Objective To identify potential biomarkers and establish a prediction model for chemotherapy-related hepatotoxicity susceptibility based on plasma endogenous metabolites of colorectal cancer(CRC)patients before chemotherapy.Methods The plasma samples of 50 CRC patients before capecitabine chemotherapy and the records of their chemotherapy-related hepatotoxicity during the follow-up were collected.An ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)was used to perform untargeted metabolomic analysis.Based on bioinformatics analysis,differential analysis,correlation analysis,and random forest were used to screen for hepatotoxicity-related plasma endogenous metabolites.All samples were randomly assigned(7∶3)to training set or test set.A multivariate logistic regression model was established to predict the hepatotoxicity of capecitabine chemotherapy based on the training set data.The prediction effects of the model in the training,test and entire sets were evaluated by receiver operating characteristic(ROC)curve analysis.Results The endogenous metabolites related to hepatotoxicity in the plasma of CRC patients before chemotherapy were mainly lipid endogenous metabolites.A series of potentially important predictive biomarkers for hepatotoxicity susceptibility were identified,including sphingamine-1-phosphate,ceramide,galactose,arachidonic acid,tyrosine,biliverdin,myristic acid,phosphatidylcholine(35∶1),phosphatidylethanolamine(36∶1),and hexadecanoic acid.The area under curve values of the prediction model based on the above biomarkers in the training,test and entire sets were 0.946(95%confidence interval[CI]0.842-1.000),0.920(95%CI 0.720-1.000),and 0.912(95%CI 0.810-0.982),respectively.Conclusion The endogenous metabolites in the plasma of CRC patients before chemotherapy can effectively predict the hepatotoxicity of capecitabine chemotherapy.These hepatotoxicity biomarkers indicate that susceptible patients have characteristics related to lipid metabolism disorders.

Objective To investigate the clinical significance of hepatocyte nuclear factor 4α(HNF4α)in rectal cancer and its relationship with prognosis.Methods Real-time PCR was designed to detect the expression of HNF4αon mRNA level and the immunohistochemistry was used to determine the expression of HNF4αon protein level in rectal cancer tissue.The relationship between HNF4αexpression and clinical characteristics was also analysed.The Kaplan-Meier method was used for univariate analysis and a Cox proportional hazards regression model was performed for multivariate analysis.Results HNF4αwas low expressed both on mRNA (t=6.092,P<0.001)and protein level (χ2 =15.230,P<0.001)in rectal cancer tissue.HNF4αexpression on protein level was related with the clinical stage (χ2 =48.311,P<0.001),depth of invasion (χ2 =23.911,P<0.001),histological differentiation (χ2 =20.787,P<0.001),lymph node metastasis (χ2 =39.064,P<0.001)and distant metastasis (χ2 =5.146,P=0.04),while age and gender were not relevant.The cumulative 3-year overall survival of patients with low HNF4αexpression (43.8%)was much worse than the patients with high HNF4αexpression (95 .5%),and the difference was statistically sig-nificant (P<0.001).Univariate analysis revealed that HNF4αexpression (χ2 =28.778,P<0.001),differ-entiation (χ2 =26.680,P<0.001 ),clinical stage (χ2 =32.702,P<0.001 ),depth of invasion (χ2 =6.226,P=0.013),lymph node invasion (χ2 =15.270,P<0.001)and distant metastasis (χ2 =21.817, P<0.001)were statistically significant worse predictors for rectal cancer,whereas age and gender were not rel-evant.The multivariate Cox proportional hazard analysis revealed that HNF4αlow expression (RR=6.084, P=0.028)was independent prognostic markers for 3-year overall survival in the patients with rectal cancer. Conclusion HNF4αwas closely related to the tumorigenesis and progression of rectal cancer,which is an independent prognostic marker for rectal cancer,and which may be an effective target for the therapy of rectal cancer.

In view of the characteristics of the learning curve for medical students,the ' three phases and seven steps' case-based learning model was designed and implemented by Changzheng Hospital,the Second Military Medical University.This model was carried out in the theoretical study stage,the first round of internship and the second round of internship.Cases of single diseases,multiple diseases involving variant systems and a variety of diseases involving different department were enrolled for analysis and discussion.Implementation of each case study was divided in seven procedures:determining learning objective and choosing typical case,studying case and raising questions,panel discussions and establishment of common problems,looking up for information to answer questions and preparing report slide,large group discussions,summary and evaluation.'Three phases and seven steps' case based learning model ensure the width and depth of basic medical knowledge learned by the students.With the practice of this model,the basic medical knowledge was constructed systemically and comprehensively by medical students.Students' abilities of problem-analyzing and problem-solving as well as clinical research were developed.This model was effective according to our practice and was worth spreading out.