Part One:Objective:To explore the medication rules of Professor Hu Xiaomei in the treatment of chronic aplastic anemia(CAA)by analyzing the outpatient medical records of Professor Hu through data mining.Methods:1.Establish the TCM clinical medical record database of Professor Hu in the treatment of CAA.2.Eligible medical records were screened according to the inclusion and exclusion criteria.3.The data in the selected medical records were standardized.4.Microsoft Excel was used to calculate the general condition of patients,the frequency of traditional Chinese medicine,the nature,taste and meridian-tropism of drugs,and R was used for K-means cluster analysis and association rule analysis based on Apriori.5.The association rules were imported into Gephi for topology analysis to obtain the core prescription.Results:1.General conditions of patients:a total of 111 patients were screened out,with a total of 553 prescriptions.The median age of the patients was 34 years old,the male to female ratio was 15/22,and the proportion of patients with kidney Yang deficiency,kidney Yin deficiency,and kidney Yin and Yang deficiency was 31.3%,50.9%and 17.0%,respectively.2.Herbs frequency:there were 143 kinds of herbs in 553 prescriptions.There were 50 herbs in the top 10%of occurrence frequency,and the top 10 were:Poria Cocos>.Grimonia Pilosa>Ripe Rehmannia>Cornus>Codonopsis>Yam>Moutan>mulberry>Rhizoma alismatis>Eclipta.3.flavors,properties and channel tropisms of herbs:(1)The top three flavors of herbs in Professor Hu’s prescription for treating CAA with different syndroms were sweet>bitter>spicy.(2)The top three properties of herbs in Professor Hu’s prescription for treating CAA with different syndroms were mild>warm>cold.(3)The top three channel tropisms of herbs in Professor Hu’s prescription for treating CAA with different syndroms were kidney>liver>spleen.4.herbs clustering:(1)The core cluster combination of prescription drugs for patients with kidney Yang deficiency syndrome was Yougui Pill combined with Sijunzi Decoction:Cooked Rehmanniae Radix,Cornus,Yam,Codonopsis Pilosula,Fried Atractylodes Rhizoma,Poria,Licorice,Mulberry,Hairyvein Agrimony,Selaginella,Eclipta.(2)The core cluster combination of prescription drugs for patients with kidney Yang deficiency syndrome was Zuogui Pill combined with Sijunzi Decoction:Cooked Rehmannia,Yam,Cornus,Achyranthes,Tortoise Shell,Eucommia,Asparagus,Ophiopogon,Mulberry,Codonopsis,Fried Atractylodes,Poria,Fried Licorice,Moutan Peel,Rhizoma Alismati,Sage Herb.(3)The core cluster combination of prescription drugs for patients with kidney Yang deficiency syndrome was Yougui Pill,Erzhi Pill,Danggui Buxue Decoction combined with Sijunzi Decoction:Hairyvein Agrimony,Ligustrum Lucidum,Cooked Rehmanniae,Epimedium,Fried Atractylodes Rhizoma,Cornus Officinalis,Lotus,Fructus Psoraleae,Angelica,Pericarpium Citri Reticulatae,Mulberry,Roasted Astragalus Membranaceus,Yam,Codonopsis,Rhizoma Rhizoma Polygonati,Wolfberry,Poria,Cuscuta,Polygonum Multiflorum.3.Core prescription:(1)Based on the topological analysis of the association rules of kidney Yang deficiency syndrome,the core prescriptions were:Cooked Rehmannia,Codonopsis,Cynomorium Songaricum,And Hairyvein Agrimony;kidney.(2)The core prescriptions obtained by the topology analysis of the association rules of kidney Yin deficiency syndrome were:Cooked Rehmannia,Cornus Officinalis,Yam,Poria,Codonopsis,Hairy vein Agrimony,Peony Bark,Rhizoma Alismatis.(3)Based on the topological analysis of the association rules of kidney yin-yang deficiency syndrome,the core prescriptions were:Cooked Rehmannia,Cornus Officinalis,Codonopsis,Hairy vein Agrimony,Ligustri Lucidum,Herba Epimedii.Conclusions:1.The properties of Professor Hu’s prescriptions for treating CAA of various syndrome types are generally mild,warm and cold,the flavors are sweet,bitter and spicy,and the meridians are mainly kidney,liver and spleen.2.The core herbs combination of Professor Hu in the treatment of CAA:the core herbs combination of kidney Yang deficiency syndrome is the addition and subtraction of Yougui