Objectives:This randomised controlled trial assessed the effectiveness and safety of weekly 56.5 μg teriparatide (SAL056) compared to alendronate in postmenopausal women in China with osteoporosis at high risk of fractures over 48 weeks. Methods:This phase 3, multicentre, randomised, open-label, active-controlled, parallel-group, non-inferiority trial enrolled postmenopausal women aged 45-80 years with osteoporosis at 37 centres in China. Participants were randomised (1:1) to receive either subcutaneous teriparatide 56.5 μg weekly or 70 mg oral alendronate weekly for 48 weeks, with the primary efficacy assessment at Week 48. Results:Between November 2021 and September 2023, 493 patients were enrolled (243 in the teriparatide group and 250 in the alendronate group). The primary endpoint, lumbar spine bone mineral density (BMD) at L1-L4, showed a significantly greater increase in the teriparatide group compared to the alendronate group at Week 48 (5.01% vs. 4.20%, mean difference 0.80%, P = 0.025). Sensitivity analysis confirmed these results. At Weeks 24 and 48, teriparatide also resulted in higher hip BMD than alendronate (1.50% vs. 1.46%, P > 0.05 and 3.27% vs. 1.67%, P < 0.001). Procollagen type 1 N-terminal propeptide (P1NP) levels in the teriparatide group increased transiently at Week 12, then declined toward baseline by Weeks 24 and 48, and a decrease in serum cross-linked c-terminal telopeptide of type I collagen (S-CTX) levels from baseline to the end of treatment. Meanwhile, in the alendronate (a typical bone resorption inhibitor) group, CTX level remained continuously suppressed from the baseline. Clinical fracture rates were lower in the teriparatide group than in the alendronate group at Weeks 24 (1.2% vs. 2.8%, P > 0.05) and 48 (1.7% vs. 4.0%, P > 0.05). Teriparatide was generally safe and well tolerated. Conclusions:Teriparatide (56.5 μg once weekly) was more effective than alendronate in treating postmenopausal osteoporosis with a high fracture risk, significantly increasing L1-L4 BMD over 48 weeks. It was safe, well tolerated, and had a safety profile similar to that of Teribone®. The translational potential of this article:This study demonstrates that once-weekly teriparatide significantly improves bone mineral density and reduces fracture risk in postmenopausal osteoporosis patients. As a patient-friendly alternative to daily injections, it may enhance adherence and inform clinical guidelines, representing a promising strategy for patients and healthcare systems.

Introduction: Prokineticin 2 (PROK2) is a secreted protein, that plays a critical role in the circadian regulation of energy homeostasis. However, its association with type 2 diabetes mellitus (T2DM) and diabetes-related complication remains poorly understand. This study aimed to investigate the relationship between serum PROK2 levels, T2DM and diabetic kidney disease (DKD). Methods A total of 255 participants were enrolled, including 40 healthy controls and 215 patients with T2DM. DKD was defined as a urinary albumin-to-creatinine ratio (UACR) ≥ 0.03 g/g, or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m². Serum PROK2 concentrations were quantified using enzyme-linked immunosorbent assay. Binary logistic regression models were applied to evaluate the associations between PROK2 levels and the risks of T2DM and DKD. Correlation analyses were performed to assess the relationships between PROK2 and renal function indicators, including UACR and eGFR. Results Serum PROK2 levels differed significantly among the study groups ( P < 0.05), with the lowest concentrations observed in patients with DKD. After adjustment for potential confounders, higher serum PROK2 levels were independently associated with a lower risk of T2DM (odds ratio [OR] = 0.492, P = 0.001) and DKD (OR = 0.679, P = 0.046). Furthermore, PROK2 levels were negatively correlated with UACR ( r =–0.212, P = 0.0007) and positively correlated with eGFR ( r = 0.271, P < 0.0001). Conclusion Serum PROK2 levels are significantly reduced in patients with T2DM, particularly among those with DKD. These findings suggest that PROK2 may serve as a novel circulating biomarker for assessing renal impairment in individuals with T2DM.

