis was carried out according to modern classification criteria. the selection of patients was carried out by the method of random sampling as they approached. the age of the patients with bmi ranged from 18 to 62 years (median age 32.1 ± 3.9 years), mostly young and mature people (86.4%). analysis of the distribution of patients by age and sex showed that women predominated among the patients, and there were almost 2 times less men. all patients examined by us, depending on the clinical manifestations of the disease, were subdivided into the following forms of imtv: 32 (22.8%) patients had a skin form (group 1), 84 (60.0%) patients had a skin-articular form (group 2 ), 12 (8.6%) had mixed skin-articular and abdominal form (group 3) and 12 (8.6%) had generalized skin-articular and renal form (group 4). the control group consisted of 20 conditionally healthy unrelated persons who did not have a history of hemostasis system pathology, corresponding in terms of sex and age to the examined main group of patients. the diagnosis and clinical form of the disease were established on the basis of complaints, history of life and disease, clinical symptoms and laboratory data. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 216 particular attention was paid to objective data and anamnesis of the disease: periodic appearance of small-point cutaneous hemorrhages, leaving behind hyperpigmentation, pain in the joints, edema, pain in the stomach during the onset of hemorrhages, blood in the urine and feces, general weakness, other symptoms and the reasons with which the patient associates the development of the disease. upper respiratory tract infections (56.4%) and drug intake (22.1%) were provoking factors for the development of imtt. 48.6% of patients had a history of allergic diseases, and 16.4% of patients noted the presence of hereditary diseases of the blood coagulation system. to assess the state of the vascular-platelet link of hemostasis, the number of platelets was counted according to fonio in peripheral blood smears by the method of phase-contrast microscopy, the aggregation of platelets was studied using the hemolysate-aggregation test in dilutions 10-2, 10-6 according to zs. barkagan, b.f. arkhipov and v.m. kuchersky (1980), platelet adhesion on fiberglass, blood clot retraction in a test tube according to v.p. baluda et al. (1980). to study the coagulation link of the hemostasis system, the activated partial thromboplastin time (aptt), prothrombin index (pti), thrombin time (tb), soluble fibrin-monomer complexes (rfmk), the amount of fibrinogen) were determined on a humaclot junior coagulometer (germany) and anticoagulant system blood by determining the activity of antithrombin iii (at iii) and xii-α dependent fibrinolysis according to g.f. eremin and a.g. arkhipov (1982), using reagents of npo renam (russia). determination of indicators of endothelial dysfunction (endothelin 1 (et-1), von willebrand factor (vwf), thrombomodulin and adhesion molecules (sicam-1)) was determined on a humareader hs (human) enzyme immunoassay analyzer using commercial eliza kits from human. all statistical analyzes were performed using sas software. quantitative variables were presented as mean ± standard deviation. in addition, when analyzing the correlations, the spearman rank test was used. p <0.05 was considered statistically significant. results and its discussion art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 217 symmetrical petechial hemorrhagic rashes on the legs up to the knee were present in 32.3% of patients in group 1 with the cutaneous form of bmi, in 29% also petechiae on the hips and buttocks, in 29% in most parts of the body. in severe cases, maculopapular rash with necrotic changes in the skin in the center and the appearance of small ulcers was observed in 16.1% of patients. at first, rashes appeared on the feet and legs, later they spread higher, the abundance of rashes correlated with the severity of bmi. the duration of the disease in patients with the cutaneous form was the shortest and amounted to 15.0 ± 2.3 days. in group 2 patients, along with skin lesions in the form of a symmetrical hemorrhagic rash, joint damage was also observed. the articular syndrome was expressed by pain and periarticular swelling, redness, disorder of motor functions, mainly in large joints. basically, 61.9% of patients had ankle joint damage, in 22.6% of cases ankle and knee joint damage, in 15.5% of cases other joints were also affected. symmetrical involvement of the joints was observed; joint deformities with impaired function were not observed. the duration of the disease in patients with skin-articular form averaged 8.7 ± 1.8 months. in group 3 patients with a mixed skin-articular and abdominal form of the disease, in addition to damage to the skin and joints, damage to the gastrointestinal tract was also observed, resulting from hemorrhage in the intestinal wall and mesentery. patients complained of vomiting, cramping abdominal pains like intestinal colic, tension and tenderness of the abdomen on palpation, but they could not pinpoint the location of pain. in 25% of patients, vomiting, abdominal pain preceded skin-articular symptoms, which made diagnosis difficult. during esophagoduodenoscopy in patients of this category, petechial rashes were observed in the mucous membranes of the stomach and duodenum 12. in 16.6% of patients, the abdominal form was complicated by intestinal bleeding, simulating acute surgical diseases of the abdominal cavity. the duration of the disease with a mixed skinarticular and abdominal form of imtv was more than 2 years, proceeded with relapses in case of violation of the diet. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 218 in group 4 of patients with a mixed skin-articular and renal form of imtv, there was kidney damage of varying degrees: in 50% of patients there was short-term unstable hematuria up to 2-3 days, in 33.3% persistent but unexpressed hematuria up to 5-7 days, and 16.7% had pronounced gross hematuria for more than 10.0 ± 0.7 days. chronic renal failure was established in 16.7% of patients in this group. the duration of the course of this form of imtv was about 1.5 years. the study of the vascular-platelet link of hemostasis in patients with imtv showed a tendency to develop moderate thrombocytosis (from 308 ± 32.3 x 109 / l to 453 ± 56.1 x 109 / l), an increase in thrombocrit from 0.26 ± 0.02% to 0 , 45 ± 0.02%. the study of the functional activity of platelets showed an increase in thrombogenic activity of platelets, manifested by an increase in the adhesive and aggregation properties of platelets by 18.6-42.7%, a shortening of the retraction time of a blood clot by 12.5-25.0%. analysis of the plasma link of hemostasis showed a pronounced shortening of the blood coagulation time and aptt, prothrombin time, thrombin time, inr, an increase in the prothrombin index, the amount of fibrinogen, and plasma tolerance to heparin. the study of the three phases of the coagulation link of hemostasis indicated pronounced hypercoagulation in all groups in relation to the control group. the dynamics of changes in hemostasiological parameters showed their relationship with the activity and severity of imtv. currently, the immunocomplex nature of imtv has been proven, in which aseptic inflammation develops in microvessels with wall destruction, thrombosis and the appearance of purpura of various localization due to the damaging effect of circulating immune complexes and activated components of the complement system [2, 11, 20]. expression of such pro-inflammatory cytokines as tumor necrosis factor-α (tnf-α) and interleukin-6 (il-6) leads to an increase in the synthesis of vascular growth factor (vegf) by endothelial cells during the acute phase of the disease [3, 6, 21] ... in this regard, we investigated the indicators of the functional activity of the endothelium showed the development of its dysfunction (table 1). thus, art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 219 dysregulation of vascular tone during imtv is associated with an increase in the production of endothelial peptides, in particular et-1, the content of which in the blood serum of patients increases statistically significantly increases depending on the form of the disease. if in the cutaneous form of bmi the content of et-1 exceeds the standard level by 15.8%, then in the cutaneous-articular, abdominal and renal forms this excess was 28.5; 30.2 and 67.1%, respectively, groups, indicating the development of vasoconstriction in patients. it should be said that at low physiological concentrations, et-1 has an effect on endothelial receptors, causing the release of relaxation factors. at the same time, at high concentrations, it activates smooth muscle cell receptors and causes persistent vasoconstriction. table 1 indicators of endothelial dysfunction in patients with imtv, m ± m groups von willebrand factor, % endothelin1, pg / ml thrombomodlin, pg / ml sicam-1, pg / ml control group, n = 20 89,89±2,56 4,10 ± 0,24 3,54±0,28 55,69±4,44 имтв skin form, n = 8 133,75±7,46* 4,75±0,54 2,44±0,22** 69,95±4,94* skin-articular form, n = 18 145,17±5,60** 5,27±0,36* 2,18±0,12*** 86,00±7,04*** abdominal form, n = 12 188,00±3,29*** 5,34±0,53* 1,93±0,17*** 110,80±11,66** renal form, n = 7 191,41±5,52*** 6,85±0,52** 1,56±0,15*** 146,83±12,86*** note: * the differences between the indices of the control group of the examined and the patients with imtv are significant (p <0.05), ** p <0.01 and *** p <0.001. along with this, we also revealed the content of vwf: exceeding the standard values by 48.8; 61.5; 109.1 and 112.9% in groups of patients with skin, skin-articular, abdominal and renal forms of the disease, respectively groups. this factor is a carrierstabilizer for the procoagulant protein fviii: c circulating in the serum in the form of a non-covalently bound complex, and is an adhesion protein during hemostasis [11]. therefore, elevated vwf levels are an indicator of endothelial damage. on the other art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 220 hand, the increased formation of collagen in the vascular wall leads to a loss of their elasticity, the ability of the vessels to dilate decreases, which is manifested by the inhibition of anticoagulant and increased procoagulant properties [3, 5]. the pathogenesis is based on the formation of immune complexes and the activation of components of the complement system, which have a damaging effect on the vascular wall [4, 6]. the main initiators of endothelial damage in psg are cytokines, which are involved in the activation of neutrophils. il-8, which activates neutrophil epithelial protein (ena-78), and t-lymphocytes are involved in providing chemotaxis of neutrophils to sites of inflammation [3, 5, 20]. circulating immune complexes cause vasculitis, which is accompanied by perivascular edema, microcirculation disorders, and hemorrhages. damage to the vascular wall leads to activation of the hemostasis system: functional activity of platelets, hypercoagulation, a decrease in the level of antithrombin iii [3, 5]. according to the literature, with thrombophilia, the content of homocysteine in the blood plasma increases [3, 6]. according to b.i. kuznik et al. (2012), hyperhomocysteinemia is the leading pathogenetic mechanism of endothelial dysfunction [6]. its oxidized form activates the formation of free radicals, inhibits the synthesis of antioxidant enzymes in endothelial cells. as a result, there is damage to the endothelial lining of blood vessels, proliferation of smooth muscle cells, activation of platelets and a decrease in the content of heparan sulfate, which is an antithrombin iii receptor (at-iii). at the same time, the binding of at-iii to endothelial cells decreases, which disrupts the atrombogenicity of the inner layer of the endothelium [3, 6]. along with this, the activation of leukocytes, the release of cytoand chemokines, and the expression of adhesion molecules are noted. in this regard, we also studied the content of serum sicam-1. studies have shown an increase in its content by 26 and 54.4% in cutaneous and skin-articular forms of imtv. in the generalized form of bmi, the level of sicam-1 increases more pronounced: in the abdominal form by 99.89%, in the renal form by 163.7% relative to the values of practically healthy individuals. these indicators were art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 221 significantly higher than the values of groups with skin and skin-articular forms of imtv. therefore, we can say an increase in the adhesive properties of leukocytes. under physiological conditions, the endothelial cell does not express adhesion molecules. an increase in the concentration of the latter on the surface of endothelial cells occurs under the action of various damaging factors: an increase in the linear shear stress in a certain part of the artery, the accumulation of oxidized lipids and lipoproteins in the subendothelial space [3, 6]. sicam-1 of fibroblasts and endothelial cells is induced by inflammatory mediators. the interaction of leukocyte β2-integrin with sicam-1 accelerates the adhesion of leukocytes and their transendothelial migration. it should be said that vascular endothelial dysfunction leads to a decrease in the activity of protein c (pc) and protein s (ps), a decrease in the affinity of thrombomodulin for thrombin, leading to a sharp drop in the activity of natural anticoagulants [3]. thrombomodulin is a receptor for thrombin expressed on endothelial cell membranes. when interacting with thrombin, the resulting thrombomodulin / thrombin complex activates protein c, i.e. thrombomodulin carries out anticoagulant regulation, since active protein c inactivates factors fva, fviiia, fxa and fxiiia, inhibits the conversion of fibrinogen to fibrin, accelerates thrombin inactivation by antithrombin iii. in this regard, we also studied the content of thrombomodulin in the blood plasma of patients with imtv. studies have shown a decrease in its content by 31.1; 38.4; 45.5 and 55.9%, respectively, in the groups with cutaneous, skin-articular, abdominal and renal forms of bmi. it should be said that the concentration of thrombomodulin increases with an increase in the ratio of the surface of the vessels to the volume of blood. this ratio changes more than 1000 times when moving from large vessels to microcirculation. in microcirculation, almost all thrombin is associated with cd141, its clotting activity is suppressed and activation is increased. the concentration of the level of thrombomodulin in plasma indicates damage to the vascular endothelium. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 222 thus, the conducted studies have shown dysfunction of the vascular endothelium in patients with imtv. the severity of these changes is minimal in the cutaneous form of the disease and sharply increases in its generalized form. in patients with a severe form of imtv, it is indicative of a hypercoagulable syndrome due to dysfunction of endothelial cells of microvessels with inhibition of anticoagulant and an increase in procoagulant components. our data demonstrate the importance of studying specific inducers of platelet aggregation, indicators of the functional activity of the vascular endothelium in patients with imtv. conflicts of interest. the authors declare no conflicts of interest. sources of financing. the study was not sponsored. authors' contributions. concept and design: all authors. collection and processing of data: all authors. submission of research materials: all authors. data analysis and interpretation: all authors. manuscript preparation: all authors. final approval of the manuscript: f.kh. inoyatova. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5576350 223 references. 1. berman yu.o., davydkin i.l., krivova s.p. folic acid in the treatment of patients with hemorrhagic vasculitis with hereditary disorders of homocysteine metabolism // bulletin of the samara scientific center of the russian academy of sciences. 2014. vol. 16, no. 5 (4). p. 1384-1388. 2. 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medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 104 art of medicine international medical scientific journal founder and publisher pascual izquierdo-egea published science may 2021 year. issued quarterly. internet address: http://artofmedicineimsj.us e-mail: info@artofmedicineimsj.us 11931 barlow pl philadelphia, pa 19116, usa +1 (929) 266-0862 art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 105 features of traumatic injuries of the oral mucosa: literature review kamalova mekhriniso кilichevna 1 ., sharipova gulnihol idievna 2 . 1 dsc., associate professor of the department of surgical dentistry of the abu ali ibn sina bukhara state medical institute, uzbekistan mexriniso.stomatolog@mail.ru 2 independent candidate of the department of therapeutic dentistry of the bukhara state medical institute named after abu ali ibn sina, uzbekistan gulniholsharipova@mail.ru abstract among the various pathological conditions of oral mucosa in children, traumatic injuries are quite widespread, which can be the result of mechanical, thermal, chemical, electrical and radiation exposure. diagnosis of traumatic injury to oral mucosa in children is often difficult, due to the variety of their manifestations in the oral cavity and the similarity of the clinical picture of diseases of different etiology and pathogenesis.knowledge of the etiology, pathogenesis, features of the clinical course, the possibilities of prevention and adequate treatment is necessary for a dentist to carry out timely diagnosis and provide qualified assistance to children with traumatic injuries of the oral mucosa. keywords: traumatic lesions, young children, inflammation, oral mucosa, prevention, diagnostics, treatment. relevance. depending on the origin, traumatic lesions of the oral mucosa (oom) are usually divided into mechanical, chemical, physical, electrical, and radiation. trauma can be acute (single exposure to a damaging factor) and chronic with prolonged exposure to a stimulus of insignificant strength [2, 12]. starting to study specific sections, the student should know the following basic general provisions: • traumatic lesions of the mucous membrane as a result of the action of various factors (mechanical, physical, chemical) occur if the intensity of their influence exceeds the physiological margin of safety of the mucous membrane (rm). • the degree of damage and clinical manifestations depend on the nature of the stimulus, time, strength of its impact, localization, individual characteristics, general condition of the body and the age of the patient. • the mucous membrane of the oral cavity has high protective and regenerative abilities. • traumatic damage to the oral cavity is quickly accompanied by its infection. mechanical traum. acute mechanical trauma (trauma mechanicaacuta) etiology: acute mechanical trauma co (usually household, transport, sports) occurs accidentally when biting, hitting or injured by various objects. most often, co of the tongue, lips and cheeks along the line of closing of the teeth suffers. mailto:mexriniso.stomatolog@mail.ru mailto:gulniholsharipova@mail.ru art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 106 clinic: clinically, it can proceed without violation of the integrity of the co (edema, hyperemia, hemorrhage) or in violation (erosion, excoriation, ulcer), which determines the severity of the course of the disease. first, pain appears, and at the site of contact, a hematoma, excoriation, erosion or ulcer may form [3, 11]. often their size, shape and localization on the so coincide with those of the traumatic agent. hematomas and superficial injuries (excoriation, erosion) disappear