WANG Zho-Yi, HUANG Zheng-De*, YANG Ping, REN Ting, LI Xin-Hui

a.Hunan University of Chinese Medicine, Changsha, Hunan 410208, China

b.Department of Psychiatry, Hunan Brain Hospital, Changsha, Hunan 410007, China

Keywords

LI Dong-Yuan

Wind-dispelling medication

Data mining

Medication regularity

Modern research

ABSTRACT

Objective To extract and analyze information on the regularity with which wind-dispelling medication was prescribed by LI Dong-Yuan and many doctors of his school of thought and to provide theoretical basis and ideas for modern clinical application to facilitate the use, research, and development of these medications.

Methods Original data on wind-dispelling medication described in LI Dong-Yuan’s works were collected, sorted and organized.Data mining and comprehensive analysis were performed by using a series of data processing softwares, such as SPSS 22.0,Modeler 18.0 and xMiner.By reviewing LI Dong-Yuan's writings on wind-dispelling medication, the number of prescriptions for wind-dispelling medication were counted.Frequency of use of wind-dispelling medication was determined, and association rules analysis, factor analysis, and core drug network analysis were used to reveal associations of the symptoms of syndromes and treatment with wind-dispelling medication and to reveal the regularity with which these medications were prescribed by LI Dong-Yuan.

Results A total of 356 prescriptions and 121 flavors of winddispelling medication were observed.Among them, five kinds of medicinal properties, seven kinds of medicinal tastes, and 12 kinds of meridians were identified.Furthermore, herbs were divided into 18 categories according to their efficacy.Statistical analysis showed that there were 23 wind-dispelling medications that were prescribed with a frequency of ≥ 60.The mainly used drugs were Saposhnikoviae Radix (Fang Feng, 防风), Bupleuri Radix (Chai Hu, 柴胡), Cimicifugae Rhizoma (Sheng Ma, 升麻),Notopterygii Rhizoma Et Radix (Qiang Huo, 羌活), Puerariae Lobatae Radix (Ge Gen, 葛根), Chuanxiong Rhizoma (Chuan Xiong, 川芎), and Ephedrae Herba (Ma Huang, 麻黄).In addition, we analyzed the association rules wind-dispelling medication and obtained 23 one-to-one drug association rules and 11 multiple-to-one drug association rules.The core drug network analysis data visualization showed core drugs used in the treatment of external wind assailing the exterior (wind-cold,wind-heat, wind-dampness, etc.), wind-stroke, and tonifying middle and replenishing Qi.Factor analysis was performed on the drugs used by LI Dong-Yuan, and finally 4 groups of wind medicine combinations were obtained.

Conclusions This data mining-based study on the regularity of wind-dispelling medication described in LI Dong-Yuan's works is of great significance, because it reveals the clinical application of its theoretical formulae and medications.

1 Introduction

LI Dong-Yuan, a famous Chinese medical expert, is one of the “four masters of Jin and Yuan Dynasties”in the history of Chinese medicine[1].As a representative of the school of “invigorating the earth”, he found the theory of the spleen and stomach.LI Dong-Yuan and his theory of the spleen and stomach are not only respected by doctors of a later time period but also widely valued[2].Winddispelling medicine plays an important role and is widely used in the treatment of the spleen and stomach disease.The concept of “wind-dispelling medicine” was first noted in theThe Theory of Spleen and Stomach(Pi Wei Lun,《脾胃论》)of LI Dong-Yuan.Wind-dispelling medicine is represented by Bupleuri Radix (Chai Hu, 柴胡), Cimicifugae Rhizoma (Sheng Ma, 升麻), Puerariae Lobatae Radix (Ge Gen, 葛根), Notopterygii Rhizoma Et Radix (Qiang Huo, 羌活), Angelicae Pubescentis Radix (Du Huo, 独活), and Saposhnikoviae Radix (Fang Feng, 防风)in LI Dong-Yuan’s writings[3].Later doctors extended this concept to all the drugs with the function of dispelling wind and resolving exterior, dispelling wind and relieving spasm, pacifying liver and extinguishing wind, expelling wind and dredging collaterals, and dispelling wind and removing dampness.

Data mining is a computational process often applied to discover, extract and analyze large datasets[4].Data mining is useful to conduct studies that aim to perform grouping or clustering and to discover dependencies[5].Numerous studies have applied data mining to analyze characteristics of traditional Chinese medicine (TCM)and have achieved considerable results[6,7].However, at present, data miningbased studies on the regularity of use of wind-dispelling medication in LI Dong-Yuan’s work has not been reported.

