OBJECTIVES: Clozapine, the gold-standard antipsychotic for treatment-resistant schizophrenia causes severe metabolic complications, including metabolic syndrome and increased type 2 diabetes (T2D) risk. A better understanding of the genetic factors influencing clozapine pharmacokinetics and the associated metabolic risk could inform precision medicine approaches to clozapine prescribing. METHODS: Using a series of genetic-epidemiological approaches, we aimed to identify candidate biomarkers associated with clozapine-induced metabolic dysfunction. Mendelian randomisation (MR) was employed to investigate evidence of causal relationships between clozapine metabolism and cardiometabolic traits. RESULTS: Higher plasma clozapine and clozapine-norclozapine ratio were associated with a higher risk of T2D and blood pressure. The phenome-scan-colocalization-MR pipeline identified traits influenced by clozapine-metabolism loci that might serve as markers of cardiometabolic risk. This pipeline identified 28 colocalizing markers associated with clozapine pharmacokinetic loci. Subsequent MR highlighted associations for 16 of these 28 biomarker candidates with cardiometabolic outcomes, which included haematological markers and excretory traits. CONCLUSIONS: These findings are hypothesis-generating and do not, in the absence of prospective clinical validation, establish causal relationships between clozapine and the identified cardiometabolic traits. They may inform the development of biomarker-guided monitoring approaches for risk stratification and early intervention, enabling a shift from reactive monitoring to predictive approaches in managing clozapine-induced metabolic dysfunction with appropriate clinical validation.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a common metabolic complication during pregnancy. Early identification of high-risk women is critical for reducing maternal and fetal complications. This study aimed to explore the predictive value of serum pentraxin 3 (PTX3) and galectin-3 in early pregnancy for GDM among Chinese women. METHODS: This retrospective case-control study recruited pregnant women with a first prenatal visit before 14 weeks of gestation. Serum samples were collected at enrollment. All participants were followed up to 24-28 weeks, and GDM was confirmed via standard 75 g oral glucose tolerance test (OGTT). Correlation analysis, ROC curve and binary logistic regression were used to evaluate predictive efficacy. A total of 120 eligible women were divided into the GDM group (n=60) and healthy control group (n=60). RESULTS: FBG, FINS, PTX3 and galectin-3 levels were markedly elevated in GDM group (P < 0.05). Both biomarkers were positively correlated with glucose and insulin indexes (P < 0.05). The AUC values of PTX3 and galectin-3 were 0.821 and 0.662 respectively. The combined detection yielded an AUC of 0.877, with a sensitivity of 86.5% and a specificity of 92.3%. PTX3 and galectin-3 were verified as independent risk factors of GDM. CONCLUSION: First-trimester PTX3 and galectin-3 can serve as effective biomarkers for GDM prediction. Combined detection improves diagnostic efficiency and facilitates early screening for high-risk populations. Due to the single-center design and 1:1 grouping inconsistent with actual GDM prevalence, further prospective multicenter studies are required to validate our findings.

BACKGROUND: Sodium-glucose transporter 2 (SGLT2) inhibitors have shown significant cardiovascular benefits in heart failure (HF) patients with diabetes mellitus or chronic kidney disease. However, their safety and efficacy in non-diabetic patients without HF presenting with acute myocardial infarction (AMI) remain understudied. METHODS: Databases including MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov were queried through August 2025 to identify randomized controlled trials (RCTs). Data were pooled using a random-effects model using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). RESULTS: Five RCTs involving 9,135 patients (SGLT2i: 4,581 and placebo: 4,554) were included. On pooled analysis, SGLT2 inhibitors were associated with significantly reduced first HF hospitalization (RR: 0.74, p=0.02), improved LVEF (MD: 2.08; p=0.002), and reduced NT-proBNP levels (MD: 12.81; p < 0.0001). No significant differences were noted in all-cause mortality and the composite of first HF hospitalization with all-cause mortality. CONCLUSION: In non-diabetic patients without HF, SGLT2 inhibitors significantly reduce the first HF hospitalization and improve LVEF following AMI. The findings of this meta-analysis suggest that future research should evaluate the cardiovascular benefits of SGLT2 inhibitors in this patient population.

