Visualization analysis of traditional Chinese medicine treatment for primary immune thrombocytopenia based on CiteSpace

Yuan-Ming Du, Bo Liu, Ji-Zhe Song, Jia-Bin Sun,*, Ying Tang,*

1 Affiliated Hospital of Weifang Medical Univesity, Weifang, China；

2 Department of Physiology of Weifang Medical Univesity, Weifang, China.

Abstract Objective: To analyze the hot spot and frontier of traditional Chinese medicine treatment for primary immune thrombocytopenia with CiteSpace softwar for visualized analysis.Methods: The relevant literature about treatment for ITP through traditional Chinese medicine was retrieved from CNKI. The CiteSpace software was used to create visualization map for authors,institutions and keywords.Results: Through visualization analysis,121 authors and 36 institutions were included in the map.The main research hot spot is the clinical effect of traditional Chinese medicine and integrated traditional Chinese and Western medicine in the treatment for ITP.Conclusion: Ratio of research about traditional Chinese medicine treatment on ITP was relatively few. In addition, the cooperation and communication were also insufficient between teams and institutions. The research hot spot mostly focuses on clinical treatment, while theoretical research was very few. There is no deep investigation on treatment mechanism.

Keyword: Traditional Chinese medicine, Primary immune thrombocytopenia, CiteSpace,Visualization analysis

Background

Primary immune thrombocytopenia is also called as idiopathic thrombocytopenic purpura (ITP), it is an immune-mediated thrombocytopenia syndrome. ITP is a common hemorrhagic disease, with main manifestation been hemorrhage, peripheral plate-reduction and megakaryocytes normal or mature hindrance[1]. The pathogenesis is excessive destruction of platelet mediated by Humoral and Cellular immune and insufficient production of platelet caused by abnormal quantity and quality of megakaryocyte [2]. Clinical manifestations include spontaneous skin petechia, ecchymosis,hemorrhage of mucous membrane and viscus,especially hemorrhage of nasal cavity, oral cavity, limbs and gums are much more common.Severe cases may be life-threatening due to intracranial hemorrhage [3]. This sickness is similar to the cases in traditional Chinese medicine like "mass formed by blood stasis""subcutaneous plaque" "ecchymosis" and so on categories. Blood overflowing skin was caused by Bleeding due to blood-heat, Yin-deficiency and Fire-excess, Qi failing to control blood and obstruction of channels by stagnant blood, which is caused by exogenous and internal injuries.Thus the skin appears with blue-purple spots or patchy ecchymosis [4]. Western medicine treats this disease mainly by glucocorticoid, gamma globulin, platelet stimulating agents, anti-CD20 monoclonal antibody splenectomy and platelet transfusion. But there are many shortcomings,such as high side effects, expensive and longterm efficacy is difficult to maintain. Chinese medicine treatment for this disease is by syndrome differentiation and treatment, that is fundamentally eliminating the cause of disease.Compared with Western medicine, traditional Chinese medicine has rarely poisonous effect,good long-term effect and receives more and more attention. In recent years, there have been more and more studies on traditional Chinese medicine treatment for ITP.

CiteSpace is an information visualization software, which is developed by Professor Chen Chaomei, Professor of Computer and Information Science, Drexel University, USA[5]. It can measure domain-specific literature and explore critical paths, knowledge break point and development trends of the scientific field [6]. CiteSpace has become a influential software in the field of information analysis.Literature on traditional Chinese medicine treatment for ITP were retrieved from the CNKI database. And then, the visualization analysis was made on authors, institutions and keywords by CiteSpace. It can sum up study context,hot spots and frontier, in order to provide information reference for the research in this field.

Data and method

Data sources

Database: CNKI； Cross-database selection:journal； Professional retrieval； Retrieval type:(SU = 'Chinese medicine' or SU = 'herbal medicine' or S = 'Chinese and Western medicine'or SU = 'traditional Chinese medicine' or SU ='Chinese herbal medicine' or SU = 'traditional medicine' or SU = 'alternative medicine') and(((SU = 'primary' or SU = 'chronic' or SU= 'immune') and SU = 'thrombocytopenic purpura') and SU = 'thrombocytopenia')；Retrieval time: unlimited； 500 literatures were retrieved, 6 unrelated literatures were excluded after screening and 494 eligible literatures were obtained； Time span: January 1960-July 2018.

Method

Literatures are exported in Refwork format and named download_***, and the CiteSpace 5.3.R3 software was used to created knowledge map of authors, institutions and keywords.

