Based on data mining to explore the medication rule of Professor Shao Zheng-bin in the treatment of coronary heart disease combined with type2 diabetes mellitus after PCI

Zhao-Long Liu, Pan Liu, Zi-Ting Ni, Zheng-Bin Shao

1. Graduate School of Anhui University of traditional Chinese medicine (Hefei 230038)

2. The First Affiliated Hospital of Anhui University of traditional Chinese medicine (Hefei 230031); Institute of cardiovascular disease of Anhui University of traditional Chinese medicine (Hefei 230031)

Keywords:

ABSTRACT

1. Introduction

Coronary heart disease (CHD) is a common cardiovascular disease, which belongs to the category of "chest obstruction" and "true heartache" in traditional Chinese medicine. As an independent risk factor and other critical diseases of CHD, diabetes plays an important role in aggravating and promoting its development. It was found that patients with coronary heart disease and type 2 diabetes have higher degree of coronary stenosis and more coronary lesions than those without diabetes. In recent years, with the recommendation of relevant guidelines, as well as the continuous progress of equipment and technology, percutaneous coronary intervention has become an important means of revascularization in patients with coronary heart disease. However, some patients still suあer from chest distress and chest pain due to incomplete revascularization, stent thrombosis, restenosis, branch vessel occlusion, inflammatory response, etc., which has become a diきcult problem after PCI. In view of this problem, western medicine often does not have a good treatment method. Shao Zhengbin, based on his many years of clinical experience and unique views, proposed the method of "benefiting qi and nourishing Yin, resolving phlegm and dredging collaterals" on the basis of syndrome diあerentiation and treatment, which is the outline of medication for coronary heart disease combined with type 2 diabetes after PCI. From January 2016 to may 2019, the outpatient prescriptions of patients diagnosed as coronary heart disease with type 2 diabetes mellitus after PCI were statistically analyzed. The data mining technology was used to analyze the drug use in the prescriptions and the association rules between the drugs, and to explore Shao Zhengbin's experience in the treatment of coronary heart disease with type 2 diabetes mellitus after PCI.

2. Data and methods

2.1 Research object

The included cases were from Shao Zhengbin outpatients, the First Aきliated Hospital of Anhui University of traditional Chinese medicine from January 2016 to may 2019, who were treated with PCI for coronary heart disease and type 2 diabetes mellitus. They were included in the prescription strictly according to the standard.

2.2 Inclusion and exclusion criteria

Inclusion criteria: 1. For the diagnosis of selected cases, refer to "internal medicine of traditional Chinese medicine" [9]； for the diagnosis of Western medicine, refer to "internal medicine" [10]； 2. For the first diagnosis, the prescription is eあective and there is a record of follow-up diagnosis； for the curative effect, refer to "standard of curative eあect for diagnosis of diseases of traditional Chinese medicine" [11], and the prescriptions and medicines are complete； 3. For the part of chest obstruction combined with thirst elimination, the syndrome diあerentiation is Qi and yin deficiency, phlegm and blood stasis combined. Exclusion criteria: 1. The first diagnosis of non coronary heart disease with type 2 diabetes stent implantation in western medicine； the second diagnosis of non chest arthralgia with diabetes mellitus in traditional Chinese medicine； 2. The treatment of invalid or aggravating cases with reference to the evaluation criteria of diagnostic eきcacy standard of traditional Chinese medicine； 3. The cases with serious basic diseases or mental disorders.

2.3 Drug information collection method and standardization

Drug information collection form mainly includes name, outpatient number, time of treatment, diagnosis and drug. The collected information of prescriptions and drugs was entered into Microsoft Office Excel 2016, and Shao Zhengbin's database of drugs after PCI for coronary heart disease and type 2 diabetes was established. In accordance with the Pharmacopoeia of the people's Republic of China (2015 Edition) and the textbook of the 12th Five Year Plan for colleges and universities of traditional Chinese medicine (Chinese pharmacy), the aliases of traditional Chinese medicine in the medicines of the other side were standardized. For example, "Fa Banxia" and "Jiang Banxia" are changed to "Banxia" and "roasted liquorice" to "liquorice"； in order to ensure the accuracy of the data, the whole process uses two people and two computers to input the data independently, and after the input, the data is checked and logically checked.

