





































Outlining the keyword co-occurrence trends in Shuanghuanglian injection research: A bibliometric study using CiteSpace III


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    ISSN : 2693 6356 

2024 | Vol 7 Issue 2 

 

 
 

 
 

Abstract— Efforts are being made to investigate the mechanical characteristics of Cenosphere 

and e- galass fibres reinforced Al7075 in this current project. Cenosphere, a low-density, low-cost 

reinforcing material, is a byproduct of coal combustion in thermal power plants and is readily 

accessible. As a result, Al 7075 metal matrix with cenosphere as reinforcement can easily 

overcome the cost barrier and may serve as the best supplement with varied physical and 

mechanical qualities for servicing a broad variety of applications providing wide usage in today's 

world. Variations in the E-glass and cenosphere were used to create the specimens. The 

specimens used in the tensile test were constructed in accordance with ASTM specifications. 

Improved features including improved specific strength, specific modulus, damping capacity, and 

superior wear resistance may be achieved by using metal matrix composites (MMCs) instead of 

ordinary alloys. The great strength-to-weight ratio of aluminium composite MMCs makes them 

the most popular. 

 
Key words: Al7075 alloy composite, E-glass, MMCs, and short E-glass fibres 
 

 

 
 
 

Outlining the keyword co-occurrence trends in Shuanghuanglian 

injection research: A bibliometric study using CiteSpace III 

Zhang a, 1, Guang Rong b, 1, Qin Meng a, *, Mang Yu c, Xie d, Jian a 

a School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, China 
b Department of Herbology, School of Biomedicine, Beijing City University, Beijing, 100094, China 

c Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 94305, USA 
d Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, Chin

 

 

 

 

 

have cast doubt on SHLI's safety. Future research 

would benefit from a streamlined synopsis of the 

SHLI studies that have already been published 

While the quantity of published papers in a given 

field of study doubles every eight years,7 it is 

becoming more and more challenging to conduc

new studies, particularly those that are inherently 

unquantifiable and unrepeatable, like qualitative 

reviews.  

A bibliometric approach has been proposed as a 

means of explaining this "quality crisis" and 

providing an alternative in situations when there is 

not enough information to conduct a review study. 

Researchers in the SHLI field have documented 

such bibliometric studies that use the prevalence 

of keywords in published articles as measures of 

the scope of the study.8,9 Although this is a new 

field of study, there are a few caveats to keep in 

mind, such as the limited number of indicators and 

the lack of consistency between them.  

neglected to do study on the field's outline, which 

includes concepts like innovation, progress, 

bottlenecks, and hotspots. To overcome these 

shortcomings, one solution is to implement 

scientific mapping based on the notion of a 

complex network. This technique can visualise 



aspects of a pool of articles that are not visible 

using more traditional methods.103rd day  

Scientific mapping is able to depict the 

development and structural links of subjects in a 

certain field by examining knowledge domains.14 

Insights into new information and underexplored 

areas of study may be revealed by this mapping, 

which reveals the interconnections, overlaps, 

interactions, and evolution of knowledge units. 

One of the applications made to enable scientific 

mapping is CiteSpace, which has seen widespread 

usage across various domains.15  

One famous contemporary formula, 

Shuanghuanglian (SHL), is made from three 

medicinal herbs: scutellaria (Scutellaria 

baicalensis Georgi), honeysuckle flower (Lonicera 

japonica Thunb.), and forsythia fruit (Forsythia 

suspensa (Thunb.) Vahl).16 Oral liquid, 

injectable, pill, and tablet are some of the dosage 

forms of SHL that have been produced so far. For 

the treatment of bacterial and viral respiratory 

illnesses, including tonsillitis, pneumonia, and 

upper respiratory tract infections, SHLI is often 

administered as a solution or powder.17 

According to traditional Chinese medicine, SHLI 

dissipates harmful heat and toxicants and 

dissipates wind heat. In 2001 and 2009, there were 

reports of serious adverse drug reactions (ADRs) 

to SHLI, including allergic reactions and 

dyspnea.Research in both the lab and the clinic 

has shown that SHLI is effective in reducing viral 

replication and lung damage (18, 19).20,21 The 

use of SHLI to treat COVID-19 infections is also 

very promising. Because vaccinations and 

particular medications take months, if not years, to 

produce, one of the main ways to deal with a 

newly emerged virus is to look into current 

medications and other substances that might work 

as effective remedies.22 The Shanghai Institute of 

Materia Medica, Chinese Academy of Sciences 

(Shanghai, China) and the Wuhan Institute of 

Virology, CAS (Wuhan, China) collaborated on a 

research that discovered that SHL oral liquid, an 

oral formulation that uses the same chemicals as 

SHLI, might suppress SARS-CoV-2.23,24. We 

anticipate that this discovery will refocus attention 

on SHL formulations, particularly SHLI, on a 

global scale. Research on SHLI has been well 

documented, and it would be helpful for 

researchers to have a scientific map that shows the 

development and structural linkages of these 

studies. Therefore, the purpose of this study is to 

examine the development and emerging trends in 

SHLI hot topics by creating a CiteSpace term co-

occurrence map of SHLI studies.  

