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Background and aims Cardiovascular disease (CVD) is associated with inflammation and abnormal lipid metabolism. However, a single inflammatory index or a single lipid index cannot accurately predict the prognosis of CVD independently because it is prone to be affected by various confounding factors. Methods This population-based cohort study included 6,554 participants from the China Health and Retirement Longitudinal Study (CHARLS) to investigate correlations. In the present study, the occurrence of CVD events such as stroke and heart disease was evaluated by considering self-reported diagnoses at the beginning of the study and during wave 4, and a restricted cubic spline model was used to investigate potential nonlinear relationships in addition to multivariate logistic regression models. Stratified analyses were performed to examine how sociodemographic characteristics may influence the results. Results Seven years of follow-up (2011–2018) revealed that 786 people (11.99%) developed CVD. According to the adjusted model, the high-sensitivity C-reactive protein (hs-CRP)-to-high-density lipoprotein cholesterol (HDL-C) ratio is a contributing factor to CVD risk (OR 1.31, 95% CI 1.05–1.64). In addition, a nonlinear relationship was observed between the hs-CRP/HDL-C ratio and the occurrence of new CVD, stroke, or cardiac issues ( P overall <0.05, Pnonlinear <0.05). Moreover, noteworthy associations between the hs-CRP/HDL-C ratio and age were detected in the stratified analysis ( P  = 0.048), indicating that younger participants had more negative effects of a high hs-CRP/HDL-C ratio. Conclusions According to the present cohort study, a high hs-CRP/HDL-C ratio is a significant risk factor for CVD, new stroke, and heart problems. Early intervention in patients with increased hs-CRP/HDL-C ratios may further reduce the incidence of CVD, in addition to focusing on independent lipid markers or independent inflammatory markers.

The genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a “genome organizer” that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development. Pioneer transcription factors (TFs) have been proposed to act as protein anchors to orchestrate cell type-specific 3D genome architecture. MyoD is a pioneer TF for myogenic lineage specification. Here the authors provide further support for the role of MyoD in 3D genome architecture in muscle stem cells by comparing MyoD knockout and wild-type mice.

To explore the relationship between physical exercise and smoking behavior among Chinese residents aged 16 years and older. Analysis based on 29,466 validated cases in the 2018 China Family Panel Studies (CFPS 2018). The chi-square test and Mann–Whitney U test were used for comparative analysis between groups. Logistic regression analysis was used to explore the relationship between physical exercise and smoking behavior. Gender and birth cohort differences in the relationship between physical exercise and smoking behavior were explored based on stratified regression analysis using gender and birth cohort as stratified variables, respectively. Robustness testing based on multiple linear regression analysis using a replacement data approach. There were 8735 cases of smokers among the respondents. After controlling for relevant confounders, there was a significant negative association between physical exercise and smoking behavior among residents [OR 0.718, 95% CI (0.673, 0.765), P < 0.01]. Physical exercise was more significantly associated with smoking behavior among male residents [OR 0.694, 95% CI (0.649, 0.743), P < 0.01], while it was not significantly associated with smoking behavior among female residents [OR 0.901, 95% CI (0.743, 1.093), P > 0.05]. Physical exercise was more significantly associated with smoking behavior in the pre-1948 (OR 0.748), 1959–1968 (OR 0.748), 1969–1978 (OR 0.812), 1989–1998 (OR 0.576) and post-1999 (OR 0.411) birth cohorts, and the association decreased over time and with social change. The results of the robustness test showed that frequency of exercise was significantly and negatively associated with smoking behavior among residents [OR 0.961, 95% CI (0.951, 0.970), P < 0.01]. Physical exercise is negatively associated with smoking behavior among Chinese residents aged 16 years and older, especially among male residents. There is a cohort effect between physical exercise and smoking behavior of the population, that is, the relationship between the two decreases with social change.

The clinical risk of cognitive disorders linked to various drugs is not well-defined. This study aimed to identify medications with notable signals for drug-related cognitive disorders and evaluate whether their US Food and Drug Administration (FDA)-approved labels include relevant safety warnings. A retrospective disproportionality analysis using FDA Adverse Event Reporting System data (2004-2024) employed four algorithms-Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-Item Gamma Poisson Shrinker (MGPS)-for signal detection. To confirm the results, a cross-database consistency check was performed with the Japanese Adverse Drug Event Report (JADER) and World Health Organization (WHO) VigiAccess databases. An analysis of 41,775 reports on drug-related cognitive disorders found significant signals for 50 medications using four algorithms. Notably, 74% of these drugs, including finasteride, diltiazem, and carbidopa/levodopa, lacked cognitive disorder warnings in FDA labels. Reporting patterns were classified into early or random failure types. Subgroup analyses showed certain drugs were disproportionately reported in vulnerable groups, such as antiepileptics in children and neurologic agents in seniors. The U.S. had the most reports. Multivariate analysis identified 43 factors linked to higher reporting odds, including conditions like depression and the use of specific drugs. Cross-database validation confirmed consistent signals for 92% of primary drug-event pairs. This pharmacovigilance analysis uncovers significant, previously unrecognized signals of drug-related cognitive disorders in various medications, most lacking label warnings. These findings highlight the need for further research, potential label updates, and increased clinical awareness, particularly in high-risk groups. Importantly, these results indicate statistical associations, not causal links, between the drugs and cognitive disorders.

