Introduction Long-term exposure to ambient air pollution is a significant public health concern, yet its specific association with skin diseases in the Chinese middle-aged and older population remains insufficiently characterized, with limited evidence on the role of individual pollutants. Material and methods We analyzed prospective data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative cohort. Participants aged ≥ 45 years from the 2011 baseline survey were followed through 2018. Annual average concentrations of PM2.5, PM10, NO2, SO2, and PM1 at participants’ community residences were assessed using satellite-based models with 1-km resolution. Skin disease was defined by a self-reported physician diagnosis or related symptoms. Multivariable logistic regression models were used to estimate odds ratios (ORs), adjusting for demographic, socioeconomic, lifestyle, and health-related covariates. Sensitivity analyses included age-restricted (≥65 years) and incident-case cohorts, and propensity score matching. Results Among 7,894 participants, long-term exposure to higher levels of PM2.5 (fully adjusted OR = 1.25, 95% CI: 1.13–1.38), PM10 (OR = 1.18, 95% CI: 1.04–1.32), and NO2 (OR = 1.15, 95% CI: 1.02–1.29) was significantly associated with higher odds of skin disease. Associations for SO2 and PM1 were not statistically significant. Results remained consistent across all sensitivity analyses, supporting the robustness of the findings. Conclusions This national cohort study provides evidence that long-term exposure to PM2.5, PM10, and NO2 is associated with higher odds of skin diseases among Chinese middle-aged and older adults. These findings suggest that air pollution control may represent a potential intervention target for reducing the burden of skin disease in aging populations.
Migraine is a prevalent primary headache disorder affecting 14–17% of the global population and is strongly influenced by sex hormones. However, its characteristics in transgender individuals remain poorly understood and insufficiently studied. This review synthesizes evidence from 126 publications across neurology, otorhinolaryngology, pharmacology, and psychiatry to explore potential relationships between migraine and transgender health. Findings suggest that sex-related differences in migraine extend beyond epidemiology to clinical presentation, severity, and management, and may manifest uniquely in transgender patients. Factors such as gender-affirming hormone therapy, psychosocial stress, internal conflict, minority stress, and societal stigma may contribute to an increased headache burden. Additionally, barriers to healthcare access and limited provider knowledge may further complicate diagnosis and treatment. Despite these insights, data remain limited and fragmented. Greater awareness, interdisciplinary collaboration, and further research are needed to improve understanding and to develop more personalized, inclusive, and effective approaches to migraine management in transgender populations.
Introduction We investigated the associations between glucose regulation states and the risks of adverse renal outcomes and all-cause mortality in a large outpatient population. Material and methods We retrospectively identified patients with a baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 between 2010 and 2022. Patients were categorized into glucose regulation states according to their history of diabetes and glycated hemoglobin (HbA1c) levels. Data on each patient’s renal function were obtained from electronic medical records, and survival status was confirmed through March 2023. The outcomes of interest included adverse renal outcome (≥40% reduction of eGFR from baseline) and all-cause mortality. Results A total of 43,422 patients were analyzed. After a median follow-up of 6.9 years, patients with diabetes, stratified by HbA1c levels (<7.0%, 7.0 to <9%, and ≥ 9%), exhibited a significantly higher risk of adverse outcomes (adjusted HR 1.922, 2.376 and 3.306, respectively, all p<0.001) compared with those with normal glucose tolerance. In contrast, there was no significant difference in adverse outcomes between patients with prediabetes and those with normal glucose tolerance (adjusted HR 1.090, p=0.107). Conclusions Compared with normal glucose tolerance, patients with diabetes had a higher risk of adverse outcomes, even among those with an HbA1c <7%. Maintaining glycemic control within the non-diabetic range may help mitigate long-term adverse renal outcomes.