Background:The HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) score integrates key parameters reflecting nutritional and immune status. However, its prognostic value for in-hospital mortality in sepsis patients remains underexplored. Objective:To investigate the association between HALP score and in-hospital mortality in sepsis patients using two large critical care databases. Methods:We conducted a retrospective cohort study including adult patients with Sepsis-3 from the eICU Collaborative Research Database (derivation cohort, n = 12,899) and the MIMIC-IV database (validation cohort, n = 3,726). HALP was calculated as (hemoglobin × albumin × lymphocyte count)/platelet count, using first available values upon ICU admission. Restricted cubic spline (RCS) models assessed nonlinear relationships between HALP and mortality. Kaplan-Meier survival curves and multivariable Cox regression models, adjusted for demographics, comorbidities, laboratory values, and Acute Physiology Score III, evaluated survival differences between low- and high-HALP groups. Segmented Cox regression examined associations below and above RCS-derived thresholds. Results:A total of 16,625 patients were analyzed. RCS analysis demonstrated significant nonlinear associations between HALP and in-hospital mortality in both cohorts (overall P < 0.001; nonlinearity P < 0.001 in eICU, P = 0.002 in MIMIC-IV), with an inflection point near 12.45. Below this threshold, each unit increase in HALP was associated with a 3% reduction in mortality risk (eICU: HR 0.97, 95% CI 0.95-0.99, P = 0.002; MIMIC-IV: HR 0.97, 95% CI 0.94-0.99, P = 0.008). Kaplan-Meier analyses showed significantly higher survival in the high HALP group (eICU: log-rank P = 0.005, HR 0.882, 95% CI 0.808-0.962; MIMIC-IV: log-rank P < 0.001, HR 0.723, 95% CI 0.607-0.862). Multivariable Cox regression confirmed that high HALP remained independently protective after full adjustment (eICU: HR 0.90, 95% CI 0.82-0.98, P = 0.017; MIMIC-IV: HR 0.85, 95% CI 0.74-0.98, P = 0.028). Conclusion:The HALP score demonstrates robust prognostic value for predicting in-hospital mortality in sepsis patients, with consistent nonlinear relationships validated across two large databases. Its simplicity and reliance on routine laboratory parameters support potential clinical application in sepsis risk stratification.

BackgroundPrevious studies have demonstrated that carvacrol (Car) ameliorates vascular and hepatic injury in db/db mice, but its low bioavailability limits clinical translation.MethodsTo address this, this study constructed carvacrol-loaded polymeric nanoparticles (Car@PLGA-NPs) to enhance carvacrol bioavailability and fully explore its novel mechanisms of action on islet function and gut homeostasis in a diabetic model. We used C57BL/6J db/db mice to measure serum fasting blood glucose, oral glucose tolerance (OGTT), insulin tolerance (ITT), and lipid profiles. Fecal samples were collected for 16S rRNA sequencing to analyze gut microbiota composition and its correlation with host indices. Pancreatic and intestinal tissues underwent histopathological staining, immunofluorescence, and Western blotting to detect endoplasmic reticulum (ER) stress-related protein expression levels (p-IRE1α, XBP1S, PERK, p-ElF2α).ResultsResults demonstrated that Car@PLGA-NPs, compared to free carvacrol, significantly improved insulin sensitivity, reduced fasting blood glucose, ameliorated dyslipidemia, attenuated inflammation, and mitigated oxidative stress in db/db mice. 16S rRNA sequencing revealed that Car@PLGA-NPs remodeled the gut microbiota composition, with Alloprevotella abundance showing a negative correlation with colonic ER stress proteins (p-IRE1α and p-ElF2α). Immunofluorescence and Western blotting further confirmed that Car@PLGA-NPs significantly suppressed the expression of ER stress-related proteins (p-IRE1α, XBP1S, PERK, p-ElF2α) in both islet and colonic tissues, demonstrating superior efficacy to free carvacrol.ConclusionsCollectively, this study confirms that the PLGA nanocarrier effectively enhances carvacrol bioavailability. Car@PLGA-NPs improve islet function and intestinal homeostasis in diabetic mice by remodeling the gut microbiota and subsequently inhibiting ER stress in pancreatic and intestinal tissues, providing a novel nano-drug delivery system and a “microbiota-ER stress” regulatory axis for diabetes treatment.