ObjectiveTo explore the lived experiences of novice nurses during their transition from participation in the ‘Attending Rounds’ clinical case mentoring training model to independent clinical practice, and to understand its influence on their development of clinical competence, role identity and team collaboration.DesignA descriptive phenomenological study using semistructured, face-to-face interviews, guided by Colaizzi’s seven-step method of data analysis.SettingTwo large teaching hospitals in eastern China, representing secondary and tertiary levels of care.Participants12 novice nurses (nine female, three male; aged 22–29 years; bachelor’s or master’s degree holders) who had completed the ‘Attending Rounds’ training at least four times and subsequently entered clinical practice. Participants were recruited purposively to ensure variation in demographic and educational backgrounds.InterventionsNot applicablePrimary outcome measuresThe primary outcomes were novice nurses’ lived experiences and perceptions of the ‘Attending Rounds’ model, captured through semistructured interviews and analysed using Colaizzi’s phenomenological method.Secondary outcome measuresExperiential domains included: (1) skill improvement—enhanced clinical judgement, patient management and ward management; (2) learner anxiety and growth—initial discomfort and stress evolving into confidence and resilience; (3) role modelling—professional inspiration and learning through observation of senior nurses and (4) team cohesion—improved communication, collaboration and patient-centred care.ResultsFour overarching themes with 12 subthemes were identified: (1) skill improvement (clinical judgement, patient and ward management); (2) stress and growth (initial anxiety and adaptation leading to confidence); (3) role modelling (learning from senior nurses, leadership inspiration) and (4) team cohesion (enhanced collaboration, strengthened patient-centred care). Nurses described initial discomfort and anxiety, but over time developed greater competence, confidence and awareness of professional responsibilities.ConclusionsThe ‘Attending Rounds’ model facilitated novice nurses’ transition into clinical practice by integrating structured case-based learning, role modelling and team collaboration. While stress and anxiety were common at the outset, these experiences were ultimately perceived as catalysts for growth. Findings suggest the model may be further refined to support novice nurses’ professional identity formation and clinical competence.

Background Propofol is a commonly used anesthetic. However, its effects on glioma growth and recurrence remain largely unknown. Methods The effect of propofol on glioma growth was demonstrated by a series of in vitro and in vivo experiments (spheroidal formation assay, western blotting, and xenograft model). The acyl-biotin exchange method and liquid chromatography-mass spectrometry assays identified palmitoylation proteins mediated by the domain containing the Asp-His-His-Cys family. Western blotting, co-immunoprecipitation, quantitative real-time polymerase chain reaction, co-immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assays were used to explore the mechanisms of the γ -aminobutyric acid receptor (GABA A R)/Src/ZDHHC5/EZH2 signaling axis in the effects of propofol on glioma stem cells (GSCs). Results We found that treatment with a standard dose of propofol promoted glioma growth in nude mice compared with control or low-dose propofol. Propofol-treated GSCs also led to larger tumor growth in nude mice than did vector-treated tumors. Mechanistically, propofol enhances the stem-like properties of gliomas through GABA A R to increase Src expression, thereby enhancing the palmitoylation of ZDHHC5-mediated EZH2 and Oct4 expression. Conclusion These results demonstrate that propofol may promote glioma growth through the GABA A R-Src-ZDHHC5-EZH2 mechanism and are helpful in guiding the clinical use of propofol to obtain a better patient prognosis after the surgical resection of tumors.

