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Background The inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD. Methods The data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk. Results Overall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31–2.20) for all-cause mortality, and 2.00 (1.39–2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001). Conclusion MMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.

The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features of the TME include metabolic reprogramming, hypoxia, chronic inflammation, and tumor immunosuppression. Previous studies suggest that senescence‐associated secretory phenotypes that mediate intercellular information exchange play a role in the dynamic evolution of the TME. Specifically, hypoxic adaptation, metabolic dysregulation, and phenotypic shifts in immune cells regulated by cellular senescence synergistically contribute to the development of an immunosuppressive microenvironment and chronic inflammation, thereby promoting the progression of tumor events. This review provides a comprehensive summary of the processes by which cellular senescence regulates the dynamic evolution of the tumor‐adapted TME, with focus on the complex mechanisms underlying the relationship between senescence and changes in the biological functions of tumor cells. The available findings suggest that components of the TME collectively contribute to the progression of tumor events. The potential applications and challenges of targeted cellular senescence‐based and combination therapies in clinical settings are further discussed within the context of advancing cellular senescence‐related research.

Digital health (DH) provides a valuable opportunity for accessible and efficient palliative care delivery. In recent years, an expanding body of systematic reviews and meta-analyses has examined DH-based interventions in palliative care. However, their conclusions regarding effects remain inconsistent, often constrained by methodological limitations and the variable quality of primary studies, making it difficult to form a coherent appraisal. This umbrella review aimed to examine, appraise, and synthesize previous systematic reviews and evaluate the role of DH-based services on palliative care, and to identify barriers to using DH-based services in these settings. Systematic reviews with or without meta-analysis focusing on DH within palliative care settings were considered eligible. Seven electronic databases, including PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wangfang, and VIP, were searched for eligible studies published from inception to April 2024. The inclusion criteria were identified based on the principles of the PICOS (Population, Intervention, Comparison, Outcomes, and Study Type) framework. Two reviewers independently screened records and extracted data. Eligible studies were appraised for methodological quality using the JBI (Joanna Briggs Institute) Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. A narrative synthesis, supported by tabulated summaries of the results, was used in this umbrella review. A total of 25 systematic reviews (4 with meta-analyses) published between 2012 and 2024 met our inclusion criteria, most of which were evaluated as moderate quality. Reported outcomes ranged from symptom management effectiveness to psycho-social burden (ie, mood, distress, and emotional well-being), quality of life, caregiver burden, decision-making, cost-effectiveness, communication, self-efficacy and self-management efficacy, resource use, family empowerment, and acceptability. The effect of DH-based interventions for palliative care was basically consistent, with all included reviews reporting either significant improvements or noninferiority of DH-based interventions as compared to usual care. Technical challenges, organizational factors, ethical concerns, resource constraints, nonverbal communication, and perceptions were considered as barriers to the use of DH-based services. Across included reviews, DH was found to be beneficial or noninferior to standard care, with no reported adverse effects, supporting its safety and feasibility as a mode of service delivery. To ensure successful implementation and long-term sustainability, a multifaceted strategy is needed that integrates technological enhancements and training, organizational commitment, ethical safeguards, infrastructure development, and equitable access. PROSPERO CRD42024539963; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024539963.

Background Despite being driven by a strong sense of duty and familial obligation, providing care for patients nearing the end of life poses challenges for family caregivers. Telemedicine has rapidly gained traction as a transformative approach to healthcare delivery, offering an array of benefits that could be particularly valuable in end-of-life care. However, research on the perspectives of telemedicine-based services among family caregivers of patients with end-of-life cancer is limited. Therefore, this study aims to explore the perspectives and preferences of telemedicine-based services among family caregivers of patients with end-of-life cancer and provide a framework for developing and executing a tailored telemedicine-based end-of-life care program that addresses the unique needs of family caregivers in mainland China. Method A descriptive phenomenological approach was used. Family caregivers were selected using purposive sampling at a tertiary cancer hospital. One-on-one semi-structured interviews were conducted with the participants from November to December 2022. Colaizz’s method was used to analyze the interviews. Results Fourteen participants participated in interviews. Three themes and ten subthemes were identified: motivation to receive telemedicine services (relief from the burden of home care; access to professional health care services), supportive care needs for telemedicine services (support for symptom management; negative emotional adjustment; death education; daily life care guidance), and functional expectations of telemedicine service platforms (ease of use; real-time online guidance and response; personalized automatic reminder; targeted matching push of health knowledge). Conclusion Family caregivers expressed interest in telemedicine-based services and identified various care needs before receiving telemedicine services. The findings of this study can help policymakers and healthcare providers develop more effective and culturally appropriate telemedicine-based service programs that can better support family caregivers of end-of-life cancer patients.