This study aimed to assess whether admission plasma lipopolysaccharide-binding protein (LBP), procalcitonin (PCT), and lactate could improve detection of nosocomial infection in cirrhotic patients presenting with upper gastrointestinal bleeding (UGIB). A retrospective analysis was conducted in 196 consecutive adults with cirrhotic UGIB admitted between January 2021 and January 2025, in whom index biomarkers were defined as the first blood samples obtained within 24 h of hospital arrival and before any diagnosis of nosocomial infection. Nosocomial infection within 28 days of admission occurred in 58 of 196 patients. Compared with noninfected patients, those with nosocomial infection had higher WBC, CRP, PCT, LBP, lactate, international normalized ratio (INR), and total bilirubin (TB), lower albumin and sodium, a higher neutrophil-to-lymphocyte ratio (NLR), and a lower lymphocyte-to-monocyte ratio (LMR). Individual discrimination was excellent for LBP (area under the curve [AUC] 0.967), CRP (0.918), WBC (0.914), lactate (0.910), and PCT (0.901). In multivariable analysis, LBP, CRP, and albumin remained independently associated with nosocomial infection. A WBC + CRP model achieved an AUC of 0.975, whereas LBP + CRP + albumin and LBP + PCT + lactate panels yielded AUCs of 0.997 and 0.999, respectively; both LBP-based panels significantly outperformed WBC + CRP. An admission LBP + CRP + albumin model provides a pragmatic, high-performing tool for early risk stratification, while an LBP + PCT + lactate panel offers near-perfect discrimination as an expanded option; these LBP-based tri-marker models may help refine early risk stratification and targeted management in cirrhotic patients with UGIB.

Prospective evidence linking greenness and cardiovascular disease (CVD) in rapidly urbanizing developing countries remains limited. Here, among 159,590 adults aged ≥40 years from the nationwide China Cardiometabolic Disease and Cancer Cohort with a median follow-up of 10.1 years, we examine the association between residential greenness, measured by satellite-derived normalized difference vegetation index (NDVI) within 500 m of residence, and incident CVD, and evaluate its joint effects with cardiovascular health as defined by Life’s Essential 8. Individuals in the highest quartiles of contemporaneous, one-year, and cumulative NDVI consistently show lower CVD risk compared with those in the lowest quartiles, although associations vary across subpopulations. Notably, individuals with high cardiovascular health scores living in low-NDVI areas exhibit similar CVD risk to those residing in high-NDVI areas. These findings highlight the complementary importance of both green infrastructure and healthy lifestyles in reducing CVD risk in rapidly urbanizing regions of China.

Diabetic retinopathy (DR) is recognized as a major pathological contributor to blindness, and timely screening is required to prevent progressive sight loss. Modern computer vision strategies formalize DR severity assessment as a multi-class classification problem. Supervised end-to-end models have achieved promising results, but two key challenges remain. Firstly, imbalanced data distributions cause end-to-end models to favor the dominant categories, limiting the precise detection of infrequent categories. Secondly, effectively modeling the inherent ordinal relationships between different severity levels is essential for achieving accurate and consistent classification. This work introduces a contrastive learning framework for DR grading, consisting of a k-positive contrast branch and a novel ordinal adjustment marginal classification branch, to address the two challenges in DR grading. On three challenging DR grading datasets, the proposed method achieves competitive and consistent performance, comparing favorably with existing approaches. Specifically, on APTOS2019, our method achieves an accuracy of 86.69% and a weighted Kappa of 92.50%. On Messidor-2, it attains an accuracy of 81.91% and a weighted Kappa of 87.28%. Meanwhile, on the DDR dataset, it records an accuracy of 83.16% and a weighted Kappa of 84.57%. Extensive experiments demonstrate the effectiveness of our method and its potential for generalization to other imbalanced ordinal classification tasks. Code will be released at https://github.com/liluhu0/KCOC.