2.4 Data processing

After data entry is correct, lock the database and export the data to SPSS database format file. Use Microsoft Office Excel 2016 to analyze the frequency of drug use； use SPSS statistic 24.0 software to classify the data → cluster analysis → system cluster analysis → cluster method: group connection, measurement interval: Pearson correlation cluster analysis, the results are displayed in the tree chart； factor analysis, factor analysis uses the principal component analysis method, rotation method uses the maximum varianceMethods:SPSS modeler 18.0 was used to analyze the data by classification, association and Apriori (the minimum support was 50%, and the minimum confidence was 80%)； graph, network and threshold were used.

3.Results

3.1 High frequency drugs

In this study, 133 medical cases were included, involving 86 drugs and 1966 drug frequency, with an average of 15 drugs per case. Among them, the top 20 drugs used more than 30% (1334 times in total, accounting for 67.8%) and the top 10 drugs used more than 10% (1596 times in total, accounting for 81.2%). See Table 1 for details.

3.2 High frequency drug efficacy

By using computer program, 86 drugs in the prescription are corresponding to the drug eきcacy after standardized treatment. Microsoft Excel 2016 software is used for classification andsummary, and the results after summary are sorted. The results showed that the main treatment method was "Invigorating Qi and Yin, resolving phlegm and dredging collaterals", and the methods of invigorating the spleen and Qi, nourishing the heart and tranquilizing the mind, etc. See Table 2 for details.

Table 1 High frequency drugs (frequency ≥ 10%) prescribed by Shao Zhengbin after PCI for coronary heart disease with type 2 diabetes mellitus

Table 2 High frequency drug eきcacy of Shao Zhengbin's prescription after PCI for coronary heart disease combined with type 2 diabetes mellitus (top 9)

Table 3 2-way correlation analysis of high-frequency drugs prescribed by Shao Zhengbin in the treatment of coronary heart disease with type 2 diabetes mellitus after PCI

3.3 Correlation analysis

Fig.1 network diagram of high frequency drugs in prescriptions after PCI for coronary heart disease and type 2 diabetes mellitus treated by Shao Zhengbin

3.4 Cluster analysis

According to the results of the dendrogram, 7 clustering formulas (C6 is the single drug selected and explained by Shao Zhengbin after referring to the clustering analysis results) can be concluded. Among them, "Astragalus, Huangjing, chuanxiong, dandelion, dangshen, pinellia", "Danshen, Fuling, Gualou" and other drug combinations are consistent with Shao Zhengbin's clinical drug mix Wu rules. See Figure 2 and table 4 for details.

Figure 2 cluster analysis tree of high-frequency drugs after PCI of Shao Zhengbin for coronary heart disease and type 2 diabetes mellitus

3.5 Factor analysis

Kmo and Bartlett test were carried out for 20 drugs with a frequency of more than 20%. The data met the factor analysisstandard (P ＜ 0.05), and 6 common factors were obtained. The abscissa in the lithotripsy chart represents the high frequency drug serial number which is completely consistent with the noun in Table 2. From the lithotripsy chart, it can be seen that in the straight line of three consecutive points, starting from the sixth point, the line of three consecutive points starts to be smooth, and from the At the beginning of the sixth point, when the eigenvalue is less than 1, six factors can be considered to be analyzed. See Table 5 and figure 3 for details.

Table 4 cluster analysis results of high frequency drugs after PCI of Shao Zhengbin in treating coronary heart disease with type 2 diabetes mellitus

Table 5 drug composition and loading coeきcient of common factors in factor analysis

Fig.3 high frequency drug factor analysis of Shao Zhengbin's prescription after PCI for coronary heart disease combined with type 2 diabetes mellitus