OBJECTIVE: The war in Sudan, which began in April 2023, has displaced millions and severely disrupted the healthcare system. This study assessed the association between armed conflict, displacement, and glycemic control in people living with diabetes (PWD), as well as the prevalence of diabetes-related complications in this context. RESEARCH DESIGN AND METHODS: This is a cross-sectional study. Using systematic random sampling, 385 displaced adults living with diabetes, aged 19 years or older, were recruited. The study was conducted at the diabetes center in Port Sudan from October 2024 to May 2025. Data on sociodemographic characteristics, clinical history, and barriers to care were collected through structured questionnaires. Bivariate analyses and binary logistic regression were used to identify factors associated with uncontrolled diabetes. RESULTS: Participants had a mean age of 53 ± 12 years; 51.4% were female. All were displaced because of the armed conflict. The mean HbA1c was 9.38% (± 2.42); only 16.6% of participants achieved glycemic control (HbA1c < 7.0%). Poor adherence to diabetes management was reported by 15.8% of patients, with an average HbA1c of 12.09% in this group. A high prevalence of complications was observed, with 26.5% and 20.8% of patients having diabetic foot and diabetic retinopathy, respectively. In regression analysis, poor adherence was the sole factor significantly associated with uncontrolled diabetes (OR 41.96, 95% CI [11.04, 159.52],  < 0.001). Female gender and higher education were associated with higher mean HbA1c in bivariate analysis (9.63% vs. 9.11%,  = 0.015;  = 0.007, respectively) but were not independent predictors in the multivariate model. Stress exposure was nearly universal (99.2%) but not significantly associated with glycemic control in this sample. CONCLUSIONS: In this cross-sectional study of displaced PWD, the context of armed conflict in Sudan was associated with a high prevalence of poor glycemic control; diabetic foot syndrome was present in 26.5% and retinopathy in 20.8% of participants; as these were self-reported and patient overlap was not assessed, these figures represent individual prevalences rather than cumulative burden. Adherence to management was the key modifiable factor correlated with glycemic outcomes. These findings highlight an urgent need for conflict-sensitive diabetes management strategies. Humanitarian responses should consider ensuring reliable, affordable access to care and support programs as a potential means to address the cascade of diabetes-related complications in conflict settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-02009-z.

is an uncommon cause of human infection and a rare cause of septic arthritis. We report an 81-year-old woman with diabetes mellitus, chronic kidney disease, gout, and dementia who developed septic arthritis of the distal interphalangeal joint of the right third finger during hospitalization for bacteremia. Computed tomography demonstrated erosive joint destruction with an adjacent abscess. Surgical incision, drainage, and arthrotomy revealed septic arthritis with associated abscess formation and degeneration of the terminal extensor tendon. Operative cultures grew together with multiple anaerobic organisms. The patient underwent surgical debridement, followed by prolonged oral doxycycline therapy and a short course of metronidazole for polymicrobial anaerobic coverage, resulting in complete clinical resolution. This case highlights an uncommon cause of native joint septic arthritis and emphasizes the importance of considering unusual pathogens in patients with pre-existing joint disease and atypical clinical presentations.

Pulmonary nocardiosis is an uncommon but potentially serious infection caused by aerobic actinomycetes of the genus Nocardia. It predominantly affects individuals with impaired immunity or underlying structural lung disease, but can also occur in apparently immunocompetent hosts. The clinical and radiological features often overlap with tuberculosis and fungal infections, particularly in endemic regions, leading to frequent misdiagnosis and delay in appropriate therapy. We present a series of three patients with microbiologically confirmed pulmonary nocardiosis, each representing different clinical backgrounds. The first case involved a middle-aged male with poorly controlled diabetes mellitus presenting with chronic cough and bilateral pulmonary infiltrates. Imaging revealed patchy peribronchial opacities, and bronchoalveolar lavage (BAL) demonstrated filamentous, weakly acid-fast organisms on modified acid-fast staining. The second case was an elderly female with underlying bronchiectasis who presented with increased cough and expectoration; imaging showed bronchiectatic changes with superimposed infiltrates, and BAL confirmed Nocardia infection. The third case involved an elderly male with recent immunosuppressive therapy who presented with acute respiratory symptoms and radiological evidence of multifocal consolidation; microbiological evaluation confirmed nocardiosis. All patients were treated with appropriate antimicrobial therapy, including trimethoprim-sulfamethoxazole as the backbone, with additional agents such as imipenem or linezolid in selected cases. Clinical improvement was observed in patients who adhered to therapy, with symptomatic relief and partial radiological resolution on follow-up. This case series underscores the varied clinical presentation and imaging spectrum of pulmonary nocardiosis. Diabetes mellitus, structural lung disease, and immunosuppressive therapy emerged as key predisposing factors. The condition often mimics tuberculosis or bacterial pneumonia, making microbiological confirmation using modified acid-fast staining crucial. Early diagnosis and prompt initiation of appropriate therapy significantly influence patient outcomes. Pulmonary nocardiosis should be considered in patients with nonresolving pulmonary infiltrates, especially in the presence of risk factors such as diabetes, bronchiectasis, or immunosuppression. A high index of suspicion, combined with timely microbiological diagnosis and appropriate antimicrobial therapy, is essential to improve prognosis and reduce morbidity.