relatively quickly (within 1-3 days). in case of secondary infection, erosion can turn into a long-term non-healing ulcer. the base of the ulcer on palpation is painful, infiltrated. diagnostics: as a rule, it is not difficult, the cause is easily identified after taking anamnesis, and an objective examination allows you to establish the localization and depth of damage to the tissues of the oral cavity. treatment: in case of severe pain, apply, irrigate or rinse 0.5 1% solution of novocaine, 0.5 1% solution of lidocaine, if necessary, stop bleeding using 0.5 1% solution of hydrogen peroxide , 5% solution of aminocaproic acid. for deep wounds, surgical treatment stitches. it is enough to treat shallow lesions with ordinary non-irritating warm antiseptic agents (0.5% solution of chlorhexidinebigluconate, 0.2% solution of furacilin, 0.5% solution of etonium, 1% solution of dimexidum, 1% solution of hydrogen peroxide, etc.)and prescribe rinsing the mouth with artificial lysozyme, potassium permanganate solution, and in the presence of erosion add applications with keratoplastic agents (colanchoe juice, aloe juice, "ektericid", oil solution of vitamins a, e and etc.) [7, 22]. if the wound is already covered with plaque, there is an infiltration, then its course is delayed. for treatment, application of solutions of proteolytic enzymes (solution of trypsin or chymopsin) is used for 8-10 minutes, after which necrotic tissue or fibrinous plaque is removed mechanically, and the ulcer or erosion is treated with antiseptics.with the advent of pure granulations, drugs are used that improve the reparative properties of tissues (solcoseryl dental adhesive paste) and keratoplastic agents. it is necessary to examine the dentition and, in order to prevent chronic trauma, to treat caries and its complications, restoring the anatomical shape of the crown of the affected tooth or polishing its sharp edge [1, 9, 18]. chronic mechanical trauma (trauma mechanicachronica. etiology and pathogenesis: it occurs quite often, especially among the elderly who use plate prostheses. the plate prosthesis transmits chewing pressure not only to the teeth, but also to co, delays the self-cleaning of the oral cavity, which leads to a violation of the established balance between different types of microorganisms, and changes the analyzing function of co receptors.these changes are often the starting point for the development of co pathology and neurostomatological diseases or exacerbation of chronic foci that were in remission. chronic mechanical trauma is caused by sharp edges of the teeth when they are damaged by caries or pathological abrasion, in the absence of teeth and malocclusion, poorly manufactured or worn out orthopedic structures, orthodontic appliances, dental calculi, bad habits, etc [10]. chronic mechanical trauma is observed more often in the elderly due to a decrease in the height of the bite, dysfunction of the temporomandibular joint, the art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 107 presence of terminal defects in the dentition, periodontitis of the ii-iii degree, a decrease in mucosal turgor, and a slowdown in the processes of epithelial regeneration. thus, a long-term traumatic factor triggers and maintains a chronic focus of inflammation with the formationcongestive hyperemia, edema, at the site of which erosion may occur, and then an ulcer, which is called decubital, or traumatic. with a prolonged course, the edges and base of the ulcer become denser, its depth is different up to the muscle layer, malignancy is possible [19]. clinic: the presence of a chronic traumatic lesion of the oral mucosa without violating its integrity (edema, hyperemia, hemorrhage) may not disturb the patient, but in the presence of an ulcermost of them complain of a burning sensation, swelling, discomfort, soreness in a certain place, aggravated by eating and talking. the clinical course in older people is more severe than in young people. such an ulcer is localized more often on the tongue, on the lips, cheeks along the line of closing the teeth, as well as within the prosthetic field. as a rule, it is solitary, painful, surrounded by an inflammatory infiltrate, its bottom is covered with fibrinous bloom. regional lymph nodes are enlarged, painful on palpation, mobile. inflammation can be focal and diffuse. it is accompanied by edema and hyperemia of co, against the background of which hemorrhages, erosion and hyperplasia of co in the form of granularity are possible, which is a prognostically unfavorable sign. in addition, at the site of injury to the co by the edge of the prosthesis along the transitional fold, a proliferative process and the development of lobular fibroma, which has the form of several folds, may occur,parallel to the edge of the prosthesis, and with a poorly fitted prosthetic bed on the upper jaw, papillomatosisof the palate occurs. with the habit of biting or sucking lips, tongue, cheeks, the co (mainly along the line of closing the teeth) takes on a peculiar appearance: it swells, has a white macerated surface in the form of spots or large indistinctly limited areas or a fringed appearance (as if eaten by a moth) due to many small shreds of unevenly eaten epithelium. the lesion has an asymptomatic course, but with deep biting, erosions are formed, painful when exposed to chemical stimuli. synonyms: "mild leukoplakia", "cheek biting". differential diagnosis: chronic trauma due to the habit of biting co should be differentiated from candidiasis (absence of fungi of the genus candida at microscopic examination), white cancellous nevus of cannon, which manifests itself from early childhood and progresses over the years: co of the cheeks looks thickened, with deep folds, spongy. stopping co biting leads to spontaneous recovery [4, 20]. chronic traumatic ulcer of oopr should be distinguished from cancerous ulcer, trophic ulcer, tuberculous ulcer, hard chancre. traumatic ulcers are characterized by the presence of an irritating factor, the presence of a painful infiltrate, and the absence of specific changes in cytological examination. elimination of the traumatic factor, as a rule, leads to the healing of the ulcer in 5 to 6 days. with prolonged existence of an ulcer, its base and edges can become denser ("infiltrative shaft") due to chronic inflammation; co around the ulcer is edematous, hyperemic, the bottom of the ulcer becomes bumpy, covered with a bloom [15]. soreness persists on palpation of the ulcer. lymph nodes are enlarged, painful, art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 108 mobile. long-termnon-healing ulcers can become infected with fusospirochetes, candida, and also become malignant [8]. a cancerous ulcer differs from a traumatic one by a greater density of edges and bases, by the presence of growth along the edges (in the form of cauliflower) and sometimes by their keratinization. after elimination of the irritant, healing does not occur. cytological or histological examination of cancerous ulcers reveals atypical cells. lymph nodes are painless on palpation, soldered in the form of conglomerates, motionless. tuberculous ulcers are characterized by soreness, soft, undermined "creeping" edges, their bottom is granular (treel's grains are microabscesses), yellowish. they are not epithelized after removal of the stimulus. in a cytological study, epithelioid cells and giant cells of pirogov-langhans are found, in a bacterioscopic study mycobacterium tuberculosis (koch's bacillus). a hard chancre differs from a traumatic ulcer by the presence of a dense cartilaginous infiltrate that surrounds the ulcer, with smooth edges, a smooth meatred bottom with a "greasy" coating, painless on palpation. the surrounding chancre is unchanged. regional lymph nodes are enlarged, painless, indurated (scleroadenitis) [14, 16]. the diagnosis is clarified by the detection of pale treponema in the discharge of the ulcer. the wasserman reaction (as well as rif, and later ribt) becomes positive 3 weeks after the onset of a hard chancre. a trophic ulcer differs from a traumatic one by a longer existence, a sluggish course, mild signs of inflammation, the presence of general diseases in the patient (most often of the cardiovascular system). elimination of the alleged traumatic factor does not cause the ulcer to heal [2, 12]. treatment: provides for the mandatory elimination of the traumatic agent, treatment of the oral cavity and ulcers with antiseptic solutions, pain relief. if necrotic tissues are present, they are removed mechanically under anesthesia or with the help of proteolytic enzymes. pure erosion and ulcers are treated with keratoplastic preparations ("regenkur", "dibunol", "sanguirithrin", rosehip oil, sea buckthorn oil, vitamin a oil solution, kolanchoe juice,"solcoseryl", "olazol", "hyposol-n", etc.). treatment of the lobular form is surgical. the basis for suspicion of malignancy of traumatic injury are traumatic ulcers with infiltration at the base, which do not heal within 2 3 weeks after elimination of the causative factor. prevention of traumatic injuries consists in the elimination of irritating factors in the oral cavity and its timely sanitation. chemical trauma (trauma chymica. chemical damage occurs when chemicals come into contact with ocpr. it can be acute or chronic. acute chemical damage occurs when high concentrations of chemicals enter the ocp. most often this happens when they are mistakenly used in everyday life, at work, when attempting suicide, during an appointment with the dentist. ocd burns can occur upon contact with acids,alkalis, the use of arsenic paste, phenol, formalin, formalin-resorcinol mixture, silver nitrate. the clinical picture of the lesion (hyperemia, edema, erosion, necrosis, ulcer) depends on the nature of the chemical, its amount, concentration and duration of action, the structure of co in the contact area. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 109 a burn with acids leads to the appearance of coagulation necrosis a dense brown film from sulfuric acid, yellow from nitric acid, gray-white from other acids. the phenomena of inflammation with edema and hyperemia are expressed near the film. a burn with alkalis leads to colliquation necrosis of the oas without the formation of a dense film, the process spreads over the surface and into the depths. from the action of alkalis, the lesion is deeper than with acid burns, and captures all layers of the oas. after rejection of necrotic tissue, very painful erosive or ulcerative surfaces are exposed, which heal very slowly. treatment. it is necessary to quickly remove the damaging chemical and rinse the mouth with a weak solution of a neutralizing agent. for acid burns, soapy water, 1% lime water, burnt magnesia, 0.1% ammonia solution (15 drops per glass of water) are used. alkalis are neutralized with a 0.5% solution of acetic or citric acid, as well as with a solution of hydrochloric acid (10 drops per glass of water) and thereby stop the further penetration of the chemical into the tissues.to reduce the absorption of concentrated solutions of silver nitrate, a 2 3% solution of sodium chloride or lugol's solution is used, while insoluble silver compounds are formed. when affected by phenol, co is treated with castor oil or 50% ethyl alcohol. further treatment of patients with chemical burns of oopr is carried out according to the example of treatment of an acute nonspecific inflammatory process: pain relievers are prescribed, weak solutions of antiseptic agents in the form of oral baths, rinses, drugs that accelerate epithelization (1% citral solution in peach oil, methyluracil ointment, vitamins a and e , "tsigerol", "hyposol-n") [10, 11, 13, 18]. physical trauma (trauma physica. the most common injuries of the osr caused by physical factors are thermal (effects of high and low temperatures), electric shock (burns, electrochemical galvanosis) and radiation injuries (with the localized effect of large doses of ionizing radiation). co burns can be caused by hot food, steam, hot objects, fire, hot air. under the influence of hot water or steam, acute catarrhal stomatitis develops, which is accompanied by pain. co is getting dramaticallyhyperemic, maceration of the epithelium is noted. with a severe burn, the epithelium sloughs off in thick layers or bubbles appear, in the place of which extensive superficial erosion or ulcers form. the accession of a secondary infection and the action of local irritating factors complicates the course and slows down the epithelialization of the affected areas [17]. treatment. the area of the co burn should be anesthetized with local anesthetics, antiseptic treatment should be carried out, enveloping and antiinflammatory drugs should be prescribed along with antimicrobial agents. in the dehydration phase, keratoplastic agents are used [14]. with the effect of low and ultra-low temperatures on the osr, the doctor meets mainly during cryotherapy of various lesions of the co and periodontal. in this case, a sharp acute catarrhal inflammation immediately occurs in the focus of cryotherapy a bubble,which after 1 2 days passes into necrosis. in the postoperative period, in the first hours after cryodestruction, oral baths or rinsing with art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 110 antiseptic agents are prescribed, and with the development of necrosis, therapy is carried out as in ulcerative necrotizing stomatitis [6]. co electrical injury is often associated with electrotherapy (galvanization, electrophoresis) or the development of galvanism in the oral cavity. a galvanic burn is formed at the site of contact of the active electrode with co in violation of the electrophoresis technique. clinically defined continuous painful erosion, surrounded by reactive inflammation of adjacent tissues, accompanied by a painful reaction of regional lymph nodes [2, 13]. galvanism is the occurrence of registered electrochemical potentials in the oral cavity in the presence of heterogeneous metal inclusions, without pronounced subjective and objective signs (this is a phenomenon) [21]. the presence of dissimilar metal inclusions contributes to the occurrence of electrochemical reactions, the accumulation of electromotive force at the interface between the metal and the oral fluid, which ensures the emergence of galvanic pairs. according to t.e. nikitina, the value of the electrochemical potential (ecp / microvolt) 120 -140 µv is the conditional rate of electric current, over 140 µm is the risk of developing galvanosis and its complications. the significant content of metals in the oral fluid determines their accumulation in co, soft tissues of the oral cavity, jaw bones and their constant entry into the gastrointestinal tract, which leads to their spread throughout the body and the emergence of sensitization to metals, metabolic disorders, and chronic diseases [1]. galvanosis pathological changes of a local and general nature that arise as a result of electrochemical interaction between metal inclusions in the oral cavity (this is a symptom complex). galvanosis contributes to the development of glossalgia, leukoplakia, lichen planus, and is also an aggravating factor in the already existing pathology of oral mucosa and can lead to microbial imbalance and the development of oral candidiasis. clinical picture: clinical manifestations of galvanosis of ocpd depend on current strength, time of its influence and individual tissue sensitivity. with galvanosis, patients complain of a metallic taste in the mouth, perversion of taste sensitivity, burning or tingling sensation, pain in the tongue, cheeks, dryness or hypersalivation, slight irritability, headache, weakness. galvanic currents can cause hyperkeratosis or burns that occur on the tip, lateral and lower surfaces of the tongue, much less often on the cheeks, lips, palate. clinically manifested by catarrhal or erosive-ulcerative lesions. with catarrhal lesions, bright hyperemia, edema and burning sensation occur. the foci of inflammation are clearly demarcated from the unchanged surface of the oral mucosa [6]. the erosive-ulcerative form is rare, characterized by focal or diffuse inflammation of co with the formation of single or multiple erosions (sometimes ulcers or blisters), covered with a whitish-gray coating. diagnostics. to establish a diagnosis of galvanosis, at least 5 criteria must be met: 1) the presence of a metallic taste in the mouth; art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 111 2) subjective symptoms, more pronounced in the morning and persisting throughout the day; 3) the presence of two or more metal inclusions in the oral cavity; 4) determination of the potential difference between metallic inclusions(registration); 5) improvement of the patient's well-being after removal of prostheses from the oral cavity. to detect galvanic phenomena in the oral cavity, the lira-100 device is used. treatment. etiotropic therapy of co galvanosis is reduced to the removal of prostheses and fillings from heterogeneous metals from the oral cavity. in addition, protease inhibitors are used in the early stages of catarrhal oral mucosa lesions, antiinflammatory and antiseptic agents. the lesion is treated with 5% unithiol solution. galvanic burns, which occur with erosions, ulcers, blisters and are accompanied by severe pain, are treated with antiseptic agents together with local anesthetics (4-10% anesthesin oil solution, 10% alcoholic propolis solution with glycerin (1: 1), 20-40% solution dmso). in the first phase of the wound process, it is advisable the use of nitacid, which has a high osmotic activity and a wide range of antimicrobial action. anesthetic and anti-inflammatory effect has a tincture of plantain, green tea, nettle leaves. to improve the epithelialization of the affected areas, use "hyposol-n", "solcoseryl" (ointment, jelly), "erbisol", "spedian" liniment, "vinilin", anti-burn liquid, etc. the drugs of choice are the following drugs (barer g.m.) [11, 14, 21]. for application anesthesi. benzocaine / glycerin topically 5/20 g before each meal, until clinical improvement or lidocaine, 2.5-5% ointment or 10% aerosol, topically before each meal, until clinical improvement. for the treatment of the oral cavity and elements of mucosal lesions and preventing their infection hydrogen peroxide, 1% solution, topically 1 2 times or potassium permanganate, 0.02% solution, topically 1 2 times or chlorhexidinebigluconate, 0.06% solution, topically 1 2 times or ethacridine lactate, 0.05% solution, topically 1 2 times. for cleaning the surface of erosions and ulcers trypsin 5 mg (in isotonic sodium chloride solution, 5.0 ml) topically 1 2 r / day.or chymotrypsin 5 mg (in isotonic sodium chloride solution, 5.0 ml) topically 1 2 r / day. if necessary, correction of the psychoemotional sphere (for example, with buccal biting) vitamin b 1 20 30 mg. per day inside or 6% solution in / m 1 time per day. 1 2 ml., 10 days. vitamin b 12 / m 1 2 ml. 1 time per day, 10 days. valerian rhizomes extract inside 1 tablet 1 2 r / day, long-term or glycine sublingual 0.1 g 2 3 r / day, long-term "diazepam" inside 5 15 mg 1 2 r / day, 4 weeks.or "medazepam" inside 10 mg 2 3 r / day., 4 weeks. to accelerate the healing of affected areas sea buckthorn oil topically on a cleansed area of the affected mucous membrane 1 3 r / day, until clinical improvement or "solcoseryl" ointment or dental adhesive paste, topically on a cleansed area of the affected mucous membrane 1 3 r / day, until clinical improvement or rosehip oil topically on the cleaned area of the affected mucous membrane 1 3 r / day, until clinical improvement. