Sepsis-associated acute lung injury (SALI) is characterized by endothelial barrier dysfunction and capillary leakage. Ulinastatin (UTI), a serine protease inhibitor with recognized clinical benefits in sepsis, has been reported to protect endothelial function, but the underlying mechanisms remain incompletely defined. This study investigated the protective effects of UTI against SALI and its specific mechanism of action. We found that UTI attenuated lung injury and endothelial dysfunction in both cecal ligation and puncture (CLP)-induced septic rats and LPS-stimulated human umbilical vein endothelial cells (HUVECs). UTI treatment reduced the expression of angiopoietin-2 (Ang-2), a key mediator of vascular destabilization, and exerted similar protective effects on endothelial function as dexamethasone (DEX). Mechanistically, UTI was demonstrated to have a stable interaction and favorable binding affinity to PI3K by docking and activating the PI3K/Akt signaling pathway. This led to phosphorylation and subsequent nuclear export of the transcription factor FoxO1, thereby suppressing FoxO1-dependent Ang-2 transcription. The protective effects of UTI on capillary leakage and junctional protein integrity were abolished by the PI3K inhibitor wortmannin. In conclusion, our findings demonstrate that UTI alleviates SALI by disrupting an Ang-2-mediated vicious cycle via the PI3K/Akt/FoxO1 pathway, revealing a novel mechanistic insight into its therapeutic action against sepsis-induced vascular leakage.

Abstract Objective Sepsis is a life-threatening condition characterized by a dysregulated host response to infection. Although serum creatinine and albumin are well-established prognostic biomarkers, the clinical utility of the creatinine-to-albumin ratio (CAR) in sepsis remains insufficiently elucidated. This study aimed to investigate the nonlinear association between CAR and 28-day mortality and to develop a machine learning-based prediction model for risk stratification in critically ill patients with sepsis. Methods Clinical data from 5511 sepsis patients were extracted from the MIMIC-IV (v3.1) database, with external validation conducted in 545 patients from the Intensive Care Unit (ICU) of Lanzhou University Second Hospital. CAR was calculated at ICU admission, and patients were stratified into quartiles. Restricted cubic splines (RCS), Cox proportional hazards regression, and Kaplan–Meier curves were used to evaluate the CAR-mortality association. LASSO regression and the Boruta algorithm were employed for feature selection. Seven ML models were developed to predict 28-day mortality, with performance assessed via discrimination (AUC), calibration (Brier score), and decision curve analysis (DCA). Results CAR showed a nonlinear dose–response relationship with 28-day mortality (P for nonlinearity < 0.001). In multivariable Cox regression analysis, higher CAR was associated with an increased risk of 28-day mortality (adjusted HR = 1.31, 95% CI 1.17–1.47, P < 0.001). Both LASSO and Boruta identified CAR as a prognostic factor. The XGBoost model including CAR showed good predictive performance (AUC = 0.812, 95% CI 0.786–0.837). The calibration was acceptable (Brier score = 0.1341), and the model showed potential clinical value. Conclusions CAR was nonlinearly associated with 28-day and in-hospital mortality in patients with sepsis and remained associated with mortality risk. An XGBoost-based model incorporating CAR demonstrated good discriminative performance. These findings suggest that CAR may serve as a simple and readily available complementary marker for prognostic assessment in sepsis.

Heavy metal cadmium (Cd) exposure is associated with increased cardiovascular disease (CVD) risk, yet sex-specific differences in Cd exposure’s impact on CVD patient mortality and underlying mechanisms remain unclear. Using the national health and nutrition examination survey (NHANES) database and its follow-up mortality data (1,413 CVD patients: 652 deaths [46.14