Introduction The association between serum iron levels and type 2 diabetes mellitus (T2DM) remains unclear. Material and methods In total, 19,483 participants from the National Health and Nutrition Examination Survey (NHANES) 2009–2018 were included in this study. The weighted t-test and chi-squared test were used to compare differences in iron levels and covariates between individuals with and without T2DM. Subsequently, weighted multivariate logistic regression models were constructed to assess the association between iron levels and T2DM risk. Furthermore, Mendelian randomization (MR) analysis was conducted to evaluate the causal effect of iron levels on T2DM. Sensitivity analysis and Steiger’s test were employed to validate the dependability and effectiveness of the MR findings. Results Weighted multivariate logistic regression analyses revealed a statistically significant inverse association between iron levels and T2DM risk, with odds ratios of 0.955, 0.948, and 0.983 in models 1, 2, and 3, respectively. Receiver operating characteristic curve analysis implied that iron levels accurately identified patients with T2DM. MR analysis demonstrated a marked causal impact of iron levels on T2DM risk, and iron levels represented a protective factor to some extent. Sensitivity analysis confirmed the robustness of the MR findings, and Steiger’s test confirmed the plausibility and validity of the causal effect direction of iron levels on T2DM. Conclusions This study supported a negative correlation between iron levels and T2DM risk, which holds potential clinical significance for T2DM prevention and early risk assessment.
Introduction Acute lung injury (ALI) is characterized excessive inflammatory signaling and uncontrolled cytokine production. Tristetraprolin (TTP) is a key post-transcriptional regulator of inflammatory cytokines that negatively regulates inflammatory pathways. PP2A emerges as an important player to activate TTP. However, whether pharmacological activation of PP2A can restore TTP activity and thereby attenuate ALI remains unexplored. Material and methods A lipopolysaccharide (LPS)-induced mice model of ALI and LPS-stimulated RAW264.7 macrophages were used to evaluate the effects of FTY720 or siRNA PP2A. Lung injury and inflammation were assessed by histopathology, wet-to-dry weight ratio, bronchoalveolar lavage fluid analysis, and cytokine quantification. PP2A activity, p38 MAPK and TTP phosphorylation, and gene expression were analyzed using phosphatase assays, Western blot, ELISA, and quantitative RT-PCR. Results Pretreatment of FTY720, a well-established PP2A activator, significantly alleviated LPS-induced lung injury, inflammatory cell infiltration, and inflammatory cytokines release in vivo. Treatment with PP2A siRNA blocked the improvement effect induced by FTY720 in LPS-induced lung injury mice. LPS exposure significantly impaired PP2A activity without altering PP2A protein abundance, whereas FTY720 restored PP2A activity in lung tissues. Mechanistically, PP2A activation suppressed p38 MAPK phosphorylation and/or promoted dephosphorylation of TTP in LPS-induced macrophages. Moreover, PP2A activation by FTY720 inhibited p38 MAPK and TTP phosphorylation without affecting TTP transcription, leading to reduced inflammatory cytokine production. Conclusions Our findings demonstrate that PP2A activation blocked inflammatory responses by reprogramming the TTP activity. Pharmacological targeting of PP2A may represent a promising strategy for the treatment of acute lung injury.
Introduction Exercise training has cardioprotective effects after myocardial infarction (MI), but the associated molecular pathways remain incompletely defined. The novel aspect of this work is the comparison of short-term and extended post-MI ET while examining the angiotensin II type 1 receptor (AT1R)/TGF-β1/Smad axis as an associated anti-fibrotic pathway. Material and methods Sprague-Dawley rats were assigned to four groups: sham control, MI-sedentary, MI with 4-week Exercise training (MIex1), and MI with 12-week of exercise training (MIex3). ET began three days after coronary artery ligation. After 12 weeks, echocardiography and hemodynamic measurements were performed, and left ventricular (LV) tissue was collected for histological and molecular analyses. Results Compared with MI-sedentary rats, MIex1 rats showed increased LV systolic pressure, ±dP/dtmax, ejection fraction, and fractional shortening, along with decreased LV end-diastolic pressure and LV diameters. Twelve-week Exercise training further enhanced functional outcomes. Both ET groups reduced collagen volume fraction and collagen I/III expression. ET was also associated with lower cardiac Ang II, AT1R, TGF-β1, and phosphorylated Smad2/3, with stronger effects after 12 weeks of Exercise training. Conclusions Exercise reduces myocardial fibrosis following MI and preserves cardiac function, an effect that may be amplified by extended exercise training. Downregulation of AT1R-mediated TGF-β1/Smad signaling may be associated with these cardioprotective effects.
