| Part 1:Retrospective study of Shugan Jianpi Huayu Decoction combined with antiviral drugs in the treatment of compensatory hepatitis B cirrhosisObjective:A retrospective study was conducted to evaluate the curative effect of Shugan Jianpi Huayu Decoction combined with antiviral drugs in the treatment of patients with liver stagnation,spleen deficiency and blood stasis syndrome in compensatory hepatitis B cirrhosis.Method:A retrospective analysis was conducted on 207 patients diagnosed with liver depression,spleen deficiency and blood stasis syndrome of hepatitis B cirrhosis in the outpatient department and ward of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2017 to December 2020,including 145 males and 62 females.According to whether the patients received the prescription of Shugan Jianpi Huayu Decoction,they were divided into Integrated traditional Chinese and Western medicine group(95 cases)and Western medicine group(112 cases).The compensatory stage of hepatitis B cirrhosis was used as the observation starting point,the time of decompensation stage or liver cancer was used as the observation end point,and the patients without endpoint events were used as the observation end point on December 31,2021 to collect clinical data before and after treatment.The changes of liver stiffness measurement(LSM),portal vein trunk width and liver function were compared between the two groups before and after treatment,and the decompensation,the incidence of liver cancer and prognostic factors were analyzed,so as to retrospectively study the curative effect of Shugan Jianpi Huayu formula combined with antiviral drugs.Results:1.Comparison of inspection results: Intra-group comparison: after Integrated traditional Chinese and Western medicine treatment,LSM value,portal vein trunk width,spleen size,liver function indexes ALT,AST,GGT and TBIL decreased,ALB increased,HBV-DNA negative rate increased,and the differences were statistically significant(P < 0.05).After Western medicine treatment,LSM value and spleen size decreased,ALT,AST and GGT of liver function indexes decreased,HBV-DNA negative conversion rate increased,and the differences were statistically significant(P< 0.05).TBIL and ALB of liver function indexes in the Western medicine group did not improve significantly compared with before treatment.There was no significant improvement in portal vein trunk width compared with before treatment,and the differences were not statistically significant(P > 0.05).Comparison between groups:after treatment,the improvement degree of LSM value and portal vein trunk width in the Integrated Chinese and Western medicine group was better than that in the Western medicine group(P < 0.05).After treatment,there was no significant difference in AST,ALB and TBIL between the two groups(P > 0.05),and the improvement degree of ALT and GGT in the Integrated Chinese and Western medicine group was better than that in the Western medicine group(P < 0.05).After treatment,there was no significant difference in HBV-DNA negative rate between the two groups(P > 0.05).2.Changes in non-invasive detection model of cirrhosis: Intra-group comparison:the APRI and GPR of non-invasive diagnostic model of cirrhosis in the Integrated Chinese and Western medicine group decreased after treatment compared with before treatment,and the differences were statistically significant(P < 0.05),while FIB-4had no significant difference(P > 0.05).There was no statistical difference between non-invasive diagnostic model after treatment and before treatment in Western medicine group(P > 0.05).Comparison between groups: after treatment,the improvement of APRI and GPR of non-invasive diagnostic model of cirrhosis in the Integrated Chinese and Western medicine group was better than that in the Western medicine group,and the differences were statistically significant(P < 0.05),while there was no statistical difference in FIB-4 between the two groups(P > 0.05).3.Occurrence of end point events: There were 3 patients in the Integrated Chinese and Western medicine group entered the decompensation stage,and 12 patients in the Western medicine group entered the decompensation stage.There was statistical significance in the incidence of decompensation between the two groups(P< 0.05).There were 1 patient in the Integrated Chinese and Western medicine group and 8 patients in the Western medicine group developed liver cancer.The comparison between the two groups of patients with liver cancer was statistically significant(P <0.05).The cumulative incidence of decompensation and liver cancer in the Integrated Chinese and Western medicine group was lower than that in the Western medicine group.There were statistical differences between logrank test and Breslow test(P <0.05).4.Cox multivariate analysis: the risk factor of decompensation was drinking history(HR=7.962,95%CI:1.574-40.27,P=0.012),and the protective factor was the treatment of Shugan Jianpi Huayu Decoction(HR=0.172,95%CI:0.037-0.797,P=0.024).The risk factors of liver cancer were family history of liver cancer(HR=71.285,95%CI:0.001-71.285,P=0.001),AFP(HR=1.042,95%CI:0.024-1.042,P=0.024).Shugan Jianpi Huayu Decoction(HR=0.082,95%CI:0.07-0.082)may be a protective factor for hepatocarcinogenesis,but there was no significant difference(P=0.07).Conclusion:Shugan Jianpi Huayu Decoction Combined with antiviral drugs can improve LSM value,portal vein trunk width,liver function(ALT,GGT)and the level of APRI and GPR in the non-invasive diagnosis model of liver cirrhosis,and r educe the incidence of decompensation and liver cancer.The curative effect of the Integrated Chinese and Western medicine group was better than that of Wes tern medicine group.Part 2:Discussion on the mechanism of Shugan Jianpi Huayu Decoction in the treatment of compensatory hepatitis B cirrhosis based on network pharmacology and molecular dockingObjective:To further explore the possible active ingredients and mechanism of Shugan Jianpi Huayu Decoction in the treatment of compensatory hepatitis B cirrhosis based on network pharmacology.Method:The active ingredients and action targets of Shugan Jianpi Huayu Decoction were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID).Gene Cards database was used to search for compensatory hepatitis B cirrhosis related targets.The targets of disease were obtained by intersection of drug active ingredients,and the drug-component-target network was constructed by Cytoscape software,and the key active ingredients were screened according to degree value.The interaction network of target proteins was constructed through STRING online database,and the core targets were screened according to Count value.R software was used to perform GO function analysis and KEGG pathway analysis for common targets,and Auto Dock Tools was used to verify the analysis results.Results:1.A total of 149 active ingredients of core prescription drugs were obtained,and204 intersection targets were screened,of which 105 were corresponding to the intersection targets,and 5 core active ingredients were screened,namely Quercetin,Kaempferol,β-Sitosterol,Naringenin,Luteolin.2.Through PPI network analysis,five core targets were screened,including AKT1,TNF,IL6,TP53 and VEGFA.3.Go enrichment analysis showed that the intersection targets mainly involved 172 molecular functions,such as DNA binding transcription activation activity,RNA polymerase II specificity,receptor ligand activity,cytokine receptor binding,cytokine activity,etc.The enrichment results of KEGG pathway showed that the intersection targets were significantly enriched in 187 signal pathways such as hepatitis B signal pathway,PI3K-Akt signal pathway and TNF signal pathway.4.Molecular docking results show that β-Sitosterol and AKT1,β-Sitosterol and P53,Naringenin and P53,Luteolin and P53 were the best four combinations,and the combinations were good.Conclusion:Shugan Jianpi Huayu Decoction may act on AKT1,TNF,IL6,TP53,VEGFA and other targets by regulating hepatitis B pathway,PI3K-Akt signal pathway,TNF signal pathway and other pathways,so as to play a role in the treatment of compensated hepatitis B cirrhosis. |
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