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 112 as an anti-inflammatory, immunostimulating agent that improves tissue trophism retinol acetate oil solution, topically on the affected areas 5 6 times per day, until clinical improvement. as an active antioxidant to stimulate protein synthesis, reduce capillary permeability vitamin e, solution, topically on the affected areas 5 6 r / day, until clinical improvement. in order to regulate redox processes, stimulate tissue regeneration, activate phagocytosis and antibody synthesis ascorbic acid inside 50 100 mg 3 5 r / day or 5% solution in / m 1 ml 1 r / day, 20 40 days. in order to normalize the metabolism of fatty acids, stimulate the formation of acetylcholine, steroid hormones, utilize amino acid deamination products calcium pantothenate inside 0.1 g 2 4 r / day or 5% solution locally in the form of applications for long-term non-healing erosion 2 4 r / day or 10% ppi / m 2 ml 1 2 r / day, 20 40 days to activate the processes of hematopoiesis and maturation of erythrocytes, tissue regeneration cyanocobalamin inside 0.00005 g 1 r / day, 20 40 days. folic acid inside 0.0008 g 1 r / day, 20 40 days. in order to regulate tissue respiration, metabolic processes riboflavin inside 0.005 0.01 g 1 r / day, 20 40 days in order to normalize metabolic processes and peripheral blood supply nicotinic acid orally after meals 0.025 0.05 g 3 r / day, 20 40 days.or 1% solution i / v, i / m or under the lesion 1 ml 1 r / day, 10 15 days. radiation injury. radiation injury is a lesion of the oral mucosa that most often occurs during radiation therapy of neoplasms of the maxillofacial region. when carrying out radiation therapy of neoplasms of the maxillofacial region, unaffected areas of the oral mucosa are also exposed to radiation. the response of different areas of the oas to irradiation is not the same and has some clinical features depending on the type of radiation therapy, single and total radiation dose, tissue radiosensitivity and the state of the oral cavity up to irradiation. the first clinical signs of a violation of the oss state appear in areas covered with non-keratinized epithelium (hyperemia, edema) and increase with increasing radiation dose. then, due to increased keratinization, the oss becomes cloudy, loses its luster, becomes denser, and becomes folded. with further irradiation, this keratinized epithelium is rejected in places, as a result of which erosions appear, covered with a sticky necrotic plaque (focal membranous radiomucositis). if the necrosis spreads to the adjacent areas, then the erosion merges and a drainage diffuse membranousradiomucositis occurs. it is especially sensitive to co irradiation of the soft palate: here radiomucositis immediately appears, without the keratinization phase. in the areas of the oas, which are normally covered with keratinized epithelium, only focal desquamation of the epithelium or single erosions occur. further development of the process is complicated by damage to the salivary glands, the epithelium of which is very sensitive to radiation. in the first 3 5 days, salivation can be increased, and then persistent hyposalivation quickly sets in. after 12 14 days, xerostomia develops, which is accompanied by dysphagia, perversion andloss of taste. later, hyperemia of the tip and lateral surfaces of the tongue and atrophy of its papillae appear. radiation changes in the oral cavity are largely reversible. after the termination of the irradiation, the osr in 2 3 weeks returns to the relative norm. however, with a art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 113 large absorbed dose (5000 6000 rad), irreversible changes in the salivary glands and oss (hyperemia, atrophy, radiation ulcers) may occur [1, 15]. in the prevention of radiation injuries, the rehabilitation of the oral cavity is of great importance. it should be carried out in the following sequence: 1) removal of mobile and decayed teeth with chronic lesions in the periodontium, followed by suturing no later than 3 5 days before the start of radiation therapy. 2) removal of supraand subgingival calculus, curettage of periodontal pockets. 3) filling of all carious cavities. in this case, metal prostheses and amalgam fillings must be removed or made on the dentition rubber or plastic protective caps with a thickness of 2 3 mm and applied directlybefore a radiation therapy session. instead of mouth guards, you can use tampons soaked in vaseline oil or novocaine. 10-30 minutes before irradiation, a cystamine hydrochloride radioprotector 0.2-0.8 g or mexamine 0.05 g orally for 30-40 minutes is prescribed. before irradiation. immediately before irradiation, the oss is irrigated with an adrenaline solution in isotonic sodium chloride solution (2: 100) or adrenaline is injected under the skin, and the oss is treated with prednisone. at the initial manifestations of the radiation reaction, the oss and gums are treated 4 5 times a day with weak solutions of antiseptics. in the midst of a radiation reaction, a 1% solution of novocaine or trimecaine, a 1% solution of dicaine, a 10% oil emulsion of anestezin are used to anesthetize oss, periodontal pockets are washed with a warm solution of antiseptic agents, enzymes are applied with antibiotics, and then oss is treated with drugs such as hyposol -n "," sanguirithrin ", rosehip or sea buckthorn oil. at this time, the removal of teeth, tartar and curettage of periodontal pockets are contraindicated. therapy of post-radiation reactions and complications is aimed at increasing the body's resistance, a decrease in tissue permeability, as well as the elimination of factors that negatively affect the osr. prescribe "splenin", sodium nucleinate, batiol, rutin, nicotinic acid, vitamin b6, b12, "aevit", calcium preparations, "galascorbin". relative normalization of the oral mucosa occurs in 2 3 months. radiation sickness. radiation sickness is a disease that develops as a result of exposure to the body of ionizing radiation. distinguish between acute and chronic forms of radiation sickness. acute radiation sickness (ars) develops from a short-term (from several minutes to 1 3 days) exposure to the body γ rays and a neutron flux in doses exceeding 1 gy (gray), and is characterized by a phasic flow and polymorphism of the clinical picture. in the ars clinic, bone marrow (1 10 gy), intestinal (10 20 gy), toxemic (20 80 gy), cerebral (80 gy) forms are distinguished. when irradiation is less than 1 gy, one speaks of radiation injury. ionizing radiation causes metabolic changes in stem cells, lymphocytes, small intestinal epithelium, etc. there are five periods during the course of the disease: 1) the period of the primary reaction to radiation; 2) the latent period, or the period of imaginary well-being; 3) the period of pronounced clinical manifestations or peak; art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 114 4) the period of the permit; 5) the period of late complications and consequences of the lesion. clinic first period: general weakness, dizziness, headache, drowsiness, nausea, vomiting, diarrhea, nosebleeds, fever, loss of consciousness, flushing of the skin, injection of the sclera. dryness, metallic taste appears in the oral cavity, the sensitivity of the oral cavity decreases; it swells, hyperemia appears, punctate hemorrhages may occur. in the teeth, no visible clinical changes are observed, however, already at this stage, inhibition of phosphorus-calcium metabolism occurs, which in the iii period develops into structural and morphological changes. in the blood, neutrophilic leukocytosis, reticulocytosis, lymphopenia are found. the duration of the period of the primary reaction is up to 2 days. the second period begins on the 3rd day after irradiation and lasts 2-4 weeks. it is characterized by a relative improvement in general condition. there are no changes in the oral cavity, but the number of leukocytes and lymphocytes continues to fall, and the inhibition of hematopoiesis is noted. the third period is observed from 7 to 12 days after irradiation and lasts 3 to 4 weeks. it is characterized by a severe general condition caused by hematological, gastrointestinal disorders, increased bleeding, fever, and multiple complications. inhibition of hematopoiesis progresses. in the oral cavity, there is a pronounced hemorrhagic syndrome. necrotizing ulcerative gingivitis and stomatitis gradually develop. the mucous membrane of the lips, cheeks and tongue is covered with a whitish, viscous mucus. in severe cases, necrosis can spread with co to the underlying soft tissues and bone, leading to sequestration and possible fractures of the jaws. tonsils are covered with a dirty gray, hard-to-remove plaque, under which a bleeding surface opens. swallowing food is almost impossible due to severe pain. a putrid odor comes from the mouth. regional lymph nodes are enlarged and painful on palpation [2, 12]. the fourth period begins on the 4th week after irradiation and lasts 1 3 months. it is characterized by the slow reversal of disease symptoms. the fifth period begins from 5 6 weeks after exposure and lasts 3 or more months. it is characterized by residual ars in the form of long-term hematopoietic disorders (leukopenia, thrombopenia, erythropenia). transitions to leukemia (myelosis, reticuloendotheliosis) and various somatic pathologies in the oral cavity are possible. changes in the hard tissues of the teeth are noted chipped, as if pitted edges of the enamel, pathological abrasion. all this is combined with many cavities,localized mainly in the cervical region and on the approximal surfaces. there is circular caries, clouding of the enamel and the appearance of dark spots on it. areas of enamel demineralization are noted, dentin is easily removed in layers using an excavator. generalized periodontitis of the i-iii degree, oral dysbiosis, xerostomia, areas of hyperkeratosis, cyanoticity develop. the tongue is increased in size. neurostomatological symptoms appear: intermittent tingling sensation, creeping creeps, burning sensation and intense pain in the oral cavity, reminiscent of attacks of trigeminal neuralgia [5]. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 115 chronic radiation sickness (crs) occurs with prolonged external exposure to small doses of ionizing radiation, usually develops in people who, by the nature of their activities, encounter radioactive radiation (radiologists, etc.) and violate safety regulations. allocate mild (i degree), medium (ii degree) and severe (iii degree crs). clinic: the initial manifestation of crs is changes in the nervous system, which have the character of neurosis with autonomic disorders. in the future, disorders of neurogenic regulation, the cardiovascular system and the development of hemorrhagic syndrome join. in addition, there are dysfunctions of the gastrointestinal tract, liver, metabolism and the endocrine system. in the oral cavity, crs manifests itself in grade iii in the form of persistent gingivitis, bleeding gums, glossalgia and glossitis [21]. crs diagnosis is complex and is based on the study of peripheral blood and bone marrow. treatment ars requires physical and mental rest, high-calorie food, plenty of fluids, sedatives, antiemetics, detoxification, antihemorrhagic drugs, plasma substitutes. dairy and lactic acid products are recommended. prevention of inflammation of the oral mucosa is aimed at increasing the body's resistance and eliminating factors that have a negative effect on co (traumatic factors, infection.). removal of teeth and tartar, curettage of periodontal pockets, use of cauterizing agents are contraindicated. it is advisable to prescribe ascorutin, nicotinic acid, "aevita", vitamins b6, b12, calcium preparations. recommended processingoral cavity with weak antiseptic solutions. to increase local immunity in the oral cavity, rinse with artificial lysozyme, "immudon", is prescribed. for anesthesia, 1% solution of trimecaine, 2% solution of lidocaine, 10% suspension of anestezin in oil, oil solution of propolis, 1% solution of sodium mefenaminate are used. shown are the applications of enzymes trypsin, chymotrypsin (10 ml of 0.25% novocaine + 10 mg of the enzyme), as well as honsuride. on the treated surfaces, applications are made with anti-inflammatory and keratoplastic agents. use pastes and periodontal dressings withantibiotics, glucocorticoids, sodium mefenaminate, prepared in rosehip oil and sea buckthorn oil, vitamins a and e. in the period of long-term consequences, a complete sanitation of the oral cavity is carried out. it is better to use glass ionomer cements. movable and decayed teeth with chronic foci of infection at the apex are removed with subsequent suturing on the hole. suturing of the hole is necessary due to increased bleeding and poor blood clotting. this must also be taken into account when removing dental plaque, especially subgingival calculus, periodontal surgery. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 116 references 1. dentistry of children and adolescents / ralph e. mcdonald [et al.]; per. from english; ed. ralph e. mcdonald, david r. avery. m .: medical information agency, 2003.s. 516-523. 2. diseases of the oral mucosa / lm lukinykh [and others]; ed. l.m. lukins. n. novgorod: publishing house of the nizhny novgorod state medical university. academies, 2000. s.20-56. 3. e. е. maslak., v. naumova., kamalova m.k. relationship between general and oral diseases: literature review // american journal of medicine and medical sciences. америка, 2020. vol.10(9). р. 690-696. 4. elizarova, v.m., s.yu.,drobotko l.n. lesions of the oral mucosa of traumatic origin / v.m. elizarova, s.yu. strakhova, l.n. drobotko // medical assistance. 2007. no. 2.p.41-43. 5. gorbacheva, k.a. clinical and functional state of the oral cavity organs in children living in areas of radioactive contamination: abstract of the thesis. ... candidate of medical sciences // k.a. gorbachev; minsk state medical institute minsk, 1993. 16 sec. 6. kamalova m. k. medico-social and clinical-economic analysis of the treatment and prevention of dental caries in preschool children // "tibbiyotda yangi kun" scientific-abstract, cultural and educational journal. bukhara, 2020. №3(33). p. 79-80. 7. kamalova m. k., e.e. maslak., i.v. fomenko., a.l. kasatkina., t.n. kamennova., t.g. khmizova., k.v. nikitina.reasons for primary teeth extraction in children aged 1-14 years: a retrospective study // palarch’s journal of archaeology of egypt. нидерланды, 2020. vol.17. №6. р. 13947-13964. 8. kamalova m. k., rakhimov z. k., pulatova sh. k. optimization of prevention and treatment of dental caries in preschool children // "tibbiyotda yangi kun" scientific-abstract, cultural and educational journal. bukhara, 2019. №4 (28). p. 166-168. 9. kamalova m.k., fomenko, i. v., dmitrienko, d. s., matvienko, n. v., arjenovskaya, e. n., gevorkyan, a. g., maslak, e. e. (2020). reasons for 1-17-yearold children to visit a dentist during the covid-19 pandemic. european journal of molecular and clinical medicine, 7(7), 546-558. retrieved from www.scopus.com 10. kamalova m.q., sharipova g.i. «british medical journal». лондон, 2021. vol. 1, № 2. р. 165-173. 11. kamalova m.q., sharipova g.i. materials of the republican 31multidisciplinary online distance conference on «scientific and practical research in uzbekistan» part-18. tashkent, 2021. р. 11-13. 12. kamalova m.q., sharipova g.i. mechanical injuries oral cavity of early childhood children and preschool age // «cutting edge-science» international scientific and practical conference. usa, 2021. – р. 7-8. 13. kamalova m.q., sharipova g.i. results of screening of traumatic injuries of the oral cavity of preschool children // asian journal of multidimensional research, индия. 2021. vol 10, issue 8. р. 32-36. art of medicine volume-1 international medical scientific journal issue-2 10.5281/zenodo.5517719 117 14. kamalova m.q., sharipova g.i. traumatic injuries of the oral mucosa in young children // «tibbiyotda yangi kun» научно реферативный, культурно просветительский журнал. бухара, 2021. №3(35). с. 117-121. 15. kamilov h.p., kamalova m.k. improving the effectiveness of complex treatment of acute herpetic stomatitis in children / / norwegian journal of the international science international scientific journal. norway, 2017.no. 10.pp. 3537. 16. kamilov h.p., kamalova m.k. modern approaches in the treatment of ronic recurrent herpetic stomatitis in children // "achievements of science and education" international scientific journal moscow, 2018. -№3 (25). pp. 46-48. 17. kamilov h.p., kamalova m.k. the use of laser therapy in the treatment of chronic recurrent herpetic stomatitis in children // scientific journal european science review vienna, 2018. no. 7-8.pp. 120-121. 18. leontyeva v.k., kiselnikova l.p. children's therapeutic dentistry. national leadership.m .: geotar-media, 2010 .625 p. 19. lutskaya i.k. diseases of the oral mucosa. m., 2014 .224 p. 20. persin l.s., elizarova v.m., dyakova s.v. children's dentistry. m., 2003. 265-269 p. 21. vokhidov u.g., kamalova m.k. the use of various techniques in the treatment of traumatic injuries of the oral mucosa in children // european journal of molecular & clinical medicine. англия, 2020. vol. 7. issue 7. – р. 3743-3748. 