Research On The Medication Rules And Mechanism Of Action Of Traditional Chinese Medicine In The Treatment Of Refractory Gout Based On Data Minin

Objective1.To investigate the clinical characteristics of patients with refractory gout and the clinical efficacy and safety of Chinese medicine in the treatment of refractory gout through a retrospective analysis of case data from the rheumatology departments of Guang’anmen Hospital and Wangjing Hospital of the Chinese Academy of Traditional Chinese Medicine.2.Based on data mining technology,to explore the drug use pattern of TCM in the treatment of refractory gout,and to explore its core drug group,in order to provide an effective basis for the TCM treatment of refractory gout.3.Based on network pharmacology,predict the mechanism of action of the core drug group in the treatment of refractory gout.Methods1.In a cross-sectional study,the basic clinical data and initial prescriptions of patients with refractory gout attending the rheumatology departments of Guang’anmen Hospital and Wangjing Hospital of the Chinese Academy of Traditional Chinese Medicine were collected and an Excel database was established.The clinical characteristics and clinical indicators of patients with refractory gout before and after treatment were statistically analyzed using Excel software and SPSS26.0 software,respectively.2.Application of the Traditional Chinese Medicine Inheritance Assist Platform V3.0 for drug frequency,efficacy classification,four qi and five tastes attribution,association rules and clustering analysis on the initial prescriptions of the included patients with refractory gout.3.The molecular mechanism of action of the core group of drugs for the treatment of refractory gout was explored through a network pharmacology approach.Firstly,the active ingredients of each herbal medicine in the core drug group were searched and screened through the TCMSP database to screen the protein targets of the action of these compounds.Refractory gout-related genes were obtained from GeneCards,DisGeNET,TTD and other database platforms,and candidate genes were obtained by extracting intersection networks with drug action targets.The "core drug group-compound-target-refractory gout" network was constructed by Cytoscape 3.8.2 software,the PPI network was constructed by STRING platform,and finally the DAVID Finally,DAVID v6.8 database was used to perform Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis to try to elucidate the relevant targets and important signaling pathways of core pharmacophore for the treatment of refractory gout and to explore its mechanism of action.Results1.Clinical characteristics of patients with refractory gout and the clinical efficacy and safety of Chinese medicine in the treatment of refractory gout(1)Clinical characteristics:A total of 191 patients were included in this study,177 males and 14 females,with a predominance of young and middle-aged population.The mean age of the patients was 46.69 ± 13.71 years,the mean duration of disease was 9.09 ±4.36 years,the mean number of joints involved was 5.59 ± 1.82,and 28.27%of the patients had a family history of gout.Alcohol consumption was the most common trigger of the disease,and 28 co-morbidities were observed,of which hyperlipidemia was the most common.The distribution of the tongue and pulse was mainly based on red tongue,yellow greasy coating and slippery pulse.The evidence typology was dominated by the evidence of damp-heat accumulation.Patients received four types of western drug treatments for gout,including non-steroidal anti-inflammatory drugs,glucocorticoids,colchicine,uric acid-lowering drugs and alkalizing urine drugs.(2)Clinical efficacy and safety:compared with those before treatment,the differences in blood uric acid,C-reactive protein,erythrocyte sedimentation rate and blood creatinine in patients with refractory gout were statistically significant(P<0.05),while the differences in urea nitrogen,alanine aminotransferase and aspartate aminotransferase levels were not statistically significant(P>0.05).2.The rule of medicine and core group of medicine in the treatment of refractory gout in Chinese medicine(1)The 191 prescriptions included in this study involved 231 herbal medicines with a cumulative frequency of 3154 times,and the average of the included individual prescription drugs was 16.54 ± 2.46.There were 62 drugs with frequencies ≥ 15 times,and the top 10 in order were:Coix lacryma,Atractylodes lacryma,Atractylodes macrocephala,Plantago lanceolata,Phellodendron chinensis,Poria cocos,Glycyrrhiza glabra,and Rhizoma Dioscorea.