Objective:To analyze the awareness of and factors influencing the adjusted national immunization schedule for the diphtheria-tetanus-acellular pertussis (DTaP) vaccine among grassroots immunization service personnel in China.Methods:Based on the snowball sampling method from January to February 2025, immunization service personnel from all provinces of China were selected from the "Tingting Experts Talk" WeChat platform, with concurrent dissemination through the "National Vaccine-Preventable Diseases Communication Group" WeChat group. The questionnaire included basic demographic characteristics and knowledge of the DTaP vaccine immunization policy (13 questions in total). Respondents who answered ≥10 questions correctly were defined as being aware of the policy adjustment. The multivariable logistic regression analysis was performed to identify factors influencing awareness.Results:A total of 8 030 valid questionnaires were collected from 29 provinces, with a valid response rate of 92.91%. The overall awareness accuracy rates among the Centers for Disease Control and Prevention (CDC) personnel and the point of vaccination (POV) staff were 74.1% and 62.5%, respectively. The awareness rate of the core points of policy adjustment among the research subjects exceeded 90%. Among the questions regarding the operational details of policy implementation, the correct rate of answering questions related to the catch-up vaccination principles was relatively low (37.1%-74.0%). The multivariate logistic regression analysis showed that, compared with those with primary titles, CDC personnel with senior titles had higher mastery of the policy adjustment, with an OR (95% CI) value of 2.238 (1.343-3.730). Compared with those engaged in disease surveillance and immunization strategy research, CDC personnel with other work types had lower awareness of the policy adjustment, with an OR (95% CI) value of 0.404 (0.195-0.833). Compared with those in western regions, with primary titles, and without relevant training, POV staff in central regions, eastern regions, with intermediate titles, with senior titles, with one relevant training session, and with ≥2 relevant training sessions had better awareness of the program adjustment, with OR (95% CI) values of 1.214 (1.085-1.358), 1.412 (1.246-1.600), 1.606 (1.446-1.784), 1.737 (1.443-2.091), 2.254 (1.509-3.366), and 2.674 (1.769-3.981), respectively. Compared with those engaged in information registration/recipient notification, POV staff with vaccination services and other work types had lower awareness of the program adjustment, with OR (95% CI) values of 0.713 (0.633-0.803) and 0.508 (0.427-0.604), respectively. Conclusion:Although grassroots immunization service personnel show an insufficient mastery of certain catch-up vaccination knowledge, they demonstrate a good understanding of overall principles and routine immunization schedules shortly after the policy adjustment, which can effectively ensure an orderly transition between old and new immunization strategies.

Objective To investigate the characteristics of left ventricular hypertrophy in patients with primary aldosteron-ism(PA)accompanied by varying severity of obstructive sleep apnea(OSA),and to further identify potential factors contributing to ventricular hypertrophy in this population.Methods A retrospective analysis was performed on 308 patients with PA who received treatment at Kunming Medical University Affiliated Cardiovascular Hospital from January 2021 to June 2022.For com-parison,309 hospitalized patients diagnosed with essential hypertension(EH)during the same period were included as the control group.According to polysomnography findings,the patients were categorized into PA/EH with OSA group and PA/EH without OSA group.PA patients with OSA were further stratified into mild,moderate,and severe OSA subgroups based on the apnea-hypopnea index(AHI).Demographic characteristics,biochemical profiles,and echocardiographic parameters were compared across the groups.Results Compared to the EH groups with or without OSA,interventricular septal diastolic thickness(IVS-DT),left ventricular mass index(LVM),and left ventricular mass index(LVMI)was increased in PA with OSA group(all P＜0.05).The body mass index(BMI)was increased in both the PA with OSA group and EH with OSA group compared to their counterparts without OSA(all P＜0.05).Within the three subgroups of PA patients with OSA,left ventricular end-diastolic di-mension(LVEDD),IVSDT,left ventricular posterior wall diastolic thickness(LVPWDT),and LVM measurements were in-creased in severe OSA group compared to the mild OSA group(all P＜0.05).Conclusion Aldosterone is an independent risk factor from OSA for left ventricular hypertrophy;In PA patients with OSA,cardiac impairment is severer in the moderate and severe OSA subgroups compared to those without OSA,and the severity of cardiac impairment escalates as OSA severity increa-ses.These findings highlight the necessity of screening for OSA in PA patients to stratify cardiac impairment risk and enable early therapeutic intervention.

