Study On The Correlation Between The Characteristics Of Spleen Deficiency And Intestinal Flora In Colorectal Cancer Based On Different Clinical Stages

This study is mainly divided into two parts:literature review and clinical research.The review part first discusses the pathogenesis of colorectal cancer and the latest research progress in clinical treatment application from the perspective of intestinal microbiota;secondly,the theoretical mechanism of TCM "treatment of colorectal cancer from the spleen" is described from the perspective of intestinal microbiota.Clinical research part:First,analyze the characteristics of spleen-qi deficiency syndrome in patients with colorectal cancer at different clinical stages by using two methods for determining spleen-qi deficiency(Spleen-qi deficiency scale-diagnosis criteria for spleen-qi deficiency);secondly,analyze the characteristics of spleen-qi deficiency in patients with colorectal cancer at different clinical stages;Exploring the correlation between clinical staging,spleen-qi deficiency characteristics,intestinal flora distribution and TB lymphocyte subsets.Clinical research:OBJECTIVE:Analyze and compare the distribution of spleen-qi deficiency in patients with different clinical stages of colorectal cancer through a combination of objective quantitative and qualitative research,and explore the influence of the characteristics of spleen-qi deficiency and related factors from the perspective of intestinal flora and TB lymphocyte subsets.Methods:Adopting prospective clinical observation and research,using convenient sampling method,cross-sectional clinical information and biological samples of 96 patients with colorectal cancer who were treated in Xiyuan Hospital of China Academy of Chinese Medical Sciences,Peking University Cancer Hospital wards and outpatient clinics between March 2018 and December 2020(Stool,peripheral blood)collection.The main observation index is the distribution characteristics of spleen-qi deficiency in patients with colorectal cancer,and the degree of spleen-qi deficiency in the enrolled patients was objectively quantified by using the TCM Spleen Qi Deficiency Scale-Spleen-qi Deficiency Dimensions,Two attending physicians in the Department of Oncology of Traditional Chinese Medicine independently judged whether the enrolled patients were spleen-qi deficiency according to the "Guiding Principles of Clinical Research on the Treatment of Spleen-qi Deficiency Syndrome with New Chinese Medicines"and gathered unified opinions.Other clinical information includes the patient's disease characteristics(primary tumor site,clinical stage,pathological type,genetic testing type,etc.)and personal information characteristics(gender,age,weight,height,etc.).Exploratory indicators include the diversity of the patient's intestinal flora and peripheral blood TB lymphocyte subpopulations,which were detected by 16srRNA and flow cytometry techniques.The SPSS26.0 statistical software was used to test the consistency of the two methods for determining spleen-qi deficiency,and to test the difference in the degree and distribution of spleen-qi deficiency in patients with colorectal cancer at different clinical stages,and to conduct multivariate analysis of clinical information related to spleen-qi deficiency.At the same time,the biodiversity analysis of the intestinal flora was carried out on different clinical stages and patients with spleen qi deficiency and non-spleen qi deficiency through the health information analysis platform(http://cloud.majorbio.com).The group is used as an environmental factor to analyze the correlation between flora species and samples.Result:1.Comparison of the consistency of the two diagnostic methods of spleen-qi deficiencyThe Traditional Chinese Medicine Spleen Qi Deficiency Scale(TCM-SDS-5)is consistent with the traditional diagnostic criteria for spleen-qi deficiency in the diagnosis of patients with colorectal cancer with spleen-qi deficiency(Cohen's kappa=0.116 P=0.264);2.Analysis of Spleen Qi Deficiency Syndrome in TCM Patients with Colorectal Cancer with Different Clinical Features2.1 Characteristics of spleen qi deficiency in different clinical stagesIn the results of the TCM Spleen Qi Deficiency Scale(TCM-SDS-5),there was no significant difference in spleen qi deficiency scores between patients with stage ? colorectal cancer and those with stage ?-? and stage ?(H=5.14 P=0.076);TNM staging and There is a positive correlation between the scores of spleen qi deficiency(Kendall's tau-b=0.192,P=0.022);compared with early and mid-stage patients(stage ?-?),patients with advanced colorectal cancer(stage ?)have higher scores of spleen qi deficiency and The difference was statistically significant(4.11±1.39 vs.3.73±1.97,P=0.032<0.05);Logistic regression analysis showed that after controlling for tumor primary site,age group and genetic status factors,clinical staging(late,early and mid-term)had independent influence factors on TCM-SDS-5 spleen-qi deficiency grouping(B=3.734,P=0.015);In the results of the traditional diagnostic criteria for spleen-qi deficiency,the spleen-qi deficiency group and the non-spleen-qi deficiency group were in TNM staging,early and mid-term(?