Objective To explore the effect of 1a,25(OH)2 D3 on circadian clock gene expressions in cardiac myocytes.Methods Cultured cardiac myocytes isolated from 7 -day -old Sprague -Dawley(SD)rats were identified by immunofluorescence.The medium including 1a,25 (OH)2 D3 (final concentrations were 0 nmol/L,1 nmol/L, 10 nmol/L,50 nmol/L and 100 nmol/L)were added to primary myocardial cells to culture for 2 h and then total RNA was extracted.Real -time polymerase chain reaction (RT -PCR)was applied to analyze myocardial cells circadian clock gene (Bmal1,Per2,Rev -erba)transcript levels to determine optimum concentration of 1a,25(OH)2 D3 .Then, the primary myocardial cells cultured for 72 h were divided into 3 groups:the control group was of serum -free culture medium;serum shock group was of DMEMcontaining 50%volume fraction of horse serum cultured 2 h;1a,25(OH)2 D3 treatment group receiving 1a,25 (OH)2 D3 at optimal concentration cultured 2 h.The cells were collected at 7 time points (0 h,4 h,8 h,12 h,16 h,20 h,24 h)and then total RNA was extracted.RT -PCR was applied to analyze circa-dian clock gene (Bmal1,Per2,Rev -erba)transcript levels in the myocardial cells.Results In the presence of 50 nmol/L 1 a,25(OH)2 D3 ,the Bmal1 mRNA expression showed the highest level,but the Per2 and Rev -erba mRNA expression levels were minimum.Compared with the control group,both 1a,25 (OH)2 D3 treatment group and serum shock group caused day -cycle rhythmic oscillation in circadian clock genes(Bmal1,Per2,Rev -erba)in the cardiac myocytes.And the expressions pattern of Bmal1 and Per2 genes were in the opposite phase.While Bmal1 gene expres-sion appeared at peak at 12 h,Per2 gene expression appeared in a trough.Expression of Rev -erba gene trend began to rise at 8 h,and the highest expression level appeared at 12 -16 h.Conclusions 1a,25(OH)2 D3 can affect Bmal1, Per2 and Rev -erba mRNA expressions of circadian clock genes in the cardiac myocytes.

In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc.4 overexpression on heart development in zebrafish. The overexpression of uc.4 influenced cell differentiation by inhibiting the TGF-beta signaling pathway and suppressed heart development in zebrafish, resulting in cardiac malformation. Taken together, our findings show that uc.4 is involved in heart development, thus providing a potential therapeutic target for CHD.

Objective To observe the changes in serum a proliferation inducing ligand(a proliferation inducing ligand,APRIL)and N-myc downstream regulated gene 1(N-myc downstream regulated gene 1,NDRG1)levels,and analyze their diagnostic value for ovarian endometrioma(OEM).Methods From July 2021 to July 2022,132 patients with OEM who visited Zigong First People's Hospital were regarded as the observation group,and regular follow-up was conducted.According to the prognosis of these patients,they were grouped into the recurrence group(n=50)and the non recurrence group(n=82).Meanwhile,78 healthy individuals who had their medical checkups at the hospital during the same period were the control group.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum APRIL and NDRG1 levels,and the general data of the recurrent and non recurrent groups were compared.Logistic regression analysis was applied to analyze the relevant factors affecting the prognosis of OEM.Pearson analysis was applied to explore the correlation between serum APRIL and NDRG1 levels in patients with OEM.Receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic value of serum APRIL,NDRG1 levels and their combination for OEM.Results Compared with the control group,APRIL level(35.28±6.81ng/ml vs 26.37±3.19ng/ml)and NDRG1 level(124.39±15.67μg/L vs 9.67±10.82μg/L)in observation group were increased,and the differences were significant(t=10.864,17.278,all P<0.05).Compared with the non recurrence group,the serum levels of APRIL(40.38±7.88ng/ml vs 32.16±6.18ng/ml)and NDRG1(132.04±19.83μg/L vs 119.73±13.16μg/L)in the recurrence group were increased,and the differences were significant(t=6.668,4.287,all P<0.05).Logistic regression analysis showed that serum APRIL and NDRG1 levels were risk factors for the prognosis of patients with OEM(Waldχ2=11.839,28.437,all P＜0.001).Pearson method analysis results showed a positive correlation between serum APRIL level and NDRG1 level in patients with OEM(r=0.439,P<0.001).The area under the curve(AUC)of combined diagnosis of serum APRIL and NDRG1 levels in patients with OEM was 0.849,with a sensitivity and specificity of 73.95%and 85.37%,respectively,which was better than the single prediction of APRIL and NDRG1(Z =2.644,2.094,P=0.008,0.036).Conclusion The serum levels of APRIL and NDRG1 were increased in patients with OEM.The combination of the two has high clinical value in the diagnosis of OEM,which may be closely related to the prognosis of patients with OEM.

