| This study is divided into two parts:literature review and clinical study.The review part firstly discussed the latest research progress of Chinese medicine symptoms and etiology of colorectal cancer patients during chemotherapy;secondly,it discussed the clinical symptoms of colorectal cancer patients and their intestinal microbial changes during chemotherapy.The clinical research section firstly explores the symptoms and their evolution patterns of colorectal cancer patients before and after chemotherapy and in different chemotherapy regimen groups,and secondly analyzes a series of influencing factors based on the changes of spleen and kidney deficiency symptoms and symptom scales before and after chemotherapy in colorectal cancer patients,combined with blood routine,liver and kidney function,tumor markers,objective efficacy of chemotherapy and intestinal flora.Clinical study:Objective of the study:To explore the dynamic evolution of symptoms and signs based on spleen and kidney deficiency during chemotherapy in colorectal cancer patients,to clarify the core intervention points and treatment points during chemotherapy,and to explore the factors influencing the changes of signs and symptoms during chemotherapy in intestinal cancer patients from relevant scales,intestinal flora and laboratory tests,and efficacy evaluation.Methods:Using a prospective longitudinal study,60 patients with colorectal cancer treated with 5-FU-based drug chemotherapy in the outpatient or inpatient wards of the Department of Oncology,Xiyuan Hospital,Chinese Academy of Traditional Chinese Medicine between June 2022 and December 2022 were collected.Information was collected according to the designed questionnaire,which was divided into four parts.The first part was a baseline survey,including age,gender,date of birth,height,weight,and BMI of chemotherapy patients.The second part was a tumor pathology survey,including primary tumor site,surgical site and procedure,metastatic site,KPS score,pathological typing,differentiation degree,genetic examination,combined diseases,chemotherapy regimen,etc.of intestinal cancer in the included population.The third part is the Chinese medicine evidence and MDASI scale,ESAS scale,spleen deficiency and kidney deficiency scale,and anxiety and depression scale collection and observation.In the fourth part,patients underwent routine blood tests,biochemical and tumor marker tests 1 day before each chemotherapy treatment,and stool samples were collected from 10 patients with baseline evidence of Spleen-Qi deficiency or Kidney-Yang deficiency and commissioned to Shanghai Meiji Biological Co.Other data were entered into Epidate version 4.6.0.6 software and exported later for statistical analysis using SPSS 26.Research results:1.Changes in TCM symptoms before and after chemotherapyAmong the 60 patients,the evidence of spleen deficiency and qi stagnation was the most frequent before chemotherapy,followed by the evidence of qi and blood deficiency,and the evidence of spleen deficiency and qi stagnation began to decline after one cycle of chemotherapy,while the evidence of qi and blood deficiency began to increase after two cycles of chemotherapy.The spleen deficiency and qi stagnation evidence gradually decreased after chemotherapy,and there was a statistical difference between before and after chemotherapy(P=0.012).Spleen qi deficiency showed an upward trend after chemotherapy,while kidney yang deficiency showed no significant change,and no statistical difference was observed in the pre-and post-chemotherapy comparisons(P>0.05).Further comparison of changes in the degree of spleen deficiency and kidney deficiency before and after chemotherapy with different regimens using the spleen deficiency and kidney deficiency scale scores did not show any significant statistical difference(P>0.05).However,the spleen deficiency and kidney deficiency scores in the irinotecan+5-FU group were higher than those in the other two groups,and there was a statistically significant difference between the spleen deficiency scores in the irinotecan+5-FU group and the capecitabine monotherapy group after 2 cycles of chemotherapy(P=0.017).2.Changes of objective indexes before and after chemotherapyAmong the 60 patients,blood routine showed a gradual decrease in RBC,NE,and PLT after chemotherapy,with statistical differences(P<0.05)compared before and after chemotherapy.The grouping of chemotherapy regimens showed that RBC,WBC and NE in the oxaliplatin+5-FU group and irinotecan+5-FU group showed a decreasing trend after chemotherapy,with statistical differences before and after chemotherapy(P<0.05),and there were no significant statistical differences in blood routine indexes before and after chemotherapy in the single-agent capecitabine group(P>0.05).Regarding biochemical indexes,ALP,TBIL and SCr showed a decreasing trend after chemotherapy,while γ-G and AST showed an increasing trend with chemotherapy cycles,with statistical differences before and after chemotherapy(P<0.05).The grouping of chemotherapy regimens showed that ALP,AST,Scr and TBIL showed a decreasing trend and y-G showed an increasing trend before and after chemotherapy in the three regimens,and there was a statistical difference.