The Clinical Experience In Treating Uveitis Of Professor Zhou Wanyu Based On Collateral Disease Theory And Network Pharmacology Research Of Core Prescription

Study 1 Clinical research Professor Zhou Wanyu’s clinical experience in the treatment of uveitisObjective Use the traditional Chinese medicine inheritance auxiliary platform to analyze the medication rule of Professor Zhou Wanyu in the treatment of uveitis from the collaterals,excavate the core prescriptions for the treatment of uveitis,and discuss its clinical experience in detail.Methods Through retrospective research methods,the data of uveitis cases treated by Professor Zhou Wanyu of Xiyuan Hospital of China Academy of Chinese Medical Sciences from May 2019 to October 2020 were collected,including patient information,syndrome differentiation,prescription drugs,and drug dosages.Wait,build a database.Preprocess the data,standardize the names of the syndromes,split the elements of the syndromes,and unify the names of traditional Chinese medicine.The unified data is entered into the clinical collection system of the TCM inheritance auxiliary platform software version 2.5 in the form of two-person double entry,and the "Statistical Report" module of the TCM inheritance auxiliary platform is used to analyze the syndrome elements,symptom frequency,drug frequency,and four gas and five flavor distributions,Return distribution,etc.for statistics;apply the "data analysis" module,based on association rules,and use support and confidence as constraints to analyze the frequency and relevance of drug combinations;apply entropy clustering method,take relevance and penalty as Constraint,get a new prescription drug combination,and extract the core prescription.Result1 General information:A total of 107 uveitis patients and 255 prescriptions were screened out in this study.There were 43 males and 64 females,male:female=1:1.49,and the average age was 41.02 years.In the 107 patients of uveitis,the number of anterior uveitis,generalized uveitis,posterior uveitis,Intermediate uveitis is 47,47,9 and 4.2 Syndrome elements:A total of 4 disease elements and 9 disease elements were extracted.The main disease location elements are liver,followed by kidney,spleen,and heart;the disease elements are positive,including fire/heat,damp-heat,wind-heat,rheumatism,phlegm and blood stasis,and collateral obstruction,of which fire/heat is the main one;it belongs to deficiency The pathogenic factors of the syndrome include yin deficiency,qi deficiency,and yang deficiency,among which yin deficiency is the main one..3 Frequency of Chinese medicine:225 prescriptions involved 160 Chinesemedicines,and used 3540 times.The top 10 were Angelica,Atractylodes,Lily,Licorice,Honeysuckle,Scrophulariaceae,Poria,Astragalus,Xu Changqing,Chuanxiong.There are 27 flavors of drugs used more than 36 times.4 Nature and flavor return to meridian:the frequency of the four qi of drugs from high to low:cold,warm,calm,cold,hot;In the distribution frequency of five flavors of medicine:sweet,bitter,and pungent are the highest;In the distribution frequency of the meridian of the drug:lung,heart,liver,and spleen are the highest,followed by stomach and kidney.5 Analysis of drug combination:Taking the number of support degrees as 92,a total of 64 commonly used drug combinations were obtained,including 10 drugs including Angelica,Atractylodes,Lily,Licorice,Honeysuckle,Scrophulariaceae,Poria,Astragalus,Xu Changqing,Chuanxiong.Set the confidence level to 0.95,and perform association rule analysis on the drug combination.The number of drug combination with the highest confidence are 20;the correlation coefficient is 5,the penalty coefficient is 2,and the entropy clustering method is applied to the new prescription According to the analysis,3 core drug combinations of the new prescription and 3 new prescriptions were obtained.Extract the core prescriptions of Professor Zhou Wanyu for the treatment of uveitis,named Simiao Yongan Decoction:Honeysuckle,Scrophulariaceae,Angelica,Licorice.Conclusion based on the Collateral Disease Theory,wet,fire and blood stasis is the basic pathological factors,dampness,fire,and stasis long accumulate poison and the stasis of eye Collateral is uveitis pathological process of the disease,eye Collateral impaired by toxin is the core and pathogenesis.Professor Zhou Wanyu’s treatment of uveitis is based on the basic principles of invigorating qi,activating blood,detoxifying and dredging collaterals,and using Simiao Yongan Decoction as the core prescription;On the basis of following the principle of"Tongluo for use",put forward the idea that "Tongluo" should put qi