The publication of the 2023 Global Definition of ARDS has further unveiled the clinical heterogeneity of sepsis-induced acute respiratory distress syndrome (ARDS), rendering traditional systemic biomarkers insufficient for precisely characterizing lung-specific pathological changes. Cell-specific exosomes, owing to their high stability and high fidelity to the molecular signatures of their parent cells, have emerged as a highly promising tool for liquid biopsy. This review aims to elucidate how exosomes construct a multidimensional communication network within the compromised alveolar-capillary barrier. Beyond exploring the traditional function of exosomes as inflammatory vectors, we provide an in-depth analysis of the mechanisms by which alveolar epithelial exosomes propagate ferroptosis and mitochondrial damage in a wave-like manner, and how macrophage exosomes drive immunometabolic reprogramming via glycolysis and histone lactylation to sustain the inflammatory state. Furthermore, we elaborate on the central role of endothelial exosomes in vascular leakage and immunothrombosis, proposing a novel hypothesis that they may serve as mediators propagating cuproptosis within the vascular bed. Finally, by integrating advances in single-cell omics and analyzing technical barriers such as isolation specificity and timeliness, we propose a precision medicine framework based on exosomal molecular fingerprints. This strategy aims to utilize exosomes for ARDS subphenotyping, thereby promoting a paradigm shift in clinical practice from syndrome management to mechanism-driven theranostics.

The triglyceride-glucose (TyG) index, a marker of insulin resistance, is associated with outcomes in critical illness; however, its predictive role for 28-day mortality in Asian patients with sepsis has not been established. To address this, the current investigation was designed to evaluate its prognostic significance and to construct a risk prediction model for short-term mortality. This retrospective study analyzed sepsis patients admitted to the intensive care unit (ICU) of the Second Hospital of Lanzhou University from January 1, 2018 to December 31, 2023. Participants were randomly split into training/validation cohorts (7:3 ratio). Multivariate logistic regression identified independent predictors. A nomogram was constructed by these predictors and it was validated using ROC curves (ROC), calibration plots, and decision curve analysis (DCA). A nomogram integrating seven variables-age, respiratory failure within 48 h, multiple organ dysfunction syndrome (MODS) within 48 h, international normalized ratio (INR), lactate level, prognostic nutrition index (PNI), and TyG index-predicted 28-day mortality with AUCs of 0.855 (training, 95% CI: 0.818-0.891) and 0.826 (validation, 95% CI: 0.764-0.887), outperforming SOFA and APACHE II scores. Calibration curves confirmed alignment with actual outcomes, and DCA demonstrated broad clinical utility. The TyG index is an independent predictor of 28-day sepsis mortality. The validated nomogram based on the TyG index enhances risk stratification, aiding clinicians in early decision-making to improve patient outcomes and care quality.

The accumulation of per- and polyfluoroalkyl substances (PFAS) in human tissues is known. However, PFAS accumulation in the lung tissue of lung cancer patients remains unexplored. We examined the distribution of 26 PFAS in lung tissues and found a total concentration ranging from 0.75 to 368ng/g, with perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) identified as predominant compounds. Perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) were the most prevalent, and a firefighting-related exposure pattern was observed in male patients. PFAS accumulation was observed in older females and middle-aged males. This may be attributed to reduced menstrual clearance in females and protein-binding correlations in males. A negative correlation was found between carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and perfluoropentane sulfonic acid (PFPeS) and N-ethyl perfluorooctane sulfonamido acetic acid (N-EtFOSAA) concentrations in lung tissue. A significant negative correlation of perfluorobutanoic acid (PFBA), PFOA and a positive correlation of PFOS and perfluorononanesulfonic acid (PFNS), with CYFRA 21-1 was discerned. PFAS concentrations showed significant negative correlations with neuron-specific enolase (NSE) levels in patients over 60 years. This research highlights PFAS accumulation in lung tissues and the need for further studies associating exposure with health outcomes.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury.MethodsNewly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics.ResultsRenal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca2+-Mg2+-ATPase.ConclusionsMitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