Objective:To compare research hotspots in digital transformation of higher education in China and abroad and analyze the research trends through the bibliometric method and text analysis method, and to offer advice and suggestions for digital transformation of higher education in China.Methods:The relevant literature in Web of Science and China National Knowledge Infrastructure from the establishment of the databases to April 1, 2023 were retrieved. Citespace and VOSviewer were used to visually compare the research hotspots and trends in digital transformation of higher education in China and abroad from the perspectives of number of published papers, journal, author, country, cooperation network, keyword co-occurrence and clustering, and keyword burst.Results:The results showed that both international and domestic researchers paid attention to the practical significance and development model of digital transformation of higher education in the context of rapid development of science and technology and the post-pandemic era. International researchers emphasized the advantages and disadvantages of digital transformation from the aspects of connotation, practice logic, and theoretical framework, while Chinese researchers focused on clarifying the principles related to digital transformation, summarizing the experience of other countries, and exploring the development path. The application of educational technology and the digital literacy of teachers and students had become research hotspots in China and abroad.Conclusion:The research on digital transformation of higher education has gradually shifted from theoretical system to practice effect. In the future, with the continuous deepening of theoretical research, how to improve the effectiveness of digital transformation of higher education is a research direction worthy of attention.

Objective:To explore the application of a scenario-based onsite first-aid skills station in objective structured clinical examination (OSCE).Methods:Based on common scenarios and cases in medical practice, an evaluation framework of the OSCE onsite first-aid skills station—containing assessment indicators, exam room setting, examiner training, and assessment process—was designed to evaluate the onsite first-aid competencies of medical graduates of the five-year program for three consecutive years. SPSS 24.0 was used to perform the Kruskal-Wallis test and Pearson correlation analysis to calculate the correlation between course examination scores and OSCE onsite first-aid skills station assessment scores. Excel was used to calculate the difficulty index and discrimination index of test items.Results:The graduates' OSCE onsite first-aid skills station assessment scores were improved year by year, with a mean score of about 80 points. The station assessment items showed a moderate difficulty level (0.7-0.8), a good discrimination level (>0.4), and good internal consistency (Cronbach's α>0.7). The examiners and examinees had a high recognition of the design and effectiveness of this station assessment method. There was a positive correlation between the OSCE scores and corresponding course scores (2016, r=0.245, P=0.001; 2017, r=0.108, P=0.026; 2018, r=0.198, P=0.006). Conclusions:Through scientific scoring and strict examination management, the OSCE scenario-based onsite first-aid skills station can effectively evaluate examinees' injury treatment competencies in different situations, which can provide a reference for course teaching.