22. yatsuk, a.i. assessment of the effect of low doses of ionizing radiation on the oral mucosa in children: abstract of the thesis. ... candidate of medical sciences / a.i. yatsuk; minsk state medical institute minsk, 1994.20 p. login | art of medicine. international medical scientific journal login art of medicine. international medical scientific journal art of medicine. international medical scientific journal current about the journal instruction instructions for authors regulations aims and scope license agreement open access statement ethical policy peer-review policy plagiarism policy 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polanya mirip fog layer mahjong wins 2 perubahan pola konsumsi terlihat pascabencana trennya mirip shift reel mahjong ways 3 aktivitas wisata alam masuk tahap evaluasi skemanya mirip access check mahjong wins kepadatan permukiman perbesar dampak cuaca efeknya seperti overstack mahjong ways 2 distribusi bantuan darurat gunakan skema cepat ritmenya mirip fast spin mahjong ways 3 kondisi laut mulai tenang bertahap transisinya mirip calm phase mahjong wins pengawasan wilayah rawan dilakukan bergilir sistemnya mirip patrol mode mahjong ways 2 harga logam mulia bergerak stabil polanya mirip locked multiplier mahjong ways 3 pola hujan bergeser dari prediksi awal geraknya mirip offset reel mahjong wins perbaikan jembatan darurat mulai dikerjakan ritmenya mirip fix combo mahjong ways 2 aktivitas transportasi umum tambah jadwal khusus efeknya seperti extra turn mahjong ways 3 cuaca mendadak berubah ganggu rencana harian efeknya mirip disrupted spin mahjong wins distribusi pangan dijaga lewat sistem cadangan skemanya mirip backup supply mahjong ways 2 aktivitas relawan terus mengalir dari berbagai wilayah dinamikanya mirip team combo mahjong ways 3 pemantauan sungai dilakukan nonstop sistemnya mirip live counter mahjong wins kualitas tanah pertanian terdampak cuaca basah dampaknya mirip soil debuff mahjong ways 2 penyesuaian jam kerja diterapkan sementara polanya mirip time shift mahjong ways 3 aktivitas malam dibatasi demi keselamatan aturannya mirip night lock mahjong wins distribusi energi masuk tahap normalisasi prosesnya mirip power restore mahjong ways 2 fenomena alam tak biasa picu diskusi lingkungan dampaknya mirip discovery mode mahjong ways 3 kegiatan komunitas warga mulai bangkit suasananya mirip revival spin mahjong wins kualitas lingkungan dipantau lewat indikator baru sistemnya mirip eco meter mahjong ways 2 arus barang antarwilayah berjalan bertahap ritmenya mirip smooth reel mahjong ways 3 kesiapsiagaan wilayah hadapi musim ekstrem ditingkatkan statusnya mirip survival mode mahjong wins pemulihan ekonomi lokal mulai terlihat prosesnya mirip gradual win mahjong ways 2 aktivitas kreatif warga tumbuh di tengah tantangan semangatnya mirip fresh spin mahjong ways 3 pola angin baru muncul di wilayah pesisir geraknya mirip direction shift mahjong wins distribusi bantuan fokus wilayah paling rentan skemanya mirip target spin mahjong ways 2 kualitas udara membaik usai hujan panjang transisinya mirip clean board mahjong ways 3 aktivitas pertanian masuk fase penyesuaian musim strateginya mirip adaptive play mahjong wins pemantauan cuaca digital jadi andalan informasi sistemnya mirip auto guide mahjong ways 2 kepadatan arus lokal terjadi di jam tertentu polanya mirip peak reel mahjong ways 3 distribusi air bersih gunakan sistem bergilir skemanya mirip rotation mode mahjong wins perubahan iklim lokal terasa lebih cepat efeknya mirip accelerated tile mahjong ways 2 aktivitas pembersihan lingkungan dilanjutkan prosesnya mirip clean sweep mahjong ways 3 penguatan ketahanan wilayah jadi fokus utama strateginya mirip defense mode mahjong wins optimisme warga muncul meski tantangan datang penutupnya mirip big finish mahjong ways 2 pemulihan sosial berjalan seiring infrastruktur alurnya mirip parallel spin mahjong ways 3 fenomena alam jadi bahan edukasi lingkungan dampaknya mirip knowledge bonus mahjong wins stabilitas wilayah diuji oleh cuaca tak menentu tekanannya mirip endurance mode mahjong ways 2 aktivitas harian berangsur kembali normal alurnya mirip reset board mahjong ways 3 fenomena pagi berkabut picu penurunan aktivitas warga polanya mirip fog mode mahjong ways lonjakan pengunjung di area publik terjadi mendadak ritmenya mirip crowd spin mahjong wins harga kebutuhan harian bergerak tidak stabil polanya mirip volatile board mahjong ways 2 suasana kota mendadak lengang di jam sibuk efeknya mirip empty reel mahjong wins 3 perubahan cuaca cepat picu penyesuaian jadwal alurnya mirip shift phase mahjong ways gangguan jalanan terjadi akibat genangan ringan situasinya mirip sticky path mahjong wins aktivitas pedagang musiman meningkat tajam ritmenya mirip seasonal bonus mahjong ways 2 kualitas udara menurun di area padat efeknya mirip smog layer mahjong wins 3 fenomena senja berwarna oranye jadi sorotan kejadiannya mirip flame tile mahjong ways mobilitas warga melambat di pagi hari ritmenya mirip slow spin mahjong wins kepadatan kendaraan terjadi di jalur alternatif polanya mirip reroute mode mahjong ways 2 perubahan pola konsumsi terlihat jelas alurnya mirip behavior shift mahjong wins 3 aktivitas digital mendominasi malam hari ritmenya mirip night spin mahjong ways suasana permukiman mendadak ramai efeknya mirip full board mahjong wins fenomena angin kering picu debu tebal situasinya mirip dust storm mahjong ways 2 aktivitas pagi terhambat kondisi jalan licin efeknya mirip slippery tile mahjong wins 3 harga produk lokal bergerak naik perlahan polanya mirip gradual multiplier mahjong ways peningkatan aktivitas luar ruang terlihat jelas ritmenya mirip outdoor bonus mahjong wins perubahan ritme kota terasa sejak akhir pekan alurnya mirip city shift mahjong ways 2 gangguan layanan digital terjadi singkat situasinya mirip blink lag mahjong wins 3 kawasan kuliner dipadati pengunjung sore hari ritmenya mirip food frenzy mahjong wins aktivitas transportasi umum mengalami penyesuaian polanya mirip schedule shift mahjong ways 2 penurunan aktivitas siang hari terpantau ritmenya mirip low phase mahjong wins 3 fenomena langit cerah tak biasa terjadi kejutannya mirip golden sky mahjong ways mobilitas antar wilayah meningkat bertahap ritmenya mirip speed up mahjong wins aktivitas sosial beralih ke ruang terbuka polanya mirip open board mahjong ways 2 kepadatan area hiburan terjadi mendadak efeknya mirip crowd burst mahjong wins 3 perubahan pola tidur warga jadi sorotan ritmenya mirip time shift mahjong ways fenomena suhu malam lebih hangat dari biasanya efeknya mirip heat trigger mahjong wins trending discover mahjong ways masuk zona jp karena pola ini observasi data scatter mahjong ways muncul beruntun saat auto spin identifikasi frame kemenangan burst win mahjong terlihat lebih rapi observasi data malam lonjakan pembayaran mahjong ways melebihi biasanya indikasi statistik sesi pgsoft mahjong terlihat meledak di malam hari mahjong wins memasuki mode kombinasi panjang dan wild beruntun evaluasi data simbol mahjong ways meningkatkan intensitas kombinasi insight multiplier dinamis kenaikan multi wild sejalan distribusi simbol mahjong wild progresif multiplier mahjong ways naik mengikuti ritme simbol eksperimental mahjong ways tampilkan respons reel lebih agresif menjelang malam monitoring scatter berkesinambungan mahjong ways masuk fase ganas studi reel bernilai tinggi mahjong ways dalam zona volatilitas rendah laporan khusus grafik mahjong pg soft mengungkap momentum tinggi pemantauan scatter bertingkat tumble mahjong ways hadirkan lonjakan kemenangan tren performa terbaru tumble mahjong ways dukung stabilitas payout data terbuka mahjong ways masuk fase panas berdasarkan monitoring sistem riset mendalam mahjong ways memasuki zona kombinasi intens log tumble beruntun peningkatan intensitas kemenangan mahjong ways jalur reel mahjong ways mengungkap tahap awal menuju tumble berantai pemetaan pola emas sinkronisasi simbol gold pada siklus mahjong ways pemantauan sistem reel balance mahjong wins terlihat aktifkan mode tumble perilaku reel mahjong wins identifikasi stabilization phase penghasil jp riset korelasi spin mahjong ways mengarah ke fase kombinasi ganas pola temporal mahjong ways menemukan jendela optimal tumble panjang fitur tersegmentasi mahjong wins 2 menjelang scatter muncul beruntun studi pola momentum track mahjong wins mengarah ke multiplier tinggi pre alignment mahjong wins 2 menunjukkan distribusi simbol pemodelan jalur putaran mahjong ways ungkap progressive momentum algoritmik lanjutan mahjong ways ungkap multi trigger sequence tersembunyi flow correction mahjong ways ternyata kunci utama untuk big hit mahjong ways pattern watch rotasi simbol masuk fase aktif sinyal pola mahjong ways terbaca perubahan ritme reel makin jelas daily insight kombinasi kecil mahjong ways mengarah besar pantauan slot terkini mahjong ways jaga tren pembayaran statistik big hit mahjong wins menguat saat masuki zona panas pemantauan reel mahjong transisi pola cepat terjadi di sesi malam mode turbo mahjong ways mulai dilirik berkat hasil positif real time pola tumble mahjong yang sering hasilkan hit besar performa mahjong wins menunjukkan lonjakan kombinasi di fase malam studi intensitas tumble mahjong ways beralih ke mode cepat signal watch grid tampil lebih seimbang di mahjong ways pgsoft menguat di statistik slot dengan performa konsisten laporan khusus struktur pola mahjong ways masuk fase ganas persaingan provider meningkat pgsoft dan pragmatic tak terbendung riset eksklusif pergerakan reel mahjong pg soft membentuk tumble panjang mahjong ways kian stabil pola scatter terlihat lebih teratur data rekaman sesi mahjong pgsoft menampilkan konsistensi tumble panjang pola scatter mahjong ways terbaca lebih aktif di sesi tertentu pemantauan grafik gold wild mahjong ways banjir dalam siklus malam analisis data terpadu pergerakan reel mahjong pgsoft menunjukkan arah jp terdeteksi aktif tumble dan wild mahjong bergerak lebih sinkron analisis struktur mahjong ways simbol premium lebih responsif bonus mahjong ways muncul intens menarik perhatian pemain observasi grid mahjong jalur kombinasi tinggi mulai terbentuk laporan perkembangan aktivitas reel mahjong wins meningkat signifikan log putaran mahjong temukan akumulasi momentum sebelum multi melejit pragmatic play tahan tekanan dengan kinerja rtp seimbang ritme spin mahjong ways alami perubahan rtp ikut bergerak observasi frekuensi mahjong ways scatter hadir lebih sering mahjong ways naik daun berkat tren rtp yang terjaga persaingan antar provider slot semakin terasa sengit pragmatic play menjaga ritme permainan tetap konsisten rekap slot harian mahjong ways tetap jaga stabilitas hasil peta kompetisi provider slot terus mengalami perubahan daya tarik mahjong ways tetap terjaga di tengah tren slot mahjong ways tetap diminati berkat performa yang terjaga indikasi positif terlihat dari performa terbaru mahjong ways mahjong ways tunjukkan pola permainan yang lebih bersahabat pgsoft kembali menjadi sorotan berkat kinerja slot yang solid catatan aktivitas terbaru mahjong ways masih stabil di pembayaran mode turbo mahjong ways dinilai membawa dampak nyata pola permainan mahjong ways terbaca lebih ramah pemain dampak mode turbo mahjong ways mulai terlihat jelas mahjong ways menunjukkan aliran permainan yang semakin lancar bonus mahjong ways tampil lebih aktif di sejumlah sesi kemunculan bonus mahjong ways terlihat lebih rapat dari biasanya pgsoft kian kokoh lewat catatan slot berkinerja tinggi mahjong ways memperlihatkan alur spin yang semakin mengalir pergerakan statistik mahjong ways isyaratkan peluang menarik pragmatic play konsisten menjaga keseimbangan permainan analisis slot pragmatic play pertahankan kinerja konsisten bonus di mahjong ways terlihat lebih sering hadir di beberapa putaran kompetisi antar provider slot terus berjalan ketat mahjong ways jadi sorotan pemain setelah bonus beruntun aktif mahjong ways memperlihatkan pola main yang lebih menguntungkan mahjong ways menunjukkan lonjakan scatter menarik sepanjang hari mahjong ways menunjukkan ritme permainan yang semakin konsisten mahjong ways trending setelah aktivasi pola pembayaran baru mode spin khusus dorong rtp mahjong ways naik drastis mode turbo mahjong ways mulai memberi hasil yang menarik pantauan terbaru mahjong ways masih menjaga alur pembayaran persaingan provider semakin panas pgsoft vs pragmatic play pgsoft catat rekor baru di statistik slot mingguan pgsoft tetap jadi perhatian lewat kinerja slot yang solid pola turbo mahjong ways bawa kesempatan menang besar pemain popularitas mahjong ways bertahan berkat performa yang terjaga pragmatic play menjaga stabilitas di tengah perubahan tren slot riset harian scatter mahjong ways sering muncul di mode terpilih sinyal performa positif terbaca dari aktivitas terbaru mahjong ways zona rtp mahjong ways terpantau stabil di segmen populer kejutan tengah putaran mahjong wins antar alwi raih jp fantastis tak sia sia menunggu pola mahjong ways antar yoga raih cuan besar skema jitu mahjong baca denyut reel dan raih free spin terlama kesempatan emas mahjong wins 3 mudah jp player langsung untung bocoran pro player tanda tanda jp baesar muncul di mahjong ways aktivitas ekonomi mikro melesat ritmenya mirip gradual win mahjong mahjong anti gagal scatter awal dan teknik gradual surfing terbukti keajaiban mahjong ways 2 dina di surabaya raup cuan super cepat pola aman mahjong wins pecah nominal jadi kunci taruhan lebih efektif strategi senyap rtp aktif mahjong ways yang bikin kemenangan brutal bukan kebetulan pola gerak simetris reel mahjong wins momen scatter scatter hitam mahjong bawa keberuntungan murid guru les malam versi viral mahjong wins pragmatic penasaran jadi cuan fantastis terungkap cara menang cepat mahjong ways saat player lain berhenti trik mahjong membaca pola halus di grafik reel untuk jp cepat agenda rahasia mahjong ways pgsoft memburu jp tajam tanpa ribet main tanpa panik pola rtp aktif mahjong yang mengarah ke cuan besar lipatan ledakan tumble mahjong ways trik ampuh bikin cuan meledak mahjong wins 3 rahasia para pengamat diam yang sukses raup cuan jangan lewatkan pola spin mahjong bisa buka bonus multi ganas aktivitas ekonomi mikro tunjukkan pergerakan positif ritmenya mirip soft win mahjong ways 2 gangguan sinyal terjadi di jam tertentu situasinya mirip signal drop mahjong wins 3 wilayah pinggiran mulai ramai aktivitas ritmenya mirip expansion zone mahjong ways kondisi jalan berlubang picu kewaspadaan efeknya mirip hazard tile mahjong wins aktivitas pagi warga terlihat lebih lambat ritmenya mirip slow start mahjong ways 2 fenomena alam unik terlihat di sungai kota kejadiannya mirip water shift mahjong wins 3 lonjakan penggunaan transportasi alternatif terjadi ritmenya mirip route switch mahjong ways aktivitas digital edukatif meningkat ritmenya mirip learning mode mahjong wins perubahan cuaca ringan picu penyesuaian aktivitas alurnya mirip soft reset mahjong ways 2 kawasan padat jadi titik fokus keamanan situasinya mirip alert tile mahjong wins 3 aktivitas malam hari lebih ramai dari biasanya ritmenya mirip turbo spin mahjong ways fenomena awan rendah terlihat menyentuh gedung efeknya mirip low cloud mahjong wins perubahan pola perjalanan warga terpantau polanya mirip path shuffle mahjong ways 2 aktivitas sosial virtual meningkat tajam ritmenya mirip online boost mahjong wins 3 wilayah tengah kota alami kepadatan sementara efeknya mirip temporary lock mahjong ways kondisi lingkungan jadi topik perbincangan warga alurnya mirip awareness mode mahjong wins fenomena cahaya malam tak biasa terjadi kejutannya mirip neon tile mahjong ways 2 aktivitas pasar pagi mulai ramai lebih awal ritmenya mirip early spin mahjong wins 3 mobilitas kendaraan berat berkurang signifikan polanya mirip load reduce mahjong ways perubahan jadwal kegiatan terjadi bertahap alurnya mirip phase shift mahjong wins aktivitas warga beralih ke jam fleksibel ritmenya mirip adaptive spin mahjong ways 2 fenomena alam lokal picu rasa ingin tahu efeknya mirip mystery event mahjong wins 3 kepadatan ruang publik terpantau stabil ritmenya mirip balanced board mahjong ways aktivitas ekonomi kreatif mulai meningkat ritmenya mirip growth spin mahjong wins cuaca bersahabat bantu aktivitas harian efeknya mirip smooth mode mahjong ways 2 wilayah baru jadi pusat aktivitas warga ritmenya mirip new hub mahjong wins 3 perubahan dinamika kota terasa signifikan polanya mirip city mode mahjong ways aktivitas transportasi berjalan lebih lancar ritmenya mirip clear path mahjong wins fenomena sosial ringan jadi bahan diskusi alurnya mirip viral tile mahjong ways 2 kondisi umum kota terpantau stabil tandanya mirip green signal mahjong wins 3 aktivitas warga kembali ke pola normal ritmenya mirip default spin mahjong ways fenomena alam kecil picu dokumentasi warga efeknya mirip snapshot bonus mahjong wins kepadatan jalan raya mulai berkurang ritmenya mirip load down mahjong ways 2 aktivitas publik berjalan lebih tertib ritmenya mirip control board mahjong wins 3 cuaca stabil dukung produktivitas warga efeknya mirip lucky flow mahjong ways wilayah aman dipadati aktivitas ringan ritmenya mirip safe zone mahjong wins perubahan ritme harian terjadi secara alami polanya mirip natural shift mahjong ways 2 aktivitas sosial berjalan seimbang ritmenya mirip balanced spin mahjong wins 3 fenomena kota kembali hidup di akhir pekan efeknya mirip weekend bonus mahjong ways aktivitas pagi hari di kawasan bisnis meningkat ritmenya seperti early spin mahjong ways cuaca lembap picu penurunan visibilitas situasinya mirip fog mode mahjong wins harga kebutuhan harian bergerak tipis polanya seperti soft multiplier mahjong ways 2 fenomena awan gelap datang mendadak visualnya mirip dark effect mahjong wins 3 lonjakan minat belanja daring terpantau antusiasmenya seperti frenzy spin mahjong ways tekanan panas udara uji ketahanan warga situasinya layaknya overheat mahjong wins 2 wilayah rawan genangan tingkatkan kewaspadaan tandanya mirip early warning mahjong ways 3 mobilitas siang hari melambat alurnya seperti slow reel mahjong wins perubahan pola konsumsi digital kian terlihat arahannya mirip shift mode mahjong ways 2 fenomena alam singkat picu perhatian publik efeknya layaknya mini bonus mahjong wins 3 interaksi sosial komunitas lokal menguat kekompakannya seperti free spin mahjong ways akhir sesi mahjong ways menutup putaran dengan gain konsisten analisis scatter track kenaikan pemicu free spin mahjong mulai terpantau analitik mahjong ways memasuki mode efisien tanpa volatilitas tinggi audit pergerakan reel mahjong ways mempertahankan intensitas tumble data statistik terbaru scatter mahjong pg soft terdistribusi banyak data valid mahjong ways jaga konsistensi zona drop wild x10 evaluasi profit route reel mahjong ways masuk fase peluang maksimal fase permainan mahjong masuk mode gain setelah repetisi minor grafik performa harian mahjong ways mengarah ke zona profit konsisten kajian statistik lapis reel mahjong ways memperlihatkan struktur pembayaran laporan investigatif mahjong ways menunjukkan sinyal return tinggi line reaction respons baris tengah pada kombinasi berlapis mahjong ways mahjong ways update aktivitas simbol mengalami lonjakan bertahap observasi data reel berkelanjutan mahjong ways menjaga ritme return rekaman statistik dinamis mahjong ways menyusun momentum multiplier riset frekuensi scatter mahjong ways muncul lebih cepat dari estimasi sinkronisasi simbol mahjong ways mengarah ke alur bayar efisien symbol elevation kenaikan posisi simbol mengubah alur spin mahjong ways temporal aktivitas tumble mahjong ways berubah signifikan di jam subuh tracking simbol aktif mahjong wins mengalami lonjakan sinkron harga logam mulia bergerak stabil grafiknya mirip balanced tile mahjong wins 2 cuaca sejuk tak biasa terjadi di perkotaan situasinya seperti cooldown mahjong ways 3 distribusi kebutuhan pokok tetap terjaga ritmenya layaknya auto spin mahjong wins fenomena urban ringan jadi perbincangan dampaknya mirip soft scatter mahjong ways 2 kepadatan transportasi muncul di titik tertentu kondisinya seperti tile lock mahjong wins 3 perubahan arah angin picu penyesuaian aktivitas responsnya mirip adaptive mode mahjong ways lonjakan konsumsi konten digital terpantau polanya seperti win streak mahjong wins 2 gelombang laut sedang ganggu aktivitas nelayan dampaknya layaknya wave pattern mahjong ways 3 tekanan aktivitas harian berangsur menurun ritmenya melambat seperti slow spin mahjong wins langit berawan tebal dominasi wilayah kota nuansanya mirip dark mode mahjong ways 2 distribusi informasi harian berjalan lancar alurnya rapi layaknya auto collect mahjong wins 3 aktivitas usaha kecil mulai stabil progresnya seperti level up mahjong ways cuaca hangat mendadak terasa perubahannya mirip warm phase mahjong wins 2 lonjakan kegiatan sosial terpantau akhir pekan soliditasnya seperti full board mahjong ways 3 harga energi bergerak konsolidatif dinamikanya layaknya roller spin mahjong wins kepadatan kawasan hunian naik bertahap situasinya seperti full reel mahjong ways 2 fenomena musiman datang lebih awal polanya mirip early event mahjong wins 3 warga menyesuaikan jam aktivitas harian ritmenya seperti meta shift mahjong ways cuaca cerah bertahan lebih lama situasinya layaknya clear board mahjong wins 2 distribusi barang harian kembali normal alurnya stabil seperti normal spin mahjong ways 3 tekanan lingkungan lokal picu evaluasi ringan prosesnya mirip checkpoint mahjong wins aktivitas media sosial meningkat tajam intensitasnya layaknya rapid spin mahjong ways 2 fenomena sosial ringan jadi viral lokal efeknya seperti epic spark mahjong wins 3 pelaku usaha mikro bertahan di tengah tantangan ketangguhannya mirip survival mode mahjong ways cuaca tak konsisten uji rencana harian warga polanya acak layaknya random spin mahjong wins 2 wilayah rawan angin kencang tingkatkan antisipasi tandanya mirip warning tile mahjong ways 3 permintaan kebutuhan rumah tangga naik tipis polanya seperti demand boost mahjong wins aktivitas kreatif lokal mulai bergairah perkembangannya seperti unlock feature mahjong ways 2 fenomena alam skala mikro terjadi singkat dampaknya ringan layaknya mini effect mahjong wins 3 penyaluran bantuan harian berjalan konsisten ritmenya seperti auto run mahjong ways cuaca berubah drastis dalam waktu singkat situasinya mirip fast switch mahjong wins 2 tekanan aktivitas perkotaan meningkat sementara intensitasnya seperti frenzy mode mahjong ways 3 harga komoditas mulai