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Objective:To investigate the expression of vitamin D receptor(VDR)in biliary epithelial cells of children with biliary atresia(BA)and explore the correlation between VDR epression levels and clinical pathological prognosis.Methods:A total of 48 BA patients who underwent Kasai surgery in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi′an Jiaotong University from January 2017 to December 2020 with confirmed pathological results were selected as the study subjects.Immunohistochemistry was used to determine the expression of VDR in biliary epithelial cells, and Masson staining was used to determine the degree of liver tissue fibrosis.Based on the VDR expression levels, the 48 BA patients were divided into the significantly low VDR expression group(30 cases)and the normal/high expression group(18 cases).Laboratory testing results within 1 week before Kasai surgery and liver shear wave elastography(SWE)data were collected for all patients.Follow-up was conducted for a period of 0 to 60 months after Kasai surgery or liver transplantation, meanwhile, the occurrence of refractory cholangitis and auto-liver survival time were collected.Results:There was a negative correlation between the degree of liver fibrosis and SWE value in children with BA( r=-0.805, P<0.01).In comparison between the two groups, the significantly low VDR expression group had higher SWE values[(20.57±1.28)kPa vs.(18.02±1.41)kPa, P<0.05], higher liver injury biochemical indicators[ALT(215.8±24.7)U/L vs.(182.6±21.2)U/L, P=0.021; AST(165.4±22.3)U/L vs.(139.6±21.4)U/L, P=0.014], a higher frequency of post-Kasai surgery refractory cholangitis(60.00% vs.22.22%, P=0.037), and a shorter median autologous liver survival time(27.00 months vs.36.00 months, P=0.032)than those in the normal/high expression group. Conclusion:The significant decrease in VDR expression in biliary epithelial cells may serve as an indicator of poor prognosis in BA.
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OBJECTIVE To systematically evaluate the efficacy and safety of new oral anticoagulants （NOACs） in patients with nonvalvular atrial fibrillation after left atrial appendage occlusion （LAAO）. METHODS Retrieved from PubMed， Embase， Web of Science， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） and cohort studies about NOACs （trial group） versus warfarin or dual antiplatelet agents （control group） were collected during the inception and November 2022. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 10 studies were included， involving 2 RCTs and 8 cohort studies， with a total of 2 653 patients. RCT results showed that there was no statistically significant difference in the incidence of device-related thrombosis （DRT）， stroke/ systemic embolism （SSE）， major bleeding events， total bleeding events or all-cause mortality between 2 groups （P＞0.05）. Results of cohort studies showed that compared with dual antiplatelet agents， there was no statistically significant difference in the incidence of DRT， stroke/SSE， major bleeding events or all-cause mortality in the trial group （P＞0.05）. Compared with warfarin， the incidence of DRT [RR＝0.40， 95%CI （0.19，0.82）， P＝0.01] and total bleeding events [RR＝0.28， 95%CI （0.18， 0.44）， P＜ 0.000 01] in the trial group were decreased significantly； there was no statistical significance in the incidence of stroke/SSE， major bleeding events or all-cause mortality （P＞0.05）. CONCLUSIONS For patients with nonvalvular atrial fibrillation after LAAO， NOACs have comparable antithrombotic efficacy and safety with dual antiplatelet agents， and the incidence of DRT and total bleeding events are lower than warfarin.
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Rivaroxaban, a novel oral anticoagulant drug, is widely prescribed in clinical practice. Rivaroxaban offers predictable pharmacokinetic and pharmacodynamic properties, a lowprobability of drug-drug and food-drug interactions. Compared with warfarin, rivaroxaban does not require continuous therapeutic monitoring and can be administered in fixed doses.However,in certain emergency clinical situations, such as bleeding, acute stroke, acute kidney injury, prior to urgent surgery and in the suspected accumulation of durg, plasma concentration monitoring of rivaroxaban is necessary and important for patients. Existing studies proved that there were significant individual variability and wide range in the plasma rivaroxaban concentration, which increased the risk of clinical use. Therefore, Data in the degree of rivaroxaban concentration may provide recommendations for the clinical application to promote medication safety and individuality in the future. This article collected the latest literatures and case reports related to research progress of rivaroxaban plasma concentration monitoring, and Summarized influencing factors, monitoring methods, so as to provide a basis for further study on rational use of rivaroxaban in clinical.
