Study On The Mechanism Of Traditional Chinese Medicine Treatment Of Colorectal Cancer Based On Evidence And Data Mining

Objective:Based on evidence-based medicine,the clinical efficacy of traditional Chinese medicine(TCM)combined with FOLFOX in the treatment of Colorectal Cancer(CRC)is meta-analyzed.The data mining research method was used to explore and analyze the medication rules of TCM treatment of CRC in real world,and the core TCM group was obtained,providing effective reference value for the research of TCM treatment of CRC.The potential mechanism of action of the core Chinese medicine group in the treatment of CRC was analyzed using the network pharmacological research method.Method:(1)Meta analysis methodFormulate relevant search formulas according to the research objectives,the relevant retrieval strategies were developed in China National Knowledge Network(CNKI),Chinese Biomedical Literature(CBM),Web of Science,Cochrane Library databases etc.TCM with FOLFOX chemotherapy regimen(oxaliplatin,calcium folinate and fluorouracil)in the treatment of CRC was the combined group,CRC was treated with FOLFOX alone as the control group in the Randomized controlled trial(RCT)related clinical research literature,Exclude the literature that does not meet the requirements,extract the corresponding data in the literature,R 4.2.2 and R studio software were used for Meta analysis of the data.(2)Data mining analysis methodsClinical prescriptions of TCM for CRC were collected from a number of tertiary grade A hospitals in Jiangxi Province.High frequency drug flavor normalization,association rules,drug dosage,drug clustering and complex network analysis were used to mine and analyze the collected prescriptions by R 4.2.2,R Studio and Excel2019.To study the medication rule of TCM compound for CRC and analyze the core TCM combination.(3)Network Pharmacology Method and Molecular dockingThe core TCM combination for CRC treatment was obtained through data mining,The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature were used to search and select the core TCM active compounds and their corresponding targets,and the target gene names were obtained by gene annotation in Uni Prot database.In Gene Cards,0nline Mendelian Inheritance in Man(OMIM)and Dis Ge NET databases were used to search and screen CRC disease targets.The software R 4.2.2 and R Studio were used to conduct Wayne analysis on the target data sets of TCM and diseases,and obtain the common targets of TCM and diseases.The target data set was uploaded to Cytoscape3.7.2,and the network diagram of "TCM Compound-disease intersection target" was constructed.Then,the intersection target genes were imported into STRING database to construct PPI network,and the core targets were screened out.Genetic ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed using R 4.2.2 and R Studio software.Finally,Auto Dock Tools 1.5.6 software was used for molecular docking of important active compounds and key targets.Result:(1)Evidence-based medicine method study on the treatment of CRC by TCM combined with FOLFOX versus FOLFOX alone,A total of 71 clinical studies were included,including 5696 patients,2885 patients in the combination group and 2811 patients in the control group.The results of meta-analysis showed that TCM combined with FOLFOX was superior to FOLFOX alone in improving the short-term clinical efficacy,Castigna score,T lymphocyte factor level,reducing adverse reactions in all aspects,and reducing TCM syndrome score and tumor marker score(P < 0.05).(2)The data mining method was used to explore the medication rules and core TCM in the treatment of CRC with clinical prescriptions in real world.A total of 461 effective prescriptions in the real world were obtained from the clinical study,involving 367 TCM.The frequency of drug use in descending order was Codonopsis,White atractylodes rhizome,Glycyrrhiza,Poria cocos,Coix Seed,Tangerine peel,Angelica,Fructus amomi,Yam,Hedyotis willd and Astragalus.It was found that the main TCM for CRC were deficiency tonifying drugs,heat clearing drugs,water and moisture clearing drugs.According to the statistics,the properties of sexual taste were mainly Pingping and warming,the medicinal taste were mainly sweet,bitter and xin,and the spleen,lung and stomach channels were mainly.The analysis of association rules shows that [White atractylodes rhizome-Codonopsis],[Poria cocos,White atractylodes rhizome-Codonopsis],[Poria cocos,Glycyrrhiza,White atractylodes rhizome-Codonopsis],[Glycyrrhiza,White atractylodes rhizome,Codonopsis-Poria cocos],[Yam,Poria cocos,White atractylodes rhizome,Codonopsis-Glycyrrhiza],[Yam,Poria cocos,White atractylodes rhizome,Codonopsis-Tangerine peel],[Yam,Poria cocos,Glycyrrhiza,White atractylodes rhizome,Codonopsis-Tangerine peel],were the highest support combination in the same group,respectively.The complex network analysis showed that Codonopsis,glycyrrhiza,White atractylodes rhizome,Poria cocos,Coix Seed,Hedyotis willd,Angelica,Tangerine peel,Pinellia,Sand kernel,Yam,Astragalus and White peony root were the core TCM.Based on the above research results,The core TCM combination is Codonopsis,White atractylodes rhizome,Poria cocos,Tangerine peel,Yam.(3)The network pharmacology method was used to mine the active compounds and study the mechanism of action in the core TCM combination obtained from data mining.Results 49 effective compounds and 161 targets were obtained.The main effective components of core TCM combination are luteolin,apigenin,nobiletin,tectorigenin,naringenin.Important targets were TP53,EGFR,CASP3,TNF,AKT1,MAPK3,PTGS2,JUN,MMP9,IL6,HIF1 A,VEGFA,CCND1 and FOS.GO enrichment analysis showed that it may be related to cell response to UV,oxidative stress,transcription regulatory complex,protein kinase complex,RNA polymerase Ⅱspecific DNA-binding transcription factor binding,and ligand-activated transcription factor activity.KEGG pathway enrichment analysis showed that the key enrichment pathways were PI3K/Akt signaling pathway,IL-17 signaling pathway,apoptosis,HIF-1 signaling pathway,TNF signaling pathway,etc.The results of molecular docking showed that the docking energies of 14 targets and 5 active compounds were all less than-5k J/mol,indicating that the docking was good.Conclusion:(1)Meta-analysis showed that TCM combined with FOLFOX in the treatment of CRC could significantly improve the clinical efficacy of CRC patients and reduce adverse reactions in all aspects,indicating that Chinese medicine in the treatment of CRC has an obvious effect of attenuating toxicity and enhancing efficacy.(2)The data mining study showed that the real world TCM prescriptions for CRC were mainly sweet,bitter and occult in taste,flat and warm in nature,deficiency supplementing and heat clearing.In the early stage of CRC pathogenesis,damp-heat and blood-stasis were the main drugs,while in the late stage,positive deficiency and evil substance were the main drugs,and deficiency supplementing and heat clearing and jiedu powder were the main drugs.In the treatment group,Codonopsis,White atractylodes rhizome,Poria cocos,Tangerine peel,Yam were the core TCM combination.(3)The results of network pharmacology showed that the main chemical components of CRC in the core TCM combination were flavonoids,and CRC was inhibited through PI3K/Akt signaling,IL-17 signaling and other pathways to regulate cell process and cycle,anti-inflammatory response,regulation of gene expression,and anti-angiogenesis.