Clinical Observation On The Improvements Of Liver Regeneration Microenvironment In The Treatment Of Advanced Liver Cancer With The Method Of "Tonifying The Kidney To Promote Liver Regeneration And Repair By Effecting Stem Cells And Their Microenvironment"

Objective:Objective To observe the clinical efficacy of "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment" method in the treatment of advanced liver cancer by randomized controlled clinical trial(RCT),and explore its mechanism of improving liver regeneration microenvironment of liver cancer,so as to provide high-level evidence-based medicine for clinical application.Methods:1.A total of 126 patients with advanced liver cancer who were admitted to the Department of Liver Diseases of Shaanxi Provincial Hospital of Traditional Chinese Medicine from January 2017 to June 2020 were randomly divided into three groups based on random number table.42 cases in the western medicine control group(hereinafter referred to as the Western medicine group)were treated with western medicine comprehensive treatment,42 cases in“tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment” single treatment group(hereinafter referred to as TCM group)were treated with Diwu Yanggan decoction,Kangdu Ruanjian Decoction and Zuogui Pill,treatment plan of syndromedifferentiation;42 cases in the comprehensive treatment group(hereinafter referred to as the traditional Chinese medicine and Western medicine group)were treated with Diwu Yanggan reci Pe,Kangdu Ruanjian recipe and Zuogui Pill on the basis of the western medicine treatment group.after selection,there were 10 patients falling of(6 cases in TCM group,3 cases falling of due to loss of follow-up,3 cases falling of due to failure to insist on treatment;4cases in Western medicine group,2 cases falling of due to inconvenience of remote medical treatment,2 cases falling of due to failure to insist on treatment).Finally,116 cases were included in the statistical analysis of case data,including 38 cases in Western medicine control group(Western medicine group),42 cases in “tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment” comprehensive treatment group(the traditional Chinese medicine and Western medicine group);36 cases in“tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment”single treatment group(TCM group).The study passed the ethical review of the Hubei provincial Hospital of Traditional Chinese Medicine,and completed the clinical trial registration at the China Clinical Trial Registration Center(the first-level registration body of the World Health Organization International Clinical Trial platform),registration number: Chi CTR-IOR-17011439.All patients participating in the study voluntarily signed an informed consent form.Compare the survival rate and survival time of the three groups at 3 months and 6 months after treatment;compare the blood routine,fecal routine plus occult blood,liver function,blood sugar,blood lipid,kidney function and other indicators 3 months after treatment,and compare the three groups of treatment TCM syndrome scores and quality of life scores around 3 months,and independent Factors affecting patient survival were analyzed.2.According to the different treatment schemes:Chinese medicine group,western medicine group,Chinese and western group,20 subjects in each group.Three months after the start of treatment,a total of 60 sera from each group were collected,and 18 sera from the normal population were collected.The suspension chip system is used to detect the serum liver regeneration-related cytokines Granulocyte Colony Factor(G-CSF),Hepatocyte Growth Factor(HGF),Interferon-γ(IFN-γ),interleukin-6/8/18(Interleukin-6,IL-6,Interleukin-8,IL-8,Interleukin-18,IL-18),Platelet Derived Growth Factor(,PDGF-BB),Stem Cell Factor(SCF),and Tumor Nnecrosis Factor-α(TNF-α)content,and observe the effects of traditional Chinese medicines that embody "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment" on these cytokines.Results:(1)Comparison of the survival rate and survival period of the three groups of patients before and after treatment:after 3 months and 6 months of treatment,there were significant differencess in survival rates among the traditional Chinese and western medicine group(TCM and WM groups)and the traditional Chinese medicine group(TCM groups)and the western medicine group(WM groups)(88.10% vs 72.22% vs 52.63%),(71.43% vs 58.33% vs34.21%)(P < 0.05).after treatment,there was a significant differencess in the survival time among the three groups(23.861 ± 17.55VS20.08 ±19.86VS15.95 ± 16.44)(P < 0.05).(2)The tumor size of the three groups of patients before and after treatment:There was no statistically significant differences in the Comparison between the TCM and WM groups,TCM group and WM group as well as in the measurement time before and after treatment(P > 0.05).(3)Comparison of liver function indexes of three groups before and after treatment:after treatment,the levels of direct bilirubin,indirect bilirubin,alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase in the Chinese and Western medicine group were significantly lower than those before treatment(P < 0.05),and there was no significant differences between the two groups(P > 0.05).The level of cholinesterase in TCM group after treatment was significantly higher than that before treatment,and there was no significant differences between the two groups(P > 0.05).The albumin levels of the three groups before and after treatment were statistically significant(P < 0.05);There was significant differences between the two groups(P < 0.05).