(P<0.05).As for tumor markers,CEA,CA242,CA199,CA153 and CA125 showed a decreasing trend in general,with statistical differences before and after chemotherapy(P<0.05),and the comparison between groups according to different outcomes of efficacy evaluation after chemotherapy showed that compared with SD and PR groups,tumor markers CEA,CA242 and CA199 were higher in PD group after chemotherapy,and there were statistical differences(P<0.05).3.Changes in MDASI symptom scale and ESAS symptom scale scores before and after chemotherapyAmong the 60 patients,the MDASI symptom scale showed that the incidence and scores of symptoms were mainly in the areas of forgetfulness,sleep,fatigue,appetite,pleasure of life and housework during chemotherapy;the ESAS scale showed that fatigue,sleepiness,appetite,sleep and happiness were the main symptom burdens during chemotherapy,and the repeated measures ANOVA showed that there was no statistically significant difference in the symptom scores of the two scales before and after chemotherapy.Repeated measures ANOVA showed that there was no statistically significant difference(P>0.05)between the two scales before and after chemotherapy;subgroup analysis of different chemotherapy regimens showed no statistically significant difference(P>0.05)between the symptom scores before and after chemotherapy.4.Changes in anxiety and depression scores before and after chemotherapyRepeated measures ANOVA showed that there was no statistically significant difference in anxiety and depression scale scores before and after chemotherapy in 60 patients(P>0.05).Subgroup analysis of different chemotherapy regimens showed that anxiety scores increased in the irinotecan+5-FU group after chemotherapy,with statistically significant differences compared with those before chemotherapy(P<0.05).5.Analysis of factors related to the change of symptoms before and after chemotherapy5.1 Correlation between chemotherapy efficacy and changes in symptomsThe correlation analysis before and after chemotherapy suggested that the outcome PD before chemotherapy was positively correlated with the change of evidence of spleen deficiency and qi stagnation(P=0.041).After 1 cycle of chemotherapy,the outcome PD was positively correlated with the change of spleen qi deficiency evidence(P=0.029).The efficacy evaluation outcomes PR and SD were not significantly correlated with all evidence changes(P>0.05).5.2 Correlation between objective indicators and evidence changesMultiple disorder logistic analysis showed that HGB before chemotherapy was negatively correlated with spleen and kidney yang deficiency,spleen deficiency and qi and blood deficiency(P<0.05),and HGB after 1 cycle of chemotherapy was negatively correlated with spleen qi deficiency(P=0.039);RBC,WBC,NEU and PLT were not significantly correlated with changes in symptoms(P>0.05).The correlation analysis of biochemical indexes suggested that SCr before and after chemotherapy was negatively correlated with the change of liver and kidney yin deficiency evidence(P<0.05);ALT,AST,ALP,TBIL and y-G were not significantly correlated with the change of evidence(P>0.05).The correlation analysis of tumor markers suggested that CA199 was positively correlated with the change of spleen qi deficiency evidence after 2 cycles of chemotherapy(P=0.045)and CA242 was negatively correlated with the change of spleen qi deficiency evidence(P=0.036);CEA,CA724,CA125 and CA153 were not significantly correlated with the change of evidence(P>0.05).5.3 Correlation between chemotherapy regimen and changes in evidenceMultivariate unordered logistic analysis suggested that the irinotecan+5-FU group had a positive correlation with the change of spleen qi deficiency evidence after 1 cycle of chemotherapy(P=0.043),and the oxaliplatin+5-FU group and capecitabine monotherapy group did not show any significant correlation with all evidence changes(P>0.05).5.4 Correlation between anxiety and depression scores and changes in evidenceMultivariate logistic analysis suggested that anxiety and depression scores after 1 cycle of chemotherapy were positively correlated with changes in Spleen Qi Deficiency Certificate and Kidney Yang Deficiency