menemukan titik seimbang polanya mirip balanced spin mahjong wins aktivitas warga terpantau lebih teratur prosesnya seperti cooldown mahjong ways 2 fenomena lingkungan lokal jadi topik diskusi dampaknya mirip chain effect mahjong wins 3 lonjakan aktivitas rekreasi terlihat akhir pekan antusiasmenya layaknya final spin mahjong ways cuaca ekstrem ringan tak ganggu aktivitas utama ketahanannya mirip shield mode mahjong wins 2 distribusi informasi akurat terjaga stabil alurnya rapi seperti verified spin mahjong ways 3 aktivitas publik berjalan harmonis stabilitasnya layaknya safe spin mahjong wins fenomena alam mulai mereda bertahap prosesnya seperti reset stage mahjong ways 2 wilayah terdampak gangguan ringan mulai pulih pemulihannya mirip recovery feature mahjong wins 3 interaksi sosial masyarakat tetap solid kekuatannya seperti full combo mahjong ways cuaca mendukung aktivitas produktif situasinya seperti green light mahjong wins 2 mobilitas malam hari naik perlahan ritmenya mirip night spin mahjong ways 3 harga pangan bergerak stabil polanya seperti stable rtp mahjong wins fenomena urban musiman muncul kembali dampaknya layaknya big trigger mahjong ways 2 aktivitas warga lebih tertata dibanding sebelumnya ritmenya seperti clean board mahjong wins 3 tekanan perkotaan mulai melonggar prosesnya bertahap seperti calm mode mahjong ways distribusi kebutuhan harian berjalan mulus alurnya seperti smooth spin mahjong wins 2 fenomena alam jadi bahan obrolan publik viral layaknya highlight effect mahjong ways 3 aktivitas ekonomi harian terjaga konsisten ketahanannya seperti base rtp mahjong wins cuaca ekstrem lokal perlahan reda situasinya seperti end phase mahjong ways 2 lonjakan mobilitas transportasi terpantau jelas intensitasnya layaknya rush spin mahjong wins 3 kawasan perkotaan kembali bergerak dinamis ritmenya seperti resume spin mahjong ways curah hujan ekstrem picu banjir baru situasi seperti dead spin mahjong ways pencarian korban berlanjut di area sulit progres lambat ala low rtp mahjong wins 2 distribusi bantuan terhambat medan ritmenya delay reel mahjong ways 3 warga mengungsi ke tempat aman ketahanan seperti survival mahjong wins sungai naik cepat lewati ambang arus liar seperti chaos reel mahjong ways longsor susulan tutup akses desa kondisi berat ala overheat mahjong wins 3 evakuasi malam hari dipercepat gerak cepat ala turbo spin mahjong ways wilayah terpencil mulai terjangkau harapan muncul seperti scatter mahjong wins cuaca tak stabil ganggu aktivitas pola acak ala random tile mahjong ways 2 pemulihan jembatan sementara dipasang progres long spin mahjong wins 3 harga bahan pokok naik musiman pola increment mahjong ways pasar rakyat padat menjelang libur lonjakan bonus crowd mahjong wins 2 daya beli uji ketahanan rumah tangga shield mode mahjong ways 3 distribusi pangan tertahan hujan delay spin mahjong wins transaksi nontunai melonjak efek rtp boost mahjong ways 2 permintaan produk lokal menguat stabil steady spin mahjong wins 3 harga komoditas bergejolak harian volatility mahjong ways konsumsi tetap terjaga di tengah tekanan endurance mahjong wins arus belanja daring menguat progressive win mahjong ways 2 pasar kawasan tunjukkan konsolidasi reset board mahjong wins 3 kepadatan lalu lintas puncak sore full reel mahjong ways pengaturan arus kurangi titik macet mini win mahjong wins 2 transportasi massal dipadati penumpang continuous reel mahjong ways 3 perbaikan jalan fokus titik rawan target lock mahjong wins mobilitas harian naik signifikan overload mahjong ways 2 insiden ringan picu antrean panjang domino mahjong wins 3 skema pengalihan jalur diterapkan reroute spin mahjong ways arus balik terpantau lebih dini reverse spin mahjong wins 2 pengawasan jalur vital ditingkatkan early trigger mahjong ways 3 waktu tempuh berangsur normal clear reel mahjong wins gangguan layanan digital picu keluhan lag mode mahjong ways 2 pemulihan sistem dilakukan bertahap slow recovery mahjong wins 3 lonjakan akses bebani infrastruktur overheat reel mahjong ways proteksi data diperkuat menyeluruh guard mode mahjong wins 2 integrasi fitur baru masuk uji publik combo link mahjong ways 3 otomasi proses pangkas biaya mini win mahjong ways kinerja platform dijaga stabil long game mahjong wins 2 uji beban sistem berhasil dilalui shield mode mahjong ways 3 kecepatan akses jadi prioritas fast reel mahjong ways sinkronisasi layanan dipercepat smart spin mahjong wins 2 babak penentuan turnamen regional dimulai last reel mahjong ways 3 persaingan ketat hingga akhir high volatility mahjong wins hasil mengejutkan ubah peta laga tile shift mahjong ways 2 performa kolektif tim konsisten steady spin mahjong wins 3 laga krusial picu antusias publik bonus stage mahjong ways strategi bertahan jadi kunci smart play mahjong wins 2 aktivitas rekreasi air menarik minat warga kota energinya seperti splash bonus mahjong ways 3 penyesuaian jam operasional layanan umum diterapkan polanya mirip time align mahjong wins harga bahan pokok relatif stabil di awal bulan dinamikanya seperti steady mode mahjong ways 2 lonjakan aktivitas komunitas olahraga terpantau momentumnya seperti active win mahjong wins 3 gangguan cuaca hambat distribusi sementara situasinya seperti delay tile mahjong ways aktivitas wisata budaya kembali ramai atmosfernya seperti heritage bonus mahjong wins 2 distribusi energi alternatif menjangkau area baru skemanya seperti power shift mahjong ways 3 minat masyarakat pada produk ramah lingkungan meningkat energinya seperti green win mahjong ways kepadatan jalur wisata alam terjadi saat cuaca cerah polanya mirip peak reel mahjong wins 2 harga sewa akomodasi bergerak fleksibel dinamikanya seperti dynamic rate mahjong ways 3 aktivitas edukasi nonformal kembali diminati energinya seperti skill bonus mahjong wins 2 harga komoditas regional tunjukkan tren positif dinamikanya seperti uptrend reel mahjong ways 3 gangguan cuaca ringan tidak hambat aktivitas utama situasinya seperti soft mode mahjong ways aktivitas pagi di kawasan olahraga terlihat padat atmosfernya seperti warmup spin mahjong wins 2 distribusi bantuan sosial berjalan terpadu skemanya seperti chain support mahjong ways 3 minat belanja akhir pekan meningkat di pusat kota alurnya seperti weekend reel mahjong ways kualitas jalan lingkungan dijaga untuk mobilitas warga polanya mirip path guard mahjong wins 2 aktivitas ekonomi skala menengah terlihat stabil energinya seperti mid win mahjong ways 3 harga kebutuhan musiman bergerak ringan dinamikanya seperti minor reel mahjong ways kepadatan area rekreasi terjadi menjelang malam atmosfernya seperti twilight spin mahjong wins 2 aktivitas komunitas sosial terpantau aktif sepanjang pekan energinya seperti social chain mahjong ways 3 tim u22 tersingkir dari turnamen regional alurnya seperti comeback gagal di mahjong wins 3 regulasi keamanan terbaru dinilai bertabrakan dengan putusan hukum situasinya mirip deadlock mahjong ways 2 pengamen biola bertahan hidupi keluarga di tengah razia kisahnya seperti mode survival mahjong wins gedung tanpa sistem peringatan terbakar kekacauan terjadi layaknya scatter chaos mahjong ways belasan jenazah ditemukan mengapung di perairan misterinya mirip hidden tile mahjong wins 2 kecerdasan buatan kewalahan hadapi ribuan bahasa lokal kondisinya seperti error mode mahjong ways kebakaran gedung strategis diduga sabotase data polanya mirip trap feature mahjong wins 3 klasemen turnamen regional berubah drastis persaingan ketat layaknya turbo spin mahjong ways 2 skor langsung laga penentuan berubah cepat momentumnya mirip multiplier mahjong wins media negara tetangga soroti kekalahan dramatis reaksinya seperti near miss mahjong ways modus penipuan digital kian canggih skemanya mirip pola berlapis mahjong wins 2 parasut nyangkut di pesawat saat terbang ketegangannya seperti high risk spin mahjong ways idol populer tinggalkan grup musik dampaknya mirip reset feature mahjong wins korban jiwa bencana alam terus bertambah situasinya seperti long spin mahjong ways 3 spin-off bisnis infrastruktur jadi katalis pasar polanya mirip early bonus mahjong wins bangunan liar di area pemakaman dibongkar bertahap prosesnya seperti clear board mahjong ways harga cabai melonjak jelang libur panjang pergerakannya mirip volatile spin mahjong wins 2 larangan mencuci pakaian bersamaan diingatkan kembali alasannya seperti risk control mahjong ways penyebab kematian korban kebakaran gedung diungkap faktanya mirip reveal tile mahjong wins pelunasan kredit dipercepat demi stabilitas keuangan strateginya seperti cash out mahjong ways atlet daerah sumbang medali perunggu pencapaiannya mirip small win mahjong wins evakuasi pohon tumbang rampung arus lalu lintas normal kembali seperti reset mahjong ways pembangunan kawasan pemerintahan baru dimulai proses awalnya mirip early spin mahjong wins 3 tambang bermasalah picu polemik lingkungan situasinya seperti high volatility mahjong ways bantuan keuangan daerah bencana diatur ulang skemanya mirip balance adjustment mahjong wins analisis geopolitik global makin menguat polanya seperti chain reaction mahjong ways 2 transisi energi dorong lapangan kerja baru peluangnya mirip bonus unlock mahjong wins matcha langka picu kekhawatiran global fenomenanya seperti rare symbol mahjong ways puncak hujan meteor capai ratusan per jam kecepatannya mirip turbo mode mahjong wins bumi ternyata miliki ekor plasma raksasa temuannya seperti secret feature mahjong ways hotel tertinggi dunia jadi sorotan wisata skalanya mirip max multiplier mahjong wins 3 penertiban tempat pembuangan ilegal diperluas langkahnya seperti board cleanup mahjong ways aksi solidaritas pelajar untuk korban bencana mengalir energinya mirip free spin mahjong wins film thriller penerbangan tuai perhatian alurnya seperti suspense mode mahjong ways 2 aplikasi baru permudah lelang kendaraan inovasinya mirip auto spin mahjong wins kasus kejahatan seksual di daerah wisata diungkap kronologinya mirip dark pattern mahjong ways perbaikan infrastruktur pascabencana dilakukan patungan modelnya seperti co-op spin mahjong wins eksekusi bangunan adat tuai perdebatan situasinya mirip locked feature mahjong ways tips merawat hewan peliharaan agar lebih dekat pendekatannya seperti slow build mahjong wins kasus narkotika libatkan aparat desa penanganannya mirip risk control mahjong ways 2 kepadatan lalu lintas usai hujan deras kondisinya seperti jammed reel mahjong wins warga bertahan lewati banjir demi kebutuhan keluarga perjuangannya mirip last spin mahjong ways 3 jadwal semifinal turnamen regional resmi dirilis ketegangannya mirip final round mahjong wins pengumuman juri ajang musik tuai kejutan efeknya seperti sudden feature mahjong ways aksi donasi publik di ruang terbuka ramai disorot antusiasmenya mirip big win mahjong wins akses jalan lintas timur kembali dibuka pemulihannya seperti reconnect mahjong ways pembangunan flyover strategis dipantau langsung progresnya mirip progress bar mahjong wins sorotan dunia kampus memanas dinamika akademik mengalir seperti pola mahjong ways isu keabsahan dokumen publik bergulir alurnya mirip mystery tile mahjong wins 2 evaluasi jalur kombinasi mahjong ways menunjukkan tren positif bertahap breakdown reel mahjong saat simbol premium turun rapi di fase akhir insight reel mahjong menghasilkan wild berantai saat bet dinaikkan riset meta mahjong ways: pergerakan reel terkunci mengubah alur kemenangan pergerakan simbol mahjong ways menunjukkan fase konsolidasi kemenangan eksperimen taruhan mahjong ways: perubahan bet membuka pola wild unik pola tumble naik turun membawa hasil lebih stabil di mahjong grid mahjong ways memperlihatkan peluang lebih besar di zona panas studi ritme mahjong ways masuk fase quiet sebelum wild meledak area kiri atas teridentifikasi sebagai pemicu scatter premium mahjong ways pattern accumulation mengumpulkan scatter mahjong ways secara bertahap evaluasi sistem mahjong wins 2 menunjukkan ritme stabil sepanjang sesi reel acceleration scan mempercepat transisi kombinasi besar mahjong ways analisis mekanis terukur: mahjong ways bergerak ke mode high return micro tumble report: pergeseran kecil memicu kombinasi panjang mahjong ways frekuensi mahjong mengalami lonjakan high return di jam utama pola kombinasi mahjong ways memperlihatkan aktivitas scatter berlapis combo chain signal pg soft memperlihatkan potensi multi di mahjong ways laporan indeks performa mahjong ways dalam menjaga konsistensi multiplier pre-freespin mapping membocorkan jalur perolehan scatter mahjong ways pemetaan data volatilitas mahjong ways konsisten menghasilkan multiplier tinggi observasi pro wild mahjong ways menguat pada sesi bermain panjang analisis mikro pergerakan mahjong ways terbaca menuju fase high return data rotasi mahjong ways terpantau seimbang menuju kombo besar statistik real-time mahjong wins 3 menjaga konsistensi scatter aktif reel dynamics: gerak reel mahjong ways menjaga momentum kemenangan audit berbasis data mahjong ways mempertahankan intensitas tumble beruntun pattern reel sync wave mahjong wins 2 mengantar tumble berlapis pola reel pressure mahjong ways teridentifikasi sebagai pemicu lonjakan multiplier pengamatan drift zone mahjong wins menghasilkan scatter hitam ganda pemantauan mendalam mahjong wins dalam aktivasi multiplier bertahap pengamatan sistematis scatter mahjong wins lebih padat di malam hari scatter density radar mahjong ways menunjukkan lonjakan frekuensi mendadak pemain pro wild mahjong ways terpantau aktif pada interval pendek studi kinerja wild mahjong wins muncul konsisten tanpa penurunan rng pulse reading mahjong ways mendeteksi perubahan irama spin wild activation zone mahjong ways mengarah ke kepadatan simbol reel timing audit menahan tumble mahjong ways sebelum multiplier aktif spin cycle breakdown mahjong ways masuk loop kemenangan beruntun laporan rotasi mahjong ways mengalami sinkronisasi simbol beruntun analisis waktu main mahjong ways optimal saat sesi malam consistency map struktur spin mahjong ways yang jarang gagal data real time malam hari mahjong wins masuk fase burst deteksi pola awal mahjong ways tampilkan sinyal tumble berantai deteksi pola tersembunyi mahjong bangun kombo panjang dari spin tenang evaluasi pergerakan tumble mahjong wins aktifkan wild secara beruntun evaluasi pola malam mahjong wins memperlihatkan wild lebih sering grafik momentum mahjong wins memperlihatkan arah mode high return grafik tren malam mahjong ways terlihat naikkan intensitas kemenangan grid shift monitoring perubahan tata letak wild mahjong ways heat tracking zona panas rtp di dalam reel mahjong ways insight teknis sinkronisasi simbol mahjong ways dorong multiplier laporan tren discover mahjong pgsoft aktifkan mode agresif laporan tren terbaru mahjong wins masuk fase produktif berkelanjutan monitoring data reel mahjong ways masuk zona kombinasi padat observasi sesi malam mahjong ways tunjukkan ritme hit lebih cepat pemindaian pola aktif mahjong ways mulai dorong kombinasi berlapis percikan wild mahjong ways di awal spin menuju win besar reel depth observation mahjong ways hadirkan wild menjelang freespin reel flow stability indikasi mahjong ways sebelum profit melonjak reel frequency mahjong mengukur intensitas spin menuju profit stabil ritme putaran mahjong ways picu kombo tanpa trigger bonus scatter momentum check mahjong ways masuk fase pemanasan bonus scatter pulse mode ritme kemunculan scatter dalam perubahan grid spin flow monitor arah gerak simbol mahjong ways mengalami reposisi spin orbit rotasi reel mahjong yang mengarah ke freespin cepat statistik harian mahjong wins bergerak konsisten di mode aktif scatter statistik pergerakan simbol mahjong wins stabilkan burst win tumble interval study jarak antar runtuhan jadi penanda mode tinggi wild expansion alert peringatan wild mulai meluas di reel mahjong sinkron reel mahjong ways 2 memasuki fase aktivasi bonus bertahap pemantauan statistik real time mahjong ways masuki fase multiplier grafik performa super pgsoft mahjong mengalami akselerasi tumble indeks volatilitas wild mahjong pgsoft bertahan di zona produktif analisis distribusi simbol mahjong wins mengarah ke skema efisien data pemain pro zona agresif mahjong ways terpicu malam hari audit statistik jalur multiplier menengah mulai aktif di mahjong ways evaluasi statistik grid mahjong wins menjaga stabilitas kombinasi tinggi studi pergerakan simbol wild mahjong konsisten bangun nilai high return studi korelatif kenaikan wild mahjong sejalan dengan intensitas multi hit analisis pola numerik mahjong ways memicu rentetan pengali stabil struktur kombinasi mahjong wins terlihat lebih teratur hasilkan jp statistik mahjong wins 3 mengidentifikasi fase transisi menuju kombinasi besar pemantauan scatter mahjong wins 3 terdeteksi aktif setelah malam hari grafik pergerakan mahjong wins alami lonjakan multiplier bertahap laporan kuantitatif mahjong ways menunjukkan lonjakan multiplier bertahap reel density kepadatan simbol wild mahjong dalam zona tengah pemantauan statistik berkelanjutan mahjong ways menguat di sesi malam insight wild run distribusi wild mahjong ways menguat mendekati bonus tracking pola emas mahjong ways menampilkan aktivasi gold frame beruntun pemantauan data dinamis mempercepat siklus tumble mahjong ways laporan teknik pg soft mahjong ways memasuki mode sinkronisasi simbol pemantauan intensif wild pola kemunculan mahjong ways lebih terstruktur riset reel motion pola mahjong ways mulai menemukan jalur kemenangan uji pola terbaru mahjong ways bereaksi berbeda pada skema spin ini studi scatter reaction mahjong ways mengarah ke siklus free spin laporan eksploratif pergerakan simbol wild mahjong ways semakin sinkron mahjong ways memperlihatkan arah kemenangan progresif secara beruntun rekaman statistik mahjong ways mengarah ke fase multi aktif mahjong ways masuk jalur ganas berdasarkan pergerakan simbol wild mahjong tips pola main agar sesi panjang tetap menguntungkan tracking tendensi baru spin mahjong ways masuk mode mixed behavior analisis sesi aktif mahjong ways dorong kombo berlapis di waktu malam siklus tersembunyi mahjong phase loop tengah yang membawa jp reel density report rapatan simbol jadi kunci mode menang mahjong auto jackpot cara rahasia mahjong yang diam dipakai player data eksperimen sesi malam respons mahjong ways terlihat lebih tajam deteksi pola tersembunyi mahjong ways naikkan frekuensi kombinasi nilai betting tepat mahjong ways pgsoft langsung lancar sekejap mahjong phase break pecahnya mode tenang menuju spin agresif symbol lift mahjong kenaikan distribusi premium sebelum big hit variabel reel mahjong ways mengarah pada distribusi simbol stabil kajian kombinasi simbol intensitas hit mahjong ways naik bertahap wild tempest signal deteksi badai wild di mahjong ways statistik jam prime time mahjong pgsoft masuk mode ledakan kombinasi breakdown frame kemenangan struktur burst mahjong terbaca lebih stabil ritme alam dan mahjong saat pola harian bisa reset mendadak vector shift pergeseran sudut reel mahjong menuju mode profit mahjong ways pgsoft diserbu pemain server hampir tak tertahan analisis mode tengah mahjong ways menyentuh jalur kombinasi efektif terbongkar formula mahjong bisa lipat gandakan saldo dalam menit analisis tren malam hari mahjong ways mulai masuk fase jp observasi pola panjang mahjong wins aktifkan wild secara beruntun sync momentum keselarasan wild mendorong tumble mahjong beruntun salah baca rtp mahjong ways begini cara untung maksimal putaran awal mahjong wins penuh cuan ikuti pola thermal rise ini route analyzer mengurai jalur tumble mengarah ke jp mahjong cuan maksimal pola reverse spin mahjong ways 2 mulai terpantau pemantauan reel mahjong wins tunjukkan burst win lebih konsisten grafik pola reel mahjong wins mengarah ke fase hit panjang observasi jalur scatter mahjong ways meningkatkan presisi trigger scatter pattern watch fs mahjong ways bergerak di zona panas