Introduction Burn injury causes cellular and metabolic dysfunction associated with mitochondrial damage, oxidative stress and impaired epidermal regeneration, delaying wound healing and raising the risk of chronic complications. As a key metabolic enzyme connecting the tricarboxylic acid cycle (TCA) cycle to lipid synthesis and epigenetic regulation, ATP citrate lyase (ACLY) maintains mitochondrial homeostasis and redox balance, while its role in thermal skin repair remains unclear. Material and methods RNA-seq analysis identified molecular changes in thermal injury, while polymerase chain reaction (PCR) and Western blot were used to validate ACLY expression in burn-injured skin tissue. To dissect ACLY function in wound repair, we performed in vivo AAV-mediated ACLY knockdown. A panel of assays was also conducted in in vivo and in vitro ACLY-overexpression models, including hematoxylin and eosin (HE), immunohistochemistry, 5-ethynyl-2-deoxyuridine (EdU) assay, Transwell migration and invasion, transferase dUTP nick end labelling (TUNEL) staining, acetyl coenzyme A (acetyl-CoA) and ATP quantification, malondialdehyde (MDA) and glutathione (GSH) detection, as well as JC-1 and 2,7-dichlorofluorescin diacetate (DCFH-DA) staining. Results ACLY expression was markedly downregulated in burn tissues with associated metabolic reprogramming. In vivo AAV-mediated ACLY knockdown markedly aggravated burn injury and impaired wound repair. In contrast, ACLY overexpression improved repair outcomes in both in vivo and in vitro thermal injury models. It relieved oxidative damage by lowering reactive oxygen species (ROS) and MDA, maintained mitochondrial integrity through modulating mitochondrial dynamics, attenuated inflammatory response and cellular apoptosis, and enhanced keratinocyte proliferation as well as migration, ultimately accelerating epidermal regeneration and wound healing. Conclusions ACLY plays an important role in regulating mitochondrial stability and epidermal repair following burns. These findings provide novel insights into metabolic mechanisms underlying tissue regeneration and suggest that ACLY may represent a potential therapeutic target for burn healing and regenerative medicine.
Introduction Persistent pain is a common long-term sequela in breast cancer survivors treated with chemotherapy and may involve neuropathic pain and central sensitization (CS). However, few studies have examined these mechanisms together and their association with specific sensory symptoms. Material and methods A multicenter cross-sectional study was conducted in four Spanish hospitals between September 2022 and January 2025. A total of 254 women with surgically treated breast cancer who had completed chemotherapy were included. Neuropathic pain was assessed using the Spanish version of the Douleur Neuropathique 4 (DN4), CS using the Central Sensitization Inventory (CSI), and pain intensity and sensory symptoms (paresthesia, tingling, and thermal sensitivity) using visual analog scales. Between-group comparisons according to the presence of neuropathic pain and central sensitization, as well as analyses of their independent and combined effects on pain intensity and sensory symptoms, were performed. Results Participants reported moderate pain intensity, with clinically relevant neuropathic pain features and CS. Patients with neuropathic pain (DN4 ≥ 4) showed significantly higher pain intensity and greater severity of all sensory symptoms (all p < 0.001). Similarly, participants with CS reported higher pain intensity and greater severity of tingling and thermal sensitivity. Neuropathic pain and CS were independently associated with increased symptom burden and frequently coexisted. Conclusions Neuropathic pain and CS are common and overlapping components of persistent pain in breast cancer survivors treated with chemotherapy and are associated with greater pain intensity and sensory symptom severity. Concurrent assessment of both mechanisms may improve the clinical characterization and management of post-chemotherapy pain.
Introduction Obesity is closely associated with the risk of cancers. This study analyzed national population surveys from the United States and China to investigate the association between weight-adjusted waist index (WWI) and thoracic cancer. Material and methods Data from two national population surveys were used in the study. Logistic regression analysis was used to analyze the association between WWI and thoracic cancer. Restricted cubic spline (RCS) analysis was used to investigate a potential nonlinear relationship. The stability of this relationship across different subgroups was assessed through subgroup analysis. ROC curve analysis facilitated the evaluation of different obesity indicators in terms of their efficacy in predicting thoracic cancer. Results A relationship between thoracic cancer and WWI was identified. RCS analysis confirmed the nonlinear relationship between thoracic cancer and WWI (p for nonlinear < 0.001). The analysis of subgroups indicated that the association between thoracic cancer and WWI was broadly applicable across different populations, further confirming the robustness of the study findings. ROC analysis showed that WWI possessed satisfactory predictive capability for thoracic cancer. Conclusions The study showed that WWI was independently associated with thoracic cancer prevalence in both the United States and Chinese populations. Furthermore, the accuracy of WWI in predicting thoracic cancer risk surpasses that of conventional obesity indicators.