BACKGROUND:We investigated the association between food-derived dietary magnesium intake and all-cause mortality among adults with chronic kidney disease. METHODS:We analysed data from adults aged ≥20 years with CKD who participated in the National Health and Nutrition Examination Survey between 1999 and 2018. Mortality status was ascertained through linkage to the National Death Index through 31 December 2019. Multivariable Cox proportional hazards models were used to evaluate the association between dietary magnesium intake and all-cause mortality. Restricted cubic spline analysis, Kaplan-Meier survival analysis, subgroup analyses, and sensitivity analyses were also performed. RESULTS:A total of 8,104 CKD patients were included in this cohort study with a median follow-up of 85 months, during which 3,134 (38.7%) died from all causes. In the fully adjusted Cox model, each 100 mg/day increase in dietary magnesium intake was associated with a 7.5% lower risk of all-cause mortality (HR = 0.925, 95% CI 0.881-0.971; P = 0.002). Compared with the lowest quartile, adjusted hazard ratios were 0.978 (95% CI 0.883-1.083) for Q2, 0.904 (95% CI 0.804-1.016) for Q3, and 0.866 (95% CI 0.744-1.007) for Q4, with a significant trend across quartiles (P for trend = 0.036). RCS analysis demonstrated a significant overall association with no evidence of nonlinearity (P for overall association = 0.009; P for nonlinearity = 0.472). Kaplan-Meier analysis showed higher survival probabilities among participants with higher dietary magnesium intake. CONCLUSIONS:Higher dietary magnesium intake was independently associated with a lower risk of all-cause mortality among adults with CKD. These findings suggest that adequate dietary magnesium intake may represent an important nutritional factor associated with prognosis in CKD. Further prospective studies and randomised clinical trials are warranted to determine whether increasing dietary magnesium intake can improve clinical outcomes. SUMMARY STATEMENT:Higher dietary magnesium intake was independently associated with lower all-cause mortality among patients with chronic kidney disease in NHANES 1999-2018. These findings highlight the potential protective role of adequate magnesium intake in improving long-term survival in this population.

Body roundness index (BRI) is an innovative anthropometric indicator that reflects visceral adiposity and body composition. Although its association with mortality has been studied in both general and metabolic populations, its prognostic value in individuals with established atherosclerotic cardiovascular disease (ASCVD) remains unclear. This study aimed to investigate the association between BRI and all-cause and cardiovascular mortality in a nationally representative cohort of American adults diagnosed with ASCVD. Data were collected from 10 continuous cycles (1999-2018) of the National Health and Nutrition Examination Survey. In total, 2071 adults with self-reported ASCVD were included. The BRI was calculated from the waist circumference and height. Mortality outcomes were ascertained via linkage to the National Death Index in December 2019. Multivariate Cox proportional hazards regression models, restricted cubic splines, and subgroup analyses were used to assess associations. During a median follow-up of 6.9 years, 828 all-cause and 280 cardiovascular deaths occurred. A U-shaped nonlinear relationship was observed between the BRI and mortality (P-nonlinearity < .001). The inflection points were 5.54 for all-cause mortality and 6.09 for cardiovascular mortality. Below these points, the BRI was negatively correlated with mortality; above these points, each unit increase in the BRI significantly increased the risk of all-cause (hazard ratio = 1.114, 95% confidence interval: 1.113, 1.115) and cardiovascular mortality (hazard ratio = 1.101, 95% confidence interval: 1.099, 1.102). Subgroup analyses indicated that the associations were modified by gender, socioeconomic status, lifestyle behaviors, and comorbidities. In adults with ASCVD, the BRI is associated with both all-cause and cardiovascular mortality in a U-shaped manner, with the optimal risk observed within the range of approximately 5.5 to 6.0. BRI may serve as a valuable tool for risk stratification and personalized management in high-risk populations.

[This corrects the article DOI: 10.1016/j.mtbio.2025.102490.].

PVT1 (Plasmacytoma Variant Translocation 1), a long non-coding RNA (lncRNA), is a critical player in diverse biological processes, particularly cancer biology. This review comprehensively examines PVT1’s multifaceted roles and molecular mechanisms. We delve into its predominant oncogenic functions while highlighting notable exceptions, offering new perspectives on its biological diversity. A key focus is the subcellular localizations of PVT1 across various cancers – an aspect underexplored in previous reviews despite its significant impact on function and regulatory mechanisms. Detailed mechanistic insights include PVT1’s linear and circular isoforms acting as miRNA sponges, its encoding of miRNAs, the influence of 8q24 rearrangements, and its regulation of protein stability/activity, and transcription. Furthermore, we examine PVT1’s functional elements, illuminating unexplored structural and regulatory features. The clinical implications of PVT1 as a biomarker and therapeutic target in oncology are also discussed. By synthesizing existing knowledge and introducing previously less-explored facets, this review aims to provide a comprehensive and up-to-date resource on PVT1’s role in health and disease.