pemahaman pola terkini mengarah pada keunggulan di rangkaian game pgsoft mahjong ways memperlihatkan arah positif berdasarkan pembacaan terakhir peralihan cara bermain membawa dampak nyata pada mahjong ways stabilitas gerak reel mahjong ways mengarah ke wild berlapis symbol pressure index mahjong ways berada di ambang bonus mahjong ways tunjukkan respons tinggi saat pola permainan disesuaikan mahjong wins masuk jalur multi x10 berdasarkan data terbaru pragmatic play memunculkan kejutan lewat kestabilan hasil yang terjaga reel harian mahjong mengarah ke return konsisten di sesi malam pgsoft menjadi pusat perhatian usai capaian maksimal terekam jelas pemetaan jalur jp mahjong wins menghasilkan tumble panjang lebih terstruktur transition watch mahjong ways berpindah mode tanpa fluktuasi tajam stability report fs mahjong ways muncul konsisten tanpa ribet isyarat kuat mengarah pada mahjong ways yang sedang ramah permainan spin tempo kecepatan putaran mahjong ways melonjak di fase ganas pattern stabilizer reel menjaga konsistensi jalur kemenangan mahjong ways symbol load insight simbol premium mahjong ways terdistribusi merata mahjong ways menarik minat setelah grafik internal bergerak naik monitoring waktu nyata aktivitas wild mahjong wins semakin terstruktur pemantauan jalur aktif mahjong ways tingkatkan multi kombinasi tinggi pola wild mahjong wins 2 lebih stabil saat transisi bet halus respons reel mahjong bereaksi positif di mode semi stabil laporan performa harian mahjong ways tunjukkan konsistensi payout tumble chain observation rantai wild mahjong mengarah ke mode burst riset distribusi wild mahjong ways beralih ke skema progresif catatan waktu nyata menempatkan mahjong ways dalam situasi menguntungkan flow tracker alur tumble terlihat lebih galak di mahjong ways mahjong ways dinilai sedang bersahabat berdasarkan jejak permainan terbaru tekanan-mental-meningkat-jelang-final-dead-spin-moment-mahjong-ways-3 peluang-tiket-final-terbuka-scatter-window-mahjong-wins jadwal-padat-uji-stamina-marathon-spin-mahjong-ways-2 kemenangan-tipis-tentukan-langkah-last-hit-mahjong-wins-3 kabut-pekat-selimuti-perkotaan-fog-mode-mahjong-ways suhu-tinggi-picu-risiko-kesehatan-overheat-alert-mahjong-ways-3 gelombang-laut-tinggi-hambat-pelayaran-all-in-risk-mahjong-wins panas-berkepanjangan-tekan-aktivitas-cooldown-needed-mahjong-wins-3 debit-sungai-naik-turun-tak-stabil-bouncing-tile-mahjong-wins-2 pesisir-hadapi-ancaman-abrasi-long-term-risk-mahjong-ways-3 pemantauan-cuaca-diperketat-harian-guard-mode-mahjong-wins festival-lokal-kembali-ramai-bonus-crowd-mahjong-ways pameran-kreatif-tarik-pengunjung-flow-win-mahjong-wins-2 tren-hiburan-digital-kian-kuat-viral-spin-mahjong-ways-3 serial-lokal-mendominasi-tontonan-jackpot-feel-mahjong-wins musik-independen-dilirik-luas-rising-reel-mahjong-ways-2 pertunjukan-virtual-raih-audiens-baru-big-win-scale-mahjong-wins-3 kreator-konten-alami-lonjakan-eksposur-rtp-boost-mahjong-ways minat-baca-digital-terus-naik-slow-gain-mahjong-wins konsumsi-herbal-masuk-rutinitas-small-win-effect-mahjong-wins-2 aktivitas-fisik-ringan-digemari-stable-spin-mahjong-ways-3 pola-istirahat-seimbang-disorot-recovery-mode-mahjong-wins kesadaran-kesehatan-mental-menguat-mindful-play-mahjong-ways-2 kebiasaan-sehat-terjaga-konsisten-steady-reel-mahjong-ways-3 penanaman-pohon-diperluas-bertahap-growth-tile-mahjong-wins-2 kesadaran-daur-ulang-meningkat-repeat-win-mahjong-wins kualitas-air-bersih-dijaga-ketat-clear-reel-mahjong-ways-2 edukasi-lingkungan-menjangkau-pelajar-early-game-mahjong-ways adaptasi-iklim-jadi-agenda-utama-shift-strategy-mahjong-ways-3 inovasi-urban-tingkatkan-kenyamanan-smart-city-spin-mahjong-ways penataan-kawasan-publik-dipercepat-flow-board-mahjong-wins-2 transportasi-ramah-lingkungan-diuji-green-mode-mahjong-ways-3 manajemen-air-kota-diperkuat-stability-reel-mahjong-wins sistem-peringatan-dini-dioptimalkan-early-trigger-mahjong-ways-2 tata-kelola-ruang-terbuka-diperbaiki-balance-mode-mahjong-wins-3 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aktivitas-transportasi-malam-terpantau-stabil-ritmenya-seperti-night-cycle-mahjong-wins-2 harga-komoditas-global-bergerak-campuran-sepanjang-pekan-dinamikanya-mirip-mixed-reel-mahjong-ways-3 distribusi-produk-pertanian-lokal-dipercepat-skemanya-seperti-harvest-boost-mahjong-ways kepadatan-area-perbelanjaan-terlihat-jelang-libur-atmosfernya-seperti-crowd-spin-mahjong-wins-2 aktivitas-pasar-malam-terpantau-stabil-hingga-larut-atmosfernya-seperti-night-loop-mahjong-wins perbaikan-fasilitas-publik-dilakukan-bertahap-skemanya-seperti-repair-mode-mahjong-ways-2 lonjakan-permintaan-transportasi-umum-terjadi-di-akhir-pekan-alurnya-seperti-shared-spin-mahjong-wins-3 kualitas-lingkungan-perkotaan-ditingkatkan-melalui-penataan-polanya-mirip-clean-grid-mahjong-ways aktivitas-rekreasi-keluarga-naik-di-ruang-terbuka-energinya-seperti-family-win-mahjong-wins-2 harga-produk-laut-bergerak-stabil-mingguan-dinamikanya-seperti-calm-wave-mahjong-ways-3 gangguan-teknis-ringan-hambat-layanan-digital-situasinya-seperti-minor-lag-mahjong-wins distribusi-barang-kebutuhan-harian-terjaga-lancar-skemanya-seperti-supply-lock-mahjong-ways-2 minat-wisata-pegunungan-terpantau-konsisten-momentumnya-seperti-hill-bonus-mahjong-wins-3 kepadatan-transportasi-antarwilayah-terjadi-di-jam-tertentu-polanya-mirip-cross-spin-mahjong-ways alokasi modal dan rtp terbaik untuk menang konsisten di mahjong ways dokumentasi pembayaran akurat kunci strategi jp di mahjong ways fitur tersembunyi pgsoft mahjong bikin pemain baru langsung raup jp mahjong kini lebih gampang simak cara main dan strategi terbarunya mahjong wins daya tarik dari simbol baru dan kemenangan bertahap modal aman cuan terjaga trik mahjong wins khusus deposit dana natal dan tahun baru 2026 mahjong ways banjir jp fantastis strategi scatter wild terarah kunci jp besar di mahjong ways 2 trik cerdas mahjong stabilkan rtp sejak awal untuk hasil maksimal trik simbol emas mahjong gandakan multiplier raup menang besar bukan sekadar spin strategi solid menjaga modal di mahjong ways cuan tahan lama terbukti rahasia pengaturan koin di mahjong ways dari nol ke fantastis kisah yusuf menaklukkan mahjong ways mahjong wins dibongkar pola menang efektif yang sudah teruji rtp hijau aktif gunakan pola ini untuk amankan jp mahjong saatnya gas mahjong ways lagi panas sensasi cuan besar menanti sedikit yang pakai teknik kontrol tempo rtp stabil di mahjong skema juara mahjong pola terencana agar setiap spin ke cuan strategi putaran terlarang rtp jam ini sering pecah di mahjong strategi teknikal mahjong pola spin efektif pemicu bonus besar klarifikasi infrastruktur nasional muncul situasinya seperti false spin mahjong ways 2 tim regional menang telak namun gugur nasibnya mirip near win mahjong wins 3 gelombang penolakan budaya digital muncul efeknya seperti chain feature mahjong ways kasus kekerasan domestik terungkap kronologinya mirip long spin mahjong wins konten dewasa picu kontroversi publik dampaknya seperti high risk mode mahjong ways 3 proyek wisata bermasalah berlanjut proses hukumnya seperti slow build mahjong wins 2 polemik warisan budaya memanas dinamikanya mirip locked tile mahjong ways laporan keluarga korban menguat tekanannya seperti turbo spin mahjong wins 3 panduan ai visual ramai dicari tren editannya mirip scatter mahjong ways 2 pertemuan elit daerah bahas isu strategis alurnya seperti setup spin mahjong wins video teguran otoritas viral reaksinya seperti shock mode mahjong ways tim olahraga menang tapi tersingkir skenarionya mirip dead spin mahjong wins 2 ancaman siklon tropis diwaspadai pergerakannya mirip rolling reel mahjong ways 3 ramalan shio tahun mendatang dibahas polanya seperti predict spin mahjong wins layanan digital global dibedah ekosistemnya mirip multiplier mahjong ways penganugerahan internasional digelar atmosfernya seperti bonus round mahjong wins 3 daftar film horor terpopuler dirilis ketegangannya mirip free spin mahjong ways kemenangan tim usia muda tak cukup nasibnya seperti almost scatter mahjong wins 2 rancangan regulasi pendidikan bocor isinya seperti hidden rule mahjong ways promo belanja akhir tahun meledak ritmenya mirip rapid spin mahjong wins pesan stabilitas keuangan disampaikan strateginya seperti safe mode mahjong ways ancaman pembekuan layanan berujung pujian dramanya mirip reversal spin mahjong wins 3 kasus penyalahgunaan dana terbongkar jalurnya seperti trap tile mahjong ways 2 kebakaran permukiman timbulkan duka dampaknya seperti burn reel mahjong wins banjir lahar terjang wilayah sungai alirannya mirip cascade mahjong ways seruan kolaborasi publik-swasta menguat polanya seperti combo feature mahjong wins 2 pendaki remaja jatuh di pegunungan tragedinya seperti sudden drop mahjong ways 3 reuni serial lawas picu haru emosinya mirip emotional spin mahjong wins pilihan hidup mandiri jadi sorotan jalurnya seperti solo mode mahjong ways inisiatif lingkungan global dipercepat targetnya seperti maxwin chase mahjong wins 3 festival edukasi anak digelar metodenya mirip learning spin mahjong ways 2 daftar musisi viral tahun ini dirangkum polanya seperti trending tile mahjong wins badai terjang kamp pengungsi dampaknya seperti chaos mode mahjong ways bantuan kemanusiaan mengalir deras prosesnya seperti recovery spin mahjong wins 2 riset medis ungkap temuan baru datanya seperti unlock feature mahjong ways 3 tim regional raih medali jalannya seperti clean win mahjong wins insiden lalu lintas pelajar disorot kronologinya mirip chain reaction mahjong ways perubahan identitas budaya diperdebatkan alurnya seperti split path mahjong wins 2 temuan arkeologi pertanian kuno terungkap prosesnya mirip discovery spin mahjong ways 3 klasemen turnamen regional berubah cepat pergerakannya seperti fast reel mahjong wins kebijakan pajak wisata dibahas global skemanya seperti balance mode mahjong ways momentum solidaritas bencana menguat efeknya seperti full scatter mahjong wins 3 laga klub eropa panas intensitasnya mirip overheat spin mahjong ways diskon tarif transportasi diluncurkan dampaknya seperti boost mode mahjong wins 2 prediksi siklon baru dirilis polanya seperti warning spin mahjong ways 3 sorotan aksesori kesehatan tokoh dunia viral fenomenanya mirip random trigger mahjong wins gugatan platform digital ditanggapi strateginya seperti counter spin mahjong ways alasan ugal-ugalan pengemudi terungkap jalurnya seperti risk spin mahjong wins 2 wisuda program teknologi digelar atmosfernya seperti achievement spin mahjong ways 3 target transaksi belanja nasional naik ambisinya seperti jackpot path mahjong wins segmentasi fitur mahjong wins 2 dan kemunculan scatter beruntun analisis jalur profit reel mahjong ways mengarah ke zona optimal observasi simbol inti bernilai tinggi mahjong muncul di sesi malam pemeriksaan reel: intensitas tumble mahjong ways tetap stabil monitoring sesi mahjong ways mengalami peningkatan kombo beruntun struktur simbol dan pergeseran scatter mempengaruhi putaran mahjong ways ringkasan observasi mahjong ways menunjukkan kemenangan konsisten pembacaan sistem internal engine mahjong wins mempercepat scatter pemantauan perilaku reel mahjong sebagai indikator fase ganas alur spin terbaca: mahjong wins 3 bergerak ke arah freespin mahjong wins mengaktifkan rangkaian kombinasi panjang berurutan data aktual multi rendah berulang menjadi indikator awal jp mahjong pemetaan simbol dan intensitas formasi wild mahjong mengalami akselerasi observasi ritme spin mahjong ways sinkron dengan pola multiplier pg soft mahjong ways memperlancar jalur kombinasi menjelang bonus hubungan ritme wild dan nilai pengali mahjong ways menghasilkan jp performa aktual tumble mahjong ways menjaga konsistensi pembayaran analisa auto spin scatter mahjong ways mulai terkunci konsisten mapping kemenangan: struktur burst win mahjong tampil lebih padat pemantauan intensif scatter muncul bertahap sebelum mode pengganda observasi struktur grid jalur efisien mahjong ways penghasil multi x10 data perilaku mesin mahjong wins mengungkap eskalasi scatter bertahap jejak putaran mahjong wins ungkap fase penumpukan kombinasi tinggi laporan makro & mikro mahjong ways alami sinkronisasi wild berantai riset lanjutan memperlihatkan impulse route mahjong hadirkan kombo besar pemantauan rtp pg soft mahjong ways mengalami kenaikan konsisten signal data valid jalur kombinasi ganda mahjong ways mulai terlihat analisis pergerakan pro pg soft mahjong ways memasuki zona pengganda symbol reaction mode: respons visual saat kombinasi mahjong ways terputus kajian reel cepat mahjong wins merespons lebih ganas di jam subuh pemodelan statistik mahjong wins mengarah ke zona transisi multiplier pattern reel signal fusion mahjong wins aktif hadirkan scatter hitam studi dinamika mahjong ways menemukan aliran stabil menuju big hit data lapangan mahjong ways masuk tahap distribusi hit merata analisis spin berlapis mahjong ways menunjukkan awal tumble intens segmentasi data mahjong ways menemukan jendela momentum kemenangan monitoring intensitas wild mahjong ways sering menghasilkan jp mahjong symbol frequency map: persebaran simbol berdasarkan intensitas visual momentum shift: perubahan arah mahjong ways di mid game struktur kombinasi mahjong ways mengarah ke tumble beruntun data historis menunjukkan aktivasi kombinasi menengah mahjong ways efisiensi skema simbol mahjong wins terlihat dari penyebaran data indikasi multiplier muncul dari statistik terbaru mahjong ways transisi pola kombinasi mahjong wins 3 terdeteksi via data statistik statistik simbol mahjong menggambarkan awal fase performa panas hubungan intensitas multi hit dan pertumbuhan wild mahjong ways jalur perhitungan menengah mahjong ways terbuka berdasarkan audit data analisis ritme internal mahjong ways menunjukkan scatter bertahap konsistensi kombinasi tinggi terjaga dalam grid statistik mahjong wins distribusi simbol wild terkonsentrasi di area reel tengah mahjong ways kecepatan kendaraan saat insiden dianalisis datanya seperti frame check mahjong ways respons publik atas kegagalan lolos turnamen menguat reaksinya seperti tilt mode mahjong wins 2 banjir luapan sungai terjang permukiman polanya mirip alur tekanan mahjong ways distribusi bantuan darurat tetap stabil di wilayah terdampak seperti ritme mahjong ways 2 pemulihan listrik berjalan bertahap progresnya serupa mode build up mahjong wins harga energi bersubsidi diperpanjang di zona bencana skemanya mirip delay feature mahjong wins 2 operasi darurat logistik meningkat di beberapa daerah dinamikanya seperti mahjong wins 3 evakuasi anak korban banjir berlangsung dramatis alurnya mirip cutscene mahjong ways penyebaran informasi palsu soal bantuan sosial terbantahkan mirip fake scatter mahjong ways 2 aktivitas ekonomi daerah bangkit perlahan usai bencana seperti recovery mode mahjong wins pasokan kebutuhan pokok dijaga ketat polanya stabil layaknya mahjong wins 2 harga logam mulia naik tajam hari ini lonjakannya serupa multiplier mahjong wins 3 fluktuasi nilai tukar mereda geraknya mirip calm spin mahjong ways pasar investasi domestik menguat alurnya seperti early win mahjong ways 2 aset keuangan berbasis syariah cetak rekor baru seperti jackpot mahjong wins pameran industri dan arsitektur digelar skala global antusiasmenya mirip event mahjong wins 2 pemulihan infrastruktur terus dikebut prosesnya seperti long spin mahjong ways operasi keamanan ungkap aktivitas terlarang di hunian mewah polanya mirip hidden tile mahjong ways 2 kasus kejahatan terorganisir berakhir vonis berat dramanya serupa final spin mahjong wins 3 tren kesehatan unik dunia medis diuji metodenya tak biasa seperti bonus mode mahjong ways fenomena medis langka jadi sorotan global dampaknya mirip wild effect mahjong wins teknologi antariksa biaya rendah mulai diperkenalkan terobosannya seperti scatter mahjong ways 2 cuaca ekstrem mengganggu aktivitas pengungsi situasinya mirip high volatility mahjong wins program lingkungan tanam mangrove digencarkan efek jangka panjangnya seperti slow win mahjong ways mitigasi abrasi pesisir diperkuat polanya terukur layaknya mahjong wins energi hijau didorong lewat inovasi baru arahnya seperti upgrade feature mahjong wins 2 tren pernikahan global bergeser ke konsep ramah lingkungan mirip meta baru mahjong ways longsor susulan dievaluasi dari hulu sungai alurnya seperti chain reaction mahjong wins 3 perubahan iklim dinilai perlu evaluasi daya dukung alam mirip risk control mahjong ways harga produk elektronik diprediksi naik polanya seperti rising odds mahjong wins krisis komponen global pengaruhi pasar teknologi dampaknya seperti nerf mode mahjong ways 2 promo belanja nasional disambut antusias ramainya mirip event spin mahjong wins diskon kuliner dan gaya hidup serentak digelar efeknya seperti free spin mahjong wins 2 destinasi wisata tawarkan promo akhir tahun lonjakannya mirip scatter rush mahjong ways rekomendasi perangkat gaming tingkatkan akurasi presisinya seperti perfect hit mahjong wins solusi pelacak barang jadi incaran fungsinya mirip auto track mahjong ways distribusi bantuan sosial tetap berjalan di area bencana ritmenya seperti safe mode mahjong wins penanganan darurat bencana dioptimalkan multi jalur skemanya mirip split path mahjong ways 2 pemulihan sosial ekonomi korban banjir mulai terlihat prosesnya seperti comeback mahjong wins 3 wilayah selatan alami kekurangan cabai dan bawang putih jelang akhir tahun polanya seperti slow build mahjong ways tim regional gagal lanjut meski menang telak alurnya mirip comeback gagal di mahjong wins pertandingan sengit berlangsung live ritmenya seperti turbo spin mahjong ways 2 tim regional tersingkir dramatis endingnya mirip last spin mahjong wins 3 hujan badai picu pohon tumbang timpa kendaraan situasinya seperti random hit mahjong ways bibit siklon baru terpantau ancaman dampaknya mirip chain feature mahjong wins 2 empat orang ditemukan tewas di dalam mobil kronologinya seperti mystery tile mahjong ways fenomena alam terekam kamera getarannya mirip shockwave mahjong wins 3 satwa menggemaskan bermain di salju momennya seperti bonus santai mahjong ways 2 insiden udara ekstrem terjadi saat aksi terjun tegangnya seperti high risk spin mahjong wins rumah sakit rusak parah akibat serangan dampaknya seperti full board collapse mahjong ways puluhan satwa laut terancam punah direhabilitasi prosesnya seperti recovery mode mahjong wins 2 siklon tropis berpotensi menguat polanya mirip escalating reel mahjong ways 3 larangan ambil kayu pasca banjir diterapkan alurnya seperti lock feature mahjong wins wilayah jadi sarang kejahatan siber global jaringannya mirip hidden network mahjong ways aktivitas tektonik meningkat tajam pergerakannya seperti volatile spin mahjong wins 3 kios hangus terbakar usai kerusuhan situasinya mirip board reset mahjong ways 2 teknologi robot gantikan pekerja ritel perubahannya seperti auto spin mahjong wins atlet beregu diuji mental dan teknik tekanannya seperti long spin mahjong ways kecelakaan lalu lintas masuk tahap penyidikan prosesnya mirip step-by-step mahjong wins sistem keamanan digital diperketat efeknya seperti anti loss mode mahjong ways 3 teknologi ai mampu ciptakan visual palsu realistis risikonya seperti fake scatter mahjong wins warga uji kualitas bahan bakar mandiri hasilnya seperti manual spin mahjong ways gempa besar picu peringatan tsunami dampaknya seperti sudden drop mahjong wins 2 aksi penodaan kitab suci berujung penangkapan kasusnya seperti trigger sensitif mahjong ways aturan baru aparat perluas jabatan publik dampaknya seperti multi role feature mahjong wins satuan khusus tagih denda triliunan dari korporasi langkahnya seperti big win mahjong ways 3 pejabat ekonomi protes ai disamakan lembaga lain reaksinya seperti miss hit mahjong wins lembaga riset tawarkan alat mahal ke aparat pajak negosiasinya seperti buy feature mahjong ways janji bangun ulang rumah korban bencana harapannya seperti