-?)There was no statistically significant difference between stage)and late stage(stage ?)(P>0.05).2.2 Spleen Qi Deficiency Syndrome and TB Lymphocyte SubgroupIn the results of the TCM Spleen Qi Deficiency Scale(TCM-SDS-5),the difference in the absolute value of HLA cells between the spleen qi deficiency group and the non-spleen qi deficiency group was statistically significant(45.5,IQR 50.8 vs.28 IQR 52,U=208 P=0.049 In the results of the traditional diagnostic criteria for spleen-qi deficiency,the absolute value of DNT cells in the spleen-qi deficiency group was higher than that in the non-spleen-qi deficiency group,and the difference was statistically significant(58.8,IQR 125 vs.39.5,IQR 31,U=173.50 P=0.030).3.Clinical staging and intestinal floraThere is a statistically significant difference in the distribution of sob's index between patients with advanced colorectal cancer(stage ?)and early-stage colorectal cancer(stage I-?)(412.06±168.45 vs.304.92±149.6,P=0.0035);different TNMs There are significant differences in bacterial communities in patients with staged colorectal cancer(R=0.1925,P=0.002);there are significant differences in bacterial communities in patients with early and mid-stage colorectal cancer(stage ?-?)and patients with advanced colorectal cancer(stage IV)(R=0.1791,P=0.001);Faecalibacterium,Lachnoclostridium,Roseburia,and unclassified f_Lachnospiraceae have statistically significant differences among colorectal patients with stage ?-?,stage ? and ?(P<0.001,P<0.05);The abundance of Faecalibacterium,Alistipes,and Phascolarctobacterium in the mid-stage patient sample group(stage ?-?)was significantly lower than that in the late-stage group and the difference was statistically significant(P<0.05),while the early and mid-stage patient sample group(stage ?-?)had Bacteroides abundance The degree was significantly higher than that of the late group and the difference was statistically significant(P<0.05).4.Intestinal flora and environmental factors in different clinical stagesThe scores of the Spleen Qi Deficiency Scale of Traditional Chinese Medicine(TCM-SDS-5)are significantly correlated with the microbial community structure of samples from different TNM stages(r2=0.683 P=0.001);the intestinal microbial community structure of different TNM stages is related to TH cells(r2=0.149 P=0.02),TC cells(r2=0.162 P=0.01),total B cells(r2=0.471 P=0.001),total T cells(r2=0.299 P=0.001),NK cells(r2=0.323 P=0.001)are significant Correlation;the structure of the intestinal microbial community in patients with early,middle and late stages is related to TH cells(r2=0.321 P=0.001),TC cells(r2=0.389 P=0.001),total T cells(r2=0.334 P=0.002),NK cells(r2=0.165 P=0.045)there is a significant correlation,total B cells have no correlation with the microbial community structure(P>0.05).5.Intestinal flora and cellular immunity analysis of spleen qi deficiency and non-spleen qi deficiency groups in the early,middle and late stagesThe early and mid-term non-spleen qi deficiency group and the late non-spleen qi deficiency group had statistically significant differences in the distribution of Alpha diversity(P=0.001);the early and mid-term spleen qi deficiency group,the early and mid-term non-spleen-deficiency group,the advanced spleen-deficiency group,and the advanced non-spleen-deficiency group were in colorectal cancer There were significant differences in the composition of the bacterial community of the patients(R=0.1183 P=0.001);Faecal ibacterium,Bifidobacterium,and Roseburia had extremely significant or significant differences among the four groups(P<0.001,P<0.05).Conclusion:1.The two methods based on objective quantitative and qualitative judgments are consistent in the judgment of spleen-qi deficiency in patients with colorectal cancer,and TCM-SDS-5 is more sensitive to the diagnosis of spleen-qi deficiency2.TNM staging is positively correlated with the score of spleen deficiency.Patients with advanced colorectal cancer(stage ?)have a higher degree of spleen qi deficiency than patients with early and mid-stage colorectal cancer(stage ?-?).3.There are differences in the composition and distribution of intestinal flora in patients with stage ?-?,stage ?,?,early and mid-stage(?-?)and advanced(stage ?)colorectal cancer,and are related to the degree of spleen qi deficiency and TB lymphocyte subpopulation.There is a correlation between groups.4.There are differences in the composition and distribution of the intestinal flora of the four groups of colorectal cancer patients in the early and mid-term(stage ?-?)spleen qi deficiency group,non-spleen qi deficiency group,advanced(stage ?)spleen qi deficiency group,and non-spleen qi deficiency group.