AIM: In type 2 diabetes mellitus (T2DM), Metabolic dysfunction-associated steatotic liver disease (MASLD) is emerging as a significant health problem; however, the treatment options appear to be restricted despite an overlap between MASLD and diabetes. The present trial was conducted to investigate the efficacy of SGLT-2 inhibitor (dapagliflozin) in improving the metabolic and liver parameters in MASLD and type 2 diabetes. MATERIALS AND METHODS: A 24-week randomized controlled trial evaluated the role of dapagliflozin (10 mg/day) in MASLD and T2DM patients. 1:1 randomization was done into dapagliflozin plus standard care (n = 34) or standard care alone (n = 30). Changes in liver steatosis (Ultrasonography [USG]), fibrosis (fibroscan, fibrosis-4, and aspartate aminotransferase (AST)-to-platelet ratio index [APRI]), and biochemical markers were analyzed. Data were analyzed using SPSS, and P < 0.05 was considered significant. RESULTS: At the 24-week follow-up, a significant reduction in AST (P = 0.027) and alanine aminotransferase (P = 0.002) levels was observed in the dapagliflozin group. Significant decline in triglycerides (P = 0.020) and an increase in high-density lipoprotein cholesterol (P = 0.001) were observed. No significant differences were observed in liver stiffness measurement, FIB4, and glycated hemoglobin levels; however, the APRI score declined significantly (P = 0.038). The intervention group maintained a higher body mass index (P = 0.037) but showed hepatic improvements. No adverse events were reported during the trial, and the drug was well-tolerated. CONCLUSIONS: Dapagliflozin (SGLT-2 inhibitor) significantly reduces markers of dyslipidemia and liver injury in MASLD and type 2 diabetes patients, and this effect appears to be independent of weight loss. Results of a 24-week trial showed a decrease in inflammation; a longer-duration trial will establish significant improvement in hepatic fibrosis.

Endobronchial tuberculosis is a distinct form of pulmonary tuberculosis involving the tracheobronchial tree and may present with varied bronchoscopic appearances. The tumorous subtype is rare and can closely mimic malignancy both clinically and radiologically, leading to diagnostic dilemmas and potential delays in appropriate treatment. A 45-year-old female presented with a 1-month history of progressive dyspnea (modified Medical Research Council Grade II), cough with mucoid expectoration, low-grade fever with evening rise, and significant weight loss. She was a known case of obstructive airway disease and type 2 diabetes mellitus. Chest radiography revealed a nonhomogeneous opacity in the left hilar region with bilateral hyperinflation. High-resolution computed tomography (CT) showed a well-defined lobulated hypodense mass in the lingular segment of the left lung, while contrast-enhanced CT demonstrated an irregular soft-tissue lesion extending from the hilum to the left upper lobe with branching projections, raising suspicion of malignancy. Bronchoscopy revealed a vascular, nonpedunculated polypoidal mass in the left lingular segment, causing luminal narrowing. However, cytology and histopathology were negative for neoplastic cells. Bronchoalveolar lavage CBNAAT detected Mycobacterium tuberculosis with rifampicin sensitivity, confirming the diagnosis of endobronchial tuberculosis. The patient was initiated on standard antitubercular therapy for 6 months, resulting in symptomatic improvement. Follow-up imaging and bronchoscopy showed partial resolution with residual lesion, leading to extension of therapy to a total of 9 months. Continued clinical and radiological improvement was observed. Tumorous endobronchial tuberculosis can closely mimic lung malignancy and should be considered in the differential diagnosis of endobronchial masses, especially in endemic regions. Early bronchoscopy combined with molecular diagnostic tools such as CBNAAT is crucial for accurate diagnosis and timely initiation of therapy, thereby preventing unnecessary invasive procedures and long-term complications such as bronchial stenosis.

INTRODUCTION: Seroma is the most common postoperative complication following mastectomy and may result in additional postoperative interventions and increased treatment burden. However, its etiology and predictive factors remain insufficiently understood. This study aimed to identify predictors of postoperative seroma formation. MATERIALS AND METHODS: We conducted a retrospective analysis of 245 patients (301 breasts) who underwent conventional mastectomy or skin-/nipple-sparing mastectomy, with or without immediate implant reconstruction and axillary surgery, at the University Hospital Leipzig between 2019 and 2023. Variables analyzed included epidemiological characteristics, neoadjuvant chemotherapy, tumor status, perioperative factors, and wound drainage output. Seroma formation was assessed via drains placed in the breast and axilla. Statistical analyses included univariable and multivariable regression and random forest modeling. RESULTS: In univariable analyses, higher body mass index (BMI), longer surgical duration, diabetes mellitus, hypertension, advanced tumor stage, and elevated C-reactive protein levels were associated with increased breast seroma formation. Random forest analysis identified BMI, number of resected lymph nodes, surgical duration, hypertension, and diabetes as key predictors, all of which remained significant in multivariable models. For axillary seroma, BMI, number of resected lymph nodes, and tumor stage were significant in univariable analyses, while BMI and number of resected lymph nodes remained significant in multivariable models. CONCLUSION: Seroma formation is primarily influenced by BMI, extent of lymph node removal, and surgical duration, with hypertension and diabetes as additional risk factors for breast seroma.