[This corrects the article DOI: 10.1016/j.mtbio.2025.101548.].

The study aims to investigate the potential of glycolipid metabolism 6 factors (GLM6) and glycolipid metabolism 7 factors (GLM7) indexes in identifying high-risk populations for various diseases during routine screening, and to evaluate the potential of GLM6 for long-term dynamic monitoring of disease risk. Research data were obtained from the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression, Cox regression, and restricted cubic spline (RCS) curve analysis were employed to examine correlations between exposure variables and outcome variables. The eXtreme Gradient Boosting (XGBoost) machine learning algorithm was used to establish models evaluating the predictive efficacy of GLM7 and GLM6 indicators. Subgroup analyses were conducted based on age, gender, smoking status, and drinking status. The composite indicators GLM7 and GLM6 showed significant positive correlations with the risk of 9 disease categories, 14 specific diseases, and mortality, with no association observed only for hyperthyroidism. The XGBoost model built on GLM6 performs comparably to the GLM7 model in terms of predictive ability for most diseases and has the potential to identify high-risk populations for various diseases during routine examinations. GLM7 and GLM6 demonstrate sound predictive capabilities for cardiovascular categories and metabolic diseases in the XGBoost model. In the cohort, the baseline GLM6 index, cumulative GLM6 index, and GLM6 dynamic clustering group were significantly positively correlated with cardiovascular disease (CVD) and diabetes (DM). The highest tertile of the cumulative GLM6 index, combined with an unfavorable GLM6 dynamic clustering group, was associated with the highest risk of new-onset CVD and DM, demonstrating a high risk of CVD and DM associated with long-term high GLM6 exposure. Furthermore, female exhibited higher disease risk under prolonged high GLM6 exposure. GLM6 and GLM7 show potential as biomarkers for identifying individuals at high risk of CVD and DM in large-scale population screenings. They can help establish long-term disease risk monitoring networks, and following future multicenter validation studies, they are expected to support the optimization of clinical decision-making and promote the targeted allocation of public health resources. Not applicable.

There is an urgent need to implement population-based actions to prevent diabetes mellitus (DM) in China. However, the current knowledge is limited on a prospective association of seafood intake with DM risk in Chinese adults. We aimed to determine the association between seafood consumption and the incident DM in a nationwide cohort of Chinese populations. A prospective cohort study of 104,816 participants, free of DM, aged ≥ 40 years across various geographical regions in China was conducted at baseline (China Cardiometabolic Disease and Cancer study). Habitual consumptions of seafood were assessed using a semi-quantitative food frequency questionnaire, and DM was diagnosed according to the WHO 1999 criteria. Primary outcomes were the incident DM, presented as hazard rations (HRs) with 95

BACKGROUND:The genetic architecture of circulating amino acids (AAs) and microbiota-related metabolites (MRMs) in relation to cardiometabolic disease remains poorly characterized in East Asian populations, limiting ancestry-specific insights. METHODS:In a prospective cohort of 2953 Chinese individuals, we performed a large-scale genome-wide association study (GWAS) of 28 serum AAs and 22 MRMs. We conducted a cross-ancestry comparison of variant-metabolite associations. Using colocalization and Mendelian randomization (MR), we further investigated causal roles of 50 AAs and MRMs in 25 cardiometabolic diseases from the BioBank Japan. Furthermore, we explored differences in the genetic regulation of these metabolites between incident T2DM cases and healthy controls. RESULTS:We identified 33 metabolite-variant associations, 22 of which were previously unreported, and revealed several loci specific to East Asian ancestry. Integrative colocalization and MR analyses established 49 causal relationships between metabolite levels and cardiometabolic diseases, most notably implicating genetically predicted N-acetyltryptophan to increased risk of type 2 diabetes. Moreover, we observed distinct patterns of genetic regulation between T2DM cases and controls, highlighting substantial heterogeneity of effects and dynamic gene-disease interplay. CONCLUSIONS:These findings offer crucial insights into the ancestry-specific genetic determinants of metabolic traits, and shed new light on their causal roles in the etiology of cardiometabolic diseases in East Asian populations.