IQ motif-containing proteins can be recognized by calmodulin (CaM) and are essential for many biological processes. However, the role of IQ motif-containing proteins in spermatogenesis is largely unknown. In this study, we identified a loss-of-function mutation in the novel gene IQ motif-containing H ( IQCH ) in a Chinese family with male infertility characterized by a cracked flagellar axoneme and abnormal mitochondrial structure. To verify the function of IQCH, Iqch knockout (KO) mice were generated via CRISPR-Cas9 technology. As expected, the Iqch KO male mice exhibited impaired fertility, which was related to deficient acrosome activity and abnormal structures of the axoneme and mitochondria, mirroring the patient phenotypes. Mechanistically, IQCH can bind to CaM and subsequently regulate the expression of RNA-binding proteins (especially HNRPAB), which are indispensable for spermatogenesis. Overall, this study revealed the function of IQCH, expanded the role of IQ motif-containing proteins in reproductive processes, and provided important guidance for genetic counseling and genetic diagnosis of male infertility.

Ferroptosis is a regulatory cell death process pivotal in myocardial ischemia–reperfusion (I/R) injury. However, the precise mechanism underlying myocardial ferroptosis remains less known. In this study, we investigated the pathophysiological mechanisms of methylmalonic acid (MMA) associated with ferroptosis activation in cardiomyocytes after I/R. We found an increase level of MMA in patients with acute myocardial injury after reperfusion and AC16 cells under hypoxia/reoxygenation (H/R) condition. MMA treatment was found to be associated with excessive oxidative stress in cardiomyocytes, leading to ferroptosis-related myocardial injury. In mice with I/R injury, MMA treatment aggravated myocardial oxidative stress and ferroptosis, which amplified the myocardial infarct size and cardiac dysfunction. Mechanistically, MMA promoted NOX2/4 expression to increase reactive oxygen species (ROS) production in cardiomyocytes, aggravating myocardial injury. Notably, the increased ROS further activated ferroptosis by inhibiting solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression. In addition, MMA decreased the ectopic nuclear distribution of nuclear factor E2-related factor 2 (NRF2) by increasing the interaction between NRF2 and kelch-like ECH-associated protein 1 (KEAP1). This impeded the activation of GPX4/SLC7A11, downstream of NRF2, activating ferroptosis and aggravating myocardial cell injury. Collectively, our study indicates that MMA activates oxidative stress and ROS generation, which induces ferroptosis to exacerbate cardiomyocyte injury in an I/R model. These findings may provide a new perspective for the clinical treatment of I/R injury and warrant further investigation.

Many studies have recently been done on understanding the sources and formation mechanisms of atmospheric aerosols at ground level. However, vertical profiles and sources of size-resolved particulate matter within the urban boundary layer are still lacking. In this study, vertical distribution characteristics of size-segregated particles were investigated at three observation platforms (ground level, 118 m, and 488 m) on the 610 m high Canton Tower in Guangzhou, China. Size-segregated aerosol samples were simultaneously collected at the three levels in autumn and winter. Major aerosol components, including water-soluble ions, organic carbon, and elemental carbon, were measured. The results showed that daily average fine-particle concentrations generally decreased with height. Concentrations of sulfate and ammonium in fine particles displayed shallow vertical gradients, and nitrate concentrations increased with height in autumn, while the chemical components showed greater variations in winter than in autumn. The size distributions of sulfate and ammonium in both seasons were characterized by a dominant unimodal mode with peaks in the size range of 0.44–1.0 µm. In autumn, the nitrate size distribution was bimodal, peaking at 0.44–1.0 and 2.5–10 µm, while in winter it was unimodal, implying that the formation mechanisms for nitrate particles were different in the two seasons. Our results suggest that the majority of the sulfate and nitrate is formed from aqueous-phase reactions, and we attribute coarse-mode nitrate formation at the measurement site to the heterogeneous reactions of gaseous nitric acid on existing sea-derived coarse particles in autumn. Case studies further showed that atmospheric aqueous-phase and heterogeneous reactions could be important mechanisms for sulfate and nitrate formation, which, in combination with adverse weather conditions such as temperature inversion and calm wind, led to haze formation during autumn and winter in the Pearl River Delta (PRD) region.

Background Nursing informatics (NI) competency is a required core competency for high-quality care in digitally enabled healthcare environments. Given the increasing reliance on digital health in palliative care settings, it becomes crucial to evaluate the NI competency of nurses to ensure the seamless integration and effective utilization of digital health in their clinical practice. This study aimed to investigate the level of NI competency and explore its associated factors among palliative care nurses in mainland China. Methods A cross-sectional design was conducted for this study, involving a total of 409 palliative care nurses from 302 hospitals in mainland China. Anonymous data were collected through a self-designed sociodemographic questionnaire, the Nursing Informatics Competency Scale (NICS) and the Innovative Self-Efficacy Scale. Results The total score of the NICS was 129.19 ± 22.02, which indicated that Chinese palliative care nurses had a moderate level of NI competency. There was a positive correlation between innovative self-efficacy and NI competency ( r  = 0.602, P  < 0.01). The hospital level and innovative self-efficacy were identified as statistically significant factors influencing nurses’ NI competency based on multiple linear regression analysis results. These associated factors could explain 35.1% of the difference in NI competency. Conclusions This study found that palliative care nurses in mainland China exhibited moderate levels of NI competency and identified the hospital level and innovative self-efficacy as associated factors of nurses’ NI competency. Measures such as developing supported strategies, including targeted NI training programs by nursing education managers of primary-level hospitals and creating a positive culture of innovation by healthcare institutions can be considered to improve the level of NI competency among Chinese palliative care nurses.