In this study, we applied data mining technology to discover and explore the frequency of use of winddispelling medicine and to perform association rules analysis, factor analysis, and core drug network analysis.We aimed to reveal the characteristics of syndrome and those of treatment with wind-dispelling medication and to reveal the regularity of this medication in prescriptions by LI Dong-Yuan.

2 Methods

2.1 Data sources

We sorted and counted the prescriptions involving wind-dispelling medication in LI Dong-Yuan’s writings:Differentiation of Endogenous and Exogenous Diseases(Nei Wai Shang Bian Huo Lun,

《内外伤辨惑论》),Secret Book of Orchid Chamber(Lan Shi Mi Cang,《兰室秘藏》),The Theory of Spleen and Stomach(Pi Wei Lun,《脾胃论》),Medical Invention(Yi Xue Fa Ming,《医学发明》),Dong-Yuan Trial Formula(Dong Yuan Shi Xiao Fang,《东垣试效方》), andThe secret of living law(Huo Fa Ji Yao,《活法机要》).

2.2 Inclusion and exclusion criteria

2.2.1 Inclusion criteria(1)Medical cases or discussions with detailed and clear description of the clinical manifestations, syndromes, and treatment methods.(2)Medical cases or discussions with prescriptions explicitly suggesting the use winddispelling medication.(3)The prescribed compositions include Chinese herbal medicines, to be administered as decoctions, powders, or pills.(4)Prescriptions include at least two or more clinical manifestations to describe the patient’s disease situation.(5)If medical cases or discussions involved several follow-up visits, inclusion were based on the clinical effects of the second diagnosis.(6)LI Dong-Yuan’s writings that corresponded only to winddispelling medication.

2.2.2 Exclusion criteria(1)Medical cases or discussions without a description of clinical manifestations or prescriptions.(2)Medical cases or discussions involving incomplete use of drugs or those with defective records.(3)Medical cases or discussions with 5 or more treatments for the same disease.(4)Prescriptions that do not include winddispelling medication, or involve other treatment methods, such as acupuncture, massage, etc.(5)Medical cases or discussions that do not mention the treatment effects or those without obvious treatment effects.(6)When medical cases or discussions were similar or were repeated in different writings, the earliest medical cases or discussions in the year of writing were recorded, and the others were excluded.

2.3 Establishment of database

Microsoft Office Excel 2017 was used to establish an application database and an attribute database for LI Dong-Yuan’s wind-dispelling medication.The application database includes information on patient's clinical manifestations, tongue and pulse images, prescription’s name, composition,provenance, etiology, pathogenesis, syndrome type and treatment.The attribute database includes information on the name and classification, Siqi,Wuwei, meridian and efficacy of wind-dispelling medication.

2.4 Data preprocessing

Because of inconsistencies in description or the literature, data preprocessing was performed before data analysis.LI Dong-Yuan’s writings were characterized by irregular terminologies, a more classical writing style, unstructured descriptions, and qualitative data.Raw data were cleaned, integrated,and specificated[8].Cleaning involved residual value processing, eliminating noise data, cleaning isolated data, etc.Data integration involved integration and processing of the data in several initial data sources,and subsequently, the data were unified into a database in the same format.The data protocol was to minimize of the quantity of data to be processed by identifying the database that needs data mining[9].

2.5 Data mining technology

After preprocessing the raw data in LI Dong-Yuan's works, statistical and mining softwares such as SPSS 22.0, Modeler 18.0, xMiner, etc.were applied to determine the frequency of use of wind-dispelling medication and to perform association rule analysis,factor analysis, cluster analysis and core drug network analysis.

2.6 Analysis method

2.6.1 Descriptive analysisMicrosoft Office Excel 2017 was used to determine the frequency of drug use, category attributes and other information.The frequency of use of the drug was determined using the following formula: (number of times of a particular Chinese medicine is used/the total number of prescriptions)× 100%.The drugs were classified according to characteristics such as medicinal properties, taste, efficacy, and class of medicine.Subsequently, the total and relative frequencies of use of TCMs corresponding to various characteristics were determined.Finally, distribution of drugs in various aspects were obtained.