BACKGROUND Perioperative serum albumin (ALB) levels affect the outcomes of patients undergoing gastrointestinal surgery. ALB supplementation in patients with low protein levels may therefore be beneficial. However, the specific effects of and optimal levels for serum ALB supplementation remain to be elucidated. AIM To develop and validate a nomogram for predicting severe complications on the basis of the serum ALB concentration and to establish optimal postoperative serum ALB concentration ranges. METHODS A total of 409 patients who underwent gastrointestinal surgery were randomly divided into a training cohort and a validation cohort. Patients with Clavien-Dindo grade II or higher complications were classified as having severe complications. A nomogram was developed on the basis of the serum ALB concentration to predict the risk of severe complications. Receiver operating characteristic curve, calibration curve and decision curve analysis were performed to validate the nomogram. The χ 2 test was used to compare the incidence of severe complications across different ALB ranges. RESULTS Logistic regression analysis revealed that the American Society of Anesthesiologists grade, surgery duration, preoperative serum ALB concentration, and age were significant predictors of severe complications. The nomogram developed using these predictors yielded an area under the area under the curve of 0.728 in the training cohort and 0.700 in the validation cohort; the calibration curves demonstrated good consistency between the predicted and observed probabilities in the two cohorts. Decision curve analysis demonstrated that the nomogram provided net benefits in predicting severe complications within threshold probability ranges of 19%-81% and 9%-66% in the two cohorts. Compared to those with relatively low peak postoperative serum ALB concentrations, patients with relatively high concentrations had a significantly lower incidence of severe complications (60.5% vs 40.7%; P = 0.041). CONCLUSION A nomogram that incorporates four clinical characteristics could be valuable for predicting the risk of severe complications. An appropriate range of serum ALB concentrations may be associated with a lower incidence of severe complications.

Background/Objectives: Both adiposity and nutritional-inflammatory status influence glucose metabolism; however, their longitudinal associations with glycemic changes in non-diabetic populations remain unclear. We examined the independent, interactive, and joint associations of body mass index (BMI) and prognostic nutritional index (PNI) with the 3-year change in HbA1c (ΔHbA1c). PNI, a composite marker of serum albumin and peripheral lymphocyte count, reflects both protein nutritional status and systemic immune competence. We hypothesized that BMI and PNI would each independently predict ΔHbA1c and that their joint profiling would identify higher-risk subgroups. Methods: A total of 9414 non-diabetic adults from the Shanghai Suburban Adult Cohort were included. Participants with diabetes at baseline (defined as fasting plasma glucose ≥ 7.0 mmol/L, 2-h post-load glucose ≥ 11.1 mmol/L, HbA1c ≥ 6.5%, or self-reported physician diagnosis of diabetes or use of glucose-lowering medications) were excluded. BMI was measured, and PNI was calculated as serum albumin + 5 × lymphocyte count. ΔHbA1c was assessed over a 3-year period. Multivariable linear regression, interaction testing, and joint stratification were performed. Covariate selection was guided by prior biological plausibility, and model adequacy was evaluated using the Akaike Information Criterion (AIC). Results: Both BMI (β = 0.013% per kg/m2, 95% CI: 0.011-0.016, p < 0.001) and PNI (β = 0.002% per unit, 95% CI: 0.000-0.004, p = 0.019) were independently and positively associated with ΔHbA1c. No significant interaction was observed (p = 0.431). High BMI (≥24 kg/m2) was associated with glycemic worsening irrespective of PNI level (β ≈ 0.075%, p < 0.001). Among normal-weight individuals, higher PNI was associated with a modest increase in ΔHbA1c (β = 0.031%, p = 0.007). Conclusions: Although the absolute effect sizes were modest at the individual level, BMI was consistently and independently associated with glycemic deterioration therefore, even small per-unit increases may translate into meaningful risk at the population level given the high prevalence of overweight and obesity. PNI showed a small positive association, suggesting that in relatively healthy populations a higher PNI may partly capture subtle pro-glycemic factors-such as low-grade inflammation or higher protein intake-rather than representing unambiguous nutritional benefit. The absence of interaction suggests that BMI and PNI act through largely independent pathways. These findings extend prior evidence by demonstrating that PNI provides modest additional glycemic information beyond BMI in non-diabetic community-dwelling adults, particularly among those of normal weight.