Obesity is a complex metabolic disorder associated with dysregulated lipid metabolism and impaired adipose tissue function, resulting in the development of various chronic diseases such as diabetes mellitus. Plant-based therapeutic strategies, targeting the inhibition of digestive enzymes, have gained increasing attention as potential safe alternatives to synthetic drugs. This study investigated the inhibitory effect of root and leaf extracts of Hypoxis hemerocallidea Fisch., C.A.Mey. & Avé-Lall. and Pentanisia prunelloides (Klotzsch ex Eckl. & Zeyh.) Walp, against α-amylase, α-glucosidase, and pancreatic lipase, and related these activities to metabolite profiles to explore their potential relevance in obesity-associated metabolic dysfunctions. The results showed that H. hemerocallidea leaves exhibited a strong inhibitory activity against pancreatic lipase (98.68%) and α-glucosidase (98.10%), while α-amylase was considerably lower (11.71%). In P. prunelloides, both roots and leaves showed a strong α-glucosidase inhibitory activity of 99.02% and 96.38%, respectively. Moderate α-Amylase inhibitory activity was observed in the roots of H. hemerocallidea (53.14%), and P. prunelloides (50.63%), with the inhibition levels comparable to the lipase standard inhibitor acarbose (55.65%). Metabolite profiling using liquid chromatography-mass spectrometry (LC-MS) analysis revealed diverse putatively identified bioactive metabolites, including flavonoids, phenolic acids, phenolic glycosides, proanthocyanidins, saponins, terpenoids, and xanthones. Correlation and multivariate analyses suggested potential associations between metabolite abundance and enzyme inhibitory activities. Collectively, these findings suggest that both plant species possess substantial metabolite diversity and promising in vitro enzyme inhibitory activities, with H. hemerocallidea exhibiting comparatively stronger inhibitory activity. However, no compound isolation, cytotoxicity assessment, and in vivo validation was performed; therefore, the findings should be considered preliminary and require further pharmacological and mechanistic investigation.

BACKGROUND: Ventilator-associated pneumonia (VAP) represents a complication occurring in patients undergoing mechanical ventilation. This study aimed to develop a Bayesian network model to identify factors associated with the occurrence of VAP. METHODS: A retrospective cohort analysis was conducted using data from patients aged ≥ 60 years who underwent mechanical ventilation in the Department of Intensive care unit at the Second Hospital of Shanxi Medical University between June 2018 and June 2022. Collected variables included demographic characteristics, clinical conditions, medication use, catheterization-related data, laboratory findings, nursing-related and mechanical ventilation-related data. The chi-square test and logistic regression analysis were applied to determine factors associated with VAP. A Bayesian network model was subsequently constructed using the max-min hill-climbing algorithm. RESULTS: A total of 502 patients were included, comprising 332 males and 170 females, with a median age of 72 years (range: 60-100 years). The prevalence of VAP was 9.6% (48/502 patients). The constructed Bayesian network included 10 nodes and 17 directed edges. Direct associations with VAP were identified for antibiotic use exceeding three agents, reintubation, mechanical ventilation methods, and an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 15. Indirect associations were observed for disease category, diabetes mellitus, presence of an indwelling central venous catheter, transfusion, and corticosteroid administration. The area under the receiver operating characteristic curve for the Bayesian network model was 0.84 (95% CI: 0.79-0.90). CONCLUSION: The Bayesian network model elucidates the interrelationships among multiple factors associated with VAP. The model may provide ancillary information to help clinicians identify patient profiles associated with higher VAP risk and facilitate the implementation of early during mechanical ventilation.

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) weakened the diagnostic ability of traditional elastography ultrasound on liver fibrosis. Combi-elasto ultrasound can simultaneously reflect the information of fibrosis degree and fat accumulation, thus have better potential and generality for liver fibrosis. We aim to develop a combi-elasto ultrasound based deep learning (DL) model for fibrosis staging in suspected MASLD/MASH patients. METHODS: Patients with overweight, type-2 diabetes, hypertension or dyslipidemia, and without alcoholic, drug-induced, and genetic hepatitis history were defined as suspected MASLD/MASH patients. Fibrosis stages were classified as none or mild (F0/F1), moderate (F2), and severe (F3/F4). Combi-elasto images from ten centers were collected to build the DL model. OpenCV was applied to automatically extract image information, Resnet-50 was used to analyze image feature, and adversarial training (AT) algorithm was introduced to enhance model generality. Traditional DL model without AT algorithm, and other seven classical fibrosis models were also built to compare with AT-DL model. Subgroup analysis on pathological confirmed normal, MASLD and MASH patients were performed to test model generality. RESULTS: From January 2022 to December 2023, 295 patients from eight centers were divided into training (n = 204) and validation (n = 91) sets. 101 patients from two independent centers were collected as external test set. In test set, AT-DL model achieved significantly higher accuracy than traditional DL model (0.871 vs. 0.812, p = 0.021) and all other classical models (0.545-0.762, all p < 0.05). For pathological confirmed normal patients, AT-DL and traditional DL models had comparable accuracy (0.881 vs. 0.905, p = 0.274). However, for pathological confirmed MASLD and MASH patients, AT-DL model showed significantly accuracy than traditional DL model (0.900 vs. 0.800, p = 0.028 and 0.828 vs. 0.690, p = 0.003). CONCLUSION: Combi-elasto ultrasound based AT-DL model had satisfactory performance on fibrosis staging in suspected MASLD/MASH patients, and could reliable non-invasive monitoring of fibrosis progression.