Objective:To analyze the awareness of and factors influencing the adjusted national immunization schedule for the diphtheria-tetanus-acellular pertussis (DTaP) vaccine among grassroots immunization service personnel in China.Methods:Based on the snowball sampling method from January to February 2025, immunization service personnel from all provinces of China were selected from the "Tingting Experts Talk" WeChat platform, with concurrent dissemination through the "National Vaccine-Preventable Diseases Communication Group" WeChat group. The questionnaire included basic demographic characteristics and knowledge of the DTaP vaccine immunization policy (13 questions in total). Respondents who answered ≥10 questions correctly were defined as being aware of the policy adjustment. The multivariable logistic regression analysis was performed to identify factors influencing awareness.Results:A total of 8 030 valid questionnaires were collected from 29 provinces, with a valid response rate of 92.91%. The overall awareness accuracy rates among the Centers for Disease Control and Prevention (CDC) personnel and the point of vaccination (POV) staff were 74.1% and 62.5%, respectively. The awareness rate of the core points of policy adjustment among the research subjects exceeded 90%. Among the questions regarding the operational details of policy implementation, the correct rate of answering questions related to the catch-up vaccination principles was relatively low (37.1%-74.0%). The multivariate logistic regression analysis showed that, compared with those with primary titles, CDC personnel with senior titles had higher mastery of the policy adjustment, with an OR (95% CI) value of 2.238 (1.343-3.730). Compared with those engaged in disease surveillance and immunization strategy research, CDC personnel with other work types had lower awareness of the policy adjustment, with an OR (95% CI) value of 0.404 (0.195-0.833). Compared with those in western regions, with primary titles, and without relevant training, POV staff in central regions, eastern regions, with intermediate titles, with senior titles, with one relevant training session, and with ≥2 relevant training sessions had better awareness of the program adjustment, with OR (95% CI) values of 1.214 (1.085-1.358), 1.412 (1.246-1.600), 1.606 (1.446-1.784), 1.737 (1.443-2.091), 2.254 (1.509-3.366), and 2.674 (1.769-3.981), respectively. Compared with those engaged in information registration/recipient notification, POV staff with vaccination services and other work types had lower awareness of the program adjustment, with OR (95% CI) values of 0.713 (0.633-0.803) and 0.508 (0.427-0.604), respectively. Conclusion:Although grassroots immunization service personnel show an insufficient mastery of certain catch-up vaccination knowledge, they demonstrate a good understanding of overall principles and routine immunization schedules shortly after the policy adjustment, which can effectively ensure an orderly transition between old and new immunization strategies.

Objective To investigate the characteristics of left ventricular hypertrophy in patients with primary aldosteron-ism(PA)accompanied by varying severity of obstructive sleep apnea(OSA),and to further identify potential factors contributing to ventricular hypertrophy in this population.Methods A retrospective analysis was performed on 308 patients with PA who received treatment at Kunming Medical University Affiliated Cardiovascular Hospital from January 2021 to June 2022.For com-parison,309 hospitalized patients diagnosed with essential hypertension(EH)during the same period were included as the control group.According to polysomnography findings,the patients were categorized into PA/EH with OSA group and PA/EH without OSA group.PA patients with OSA were further stratified into mild,moderate,and severe OSA subgroups based on the apnea-hypopnea index(AHI).Demographic characteristics,biochemical profiles,and echocardiographic parameters were compared across the groups.Results Compared to the EH groups with or without OSA,interventricular septal diastolic thickness(IVS-DT),left ventricular mass index(LVM),and left ventricular mass index(LVMI)was increased in PA with OSA group(all P＜0.05).The body mass index(BMI)was increased in both the PA with OSA group and EH with OSA group compared to their counterparts without OSA(all P＜0.05).Within the three subgroups of PA patients with OSA,left ventricular end-diastolic di-mension(LVEDD),IVSDT,left ventricular posterior wall diastolic thickness(LVPWDT),and LVM measurements were in-creased in severe OSA group compared to the mild OSA group(all P＜0.05).Conclusion Aldosterone is an independent risk factor from OSA for left ventricular hypertrophy;In PA patients with OSA,cardiac impairment is severer in the moderate and severe OSA subgroups compared to those without OSA,and the severity of cardiac impairment escalates as OSA severity increa-ses.These findings highlight the necessity of screening for OSA in PA patients to stratify cardiac impairment risk and enable early therapeutic intervention.