Objective:To investigate the efficacy and prognosis of rituximab (RTX) in the treatment of M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN).Methods:It was a retrospective cohort study. The clinical data of PLA2R-associated IMN patients who received RTX treatment in the Shenzhen Second People's Hospital from September 2018 to March 2023 were collected. According to remission status of proteinuria, the patients were divided into proteinuria remission group (24-hour urinary protein quantity < 3.5 g) and non-proteinuria remission group (24-hour urinary protein quantity ≥ 3.5 g), and the clinical data between the two groups were compared. According to baseline 24-hour urinary protein quantity and estimated glomerular filtration rate (eGFR), the patients were divided into high-risk disease progression group [24-hour urinary protein quantity ≥ 8 g or eGFR < 60 ml·min -1·(1.73 m 2) -1] and non-high-risk disease progression group [24-hour urinary protein quantity < 8 g or eGFR ≥ 60 ml·min -1·(1.73 m 2) -1]. Kaplan-Meier survival curve was utilized to compare the differences of proteinuria remission rates and renal composite endpoint event survival rates between the two groups. Multivariate Cox regression analysis was utilized to identify the influencing factors of proteinuria remission and renal composite endpoint event. Results:This study included 46 PLA2R-associated IMN patients, with 31 males (67.4%). The baseline eGFR was (78.4±34.1) ml·min -1·(1.73 m 2) -1. The 24-hour urinary protein quantity was 8.33 (6.04, 12.85) g. After 14.95 (7.44, 22.15) months of follow-up, 29 patients (63.0%) achieved proteinuria remission, with remission time of 6.0 (5.0, 9.0) months. Six (20.7%) patients relapsed, with relapsed time of 17.25 (11.75, 18.28) months. CD20 in the proteinuria remission group was lower than that in the non-proteinuria remission group ( Z=2.270, P=0.023). Eleven (23.9%) patients experienced renal composite endpoint events wtih occurrence time of 16.07 (7.87, 29.63) months. Kaplan-Meier survival curve analysis indicated that there was no statistically significant difference in proteinuria remission rates (log-rank χ2=0.26, P=0.612) and renal composite endpoint event survival rates (log-rank χ2=0.25, P=0.619) between baseline 24-hour urinary protein quantity ≥ 8 g and < 8 g groups. There was no statistically significant difference in proteinuria remission rates after RTX treatment (log-rank χ2=0.77, P=0.381) and renal composite endpoint event survival rates (log-rank χ2=1.41, P=0.236) between eGFR ≥ 60 ml·min -1·(1.73 m 2) -1 and < 60 ml·min -1·(1.73 m 2) -1 groups. Multivariate Cox regression analysis showed that hypertension history ( HR=0.16, 95% CI 0.05-0.55), immunosuppressive therapy history ( HR=0.08, 95% CI 0.01-0.50), baseline eGFR < 60 ml·min -1·(1.73 m 2) -1 ( HR=0.21, 95% CI 0.05-0.92), baseline PLA2R antibody titer ≥ 100 RU/ml ( HR=0.20, 95% CI 0.06-0.69), long time between treatment and first diagnosis ( HR=1.33, 95% CI 1.12-1.57), high baseline triglyceride ( HR=1.46, 95% CI 1.02-2.08), and baseline 24-hour urinary protein quantity ≥ 8 g ( HR=8.54, 95% CI 2.08-35.12) were independent influencing factors of proteinuria remission after RTX treatment. The baseline PLA2R antibody titer ≥ 100 RU/ml was an independent influencing factor of reaching the renal composite endpoint event ( HR=7.31, 95% CI 1.23-43.62). Conclusions:The proteinuria remission rate after RTX treatment of PLA2R-associated IMN is 63.0% and the recurrence rate is 20.7%. The incidence rate of renal composite endpoint event is 23.9%. The hypertension history, immunosuppressant medication history, baseline eGFR < 60 ml·min -1·(1.73 m 2) -1, baseline PLA2R antibody titer ≥ 100 RU/ml, long time between treatment and first diagnosis, high baseline triglyceride, and baseline 24-hour urinary protein quantity ≥ 8 g are independent influencing factors of proteinuria remission, and baseline PLA2R antibody titer ≥ 100 RU/ml is an independent risk factor of renal poor prognosis in PLA2R-associated IMN patients.

OBJECTIVE：To systematically evaluate the efficacy and safety of linezolid （LZD）combined with routine anti- tuberculosis drugs in the treatment of tuberculous meningitis （TBM），so as to provide evidence-based reference for clinical medi- cation. METHODS ：Retireved from PubMed ，Cochrane Library ，Embase，CNKI and Wanfang database ，randomized controlled trials（RCT）of LZD combined with routine anti-tuberculosis drugs （trial group ）versus routine anti-tuberculosis drugs （control group）were collected from the inception to Jan. 2020. After literature screening and data extraction ， the quality of the included literature were evaluated with bias risk assessment tool recommended by Cochrane system evaluator handbook 5.2. Meta-analysis was conducted by using Rev Man 5.3 software，and sensitivity analysis and publication bias analysis were performed. RESULTS ： Totally 9 RCTs involving 602 patients were included. Meta-analysis showed that total response rate [OR ＝4.05，95％CI（2.26，7.26）， P＜0.000 01]， changes of protein content of cerebrospinal fluid [MD ＝0.48，95％CI（0.20，0.77），P＝0.000 8]，changes of white blood cells count of cerebrospinal fluid [MD ＝44.43，95％CI（20.06，68.81），P＝0.000 4]，changes of cerebrospinal fluid glucose/ synchronous blood glucose [MD ＝0.09，95％CI（0.05，0.14），P＜0.000 1] of trial group were significantly higher than those of control group. There was no statistical significance in the changes of chloride content of cerebrospinal fluid [MD ＝8.08，95％CI（－0.64， 16.80），P＝0.07] and the incidence of ADR [OR ＝1.34，95％CI（0.57，3.11），P＝0.50] between 2 groups. The results of sensitivity analysis showed that there were significant differences comparison with before exclusion when the change of protein content in cerebrospinal fluid and the change of glucose/synchronous blood glucose in cerebrospinal fluid were taken as indexes ，and there was no significant difference comparison with before exclusion when the changes of white blood cell count and chloride content in cerebrospinal fluid were taken as indexes. The results of publication bias analysis showed that there was a certain publication bias in this study. CONCLUSIONS ：LZD combined with conventional anti-tuber culosis drugs is effective and safe for TBM. Because the inconsistent results of sensitivity analysis and publication bias exists in publication bias analysis ，the conclusions need to be further confirmed by more large sample and multi-center studies.