4. Discussion

Coronary heart disease and diabetes often occur at the same time and influence each other. Coronary heart disease belongs to the category of "chest obstruction". The basic pathogenesis of the disease is that the heart vessel obstruction is blocked, and the disease nature is based on the deficiency of Qi and blood Yin and Yang, and the stagnation of Qi, blood stasis, cold coagulation and phlegm obstruction are based on the physical and pathogenic factors. Diabetes belongs to the category of "Xiaoke", whose pathogenesis is Yin deficiency and dryness heat as the standard. For a long time, the thirst is quenched, the body fluid is consumed, the deficiency of body fluid is astringent and the blood stasis is formed, the heat is dried and the fluid is refined into phlegm, and the phlegm and blood stasis are combined with each other for a long time, blocking the heart vessels and causing chest obstruction. Coronary heart disease and diabetes have the same etiology and pathogenesis. Another study found that [12], the main syndromes of coronary heart disease patients with diabetes are deficiency of both qi and Yin, blood stasis and phlegm obstruction. However, the pathological process of patients with coronary heart disease after PCI corresponds to the categories of "heart vessel obstruction" and "heart vessel obstruction" in traditional Chinese medicine. The etiology and pathogenesis of the disease is that the damage of vascular intima leads to "blood stasis, blood vessel obstruction" which belongs to the category of blood stasis syndrome. Therefore, the syndrome types of TCM in patients with coronary heart disease and type 2 diabetes after PCI are mostly deficiency of Qi and Yin, blood stasis and phlegm obstruction. Therefore, Shao Zhengbin combined with many years of clinical practice and experience, put forward the "Yiqi Yangyin, Huatan Tongluo" method as the treatment of coronary heart disease combined with type 2 diabetes after PCI medication program. The results of diagnosis and statistical analysis of this study showed that in 133 prescriptions, the top 30 flavors of HFD were dangshen, Huangjing, Danshen, Gualou, chuanxiong, chaobaizhu, etc. It can be seen from the drug frequency that Shao Zhengbin likes to use dangshen, astragalus, Huangjing and fried Atractylodes after PCI in treating coronary heart disease and type 2 diabetes mellitus. From the drug eきcacy, it has the eあect of nourishing qi and Yin. It can dredge the collaterals through supplementing qi, reflecting the drug characteristics of "Qi and Yin, Qi can move blood". In addition, it uses such drugs as Salvia miltiorrhiza, Trichosanthes and Chuanxiong to promote blood circulation and remove blood stasis and phlegm, reflecting the "benefiting qi" Nourishing Yin, resolving phlegm and dredging collaterals ".

According to Shao Zhengbin's research, the syndrome types of coronary heart disease combined with type 2 diabetes are more complex, and there are phlegm and blood stasis on the basis of qi deficiency and yin deficiency. Therefore, in patients with coronary heart disease and type 2 diabetes mellitus, Qi and yin deficiency, phlegm and blood stasis are more common [14]. Therefore, the method of Supplementing Qi and nourishing Yin, resolving phlegm and dredging collaterals should be used throughout the treatment of coronary heart disease with diabetes mellitus, which can be proved by the network display of drug association rules.

Correlation analysis showed that the related drugs with confidence ＞ 80% were dangshen, Huangjing, Danshen, Gualou, chuanxiong and chaobaizhu. Drug pairs can be divided into seven categories: Huangjing and other drug combinations: Huangjing Huangjing and Huangjing dangshen, among which Huangjing, Huangqi, huangqi and Yangyin play the effect of Invigorating Qi and generating blood, Huangjing, dangshen, tonifying spleen, saving children from mother's disease, regulating spleen and protecting heart； dangshen Huangqi should be used to invigorate middle Qi and eliminate pathogenic factors； Trichosanthes and other drugs matching: Trichosanthes - Huangqi, Trichosanthes - dangshen, Trichosanthes for clearing away heat Phlegm medicine, combined with Astragalus, dangshen and other qi invigorating drugs, can clear away heat, reduce pathogenic heat and practice Jin as phlegm, invigorate Qi and regulate qi to promote the transportation and operation of phlegm and dampness in body fluid, and play the effect of broad chest and loose knot together； combination of Danshen and other drugs: Danshen Astragalus, Danshen dangshen, Danshen is the medicine for promoting blood circulation and removing blood stasis, which is combined with appeal qi invigorating drugs to strengthen the blood circulation Function: stir fried Atractylodes rhizome Astragalus, stir fried Atractylodes rhizome is a medicine for invigorating the spleen and benefiting the Qi, which is the so-called deficiency of Qi and stagnation of Qi and blood stasis, combined with Astragalus to enhance the eあect of Invigorating Qi and promoting qi； Chuanxiong dangshen, Chuanxiong astragalus； Chuanxiong can not only activate blood and eliminate stasis, but also activate Qi and relieve pain, which is the "Qi medicine in blood", combined with the above mentioned medicine, can increase the eあect of Qi and promoting blood circulation；