 

Material and methods 

 
Data source and collection 

 
On the 30th February 2020, articles were retrieved from 

the China National Knowledge Infrastructure (CNKI), Medline 

(PubMed entry), and Embase (ovid entry) with no limitations 

on the pub- lished date. Our search terms were 

“Shuanghuanglian injection”, “Shuanghuanglian fenzhen” and 

the Boolean combination of the two. The detailed search 

strategies can be found in Supplementary Data. 

The retrieved articles were imported into Endnote to 

remove duplicates. Two authors (QZ and GR) then separately 

read the titles and abstracts to exclude those articles with 

topics irrelevant to SHLI. It should be noted that a 

bibliometric study is insensitive to the precision, but sensitive 

to the extensiveness, of included arti- cles. This tolerance is the 

result of the frequency-based algorithm of keyword 

connecting and clustering that ignores minor noise. Therefore, 

in a bibliometric study we should avoid using extremely rigid 

inclusion constraints as is required by other types of studies, 

such as a meta-analysis. 

Because the establishment of a method for manual 

association between keywords in different source 

languages has yet to be vali- dated, as well as the fact as 

indicated in a pilot search that studies of SHLI are 

overwhelmingly more frequently reported in China-based 

journals, our mapping was majorly focused on the Chinese 

data- base. Articles retrieved from English-language 

databases were also treated in CiteSpace to outline a 

separate scientific map of the area 

only if the number of citations was ≥30. If the number of 

citations 
was <30 we quit the mapping, but still used these articles as 
back- 

ground information for our qualitative discussion. 

The retrieved articles were saved as indexing records 

and transformed into an executable format using the 

“Data/ Import/ Export” function of CiteSpace. 

 
Parameter settings 

 
A pilot study showed that the earliest SHLI article was 

published in 1992; therefore, for the present study we set 

the timespan from 1992 to 2020. Other parameters 

included time slice duration, node type, slice content, line 

strength, and pruning method. More in- formation 

regarding these parameters and their functions can be 

found in a previous report.15 As is recommended by the 

developer of CiteSpace15 and in accordance with previous 

studies,25e29 we have used the following settings: a 

duration of 3 years was set for every time slice (resulting 

in 8 consecutive slices); node type was set as “Keyword”; 

treated articles were set as the top 100 keywords in each 

slice (ranked according to how often they were used); line 

strength was set to cosine; and the pruning method 

was set as 

MST + pruning the sliced network. 
 

Interpretation of network evaluation indicators 

 
To judge whether the network was successfully 



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established and to explore the potential scientific data, 

several qualitative and quantitative evaluation indicators 

reported by CiteSpace were determined and interpreted. 

These indicators were (a) frequency (abbreviated as F), 

(b) sigma,30 (c) burstiness (abbreviated as B),30 

(d) modularity (Q),31 (e) silhouette (abbreviated as S),30 

and (f) qualitative results of representative labels 

generated by two types of algorithms (tf*idf32 and log-

likelihood ratio (LLR)33). 

For interpretation, frequency is a series of values that 

quantify the importance of each node by how often it is 

presented in the included nodes, and it can be used to 

tease out weighted focuses of the field. In the present 

paper, we looked at keywords with F > 10. Sigma 

identifies the innovativeness of the topic, if there is any, 

then quantifies it. Typically, higher sigma values 

indicate more innovation. In the present paper, we set a 

value for sigma >10 as 

reflecting the potential novelty of a field. 

Burstiness, another important node indicator, ranks 

the ampli- tude of usage surges for keywords with 

significant changes in usage frequency (we would not 

expect CiteSpace to report anything if there were no 
significant changes identified). According to previous 

studies,34‒36 a keyword with B > 3 can be considered to 

have a 
meaningful value for burstiness and we used this cutoff for 
the 

present analysis. 

