Bile acid efflux pump(BSEP)is the major transporter of bile salts secreted by liver cells into the bile,the variation and inhibition of which are connected with cholestasis and drug-induced liver injury.A deep understanding of the physiological and pathological function of BSEP IS achieved by analysis and summary of diseases.The paper briefly illustrates the structure, expression,regulation,substrates,inhibitors and diseases of BSEP,in order to provide further theoretical and experimental basis for the clinical treatment.

ObjectiveControl study on the clinical efficiency and costs of fast track surgery(FTS) and traditional method was carried out in colorectal cancer patients. Methodsone hundred colorectal cancer patients were randomLy selected, 50 cases treated with conventional therapy as control group and 50 cases treated with FTS programme. The postoperative initial venting time, the incidence of complications, the hospital stay and cost index were compared between the two groups. ResultsThe postoperative initial venting time was in advance and postoperative stay was obviously shortened in FTS group. Hospitalization expenditure in FTS group was lower than that in control group. Patients recovered quickly, the result was satisfactory. The complication was not significantly different between the two groups (P ＞ 0.05 ) . ConclusionsFTS treatment can accelerate postoperative rehabilitation and elevate clinical efficiency in colorectal cancer patients during operation period. FTS treatment is a safe and effective method.

Objective:To investigate the cognition of terminal stage patients'dignity therapy,attitude towards its concept and scheme,willingness of its promotion in college students and to gain some recommendations for improvement.Methods:Combined quantitative and qualitative methods,an anonymous questionnaire survey was conducted in a convenience sample of 220 college students,of which 20 students were selected for in-depth interviews.Results:Only 17.73％ of students had a correct understanding of dignity therapy,94.98％ of them accepted its concept,92.96％ of them held a positive attitude,74.38％ of them were willing to promote dignity therapy,in which female students were dominated (P =0.041).Interview results showed that the contents of dignity therapy were to some extent stiff and not fit for Chinese patients,which might impede its promotion.Conclusion:College students lack the cognition of dignity therapy.But they hold a positive attitude and are willing to promote dignity therapy when they get to know its concept and contents.As seen,dignity therapy has a good future but there are still some obstructions in the promotion,and need to be localized.

Objective To search for independent predictive factors of diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM),construct and validate an optional machine learning(ML)model for the risk of DKD.Methods A total of 528 patients with T2DM,hospitalized in the Endocrinology Department of Chengde Central Hospital from October 2019 to September 2020,were selected as the study objects,and patients were randomly divided into a training set(370 cases),and a validation set(158 cases).The training set was divided into the DKD group(89 cases)and the non-DKD group(281 cases)according to whether DKD existed.The general data and diagnostic examination of patients were performed by univariate analysis,in which variables with statistical differences were used to screen the best predictors by least absolute shrinkage and selection operator(LASSO)regression analysis.The best predictors were used to establish eight ML algorithms by three cross-validation methods,including Logistic regression(LR),K-nearest neighbor(KNN),support vector machine(SVM),decision tree(DT),random forest(RF),naive Bayes(NB),artificial neural network(ANN),and extreme gradient lift(XGBoost).The optimal prediction model was selected by receiver operating characteristic(ROC)curve,Delong test and GiViTI calibration curve.Decision curve analysis(DCA)was used to evaluate the clinical practicability of the model.Results Age,alanine aminotransferase,creatinine,triglyceride,cystatin C,25-hydroxy vitamin D and monocyte count were independent predictive factors of DKD.Eight ML models were established based on the above 7 predictors,and the ANN model performed best in the 8 ML models.The GiViTiI calibration curve indicated that the model had good accuracy(P＞0.05),and the DCA showed that the prediction model curve had clinical practical value in the threshold probability range of 0.027-0.612.Conclusion In this study,the ANN model constructed in this study to predict the risk of DKD is helpful for early discrimination of high-risk T2DM patients with DKD.

Objectives To explore the dose-response relationship between low-dose ionizing radiation and thyroid hormone levels of radiation medical workers and provide theoretical basis for occupational health protection to this population. Methods Using a prospective cohort study design, we collected health examination reports on employees that worked on jobs with occupational exposure to radiation at hospital with individually dose monitoring data for 1 237 workers. The effective cumulative radiation dose was divided into three groups: 0～2.586 mSv, 2.586～3.757 mSv, 3.758～31.272 mSv by the interquartile range. The low-dose group was used as a reference to compare the changes in thyroid hormones of medical workers in different cumulative radiation dose groups. The generalized linear models and restricted cubic spline model were used to examine the association and dose-response relationship between the cumulative effective dose and changing thyroid hormones. Results There were statistically significant differences in changing thyroxine (T4) and Free triiodothyronine (FT3) levels among three different dose groups of 1237 subjects (P < 0.05). The results of generalized linear models analysis revealed that 2.586～3.757 mSv was a significant risk factors of changing T4, with β of 3.514 (95% confidence interval [95% CI]: 0.900～6.128) after adjusting for gender, age, working duration, occupation, medical level and smoking, while the association with changing FT3 was not observed (P > 0.05). The restrictive cubic spline (RCS) model analysis indicated a non-linear dose-response correlation between cumulative radiation dose with changing T4 (P = 0.023). Conclusion Long-term exposure to low-dose ionizing radiation could induce the thyroid damage among medical occupational population. And there is a dose-response relationship between cumulative radiation dose and changing thyroxine.