PURPOSE: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and perioperative, postoperative and fusion-related outcomes following spine surgery. METHODS: A systematic search of PubMed/ MEDLINE, Scopus, Web of Science, and the Cochrane Library was conducted from inception through December 2025 in accordance with PRISMA 2020 guidelines. Comparative studies evaluating outcomes of spine surgery in patients exposed to GLP-1RAs versus non-users were included. Random-effects meta-analyses were performed for perioperative outcomes, medical and surgical complications, reoperation and fusion-related outcomes. Subgroup analyses were conducted based on diabetes status, fusion levels and duration of follow-up. RESULTS: Twenty comparative studies with 546,668 patients were included in the analysis. GLP-1RA use was not associated with significant differences in perioperative or postoperative outcomes, including transfusion [log odds ratio (OR)=-0.25,95% CI:-0.67,0.17), operative time [mean difference (MD)=-5.3 min,95% CI:-23.9,13.3)], length of stay (MD=-0.19days,95% CI:-1.35,0.96), surgical site infection (logOR = 0.29,95% CI:-0.08,0.66), venous thromboembolism (logOR = 0.19,95% CI:-0.25,0.63), readmission (logOR = 0.31,95% CI:-0.07,0.69), reoperation (logOR = 0.12,95% CI:-0.17,0.42), or implant failure. In contrast, GLP-1RA use was associated with higher fusion success (logOR = 0.42,95% CI:0.33,0.51;p < 0.001), consistent across follow-up intervals. CONCLUSION: In the available observational literature, GLP-1RA use is not associated with increased perioperative complications following spine surgery and may be related to improved fusion outcomes. These findings provide reassurance regarding perioperative safety and suggest a potential long-term benefit in arthrodesis, although prospective studies are needed to confirm causality and define optimal perioperative management strategies. LEVEL OF EVIDENCE: III.

Fentanyl and morphine are commonly prescribed opioids for cancer-related pain; however, the comparative associations between these agents and clinical outcomes in critically ill patients with malignancies remain unclear. This study aims to examine the associations of fentanyl versus morphine with delirium, length of stay (LOS) in the intensive care unit (ICU), and short-term mortality in this population. Clinical data from critically ill adults with malignancies admitted to the ICU for the first time were derived from the Medical Information Mart for Intensive Care-IV v3.1. The primary outcome was delirium. Secondary outcomes comprised 14- and 30-day all-cause mortality and the LOS in the ICU. Logistic regression models were adopted to evaluate the association of fentanyl versus morphine with delirium; linear regression models were applied to examine the association with the LOS in the ICU; Cox proportional hazards models were adopted to analyze associations with 14- and 30-day all-cause mortality. Subgroup analyses stratified by sex, age, hypertension, diabetes mellitus, and sepsis were performed to explore the stability of the findings. Propensity score matching was conducted for sensitivity analysis. Data from 2074 critically ill patients with malignancy (1051 fentanyl users and 1023 morphine users) were analyzed. Compared with those receiving fentanyl, patients receiving morphine demonstrated a significantly diminished risk of delirium (odds ratio = 0.273, 95% confidence interval [CI]: [0.200, 0.371], p < 0.001). Morphine was linked to a shorter LOS in the ICU relative to fentanyl (β = - 0.870, 95% CI: - 1.496 to - 0.243, p = 0.007). Nonetheless, compared to fentanyl users, those receiving morphine were linked to a 114.60% elevated risk of 14-day all-cause mortality (hazard ratio [HR] = 2.146, 95% CI: [1.503, 3.066], p < 0.001) and a 70.60% heightened risk of 30-day all-cause mortality (HR = 1.706, 95% CI [1.254, 2.320], p < 0.001). In conclusion, morphine is associated with a diminished risk of delirium and a shorter LOS in the ICU among critically ill patients with malignancy, yet concurrently linked to elevated short-term mortality. These findings indicate potentially divergent outcome associations within this population and may offer a point of reference for individualized analgesic management in critically ill patients with malignancy.