Cluster analysis is to further explore the clinical drug compatibility of Shao Zhengbin in the treatment of coronary heart disease combined with type 2 diabetes mellitus after PCI. Because this paper is a summary of clinical experience, and after discussion with Shao Zhengbin, it is concluded that the seven cluster analysis results are consistent with Shao Zhengbin's clinical drug experience, and now it is reported as follows. C1 combination: Pueraria, peach kernel, fried orange peel and bupleurum root play the function of regulating qi and dredging pulse. Shao Zhengbin believes that the main pathogenesis of coronary heart disease is the blockage of heart vessels, the Qi and blood circulation of the heart is not smooth, and the obstruction of heart and chest is caused by congestion of blood. Therefore, the method of promoting blood circulation and removing blood stasis is often used throughout the clinical treatment of coronary heart disease. C2 combination: tangerine peel, fried sour jujube kernel and yam are commonly used in Shao Zhengbin's clinical medicine combination, and the compatibility of the three focuses on tonifying the heart and spleen. Shao Zhengbin thinks that the method of regulating the heart and spleen is an important link in the treatment of coronary heart disease. If the spleen and stomach are forgetful, Qi and blood will be generated. If the spleen is moving, phlegm will be moistened, blood stasis will be eliminated, and the channels of blood vessels will be smooth. In clinical application, we should pay attention to regulating the spleen and stomach and treating the heart from the spleen. C3 combination: Astragalus, Huangjing, chuanxiong, dandelion, dangshen, Pinellia ternate. Astragalus membranaceus, Huangjing and dangshen are herbs for nourishing qi and Yin. Qi is the beauty of blood. When Qi moves, blood flows. When they are used together with Chuanxiong and dandelion, they can strengthen the function of promoting blood circulation, removing blood stasis and Qi. Pinellia has a warm and pungent nature. It can be used to disperse Qi and knot. When it is warm, it can clear Yang and phlegm. It is necessary to treat cold phlegm and damp phlegm. All herbs are used together to play the function of removing phlegm and dredging collaterals. C4 combination: Salvia miltiorrhiza, Poria cocos, Trichosanthes. Salvia miltiorrhiza is bitter, cold and good at heart and liver channel. It is good at activating blood circulation, clearing blood stasis and relieving pain. The nature of Gualou (skin) is sweet and bitter, it can benefit Qi and open depression, lead phlegm to turbid down and broad chest to disperse. Poria cocos is light, seeping and sweet, invigorating the spleen and resolving phlegm. The combination of the three can make the phlegm wet and blood stasis go away. C5 combination: Fu Shen is sweet, mild and even, Gong Shanning is tranquil, invigorating the spleen and removing dampness； coix seed is used to remove dampness and Bi, and the combination of two drugs can remove dampness and phlegm, invigorating the spleen and Qi. C6 is a single drug selected and explained by Shao Zhengbin after referring to the results of cluster analysis. Stir fried Atractylodes macrocephala is longer than invigorating the spleen and Qi. It is a medicine for invigorating the spleen. Therefore, it can eliminate phlegm drink and edema, and it is a good medicine for treating phlegm drink. C7 combination: Zhu Ru, stir fried white peony； Zhu Ru is sweet and bitter, long in clearing heat and resolving phlegm, stir fried white peony, nourishing blood and accumulating Yin, and the combination of two drugs can enhance the eあect of resolving phlegm and removing blood stasis. In conclusion, Shao believes that C5 + other clustering methods can be used to treat coronary heart disease with type 2 diabetes after PCI. Factor analysis is a multivariable simplification technology, which can simplify and reduce dimensions. By decomposing the original variables, the hidden multi-level information in the variable group can be analyzed in multiple steps and levels, so as to induce the potential "categories". The variables with strong correlation can be classified into one category. Each category of variables represents a "common factor". Finally, a factor model is established to explain the main factors The relationship between children and variables. Therefore, factor analysis is objective and has the same significance and reference value of data mining compared with cluster analysis. In this analysis, six common factors were found, and similar results were obtained with cluster analysis. Among them, F1 = C2 + C4； F2 = C1 - stir fried Fructus aurantii and Bupleurum； F2 + F3 = C1 + C4； F4 + F5 = C3 + C4 - Dandelion and dangshen； in a word, cluster analysis and factor analysis are diあerent methods for data mining, but the same data can produce similar results, which also proves that Shao Zhengbin's clinical drug compatibility is regular and the data has analytical value.

In this study, frequency analysis, high frequency drug association rule analysis, cluster analysis were used to explore Shao Zhengbin's clinical drug use characteristics, scientifically and accurately get Shao Zhengbin's drug use experience, core drugs and drug composition after PCI in the treatment of coronary heart disease combined with type 2 diabetes, in order to inherit Shao Zhengbin's clinical experience.