BackgroundLung adenocarcinoma is a multifaceted disease with diverse locations and timings of gene mutations, histology, and molecular pathogenesis. Thus, identifying therapeutic target genes for lung adenocarcinoma has become a major challenge.MethodWe downloaded the gene expression profiles of 220 patients with lung adenocarcinoma from the Gene Expression Omnibus database and identified the differentially expressed genes between noncancer tissue and cancer tissue groups. Mendelian randomization analysis was performed using the exposure gene expression quantitative trait locus dataset and outcome dataset (ieu-a-965) to obtain genome-wide association studies summary data. Sensitivity analysis was used to assess the presence of pleiotropy and heterogeneity in the instrumental variables. Additionally, we performed Mendelian randomization analysis to explore the potential intersecting genes between differentially expressed and specific genes. Moreover, gene set enrichment and overall survival analyses were performed on the intersection gene.ResultsWe combined Gene Expression Omnibus and genome-wide association studies data to identify one upregulated and two downregulated genes associated with lung adenocarcinoma risk using inverse variance weight analysis as the primary analytical method. We observed that survival was significantly higher in the groups with high expressions of ANGPT1 and CD36 than in those with low expressions of these genes. POU2AF1 demonstrated inconsistency with the results obtained using Kaplan-Meier analysis and lacked statistical significance in the GSE130779 cohort.ConclusionOur results confirmed two specific target genes, CD36 and ANGPT1, based on Mendelian randomization analysis, providing new insights into the role of these target genes in mediating the development of lung adenocarcinoma.

Optimization of HbA1c, blood pressure and cholesterol, referred to as the “ABCs”, is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients with diabetes remains unclear. In this prospective cohort study, 43,732 Chinese adults aged ≥ 40 years with diabetes were included from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Participants were stratified by age (< 55, 55-<65, 65-<75, ≥ 75 years). Cox proportional hazards regression and Fine-Gray competing risk models were employed to estimate the associations of HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with all-cause, cardiovascular, and non-cardiovascular mortality across age groups. Relative importance and population attributable fractions (PAFs) were computed for each metabolic factor. During a median follow-up of 10.1 years, 3,975 deaths were documented. Age significantly modified the associations of HbA1c, SBP, and LDL-C with all mortality outcomes (all P for interaction < 0.05). Among participants aged < 75 years, HbA1c showed graded positive associations with all-cause, cardiovascular, and non-cardiovascular mortality. The SBP thresholds associated with increased mortality risk were 140 mmHg in those aged < 65 years and 160 mmHg in those aged 65–<75 years. Among those aged ≥ 75 years, however, the patterns of these associations differed markedly. Elevated mortality risk was observed only at HbA1c ≥ 9

Optimal control of hemoglobin A1c (HbA1c), blood pressure, and cholesterol (ABC risk factors) is essential for reducing cardiovascular disease (CVD) risk in individuals with diabetes. However, age-specific contributions of these factors remain inadequately characterized. Using data from the China Cardiometabolic Disease and Cancer Cohort study, we assessed the associations between ABC risk factors and incident CVD among Chinese adults with diabetes, stratified by age groups of < 55, 55 to < 65, 65 to < 75, and ≥ 75 years. Cox proportional hazards models and population-attributable fractions (PAFs) were used to quantify the associations between ABC risk factors and incident CVD. During a median follow-up of 10.1 years, 4707 incident cases of CVD were documented. Higher levels of baseline HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) were significantly associated with increased CVD risk. Age modified these associations (P interaction < 0.05), with progressively attenuated hazard ratios (HRs) observed in older age groups. Compared with HbA1c < 7.0%, HbA1c ≥ 9.0% showed stronger CVD associations in adults aged < 55 years (HR = 2.42; 95% confidence interval [CI]: 1.98-2.97) than in those aged ≥ 75 years (HR = 1.50; 95% CI: 1.12-2.02), and SBP ≥ 140 mmHg and LDL-C ≥  4.1 mmol/L were significant only in younger groups. The leading contributor to PAFs for CVD was SBP (28.3%), followed by HbA1c (12.0%) and LDL-C (9.2%), with diminishing impacts across older groups. These results underscore the importance of age-specific management of ABC risk factors in diabetes care, with the benefit of stricter risk factor management in younger adults and the need for a more flexible approach in older populations.