free spin mahjong wins 2 kapal tanker dibajak di laut lepas aksinya seperti high stake mahjong ways 3 protes wasit picu ketegangan lapangan momennya seperti dead spin mahjong wins laporan rahasia prediksi kekalahan perang besar simulasinya seperti all in mahjong ways konflik regional memanas dengan serangan terbuka eskalasinya seperti rage mode mahjong wins 3 film konser digarap dengan teknologi sinematik visualnya seperti cinematic spin mahjong ways fenomena alam musim dingin sajikan momen langka nuansanya seperti chill mode mahjong wins 2 aksi udara ekstrem hampir berujung fatal tegangnya seperti near miss mahjong ways gempa kuat mengguncang negeri kepulauan polanya mirip wild chain mahjong ways guncangan bumi picu kewaspadaan pesisir alurnya seperti trigger awal mahjong wins kunjungan ke lokasi bencana ungkap kerja lapangan berat mirip slow build mahjong ways 2 penanganan pengungsi diuji medan sulit ritmenya serupa long spin mahjong wins 3 kasus kendaraan menabrak pelajar masuk tahap lanjutan polanya mirip locked reel mahjong ways penyelidikan insiden jalan raya berlanjut alurnya seperti bonus delay mahjong wins 2 nilai mata uang global melemah tajam pergerakannya mirip free fall mahjong wins tekanan pasar internasional meningkat dinamikanya seperti volatile mode mahjong ways 3 belanja hemat akhir tahun jadi tren strateginya mirip spin efisien mahjong ways promo liburan dorong daya beli publik polanya seperti scatter awal mahjong wins diskon wisata akhir tahun ramai dimanfaatkan alurnya mirip bonus round mahjong ways 2 lonjakan transaksi liburan terlihat merata ritmenya serupa turbo spin mahjong wins event olahraga lari diserbu peserta kuotanya seperti limited spin mahjong wins 3 antusias pendaftaran event melonjak cepat polanya mirip fast trigger mahjong ways program isi ulang digital berhadiah menarik perhatian mekanismenya seperti mystery box mahjong wins hadiah premium jadi daya tarik utama alurnya serupa surprise feature mahjong ways promo kuliner akhir pekan ramai pemburu diskon polanya mirip multiplier mahjong wins 2 pastry dan kopi jadi incaran sensasinya seperti combo win mahjong ways tiket hiburan gratis ganda picu antrean alurnya mirip double scatter mahjong wins antusiasme hiburan meningkat tajam ritmenya serupa big win mahjong ways 3 kayu terseret banjir menumpuk di wilayah terdampak polanya mirip tile block mahjong ways upaya pembersihan material bencana dipercepat alurnya seperti clear board mahjong wins aksi relawan bersihkan tempat ibadah pascabanjir ritmenya serupa recovery mode mahjong ways 2 solidaritas warga meningkat di lokasi bencana polanya mirip comeback spin mahjong wins fenomena langit merah saat senja jadi sorotan efeknya mirip visual event mahjong ways 3 curah hujan lokal picu genangan singkat polanya mirip mini flood mahjong wins gangguan jalur udara terjadi sementara alurnya mirip air lock mahjong ways 2 ketersediaan pangan segar bergantung cuaca dinamikanya mirip rng mahjong wins 3 pola belanja warga bergeser ke produk tahan lama dampaknya mirip long game mahjong ways cuaca tak stabil picu penundaan agenda besar situasinya mirip pause mode mahjong wins 2 dinamika kampus nasional menghangat ritmenya menyerupai alur mahjong ways perdebatan soal validasi data publik muncul polanya seperti puzzle mahjong wins arah pembangunan infrastruktur disorot geraknya mirip step spin mahjong ways 2 kemenangan tim daerah tak berbuah lolos situasinya seperti miss hit mahjong wins 3 gelombang kritik budaya digital menguat efeknya seperti chain spin mahjong ways fenomena kekerasan keluarga terbuka alurnya mirip dark mode mahjong wins 2 konten sensitif picu perbincangan dinamikanya seperti high volatility mahjong ways 3 sengketa proyek wisata berlanjut prosesnya mirip slow reel mahjong wins polemik warisan lokal mengemuka jalurnya seperti locked feature mahjong ways 2 tekanan psikologis keluarga korban terungkap dramanya mirip long spin mahjong wins 3 lonjakan minat edit visual ai terlihat polanya seperti scatter mahjong ways dialog strategis wilayah digelar alurnya seperti setup round mahjong wins 2 rekaman teguran aparat viral dampaknya mirip shock spin mahjong ways 3 tim regional menang tipis namun gugur nasibnya seperti dead end mahjong wins ancaman cuaca ekstrem diperhitungkan pergerakannya mirip rolling tile mahjong ways 2 prediksi peruntungan tahunan dibahas polanya seperti forecast spin mahjong wins 3 ekosistem layanan digital dianalisis strukturnya mirip multiplier mahjong ways ajang penghargaan global digelar atmosfernya seperti bonus trigger mahjong wins 2 daftar tontonan horor terbaru dirilis ketegangannya mirip free spin mahjong ways 3 hasil pertandingan usia muda tak cukup alurnya seperti near scatter mahjong wins draf aturan pendidikan bocor isinya mirip hidden rule mahjong ways 2 gelombang promo akhir tahun meledak ritmenya mirip rapid spin mahjong wins 3 sinyal stabilitas keuangan disampaikan strateginya seperti safe lane mahjong ways ancaman pembatasan layanan berbalik arah dramanya mirip reversal mahjong wins 2 skema penyalahgunaan dana terungkap jalurnya mirip trap feature mahjong ways 3 kebakaran permukiman tinggalkan luka dampaknya mirip burn mode mahjong wins luapan material vulkanik terpantau alirannya mirip cascade mahjong ways 2 seruan kerja sama lintas sektor menguat polanya mirip combo mahjong wins 3 insiden pendakian berujung duka kronologinya mirip sudden drop mahjong ways momen nostalgia tayangan lawas viral emosinya mirip memory spin mahjong wins 2 pilihan hidup mandiri jadi sorotan jalurnya mirip solo path mahjong ways 3 agenda lingkungan global dipercepat targetnya mirip maxwin route mahjong wins festival edukasi anak digelar meriah metodenya mirip learning spin mahjong ways 2 tren musik populer tahun ini dirangkum polanya mirip trending tile mahjong wins 3 badai musiman terjang hunian sementara dampaknya mirip chaos mode mahjong ways distribusi bantuan darurat dipercepat prosesnya mirip recovery spin mahjong wins 2 riset medis temukan pola baru datanya mirip unlock feature mahjong ways 3 tim regional sabet medali jalannya mirip clean hit mahjong wins kecelakaan pelajar picu keprihatinan alurnya mirip chain reaction mahjong ways 2 perubahan identitas budaya diperdebatkan jalurnya mirip split path mahjong wins 3 jejak pertanian kuno terungkap prosesnya mirip discovery spin mahjong ways peta klasemen turnamen bergeser cepat geraknya mirip fast reel mahjong wins 2 rencana pajak wisata global disorot skemanya mirip balance mode mahjong ways 3 solidaritas bencana terbangun luas efeknya mirip full scatter mahjong wins laga klub internasional memanas intensitasnya mirip overheat mahjong ways 2 diskon transportasi diluncurkan dampaknya mirip boost spin mahjong wins 3 peringatan siklon baru dirilis polanya mirip alert spin mahjong ways sorotan aksesori kesehatan global viral fenomenanya mirip random trigger mahjong wins 2 respons atas gugatan platform digital muncul strateginya mirip counter play mahjong ways 3 alasan aksi ugal-ugalan terungkap jalurnya mirip risk mode mahjong wins prosesi kelulusan teknologi digelar atmosfernya mirip achievement spin mahjong ways 2 target transaksi nasional naik tajam ambisinya mirip jackpot chase mahjong wins 3 analisis kecepatan kendaraan saat insiden dirilis datanya mirip frame check mahjong ways kekecewaan publik usai gugur turnamen menggema reaksinya mirip tilt mode mahjong wins 2 evaluasi transportasi publik diperluas jalurnya mirip route scan mahjong ways 2 perubahan cuaca laut picu kewaspadaan polanya mirip tide shift mahjong wins 3 gelombang banjir mendadak mengubah pola aktivitas warga ritmenya seperti mahjong ways cuaca tak menentu picu penyesuaian jalur distribusi alurnya mirip mahjong ways 2 harga kebutuhan harian bergerak fluktuatif dinamikanya serupa mahjong wins pemulihan wilayah terdampak dilakukan bertahap skemanya seperti mahjong wins 2 lonjakan permintaan logistik terjadi secara mendadak polanya mirip mahjong wins 3 perubahan arus transportasi picu antrean panjang situasinya seperti mahjong ways aktivitas pasar tradisional kembali bergeliat irama dagangannya mirip mahjong ways 2 tekanan cuaca ekstrem ubah jadwal operasional daerah dampaknya seperti mahjong wins distribusi bantuan mengalami penyesuaian rute mekanismenya mirip mahjong wins 2 pemadaman sementara diantisipasi lewat sistem cadangan polanya seperti mahjong wins 3 harga logam mulia bergerak cepat dalam sehari lonjakannya mirip mahjong ways nilai tukar domestik tampil stabil di tengah tekanan global alurnya seperti mahjong ways 2 aktivitas investasi ritel tunjukkan tren positif polanya mirip mahjong wins arus modal jangka pendek masuk bertahap skemanya seperti mahjong wins 2 pasar keuangan menutup pekan dengan optimisme akhirannya mirip mahjong wins 3 gangguan rantai pasok global mulai terasa lokal efeknya seperti mahjong ways penyesuaian harga energi picu perubahan konsumsi alurnya mirip mahjong ways 2 ketersediaan bahan pokok dijaga ketat di daerah rawan polanya mirip mahjong 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stabilitas mahjong sebelum scatter hitam muncul rahasia pemain baru scatter mahjong ways ternyata lebih mudah dipicu ritme santai rtp tinggi titik awal rentetan kemenangan mahjong ways rtp dan pola tersembunyi ini meningkatkan kemenangan mahjong ways strategi santai mahjong wins membaca pola harian saat rtp sedang aktif terungkap begini cara menguasai rtp kemenangan mahjong ways pgsoft terungkap waktu paling optimal untuk akselerasi max win mahjong wins visual data eksklusif grafik mahjong pgsoft mengarah ke zona payout zona reel terkendali mahjong ways beroperasi pada level volatilitas tinggi tracking data scatter mahjong ways masuk siklus pengganda tinggi stabilitas reel terukur mahjong ways bergerak di zona risiko rendah monitoring statistik langsung indikasi multiplier pada mahjong ways analisis sinkronisasi reel mahjong ways 2 memasuki tahap aktivasi bertingkat peta volatilitas wild mahjong pgsoft berada di area beruntun peralihan fase mahjong ways dari spin manual ke momentum pengganda kepadatan reel distribusi simbol wild mahjong di area tengah pemindaian tumble layer mahjong ways memicu kenaikan winrate tinggi statistik mahjong wins menandai peralihan ke zona kombinasi lanjutan sinyal awal jp mahjong ways menunjukkan aktivasi kombinasi bertingkat observasi pola pemain zona intensitas mahjong ways teridentifikasi malam hari analisis korelasi data peningkatan wild mahjong seiring frekuensi multi hit evaluasi grid statistik mahjong wins menunjukkan konsistensi kombinasi tinjauan data aktivasi jalur multiplier menengah di mahjong ways uji respons mahjong ways bereaksi lebih cepat di periode malam struktur jalur jp mahjong ways membuka peluang rantai kemenangan riset reel interaktif mahjong wins tampilkan respons lebih ganas rekaman tumble aktif intensitas win mahjong ways terus menanjak trik menang mahjong ways 2 pgsoft dengan rtp harian update dari kalah jadi raja strategi baru anaelisa di mahjong wins interaksi baris tengah respons kombinasi dalam struktur berlapis mahjong ways analisis tumble mahjong pgsoft perlihatkan konsistensi wild beruntun sinyal mikro kombinasi mahjong ways memicu multi tumble berturut insight statistik malam aktivitas wild mahjong pgsoft alami lonjakan statistik kombinasi mahjong wins menanjak di fase ganas malam hari pulse effect terpantau multiplier mahjong ways pgsoft meningkat korelasi ritme wild multiplier mahjong ways terlihat meningkat drastis monitoring reel jangka pendek stabilitas ritme return mahjong ways mahjong ways mendorong kemenangan bertingkat lewat tumble berlapis laporan data grid mahjong ways menunjukkan kenaikan simbol tinggi indikator awal keuntungan mahjong ways menunjukkan fase wild beruntun main lebih cerdas menang lebih besar pola mahjong terungkap flashwave system terbaca jelas multiplier mahjong mulai mengalir riset sesi aktif mahjong wins memperlihatkan lonjakan multiplier x10 pemantauan langsung mahjong ways aktifkan pola kombinasi padat rahasia babak awal mahjong ways pola main untuk menang bonus kesadaran lingkungan meningkat warga alur tunjukkan aksi nyata observasi dinamis tumble wild mahjong ways mengalami kenaikan mendadak visual menawan dan pola jp cara mudah menang di mahjong wins step formation tahapan wild yang terbentuk berlapis di mahjong ways investigasi engine game konvergensi reel mahjong wins picu scatter berlapis analisis temporal mahjong ways dalam identifikasi fase tumble panjang dinamika subuh perubahan ritme tumble pada sistem mahjong ways bukan kebetulan jam hoki mahjong wins ini terbukti picu scatter kajian pola lanjutan mahjong ways memadatkan kombinasi kunci analisis lapangan lonjakan scatter mahjong ways terjadi saat pola tertentu pattern driftline perpindahan alur simbol mahjong ways sepanjang spin histori jejak tumble frekuensi win mahjong ways terpantau meningkat pembaruan sistem lonjakan aktivitas simbol scatter mahjong terjadi secara bertahap arah payout aktual konsistensi mahjong ways terlihat lebih terjaga pressure core mahjong ways ternyata alasan utama kenaikan multiplier data grafik terbaca ritme agresif mahjong ways alami lonjakan signifikan transisi permainan mahjong ways berpindah ke zona high gain struktur win terbaca mahjong menampilkan alur kemenangan lebih terorganisir main santai tapi mengarah jp ritme tenang mahjong terbukti efektif audit simbol premium kombinasi mahjong ways muncul lebih agresif evaluasi sistem pgsoft mahjong ways berjalan dalam mode efisiensi kajian pola momentum pada mahjong wins yang hasilkan multi tinggi analisis dinamika reel mahjong ways menunjukkan aktivasi mode progresif dinamika data mahjong ways 2 menunjukkan aktivasi bonus progresif evaluasi simbolik mahjong ways mengarah pada skema distribusi efisien indikator data stabilitas wild mahjong dalam rentang produktif kajian distribusi simbol mahjong wins mengarah pada optimasi maksimal laporan statistik multiplier mahjong ways mulai terbentuk bertahap observasi reel tengah: kepadatan wild mahjong ways terlihat konsisten pembacaan data langsung mengindikasikan pergerakan multiplier mahjong ways pemodelan statistik intensitas simbol wild mahjong terpantau konsisten pendekatan algoritmik lanjutan dalam membaca urutan trigger mahjong ways perubahan minor efek besar: pola mahjong ways hari ini pola waktu subuh: dinamika tumble mahjong ways mengalami peningkatan rilis data terbaru: distribusi scatter mahjong pg soft meningkat sinyal sistem mahjong ways memperlihatkan return rate lebih tinggi snapshot permainan: stabilitas mekanisme reel mahjong ways dalam satu sesi studi reel mahjong ways mengalami penyesuaian kombinasi tinggi tracking malam hari: kombinasi panjang mahjong ways tercatat lebih sering trend analysis sinkronisasi simbol wild dan ritme spin mahjong ways visual data momentum positif mahjong ways terkonfirmasi grafik terbaru waktu terbaca: mahjong ways mengalami akselerasi tumble di fase dini buka rahasia karyawan pabrik di bekasi langsung jp mahjong ways 3 hujan deras jadi rezeki ojek pangkalan menang besar mahjong wins 3 mahjong ways bikin tajir cuma modal kecil jp besar bisa kamu raih menang besar di mahjong ways cara pemain menangkap momen withdraw menangkap kilau emas rahasia pola dan momentum spin mahjong ways 2 misi cuan mahjong wins 3 gunakan pola ini jp bisa didapat semua spin mahjong ways yang bikin heboh player baru cuma butuh 5 putaran terungkap cara cepat menang di mahjong ways dengan pola terbaru trik jitu scatter hitam dan wild mahjong ways kini mudah dicapai trik stabil mahjong wins tap timing tepat cuan datang tanpa henti optimalisasi rute jadi solusi utama skemanya seperti mahjong wins 2 koordinasi lapangan diperkuat menyeluruh alurnya mirip mahjong wins 3 aktivitas ekonomi lokal mulai bangkit perlahan ritmenya seperti mahjong ways usaha kecil menyesuaikan pola operasional alurnya mirip mahjong ways 2 strategi bertahan jangka pendek diterapkan polanya mirip mahjong wins inovasi produk jadi andalan pemulihan skemanya seperti mahjong wins 2 optimisme pelaku usaha kembali terlihat alurnya mirip mahjong wins 3 pola konsumsi rumah tangga alami perubahan ritmenya seperti mahjong ways pengeluaran prioritas jadi fokus utama alurnya mirip mahjong ways 2 permintaan barang sekunder menurun sementara polanya mirip mahjong wins strategi hemat mulai diterapkan luas skemanya seperti mahjong wins 2 keseimbangan keuangan jadi perhatian publik alurnya mirip mahjong wins 3 lingkungan perkotaan alami penyesuaian aktivitas ritmenya seperti mahjong ways ruang publik digunakan lebih terbatas alurnya mirip mahjong ways 2 pengelolaan sampah jadi sorotan musiman polanya mirip mahjong wins inisiatif kebersihan ditingkatkan lokal skemanya seperti mahjong wins 2 kesadaran lingkungan tumbuh bertahap alurnya mirip mahjong wins 3 fenomena sosial baru muncul di masyarakat ritmenya seperti mahjong ways interaksi warga bergeser ke ruang digital alurnya mirip mahjong ways 2 pola komunikasi publik jadi lebih cepat polanya mirip mahjong wins distribusi informasi dilakukan multikanal skemanya seperti mahjong wins 2 respons kolektif terbentuk secara alami alurnya mirip mahjong wins 3 krisis pasokan pangan regional mulai terasa dinamikanya mirip slow reel mahjong ways cuaca ekstrem datang bertubi-tubi polanya seperti volatile spin mahjong wins tekanan harga bahan pokok meningkat ritmenya serupa build up mahjong ways 2 gangguan distribusi picu kelangkaan situasinya mirip lock board mahjong wins wilayah rawan banjir alami lonjakan debit air efeknya seperti cascade mahjong wins 3 aktivitas alam tak stabil terpantau geraknya mirip random scatter mahjong ways pusat permukiman terendam mendadak alurnya seperti sudden drop mahjong wins 2 peringatan cuaca dini dikeluarkan polanya serupa signal spin mahjong ways 3 gelombang tinggi ganggu jalur laut tekanannya mirip high risk mode mahjong wins musim tanam terhambat anomali iklim prosesnya seperti delay spin mahjong ways lonjakan permintaan pasar picu kepanikan situasinya mirip overheat mahjong wins 2 gangguan listrik massal terjadi bertahap skemanya seperti chain effect mahjong ways 3 tekanan ekonomi harian meningkat perlahan polanya mirip long play mahjong wins nilai tukar berfluktuasi tajam pergerakannya seperti turbo reel mahjong ways 2 akses logistik terputus sementara dampaknya mirip board freeze mahjong wins cuaca panas ekstrem picu kekeringan lokal efeknya seperti dry spin mahjong ways hujan lebat datang di luar prediksi alurnya mirip surprise feature mahjong wins 3 arus transportasi tersendat akibat alam ritmenya seperti slow mode mahjong ways pusat aktivitas warga lumpuh mendadak situasinya seperti full stop mahjong wins perubahan musim terjadi lebih cepat polanya mirip fast forward mahjong ways 2 tekanan sosial meningkat akibat krisis dinamikanya seperti risk stack mahjong wins lonjakan kebutuhan mendesak terjadi serentak efeknya seperti multi hit mahjong ways 3 gangguan sistem umum picu antrean panjang skemanya mirip queue spin mahjong wins wilayah pesisir alami abrasi parah 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ritmenya seperti uptrend spin mahjong ways 3 kepadatan lalu lintas meningkat drastis situasinya mirip traffic jam reel mahjong wins 2 perubahan tekanan udara picu badai lokal polanya seperti storm feature mahjong ways wilayah pegunungan alami longsor susulan alurnya mirip chain collapse mahjong wins 3 gangguan komunikasi terjadi mendadak efeknya seperti signal lost mahjong ways 2 krisis energi lokal picu pembatasan jam operasi skemanya mirip power save mahjong wins cuaca buruk hambat aktivitas penerbangan ritmenya seperti delayed spin mahjong ways 3 debit sungai naik di atas normal alurnya mirip overflow mode mahjong wins 2 tekanan hidup harian meningkat tajam dinamikanya seperti high volatility mahjong ways fenomena kabut tebal tutupi permukiman visualnya mirip smoke screen mahjong wins 3 pola konsumsi warga berubah akibat