Transient receptor potential vanilloid-1(TRPV1) channel is a non-selective ligand-gated cationic channel with multiple activation mechanisms in the transient receptor potential subfamily. In recent years, a large number of studies have found that TRPV1 plays an important role in the field of cardiovascular diseases such as hypertension and atherosclerosis. With the in-depth study of traditional Chinese medicine, it has been found that Chinese medicine monomers and their active components can activate or inhibit TRPV1 channels, which has certain potential in the study of cardiovascular diseases. In this paper, the role of TRPV1 channel in cardiovascular diseases and the research progress of traditional Chinese medicine prevention and treatment of cardiovascular diseases based on TRPV1 channel are reviewed, in order to provide new ideas for prevention and treatment of cardiovascular system diseases.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To understand the incidence trend of meningococcal meningitis from 1990 to 2023 and major pathogenic serogroups of Neisseria ( N.) meningitidis from 2006 to 2023 in China and the time trend of the incidence of meningococcal meningitis caused by main pathogenic serogroups, and provide reference for the prevention and control of meningococcal meningitis. Methods:The study used the data from "National Epidemic Data Compile" from 1990 to 2003 and the data from China Notifiable Infectious Disease Reporting System from 2004 to 2023 to analyze the incidence trend of meningococcal meningitis in China from 1990 to 2023 by Joinpoint regression method. Based on the data of the national meningococcal meningitis surveillance information reporting and management system from 2006 to 2023, the incidence of meningococcal meningitis caused by different serogroups of N. meningitidis was described and analyzed, and the trend χ2 test was performed to analyze the change of the incidence of meningococcal meningitis caused by N. meningitidis A, B, and C. Results:The overall incidence of meningococcal meningitis in China showed a downward trend from 1990 to 2023 [average annual percent change (AAPC)=-14.80%, P<0.001], with the most obvious decline from 2005 to 2012 [annual percent change (APC)=-31.01%, P<0.001]. The incidence of meningococcal meningitis decreased in both men and women (AAPC=-14.69% and -15.05%, both P<0.001). A total of 1 178 serogroup specific cases of meningococcal meningitis were reported in China from 2006 to 2023, the proportion of serogroup C was highest (32.5%), followed by unclassified (22.3%), B (20.1%), A (18.4%), W (4.5%), Y (2.0%) and X (0.2%). The results of trend χ2 test indicated that the incidence of meningococcal meningitis caused by N. meningitidis A and C showed downward trends (both P<0.001) and the incidence of meningococcal meningitis caused by N. meningitidis B showed an upward trend in general population and young children (0-4 years old group) from 2006 to 2023 (both P<0.05). Conclusion:The incidence of meningococcal meningitis showed a downward trend in China from 1990 to 2023, but it is still necessary to pay more attention to the incidence of meningococcal meningitis caused by N. meningitidis B in age group aged 0-4 years and by multi serogroups at same time in general population.

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate C_pk integrated Bootstrap-t. The C_pk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10^-15 g/L, and the quantitative limit reached 1.0 × 10^-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (K_D) of 5.701 × 10^-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a K_D of up to 4.181 × 10^-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.