Introduction The remnant cholesterol to high-density lipoprotein cholesterol ratio (RC/HDL-C) reflects atherogenic lipid burden. We investigated its association with mortality in patients with chronic obstructive pulmonary disease (COPD) and the mediating role of body mass index (BMI). Material and methods This cross-sectional study included 1,307 COPD patients from NHANES 2007–2018. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines (RCS) were employed to assess dose-response relationships. Mediation analysis was conducted to quantify the extent to which BMI mediated the association between RC/HDL-C and mortality. Results During a median follow-up of 104 months, 226 all-cause and 74 cardiovascular deaths occurred. After adjusting for potential confounders, elevated RC/HDL-C was independently associated with higher risks of all-cause (HR = 2.16, 95% CI: 1.64–2.86) and cardiovascular mortality (HR = 3.30, 95% CI: 2.19–4.99). Mediation analysis indicated that BMI exerted a suppression effect on the association with all-cause mortality, masking 11.0% of the RC/HDL-C-associated risk. However, no significant mediating effect of BMI was observed for cardiovascular mortality. Stratified analyses indicated that these associations were more pronounced in patients younger than 65 years. Conclusions RC/HDL-C is independently associated with all-cause and cardiovascular mortality in COPD patients. While higher BMI partially suppresses the association between RC/HDL-C and all-cause mortality, no mediating effect is observed for cardiovascular mortality. The associations were more pronounced in younger patients, suggesting potential value for risk stratification in this subgroup.
Introduction Metabolic syndrome (MetS) involves dyslipidaemia and inflammation. However, the joint association of high-sensitivity C-reactive protein (hsCRP) and residual cholesterol (RC) with the risk of MetS remains unclear. Material and methods This longitudinal study enrolled 7,063 participants from the China Health and Retirement Longitudinal Study (CHARLS). Participants were grouped by median RC (17 mg/dl) and hsCRP threshold (1 mg/l). Multivariate logistic regression and restricted cubic spline (RCS) analyses were used to evaluate the joint association of RC and hsCRP with the risk of MetS. Results During the 4-year follow-up period, 920 participants (11.5%) developed new-onset MetS. Compared with the group with low RC and low hsCRP, the fully adjusted odds ratio (OR) was 1.43 (p = 0.005) for the high RC only group and 2.56 (p < 0.001) for the group with both elevated levels, with a significant trend (p < 0.001). The residual cholesterol inflammation index (RCII) was positively associated with incident MetS risk. The fully adjusted OR (with 95% confidence interval [CI]) for quartile (Q) 4 vs. Q1 was 2.52 (1.92–3.30, p < 0.001), with a non-linear trend (p < 0.001). This association was consistent across age, sex, and BMI subgroups (all p for interaction > 0.05) and remained robust after excluding participants taking lipid-lowering drugs and using multiple imputation. Conclusions Elevated hsCRP and RC were independently and synergistically associated with a higher MetS risk. Combined evaluation of inflammatory and lipid-related markers may help identify individuals at increased risk of MetS. The findings provide further evidence of the association between these pathways and MetS development.
