Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To analyze the prevalence and risk factors of blindness and moderate to severe visual impairment among Han and Kazakh residents aged 50 years and older in Tacheng City, Xinjiang Uygur Autonomous Region.Methods:This study is a cross-sectional survey conducted using cluster random sampling from October 2015 to June 2018 in Emin County, Tacheng City, Xinjiang Uygur Autonomous Region. The study included individuals aged 50 years and older to survey blindness and moderate to severe visual impairment. Ophthalmological examinations combined with questionnaires were conducted to gather basic information. The data collected from the questionnaires included general demographic information and health conditions. The results of the eye examinations were used to diagnose a total of 12 risk factors including cataracts, glaucoma, pterygium, suspected glaucoma, glaucoma, and refractive errors. These risk factors were analyzed in relation to blindness and moderate to severe visual impairment. Univariate analysis was conducted first, followed by logistic regression to identify the significant factors.Results:A total of 2 114 patients were included in the final analysis, among which the prevalence of moderate to severe visual impairment was 18.54% (392/2 114), and the prevalence of blindness was 2.74% (58/2 114). Univariate analysis showed that blindness and moderate to severe visual impairment were associated with age ( χ2 = 32.97, P < 0.05), hypertension ( χ2 = 3.48, P < 0.05), age-related cataract ( χ2 = 17.43, P < 0.05), glaucoma ( χ2 = 3.90, P < 0.05), macular degeneration ( χ2 = 16.04, P < 0.05), diabetes ( χ2 = 3.09, P < 0.05), pterygium ( χ2 = 2.57, P < 0.05), and fundus arteriosclerosis ( χ2 = 2.31, P < 0.05). Multivariate logistic regression analysis indicated that moderate to severe visual impairment was correlated with age (50 to < 60 years: OR = 2.91, 95% CI: 0.44-13.45; 60 to < 70 years: OR = 3.52, 95% CI: 0.73-8.77; 70 to < 80 years: OR = 4.31, 95% CI: 0.85-8.96), ethnicity ( OR = 4.45, 95% CI: 0.56-5.95), sex ( OR = 0.47, 95% CI: 0.34-0.64), age-related cataract ( OR = 1.67, 95% CI: 1.05-2.65), glaucoma ( OR = 2.97, 95% CI: 1.67-5.30), and coronary heart disease ( OR = 2.56, P < 0.05). Blindness was correlated with age (70-79 years: OR = 1.54, 95% CI: 1.12-2.11), sex ( OR = 0.67, 95% CI: 0.34-0.64), glaucoma ( OR = 1.65, 95% CI: 0.42-6.49), diabetes ( OR = 2.05, 95% CI: 1.35-3.09), and coronary heart disease ( OR = 1.92, 95% CI: 1.07-3.43). Among these, age (70-79 years), glaucoma, diabetes, and coronary heart disease were identified as risk factors for blindness, while sex was observed as a protective factor against blindness in this region. Based on univariate and multivariate analyses as well as clinical practice, it was concluded that age (50 to < 60 years: OR = 4.42, 95% CI: 1.31-14.92; 60 to < 70 years: OR = 4.49, 95% CI: 1.70-11.84; 70 to < 80 years: OR = 3.19, 95% CI: 1.29-7.87), age-related cataract ( OR = 1.67, 95% CI: 1.05-2.65), and glaucoma ( OR = 2.97, 95% CI: 1.67-5.30) were identified as significant risk factors for moderate to severe visual impairment. Glaucoma ( OR = 1.65, 95% CI: 0.42-6.49) and diabetes ( OR = 2.05, 95% CI: 1.35-3.09) were identified as the main risk factors for blindness in this region (both P < 0.05). Conclusions:In Tacheng City, Xinjiang Uygur Autonomous Region, the prevalence rates of moderate to severe visual impairment and blindness among Han and Kazakh residents are relatively high. Age-related cataracts and glaucoma are the primary causes, while age and diabetes are the main risk factors.