BACKGROUND:Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, frequently induces myocardial injury, which stands as one of its most common and severe complications and a key factor contributing to poor patient prognosis. This study aims to investigate the protective effect of Artesunate (AS) on sepsis-induced myocardial injury (SIMI) and to elucidate the underlying molecular mechanisms by integrating network pharmacology prediction with experimental validation. METHODS:Sepsis was induced in male Wistar rats using the cecal ligation and puncture (CLP) method, and the rats were randomly divided into five groups (n = 6/group): Ctrl, Sham, CLP, AS + CLP, and vehicle + CLP. To assess the cardioprotective effect of AS, serum levels of myocardial injury markers (BNP, LDH, CK-MB, hs-cTnI) were measured by ELISA, and myocardial histopathology was evaluated by H&E staining. The potential targets and pathways of AS against SIMI were then predicted using network pharmacology. Serum inflammatory cytokines (IL-6, TNF-α) and oxidative stress markers (SOD, MDA) were further examined by ELISA, and cardiomyocyte apoptosis was assessed by TUNEL staining. Finally, the expression of key proteins in the JAK2/STAT3 signaling pathway in myocardial tissue was determined by Western blotting to explore the underlying mechanism. RESULTS:AS significantly ameliorated pathological damage and reduced serum myocardial enzyme levels in septic rats compared to the CLP group. Network pharmacology identified 68 potential targets of AS. GO analysis revealed their primary enrichment in molecular functions such as kinase regulator activity, while KEGG enrichment analysis showed their significant association with pathways including inflammatory response. Molecular docking demonstrated favorable binding affinities between AS and core targets such as STAT3. Experimental validation further showed that AS treatment significantly decreased serum concentrations of IL-6 and TNF-α, increased SOD activity while reducing MDA content, and lowered the myocardial cell apoptosis index. Moreover, AS administration notably downregulated the protein expression levels of p-JAK2 and p-STAT3 in myocardial tissue. CONCLUSION:Based on network pharmacology prediction and experimental validation, it was demonstrated that AS protects against SIMI by inhibiting the JAK2/STAT3 signaling pathway, thereby alleviating inflammation, oxidative stress, and cardiomyocyte apoptosis. These findings provide compelling pharmacological evidence for the drug repurposing of Artesunate.

Aim: Sepsis is a potentially fatal condition characterized by organ failure resulting from an abnormal host response to infection, often leading to liver and kidney damage. Timely recognition and intervention of these dysfunctions have the potential to significantly reduce sepsis mortality rates. Recent studies have emphasized the critical role of serum exosomes and their miRNA content in mediating sepsis-induced organ dysfunction. The objective of this study is to elucidate the mechanism underlying the impact of miR122-5p on sepsis-associated liver and kidney injury using inhibitors for miR-122-5p as well as GW4869, an inhibitor targeting exosome release. Materials and Methods: Exosomes were isolated from serum samples of septic rats, sepsis patients, and control groups, while liver and kidney tissues were collected for subsequent analysis. The levels of miR-122-5p, inflammation indices, and organ damage were assessed using PCR, ELISA, and pathological identification techniques. Immunohistochemistry and Western blotting methods were employed to investigate the activation of inflammatory pathways. Furthermore, big data analysis was utilized to screen potential targets of miR-122-5p in vivo. Key Findings: Serum exosomal levels of miR-122-5p were significantly elevated in septic patients as well as in LPS-induced septic rats. Inhibition of miR-122-5p reduced serum pro-inflammatory factors and ameliorated liver and kidney damage in septic rats. Mechanistically, miR-122-5p upregulated TAK1, downregulated SIRT1, and facilitated NF-xB activation. Conclusion: Serum exosomal miR-122-5p promotes inflammation and induces liver/kidney injury in LPS-induced septic rats by modulating the TAK1/SIRT1/NF-xB pathway, highlighting potential therapeutic targets for sepsis management.

