Drawing upon the relevant guidances on the bioequivalence study in China,referring to the requirements of international advanced supervision organization,considering the characteristics of the circulatory system drugs,this paper provides several considerations on the bioequivalence studies of the oral solid preparation generic drugs in the circulatory system.

Objective This study employs the Geographically and Temporally Weighted Regression(GTWR)model to assess the impact of meteorological elements and imported cases on dengue fever outbreaks,emphasizing the spatial-temporal variability of these factors in border regions. Methods We conducted a descriptive analysis of dengue fever's temporal-spatial distribution in Yunnan border areas.Utilizing annual data from 2013 to 2019,with each county in the Yunnan border serving as a spatial unit,we constructed a GTWR model to investigate the determinants of dengue fever and their spatio-temporal heterogeneity in this region. Results The GTWR model,proving more effective than Ordinary Least Squares(OLS)analysis,identified significant spatial and temporal heterogeneity in factors influencing dengue fever's spread along the Yunnan border.Notably,the GTWR model revealed a substantial variation in the relationship between indigenous dengue fever incidence,meteorological variables,and imported cases across different counties. Conclusion In the Yunnan border areas,local dengue incidence is affected by temperature,humidity,precipitation,wind speed,and imported cases,with these factors'influence exhibiting notable spatial and temporal variation.

Objective:To explore the effects of the scaffolding-based flipped classroom approach in the teaching of Infectious Disease Nursing. Methods:We assigned 152 students of nursing and midwifery majors of grade 2018 (experimental group) to be taught using the scaffolding-based flipped classroom approach and 182 students of grade 2017 (control group) to be taught using the traditional lecture method. Teaching effects were evaluated through students' exam performance and a questionnaire survey. Numerical data were analyzed using the χ2 test and t test with the use of SPSS 18.0, and text data were processed using NVivo 11 for thematic analysis. Results:The experimental group and control group showed significant differences in the interim exam score (83.19±7.96 vs. 79.62±3.14, P<0.001) and final exam score (78.47±6.92 vs. 73.16±8.24, P<0.001). The students of grade 2018 had a high level of participation in online learning. The questionnaire results showed that the scaffolding-based flipped classroom was well recognized in terms of students' overall perception, perceived course quality, perceived value of learning, and satisfaction and the open-ended question, with low scores for learner complaints and loyalty. Conclusions:The scaffolding-based flipped classroom is feasible in the teaching of Infectious Disease Nursing, which can improve students' academic performance and overall competence.

Purpose::Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI.Methods::A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region ( n =21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. Results::In 2019, there were 27.16 million (95% uncertainty intervals ( UI): 23.36 -31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298 -401) and 599 per 100,000 population (95% UI: 573 -627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% --0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% -0.06%). TBI caused 7.08 million (95% UI: 5.00 -9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 -117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. Conclusions::The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Objective: To analyze the risk factors of coronary artery occlusion in female patients with ischemic angina pectoris. Methods: Clinical data of 1 600 patients (666 females and 934 males) who underwent coronary angiography from January 2013 to December 2015 due to angina pectoris in 6 major coronary intervention centers in China were retrospectively analyzed. The clinical characteristics were compared between the female and male groups, and between the non-obstructive coronary artery disease (INOCA) and ischemic obstructive coronary artery disease (IOCA) subgroups of female subjects with angina pectoris. The risk factors related to the degree of coronary artery occlusion in female patients were analyzed. Results: In the enrolled patients who underwent coronary angiography for angina pectoris, female group was older than the male group, and the proportion of patients with hypertension, diabetes and ischemia accompanied by IOCA was significantly higher than that of the male group (P<0.05). Univariate analysis showed that age≥65 years, hypertension, diabetes, and typical angina symptoms were associated with an increased risk of IOCA in female patients with angina pectoris. Multivariate regression analysis showed that age≥65 years old (OR=1.784, 95%CI: 1.146-2.776, P=0.010), hypertension (OR=1.782, 95%CI: 1.201-2.644, P=0.004) and typical angina symptoms (OR=1.642, 95%CI: 1.127-2.393, P=0.010) were independent risk factors for female patients with angina pectoris diagnosed as IOCA. The correlation analysis between the number of risk factors and the type of coronary artery disease obstruction showed that the incidence of INOCA decreased significantly with the increase of the number of risk factors, from 45.5% to 14.2%. The incidence of IOCA increased significantly with the number of risk factors, from 54.5% to 85.8% (P for trend<0.001). Conclusion: The incidence of INOCA in female patients with angina pectoris suspected of coronary heart disease is higher than that of male. The incidence of IOCA increased significantly, and the incidence of INOCA decreased significantly in proportion to the increase of the number of combined risk factors.
Humans ; Male ; Female ; Aged ; Coronary Artery Disease/complications* ; Retrospective Studies ; Angina Pectoris/epidemiology* ; Risk Factors ; Coronary Angiography ; Hypertension/complications* ; Coronary Occlusion/complications* ; Ischemia/complications*