The values for Q and S ranged from 0 to 1 and e1 to 1, 

respec- tively. These indicators are used to assess how 

well the field is split into clusters (each cluster represents 

a particular research focus). CiteSpace only calculates an 

overall value for S, whereas for Q both an overall value 

and individual values for each cluster are reported. A Q 

value close to 1 indicates better-defined clusters and an S 

value close to 1 indicates confidence in how the nodes are 

clustered. According to a previous report,12 we 

considered that the results 
 

with both Q > 0.3 and an overall S value S > 0.6 indicated 

successful clusters, and any individual cluster with S > 0.8 

as having a meaningful research field focus worth further 

discussion. 

The results of tf*idf, LLR, and mutual information (MI) 

provide qualitative information about the research focus of 

each cluster. The algorithms are developed based on 

different text-mining assump- tions; therefore, their results 

can be complementary to each other. 

 

 
Network layouts and representation 

 
The resulting keyword co-occurrence map shows various 

in- formation including the executing version of CiteSpace, 

computing speed, slice profile, the node, and other network 

evaluation values mentioned above. 

In the middle of the map is the CiteSpace-visualized 

merged network based on several networks corresponding 

to the snapshots of consecutive slices we have set. The 

merged network character- izes the development of the 

field over time, showing the most important footprints of 

the related research activities. The network is merged in a 

semi-automatic manner, i.e. the duplicate nodes and lines 

among slices are automatically merged through the built-in 

algorithm of CiteSpace, and different nodes with the same 

conno- tation are manually merged by the “Alias List” 

function as described in a previous report.15 Each dot 

represents a keyword in the network (we call this dot a 

node in the present study). CiteSpace can generate 

networks of other types of nodes, such as term, author, 

reference, and keyword. As we have set the node type as 

“Keyword”, the nodes in this study solely represent 

keywords. The lines that connect nodes are co-occurrence 

links (these correspond to the scientific topic in question). 

The colors of these nodes and lines are designed to show 

when a connection was made for the first time, and we can 

distinguish them by referring to the upper- most caption. 
In the merged network, the size of a node is proportional 
to how 

many times a keyword is used. The keyword usage history is 

visualized in terms of „„tree rings‟‟ of different colors and 

thick- nesses. The thickness of a ring is proportional to how 

many times the keyword is used in a particular period that is 

represented by the ring color. Nodes with usage bursts are 

visualized by rings colored in red. 

Individual nodes can be aggregated into clusters based 

on their interconnectivity to represent strong relationships 

in the field in question. This aggregation will generate 

another picture, where nodes and links are replaced by 

clusters with labels displayed in red prefixed by the cluster 

number (#). The labels are identified auto- matically by the 

LLR algorithm. The results of the two other text- mining 

algorithms can be explored through several more mouse 

clicks.15 

 

Results 

 
A total of 270 and 234 articles in English were 

retrieved from Medline and Embase, respectively. After 

duplicate removal, 299 articles remained. Through 

manual examination, 280 articles were further excluded 

because of their irrelevance to SHLI. The remain- ing 19 

articles (<30) were not sufficient to build a separate scientific 

map, and the full texts were retrieved to provide 

background in- formation for the qualitative discussion. 

A total of 811 articles were retrieved. The number of 

resulting nodes and lines before merging are shown in 

Table 1. A knowledge map showing how the field of SHLI 

progressed over time was successfully generated. 

 
General features of the retrieved articles 

 
The types of studies in the 811 retrieved articles 

included clinical studies (n ¼ 614), animal experiments (n 

¼ 45), in vitro experiments (n ¼ 16), processing and 

detection techniques (n ¼ 126), and literature reviews (n 

¼ 10) (Fig. 1A). The number of articles on a yearly basis 
peaked in the year 2000, followed by a sharp decrease 

until the number essentially plateaued during the first ten 

years of the 21st century with modest fluctuations. 

However, the last decade has seen a steady decline in the 

number of articles (Fig. 1B). The journals publishing the 8 

highest numbers of SHLI articles are shown in Fig. 1C, 

with the Heilongjiang Medicine Journal ranking 

highest (n ¼ 33). The research institutes of the first 



authors who 
published SHLI articles are overwhelmingly located in Heilongjiang Province, China (Fig. 1D). 