(4)The white blood cell level of the three groups of patients after treatment:after treatment,the levels of white blood cells,neutrophil /lymphocyte ratio and platelet in the three groups were significantly different(P < 0.05).after treatment,the creatinine levels of the three groups were significantly higher than that of the western medicine group,the traditional Chinese medicine group and the western medicine group(P < 0.05).(5)The intra-subject differencess in the TCM syndrome scores of the three groups of patients before and after treatment:Before and after treatment,the intra subject differences of TCM syndrome score based on time Factor and inter subject effect based on group were statistically significant(P < 0.05).The TCM syndrome scores of the three groups after treatment were significantly lower than those before treatment,and the differences was statistically significant(P < 0.05).after treatment,the scores of TCM syndrome in TCM group and WM group were significantly lower than those in WM group(P < 0.05).(6)Comparison of the scores of the three groups of patients before and after treatment:The scores of patients physiological function of the three groups after treatment were significantly higher than those before treatment,with statistical significance(P < 0.05).after treatment,there were significantdifferencess in the scores of social function between the western medicine group,the traditional Chinese medicine group and the western medicine group(P < 0.05).Three groups of patients in the physiological function,physical pain,general health of the three dimensions of the score between groups,there was statistical significance(P < 0.05),and after two groups of Comparison,western medicine group and traditional Chinese medicine group,western medicine group of physiological function,physical pain,general health of the three dimensions of the score between groups,the differences was statistically significant(P<0.05).(7)The expression level of HGF The differences was statistically significant(2255.17 vs 1097.76 vs 1072.39 vs 882.67)(P < 0.05).It is suggested that the over expression of HGF can be inhibited to a certain extent by "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment" alone or combined with western medicine.(8)The expression levels of IL-6 The differences was statistically significant(5638.03 vs 5166.45 vs 12842.5 vs 24559.34)(P < 0.05).The expression level of IL-6 in TCM group and TCM group was significantly lower than that in normal group(P < 0.05).It is suggested that the over expression of IL-6 can be inhibited to a certain extent by "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment" alone or combined with western medicine.(9)The expression of IL-18 There was no significant differences among Western medicine group,western medicine group and traditional Chinese medicine group(120.345 vs 82.61 vs 78.58)(P > 0.05),but they were higher than normal group(75.165).It is suggested that the expression of IL-18 can also be promoted by "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment" alone or combinedwith western medicine.(10)The expression level of PDGF-BB The differences was not statistically significant(4677.18vs6140.6vs5534.885)(P > 0.05).But the TCM group was lower than the western medicine group and the western medicine group,and closer to the normal group(4401.67).It is suggested that "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment" can inhibit the overexpression of PDGF-BB.(11)The expression level of TNF-α There were significant differencess among Western medicine group,traditional Chinese medicine group,traditional Chinese medicine group and normal group(735.955vs244.93vs573.46vs1037.25)(P < 0.05).TNF-α in TCM and WM group-α The expression level was significantly lower than that of the normal group(P < 0.05).It is suggested that "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironmen" alone can better inhibit the over expression of TNF-α.Consequence:The treatment of advanced liver cancer with "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironmen" can significantly improve the survival rate and survival time of patients with advanced liver cancer at 3 months and 6 months,and improve the clinical symptoms of patients with advanced liver cancer.At the same time,it can improve the various biochemical indexes.It can significantly reduce the TCM syndrome scores of patients with advanced liver cancer and improve the quality of life of patients.One of the curative effects of "tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironmen" in the treatment of patients with advanced liver cancer may be through inhibiting the overexpression of HGF,PDGF-BB,TNF-a andIL-6 in patients with advanced liver cancer,while increasing the level of IL-18 in patients with advanced liver cancer.expression to improve the liver regeneration microenvironment of liver cancer and its related inflammatory microenvironment,immune microenvironment,angiogenesis microenvironment,etc.