Results and analysis

Analysis of time distribution of the number for published paper

Over time the number of published literature can reflect the development of a certain field. This study made statistics on the included literatures in chronological publication order (Fig. 1). In 1960, the first paper about Chinese medicine treatment for ITP was Zheng Huibo's "My View on Clinical Classification and Treatment for Thrombocytopenia in Traditional Chinese Medicine", which published in Jiangsu Med J.1960-1992, it was the initial stage of relevant research. Few papers were published in this stage, the highest was 1985, with only 6 papers.From 1992 to 2010, the number of published papers in this field was on the rise, and entered a stable period. The average number of papers has reached 11.77. 2010-2015, the number of published papers in this field have entered a rapid growth stage. In 2015, the number of published papers reached 37 and entered the peak of dispatch. 2016-2018, the number of publications in this field showed a slowly decreasing trend, but still exceeded 30 per year.As of July 2018, 12 papers have been published,the annual number of publications is expected to exceed 30.

Figure 1 Time distribution of related literature of Chinese medicine treatment for ITP

Author visualization map

Setting up time in CiteSpace from 1960 to 2018. Cutting point every 5 years. Node point selects author. TopN selects 50. Pruning selects Pathfinder, Pruning the merged network.Through visualization analysis on author of traditional Chinese medicine treatment for ITP, we can understand the number of papers published by main researchers and the cooperation among the author. In the map created by CiteSpace, each node represents an author, the size of the node represents the volume of the author's publishing, and the lines between nodes represent the cooperation between authors. 121 authors were included in the map, forming 169 lines (Fig. 2). 6 authors published more than five articles (Tab. 1),forming 5 major research teams.

Table 1 Main author of Chinese medicine treatment for ITP (Number of published papers ≥ 5)

Institution visualization map

Setting up time in CiteSpace from 1960 to 2018. Cutting point every 5 years. Node point selects institution. TopN selects 50. Pruning selects Pathfinder, Pruning the merged network.Scientific research insititions are the main positions of scientific research. Through visualization analysis on institution, we can understand the distribution of main research strength and the direction of main institution in certain fields. In the visualization map of institutions, each node represents a institution,the size of nodes is positively correlated with the number of papers published by institution, and the lines between nodes represents the cooperative relationship among institutions.Firstly, the name of institution was standardized.The hospitals were no longer divided into departments. The different names (former names)of the same institution were regulated as current names. Thirty six institutions were included in the map, forming 13 lines (Fig. 3). The map showed that there were fewer institutions and fewer connection between institutions in this field. Nine institutions published more than 5 papers (Tab. 2). Among them, the largest number of papers were published by Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, which published 13 papers independently.

Table 2 Main author of Chinese medicine treatment for ITP (Number of published papers ≥ 5)

Figure 3 Institution visualization map of traditional Chinese medicine treatment for ITP

Keyword visualization map

Setting up time in CiteSpace from 1960 to 2018. Cutting point every 5 years. Node point selects keyword. TopN selects 50. Pruning selects Pathfinder, Pruning the merged network.Keyword can reflect the main content of scientific literature. Through visualization analysis on keyword, we can understand the main research contents, directions, development trends, hotspot and frontier of a certain field.First of all, the keywords with same meaning but different expressions are merged. The high frequency keywords are shown in Tab. 3. The keyword map is shown in Fig. 4. 159 keywords were included in the map. By analyzing the keywords with frequency greater than or equal to 20, we can know that the main research contents in this field are the treatment of traditional Chinese medicine and integrated traditional Chinese and Western medicine,symptoms, clinical efficacy, platelet count and so on.

Table 3 High-frequency keywords of Chinese medicine treatment for ITP( ≥ 20)

Figure 4 Visualization map of keyword of Chinese medicine treatment for ITP

The keywords with high centrality betweenness has transitional significance [7]. What has a purple outer ring is the high betweenness centrality keywords with betweenness centrality greater than or equal to 0.1. There were 20 high betweenness centrality keywords in this field. As we can see from Tab. 4, 'Hemorrhage symptom'had highest betweenness centrality (0.59). The higher betweenness centrality keyword, the more research around it, the more important it is in the field.