Certificate(P<0.05).anxiety scores after 2 cycles of chemotherapy were positively correlated with changes in Spleen Qi Deficiency Certificate(P=0.026),and no significant correlation was seen with changes in Kidney Yang Deficiency Certificate(P>0.05).depression scores after 2 cycles of chemotherapy were positively correlated with changes in Kidney Yang Deficiency Certificate There was a positive correlation(P=0.016)between depression scores and changes in Spleen-Qi deficiency evidence after 2 cycles of chemotherapy,and no significant correlation(P>0.05)with changes in Spleen-Qi deficiency evidence.5.5 Detection of intestinal microbial diversityAlpha diversity analysis and Beta diversity analysis suggested that there was no statistical difference in the distribution and abundance of intestinal flora before and after chemotherapy(P>0.05).The community Bar and Pie plots suggested that the flora before chemotherapy was dominated by the phylum Thick-walled,Aspergillus,Aspergillus,Actinomycetes,and Warty Microflora,and with the increase of chemotherapy cycle,the number of Thick-walled and Aspergillus phylum decreased and that of Aspergillus and Actinomycetes increased.Genus-level difference test showed that the number of Streptococcus pepticus genera before and after chemotherapy was statistically different(P=0.025).Clinical correlation factor analysis showed that WBC,HGB,NEU,and PLT were associated with the composition of the bacterial community before and after chemotherapy(P<0.05),and RBC did not show an association(P>0.05).Biochemical index association analysis showed that ALT,y-G,and SCr were associated with colony composition(P<0.05);ALP,AST,and TBIL did not show an association with them(P>0.05).Tumor association analysis showed that CEA,CA199,CA242,CA724 were associated with colony composition(P<0.05),CA125,CA153 did not show association with them(P>0.05).ANOSIM and PLS-DA analysis suggested that individual differences within the intestinal flora group varied greatly between spleen qi deficiency and non-spleen qi deficiency evidence,and the number of thick-walled flora was basically the same in both,but The phylum Aspergillus was more abundant in the spleen qi deficiency evidence than in the non-spleen qi deficiency evidence,while the phylum Bacteroidetes,Actinobacteria,and Warty Microflora were more abundant in the non-spleen qi deficiency evidence than in the former.Species difference analysis showed that at the genus level,there were significant or highly significant differences in the composition of Clostridium spp.,E.faecalis spp.,E.rumefaciens spp.,Typhimurium spp.and Prevotella spp.between the two groups(P<0.001,P<0.05).6.Analysis of differences in intestinal microbiota in different chemotherapy evaluation groupsSobs index showed that the changes of intestinal microbiota abundance in PR,SD and PD groups were basically the same.The community Bar plot showed that the distribution of intestinal microorganisms was more extensive in the thick-walled phylum of patients in the PR group,more abundant in the SD group of patients in the anamorphic phylum,and basically the same in the PD group of patients in the thick-walled phylum,anamorphic phylum,and anamorphic bacillus spp.PCoA analysis showed that the intestinal microbial composition was different among the three groups(P=0.009),and further ANOSIM analysis showed that the intergroup differences among the three groups were greater than the intra-group differences(P=0.004),suggesting a significance of grouping according to the assessment of effectiveness.The test of between-group variability suggested that there were statistically significant or highly significant differences in the genus composition of Streptococcus spp.,Clostridium pratense,and Citrobacter spp.in the 3 groups at the genus level(P<0.001,P<0.05).The 3 groups at the phylum level had statistically significant differences(P<0.05)in the composition of the phylum Aspergillus,Desulfovibrio.Conclusion:1.Before chemotherapy,colorectal cancer patients were mainly suffering from spleen deficiency and qi deficiency,and after chemotherapy,spleen deficiency and qi deficiency decreased and qi and blood deficiency increased.2.The evaluation of tumor efficacy,chemotherapy regimen,objective indicators,anxiety and depression are all correlated with the change of symptoms to different degrees.3.Before and after chemotherapy,there were differences in the abundance,composition and distribution of intestinal microorganisms between spleen qi deficiency and non-spleen qi deficiency evidence,and the composition and distribution of intestinal microbial community may be correlated with the outcome of tumor efficacy. |
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