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective To retrospectively analyze the association between metabolic factors and high-risk colorectal adenoma(CRA).Methods The medical records of patients aged 18-75 years who underwent their initial colonoscopy at Karamay Central Hospital of Xinjiang Uygur Autonomous Region from Jul 2000 to Mar 2017 were collected.The comparison between normal colonoscopy(NC)and high-risk CRA patients was conducted using an unpaired t-test,while chi-square test was used for categorical variables.Least absolute shrinkage and selection operator(LASSO)regression and Logistic regression were utilized to analyze the association between metabolic factors and high-risk CRA.Results A total of 1 798 patients meeting the inclusion and exclusion criteria were enrolled and divided into normal colonoscopy(NC)findings group(n=972)and high-risk CRA group(n=826).The high-risk CRA group exhibited significantly lower levels of high-density lipoprotein cholesterol(HDL-C)in comparison to the NC group,while uric acid and fibrosis 4(FIB-4)index levels were significantly higher than those observed in the NC group(all P<0.05).Based on LASSO regression analysis,we identified 12 variables that potentially influence the occurrence of high-risk CRA,including age,gender,smoking history,alcohol consumption history,non-alcoholic fatty liver disease(NAFLD),hypertension,coronary artery disease,hyperglycemia,hypercholesterolemia,low levels of HDL-C,elevated alanine aminotransferase,and elevated gamma-glutamyl transferase.Multivariate analysis revealed that individuals aged over 50 years,male gender,cigarette and alcohol consumption,low HDL-C levels,history of NAFLD and hypertension were identified as independent risk factors associated with high-risk CRA(P<0.05).In addition,without or with adjusting for age,sex,smoking,and drinking history,patients with a high TG/HDL-C ratio(the ratio≥2.68)had a significantly higher risk of high-risk CRA than those with a low TG/HDL-C ratio(the ratio<2.68)[odds ratios(ORs)were1.430 and 1.235 respectively,all P<0.05)].Without or with adjusting variables,the ORs for NAFLD patients with FIB-4 index>2.67 were 1.849(P=0.466)and 1.435(P=0.707),respectively.Conclusion A significant association exists between metabolic factors and high-risk CRA.Independent risk factors for high-risk CRA include older age(≥50 years),male,smoking history,alcohol consumption history,low levels of HDL-C,and a history of NAFLD and hypertension.Individuals exhibiting a TG/HDL-C ratio exceeding 2.68 manifest a significantly heightened susceptibility to the development of high-risk CRA.Therefore,elderly males with one or more aforementioned metabolic abnormalities should be considered a priority population for colorectal screening.

Objective:To provide novel genetic biomarkers for the diagnosis and treatment of sepsis,bioinformatics analysis was used to screen differentially expressed genes and identify Hub genes in sepsis.Methods:Gene Expression Omnibus(GEO)database was used to retrieve gene expression datasets of sepsis and screen for differentially expressed genes(DEGs).Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to clarify the molecular mechanism of DEGs,and Hub genes were screened.Results:A total of 361 DEGs were identified,including 163 up-regulated genes and 198 down-regulated genes.Enrichment analysis revealed that these DEGs were primarily involved in antigen processing and presentation,T cell biology,cell adhesion molecules,and T cell receptor signaling pathways.CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1 were determined as optimal diagnostic biomarkers for sepsis.Conclusions:This study elucidated 10 Hub genes(CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1)as potential biomarkers for the diagnosis and treatment of sepsis.However,since the the generalizability of these Hub genes in patients with sepsis remains unvalidated,further experimental verification is still needed in the future.