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.
Ethanol ; Molecular Docking Simulation ; Network Pharmacology ; Seeds/chemistry* ; Ziziphus/chemistry* ; Plant Extracts/chemistry* ; Schisandra/chemistry* ; Fruit/chemistry* ; Technology, Pharmaceutical

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.

Objective:To verify the effect and safety of low-intensity extracorporeal shockwave therapy(Li-ESWT)in improving the symptoms of ED,and provide some reference for further related large-scale clinical trials.Methods:Twenty-six patients diag-nosed with ED received Li-ESWT with an energy of 0.09 mJ/mm2 for 20 minutes once a week for 6 four-week courses.Before and at 3,6,9,and 12 months after treatment,we obtained the IIEF-5 and Erectile Hardness Scale(EHS)scores of the patients using question-naires,recorded the incidence of treatment-related adverse reactions,compared the erectile function of the patients before and after treatment,and evaluated the effect and safety of Li-ESWT in improving ED-related symptoms.Results:Compared with the baseline,the IIEF-5 scores of the patients were significantly increased(P＜0.01)while the EHS scores slightly increased at 3 months after Li-ESWT treatment(P＞0.05),both IIEF-5 and EHS scores were dramatically increased at 6 months(P＜0.01),and both signifi-cantly higher than at 3 months.At 9 months,EHS scores remained remarkably higher than the baseline(P＜0.01)although IIEF-5 scores slightly lower than at 6 months.At 12 months,however,IIEF-5 scores decreased,though still significantly higher than the base-line(P＜0.01),and EHS scores became lower than at 6 and 9 months(P＜0.05)but still markedly higher than before treatment(P＜0.05).Adverse reactions observed during the intervention mainly included pruritus(4.35％),pain(2.90％),paresthesia(2.17％),and petechiae/ecchymosis(2.90％).Conclusion:Li-ESWT can increase the IIEF-5 and EHS scores and improve the clinical symptoms of ED patients,with a low incidence of adverse reactions during the treatment.

Objective:To evaluate the consistency of the Gleason scores of PCa patients based on preoperative biopsy with those from postoperative pathology,identify the possible factors influencing results of scoring,and construct a risk scoring model.Meth-ods:We collected the demographic and clinical data on the patients with PCa confirmed by preoperative prostate biopsy or postoperative pathology and treated by radical prostatectomy within 6 months after diagnosis.Using paired sample t-test,we identified the difference between the Gleason scores based on preoperative biopsy and those from postoperative pathology,analyzed the demographic and clinical data on the patients for relevant factors affecting the consistency of the Gleason scores,and calculated and visualized the relative risk values of the factors through Poisson regression.From the continuous variables with statistical significance,we screened independent risk factors for the difference in the Gleason scores by Lasso regression analysis,established a risk scoring model,generated risk coeffi-cients,and evaluated the predictive ability of the model using the ROC curve.Based on the results of imaging examination with statisti-cally significant differences,we constructed a column chart by logistic regression and evaluated the predictive validity of the chart using calibration curves,decision curves and ROC curves.Results:The results of paired sample t-test for 210 PCa patients showed statisti-cally significant differences between the Gleason scores from preoperative biopsy and those from postoperative pathology(P＜0.001).There were significant differences in the body weight,BMI and PSA level as well as in all other factors but prostate calcification be-tween the patients with consistent and those with inconsistent Gleason scores(all P＜0.05).An 8-factor prediction model was suc-cessfully constructed,which could predict the consistency of Gleason scores,with a better predicting performance than the single indi-cator within the model.The nomogram exhibited a C-index value of 0.85,with the calibration curve similar to the standard one,the threshold of the decision curve 0.10-0.92,and the area under the ROC curve higher than other predictive indicators.Conclusion:Based on the demographic and clinical data on PCa patients,a risk prediction model and a column chart were successfully constructed,which could effectively predict the difference between the Gleason scores from preoperative prostate biopsy and those from postoperative pathology.