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Objective:To explore the possible role and clinical significance of vitamin D receptor (VDR) in intrahepatic bile duct epithelial cells (IBDECs) in biliary atresia (BA).Methods:A retrospective analysis was performed on expression level of VDR in IBDECs of 38 BA children who underwent Kasai surgery in the Second Affiliated Hospital of Xi′an Jiaotong University and the Children′s Hospital of Xi′an Jiaotong University from January 2015 to December 2019.Expression level of VDR in IBDECs of 38 children with BA was detected by immunohistochemical staining, and that in children with choledochal cysts was detected as negative control.Masson staining was performed to examine the degree of liver fibrosis.The correlation between the expression level of VDR in IBDECs of children with BA, and the degree of liver fibrosis during operation, the incidence of refractory cholangitis after Kasai portoenterostomy and the survival time of autologous liver was analyzed.Human intrahepatic bile duct epithelial cells (HiBECs) were induced with dsRNA virus infection by polyinosinic acid-polycytidylic acid [Poly(I∶C)] in vitro, followed by detection of cell activity, apoptosis and VDR level.The differences between 2 independent groups were analyzed using Student t test.The relationship between the expression of VDR and clinicopathologic characteristics was conducted with χ2 test or Fisher′ s test.The Kaplan- Meier survival curve was used to analyze the differences in the survival time of autologous liver after Kasai in BA children with different VDR expression levels. Results:A total of 38 children with BA were included in this study.Among them, 23 cases showed no significant decrease of VDR protein level in IBDECs, and 15 cases showed a significant decrease in IBDECs.Compared with BA children without a significant decrease in VDR level in IBDECs, much severer liver fibrosis ( P<0.001) and significantly higher incidence of refractory cholangitis after Kasai procedure ( P=0.017) were detected in those with a significant decrease in VDR level.Compared with the control group, BA children with significantly lower VDR expression levels in HiBECs had a shorter autologous liver survival time ( P=0.030). Poly (I∶C) increased the apoptotic rate of HiBECs ( P<0.000 1) and decreased cell activity of HiBECs ( P<0.05), which significantly stimulated the secretion of inflammatory factors (interferon, tumor necrosis factor-α, interleukin-6) in the culture medium of HiBECs ( P<0.001). Poly (I∶C) significantly decreased the expression level of VDR protein in HiBECs ( P<0.001). Conclusions:Poly (I∶C) causes HiBECs damage and decreases VDR expression level in HiBECs of BA children, and the significantly decreased VDR expression level in IBDECs may be a marker of poor prognosis of BA.
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Finerenone is a new non-steroidal mineralocorticoid receptor antagonists, which can prevent and treat type 2 diabetes mellitus complicated with chronic kidney disease through antioxidant, anti-inflammatory and anti-fibrosis effects, and has a significant cardiovascular protection effect. Compared with traditional mineralocorticoid receptor antagonists, finerenone has a higher selectivity. In this review, the basic introduction, basic research, clinical research and limitations of finerenone were reviewed in order to provide more ideas and options for the treatment of type 2 diabetes mellitus complicated with chronic kidney disease.
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@# ObjectiveTo investigate the clinical effect of vitamin E in the treatment of nonalcoholic fatty liver disease (NAFLD) in children. MethodsPubMed, Web of Science, The Cochran Library, Embase, OVID/NEJM, CNKI, and Wanfang Data were searched for the articles on vitamin E in the treatment of NAFLD in children published up to December 2019. The data of 8 parameters were analyzed, i.e., body mass index (BMI), liver enzymes ［alanine aminotransferase (ALT) and aspartate aminotransferase (AST)］, blood lipid levels ［triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)］, and remission rate of hepatic steatosis. RevMan 5.3 was used to perform a Meta-analysis. Continuous variables were analyzed by standardized mean difference (SMD) and 95% confidence interval (CI), and the changes after intervention were analyzed; categorical variables were analyzed by risk difference (RD) and 95%CI. A fixed effects model was used for homogeneous data, and a random effects model was used for heterogeneous data. Funnel plots were used to evaluate publication bias. ResultsA total of 599 articles were retrieved, among which 9 were included in the Meta-analysis, with 607 subjects in total. Vitamin E significantly improved the level of ALT (SMD = -0.27, 95%CI: -0.48 to -0.06, P=0.01), but it did not improve the levels of BMI (SMD=-0.09, 95%CI: -0.28 to 0.10, P=0.34), AST (SMD=-020, 95%CI: -0.42 to 0.02, P=0.07), TG (SMD=-0.19, 95%CI: -0.51 to 0.12, P=0.22), TCHO (SMD=-0.11, 95%CI: -0.31 to 0.08, P=0.24), HDL (SMD=-0.02, 95%CI: -0.27 to 0.23, P=0.88), LDL (SMD= -0.04, 95%CI: -0.27 to 019, P=072), and the remission rate of hepatic steatosis (RD=0.06, 95%CI: -0.05 to 0.17, P=0.29). ConclusionVitamin E can significantly improve the level of ALT in children with NAFLD and can be considered as an adjuvant drug for clinical treatment.
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OBJECTIVE: To explore the effect of zinc oxide nanoparticles(ZnO NPs) on the oxidative damage in human alveolar type Ⅱ epithelial cell line A549.METHODS: The A549 cells in logarithmic growth phase were incubated with ZnO NPs solution at dose of 0,10,20 and 40 mg/L as 4 dose groups.The levels of reactive oxygen species(ROS) were measured by flow cytometer after 4 hours of exposure.The malondialdehyde(MDA) content and super oxide dismutase(SOD) activity were measured by microplate reader after 8 hours of exposure.RESULTS: The ROS levels in A549 cells exposed to 10,20,40 mg/L ZnO NPs were significantly increased compared with control group(P<0.05).The level of ROS increased with the exposure dose of ZnO NPs in A549 cells(P<0.01).The activities of SOD in A549 cells exposed to 10,20,40 mg/L ZnO NPs were significantly decreased compared with control group(P<0.05).The level of MDA and the ratios of MDA/SOD increased compared with control group(P<0.05).The activity of SOD in A549 cells decreased with the increase of ZnO NPs exposure dose(P<0.01),and the level of MDA and the ratios of MDA/SOD increased with the increase of exposure(P<0.01).CONCLUSION: ZnO NPs could induce lipid peroxidation in A549 cells with a dose-effect relationship.