Although cadmium (Cd) exposure has been implicated in lung cancer development, systematic investigations into its association with cancer mortality, particularly lung cancer mortality remain limited, and the molecular mechanisms driving Cd-induced tumor progression are not fully understood. In this study, we first conducted a meta-analysis of existing cohort studies to quantitatively assess the association between Cd exposure and cancer- and lung cancer-specific mortality. We then employed an integrative approach combining bioinformatics analyses, LASSO regression, and Mendelian randomization to identify and validate DHX34 as a key gene implicated in Cd-related lung carcinogenesis. These findings were further supported by molecular docking, molecular dynamics simulations, in vitro functional assays, and in vivo tumor models. Our meta-analysis showed that long-term Cd exposure significantly increased cancer mortality risk, especially in males (RR = 1.49, 95 % CI: 1.13-1.96) and in lung cancer (RR = 1.86, 95 % CI: 1.36-2.54). Integration of GSE165549 and TCGA data identified 36 Cd-related genes enriched in tumor associated pathways including cell cycle and DNA replication. LASSO regression and Mendelian randomization suggested a causal role of DHX34 in lung cancer. Molecular docking demonstrated a strong binding affinity between Cd2 + and DHX34 (binding free energy = -5.34 kcal/mol), and molecular dynamics simulations confirmed the stability of this complex. Functional assays further showed that CdCl2 exposure upregulated DHX34, thereby promoting lung cancer cell proliferation and tumor growth both in vitro and in vivo. Together, these findings provide multi-level evidence that DHX34 mediates Cd-induced lung cancer progression, highlighting the carcinogenic potential of environmental heavy metal exposure and offering new insights into molecular targets for early prevention, risk stratification, and therapeutic intervention.

With the rapid development of global metal exposure, while there is evidence indicating the toxicity of individual metals, the combined impact of mixed exposure of multiple metals on primary liver cancer (PLC) risks remains inadequately characterized. Therefore, we conducted this nested case-control study within the Jinchang cohort, including 129 incidents of PLC cases after 10 years of follow-up and 387 healthy controls matched by propensity score matching methods. Our findings showed that long-term exposure of chromium (Cr, Q2: OR = 10.63, 95% CI: 4.21-26.81; Q3: OR = 5.42, 95% CI: 2.14-13.70), zinc (Zn, Q2: OR = 2.37, 95% CI: 1.10-5.11; Q3: OR = 2.79, 95% CI: 1.32-5.88; Q4: OR = 2.83, 95% CI: 1.33-5.98), iron (Fe, Q4: OR = 0.26, 95% CI: 0.12-0.60), and aluminum (Al, Q4: OR = 0.26, 95% CI: 0.11-0.64) was identified as key contributing factors of the incidents of PLC. Serum Cr exhibited a nonlinear relationship with PLC risk (ρoverall < 0.001, ρnonlinear < 0.001), whereas Zn demonstrated a near-linear positive trend (ρoverall = 0.023, ρnonlinear = 0.395). In contrast, Fe, lithium (Li), and Al showed inverse associations with PLC incidence. Sensitivity analyses further confirmed these relationships. Additionally, significant interactions were observed among serum Cr, Zn, Fe, and Al in modulating PLC risk (ρinteraction < 0.05). These results highlighted the complex dose-dependent effects and interactions of multimetal exposures in the PLC pathogenesis and underscored the need for further mechanistic investigations.

Although environmental exposure to toxic metals and metalloids is linked with the risk of cardiovascular diseases, the evidence is limited in the elderly. We evaluated the associations between 12 plasma metal levels including aluminum (Al), titanium (Ti), strontium (Sr), lead (Pb), vanadium (V), chromium (Cr), cobalt (Co), nickel (Ni), cuprum (Cu), zinc (Zn), arsenic (As), and selenium (Se) with prevalence of hypertension in the elderly Chinese population. In this study, stratified cluster sampling was conducted among elderly residents in three communities in Gansu province from June to July 2023, with a total of 330 participants included. The concentrations of metals in whole plasma were measured using inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and restricted cubic spline analyses were used to evaluate the dose–response relationship between plasma metal levels and hypertension, with all metal concentrations log-transformed. We applied quantile g-computation (QG-comp) and Bayesian kernel machine regression (BKMR) models to examine the associations of both individual metals and metal mixtures with hypertension. After multivariable adjustments, the odds ratios (ORs) and 95