Background Recognizing symptoms and responding appropriately can reduce emergency department visits, heart failure hospitalization rates, and all-cause mortality. However, elderly patients with chronic heart failure face greater challenges in symptom recognition due to physiological decline and multiple comorbidities, which significantly impact their prognosis. Therefore, we conducted a randomized controlled trial to evaluate the effects of an age-friendly implementation tool on elderly patients’ symptom self-management capabilities, delayed medical care rates, and emergency department visit rates, providing evidence-based guidance for optimizing health management strategies in this population. Methods This protocol describes a parallel randomized controlled trial (RCT) in which evaluators and analysts used a blinded method to target elderly patients over 60 years of age with heart failure. The trial compared an intervention group ( n  = 74) with a conventional treatment group ( n  = 74). The primary outcomes are self-reported symptom recognition ability assessed via the Dutch Heart Failure Knowledge Questionnaire and self-care ability assessed via the European Heart Failure Self-Care Behavior Questionnaire. The secondary outcomes include quality of life (QoL) measured via the EuroQol-5D (EQ-5D) and delayed medical care rates. All these data will be collected at baseline, at discharge, at 3 months, and at 6 months to test the effectiveness of the age-friendly execution assistance tool. Discussion This study will confirm that elderly-friendly tools can effectively enhance self-management capabilities for elderly CHF patients, significantly reducing delayed medical care and emergency department visits. We anticipate that this tool, tailored to the physiological and cognitive characteristics of the elderly population, will provide evidence-based references for precision health management and interventions for elderly patients with similar chronic conditions. Ethics and dissemination The Medical Ethics Committee of Sir Run Run Shaw Hospital, affiliated with the Zhejiang University School of Medicine (20250513), approved this study. All participants signed a written informed consent form prior to the baseline assessment. Once the final report of the study is completed, the results will be widely disseminated in peer-reviewed journals. The public will be informed of the study results through media reports, briefings, and other means. Trial registration ChiCTR2500106241. Registered on 21 July 2025

The Bijigou intrusion is one of the largest and most well-differentiated Fe–Ti oxide-bearing layered intrusions in the Hannan massif located in the northwestern margin of the Yangtze Block, South China. Besides the mineralization-related mafic-ultramafic rocks, the intermediate-acid intrusive rocks are also exposed in the mining area, which is of great significance for the understanding the Neoproterozoic tectonic evolution of the Yangtze Block, but studies on these intermediate-acid rocks are scarce. The Bijigou mafic-ultramafic layered intrusion is surrounded by granite and cut by syenite veins. Here, we report new zircon U-Pb ages, Lu-Hf isotope composition and bulk rock geochemical data of the Bijigou syenite vein and wall-rock granite in the northwestern margin of the Yangtze Block. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) zircon U-Pb dating results show that the Bijigou syenite vein and wall-rock granite formed at 770 ± 3.5 Ma (MSWD = 0.17, n  = 28) and 810 ± 4 Ma (MSWD = 0.84, n  = 26), respectively. The zircon εHf(t) values of the syenite veins range from + 1.52 to + 5.33 (average of + 3.05), combined with its high potassium contents, negative Nb–Ta anomalies and positive Pb anomalies, suggesting that they may have originated from mantle-derived basaltic magma, which was modified by materials from subducting oceanic slab. The zircon εHf(t) and T DM2 ages of the wall-rock granite range from + 0.71 to + 5.71 (average + 3.06) and 1344 to 1659 Ma (average 1519 Ma), respectively, indicating that the granite was produced by partial melting of juvenile crust. The geochemical characteristics of the Bijigou syenite and granite indicate that they were formed in a continental margin arc setting. Thus, combined with previous studies, it suggests that there was a major subduction system along the northwestern margin of the Yangtze Block during 824–720 Ma, and the magmatism in the Hannan massif was divided into two episodes: (1) early magmatism (824–790 Ma), such as the Bijigou, Hongmiaozhen and Huangguanzhen granitoids, was derived from partial melting of the juvenile or pre-existing crust in a continental arc setting; (2) later magmatism (789–718 Ma), including Bijigou syenite, Wudumen, Erliba and Zushidian granitoids, formed in a subduction-related back-arc extensional environment. The long-term subduction system along the northwestern margin of the Yangtze Block during 824–720 Ma suggests that the Yangtze Block was previously located at the periphery of the Rodinia supercontinent.

Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

This study aimed to identify high-risk drugs for drug-induced extrapyramidal disorder (EPD) and explore their molecular mechanisms by integrating pharmacovigilance analytics with genetic and computational approaches. We performed disproportionality analysis on FAERS data (2004-2024) to detect EPD signals, time-to-onset analysis to assess risk timing, Mendelian randomization (MR) to infer causal effects of drug-target gene expression (e.g., HTR1D, ADRA2B) on EPD risk, and molecular docking to evaluate drug-target binding affinities. Metoclopramide, risperidone, and haloperidol decanoate showed the strongest EPD signals. TTO analysis revealed an early failure pattern (Weibull β <1), indicating highest risk during initial treatment. MR identified brain-expressed HTR1D and ADRA2B as causally linked to EPD risk. Molecular docking confirmed strong binding of risperidone and paliperidone to these targets. This study is the first to integratively link pharmacovigilance signals with genetic causality and structural binding insights for EPD. Our findings support deprescribing high-risk agents, preemptive genetic screening, and enhanced early monitoring to mitigate drug-induced EPD, offering a translational framework for precision pharmacovigilance.