 
General features of the keyword co-occurrence network 

 
A pair of different nodes with the same notation “双黄连粉针” and “双黄连粉针剂” was identified and manually merged as one 

node. Finally, 551 nodes with 746 lines were included for gener- ating the network shown in Fig. 2. The largest node “Shuan- 

ghuanglian powder injection” is located in the middle right of the picture, which represents the highest frequency of usage. The red 

peripheral ring of this node indicates significant burstiness merit- ing further exploration. The node‟s inner rings with a variety of 

different colors indicate the consistent focus on this topic over 24 years, but we can also determine that this keyword was most 

frequently used from 1995 to 1998 because the thickest ring is a light blue color. Other nodes with a relatively large size can also be 

readily identified. To explore the importance of the nodes in terms of frequency and burstiness, the values of nodes with F > 20 are 

shown in Table 2 and values of nodes with B > 3.0 are shown in Table 3. No values for sigma >10 were found, indicating a lack of 

novelty in the topics in the field of SHLI. 

General features of the network with clustered keywords 

 
The network with clustered nodes is illustrated in Fig. 3. The overall Q and S values were 0.73 and 0.68, respectively, indicating a 

uccessful clustering. Six individual clusters were found to have a 

 

 
 

 
General features of the included articles 

 
2010e201 100/255 224/224 Among the 811 included articles, the largest number of articles 

2013e2015 100/199 245/245 was on clinical research, followed by processing and detection 

2016e2018 

2019e2020 

100/151 

100/112 

224/224 

119/119 

 

 

 

techniques. Laboratory experiments only comprised 7.5% of 

the total. 

 

    

 

 

 

 

 

  
    

    

 

 

 

 

 

 

 



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Fig. 1. General bibliometric features of the retrieved articles. (A) The types of published studies; (B) The yearly trends in the numbers of published articles from 

1992 to 2020; (C) Top 8 journals that published the largest number of SHLI-focused articles; (D) Top 5 institutes where the largest number of the first authors 

of the published SHLI-focused articles are bas



It can be seen that before the year 2000, most SHLI studies 

focused on clinical and production techniques rather than 

labora- tory experiments. In contrast to modern medicine, 

where novel drugs are generally developed by the synthesis of 

artificial com- pounds with no previous evidence of their safety, 

traditional Chi- nese medicine (TCM) has had thousands of 

years of clinical application, which may minimize concerns over 

severe adverse effects. This makes a thorough exploration into 

the mechanism of action of Chinese medicines (CM) less 

appealing to TCM researchers than a clinical demonstration of 

their putative efficacy, and even less appealing to 

pharmaceutical enterprises compared with opti- mizing 

techniques for production. 
Interestingly, as SHLI was proven to be not as safe as 
previously 

thought, from two reports from the National Center for ADR 

Moni- toring, China in 2004 and 2009,32,33 interest was again 

directed into the area of clinical studies, because post-market 

reevaluation of the medicine began to appear necessary. 

This further added to the 

number of clinical studies. Modest peaks in the number of 

published SHLI studies were seen soon after these reports 

were published, indicating that these trends may be the 

result of concerns over se- vere adverse drug events with 

SHLI. This effect also corresponds with the high 

burstiness of the keyword “Clinical observation” (B ¼ 

7.35, 2006e2019). 
In the province where most manufacturers have 
production 

licenses for SHLI and also where the severe adverse events 

were reported, it is reasonable that local institutes will 

have a strong interest in SHLI studies. This local interest 

is demonstrated by the fact that, of the top five institutes 

where the largest number of the first authors of the 

published SHLI-focused articles is based, four are in 

Heilongjiang Province. This also corresponds to the high 

burstiness of the keyword “The 2nd CM pharmaceutical 

factory of 

Harbin” (B ¼ 9.83, 2008e2019) and the high frequency of 

the 

keywords “adverse events” and “The 2nd CM pharmaceutical fac- tory of Harbin”

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



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Fig. 2. CiteSpace-generated keyword co-occurrence network. 

 

Table 2 

Nodes with frequency higher than 20. 
 

Frequency Node*

 Cluster 
 

 

235 Shuanghuanglian powder injection
 #0 

112 Shuanghuanglian injection
 #3 

104 Adverse effect
 #4 

94 Shuanghuanglian for injection
 #4 

85 The 2nd CM pharmaceutical factory of Harbin
 #14 

79 Shuanghuanglian
 #2 

42 Powder injection
 #12 

39 Prepared CM remedy
 #1 

31 Cholorogenic acid
 #6 

29 Intravenous infusion
 #1 

 
 

Note: *Node names in this column were originally displayed in Chinese 

Characters, herein they are presented in English for the ease of readers. 

CM: Chinese medicine. 

