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 status of evidence-based nursing competence among clinical nurses in tertiary grade A hospitals of Anhui province, and analyze the influencing factors based on random forest model, so as to provide reference for improving the evidence-based nursing ability of clinical nurses and formulating intervention strategies.Methods:The convenience sampling method was used to select 543 clinical nurses from 4 tertiary grade A hospitals in Anhui Province from October to December 2022. The general data questionnaire, Evidence-based Nursing Competence Scale, Information Literacy Scale, and Nurse Innovation Ability Scale were used to investigate. The random forest model was used to evaluate the importance of the influencing factors. The Lasso regression analysis was used to complete the screening of the influencing factors. The influencing factors of the evidence-based nursing competence among clinical nurses were explored by multiple linear regression analysis.Results:A total of 543 valid questionnaires were retrieved. Among 543 clinical nurses, 55 males and 388 females, aged (32.34 ± 6.93) years old. Evidence-based nursing competence scored (45.49 ± 21.18) points, information literacy scored (73.50 ± 10.47) points, innovation ability scored (126.78 ± 21.99) points. The random forest model and Lasso regression analysis showed that the model achieved the best fit with 8 variables. In order of importance, the top 8 variables were information literacy (25.78%), innovation ability (22.37%), night shift per month (9.91%), educational background (9.19%), English proficiency (8.44%), professional title (6.71%), scientific research and innovation experience (5.17%), and professional attitude (4.50%). Multiple linear regression analysis showed that information literacy, innovation ability, and English proficiency were the influencing factors of evidence-based nursing competence among clinical nurses ( t=9.17, 7.31, 2.52, all P<0.05). Conclusions:The level of evidence-based nursing ability among clinical nurses in tertiary grade A hospitals of Anhui province needs to be improved. From the perspective of improving the information literacy among clinical nurses, nursing managers can increase the training of information retrieval ability and English ability, enhance their English literature reading skills, pay attention to the cultivation of nurses' innovation ability, stimulate the innovative consciousness and thinking among clinical nurses, formulate and implement targeted interventions, so as to gradually improve the level of evidence-based nursing ability among clinical nurses.

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.

Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment. Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγ antagonist GW9662 to confirm the involvement of this pathway in MaR1's effects. Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P＜0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P＜0.05).No significant difference in efficacy was observed between the 2 doses(all P＞0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1's protective effects.Real-time RT-PCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P＜0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P＞0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P＜0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P＜0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P＜0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P＜0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγ compared to the MaR1-LD group(all P＜0.05). Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.

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 injecting 0.1 ml/100g CaCl2-Ach mixture into the tail vein once a day for one week.The control group was injected 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 observed 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 observe changes in the expression of TGF-β,Orai1 and STIM1 proteins in ET-1/SOCC/TGF-β signaling 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,STIM1and TGF-β increased(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 To investigate the effects of pretreatment with Xuebijing injection on renal tubular injury in rats with contrast-induced acute kidney injury(CI-AKI).Methods Twenty-four Sprague-Dawley(SD)rats were selected and divided into normal group,model group,control group,and treatment group according to the random number table method,with 6 rats in each group.The animal model of CI-AKI was prepared by adopting iohexol,and the normal group was not subjected to any treatment.The rats in the treatment group were injected with Xuebijing injection via the tail vein 15 hours before modeling until 24 hours after modeling.The injection volume was 10 mL/kg for every 6 hours.The control group was injected with normal saline at the same time point.After 24 hours of modeling,the urine of rats in each group was collected to determine the levels of blood urea nitrogen(BUN)and urine N-acetyl-β-D-gluco-aminidase(uNAG),and the blood was collected to determine the levels of serum creatinine(SCr).Then the rats were killed and the kidney tissues were extracted,and then stained with hematoxylin-eosin(HE),and the pathological changes of the kidney tissues were observed under the light microscope.Results BUN,SCr and uNAG were significantly higher in the model group than those in the normal group[BUN(μmol/L):37.29±6.18 vs.6.37±1.19,SCr(mmol/L):30.43±4.44 vs.14.90±1.61,uNAG(U/L):47.77±4.71 vs.11.32±3.62,all P<0.01];BUN,SCr and uNAG levels were obviously decreased in the treatment group compared to the model group[BUN(μmol/L):9.45±3.04 vs.37.29±6.18,SCr(mmol/L):19.83±2.16 vs.30.43±4.44,uNAG(U/L):21.70±6.21 vs.47.77±4.71,all P<0.05],however,BUN and uNAG in the treatment group were still significantly higher than those in the normal group[BUN(μmol/L):9.45±3.04 vs.6.37±1.19,uNAG(U/L):21.70±6.21 vs.11.32±3.62,P<0.05 or P<0.01];SCr in the treatment group was not statistically significant compared to the normal group(μmol/L:19.83±2.16 vs.14.90±1.61,P>0.05).Under the light microscope,the renal tubular epithelial cells at the junction of cortex and dermatomedulla in the kidneys of the model group were obviously vacuolated,accompanied by cell detachment and necrosis,and the tubules were dilated,with no obvious lesions in the glomeruli.The degree of damage in the control group and the treatment group was reduced compared with that in the model group.The degree of renal tubular damage in the model group was higher than that in the normal group;while the degree of renal tubular damage in the control group was significantly lower than that in the model group;and the degree of renal tubular damage in the treatment group was lower than that in the model group.There was no statistically significant difference in the degree of renal tubular damage between the treatment group and the control group.Conclusion Xuebijing injection may exert a protective effect on renal function in rats with CI-AKI by attenuating renal tubular injury.

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.