BackgroundHyperuricemia (HUA) is a significant public health issue, ranking second only to diabetes in prevalence. While existing research demonstrates a robust correlation between these two conditions, the precise etiological mechanisms remain inadequately elucidated. This study utilized scientometric analysis to investigate the global association between HUA and diabetes.MethodsData on HUA and diabetes were retrieved from the Web of Science Core Collection database, encompassing the period from its inception until September 30, 2024. Collaboration networks were examined using VOSviewer, cluster analysis was executed with CiteSpace, and systematic mapping was conducted using Bibliometrix.ResultsBy September 30, 2024, 1,464 studies indicated a consistent yearly increase in publications connecting HUA and diabetes despite some fluctuations. The lead authors were Richard J. Johnson, Miguel A. Lanaspa, and Masanari Kuwabara, with most contributors from China, the United States, and Japan. Key institutions include China Medical University, Shanghai Jiao Tong University, and Capital Medical University. The most published journal was Nutrition, Metabolism and Cardiovascular Diseases (CVDs), whereas the most cited journal was Diabetes Care. The reference network from 1987 to September 30, 2024, identified 19 clusters highlighting key research areas in HUA and diabetes, such as metabolic syndrome, uropathology, chronic kidney disease (CKD), and CVD. Exploring pathological mechanisms and pharmacological interventions linked to diabetes concomitant with HUA has emerged as a focal point of research and a burgeoning trend within the field.ConclusionThis study is the first scientometric analysis to synthesize research trends on HUA and diabetes, revealing molecular mechanisms and treatment strategies and providing theoretical insights for future clinical use.

Aims:To evaluate the spatial-temporal changes in the incidence of type 2 diabetes related chronic kidney disease (CKD-T2DM) from 1990 to 2019, categorized by age and sex in 21 regions with different socio-demographic indexes (SDI), and to predict the incidence rate between 2020 and 2030. Methods:Data on the burden of CKD-T2DM were obtained from the Global Burden of Disease Study 2019. Age-standardized incidence rates (ASIR) were estimated by sex, age, region, SDI, and specifically in China. The trends of ASIR were assessed using Joinpoint model to calculate the average annual percentage changes (AAPCs) and their 95% confidence intervals. Prediction was conducted using the Bayesian age-period-cohort (BAPC) model. Result:In 2019, the ASIR of global CKD-T2DM increased with age in both sexes, and was highest in the older 75 age group. The ASIR of CKD-T2DM in males was higher than those in females. Overall, the global ASIR of CKD-T2DM increased from 1990 to 2019 in both sexes and all age groups. The most significant increase was observed in the 15-49 age group [males: AAPC=1.42, 95%CI:(1.35-1.49); females: AAPC=1.18,95%CI:(1.13-1.23)]. Besides, the upward trends in ASIR of CKD-T2DM were observed in most SDI regions and GBD regions. The changing trends in ASIR of CKD-T2DM in China were similar to the global trends. Finally, the predicted ASIR was also found to be increased globally and also in China in both sex from 2020 to 2030. Conclusion:The global CKD-T2DM incidence rates increased from 1990 to 2019 in both sexes, most regions and in China., and also increased globally between 2020 and 2030. Therefore, it is important to input more medical resources and establish prevention strategies for the increasing trends of CKD-T2DM.

Although studies have demonstrated the influence of meteorological factors on morbidity and mortality in type 2 diabetes mellitus (T2DM), research focusing specifically on their impact on hospitalization for T2DM with complications remains Limited.This study aimed to investigate the impact of meteorological factors on hospitalization for type 2 diabetes mellitus (T2DM) with complications. The distributed lag nonlinear modelling (DLNM) was used to investigate this effect of temperature and relative humidity (RH) on hospitalization for T2DM with complications. A total of 50,108 T2DM hospitalizations with complications were performed from 2014 to 2019 in Lanzhou, China. Compared to the reference temperature of 12.7 °C, low temperature (-4.1 °C) had harmful effects, with the maximum impact at lag0-1 (cumulative RR = 1.0265, 95