Objective To fabricate nanosilicate functionalized polycaprolactone(PCL/LAP)electrospun membrane and evaluate its role in bone marrow mesenchymal stem cells(BMSCs)-induced bone repairing.Methods The PCL/LAP electrospun membranes were fabricated via electrospinning technology and co-cultured with rat BMSCs.The cytocompatibility of the membranes was evaluated through cytoskeleton staining,live/dead cell staining and CCK-8 assay.The migration capacity of BMSCs was assessed using scratch assay,Transwell migration experiments and expression of migration-related genes(Pdgf and Tgfβ)was evaluated by qRT-PCR.The os-teogenic differentiation and pro-angiogenesis potential were determined by alkaline phosphatase(ALP)staining,alizarin red staining,expression levels of osteogenesis-related genes(Alp,Col1a1,Runx2,Bglap and Bmp2)and angiogenesis-related genes(Angpt1,Fgf2 and Vegfa)along with RUNX2 protein expression.PCL and PCL/LAP electrospun membranes conditioned medium was subsequently used to stimulate vascular endothelial cells(EAhy926).The expression of angiogenesis-associated genes(KDR,ENOS and HIF1A)was quantified by qRT-PCR.Results BMSCs adhered well to the surface of the PCL/LAP membranes,with no significant impact on cell viability(P＞0.05).PCL/LAP membranes not only promoted the proliferation(P＜0.05),migration(P＜0.05),but also enhanced ALP activity and mineralized nodule formation(P＜0.05),increased osteogenic differentiation gene and protein expression(P＜0.05)of BMSCs.Moreover,PCL/LAP promoted the expression of angiogenic genes of BMSCs(P＜0.05),to indirectly regulate angiogenesis-related gene expression in vascular endothelial cells(P＜0.05).Conclusion PCL/LAP electrospun membranes exhibit excellent biocompatibility and can promote proliferation,migration,osteogenic differentiation and BMSC-mediated angiogenic differentiation,showing great potential for bone defect repairing as barrier membrane.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To explore the application value of the integrated situational simulation teaching model based on the "Internet+"in obstetrics and gynecology clinical clerkship.Methods:Fifty-eight undergraduate students enrolled in 2019 who participated in the clinical clerkship at the Chengdu Fifth People's Hospital from June to September 2023 were selected and divided into a research group ( n=29) and a control group ( n=29) using the random number table method. The research group received the integrated situational simulation teaching model based on "Internet+", while the control group received traditional teaching methods. After clinical clerkship, theoretical tests, teacher evaluation, and questionnaire surveys were conducted to evaluate and compare the teaching effectiveness of the two groups of students. SPSS 23.0 was used for t test and chi-square test. Results:After receiving the integrated situational simulation teaching model based on "Internet+" for clinical clerkship, the research group achieved significantly higher theoretical test scores than the control group [(83.62±4.95) vs. (72.93±4.70), t=8.43, P<0.001]. The scores of all items in the mini-clinical evaluation exercise of the research group were higher than those of the control group ( P<0.01). According to the teaching feedback questionnaire, all students were satisfied with this new teaching model and reported that this model increased their interest in learning. Moreover, 86.21% (25/29) and 96.55% (28/29) of the students believed that the new model not only improved learning efficiency but also facilitated the integration of theory and practice. Conclusions:The integrated situational simulation teaching model based on "Internet+" is feasible in obstetrics and gynecology clinical clerkship and contributes to enhancing the quality of clinical clerkship teaching. This model is worthy of further research and promotion.

Objective:To provide novel genetic biomarkers for the diagnosis and treatment of sepsis,bioinformatics analysis was used to screen differentially expressed genes and identify Hub genes in sepsis.Methods:Gene Expression Omnibus(GEO)database was used to retrieve gene expression datasets of sepsis and screen for differentially expressed genes(DEGs).Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to clarify the molecular mechanism of DEGs,and Hub genes were screened.Results:A total of 361 DEGs were identified,including 163 up-regulated genes and 198 down-regulated genes.Enrichment analysis revealed that these DEGs were primarily involved in antigen processing and presentation,T cell biology,cell adhesion molecules,and T cell receptor signaling pathways.CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1 were determined as optimal diagnostic biomarkers for sepsis.Conclusions:This study elucidated 10 Hub genes(CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1)as potential biomarkers for the diagnosis and treatment of sepsis.However,since the the generalizability of these Hub genes in patients with sepsis remains unvalidated,further experimental verification is still needed in the future.