2.6.2 Association rules analysisAssociation rules analysis is used to determine correlation strength based on the degree of support and confidence[10].The degree of support (X → Y)corresponds to the support within the total database D (support), that is,the ratio of the number of associations including X and Y to the total number of associations, recorded as support (X → Y).The degree of confidence (X → Y)corresponds to the confidence within the total database D (confidence), that is, the ratio of the number of associations involving X and Y to the number of associations involving X[11].In this study,the TCM inheritance assistant platform (v2.5)software was used to sort out and record 356 prescriptions in LI Dong-Yuan’s works.The analysis of association rules finally showed high-frequency“drug-drug combinations” and “drug-symptom combinations”.The relationships between medicines and symptoms were quantitative expressed.The characteristics of LI Dong-Yuan’s wind-dispelling medication syndrome and the law of prescriptions can be revealed more intuitively and comprehensively.

2.6.3 Core drug network analysisData mining network analysis algorithm was used to obtain the core nodes (drugs)of the core drug network on the basis of node distribution characteristics of LI Dong-Yuan's wind-dispelling medicine application rule.Completion degree was calculated according to the frequency of each core node (drug).Finally, core drug network diagrams was obtained.The core prescription and the law of compatibility of peripheral drugs in complex network were further revealed.

2.6.4 Factor analysisAll the factors were sorted and divided into groups based on relativity, so that the correlation within the same group increases, and the correlation between the different groups decreases or is not related.Each group of factors represented a basic structure, called a common factor[12].

3 Results

3.1 Descriptive analysis of the use of LI Dong-Yuan's wind-dispelling medication

3.1.1 Siqi, Wuwei and Meridians analysisTo establish the drugs’ standards of properties, taste and meridian tropism, we reference to the “13thFive-Year Plan” published by China TCM Press,Chinese Materia Medica.The wind-dispelling medicines used in Chinese prescriptions by LI Dong-Yuan were associated with 121 flavors.They involved five kinds of medicinal properties, seven kinds of medicinal tastes, and 12 kinds of meridians.Among them,warm drugs, especially acrid drugs, were the most frequently used drugs.Most of the meridians were concentrated in five internal organs (liver, heart,spleen, lung, kidney).The foot Yangming stomach meridian was much higher than other meridians.The statistical results are shown in Tables 1, 2 and 3.

3.1.2 Classification analysisWe divided drugs into 18 categories according to their efficacy.The most frequently used herbs were Qi-tonifying medications,blood-tonifying medications, wind-cold dispersing medications, wind-heat dispersing medications,heat-clearing and dampness-drying medications,dampness-resolving medications, Qi-regulating medications, dampness-draining diuretic medications, water-draining and swelling-dispersing medications, and interior-warming medications(Table 4).

3.1.3 Frequency distributions analysisTwentythree wind-dispelling medications used for treating diseases were observed with a frequency of ≥ 60 in LI Dong-Yuan’s writings, accounting for 16.91% of all types of wind-dispelling medications (136 flavors).The total frequency of use of the core wind-dispelling medications was 2 453.The proportion of drug use was 58.22% (Table 5).

3.1.4 Analysis of combinations of two or more drugsAmong the drug pairs or drug combinations thatappear more than 30 times, the mainly used drugs were Saposhnikoviae Radix (Fang Feng, 防风),Bupleuri Radix (Chai Hu, 柴胡), Cimicifugae Rhizoma(Sheng Ma, 升麻), Notopterygii Rhizoma Et Radix(Qiang Huo, 羌活), Chuanxiong Rhizoma (Chuan Xiong, 川芎), Ephedrae Herba (Ma Huang, 麻黄)etc.,among which Chuanxiong Rhizoma (Chuan Xiong,川芎)- Saposhnikoviae Radix (Fang Feng, 防风)in a combination of two drugs and Chuanxiong Rhizoma(Chuan Xiong, 川芎)- Saposhnikoviae Radix (Fang Feng, 防风)- Ephedrae Herba (Ma Huang, 麻黄)in a combination of three drugs had the highest compatibility (Table 6 and 7); combinations of more than three drugs are not listed because of space limitation.

Table1 Distributions of Siqi of LI Dong-Yuan’s wind-dispelling medication

Table2 Distribution of Wuwei of LI Dong-Yuan’s wind-dispelling medication

Table3 Distribution of meridians of LI Dong-Yuan’s wind-dispelling medication

3.2 Association rules analysis

3.2.1 Drug associationsWe analyzed the association rules wind-dispelling medication and obtained 23 one-to-one drug association rules and 11 multiple-to-one drug association rules.Ephedrae Herba (Ma Huang, 麻黄)- Puerariae Lobatae Radix(Ge Gen, 葛根)and Bupleuri Radix (Chai Hu, 柴胡)-Cimicifugae Rhizoma (Sheng Ma, 升麻)→ Gentianae Macrophyllae Radix (Qin Jiao, 秦艽)showed the highest confidence (97.67% and 93.43%,respectively), and the support was 51% and 28%,respectively (Tables 8 and 9).