Table 4 High betweenness centrality keywords of Chinese medicine treatment for ITP ( ≥ 0.1)

The key words were further clustered into 10 keyword cluster tags (Fig. 5), which can reflect the hot topic of traditional Chinese medicine treatment of primary immune thrombocytopenia in this field. Tab. 5 shows the size and silhouette of per cluster. The more size of cluser there are,the higher the research heat of cluster is. The higher silhouette of cluster, the more important the cluster is. From Tab. 5 and Fig. 5, it can be concluded that the research mainly focused on clinical aspects in this fields. Regardless of symptoms, signs or drugs, most of them guide the clinical diagnosis or treatment. Theoretical research, such as the pathogenesis and the mechanism of drug action, on traditional Chinese medicine treatment of ITP was insufficiency.

Figure 5 Keyword cluster of traditional Chinese medicine treatment for ITP

Table 5 Keyword cluster of traditional Chinese medicine treatment for ITP

Discussion

ITP is an acquired autoimmune hemorrhagic disease. It is characterized by sudden acute mucocutaneous hemorrhage, gingival bleeding,epistaxis and visceral hemorrhage [8]. At present, the exact pathogenesis of ITP is not clear. It is generally accepted that there is a certain correlation with abnormal quantity and quality of megakaryocytes, increased platelet immune damage and the direct dissolution of platelets by cytotoxic T-cells[9]. Modern medicine mainly uses high-dose hormones (glucocorticoid), immunosuppressant(cyclophosphamide, vindesine, cellcept, etc.),chemotherapeutic agents (VP regimen, etc.),biological agents (rituximab), plasma exchange,immuno adsorption and other methods singly or in combination as the main treatment methods [10,11]. However, it has many problems, such as poor long-term efficacy,easy recrudescence, large side-effects, high cost, which also limit the clinical application.Traditional Chinese medicine theory has insightful views on etiology and pathogenesis of ITP and traditional Chinese medicine syndromedifferentiation and treatment, etc. There is no name of 'thrombocytopenic purpura' in Chinese medicine theory. Because its main clinical symptoms are hemorrhage (muscle bleeding,epistaxis, gingival bleeding), it belongs to the category of "mass formed by blood stasis" of traditional Chinese medicine. Symptoms such as hemorrhage, blood in the stool and so on were first recorded in Inner Canon of Huangdi. Wang Qingren's Correction on Errors in Medical Classics notes "Purpura, sugillation and bruising, there is no good description since ancient times, do not know the origin of the disease". In recent years,with the intensive study of traditional Chinese medicine for ITP, its advantages of multi-targets,multi-approach, exact curative effect and less side-effects are gradually recognized by the medical community.

The relevant literature on traditional Chinese medicine treatment for ITP was retrieved from CNKI. The CiteSpace software was used to create visualization map of authors, institutions and keywords, in order to sort out the research context, analyze the current situation and hot spots, and clarify the main research directions.

The results showed that from 1960 to 2018,there were 494 literatures about traditional Chinese medicine treatment of primary immune thrombocytopenia, with an average of 8.5 articles per year and the largest number was 37. The number of literatures were insufficient in general. From the content of literature,the curative effect of traditional Chinese medicine on primary thrombocytopenia has been affirmed. However, due to the complex clinical classification, different diagnostic criteria, syndrome differentiation and treatment of primary thrombocytopenia, and the lack of unified and standardized treatment plan or clinical pathway, clinical treatment is more inclined to stereotyped Western medicine treatment. The low attention in this direction affects clinical application and research.

According to the visualization maps of authors and institutions, 121 researchers have done relevant research in this field and formed five major teams. The main research institutions came from 36 universities of traditional Chinese medicine and their affiliated hospitals, such as Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine.Researchers had close cooperation and communication within each team, less contact between teams and institutions, and research were relatively independent. Only Chinese Academy of Chinese Medical Sciences and Hei Longjiang University Of Chinese Medicine had communication, and other cooperation is mostly subsidiary.

In summary, the pathogenesis of ITP is still unclear. In the treatment for ITP, traditional Chinese medicine can fundamentally remove the pathogeny, alleviate the toxic and side effects of western medicine, maintain the curative effect, and improve the clinical symptoms significantly. However, most of the traditional Chinese medicine treatment is limited in clinical observation, the clinical curative effect standard is not uniform. Therefore, in the future research,we should strengthen the cooperation and communication between authors and institutions,integrate resources, use modern science and technology, evidence-based medicine and other research methods, focus on the pathogenesis of ITP and mechanism of drug effect, and form a unified standard of curative effect. To make clinical treatment purposeful, targeted and improve scientifical awareness and longterm stability of traditional Chinese medicine treatment for ITP.