and blood first,and pay attention to the method of cultivating righteous qi and nourishing the heart and calming the nerves;The characteristics of medication can be summarized as:Xin Kai Kujiang,Xin Wen Tongluo and cold temperature combined use,pay attention to the rigor of compatibility,good use of right medicine and corner medicine.Study 2 Mechanism study Predictive study on the mechanism of action of core prescriptions in the treatment of uveitisObjective Use the method of network pharmacology to study the effective ingredients,main targets and pathways of the Simiao Yongan Decoction,and predict the mechanism of action of Simiao Yongan Decoction in the treatment of uveitisMethods Use the TCMSP database to retrieve all the chemical components of"Honeysuckle,Scrophulariaceae,Angelica,and Licorice" in the core recipe of Si Miao Yongan Decoction,and use the oral bioavailability and drug-like properties as the screening threshold criteria for the retrieved chemical components to establish Si Miao Yong An Tang’s drug-compound-target protein database.Download the human-source target protein gene database in the UniProtKB area of the Uniprot database,and standardize the screened target proteins to establish a drug-compound-gene target database of Simiao Yongan Decoction.Search in the GeneCards,OMIM and CTD databases with the English name of"Uveitis" as the key word,merge the search results,and screen the Uveitis-related targets.Take the intersection of the drug action target and the disease target,import the above-obtained intersection target into the STRING database,set the protein type to "Homo sapiens",and keep the other parameters as default,construct the PPI network diagram,and import the Cytoscape 3.7.1 software,Further use its "Network Analysis" function to analyze network topology attributes.According to the two important network topology parameters of node degree value distribution and node compactness,the PPI network is constructed again,and the target that both are above the average value at the same time is selected as the core target of Simiao Yongan Decoction in the treatment of uveitis.Use Metascape database to conduct online enrichment analysis of molecular function,biological process,cell composition and KEGG pathway enrichment analysis of core targets.Result1 Pharmaceutical active ingredients and related targets:23 kinds of main active ingredients of honeysuckle were extracted,with 225 target points;9 kinds of main active ingredients of scrophulariaceae,with 49 target points;2 kinds of main active ingredients from angelica,with 53 target points;92 main active components of licorice,129 target points.There are 5 active ingredients repeated in 4 traditional Chinese medicines,and there are a total of 121 active ingredients after deduplication.2 Obtain disease-related targets:acquire 21565 related targets from the CTD database,99 related targets from the OMIM data,and 1057 related targets from the GeneCard database.Combining the search results to remove duplicates,and using Inference Score≧14.59 as the screening criteria,646 Uveitis disease-related targets were obtained.3 Extract the core target:take the intersection of the active ingredient target of the drug and the target of the uveitis disease to obtain 105 common targets,import them into the STRING platform,obtain the protein interaction PPI network,and import the PPI network into the Cytoscape software.Extract 53 core targets based on the median of network topology parameters.4 Gene ontology analysis and pathway enrichment analysis:Use Metascape platform to perform KEGG signal pathway enrichment analysis and GO enrichment analysis on the core target of the core prescription for the treatment of uveitis.The parameters are set to default,and KEGG pathway 137 is obtained.the number of GO-BP biological processes is 1633,the number of GO-CC Cellular Components is 31,the number of GO-MF molecular functions is 85.Conclusion According to the results of network pharmacology,it is predicted that AKT1,TP53,MAPK3,VEGFA,TNF are the main targets of core prescriptions for the treatment of uveitis;Quercetin,Kaempferol,Luteolin as the main components;Hepatitis B,TNF signaling pathway,IL-17 signaling pathway,Toxoplasmosis,Toll-like receptor signaling pathway,Th17 cell differentiation,Influenza A,HIF-1 signaling pathway,Pertussis,Tuberculosis,Apoptosis,PI3K-Akt signaling pathway,NOD-like receptor signaling pathway may be the main pathway for the core prescription to treat uveitis.It is suggested that the multi-components of the core formula can treat uveitis by acting on multi-pathway and multi-target integrated regulation.