BACKGROUND AND OBJECTIVES:Menopausal women with chronic heart failure (CHF) exhibit unique physiolog-ical characteristics and prognostic features. The aim of this study is to analyze the significant predictive factors for the prognosis of chronic heart failure in menopausal women and the impact of different nutritional interventions on prognosis. METHODS AND STUDY DESIGN:A total of 270 menopausal women with CHF were enrolled in the study and divided into two groups based on the nutritional intervention received. Analyze the significant predictive factors of all-cause mortality, readmission rate, deterioration of cardiac function, deterioration of nutritional status, and deterioration of quality of life, as well as the impact of nutritional interven-tion on these prognoses. Build a risk score model based on significant factors in the prognostic model. Evaluate the predictive ability of the model through the ROC curve. RESULTS:Multivariate logistic regression analysis showed that NYHA grading BNP, eGFR, The level of estradiol (E2) and nutritional intervention are signif-icant influencing factors in multiple prognostic indicators, among which the enhanced nutritional support and micronutrient supplementation program in nutritional intervention have a significant protective effect on poor prognosis. The constructed nutritional risk model has good discriminative ability and robustness in predicting prognosis. CONCLUSIONS:This study identified menopausal characteristics, NYHA classification, BNP, eGFR, and estradiol levels as important prognostic predictors in menopausal women with CHF. Enhanced nutritional support and micronutrient supplementation significantly improved patient prognosis. The risk model based on nutritional intervention provides scientific basis for the management strategy of chronic heart failure in menopausal women.

Environmental factors play a critical role in the pathogenesis of abnormal blood glucose and its complications. However, research on the relationship between environmental factors, blood glucose, and mortality is limited. Using NHANES (1999-2018) data, we analyzed the association between serum Cd concentrations and all-cause and cardiovascular disease (CVD) mortality in abnormal blood glucose individuals through multivariate weighted Cox proportional hazards models. Dose-response relationships were assessed using restricted cubic splines, and interaction effects between Cd exposure and other factors were also explored. Among 11,836 participants, 2379 deaths occurred. After full adjustment, high Cd concentrations significantly increased all-cause (HR=1.55, 95 % CI: 1.26-1.91) and CVD mortality (HR=1.58, 95 % CI: 1.12-2.21) in individuals with abnormal blood glucose. Cd exhibited a nonlinear positive association with all-cause mortality (Pnonlinear=0.011) and a linear association with CVD mortality (Pnonlinear=0.224). Stratified analysis showed a stronger association in prediabetes (pre-DM) than diabetes mellitus (DM) (Pfor interaction<0.001 for all-cause mortality, Pfor interaction=0.026 for CVD mortality). A threshold effect was observed at 0.62 µg/L in pre-DM population, above which the risk of all-cause mortality increased markedly. Moreover, high Cd and hypertension exhibited a significant synergistic effect on all-cause mortality (Pfor interaction=0.047). Cd concentration is positively associated with mortality in individuals with abnormal blood glucose, particularly in the pre-DM population. These findings suggest that monitoring environmental pollutants such as Cd in the pre-DM population is crucial. Additionally, controlling blood glucose and blood pressure in populations with occupational exposure to heavy metals, such as Cd, is emphasized as an important public health measure.

Cadmium (Cd), an endocrine disruptor, has been linked to hormone-related cancers, including breast cancer (BC). However, previous studies investigating the association between Cd exposure and BC risk have yielded inconsistent results, and the effects of Cd on BC subtypes remain poorly understood. We employed logistic regression and restricted cubic splines (RCS) to examine the relationship between Cd exposure and BC. A meta-analysis was subsequently conducted to validate the association between Cd exposure and BC. Lastly, mediation analysis was applied to explore the underlying mechanisms linking Cd exposure to BC. Data from 5954 participants in the National Health and Nutrition Examination Survey (1999-2020) were analyzed. Elevated Cd levels in the fourth quartile were significantly associated with an increased BC risk (odds ratio (OR) = 3.74, 95 % confidence interval (CI): 1.45 - 9.62, Ptrend = 0.019), compared to the first quartile group. A linear dose-response relationship was seen between urinary Cd levels and BC risk (Pnon-linear = 0.532), with BC risk increasing 317 % (OR = 3.17, 95 % CI: 1.93 - 5.20, Ptrend < 0.001) for 1 μg/g creatinine increases in urinary Cd levels. The meta-analysis, which included 20 eligible studies, further observed a possible link between Cd exposure and BC risk (relative risk (RR) = 1.17, 95 % CI: 1.06 - 1.29, I2 = 83 %), particularly in estrogen receptor-positive (ER+) subtypes (RR = 1.08, 95 % CI: 1.01 - 1.16, I2 = 70 %). Mediation analysis further revealed that glycated hemoglobin (HbA1c) mediated 9.09 % of the Cd-BC risk association. In conclusion, the study results suggest a potential association between Cd levels and an increased BC risk, particularly in ER+ subtypes. Mechanistically, HbA1c was identified as a mediator in this association. These findings underscore the complex interplay between Cd exposure and metabolic dysregulation in the development of BC, highlighting the potential role of HbA1c in modulating BC risk among individuals exposed to Cd.