3.2.2 Association of symptoms and drugsAfter determining drug associations, we observed 14 association rules.The association of “Headache →Saposhnikoviae Radix (Fang Feng, 防风)” showed the highest confidence (86%)with an improvement degree of 3.59% (Table 10).

Table4 Classifications of LI Dong-Yuan’s wind-dispelling medication (Top 10)

Table5 Frequency distributions of LI Dong-Yuan’s wind-dispelling medications (top 15)

Table6 Distributions of combinations of two drugs (top 10)

Table7 Distributions of combinations of three drugs (top 10)

3.2.3 Association of syndrome types and drugsWe identified 6 association rules between symptom types and prescriptions using association rules analysis.“Heart-lung Qi deficiency → Saposhnikoviae Radix(Fang Feng, 防风)+ Atractylodis Macrocephalae Rhizoma (Bai Zhu, 白术)” presented the highest confidence (72%)with an improvement degree of 2.47% (Table 11).

3.2.4 Association of therapeutic principles and drugsWe analyzed associations between therapeutic principles and drugs using association rules analysis and obtained 23 association rules.The rule of"Scattering wind and dissipating pathogenic factors→ Saposhnikoviae Radix (Fang Feng, 防风)" showed the highest confidence of 83% with a degree of improvement of 2.78% (Table 12).

3.3 Core drug network analysis

We constructed networks using wind-dispellingmedications prescribed by LI Dong-Yuan for common wind diseases.Network diagrams show that the larger the node number, the stronger the nature of the node hub.

Table8 Drug associations as shown by association rules analysis (top 10)

3.3.1 Network of drugs associated with wind-cold assailing the exteriorThe core drugs in this network were Saposhnikoviae Radix (Fang Feng, 防风), Ephedrae Herba (Ma Huang, 麻黄), Puerariae Lobatae Radix (Ge Gen, 葛根), Notopterygii Rhizoma Et Radix (Qiang Huo, 羌活), Asari Radix Et Rhizoma(Xi Xin, 细辛), Peucedani Radix (Qian Hu, 前胡),Gentianae Macrophyllae Radix (Qin Jiao, 秦艽),Perillae Folium (Zi Su Ye, 紫苏叶), Schizonepetae Herba (Jing Jie, 荆芥), Ligustici Rhizoma Et Radix(Gao Ben, 藁本), etc.(Figure.1).

3.3.2 Network of drugs associated with wind-heat assailing the exteriorThe core drugs in this network were Gentianae Macrophyllae Radix (Qin Jiao, 秦艽), Viticis Fructus (Man Jing Zi, 蔓荆子),Arctii Fructus (Niu Bang Zi, 牛蒡子), Saposhnikoviae Radix (Fang Feng, 防风), Menthae Haplocalycis Herba (Bo He, 薄荷), Ligustici Rhizoma Et Radix(Gao Ben, 藁本), Puerariae Lobatae Radix (Ge Gen,葛根), Peucedani Radix (Qian Hu, 前胡), Bupleuri Radix (Chai Hu, 柴胡), Cimicifugae Rhizoma (Sheng Ma, 升麻), etc.(Figure 2).

3.3.3 Network of Drugs associated with winddampness assailing the exteriorThe core drugs in this network were Ligustici Rhizoma Et Radix (Gao Ben, 藁本), Chuanxiong Rhizoma (Chuan Xiong, 川芎), Gentianae Macrophyllae Radix (Qin Jiao, 秦艽),Saposhnikoviae Radix (Fang Feng, 防风), Notopterygii Rhizoma Et Radix (Qiang Huo, 羌活), Arctii Fructus (Niu Bang Zi, 牛蒡子), Angelicae Pubescentis Radix (Du Huo, 独活), Atractylodis Rhizoma (Cang Zhu, 苍术), Clematidis Radix Et Rhizoma (Wei Ling Xian, 威灵仙), Asari Radix Et Rhizoma (Xi Xin, 细辛),etc.(Figure 3).

