Study On Prescription Rules And Mechanism Of Traditional Chinese Medicine Against Primary Hepatic Carcinoma Based On Data Mining

ObjectiveTo systematically evaluate the clinical efficacy of traditional Chinese medicine(TCM)in the treatment of primary hepatic carcinoma(PHC)by using the method of evidence-based medicine.Data mining method is used to mine and analyze the medication rules of traditional Chinese medicine prescription in the treatment of PHC in the real world,so as to provide some reference for the treatment of PHC in TCM.The potential mechanism of key drug combination of TCM for PHC was analyzed by network pharmacology.Methods(1)Meta analysis methodDeveloping relevant retrieval strategies.This paper searched CNKI,CBM,VIP,Wanfang,Pub Med and Web of Science databases for clinical literatures related to randomized controlled trials of oral Chinese medicine combined with TACE and TACE alone in the treatment of PHC,extracted the data from the literatures,and made a meta-analysis of the data by revman5.3 software.(2)Data mining analysis methodsIn Nanchang,the provincial capital city of Jiangxi Province,this paper collected the Clinical Prescriptions of TCM in the treatment of PHC from some Class 3A Hospitals.Based on the traditional Chinese Medicine Inheritance platform,this paper conducted data mining on the high-frequency drugs,Four Properties,Five Tastes,Channel Distribution,associated drugs and core drug combinations in the prescriptions to analyze the medication rules of TCM in the treatment of PHC.(3)Network Pharmacology MethodFor the core drug combinations obtained from data mining,The traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)was used to retrieve the compounds and their corresponding targets of related TCM.Searching protein targets related to PHC by the Comparative Toxicogenomics Database(CTD),Mala Cards and other disease databases.The intersection of the two targets is the potential target of the core drug combination in the treatment of PHC.The protein-protein interaction(PPI)of the potential targets is analyzed by using Cytoscape 3.6.1 software and string online analysis platform,the core targets was further obtained.Through Discovery Studio 4.5 software,the core targets and active ingredients were docking.Finally,the GO biological function and KEGG metabolic pathway of potential targets were analyzed by David online analysis platform.Results(1)Through the evidence-based medicine method,the oral Chinese medicine combined with TACE was compared with TACE alone in the treatment of PHC.A total of 75 studies were included,including 7406 patients,including 3929 cases in the treatment group and 3477cases in the control group.The results of meta-analysis showed that the combination of traditional Chinese medicine in the treatment of PHC had significant advantages in the improvement of short-term curative effect,the decrease of tumor marker AFP,the improvement of liver function,the improvement of immune function,the improvement rate of TCM syndrome,the improvement rate of Karnofsky score,the improvement of survival rate and the reduction of adverse reactions(P<0.01).In addition,in the indicators of survival rate,there was no statistical significance in the 3-month survival rate,but there were significant differences in the rest(P<0.01),suggesting that TCM combined with TACE therapy can improve the long-term survival rate of patients.Sensitivity analysis results show that the results of this study are reliable and have reference value.And in the sensitivity analysis of CD8~+in immune function,the results of meta-analysis showed significant changes,suggesting that whether the combined treatment of TCM can improve the level of CD8~+still need higher quality clinical evidence.Publication bias showed that the results were symmetrical,indicating that the bias was not obvious,but there was a small sample effect.(2)Data mining methods was used to analyze the medication rule of TCM prescription in the treatment of PHC.904 TCM prescriptions were obtained from the clinical real world,involving 10 syndrome types,such as phlegm and blood stasis,positive deficiency and blood stasis,liver stagnation and spleen deficiency.The results showed that the drugs commonly used in clinical treatment of PHC were tonifying deficiency drugs,diuretic and dampness drugs,heat clearing drugs,blood activating and stasis removing drugs,Qi regulating drugs,phlegm resolving drugs and so on;the four Qi drugs were mostly cold,warm and flat,the five flavors were mostly sweet,bitter and pungent,and the meridian tropism was mainly spleen,liver,stomach,lung,heart and kidney.Atractylodes macrocephala,Codonopsis pilosula,Poria cocos,licorice,Pinellia ternata,Pericarpium Citri Reticulatae,bupleurum,Paeoniae Alba,Scutellaria barbata,Hedyotis diffusa and other drugs are in the core position,and often appear in combination with a variety of drugs.And Atractylodes macrocephala,Codonopsis pilosula,Poria cocos and Glycyrrhiza uralensis are the most common drugs,which is related to the weakness of healthy qi in PHC patients.Therefore,to strengthen Qi and spleen by Sijunzi decoction.(3)Through the method of network pharmacology,the mechanism of action of the core drug combination(hereinafter referred to as SJZB2,including Codonopsis pilosula,Poria cocos,Atractylodes macrocephala,Glycyrrhiza uralensis,Scutellaria barbata,Hedyotis diffusa)obtained from data mining was analyzed.(1)Quercetin,luteolin,apigenin,ursolic acid,wogonin and kaempferol were the main components of SJZB2;(2)18 key targets including TP53,AKT1,VEGFA and MMP9 were obtained;(3)Quercetin,luteolin,apigenin and other compounds were docking with the key targets.The docking results showed that there was a good affinity between ligand and receptor,and most of the docking compounds had anti-cancer activity,which had a certain reference value;(4)Go analysis revealed 124biological processes including negative regulation of apoptotic cells,negative regulation of cell proliferation,angiogenesis and liver regeneration,24 cell components including cytoplasm,nucleoplasm,extracellular space and mitochondria,and 46 molecular functions including enzyme binding,protein binding,homologous protein binding and transcription factor binding;(5)There are 91 KEGG signaling pathways,including cancer pathway,hepatitis B,pancreatic cancer,non-small cell lung cancer,prostate cancer,melanoma,chronic myeloid leukemia,bladder cancer,glioma,small cell lung cancer,VEGF signaling pathway,p53 signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,Toll-like receptor signaling pathway,etc.Conclusions(1)TCM combined with TACE in the treatment of PHC has more significant therapeutic effect,with the effect of increasing efficiency and reducing toxicity,prolonging the survival period of patients and improving the quality of life of patients,which fully shows that TCM has potential research and application value in the treatment of PHC.(2)The results of data mining show that the clinical treatment of PHC mainly adopts the methods of invigorating the spleen and replenishing qi,soothing the liver and regulating qi,promoting blood circulation and removing blood stasis,which is in line with the doctor’s medication rule of"strengthening the body and removing pathogenic factors,attacking and tonifying simultaneously".(3)SJZB2 mainly treated PHC by inducing apoptosis,blocking cycle,antiangiogenesis,regulating inflammation and other complex biological processes and signaling pathways,and there are complex interaction relationship between them,which coincides with the holistic view of TCM in the treatment of diseases,and the p53 signaling pathway and VEGF signaling pathway have been verified by the experimental results of relevant literatures,which provides scientific reference for the follow-up researches.