Introduction To characterize adverse-event (AE) reporting patterns and disproportionality signals for three ligustrazine-containing injectable formulations used for cardiovascular and cerebrovascular diseases: ligustrazine, Ginkgo biloba with ligustrazine, and Salvia miltiorrhiza with ligustrazine. Material and methods Publicly available WHO-VigiAccess data were searched on November 24, 2024. Reports were summarized by formulation, sex, age group, continent, year, MedDRA System Organ Class (SOC), and Preferred Term (PT). Disproportionality was assessed using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network/Information Component (BCPNN/IC), and Empirical Bayes Geometric Mean (EBGM). For each formulation, the comparator consisted of all other medicinal-product reports available through the VigiAccess/VigiBase aggregate counts. Because spontaneous-report data lack exposure denominators, results are interpreted as reporting signals rather than incidence, absolute risk, comparative clinical safety, or causal evidence. Results A total of 32,017 reports were retrieved: 12,640 for ligustrazine, 246 for Ginkgo biloba with ligustrazine, and 19,131 for Salvia miltiorrhiza with ligustrazine. Reports were overwhelmingly Asia-based. The 45–64-year age group accounted for the largest reporting proportion across formulations, and adult reports represented more than 99% of reports in each group. General disorders/administration-site conditions, skin and subcutaneous tissue disorders, gastrointestinal disorders, nervous system disorders, and vascular disorders were frequent SOC categories. Ginkgo biloba with ligustrazine showed a relatively stronger skin-disorder signal at the SOC level (ROR = 3.36; PRR = 2.78; IC = 1.48; EBGM = 2.78), but interpretation is limited by the small report volume. Salvia miltiorrhiza with ligustrazine showed prominent phlebitis-related PT signals, including superficial phlebitis (EBGM = 191.09), phlebitis (EBGM = 155.82), and infusion-site phlebitis (EBGM = 125.62). Ligustrazine reports frequently included pruritus, chest pain, nausea, dizziness, and rash. Age and sex patterns were interpreted only as reporting distributions, not as incidence peaks or susceptibility signals. Conclusions The three ligustrazine-containing injectable formulations showed different AE reporting patterns in VigiAccess. These findings should be considered hypothesis-generating pharmacovigilance signals and require validation in denominator-based, clinically annotated, and preferably prospective data sources. Clinical interpretation should account for geography, product utilization, indication, infusion practice, reporting bias, duplicate reporting, and the highly unbalanced number of reports across formulations.
Introduction Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a predominant global cause of chronic liver disease, linked to various health issues. Although sedentary behavior (SB) has been associated with MAFLD, an exact upper limit for sedentary time has not been established. This study aimed to investigate the dose-response relationship between sedentary time and MAFLD and identify potential reference values for future research and recommendations. Material and methods The study analyzed 7,705 participants from the 2017–2020 NHANES cycle, using transient elastography to identify MAFLD and liver fibrosis or cirrhosis. Sedentary time and physical activity levels were determined through a detailed questionnaire, with physical activity classified by official guidelines. Restricted cubic spline and piecewise regression analyses examined the association between sedentary time and MAFLD. Results Sedentary time demonstrated a linear dose-response relationship with MAFLD (p for non-linear = 0.647, p overall < 0.001), with sedentary behavior over 5 h daily significantly associated with higher odds of MAFLD. After adjustment for confounders, each additional sedentary hour was associated with a 7.7% increase in the odds of MAFLD (p < 0.001). Males had a higher prevalence of MAFLD, liver fibrosis, and cirrhosis than females (p < 0.001). Further analysis revealed no significant difference by sex in the association between sedentary time and MAFLD (p for interaction = 0.0974). Conclusions Prolonged sedentary time is associated with higher odds of MAFLD in US adults. Reducing excessive sedentary behavior may represent a potential strategy for MAFLD prevention, although further longitudinal studies are needed to establish evidence-based sedentary time recommendations.