Exploring the topic categories for SHLI studies 

 
The identified meaningful clusters may point to 

particular areas of research focus because each cluster is 

considered to be a group of tightly coupled keywords 

based on topic interconnectivity. A thorough exploration 

of the clusters under the computer-aided guidance of 

multiple cluster labels can lead to information on the 

studies of SHLI. Note that, as has been pointed out by the 

developer of CiteSpace, cluster labels chosen from the 

computer-aided algo- rithms tend to be more specific 

terms than those chosen by human experts. Interpretation 

from a multi-label perspective has the po- tential to 

provide additional insights complementary to bias-prone 

expert reviews, and provides a support for interpreting 

the nature of specialties.37 
 
 

 
Table 3 

Nodes with burstiness values higher than 3.0. 
 

Node* Used year Burstiness Duration Cluster 

Shuanghuanglian injection 1992 11.39 2008-2019 #3 

The 2nd CM pharmaceutical factory of Harbin 1992 9.83 1993-1997 #14 

Adverse effect 1992 7.35 2008-2011 #4 

Shuanghuanglian powder injection 1992 5.22 1998-2000 #0 

Baicalin 1992 4.79 2006-2019 #6 

Clinical observation 1992 4.57 1993-1998 #8 

Shuanghuanglian for injection (under lyophilization) 1992 3.59 2010-2019 #11 

Affecting factors 1992 3.42 2010-2019 #9 

Note: *Node names in this column were originally displayed in Chinese 
Characters, herein they are presented in English for the ease of readers. 
CM: Chinese medicine. 

 
 

 
 

Fig. 3. CiteSpace-generated network with clustered keywords. 

Note: Cluster names in this picture were originally displayed in Chinese 

Characters, herein they are presented in both Pinyin and English for the ease 

of readers. HPLC: high performance liquid chromatography. 

 

 
Table 4 

The six individual clusters that demonstrated meaningful field focus. 
 

Cluster number Number of nodes contained Sihouette tf*idf-generated label* LLR-generated label* 

0 56 0.99 Bioactivity mapping Shuanghuanglian sterile injection powder 

1 45 0.91 Equal pupils Allergic shock 

2 44 0.87 Drug preparation department Shuanghuanglian for injection 

3 43 0.85 Difficulty in respiration Keratitis 

4 37 0.88 Peristalsis Shuanghuanglian for injection administration 

5 33 0.94 Danshen powder injection Powder injection 

Note: *Node names in this column were originally displayed in Chinese 



Characters, herein they are presented in English for the ease of readers. LLR: 
log-likelihood ratio. 

 

Cluster #0 

The largest cluster, #0, starts in 2006 and contains 56 key 

words (Fig. 2 and Table 4). The tf*idf-generated label 

“bioactivity finger- print” represents a widely-adopted 

methodology for research into SHLI, and it is very interesting 

to find that the label “lyophilized SHLI powder for injection” 

generated by the LLR algorithm corre- sponds to the form of 

the drug used in this methodology. Thus, the interest in this 

area is to be expected. 

Bioactivity fingerprint analysis is a quality control model 
that builds upon spectroscopic and chromatographic 
technologies, which is different from traditional quality 
control models in the sense that fingerprinting looks at the 
“complete information” or comprehensiveness of the 
chromatogram, and displays integrated quality 
information.38 Fingerprint analysis was introduced to the 
study of SHLI and many other herbal medicines because this 
analysis can be better adapted to CM than conventional 
methods as it analyzes the overall effective components of 
an individual herb or a combination of herbs. For 
example, Wen used an immune 

fingerprint to screen for the allergenic components of SHLI 

by enzyme-linked immunosorbent assay (ELISA) combined 

with high performance liquid chromatography 

(HPLC)/mass spectrometry (MS), and 22 components in 

SHLI were found that could be adsorbed by specific anti-IgE 

antibodies and the sensitization of SHLI could be changed 

by different administration methods.39 The use of a 

bioactivity fingerprint is regarded as a great improvement 

from the conventional modern drug-centered single 

component analysis for herbal medicine, the efficacy of 

which partly depends on how the components work 

together. 