Particulate matter (PM) pollution in China is an emerging environmental issue which policy makers and the public have increasingly paid attention to. In order to investigate the characteristics, sources, and chemical processes of PM pollution in Guangzhou, field measurements were conducted from 20 November 2017 to 5 January 2018, with a time-of-flight aerosol chemical speciation monitor (ToF-ACSM) and other collocated instruments. Mass concentrations of non-refractory submicron particulate matter (NR-PM1) measured by the ToF-ACSM correlated well with those of PM2.5 or PM1.1 measured by filter-based methods. The organic mass fraction increased from 45 % to 53 % when the air switched from non-pollution periods to pollution episodes (EPs), indicating significant roles of organic aerosols (OAs) during the whole study. Based on the mass spectra measured by the ToF-ACSM, positive matrix factorization (PMF) with the multilinear engine (ME-2) algorithm was performed to deconvolve OA into four factors, including hydrocarbon-like OA (HOA, 12 %), cooking OA (COA, 18 %), semi-volatile oxygenated OA (SVOOA, 30 %), and low-volatility oxygenated OA (LVOOA, 40 %). Furthermore, we found that SVOOA and nitrate were significantly contributed from local traffic emissions while sulfate and LVOOA were mostly attributed to regional pollutants. Comparisons between this work and other previous studies in China show that secondary organic aerosol (SOA) fraction in total OA increases spatially across China from the north to the south. Two distinctly opposite trends for NR-PM1 formation were observed during non-pollution periods and pollution EPs. The ratio of secondary PM (SPM = SVOOA + LVOOA + sulfate + nitrate + ammonium) to primary PM (PPM = HOA + COA + chloride), together with peroxy radicals RO2∗ and ozone, increased with increasing NR-PM1 concentration during non-pollution periods, while an opposite trend of these three quantities was observed during pollution EPs. Furthermore, oxidation degrees of both OA and SOA were investigated using the f44∕f43 space and the results show that at least two OOA factors are needed to cover a large range of f44 and f43 in Guangzhou. Comparisons between our results and other laboratory studies imply that volatile organic compounds (VOCs) from traffic emissions, in particular from diesel combustion and aromatic compounds, are the most likely SOA precursors in Guangzhou. Peroxy radical RO2∗ was used as a tracer for SOA formed through gas-phase oxidation. For non-pollution periods, SOA concentration was reasonably correlated with RO2∗ concentration during both daytime and nighttime, suggesting that gas-phase oxidation was primarily responsible for SOA formation. However, there was no correlation between SOA and RO2∗ in pollution EPs, suggesting a dramatically changed mechanism for SOA formation. This conclusion can also be supported by different features of SOA in a van Krevelen diagram between non-pollution periods and pollution EPs. Furthermore, for pollution EPs, when NR-PM1 mass concentration was divided into six segments, in each segment except for the lowest one SOA concentration was correlated moderately with RO2∗ concentration, suggesting that gas-phase oxidation still plays important roles in SOA formation. The intercepts of the above linear regressions, which likely correspond to the extent of other mechanisms (i.e., heterogeneous and multiphase reactions), increase with increasing NR-PM1 mass concentration. Our results suggest that while gas-phase oxidation contributes predominantly to SOA formation during non-pollution periods, other mechanisms such as heterogeneous and multiphase reactions play more important roles in SOA formation during pollution EPs than gas-phase oxidation.

Backgrounds The majority of Chinese people who are nearing the end of their lives prefer to receive home-based palliative care. Telehealth, as a new service model, has the potential to meet the increasing demand for this service, especially in remote areas with limited resources. However, nurse-led telehealth-based palliative care services are still in the pilot implementation phase. Assessing the telehealth readiness among palliative care specialist nurses and identifying associated factors is crucial to facilitate the successful implementation of telehealth services. Therefore, this study aimed to examine TH readiness and its related factors among Chinese palliative care specialist nurses. Methods Four hundred nine Chinese palliative care specialist nurses from 28 provinces or municipalities participated in this study between July and August 2022. The Chinese version of Telehealth Readiness Assessment Tools (TRAT-C), and Innovative Self-Efficacy Scale (ISES-C) were used to assess the degree of TH readiness and the levels of innovative self-efficacy. Results The total score of the TRAT-C was 65.31 ± 9.09, and the total score of ISES was 29.27 ± 5.78. The statistically significant factors that influenced telehealth readiness were the experience of using telehealth platforms or services, the willingness to provide telehealth to patients, and the level of nurses’ innovative self-efficacy. The innovative self-efficacy is positively correlated to telehealth readiness ( r  = 0.482, P  < 0.01). These related factors could explain 27.3% of the difference in telehealth readiness. Conclusion The telehealth readiness of Chinese palliative care specialist nurses are at a moderate level. Measures such as providing incentives to promote nurses’ innovation self-efficacy by nurse managers, and establishing a comprehensive telehealth training system for palliative care specialist nurses should be taken to facilitate the implementation of telehealth services in the field of palliative care.