While cadmium (Cd) and lead (Pb) exposure are associated with increased mortality and selenium (Se) may mitigate these effects, large-scale epidemiological evidence remains limited and the underlying mechanisms unclear. To address this, this study utilized data from the National Health and Nutrition Examination Survey (NHANES, 2013-2017) and employed multivariate Cox models, restricted cubic splines, and interaction analyses to assess the associations of serum Se, Cd, and Pb with mortality, with mediation analysis conducted to explore the role of inflammatory pathways. Elevated blood levels of Cd (HR: 2.90, 95 % CI:1.72-4.88) and Pb (HR: 2.02, 95 % CI: 1.11-3.68) were associated with increased all-cause mortality risk. RCS analysis revealed positive linear dose-response relationships for Cd (Poverall< 0.001, Pnonlinear= 0.173) and Pb (Poverall< 0.001, Pnonlinear= 0.070), while a negative non-linear dose-response relationship was observed for Se (Poverall< 0.001, Pnonlinear< 0.001). Notably, under high Cd exposure, individuals with high Se levels had substantially lower all-cause mortality risk (HR: 1.32, 95 % CI:0.90-1.94) compared to those with low Se levels (HR: 3.43, 95 % CI:2.23-5.29). Similarly, under high Pb exposure, high Se levels (HR: 0.76, 95 % CI:0.31-1.84) were associated with a lower mortality risk compared to low Se levels (HR: 2.64, 95 % CI:1.13-6.16). Furthermore, mediation analyses indicated that neutrophil-to-lymphocyte ratio, albumin-to-creatinine ratio, and neutrophil percentage-to-albumin ratio partially mediated Se's protective effect, accounting for 16.10 %, 6.30 %, and 8.80 % of the total effect, respectively. In conclusion, Se may mitigate the detrimental effects of Cd and Pb exposure on mortality risk, potentially through the modulation of inflammatory responses.

Objectives Data on the oral health status in the Qinghai-Tibetan Plateau are limited. This study aimed to investigate the dental caries status and identify associated risk factors among 8- to 12-year-old children in Gannan, a Tibetan Autonomous Prefecture in Northwest China. Methods The study population was recruited using a multistage stratified random sampling procedure. Caries status was assessed by clinical oral examination and indicated by the decayed, missing, and filled teeth (DMFT/dmft) index. Information on sociodemographic characteristics, oral hygiene behaviours, and dietary habits was collected using a comprehensive structured questionnaire. Statistical analyses, including the chi-square test and a two-level logistic regression model, were conducted to examine the risk factors associated with dental caries. Results A total of 1024 Tibetan children were examined, revealing a dental caries prevalence rate of 89.55%, with a mean DMFT/dmft index of 4.25 ± 3.27. The two-level logistic regression model showed that initiating tooth brushing at four to 5 years old (OR = 2.295, 95% CI 1.053-5.002) and frequent dessert and candy intake (OR = 2.655, 95% CI 1.216-5.794) were risk factors for dental caries. Conversely, being 11 years (OR = 0.399, 95% CI 0.177-0.904) or 12 years old (OR = 0.396, 95% CI 0.163-0.961) and if the father's education level was high school or above (OR = 0.311, 95% CI 0.098-0.986) were indicated to be protective factors against dental caries. Conclusions The prevalence of dental caries was high in Tibetan children aged 8 to 12year-old in Gannan. Therefore, it is imperative to prioritize comprehensive home- and school-based interventions to improve the oral health of this population.