3.3.4 Network of drugs associated with wind-strokeThe core drugs in this network (middle meridians and collaterals)were Puerariae Lobatae Radix (Ge Gen, 葛根), Chuanxiong Rhizoma (Chuan Xiong, 川芎), Clematidis Radix Et Rhizoma (Wei Ling Xian, 威灵仙), Angelicae Pubescentis Radix (Du Huo, 独活),Gentianae Macrophyllae Radix (Qin Jiao, 秦艽),Angelicae Dahuricae Radix (Bai Zhi, 白芷), Saposhnikoviae Radix (Fang Feng, 防风), Bupleuri Radix (Chai Hu, 柴胡), etc.(Figure 4).

3.3.5 Network of drugs associated with tonifying middle and replenishing QiThe core drugs in this network were Saposhnikoviae Radix (Fang Feng, 防风), Cimicifugae Rhizoma (Sheng Ma, 升麻), Bupleuri Radix (Chai Hu, 柴胡), Puerariae Lobatae Radix(Ge Gen, 葛根), Gastrodiae Rhizoma (Tian Ma, 天麻),etc.(Figure 5).

Table9 Associations of drugs with a confidence of > 60% as shown by association rules analysis

Table10 Associations of symptoms and drugs as shown by association rules analysis (Top 10)

Table11 Associations between syndrome types and drugs as shown by association rules analysis

3.4 Factor analysis

In this study, Kaiser-Meyer-Olkin test (KMO)statistic was 0.512, Bartlett’s Test:χ2= 31 081.33,P< 0.01,suggesting a correlation between the factors.Factor analysis was performed using 49 types of drugs, and information on 5 drugs corresponding to common factors were obtained in the form of 5 groups of drug combinations (Table 13, Figure 6).

4 Discussion

The application of data mining technology for conducting research in the field of TCM has attributed new vitality to many corresponding ancient books and classics.Data mining enables researchers and learners to explore and study the core essence of TCM more deeply and intuitively[13].Dispelling the wind is one of the characteristics of LI Dong-Yuan's medication.In his pioneering theory of internal injury and spleen and stomach disease, the application of wind-dispelling medication is considered to play an important role.Winddispelling medication was flexibly used by LI Dong-Yuan to treat various types of disease syndromes,which led to the development of a unique "winddispelling medication" theory system.

In our study, we found that in LI Dong-Yuan’s writings, the wind-dispelling medication’s Qi were most centralized on coldness and warmness, flavors were concentrated on acridness, sweetness, and bitterness, and meridians were focused on the five internal organs; focus on the foot Yangming stomach meridian was significantly higher than that on others.Protection of the spleen and stomach is the first principle of treatment in LI Dong-Yuan’s “Spleen and Stomach Theory”[14]; he also proposed that the use of"sweet and warm medicines” can supplement middle and ascending yang and that “sweet and cold medicines” can purge fire to treat diseases of the spleen and stomach[15].Analysis of the use of wind-dispelling medication in LI Dong-Yuan’s writings showed that warm drugs accounted for 54.54% and cold drugs accounted for 20.67% of all the medications used.It has been proposed that “acrid, sweet and warm medicines” and “sweet, bitter and cold agents” are to be used non-exclusively[16].Wind-dispelling medicines are mostly acrid, bitter and sweet.The smell of acrid medicine is declared as Yang and that of acrid and sweet medicine as nourishing Yang.Both can help Yang and nourish Qi.The use of companion drugs is far better than that of simple Qi supplement drugs.Bitter drugs have the function of drying and reducing, and these can be used to dry dampness and strengthen the spleen.Acrid and bitter medicines can be used to disperse abdominal mass and stagnation, and sweet and bitter medicines are beneficial for invigorating the spleen and removing dampness[17].LI Dong-Yuan believes that internal injuries and diseases in humans often occur because of spleen and stomach damage, which is caused by various factors.When the spleen fails to transport fluid and blood, it leads to difficulties in raising Yang.The essence of the spleen is inferior to that of the lung, which then loses its sustenance.Finally, the weakness of ancestral Qi leads to the decline of Qi of the whole body.LI Dong-Yuan emphasizes the importance of using drugs in the meridians of the lung, spleen and stomach, which embody the therapeutic principle of “banking up earth to generate metal”.