Diabesity, defined as obesity accompanied by Type 2 diabetes mellitus, is characterized by metabolic dysfunction and mitochondrial impairment. Here, we investigate the role of N6-methyladenosine (mA)-mediated RNA regulation in regulating hepatic mitochondrial function and fatty acid β-oxidation during diabesity progression. Diabesity was modeled in male C57BLKS/J db/db mice, with db/m lean mice as controls; in vitro models were established using primary hepatocytes isolated from male C57BL/6J mice exposed to high glucose and palmitate. Our results showed that MCM3 was significantly downregulated in diabesity models. MCM3 overexpression improved hepatic mitochondrial function and fatty acid β-oxidation. Mechanistically, MCM3 increased NRF2 in hepatocytes by competitive combination with KEAP1. In addition, RBM15 overexpression accelerated mA-YTHDF2-mediated MCM3 mRNA decay. As expected, MCM3 knockdown negated the metabolic benefits of RBM15 knockdown. In conclusion, mA-dependent MCM3 downregulation by RBM15/YTHDF2 impaired hepatic mitochondrial function and fatty acid β-oxidation in diabesity by reducing NRF2.

The co-administration of Dapagliflozin and Sitagliptin has attracted considerable interest in the management of type 2 diabetes mellitus due to their complementary therapeutic effects. However, their simultaneous determination is analytically challenging because of the significant overlap in their native fluorescence spectra. In this study, a selective and sensitive first-derivative synchronous spectrofluorimetric method was developed for the simultaneous determination of both drugs without prior separation. The proposed approach enabled efficient spectral resolution through zero-crossing points at 348 nm and 289 nm for dapagliflozin and sitagliptin, respectively, using a constant wavelength difference (Δλ = 30 nm). The method exhibited excellent linearity over the concentration ranges of 50-1000 ng/mL and 100-2000 ng/mL for dapagliflozin and sitagliptin, respectively, covering concentration levels relevant to their reported maximum plasma concentrations (Cmax), with low limits of detection (16.02 and 31.07 ng/mL, respectively), indicating high sensitivity. The proposed method demonstrated satisfactory accuracy (mean recoveries of 100.67% and 99.86%) and precision (%RSD < 2%). The method was successfully applied to the analysis of pharmaceutical dosage forms and spiked human plasma, showing reliable recoveries. To the best of our knowledge, this is the first validated spectrofluorimetric method for the simultaneous determination of these co-administered drugs, offering a simple, cost-effective, and efficient alternative to conventional analytical techniques.

Both excessive white adipose tissue (WAT) in obesity and insufficient WAT in lipodystrophy disrupt metabolic homeostasis. Although a vicious cycle between WAT dysfunction and gut dysbiosis is known to drive insulin resistance in obesity, whether lipodystrophy impairs gut function and contributes to glucose dysregulation remains unclear. Using adipocyte-specific MDM2 knockout (Adipo-MDM2-KO) mice as a model of lipodystrophy, we identified a direct role of WAT in maintaining intestinal and gut microbiota homeostasis. Progressive adipose tissue loss in Adipo-MDM2-KO mice caused multiple intestinal abnormalities, including gut microbiota dysbiosis, altered microbial metabolism, impaired intestinal barrier integrity, defective immunoglobulin A (IgA) responses, and endotoxemia. These defects were largely reversed by transplantation of healthy subcutaneous WAT (sWAT). Moreover, fecal microbiota transplantation from Adipo-MDM2-KO mice into C57BL/6J recipients reproduced intestinal defects and glucose intolerance, whereas microbiota depletion in Adipo-MDM2-KO mice largely rescued intestinal abnormalities and partially restored glucose homeostasis. Furthermore, sWAT-secreted adipokines, including extracellular vesicles, directly modulated the abundance and growth of specific gut bacterial communities. Multi-omics analyses further linked lipodystrophy-induced microbiota and metabolomic alterations to systemic endotoxemia and impaired glucose metabolism. Altogether, our findings reveal a critical WAT-gut-microbiota axis in the regulation of intestinal homeostasis and host glucose metabolism.

AIMS: To examine longitudinal associations between type 2 diabetes mellitus (T2DM) and work participation among Australians. METHODS: Adults (≥18 years) from the Household, Income and Labour Dynamics in Australia Survey were followed from 2013 to 2017 and 2021. The exposure was T2DM status: prevalent (T2DM at baseline and follow-up), incident (no diabetes at baseline; T2DM at follow-up), or no diabetes. Outcomes were changes in work participation (transition out of or into employment) and patterns of weekly working hours (including persistent non-employment). Survey-weighted Poisson regression estimated adjusted incidence rate ratios (IRR); group-based trajectory modelling examined working hours patterns. RESULTS: Over four years, prevalent (adjusted IRR 1.57, 95%CI 1.09-2.25) and incident T2DM (adjusted IRR 1.59, 95%CI 1.12-2.25) were associated with transition out of employment, and incident T2DM with reduced transition into employment (adjusted IRR 0.22, 95%CI 0.09-0.56). These associations were no longer significant over eight years of follow-up. Prevalent T2DM was associated with persistent non-employment (adjusted odds ratio 2.04, 95%CI 1.44-2.88), and incident T2DM with lower odds of increasing working hours (adjusted odds ratio 0.44, 95%CI 0.22-0.88). CONCLUSIONS: T2DM is associated with reduced work participation, particularly immediately following diagnosis, highlighting the importance of early, targeted workplace support.

