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.

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 investigate the influence of childhood traumatic experience on internet addiction of adolescents and the mediating effect of self-concealment.Methods:Childhood trauma questionnaire(CTQ), self-concealment scale(SCS) and adolescent pathological internet use scale(APIUS) were used to investigate 532 college students.SPSS 22.0 was used for descriptive statistics, correlation analysis and regression analysis.Amos 24.0 was used for confirmatory factor analysis, and the relevant assumptions were verified through structural equation model.Results:The total scores of childhood abuse, self-concealment and adolescent pathological internet use were (37.23±11.91), (26.09±9.26) and (82.15±28.09), respectively.Correlation analysis showed that childhood trauma was positively correlated with self-concealment ( r=0.27, P<0.01). Self-concealment was positively correlated with internet addiction ( r=0.47, P<0.01). Childhood trauma was positively correlated with internet addiction ( r=0.36, P<0.01). Mediating effect test showed that childhood trauma had a significant positive predictive effect on self-concealment ( β=0.34, P<0.01), self-concealment had a significant positive predictive effect on internet addiction ( β=0.34, P<0.01), and childhood trauma had a direct predictive effect on internet addiction ( β=0.31, P<0.01). Conclusion:Childhood trauma and self-concealment have significant influence on internet addiction, and self-concealment plays a partial mediating role between childhood trauma and internet addiction of adolescents.

Objective : To investigate the effect and mechanism of endothelin-1 (ET-1) on atrial fibrosis in Atrial fibrillation (AF) rats . Methods : Fourteen adult male SD rats were randomly divided into normal control ( NC) group and Atrial fibrillation (AF) group . The rat model of Atrial fibrillation was established by inj ecting 0.1 ml/ 100g CaCl2 Ach mixture into the tail vein once a day for one week . The control group was inj ected with the same dose of normal saline . An electrocardiogram of normal or atrial fibrillation was recorded on the first day and the eighth day in each group , and echocardiography was used to monitor atrial size and cardiac function . The fibrosis of atrial was ob served using Masson and HE staining. The expression of endothelin-1 ( ET-1) , collagen-I ( Col-I) , transforming growth factor-β(TGF-β) and the store operated calcium channel (SOCC) protein Orai1 , stromal in teraction molecule 1 (STIM1) in atrial tissue were detected by Western blot. HL-1 cells were cultured and treated with gradient concentration of ET-1 for 24 hours . Western blot was used to ob serve changes in the expression of TGF-β, Orai1 and STIM1 proteins in ET-1 /SOCC/TGF βsignaling pathway of HL-1 cells . Small interfering RNA ( siRNA) transfection method was used to knock down the expression of Orai1 in HL-1 cells , then the cells were treated with appropriate concentrations of ET-1 for 24 hours , and the expression of TGF-β protein in HL-1 cells was detected by Western blot. Results : Compared with the control group , echocardiography showed a significant in crease in left atrial diameter (LAD) of the heart in atrial fibrillation rats (P < 0.05) . The HE and Masson staining results showed significant fibrosis in the myocardial tissue of AF group rats (P < 0.05) , and the Western blot re sults indicated the expression of ET-1 , Orai1 , STIM1 , TGF-β and COL-Ⅰ in the myocardial tissue of AF group significantly increased compared to the NC group (P < 0.05) . After ET 1 treatment of HL-1 cells , the protein ex pression of Orai1 , STIM1 and TGF βincreased (P < 0.05) , while knocking down Orai1 in HL-1 cells , ET-1 treat ment no longer caused the expression of TGF-β a significant upregulation . Conclusion AF caused by atrial fibril lation results in a significant increase in ET-1 expression in atrial tissue , and ET-1 /SOCC/TGF-β signal pathway promotes atrial fibrillation and fibrosis .

Objective : In the present study，the changes of left atrial matrix characteristics and the effect of cathe- ter ablation on cardiac function in elderly patients with persistent atrial fibrillation were observed．Furthermore，the application of two catheter ablation methods including circular pulmonary vein isolation combined with left atrial ma- trix modification or left atrial posterior wall isolation were compared by researchers in order to explore effectiveness and safety of the two methods in elderly persistent atrial fibrillation patients． Methods : A total of 86 elderly pa- tients with persistent atrial fibrillation were selected and divided into two groups using randomization principle ; the pulmonary vein isolation combined with left atrial matrix modified catheter ablation method was named matrix modi- fied group (43 cases) ; the pulmonary vein isolation combined with left atrial posterior wall isolation catheter abla- tion method was named posterior wall isolation group (43 cases) ．During ablation left atrial electro matrix mapping were analyzed by multipole catheter for all patients．After ablation all patients were follow-up in 12 months by car- diac color doppler ultrasound examination，ECG and Holter．The incidence of arrhythmia ，serious adverse event and complications were compared between two groups． Successful rate of single ablation and blank period recur- rence after ablation were observed in 12 months follow-up time. Results : Through electrogram mapping of left atri- um low-voltage areas or scar areas were founded in 72 cases among the 86 cases after ablation，After a 12-month follow-up，the incidence of arrhythmia in the blank period between the two groups was 41．9% ( matrix modified group) and 23. 3% (posterior wall isolation group) ，independently，P＜0. 01，successful rates of single ablation in the two groups were 83. 7% (matrix modified group) ，60. 5% (posterior wall isolation group) ，independently， P ＜0. 01 ．No adverse event occurred in the two groups．After AF ablation LVEF increased，LVEDD and LVAD significantly decreased in all of the cases．There was no significant difference between the two groups in patients ’ characters ablation time and complications rate． Conclusion Circular pulmonary vein isolation combined with left atrial matrix modification is as safe as left atrial posterior wall isolation，and it is a simplified，personalized，and more effective ablation strategy in elderly patients with persistent atrial fibrillation.

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.