The most frequently used wind-dispelling singlemedicine was Saposhnikoviae Radix (Fang Feng, 防风), which showed the highest confidence in the treatment of headache and the therapeutic principle of scattering wind and dissipating pathogenic factors.Chuanxiong Rhizoma (Chuan Xiong, 川芎)- Saposhnikoviae Radix (Fang Feng, 防风)was the most frequent combination.LI Dong-Yuan has indicated in the “Spleen and Stomach Theory” that “if you supplement the spleen and stomach, it will not work without these two guiding drugs”.Therefore, LI Dong-Yuan often used wind-dispelling medicines as menstrual medicines to dissipating pathogenic factors and to simultaneously promote Yang Qi.In his writings, he used Saposhnikoviae Radix (Fang Feng, 防风)and supplement drugs multiple times to promote Yang and to eliminate dampness.Chuanxiong Rhizoma (Chuan Xiong, 川芎)and Saposhnikoviae Radix (Fang Feng, 防风)had the highest frequency of compatibility.Chuanxiong Rhizoma (Chuan Xiong, 川芎)promotes Qi and blood circulation, dispels wind, and relieves pain,and it can treat headache caused by external winds.Saposhnikoviae Radix (Fang Feng, 防风)can cure all"diseases related to internal and external winds".Furthermore, it can scatter wind and disperse stasis,eliminate dampness, and relieve pain and spasm.Chuanxiong Rhizoma (Chuan Xiong, 川芎)relieves pain by promoting Qi and blood circulation.Saposhnikoviae Radix (Fang Feng, 防风)as a main medicine for the treatment of wind, relieves pain by dissipating coldness and eliminating dampness.

Table12 Associations between therapeutic principles and drugs as shown by association rules analysis

According to the association rules analysis,Ephedrae Herba (Ma Huang, 麻黄)- Pueraria lobata(Ge Gen, 葛根)as well as the association of Gentianae Macrophyllae Radix (Qin Jiao, 秦艽)with Bupleuri Radix (Chai Hu, 柴胡)and Cimicifugae Rhizoma(Sheng Ma, 升麻)showed a high degree of confidence and support.Bupleuri Radix (Chai Hu, 柴胡)and Cimicifugae Rhizoma (Sheng Ma, 升麻)are the main components of Middle-tonifying Qi-replenishing Decoction.In his writings, LI Dong-Yuan paid more attention to Middle-tonifying Qi-replenishing Decoction to treat spleen and stomach diseases.Compatibility of Cimicifugae Rhizoma (Sheng Ma, 升麻)with Bupleuri Radix (Chai Hu, 柴胡)is important for the efficacy of Middle-tonifying Qi-replenishing Decoction because it can rise Yang, supplement without delay, and protect the body against pathogens.

Table13 Results of factor analysis

Based on the analysis of core drug network, it was concluded that LI Dong-Yuan's understanding of compatibility of TCM is flexible and that he is good at using the compatibility rules of TCM.Different types of drug combinations can affect various aspects of the human body and achieve better results when complex pathogeneses are encountered.There were core drug combinations for external wind assailing the exterior (wind-cold, wind-heat, wind-dampness, etc.),wind-stroke, and tonifying middle and replenishing Qi.

In the treatment of internal injuries of the spleen and stomach, dampness occurs frequently.LI Dong-Yuan does not only emphasize on warming and nourishing Yang and eliminating dampness, but also on eliminating pathogens.According to factor classification, there are four types of factors, all of which are dampness-clearing drugs that embodied LI Dong-Yuan’s “treating dampness but not diuresis”principle.It reflects that LI Dong-Yuan’s treatment strategy is based on invigorating the middle warmness and replenishing Qi, and it is often combined with dampness-clearing drugs to promote Yang to treat various diseases.

With the help of modern data mining technology,we deeply explored the regularity and association rules of wind-dispelling medication prescribed by LI Dong-Yuan.The rule summarizes the characteristics and shows that the regularities of the use of prescriptions have important practical significance and value.

5 Conclusions

In this paper, we applied data mining to explore the regularity wind-dispelling medication described in LI Dong-Yuan's works.We extracted and analyzed the regularities of wind-dispelling medication prescribed by LI Dong-Yuan and many doctors of his school,and provided theoretical basis and ideas for modern clinical application.This work may be of great significance with regard to the clinical application of LI Dong-Yuan’s theoretical formulae and medications.

Acknowledgements

We thank for the funding support from the National Natural Science Foundation of China (No.81874429 and No.81603512)and Hunan Natural Science Foundation (No.2019JJ40210).

Competing Interests

The authors declare no conflict of interest.