Professor Gan Aiping’s Experience In Treating Reflux Esophagitis With Damp-heat Syndrome Of Spleen Deficiency And Network Pharmacological Research

1.Professor Gan aiping’s experience in treating reflux esophagitis with damp-heat syndrome of spleen deficiencyResearch purpose: Based on the traditional Chinese medicine inheritance computing platform(V3.0),to explore the medication experience of professor Gan in the treatment of reflux esophagitis(RE)with spleen deficiency of damp-heat syndrome.Research methods:(1)72 patients with RE with damp-heat syndrome of spleen deficiency who were in the outpatient clinic of professor Gan from december 2017 to december 2020,and extracted basic information of the patients(name,gender,age,esophagitis classification)and 210 first prescription information.(2)Carry out standardized treatment on the name,nature and flavor return of menstruation and efficacy of 119 Chinese medicines involved,and use excel table to perform statistical analysis on general conditions,frequency of single medicine,frequency of high-frequency drug types,and frequency of nature and flavor return to menstruation.(3)Use the traditional Chinese medicine inheritance computing platform(V3.0)to conduct association rule analysis and cluster analysis on the 210 first prescriptions.Research results:(1)General situation: The male to female ratio in 72 patients was 1.18:1.The age of onset is mainly in people over 40 years old.The gastroscopy classification of patients with RE with damp-heat syndrome of spleen deficiency is more common in grade B.(2)Single medicine: The total frequency of medication is 3463,involving a total of 119 traditional Chinese medicines.The top 5 single medicines are atractylodes macrocephala,lily,amomum villosum,poria and fritillaria.(3)Types of high-frequency drugs: The top 3 in the classification statistics of efficacy are tonic drugs,heat-clearing drugs,and qi regulating drugs.(4)Four Qi: The rankings from top to bottom are cold medicine,warm medicine,calm medicine,cold medicine,and heat medicine.(5)Analysis of five flavors: The rankings from top to bottom are sweet,bitter,pungent,sour,light,astringent and salty.(6)Meridian analysis: The rankings from front to back are lung,stomach,liver,spleen,heart,kidney,large intestine,gallbladder,bladder,small intestine,triple burnt,and pericardium.(7)Association rule analysis:The five drug combinations with the highest frequency are "lily,amomum villosum","atractylodes macrocephala,poria","atractylodes macrocephala,lily","lily,zhejiang fritillary" and "atractylodes macrocephala,amomum villosum".The drug combinations with confidence level greater than 0.95 are "albizia-> rose","rose-> albizia","lily,dandelion-> amomum".(8)Cluster analysis: The 3 new drug combinations were obtained,namely "atractylodes,lily,amomum villosum,polygonatum,dandelion","atractylodes,amomum villosum,poria,lily,fritillaria","atractylodes,fritillaria,baiji,poria,lily".Research conclusion: After data mining,it was concluded that professor Gan used atractylodes,lily,amomum villosum,poria,fritillaria,and other drugs for spleen-invigorating,dampness,and heat-clearing in the treatment of RE with spleen deficiency of damp-heat syndrome.The main medications are sweet cold and bitter cold.2.Discussion on the mechanism of action of core drug combinations based on network pharmacologyResearch purpose: Based on network pharmacology technology,to explore the mechanism of action of core drug combination in the treatment of RE.Research methods:(1)Search the chemical components of the core drug combination on traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),screen out the effective chemical components with oral bioavailability(OB)>30%,drug-like(DL)>0.18,and download the corresponding target protein;according to the structure of the effective chemical components in the swiss target prediction platform find the corresponding target protein;summarize the target protein information,and use the uniport database to annotate the target protein,establish the core drug combination effective chemical composition-target database,and use the cytoscape 3.7.2 software to draw the core drug-effective chemical composition-target network diagram.(2)Predict disease targets in the genecard database.(3)Use R software to take the intersection of core drug combination targets and disease targets to obtain key targets,and use the cytoscape 3.7.2 software draw core drug-key chemical components-targets-disease network diagram and key ch-emical components-target network diagrams.According to the conditions of degree value,betweenness centrality and close centrality,the effective chemical components in the key chemical components-target network graph are screened to obtain the most important key chemical components.(4)The intersection targets are included in the string database to draw protein network interaction maps,and the top 20 targets are screened out using R language and the corresponding histograms are drawn.(5)For intersection targets,use R software and related bioconductor packages for geneontology(GO)enrichment analysis and kyoto encyclopediaof genesand genomes(KEGG)enrichment pathway analysis.Research results:(1)The chemical components and targets of the core drug combination: a total of 44 species(5 species of baizhu,7 species of lily,10 species of amomum villosum,7 species of fritillaria,15 species of poria cocos)effective ingredients to find potential targets,a total of 584 targets.(2)Disease targets: A total of 2381 reflux esophagitis targets were obtained on the genecard platform.(3)Core drug-key chemical components-targets-disease network diagram: core drug-key chemical components-targets-disease network diagram has a total of 309 nodes(including 5 drug names,41 key chemical components,262 targets and 1 disease name).(4)Key chemical components and key targets acting on RE: The most important key chemical components are β-sitosterol and stigmasterol.The key targets are PIK3 CA,TP53,AKT1,MAPK1,MAPK3,APP,HRAS,CASR,HSP90AA1,CREBBP,F2,AGTR1,MAPK8,AGTR2,CDK1,EDNRA,EGFR,ESR1,HDAC1,MAPK14,F2 R,JAK2,PLCG1 PTPN11,TACR1,JUN,EDNRB,CCKBR,GHSR,HTR2 A.(5)Enrichment analysis results: There are a total of 219 GO enrichment analysis of molecular functions,involving protein serine/threonine kinase activity,endopeptidase activity,amide binding,drug binding,etc.There are 159 KEGG enrichment pathways,which mainly involve PI3K/Akt signaling pathway,c AMP signaling pathway,etc.Research conclusion: β-sitosterol and stigmasterol are the key chemical components of the core drug combination acting on RE.The core drug combination mainly acts on RE through PIK3 CA,TP53,AKT1,MAPK1,MAPK3 and other targets,mainly through the protein serine/threonine molecular functions such as kinase act ivity,endopeptidase activity,amide binding,protein tyrosine kinase activity,drug binding,PI3K/Akt signaling pathway,c AMP signaling pathway,etc.have an effect on RE.