In addition to the stimulus provided by its sound 

compatibility with CM, bioactivity fingerprint analysis has 

support from China‟s governmental funding and 

international regulations. In 2002, Na- tional Medical 

Products Administration launched an initiative in 

collaboration with 48 academic institutions to perform 

fingerprint identification on 74 types of CM injection (CMI), 

including SHLI (a lag effect is expected, which causes this 

analysis to appear as a research focus in 2006). The bureau 

also issued the Guideline for Standardized Procedure of 

Chinese Medicine Fingerprint Test, and designed two pieces 

of software for Fingerprint-based CM Simi- larity 

Detection.38 The guideline provides clear requirements and 

procedures for laboratory and instrumentation facilities, 

sample and reference collection and preparation, proper 

conditions for testing, operational processes, and the 

methods for result verifi- cation and checking. The software 

is able to compute and compare an entire body of CM 

chromatographic peaks, so that component fingerprint 

similarity can be quantified. These research efforts have 

contributed to a rigorously-designed, technically-sound 

platform for the practice of CM fingerprinting, and a good 

number of studies have been performed. Outside of China, 

fingerprinting is listed in the US Food and Drug 

Administration‟s Guidance for Industry Botanical Drug 

Products (drafted in 2000), the World Health Or- 

ganization‟s Guidelines for the Assessment of Herbal 

Medicine 
(1996), the British Pharmacopoeia (1986), the Indian 
Pharmaco- 

poeia (1998), and the US Pharmacopeia (1999e2001).38 The 

ob- jectives of these guidelines are to address the 

uncertainty and variation in the chemical components of 

medicinal plants and to enhance the authentication and 

control of the quality of herbal extracts. Thus, at least to 

some extent, interest has been aroused in SHLI 

fingerprinting in the hope that SHLI might enjoy an interna- 

tionally wider acceptance. 

 
Cluster #1 

Cluster #1 comprises 45 key words. The labels together 

indicate that this cluster focuses on the ADRs of SHLI (Fig. 2 

and Table 4). Over the past decades, the clinical applications 

of CMIs have experienced robust growth with ever-

improving quality control and processing techniques. 

However, this growth has been accompanied by an 

increasing number of reports of ADRs, which has aroused 

considerable safety concerns.40 From the LLR- generated 

labels of this cluster, we were able to identify that the most 

frequently reported ADR was “anaphylactic shock”, which 

was first reported in 1993.41 The tf*idf-generated label 

“equal pupils” is an important physical examination for 

anaphylactic shock, indi- cating the emphasis on the 

surveillance of this reaction during the clinical application 

of SHLI. Unfortunately, the concerns from an academic 

perspective were justified by the occurrence of several 

severe ADRs arousing public interest between 2006 and 

2009. Because of the increasing number of extremely 

serious ADRs, the Chinese government temporarily 

suspended sales of four types of CMIs, including SHLI. A 

previous literature review found a decrease 
in the literature reporting an ADR from CMIs, including 
SHLI, after 

sales were suspended.40 To further advance the 

development of CMIs, a comprehensive clinical reappraisal 

of CMIs is urgently needed to guide the clinical application 

of CMIs and reduce the 

 
incidence of ADRs.42 

 
Cluster #2 

Cluster #2 is labeled as “Shuanghuanglian injection” by 

LLR and as “hospital drug preparation room” by tf*idf, 

indicating concerns regarding the preparation of SHLI 

(Fig. 2, Table 4). Indeed, the standardized preparation of 

the drug requires uniform cleanroom management and a 

low possibility of drug mixture contamina- tion.43 As CMIs 

mostly contain complex ingredients, the prepara- tion 

processes are varied. The compatibility of different 

solvents, or if the mixtures are left standing for a long 

time after preparation, may cause the precipitation of 

certain ingredients through chemi- cal or physical changes 

and thus increase the amount of particulate matter.44 This 

is particularly the case for the preparation of CMIs, such 

as SHLI, which intrinsically have components of mixed 

prop- erties. A systematic review highlighted the fact that 

particulate matter present in SHLI will increase in amount 

after being prepared as an infusion, and using normal 

saline as the solvent can minimize the amount of 

particulate matter.45 The study also found significant 

variations in the SHLI components among different 

producers and among different batches of the same 

producer. Therefore, to reduce the incidences of ADRs, it is 

crucial that the solvent selection for SHLI should be 

strictly in accordance with the manufacturer‟s in- 
structions, and the time of the drug injection after 
preparation 

should be carefully controlled.46 

 
Cluster #3 

It is interesting that the labels generated by the two 

algorithms for this cluster have considerably different 

connotations (Fig. 2). The tf*idf gives “difficulty in 

breathing”, which relates to an ADR, whereas LLR gives 



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“keratitis”, one of the indications of SHLI (Table 4). By 

closer exploration of the articles, we found that this 

cluster focuses on clinical trials of SHLI that tested both its 

efficacy and safety. Most CMIs, such as SHLI, are 

produced, sold, and mar- keted based on putative, 

empirical effectiveness without first demonstrating 

safety and efficacy through clinical trials, as is 

required for pharmaceutical drugs.47‒49 With growing 

interest in 
the therapeutic effectiveness of SHLI, and safety-based 

concerns, increasing efforts have been directed toward 

acquiring scientific proof and conducting evidence-based 

evaluations regarding the efficacy and safety of SHLI. 