In four patients with diabetes and end-stage kidney disease, glycated hemoglobin A1c (HbA1c) showed marked, time-varying discordance with continuous glucose monitoring (CGM)-derived glucose management indicator, ranging from - 2.1% to + 6.2%. Anemia, erythropoiesis-stimulating therapy, iron disturbances, hemoglobinopathy, transfusion and glycemic variability contributed, supporting CGM metrics for safer assessment and treatment adjustment.

This review aimed to highlight the relevance of telehealth in improving glycaemic control among older adults living with diabetes. Articles published between 2015 and 2025 across Ovid MEDLINE database, Cumulative Index to Nursing and Allied Health Literature (CINAHL) database, Scopus Cochrane Library and Ovid Excerpta Medica Database (EMBASE) were reviewed by two authors. The methodological quality of the studies was appraised using the Critical Appraisal Skill Programme (CASP) framework. In total, nine articles were reviewed and analysed to answer two research questions (3.5 and 3.7). The effectiveness of telehealth and digital interventions in supporting older adults with diabetes were highlighted and grouped into four themes: Digital self-monitoring and telehealth in diabetes management, technology-enabled exercise and lifestyle interventions, telehealth-based psychosocial interventions and effectiveness of telemedicine and remote care. Barriers such as limited digital literacy, privacy concerns, and insufficient technical skills continue to restrict widespread adoption of telehealth for the management of older people living with diabetes. Telehealth and digital tools can complement traditional diabetes care for older adults who have limited access to in-person diabetes services. However, optimising outcomes for older people require a focus on digital literacy, equitable access, and age-friendly diabetes telehealth services.

INTRODUCTION AND OBJECTIVES: Dapagliflozin does not impact heart failure events in patients with myocardial infarction who do not have type 2 diabetes. However, its effects on patients with diabetes remain unexamined. Therefore, the main goal of this study was to assess the effect of dapagliflozin added to post-acute myocardial infarction (AMI) therapy on the occurrence of major adverse cardiovascular events (MACE), including heart failure (HF), cardiovascular death, stroke, and new acute myocardial infarction in patients with type 2 diabetes. Secondary endpoints included changes in left ventricular ejection fraction (LVEF). METHODS: In a double-blind controlled clinical trial with an 18-month follow-up, we randomly assigned 181 patients with AMI to receive 10 mg of dapagliflozin or placebo once daily, along with standardized management. Risk analysis was conducted using both intention-to-treat and per-protocol analyses. RESULTS: At the 18-month follow-up, the total number of heart failure events was higher in the placebo group (26 events; 29.5%) than in the dapagliflozin group (5 events; 5.3%) (HR 0.18; 95% CI, 0.40-0.85; p < 0.001). Final LVEF increased by 1.56% in the dapagliflozin group compared to placebo (p= 0.03). CONCLUSIONS: Early initiation of dapagliflozin as part of the standard treatment for patients with acute myocardial infarction and type 2 diabetes decreases the risk of heart failure events at 18 months, improves LVEF, and remains safe even when combined with current optimal medical therapy. (ClinicalTrials.gov NCT04717986).

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine-metabolic disorder in women of reproductive age, and is characterized by hyperandrogenism, anovulation, and polycystic ovarian morphology. Emerging molecular evidence has identified dysregulated ovarian steroidogenesis as a major contributing mechanism linking reproductive and metabolic phenotypes in PCOS, acting in concert with neuroendocrine and metabolic dysfunction. This review synthesizes current knowledge on enzymatic and regulatory perturbations driving androgen excess and estrogen deficiency in PCOS, emphasizing their mechanistic, diagnostic, and therapeutic implications. Dysregulated steroidogenic enzymes and associated signaling pathways contribute to androgen excess, impaired folliculogenesis, and metabolic dysfunction in PCOS. Importantly, these steroidogenic alterations are not uniform across all patients with PCOS but vary according to hyperandrogenic, anovulatory, ovulatory, lean, obese, reproductive, and metabolic phenotypes. Particular focus is placed on how these molecular derangements disrupt theca-granulosa cell communication, impair folliculogenesis, and promote hyperandrogenism, oxidative stress, and insulin resistance in the ovaries. This review also discusses therapeutic strategies according to evidence level, distinguishing established PCOS treatments such as lifestyle intervention, insulin sensitizers, ovulation-induction agents, hormonal regulators, and anti-androgens from investigational enzyme-specific inhibitors and speculative precision approaches such as gene editing and exosome-based delivery systems. Collectively, these insights underscore that the pathophysiology of PCOS extends beyond endocrine imbalance to encompass multi-omic alterations in metabolism and signaling. Understanding enzyme-level dysregulation offers opportunities for mechanism-based interventions that can restore steroidogenic homeostasis, improve fertility outcomes, and mitigate long-term metabolic risk. Future research should prioritize enzyme-signal interdependencies and develop personalized therapeutic strategies targeting the biochemical dysfunctions of PCOS.

