To Investigate The Regularity And Mechanism Of Professor Hu Yueqiang In Treating Acute Cerebral Infarction Based On Data Mining And Network Pharmacology

Objective: To understand the experience of Professor Hu Yueqiang in the treatment of acute cerebral infarction through data mining,and select the core drug combination,apply network pharmacology method to predict the possible mechanism of action of the core drug group,in order to summarize Professor Hu Yueqiang ’s academic thoughts in the treatment of acute cerebral infarction,in order to provide new ideas and directions for the TCM treatment and basic experiments of cerebral infarction.Methods:(1)Collect cerebral infarction patients treated by Professor Hu Yueqiang in First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine from January 2020 to June 2022,sort out the basic information and prescription information of patients who meet the inclusion and exclusion criteria,and establish a database.Excel was used to carry out frequency statistics for patient age,gender,drug use,taste meridians,and drug efficacy,SPSS Statistics27.0 and SPSS Modeler18.0 were used for data analysis,the rules were summarized,Professor Hu Yueqiang ’s therapeutic ideas and formula rules for the treatment of acute cerebral infarction were explored,and the core drug combinations were selected.(2)TCMSP database,HERB,ETCM database and literature search were used to obtain the active ingredients and their targets of the core formula,Uniprot database was used to standardize the gene name of the target protein,Gene Cards database and OMIM database were used to obtain the targets related to cerebral infarction,Wayne diagram was used to obtain the intersection targets of drugs and diseases,and Cytoscape3.7.2 software was used to construct the network diagram of "core prescription-active component-disease target".Applying STRING database,PPI networks of intersection targets were constructed and core targets were selected based on degree values by visualization.GO function and KEGG pathway enrichment analysis of intersection genes were performed using R language to finally obtain the possible mechanism of core formula in the treatment of cerebral infarction.Results:(1)Gender and age distribution: A total of 132 patients were included,including 60 female patients and 75 male patients.The main age of onset was60-79 years old.(2)Drug frequency,four qi and five flavors,meridians,and efficacy classification results of traditional Chinese medicine:A total of 156 herbs were included,and the total frequency of using herbs was 1903,and the top10 herbs were licorice root,ginger,pinellia ternata,guizhi,tangerine peel,hawthorn,aconite root,poria cocos,calamus,and atractylodes macrocephala.The four qi were mainly warm drugs,accounting for 36.05%,followed by flat and slightly cold drugs;the five flavors were mainly sweet and pungent,accounting for 50.18% and 47.71%,respectively,followed by bitter,sour,light,and salty taste;the drug meridian statistics were spleen meridian,lung meridian,stomach meridian,liver meridian,heart meridian,kidney meridian,large intestine meridian,gall bladder meridian,bladder meridian,pericardium meridian,and small intestine meridian;the efficacy of traditional Chinese medicine was classified as mainly qi-invigorating drugs in tonifying qi drugs,followed by antidotes and blood-activating and stasis-dissipating drugs.(3)Drug association rule analysis and high-frequency drug cluster analysis: The association rule was used to analyze the traditional Chinese medicines with frequency ≥ 10 times in the formula,and 6 binomial association rule combinations,20 three-item association rule combinations,13four-item association rule combinations,and 1 five-item association rule combination combinations were obtained.Through systematic clustering,three groups were clustered,the first group was keel,oyster,tortoise shell,phellodendron amurense,amomum villosum,and aconite root;the second group was: poria cocos,calamus,trichosanthes,turmeric,bupleurum,scutellaria baicalensis,wood butterfly,winter melon seed,coix seed,rhubarb,salvia miltiorrhiza,notoginseng,guizhi,hawthorn,pinellia ternate,tangerine peel,atractylodes lancea,ginger,and poria cocos;and the third group was:angelica sinensis,carthamus tinctorius,chuanxiong,astragalus membranaceus,taoren,atractylodes macrocephala,codonopsis pilosula,paeonia lactiflora.Core drug combinations were selected by association rules and network co-occurrence maps: ginger,pinellia ternata,guizhi,tangerine peel,and hawthorn.(4)Network pharmacological analysis results:(1)Screening of effective active components and targets in the core group: 42 effective chemical components and 176 drug targets were actually contained,of which the more critical active components were β-sitosterol,stigmasterol,naringenin,baicalein,and nobiletin.(2)Screening of disease targets,intersection targets and core targets: A total of 1046 targets related to cerebral infarction were screened,and there were a total of 78 intersection targets between core formula targets and disease targets,with key targets of AKT1,PPARG,CASP3,PTGS2,VEGFA,etc.;(3)GO functional enrichment analysis: a total of 1844 biological processes(BP)were obtained,involving the response to metal ions,response to extracellular stimuli,and response to nutrient levels;71 cell compositions(CC),involving membrane rafts,membrane microdomains,plasma membrane rafts,etc.;133 molecular functions(MF),mainly including nuclear receptor activity,ligand-activated transcription factor activity,and transcriptional coregulator binding,etc.;(4)KEGG enrichment analysis results: a total of 152 pathways were obtained,including lipid and atherosclerosis pathway,AGE-RAGE signaling pathway,IL-17 signaling pathway,apoptosis and TNF signaling pathways.Conclusions:(1)Etiology and pathogenesis: Professor Hu Yueqiang believes that the essence of cerebral infarction is "yang deficiency as the basis,collateral disease as the standard",yang deficiency causes wind,fire,phlegm,blood stasis evil block,so that the middle coke qi is not smooth,resulting in the normal human body "internal yang vulva" ontology structure is destroyed,so the commonly used drugs four qi is mainly warm drugs,rarely use cold drugs;five flavors are mainly sweet and pungent,pungent,sweet drugs and other yin and yang attributes are divided into yang;the drug meridians are mainly spleen meridian,lung meridian,stomach meridian;indicating that Professor Hu Yueqiang attaches great importance to protecting yang qi,pay attention to the middle coke qi operation.(2)Treatment: Following the "principle of triple energizer secondary",the clinical syndrome focuses on pulse condition.If the pulse is tight and strong,it is commonly used "Guizhi method" to Xuantong upper energizer phlegm stasis,commonly used drugs like Guizhi,Acorus calamus,Guizhi,Hawthorn,Pinellia ternate,Citrus sinensis,Atractylodes lancea,Zingiber officinale,Poria cocos;if the pulse is weak,Qianyang Fengsui Dan,Sini Decoction combined with Buzhong Yiqi Decoction are commonly used to warm the lower energizer kidney yang,and commonly used drugs like aconite root,astragalus.(3)Mechanism prediction: Through network pharmacology study,it is shown that multi-component,multi-target and multi-pathway of traditional Chinese medicine treats cerebral infarction,and the core formula may play a role in anti-inflammation,anti-oxidation and anti-atherosclerosis.