Introduction Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed for cardiometabolic indications and may exert anti-inflammatory and tissue-regenerative effects. However, their effect on tendon healing and tendon-related surgical outcomes remains unclear. In this systematic review and meta-analysis, we evaluated the available preclinical and clinical evidence on the effects of GLP-1RAs on tendon healing and related musculoskeletal outcomes. Methods A systematic search of the PubMed, Embase, Medline, Scopus, Clinical Key, Google Scholar, and Cochrane databases was conducted from database inception to December 31, 2025. Eligible studies included animal studies, human experimental studies, and retrospective clinical cohorts that evaluated GLP-1RA exposure in relation to tendon biology, tendon healing, or tendon-related orthopedic outcomes. Risk of bias was assessed using design-appropriate tools, including SYRCLE, ROBINS-I, the Newcastle-Ottawa Scale, SANRA, AMSTAR 2, and the NIH assessment tool. Results A total of 41 studies were included: eight animal studies, three human experimental studies, six retrospective cohort studies, one prospective study, 18 review or commentary articles, and five systematic reviews. Preclinical evidence generally supported the tendon-promoting effects of GLP-1RAs through the modulation of inflammation, fibroblast activity, angiogenesis, and extracellular matrix remodeling. Quantitative synthesis of two retrospective cohorts evaluating revision risk after total shoulder arthroplasty suggested a lower risk among GLP-1RA users than non-users. However, only two studies were eligible for pooling, and significant clinical heterogeneity remained across the available cohorts. Conclusions GLP-1RAs demonstrate biologically plausible tendon healing benefits in preclinical models, with a potentially favorable association with selected postoperative outcomes; however, causal inference remains limited by retrospective design, heterogeneity, and potential confounding factors.
Introduction Cancer remains a major public health burden in Poland, with a substantial proportion of cases attributable to modifiable behavioral risk factors such as smoking, obesity, and physical inactivity. These factors are socially patterned, contributing to health inequalities across socioeconomic groups. The study aimed to quantify socioeconomic gradients in key behavioral cancer risk factors in Poland. Material and methods A cross-sectional analysis was conducted using data from the Polish wave of the European Health Interview Survey (EHIS) 2019, covering a nationally representative sample of individuals aged ≥ 15 years. Educational attainment was used as an indicator of socioeconomic status (SES; high, middle, low). Prevalence of smoking, obesity (body mass index ≥ 30 kg/m²), and lack of recreational physical activity were estimated across educational groups. Socioeconomic gradients were assessed using prevalence ratios (PRs), and the estimated number of individuals exposed to each risk factor was calculated using national population estimates. Results Clear socioeconomic gradients were observed for all analyzed risk factors. Individuals with low education had higher prevalence of smoking (23.6% vs. 11.6%, PR = 2.03), obesity (21.9% vs. 11.9%; PR = 1.84), and physical inactivity (59.5% vs. 39.3%; PR = 1.51) compared to those with high education. The low-education group (41% of the population) accounted for ~47–49% of all exposures, indicating a disproportionate concentration of behavioral cancer risk. Reducing these inequalities could substantially decrease the population burden of risk factors. Conclusions Behavioral cancer risk factors in Poland are unequally distributed and disproportionately concentrated among socioeconomically disadvantaged groups. Addressing these inequalities through targeted, equity-oriented prevention strategies may help reduce the future cancer burden.
Introduction:Depression is associated with cardiovascular disease, but the impact of metabolic markers on cardiometabolic multimorbidity (CMM) remains unclear. We examined the atherogenic index of plasma (AIP) and triglyceride-glucose index (TyG) in relation to CMM risk in depressed adults from the China Health and Retirement Longitudinal Study (CHARLS) and the English Longitudinal Study of Ageing (ELSA). Material and methods:We analyzed 3,225 depressed Chinese (CHARLS) and 353 UK (ELSA) individuals aged ≥ 50 years. CMM comprised diabetes, coronary heart disease, and stroke. Metabolic dysregulation was assessed using AIP and TyG indices. Multivariable logistic regression was used to examine the associations. Results:In CHARLS, the CMM group had significantly higher AIP (0.47 ±0.29 vs. 0.36 ±0.28) and TyG (8.96 ±0.72 vs. 8.65 ±0.62) than the non-CMM group (p < 0.001). In Model 3, each unit increase in AIP was associated with CMM risk (OR = 3.93, 95% CI: 2.91-5.33, p < 0.001), similarly for TyG (OR = 2.07, 95% CI: 1.82-2.36, p < 0.001). In the ELSA validation cohort, the CMM group also had higher TyG (p < 0.001) and AIP (p = 0.004). In Model 3, each unit increase in TyG was associated with CMM (OR = 2.46, 95% CI: 1.42-4.25, p = 0.001), similarly for AIP. Restricted cubic spline analysis showed a dose-response relationship. Conclusions:AIP and TyG are independent predictors of CMM in depressed adults across different cultural contexts. These indices are promising, accessible tools for early risk stratification and targeted intervention to manage cardiometabolic multimorbidity in depression.