krisis efeknya seperti adaptive mode mahjong ways 2 gangguan pasar picu kepanikan massal situasinya seperti panic spin mahjong wins wilayah pertanian alami penurunan produksi polanya mirip weak hit mahjong ways 3 cuaca ekstrem ganggu jalur darat alurnya mirip blocked path mahjong wins 2 aktivitas laut tak normal terpantau geraknya mirip wave pattern mahjong ways lonjakan biaya hidup jadi sorotan ritmenya seperti cost up spin mahjong wins 3 suhu malam hari turun drastis efeknya seperti cold trigger mahjong ways 2 tekanan lingkungan picu migrasi warga dinamikanya mirip shift mode mahjong wins cuaca tak stabil hambat aktivitas nelayan polanya seperti risky spin mahjong ways 3 gangguan rantai pasok picu efek domino alurnya mirip cascade loss mahjong wins 2 perubahan alam terjadi tanpa peringatan situasinya seperti sudden feature mahjong ways krisis berkepanjangan uji ketahanan warga ritmenya seperti survival spin mahjong wins 3 getaran bumi mengubah aktivitas warga polanya seperti opening reel mahjong ways guncangan alam membuat pesisir siaga alurnya menyerupai early trigger mahjong wins fenomena tektonik picu kepanikan singkat ritmenya seperti quick spin mahjong ways 2 aktivitas seismik naik tajam polanya mirip volatile phase mahjong wins 3 cuaca ekstrem datang mendadak skemanya serupa random scatter mahjong ways pola awan tak biasa muncul di langit efeknya seperti mystery tile mahjong wins arus air meluap melewati batas alurnya menyerupai overflow mode mahjong ways 3 debit sungai naik cepat dalam hitungan jam ritmenya seperti turbo chain mahjong wins material alam terbawa arus deras polanya mirip unlocked tile mahjong ways tumpukan puing hambat akses wilayah alurnya seperti board block mahjong wins 2 evakuasi darurat dilakukan bertahap ritmenya seperti safe spin mahjong ways warga dipindahkan ke zona aman skemanya serupa protection mode mahjong wins distribusi bantuan dipercepat melalui jalur alternatif polanya mirip route bonus mahjong ways 2 logistik masuk ke area sulit ritmenya seperti precision spin mahjong wins aktivitas relawan meningkat drastis alurnya menyerupai combo support mahjong ways solidaritas publik mengalir tanpa henti efeknya seperti multiplier mahjong wins 3 kondisi infrastruktur dievaluasi ulang polanya mirip status check mahjong ways pemeriksaan jalur transportasi dilakukan intensif ritmenya seperti line scan mahjong wins gangguan lalu lintas terjadi di banyak titik alurnya seperti jammed reel mahjong ways 2 arus kendaraan dialihkan sementara skemanya serupa redirect spin mahjong wins insiden jalan raya picu penyelidikan lanjutan polanya mirip hidden phase mahjong ways fakta baru muncul dari lokasi kejadian alurnya seperti reveal spin mahjong wins 2 kasus kecelakaan memasuki tahap baru ritmenya seperti next level mahjong ways 3 analisis teknis difokuskan pada faktor lingkungan polanya mirip terrain mode mahjong wins tekanan pasar global menguat tiba-tiba alurnya seperti sudden drop mahjong ways nilai tukar bergerak fluktuatif tajam ritmenya seperti high risk spin mahjong wins 3 mata uang dunia alami pelemahan serentak polanya mirip chain loss mahjong ways 2 investor pilih sikap tunggu dan lihat alurnya seperti hold mode mahjong wins aktivitas perdagangan melambat sesaat ritmenya seperti cooldown spin mahjong ways sektor keuangan fokus jaga stabilitas polanya mirip balance guard mahjong wins 2 strategi likuiditas disesuaikan kondisi pasar alurnya seperti adaptive spin mahjong ways 3 tren belanja publik bergeser jelang liburan polanya mirip pattern shift mahjong ways konsumen lebih selektif pilih promo ritmenya seperti smart bet mahjong wins lonjakan kunjungan wisata terlihat merata alurnya seperti bonus trail mahjong ways 2 destinasi ramai sejak awal musim efeknya seperti early win mahjong wins 3 diskon akhir tahun picu antrean panjang polanya mirip limited event mahjong ways minat liburan naik meski tantangan cuaca ritmenya seperti risk play mahjong wins event olahraga massal diserbu peserta alurnya seperti full room mahjong ways pendaftaran ditutup lebih cepat dari jadwal efeknya seperti instant trigger mahjong wins 2 antusiasme publik pecah di hari pertama polanya mirip big hit mahjong ways 3 aktivitas lari rekreasi jadi tren baru ritmenya seperti casual spin mahjong wins pengiriman barang diprediksi melonjak alurnya seperti peak mode mahjong ways sektor logistik bersiap hadapi lonjakan ritmenya seperti load boost mahjong wins 2 jalur distribusi alternatif mulai dimaksimalkan polanya mirip side path mahjong ways 3 manajemen stok jadi fokus utama alurnya seperti inventory control mahjong wins kegiatan sosial digelar di area terdampak ritmenya seperti community bonus mahjong ways bantuan kemanusiaan datang bertahap efeknya seperti drip reward mahjong wins 2 upaya pemulihan lingkungan terus berjalan polanya mirip recovery spin mahjong ways 3 penataan ulang wilayah dilakukan perlahan ritmenya seperti slow build mahjong wins kerusakan hutan terungkap dari citra lapangan alurnya seperti exposed tile mahjong ways aktivitas ilegal menyisakan dampak panjang polanya mirip long penalty mahjong wins 2 pengawasan wilayah diperketat ritmenya seperti guard mode mahjong ways 3 pencegahan dini jadi fokus ke depan alurnya seperti pre-spin analysis mahjong wins ketegangan sosial muncul akibat isu lokal polanya mirip chaos phase mahjong ways seruan menjaga kondusivitas digemakan ritmenya seperti calm reset mahjong wins 2 literasi digital didorong untuk redam konflik alurnya seperti filter system mahjong ways 3 arus informasi palsu jadi tantangan polanya mirip fake scatter mahjong wins pendidikan akar rumput dapat sorotan positif ritmenya seperti progress unlock mahjong ways program sosial dinilai tepat sasaran alurnya seperti steady win mahjong wins 2 inovasi berbasis riset terus berkembang polanya mirip knowledge spin mahjong ways 3 publikasi ilmiah dorong solusi baru ritmenya seperti research bonus mahjong wins festival kota angkat ekonomi lokal alurnya seperti event multiplier mahjong ways aktivitas usaha mikro meningkat efeknya seperti small win stack mahjong wins 2 sektor pariwisata bangkit bertahap polanya mirip revival mode mahjong ways 3 pelaku usaha sesuaikan strategi musiman ritmenya seperti adaptive pattern mahjong wins persaingan regional makin ketat alurnya seperti versus board mahjong ways hasil pertandingan picu evaluasi menyeluruh ritmenya seperti replay mode mahjong wins 2 klasemen berubah di detik akhir polanya mirip last spin mahjong ways 3 target medali bergeser dari prediksi awal alurnya seperti rank shuffle mahjong wins jadwal padat uji ketahanan tim ritmenya seperti endurance spin mahjong ways laga penentuan hadirkan tekanan tinggi polanya mirip high stake mahjong wins 2 strategi bermain jadi kunci hasil akhir alurnya seperti smart play mahjong ways 3 ketertinggalan tak menyurutkan perlawanan ritmenya seperti comeback mode mahjong wins sektor hiburan tarik minat keluarga polanya mirip fun spin mahjong ways pertunjukan akhir tahun padati lokasi publik ritmenya seperti crowd bonus mahjong wins 2 tiket terjual habis lebih cepat alurnya seperti flash win mahjong ways 3 minat masyarakat terhadap hiburan naik polanya mirip mood booster mahjong wins pola konsumsi digital terus berkembang ritmenya seperti online spin mahjong ways teknologi jadi bagian gaya hidup harian alurnya seperti auto feature mahjong wins 2 pengenalan aset digital picu rasa ingin tahu polanya mirip new mode mahjong ways 3 perbandingan nilai kripto jadi bahasan publik ritmenya seperti versus spin mahjong wins fluktuasi pasar digital perlu disikapi bijak alurnya seperti risk filter mahjong ways edukasi finansial jadi kunci adaptasi ritmenya seperti skill upgrade mahjong wins 2 evaluasi tahunan ungkap tantangan baru polanya mirip stage clear mahjong ways 3 rencana jangka panjang mulai disusun alurnya seperti roadmap spin mahjong wins fokus keberlanjutan jadi arah utama ritmenya seperti green mode mahjong ways kolaborasi lintas sektor diperkuat alurnya seperti team combo mahjong wins 2 optimisme publik terjaga di tengah dinamika polanya mirip stable win mahjong ways 3 curah hujan tinggi picu genangan di kawasan permukiman polanya seperti putaran tak stabil mahjong ways distribusi pangan terganggu akibat cuaca buruk dampaknya menyerupai alur mahjong wins kepadatan lalu lintas meningkat sejak pagi hari situasinya mirip putaran padat mahjong ways 2 harga kebutuhan pokok bergerak fluktuatif dalam sepekan dinamikanya serupa mahjong wins 3 angin kencang sebabkan gangguan aktivitas warga kondisinya mirip mode risiko mahjong ways gelombang tinggi hambat aktivitas laut polanya menyerupai mekanisme mahjong wins 2 suhu udara naik di atas rata-rata musiman fenomenanya mirip putaran panas mahjong ways kualitas udara menurun di area padat penduduk situasinya seperti tahap sulit mahjong wins akses jalan alternatif ditutup sementara demi keselamatan keputusannya mirip kunci putaran mahjong ways 2 distribusi air bersih alami gangguan teknis dampaknya serupa pola terhenti mahjong wins 3 aktivitas perdagangan lokal melambat akibat cuaca alurnya mirip putaran panjang mahjong ways hujan lebat beruntun picu kewaspadaan warga situasinya seperti fase awal mahjong wins fenomena kabut tebal mengurangi jarak pandang efeknya mirip layar tertutup mahjong ways 2 harga hasil pertanian naik bertahap polanya serupa kenaikan bertahap mahjong wins arus sungai meluap setelah hujan panjang dinamikanya mirip putaran tidak seimbang mahjong ways 3 gangguan transportasi terjadi di jam sibuk kondisinya seperti putaran macet mahjong wins perubahan pola angin picu ketidakstabilan cuaca alurnya mirip pergeseran pola mahjong ways distribusi logistik terhambat faktor alam dampaknya serupa fase tertunda mahjong wins 2 aktivitas nelayan dibatasi demi keamanan situasinya mirip mode aman mahjong ways 3 lonjakan permintaan bahan pokok terjadi mendadak polanya mirip putaran cepat mahjong wins genangan air surut perlahan usai hujan reda prosesnya mirip tahap pemulihan mahjong ways kepadatan pasar tradisional meningkat jelang akhir pekan situasinya serupa putaran penuh mahjong wins 2 harga bahan bangunan bergerak naik tipis dinamikanya mirip perubahan nilai mahjong ways cuaca tidak menentu picu penyesuaian aktivitas harian alurnya mirip mode adaptif mahjong wins 3 akses wisata alam dibatasi sementara keputusannya seperti penguncian fitur mahjong ways perubahan musim terasa lebih cepat tahun ini polanya serupa siklus mahjong wins gangguan listrik terjadi singkat di beberapa area situasinya mirip putaran terhenti mahjong ways 2 kondisi jalan licin tingkatkan risiko perjalanan efeknya mirip mode sulit mahjong wins 3 harga ikan segar berfluktuasi akibat cuaca polanya seperti gelombang mahjong ways distribusi gas rumah tangga alami penyesuaian dampaknya mirip tahap penyeimbangan mahjong wins 2 fenomena awan tebal muncul sejak pagi kondisinya serupa latar gelap mahjong ways 3 permintaan transportasi umum meningkat tajam alurnya mirip putaran padat mahjong wins aktivitas sekolah dialihkan sementara karena cuaca keputusannya mirip mode aman mahjong ways kualitas air sungai menurun usai hujan deras situasinya serupa penurunan level mahjong wins 3 kondisi laut bergelombang picu pembatasan pelayaran risikonya mirip putaran tinggi mahjong ways 2 distribusi barang antarwilayah alami keterlambatan dampaknya mirip fase tertunda mahjong wins suhu malam hari turun signifikan fenomenanya mirip perubahan mendadak mahjong ways 3 aktivitas pertanian disesuaikan dengan pola cuaca baru alurnya serupa strategi mahjong wins perubahan tekanan udara terasa di wilayah tertentu dinamikanya mirip pergeseran putaran mahjong ways 2 genangan sementara muncul di titik rawan kondisinya serupa putaran pendek mahjong wins 3 lonjakan harga sayuran terjadi bertahap polanya mirip kenaikan bertingkat mahjong ways akses distribusi terhambat di jalur pegunungan situasinya mirip putaran terkunci mahjong wins fenomena petir intens terjadi di wilayah terbuka efeknya mirip mode intens mahjong ways 2 perubahan pola konsumsi warga terlihat jelas dinamikanya mirip penyesuaian mahjong wins 3 aktivitas wisata menurun akibat cuaca buruk dampaknya serupa putaran sepi mahjong ways kepadatan terminal transportasi meningkat drastis situasinya mirip putaran penuh mahjong wins 2 harga kebutuhan harian naik tipis dalam sepekan polanya mirip increment mahjong ways 3 gangguan jaringan komunikasi terjadi sementara kondisinya serupa putaran terhenti mahjong wins distribusi pupuk tertunda akibat curah hujan dampaknya mirip tahap tunda mahjong ways fenomena laut keruh muncul di pesisir efeknya mirip latar kabur mahjong wins 2 aktivitas perdagangan online meningkat saat cuaca buruk polanya serupa putaran alternatif mahjong ways 3 akses jalan desa rusak akibat erosi kondisinya mirip tile retak mahjong wins harga komoditas laut bergerak tidak stabil dinamikanya mirip gelombang mahjong ways 2 kondisi lingkungan memburuk di area padat situasinya serupa tahap sulit mahjong wins 3 aktivitas pengiriman dialihkan ke jalur aman keputusannya mirip mode aman mahjong ways perubahan pola tanam terjadi lebih awal alurnya serupa strategi baru mahjong wins 2 curah hujan lokal picu genangan singkat kondisinya mirip putaran pendek mahjong ways 3 distribusi barang pokok diprioritaskan ke wilayah rawan polanya mirip fokus putaran mahjong wins fenomena suhu ekstrem terjadi bertahap dinamikanya mirip mode tekanan mahjong ways 2 kepadatan jalur alternatif picu kemacetan baru situasinya serupa putaran tersumbat mahjong wins 3 aktivitas masyarakat beralih ke ruang tertutup saat hujan polanya mirip mode bertahan mahjong ways harga produk olahan naik akibat distribusi terhambat dampaknya serupa putaran mahal mahjong wins 2 kondisi cuaca ekstrem picu penundaan agenda publik alurnya mirip mode jeda mahjong ways 3 akses pelabuhan dibatasi sementara demi keselamatan keputusannya mirip kunci sistem mahjong wins fenomena angin kencang terjadi singkat efeknya mirip putaran cepat mahjong ways 2 distribusi bahan pokok dialihkan ke jalur darat strateginya mirip perubahan jalur mahjong wins 3 kualitas udara membaik usai hujan panjang prosesnya mirip pemulihan mahjong ways aktivitas produksi skala kecil terhambat cuaca dampaknya serupa putaran lambat mahjong wins 2 harga energi rumah tangga bergerak stabil polanya mirip putaran seimbang mahjong ways 3 fenomena embun tebal muncul di pagi hari efeknya mirip layar halus mahjong wins kondisi jalan retak akibat perubahan suhu situasinya serupa tile rusak mahjong ways 2 aktivitas distribusi dipadatkan di jam aman strateginya mirip timing mahjong wins 3 perubahan musim picu penyesuaian pola hidup alurnya serupa adaptasi mahjong ways harga bahan pokok lokal bertahan stabil polanya mirip putaran netral mahjong wins 2 gangguan sementara terjadi pada jalur utama kondisinya mirip mode gangguan mahjong ways 3 aktivitas sosial dialihkan ke ruang dalam polanya serupa mode bertahan mahjong wins distribusi air bersih kembali normal bertahap prosesnya mirip recovery mahjong ways 2 fenomena cuaca lokal picu variasi dampak wilayah dinamikanya mirip rng mahjong wins 3 kepadatan lalu lintas berangsur normal alurnya serupa reset mahjong ways aktivitas harian warga berjalan adaptif polanya mirip strategi stabil mahjong wins 2 sorotan aktivitas kampus meningkat dinamikanya menyerupai pola mahjong ways perdebatan validitas data publik menguat alurnya seperti rangkaian mahjong wins evaluasi proyek infrastruktur diperluas prosesnya mirip tahapan mahjong ways 2 catatan observasi stabilitas mekanisme mahjong ways dalam sesi malam dinamika simbol dan pergeseran posisi mempengaruhi stabilitas spin mahjong ways pembacaan grafik terbaru menunjukkan tren mahjong ke fase high payout snapshot statistik mahjong ways memperlihatkan distribusi scatter lebih rapat transisi halus terpantau saat mahjong ways masuk fase bayar audit independen frekuensi simbol mahjong bernilai tinggi terlihat melonjak pemantauan reel real-time menjaga konsistensi alur jp mahjong ways monitoring reel aktif mahjong ways menjaga alur return tetap seimbang data harian menunjukkan kepadatan scatter mahjong ways mengalami lonjakan analisis waktu bermain: sinkronisasi spin dan pergantian simbol mahjong ways laju kemenangan mahjong ways tetap stabil meski rotasi simbol berubah konsolidasi mode mahjong ways mereduksi variansi saat wild beruntun observasi reel aktif mahjong ways menemukan momentum jalur efisien pattern insight mahjong ways menampilkan efek wild chain lebih rapi optimasi bet mahjong ways merespons positif penyesuaian nilai spin laporan monitoring harian menunjukkan konsistensi payout mahjong ways scatter pattern review: freespin mahjong ways masuk fase multi x10 pemantauan freespin mahjong ways tampil konsisten di beberapa putaran analisis sistem mahjong ways bergerak konsisten menuju mode gain insight sesi permainan: alur pembayaran stabil terjadi di mahjong prime session detection: scatter mahjong aktif di jam trafik tinggi spin cycle analysis mahjong ways menjaga keseimbangan return tinggi stabilitas kombinasi mahjong wins menjaga ritme big hit premium audit pergerakan multiplier mahjong ways mulai membuka jalur kemenangan data pattern mahjong ways menata jalur bonus scatter lebih terstruktur bonus entry mapping: arah scatter mahjong ways mulai terbaca mahjong ways mengirim sinyal awal aktivasi pre-bonus phase combination chain insight: korelasi keterhubungan wild mahjong ways performa sistem pg soft mahjong menunjukkan arah tumble berantai micro pattern shift mahjong ways memicu win berantai grid mahjong ways mengungkap zona aktif dengan potensi wild tinggi ritme permainan mahjong ways masuki fase tenang sebelum ledakan insight reel mahjong ways: kemunculan wild berantai di fase malam indikasi scatter premium muncul dari area spesifik grid mahjong ways sinkronisasi simbol wild dan scatter mahjong ways di fase transisi kajian meta mahjong ways: perubahan alur saat reel mengalami lock struktur kombinasi mahjong ways menunjukkan adaptasi dinamis analisis jalur kombinasi mahjong ways mengarah ke tren multiplier transisi mode malam mahjong ways dari stabil ke ekspansif interaksi simbol mahjong ways membentuk sinyal kemenangan tidak langsung riset tumble mahjong ways: pola jatuh vertikal menjadi titik kejutan laporan analitis mahjong wins menjelang malam menstabilkan kemenangan monitoring frame simbol mahjong wins membentuk tumble kombinasi panjang pemantauan sesi prime mahjong wins mulai mengaktifkan wild beruntun deteksi sinyal pola mahjong ways bergerak ke zona hit padat observasi struktur kombinasi wild mahjong ways terlihat lebih terarah mode spin mahjong ways menunjukkan wild semakin sering berantai evaluasi ritme permainan mahjong ways meningkatkan konsistensi hit kajian dinamika reel mahjong wins menampilkan burst lebih ganas evaluasi posisi wild mahjong ways pada putaran dengan rtp tinggi grafik simbol wild mahjong ways membentuk jalur kemenangan alternatif dinamika simbol mahjong ways menandai pola konsolidasi hasil keterkaitan posisi reel mahjong ways dengan intensitas kombinasi beruntun mekanisme tumble wild mahjong ways menunjukkan lonjakan signifikan analisis perubahan alur scatter mahjong ways saat nilai taruhan berbeda perubahan ritme tumble mahjong ways memengaruhi distribusi wild berantai pola reel mahjong ways berubah seiring transisi fase ganas posisi wild tengah teridentifikasi sebagai pemicu scatter mahjong bernilai tinggi segmentasi area grid scatter mahjong ways dan dampaknya pada hasil observasi struktur reel mahjong ways saat intensitas wild meningkat discover signal pergerakan reel mahjong ways mengarah ke fase keuntungan hasil monitoring sistem mahjong ways terindikasi masuki mode produktif mahjong wins mengunci rangkaian simbol wild dalam durasi panjang deteksi fase ganas mahjong ways masuki siklus kombinasi padat pemantauan sesi malam aktivitas scatter pg soft mahjong alami eskalasi 