Pill and Sijunzi Decoction;the core herbs combination of kidney Yin deficiency syndrome was Zuogui Pill combined with Sijunzi Decoction;the core drug combination of kidney Yin-Yang deficiency syndrome was Yougui Pill,Erzhi Pill,Sijunzi Decoction and Danggui Buxue Decoction.3.Professor Hu’s core prescription for treating CAA of kidney Yang deficiency syndrome is:Cooked Rehmannia,Codonopsis,Cynomorium Songaricum,And Hairyvein Agrimony;the core prescription for the treatment of kidney Yin deficiency syndrome CAA:Cooked Rehmannia,Cornus Officinalis,Yam,Poria,Codonopsis,Hairyvein Agrimony,Peony Bark,Rhizoma Alismatis;the core prescription for treating CAA of kidney Yin and Yang deficiency syndrome:Cooked Rehmannia,Cornus Officinalis,Codonopsis,Hairyvein Agrimony,Ligustri Lucidum,Herba Epimedii.Part two:Objective:According to Professor Hu’s core prescription for the treatment of CAA,the co-target network between drug active ingredients and diseases will be established by network pharmacology,and the mechanism of action of Professor Hu’s core prescription for the treatment of CAA will be explored.Methods:1.To search the database and analysis platform of traditional Chinese medicine system pharmacology to screen the active ingredients and corresponding targets of core prescription drugs.For the drugs not included in the platform,to search the literature to find out their ingredients,predict their active ingredients by SwissADME,and then predict their targets by SwissTargetPrediction.2.Using "aplastic anemia" as the search term in Genecard,OMIM and Disgenet databases,the results were summarized and the targets related to AA were obtained after removing the duplication,and the common targets of drugs and AA were found by R.3.Cytoscape was used to establish the drug-active ingredient-target network and identify the major active ingredients.4.STRING and Cytoscape were used to establish the protein-protein interaction(PPI)network diagram and find out the core targets.5.GO and KEGG enrichment analysis of the co-targets of drugs and AA were performed by STRING.6.Autodock was used to perform molecular docking of the top ten active ingredients and core targets to evaluate the affinity of the main active ingredients with core targets.Results:1.The number of common targets between core prescription drugs and AA for each syndrome type was 118 for kidney Yang deficiency,85 for kidney Yin deficiency,and 87 for kidney Yin and Yang deficiency.2.The main active ingredients screened by Cytoscape degree value were quercetin,luteolin,kaempferol and myristic acid.Kidney Yin deficiency:quercetin,luteolin,kaempferol;kidney Yin and Yang deficiency:quercetin,luteolin,kaempferol,acacetin.3.The core common targets identified by the protein interaction network clusterviz were kidney Yang deficiency:CCL2,MMP9,JUN,VEGFA,IL6,IL10,CXCL8,ALB,IL1B,EGF,AKT1,IL4,IFNG,ICAM1,etc;kidney Yin deficiency:AKT1,VEGFA,IL1B,CCL2,CXCL8,MMP9,IL4,IL10,JUN,IL6 etc.Kidney Yin-Yang deficiency:AKT1,TP53,VEGFA,IL6,JUN,IL1B,HIF1A,MMP9,MYC,EGF,etc.4.The main enrichment components were cell membrane,cytoplasm,cytoplasmic matrix,etc.The main biological processes were positive and negative transcription regulation of ribonucleotide polymeraseIIpromoter,positive transcription regulation,DNA templating,drug reaction,etc.The main molecular functions were protein binding,same protein binding,enzyme binding,ATP binding,etc.The main molecular pathways enriched were PI3K-Akt signaling pathway and MAPK signaling pathway.5.The molecular docking results showed that the maximum docking energy of each group was-4.2KJ/mol,and the minimum docking energy was-11KJ/mol.Only 3 groups of molecular docking results were greater than-5kJ/mol.Conclusions:1.The main active ingredients of the core prescription:quercetin,luteolin,kaempferol,myristic acid,2.The main targets of core prescription for CAA treatment:CCL2,MMP9,JUN,VEGFA,IL6,IL10,CXCL8,ALB,IL1B,EGF,AKT1,IL4,IFNG,ICAM1,TP53,HIF1A,MYC,EGF,etc.3.The signaling pathways of the core prescription in the treatment of CAA:PI3K-Akt pathway,MAPK pathway and so on. |