 
Clusters #4 and #5 

These two clusters, unlike the broader perspectives of 

the four clusters described above, provide a further 

breakdown of the research topics of SHLI (Fig. 2). Cluster 

#4 identifies interest in a very promising new indication, 

intestinal peristalsis, as labeled by td*idf (Table 4). Intra-

abdominal adhesions following abdominal surgery 

represent a major unsolved problem, with a high reported 

incidence of 90%e100% in patients who undergo 

abdominal sur- gery,50,51 and no appreciably effective 

medicine has yet been developed.52 Some studies have 

reported the effectiveness of peristalsis in preventing the 

symptoms of intra-abdominal adhe- sions by overcoming 

the obstruction.53 According to the theory of TCM, SHLI 

may exert effectiveness by eliciting the peristaltic action of 

the intestines. This possibility has attracted a number of 

exper- imental and clinical studies on the topic with 

satisfactory results being obtained.54 Such studies are 

especially meaningful, because they explore the use of 

CMIs for patients who have conditions where there are 

no known effective treatments or when standard 
therapies have not been tolerated or have failed to lead 
to im- 

provements.54 As can be identified from both the labels 

(Table 4), studies from cluster#5 investigated the 

effectiveness of SHLI when used in tandem with 

compound Danshen in dealing with a variety of heat-

toxin-based diseases or symptoms, including pain after 

radiotherapy for nasopharyngeal carcinoma,55 chronic pelvic 

in- flammatory disease,56 and acute viral myocarditis.57 

Interestingly, the underlying rationale for combining these 

seemingly unrelated types of medicine derives from the TCM 

theory that removing blood stasis enhances the clearance of 

heat-toxin (heat-toxin in the sense of TCM is arguably similar 

to inflammation in modern medicine). 

It is very interesting that, among the six categories of topics 

identified by CiteSpace, four (#0e#3) focus on providing 

evidence for, or enhancing the quality of, SHLI from a “purely” 

science-based perspective, whereas two (#4e#5) focus on 

seemingly modern studies following an ancient TCM rationale. 

This is a vivid reflection of the status quo of the entire CM 

research area, where there exists a dispute over whether or 

not ancient TCM theory should be adhered to in scientific 

studies. In recent decades, the adherence to TCM theory has 

been declining. In the present analysis, the number of SHLI 

studies conducted from a CM perspective alone was not 

sufficient to form a cluster, and the researchers in CM must 

conduct studies under the framework of scientific 

methodologies. However, even the aggregation of positive 

results from studies of CM cannot contribute to any validation 

of ancient TCM theory, because evi- dence supporting the 

efficacy of a medicine does not extrapolate back to the 

authenticity of any historical putative theories. Re- searchers 

still need to focus on validation of the theory itself. 

 
Exploring the importance of keywords 

 
The importance of an individual keyword to the entire 

network can be determined by the frequency and burstiness. 

Keywords with high importance can be considered to 

represent hotspots in the field. 

 
Frequency 

"Shuanghuanglian injection" (n = 112) is the 

second most common term, with "Shuanghuan-

glian powder injection" being the most used (F = 

235). Given the apparent similarity in meaning 

between these phrases, we dug deeper into the 

CiteSpace Pennant Diagram Function for specific 

node observations. We observed that 

"Shuanghuanglian powder injection" is commonly 

used in articles discussing the chemical 

components and pharmacological effects of SHLI, 

whereas "Shuanghuanglian injection" is more 

commonly associated with safety, clinical 

practice, and head-to-head trials. Since 

"Shuanghuanglian injection" can convey a more 

general meaning that encompasses all the 

derivative products, the usage of these distinct 

titles is reasonable. Our position is that SHLI's 

medical names should be standardised. 

The term "Adverse events" ranks third in terms of 

frequency of use. As mentioned in the section on 

Cluster #1, the safety concerns about SHLI are 

evident in the keyword use. This should come as 

no surprise.  

 

Research medication comes from the 2nd CM 

pharma-ceutical plant of Harbin, which ranks as 

the fourth most popular term. Using a drug 

manufacturer as a keyword is frequent in CMI 

research, but it often makes little sense for the 

study of chemical medications, so this is rather 

intriguing. This is likely due to the fact that 

various manufacturers employ vastly different 

chemical components while making CMIs. We 

think this is an issue that needs further 

investigation because, after years of work on 

fingerprint component identification, SHLI 

components still haven't been standardised.  