Standard modifiable cardiovascular risk factors (SMuRFs) and non-SMuRFs are commonly used for risk stratification and therapeutic guidance after ST-elevation myocardial infarction (STEMI) in the general population. Their prognostic relevance with a potential implication for pharmacological and therapeutic management in individuals with established diabetes remains uncertain. This systematic review with meta-analysis aimed to identify prognostic factors associated with mortality in individuals with diabetes and STEMI qualifying for potential therapeutic targets. Studies evaluating prognostic factors for mortality in individuals with diabetes after STEMI were included up to May 3, 2025. Data extraction was performed independently by two reviewers. Certainty of evidence (CoE) was evaluated (GRADE). Thirty-seven studies were included, of which 25 had a high risk of bias. Mortality after STEMI in individuals with diabetes was consistently associated with non-SMuRFs (age, female sex, chronic kidney disease), acute cardiac dysfunction (Killip class III-IV, heart failure, cardiogenic shock), and atherosclerosis extent (anterior infarction, prior myocardial infarction, peripheral vascular disease). Diabetes-specific risk factors, including glycemic control parameters and insulin treatment, were also associated with increased risk of mortality (low to very low CoE). Once diabetes is established, no increased risk of mortality was observed for traditional SMuRFs, such as hypertension, smoking status, dyslipidemia, and obesity. These findings highlight the need for therapeutic strategies beyond conventional risk factor modification, with emphasis on acute hemodynamic management, tailored pharmacotherapy, and optimized glycemic control in this high-risk population. REGISTRATION PROSPERo: CRD42022378193.

Subjective sensory evaluation dominates the Chinese baijiu industry but lacks objectivity and throughput. We developed a UPLC-TQMS method quantifying 130 key flavor compounds across eight chemical classes within 13 min per run. Leveraging this analytical protocol, we constructed a comprehensive Baijiu flavor database comprising 2048 samples covering all 12 standard flavor types and three quality grades of Nongxiang base liquor. Applying Random Forest algorithms, we discriminated among flavor types with accuracy >0.93, whereas XGBoost performed optimally in quality grading with accuracy of 0.90. Moreover, validation with an independent dataset confirmed the model's reliability and generalization capacity. SHAP analysis identified key chemical markers driving flavor differentiation and quality distinctions, underscoring the strength and interpretability of our approach in decoding complex flavor matrices. This work establishes a large-scale, standardized digital flavor library for Baijiu, providing a robust framework for intelligent quality control and industry standardization.

BACKGROUND: Evidence linking antenatal glycemic control to postpartum dysglycemia and weight retention in real‑world GDM care is limited. The authors tested whether late‑pregnancy control predicts early postpartum glucose intolerance and 12‑month Postpartum Weight Retention (PPWR). METHODS: In this single‑center prospective cohort, women with GDM were enrolled from May 2021 to April 2024. Antenatal control (28-36 weeks) from routine SMBG was summarized as Time‑In‑Target (TIT). Mean fasting/postprandial glucose were recorded. The primary outcome was postpartum glucose intolerance by 75 g OGTT at 6-12 weeks, and secondary outcomes were PPWR and substantial PPWR (≥ 5 kg) at 12-months. Multivariable logistic and mixed‑effects models adjusted for prespecified confounders. RESULTS: Of 348 enrollees, 287 (82.5%) completed the postpartum OGTT and 267 (76.7%) had 12‑month weight. Postpartum glucose intolerance occurred in 82/287 (28.6%). Each 10% lower TIT was associated with higher odds of dysglycemia (adjusted OR [aOR = 1.24], 95% CI 1.10-1.39). The poorest‑ vs. best‑control quartiles had aOR = 2.15 (95% CI 1.31-3.53). Mean PPWR at 12-months was 3.4 ± 4.1 kg; each 10% lower TIT corresponded to +0.32 kg PPWR (95% CI 0.12-0.52) and increased odds of substantial PPWR ≥ 5 kg (aOR = 1.13, 95% CI 1.02-1.25), with Q4 vs. Q1 aOR = 1.92 (95% CI 1.11-3.33). CONCLUSIONS: Poorer antenatal control was independently associated with postpartum dysglycemia and greater 12‑month weight retention, supporting risk‑stratified postpartum OGTT follow‑up and early lifestyle support.