(2)Efficacy,four qi and five tastes,and distribution of attribution:Classified according to drug efficacy,there are mainly water-releasing and damp-permeating drugs,heat-clearing drugs,and deficiency-supplementing drugs.According to the information of the four qi of Chinese medicine,cold,warm and flat drugs are more frequently used.The results of the Five Flavors statistics show that sweet,bitter and pungent drugs are used most often.The drug meridians in the prescriptions mainly involved the liver,spleen and stomach meridians.(3)Drug association rule:the drugs mainly involved in the drug relationship with support≥20%are Coix seed,Atractylodes macrocephala,Phellodendron cantonensis and Chuanxiu Knee,etc.Combined with clinical drug analysis,the commonly used drug combinations obtained are Coix seed-Atractylodes macrocephala,Phellodendron cantonensis-Atractylodes macrocephala,Coix seed-Phellodendron cantonensis and Chuanxiu KneeCoix seed.(4)Drug clustering analysis:a total of five classes of drug groups:the first class for Plantain seed,Poria,Bletilla striata,Curcuma,Plantago,Cuttlebone;the second class for Coix Seed,Atractylodes,Poria,Glycyrrhiza,Zelenia,Phellodendron;the third class for Poria,Coix Seed,Rhizoma Chuanxiong,Atractylodes,Money Grass,Rhizoma Dioscorea;the fourth class for Atractylodes,Atractylodes,Coix Seed,Atractylodes,Phellodendron,Tiger Balm;the fifth class for Atractylodes,Coix Seed,Atractylodes,Plantago,Dioscorea,Glycyrrhiza.(5)Analysis of core drug groups:Combined with the data mining results,the core drug groups for the treatment of refractory gout in Chinese medicine were summarized as:Chuan Niu Knee,Coix Seed,Atractylodes macrocephala,Plantago ovata,Mian Dioscorea,and Glycyrrhiza glabra.3.Mechanism of action of core drug group for refractory gout(1)Acquisition of active ingredients and targets of the core drug group:119 active ingredients and 247 potential targets were obtained through the TCMSP database platform.(2)Refractory gout target screening:2971,3 and 1 genes were obtained by searching the GeneCards,DisGeNET,and TTD databases,respectively.All genes were combined and all duplicate genes were eliminated,and finally 544 genes were obtained.We applied the Venn diagram to intersect the genes of refractory gout targets with the potential targets of the core drug group compounds,and obtained 92 common targets.(3)Refractory gout target screening:2971,3 and 1 genes were obtained by searching the GeneCards,DisGeNET and TTD databases,respectively,and 544 genes were obtained by excluding duplicate genes.Application of Venn diagram to take the intersection of disease targets and potential action targets of compounds in the core drug group,and 92 common targets were obtained.(4)PPI network:The 92 potential targets of the core drug group for refractory gout were imported into the STRING platform after removing the free targets to construct the PPI network.A total of 85 nodes with 754 edges in this network,sorted by target degree value from largest to smallest,found that STAT3,JUN,RELA,AKT1,TNF,IL6,MAPK1 were the core targets in the network.(5)GO and KEGG enrichment analysis:The biological processes of the drug group acting on refractory gout mainly focus on:oxidative stress response,response to lipopolysaccharide,response to molecules of bacterial origin,etc.;cellular components mainly focus on:vesicle lumen,membrane micro-region,lipid rafts,etc.;molecular functions mainly focus on:signal receptor activator activity,receptor ligand activity,DNA binding region transcription factor binding,etc.;signaling pathways mainly focus on:TNF signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,AGE-RAGE signaling pathway in diabetic complications,lipid and atherosclerosis pathway,fluid shear and atherosclerosis pathway,etc.Conclusions1.Refractory gout is often characterized by dampness and heat,and "dampness," "heat,"and "stasis" may be the main characteristic factors of refractory gout.The core group of Chinese medicine is:Chuan Niu Knee,Coix seed,Atractylodes macrocephala,Plantago ovata,Rhizoma Dioscorea,Glycyrrhiza glabra.2.The active ingredients of the core drug group for the treatment of refractory gout are quercetin,kaempferol,baicalin,7-methoxy-2-methylisoflavone,methoxyisoflavone,isorhamnetin,etc.The potential targets of action are STAT3,JUN,RELA,AKT1,TNF,IL6,MAPK1,etc.,possibly through It may play a role in the treatment of refractory gout by mediating the TNF signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,AGE-RAGE signaling pathway in diabetic complications,and lipid and atherosclerosis pathway,which are involved in the regulation of immune inflammatory response,hypoxic response,accumulation process of late glycosylation end products,and lipid metabolism disorder.It reflects the action characteristics of multi-component,multi-target and multi-pathway of Chinese medicine,which provides the theoretical basis and research direction for further study.