Among the most common search terms, 

"chlorogenic acid" ranks ninth. This molecule is 

an important part of SHLI, which is responsible 

for its medicinal benefits and some of its negative 

effects, such allergies.59 A number of plants 

include cholorogenic acid or other 

pharmacologically active components, and an 

overabundance of these actions in particular herbs 

might lead to unwanted side effects.45 This issue, 

known as "off-target" consequences, is also 

present in the process of developing chemical 

medications.  

Similarly unhelpful ideas for field research are 

suggested by other frequently used keywords like 

"Shuanghuanglian" (ranked 6th), "Powder 

injection" (7th), and "Prepared CM remedy" (8th). 

We should anticipate their use since, on occasion, 

writers may choose only one or two keywords to 

characterise the area of research.  

 

The bursting  

In contrast to frequency, which shows a consistent 

interest area for certain terms over time, burstiness 

examines statistically significant fluctuations in 

keyword use over brief intervals. The high 

prevalence of the field's defining keywords 

growing in tandem with the total number of 

articles in the field may explain, like frequency, 

some of the burstiness noticed. Shuanghuanglian 

injection, Shuan-ghuanglian powder injection, and 

Shuanghuanglian for injection (under 

lyophilizing) were therefore omitted from the 

subsequent discussion.  

The emphasis on studying the effectiveness of 

SHLI through clinical trials, beginning in 2006 

and continuing to the present, is emphasised by 

the keywords "The 2nd CM pharmaceutical 

factory of Harbin" (B ¼ 9.83, 2008e2019; the 

history of its usage as a keyword has been covered 

in the section on Frequency) and "Clinical obser-

vation" (B ¼ 7.35, 2006e2019). While there are 

valid concerns about using evidence-based 

medicine to study CM, this emphasis suggests that 

evidence-based medicine's status as the clinical 

practice gold standard might keep impacting SHLI 

studies and the field of CM as a whole. The SHLI 

family of SHL formulations may suppress SARS-

CoV-2.23,24 according to promising results from 

a recent investigation. So, in the next months—or 

maybe even years—the explosiveness of this term 

will continue to soar.  

Several major adverse drug reaction (ADR) 

instances that garnered public attention between 

2008 and 2011 coincide to the surge of the term 

"Adverse effect" (7.35). While a prior study on 

terrorist incidents did reveal that news coverage 

affected the emphasis of academic research, it 

would not be surprising to see a same pattern in 

the healthcare sector.  

The fingerprint analysis and other chemical-level 

SHLI research are related to the term "Baicalin" 

(B ¼ 4.79, 2006e2019), which is one of the main 

therapeutic chemical components of SHLI. 

Similar to the popularity of evidence-based 

studies at the general level, this keyword's usage 

in SHLI research indicates that researchers are 

increasingly bringing new ideas and methods to 

the table.  

Since the term "Affecting factor" (3.42, 

2010e2019) does not really provide a clear 

definition, we dug deeper into the papers that used 

it. We discovered that this term is often used to 

describe the many sources of SHLI's negative 

effects. The compounds in SHLI that cause the 

ADRs have not been identified after years of 

research. A number of studies in recent years have 

started to look at potential multi-factoral causes of 

SHLI ADRs, including differences in production 

methods, storage conditions, and individual 

vulnerability.  

We observed a rising trend in research that 

investigate SHLI utilising current approaches 

from science-based viewpoints, as shown by the 

frequency and burstiness analyses. The safety of 

SHLI is another area of intense interest, with 

researchers beginning to rule out single-factor to 

multi-factor explanations.  

 

Conclusion 
 

Bibliometric analysis helped identify the main 

subject categories of SHLI studies and the 

historical trajectory of research hotspots. As the 

benefits and safety of SHLI were more widely 

recognised, the hotspots changed in response. 

Bioactivity fingerprint, adverse drug reaction 

(ADR) mechanism and cause identification, 

appropriate preparation, clinical evidence 

collection, and effectiveness in illnesses with no 

effective therapy and combination use are the five 

main areas of focus in SHLI research. In order to 

identify the specific areas of SHLI research that 

need more investigation, academics should zero in 

on these five broad subject areas. The present 



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    ISSN : 2693 6356 

2024 | Vol 7 Issue 2 

 

 
 

investigation suggests that the current trend 

towards studying SHLI using cutting-edge 

approaches grounded on scientific principles will 

likely persist. Future research may also 

concentrate on the novel understanding of ADRs 

as having several causes. 
 

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