The prevalence and recurrence rate of depressive disorder are high, while the recognition and cure rate are low. Early intervention can improve the quality of life of patients with depression. In clinical practice, it has been found that psychological treatments can effectively improve the symptoms and prognosis of depression.Cognitive behavior therapy(CBT) has been widely used in the treatment of depression, however, its mechanisms are still unclear. In this paper, the neuroimaging studies of patients with depression before and after CBT were summarized, and the structural or functional changes of different brain regions in patients with depression before and after CBT were described. The findings suggest that CBT improved depressive symptoms by increasing gray matter volume, activation level, and functional connectivity strength in the dorsolateral prefrontal cortex, reducing activation levels in the amygdala and parahippocampal gyrus, and restoring abnormal brain network activity or functional connectivity. Larger gray matter volume in anterior cingulate gyrus and higher activation levels in hippocampus and amygdala before treatment can effectively predict the effect of CBT in depressed patients. In the future, machine learning could be combined with brain imaging data to more accurately predict the effectiveness of CBT in treating depression.

【Objective】 To observe the effects of hsa-miR-124-3p.1 in inhibiting epithelial-mesenchymal transition （EMT）， migration and invasion of human gastric cancer cells induced by transforming growth factor β1 （TGF-β1） by targeting tumor necrosis factor receptor-associated factor 6 （TRAF6）. 【Methods】 A total of 43 gastric cancer tissues and 43 normal para-carcinoma tissues were collected. The human gastric mucosal epithelial cells GES-1 and gastric cancer cells （NCI-N87， MGC-803， BGC-823， SGC-7901， and MKN-45） were cultured. The expressions of miR-124-3p.1 and TRAF6 in tissues and cells were detected by fluorescent quantitative PCR and Western blotting. The targeted relationship between miR-124-3p.1 and TRAF6 was verified by dual-luciferase reporter gene system assay. SGC-7901 cell lines with miR-124-3p.1 and TRAF6 overexpression were constructed. The cells were induced by TGF-β1. The invasion and migration abilities of the cells were evaluated by Transwell chamber assay and scratch test. 【Results】 Compared with normal para-carcinoma tissues and normal gastric mucosal cells， the expression of miR-124-3p.1 was downregulated， while the expressions of TRAF6 mRNA and protein were upregulated in gastric cancer tissues and cells （P<0.05）. Compared with control group， expression of E-cadherin in cells was downregulated， expressions of N-cadherin and Vimentin were upregulated， invasion and migration rates of cells were increased in TGF-β1 group （P<0.05）. Compared with TGF-β1 group， after cells were transfected with miR-124-3p.1 mimic， the expression of E-cadherin was upregulated， the expressions of N-cadherin and Vimentin were down-regulated， and invasion and migration rates of cells were decreased （P<0.05）. Compared with miR-124-3p.1 mimic group， invasion and migration rates of cells were increased in TGF-β1+mimic+TRAF6 group， expressions of TRAF6， N-cadherin and Vimentin were up-regulated， and the expression of E-cadherin was down-regulated （P<0.05）. 【Conclusion】 hsa-miR-124-3p.1 is lowly expressed in gastric cancer. Overexpression of miR-124-33p.1 can inhibit EMT， cell invasion and migration induced by TGF-β1. And the action mechanism may be related to the downregulated expression of TRAF6.

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure-activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFR simultaneously . Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.

[Objective] To explore the characteristics of lifestyle behaviors and mental health status among blood donors in Guangzhou, and to investigate the correlation between donation frequency and these factors. [Methods] A cross-sectional study was conducted among 13 042 whole blood donors from 17 street blood donation sites of Guangzhou Blood Center from May to August 2020. Descriptive analysis was used to describe the characteristics of lifestyle behaviors and mental health status among blood donors in Guangzhou. Ordinal multinomial logistic regression model was used to analyze the correlation between donation frequency and these factors. [Results] It was found that some of 13 042 blood donors had unhealthy habits, such as 6.8% (698/10 214，2 828 missing values) had severe tobacco dependence, 30.6% (3 997/13 042) had low exercise levels, 38.8%（5 056/13 042）had poor sleep quality, and 2.2% (271/12 159，883 missing values) had alcohol dependence. In addition, 2.8% (364/13 042) and 1.3% (172/13 042) of the donors may have moderate to severe depression and anxiety symptoms, respectively. The results of the ordinal multinomial logistic regression model showed that exercise level was significantly negatively correlated with the degree of depression and anxiety among blood donors. With the decrease in exercise level, the possibility of depression and anxiety among donors increased significantly. BMI, household income, education level, marital status, donation frequency, alcohol consumption and smoking had no significant correlation with the mental health status of donors. [Conclusion] Improving the exercise habits of blood donors may help enhance their mental health level. It is recommended that blood station staff strengthen the content of exercise when providing health education to blood donors to maintain a healthy lifestyle. It also suggests that there may be a certain degree of under-diagnosis of mental health problems in the process of health consultation before blood donation, and conducting more comprehensive and effective mental health assessments for blood donors is recommended.