| Objective: Through a retrospective cohort study,verify the efficacy of Huazheng Sanji Decoction in improving the survival period of patients with liver cancer;Based on TMT proteomics and non-targeted metabolomics techniques,we screened and analyzed the differential proteins and biomarkers in the treatment of liver cancer with TMT alone or in combination with cisplatin,and preliminarily elucidated the mechanism of action of Huazheng Sanji Decoction in the treatment of liver cancer from the perspective of protein and metabolism.Methods:1.Retrospective analysis was conducted on patients with primary liver cancer who were treated with Huazheng Sanji Decoction and/or basic Western medicine from January 1,2014 to December 31,2020 in the Department of Hepatology,Spleen,Gastroenterology,Affiliated Hospital of Changchun University of Traditional Chinese Medicine,and Professor Liu Tiejun’s Studio of the National Medical Hall.The survival period of patients with different treatment methods was analyzed using Kaplan-meier method and Log-Rank test.2.Using TMT proteomics and non-targeted metabolomics techniques,screen and analyze the differential proteins and biomarkers of Huazheng Sanji Decoction and its combination with cisplatin in the treatment of liver cancer,and analyze and explore the mechanism of action of each group in combination with bioinformatics analysis.Results:1.According to the requirements,a total of 216 patients were included,including 137 patients in the treatment group with a median survival time of 207 days,and 79 patients in the control group with a median survival time of 76 days.The cumulative survival rates of the treatment group for six months,one year,and two years were 59.12%,38.69%,and 18.25%,respectively.The cumulative survival rates of the control group for six months,one year,and two years were 35.44%,16.46%,and 7.59%,respectively.After testing,P<0.05,there was a significant difference between the treatment group and the control group.The representative syndrome dispersing and accumulating Decoction combined with basic western medicine treatment can prolong the survival period of patients with liver cancer.2.The survival period of the treatment group in Child-Pugh A,Child-Pugh B,and ChildPugh C grades was better than that of the control group(P<0.05,with statistical significance);The survival period of CNLC stage Ia and Ib patients in the treatment group is better than that in the control group,but there is no statistical difference between the two groups.For stage IIa,IIb,IIIa,IIIb,and IV patients,the treatment group has significant advantages over the control group in terms of survival period and survival rate.3.(1)The proteomic research results showed that the expression of 4-aminobutyrate transaminase,phosphoenolpyruvate carboxykinase 2,glucose-1-phosphate uridyltransferase was up-regulated,and the expression of cyclic adenosine phosphate regulated phosphorylated protein,pigment box homologue 2 and other proteins was down regulated in the Huazheng Sanji Decoction group.(2)The expression of ribonucleoside diphosphate reductase subunit M2 and adenosine triphosphate dependent helicase DDX5 were down regulated when Hua Zheng San Ji Decoction was used in combination with cisplatin.4.Metabonomics research results show that Huazheng San Ji Decoction has the effect of recalling hypoxanthine in liver cancer cells,suggesting that hypoxanthine may be a differential potential biomarker of Hua Zheng San Ji Decoction in the treatment of liver cancer,but this result still needs further research and verification.When combined with cisplatin,the expression of L-histidine and aspartate in the histidine metabolism pathway is downregulated.Conclusion:1.Huazheng Sanji Decoction combined with basic western medicine treatment can significantly prolong the survival period of patients with liver cancer(heat toxin accumulation,liver and kidney yin deficiency syndrome),and its clinical efficacy is superior to single basic western medicine treatment.2.The treatment of liver cancer with Huazheng Sanji Decoction involves "multi-level multi target multi pathway",which can induce liver cancer cell apoptosis,inhibit its invasion,migration.Combined with cisplatin,it can enhance the sensitivity of cells to cisplatin and reduce its resistance.3.Huazheng Sanji Decoction combined with cisplatin may play an anti-tumor role by regulating the abnormal changes of metabolites such as L-amino acid and aspartate,and may play an anti-tumor role through metabolic processes such as ATP-binding cassette transporter,amino acid biosynthesis,purine metabolism,and central carbon metabolism of cancer. |
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