Exploring The Medication Rules And Mechanism Of Action Of Atrial Fibrillation With Qi Deficiency And Blood Stasis Based On Data Mining And Network Pharmacolog

Objective:1 Using data mining technology,establish a database of prescriptions for modern clinical treatment of qi deficiency and blood stasis atrial fibrillation,conduct statistical analysis of medication rules,and mine core therapeutic drugs.2 Using network pharmacology methods,the mechanism of action of core drug formulas in the treatment of qi deficiency and blood stasis atrial fibrillation was discussed,and the targets and pathways involved in the treatment were predicted,so as to provide ideas for clinical streamlining medication and follow-up research.Methods:1 Retrieve literature on traditional Chinese medicine treatment for qi deficiency and blood stasis atrial fibrillation from the databases including CNKI,CBM,Wanfang Data,and VIP database.The search period is from the establishment of the database to April 30,2023.Chinese search terms include "atrial fibrillation," as well as "qi deficiency and blood stasis,"and "nourishes qi and invigorates blood." Based on these terms,construct search strategies for each platform,then screen the literature information that meets the inclusion and exclusion criteria,and standardize the data to establish a database.Use the TCM Inheritance Calculation Platform V3.0 for statistical analysis.Set the "support" to 0.3 and the "confidence" to 0.9 for association rule analysis.Set the number of clusters to 4,and use the K-means clustering algorithm for cluster analysis to summarize the medication rules.2 We used the TCMSP database to search for effective ingredients of core drugs,setting OB≥ 30%and DL≥ 0.18.For compounds not included in TCMSP,we supplemented data from the ETCM database.The protein targets were standardized using the STRING and UniProt databases and converted to their corresponding human gene target names(gene symbol)to construct a database of drug activity targets.Disease-related targets were searched in the GeneCards database to establish a gene target database related to atrial fibrillation.The VennDiagram tool 2.1.0 was used to find the intersection of drug activity targets and disease targets and to draw a Venn diagram.Using Cytoscape 3.9.1,a "drug-active ingredient-target"network was constructed.The intersection targets were imported into the STRING database to construct a PPI network.GO and KEGG enrichment analysis was performed using the DAVID database.Finally,we predicted the key effective ingredients,key targets,and possible pathways involved in the treatment of qi deficiency and blood stasis atrial fibrillation by constructing graphs using bioinformatics tools.Results:1 A preliminary search yielded 223 articles,which were screened according to inclusion and exclusion criteria,resulting in the inclusion of 46 articles and 46 formulae involving 113 Chinese herbs with a total frequency of 565.Huangqi,Danshen,Gancao,Chuanxiong and Suanzaoren were the top five herbs used by frequency,with the use of warm-natured and cold herbs being dominant,and sweet,bitter,and pungent tastes being the main flavors used.The selection of herbs was mainly based on their effect on the liver meridian,heart meridian,lung meridian and spleen meridian,with consideration given to the kidney meridian.The combination of herbs mainly focused on the efficacy of deficiency and blood-activating and stasis-resolving drugs.The most commonly used combinations of herbs were "Huangqi,Danshen",the highest support association combinations were "Huangqi→Danshen","Danshen→Huangqi" and the highest confidence association combinations were "Huangqi,Chuanxiong→Danshen","Danshen,Chuanxiong→Huangqi","Suanzaoren,Danshen→Huangqi","Suanzaoren,Huangqi→Danshen","Danggui,Huangqi→Danshen","Danggui,Danshen→Huangqi" and "Dangshen,Huangqi→Danshen".Cluster analysis yielded four core formulae,and data mining identified a core group of herbs for qi deficiency and blood stasis atrial fibrillation:Huangqi and Danshen.2 Analysis of the core formula showed a total of 85 effective ingredients corresponding to 77 targets,1850 atrial fibrillation related targets,and 33 intersection targets between drugs and diseases.In the "drug-active ingredient-atrial fibrillation target" network,querceti,kaempferol,luteolin,7-O-methylisomucronulatol,isorhamnetin and formononetin were the effective ingredients with the highest Degree value.In the PPI network,IL6,IL-1β,CASP3,TP53 and STAT3 were the top 5 targets ranked by Degree value.The main pathways involved in drug regulation were AGE-RAGE signaling pathway in diabetic complications,Lipid and atherosclerosis,Fluid shear stress and atherosclerosis,Kaposi sarcoma-associated herpesvirus infection and Hepatitis B,etc.Conclusion:1 The core prescription for modern doctors to treat qi deficiency and blood stasis atrial fibrillation is Huangqi and Danshen.In treatment,emphasis is placed on regulating the functions of the liver,heart,lung,spleen and kidney,and simultaneously using methods to"regulate the spleen" and "nourish qi" to invigorate blood and external pathogenic factors,targeting the pathological processes of qi deficiency and blood stasis syndrome with targeted treatment.2 The results of network pharmacology studies show that the most likely effective ingredients of the core prescription are querceti,kaempferol,luteolin,7-O-methylisomucronulatol,isorhamnetin and formononetin.By regulating the targets such as IL6,IL-1β,CASP3,TP53,STAT3,etc.,they participate in signal pathways such as AGE-RAGE signaling pathway in diabetic complications,Lipid and atherosclerosis,Fluid shear stress and atherosclerosis,Kaposi sarcoma-associated herpesvirus infection,Hepatitis B,etc.,producing anti-arteriosclerosis,inhibiting inflammatory factors and adhesion factors,affecting atrial structural remodeling and electrical remodeling and regulating lipid metabolism and so on,and achieving the treatment of atrial fibrillation.