Polyols, natural nutritive sweeteners, are commonly found in the diet during pregnancy. This study investigates the association between maternal serum polyol levels and the risks of gestational diabetes mellitus (GDM) and large for gestational age (LGA) infants.

This nested case-control study matched 218 women (GDM vs non-GDM) by age and body mass index (BMI). After exclusions, the final analytic sample comprised 194 women for glucose metabolism outcomes and 177 for birth weight and LGA outcomes. Serum polyols (sorbitol, erythritol, xylitol, and maltitol) were quantified using gas chromatography coupled with time-of-flight mass spectrometry. LGA was defined as birth weight ≥90th percentile or ≥4000 g. Logistic regression was used to assess associations between polyols and GDM and LGA, with adjustment for confounders.

Among the participants, 23.7% had LGA infants, and maternal serum polyol levels were significantly higher in this group. After adjusting for confounders, a 1-SD increase in serum polyol levels was associated with increased odds of LGA (OR 1.71, 95% CI: 1.22-2.40) and GDM (OR 1.52, 95% CI: 1.09-2.14). Erythritol and sorbitol were significantly associated with the odds of LGA, while xylitol and maltitol showed no significant associations. Additionally, a 1-SD increase in serum polyol levels was linked to higher birth weight (β= 95 grams, 95% CI: 33-157 grams) and elevated homeostasis model assessment for insulin resistance (β= 0.32, 95% CI: 0.12-0.52).

Elevated maternal serum polyol levels were positively associated with the risks of GDM, LGA infants, and higher birth weight.

The global prevalence of metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD), continues to rise, representing a major global health threat and economic burden. Dihydroberberine (DHB), a reduced derivative of berberine (BBR), has recently garnered attention due to its superior lipophilicity and intestinal absorption. Pharmacokinetic studies suggested that DHB achieves significantly higher blood concentrations compared to BBR at equivalent doses. This review systematically synthesized the current preclinical evidence regarding the metabolic regulatory mechanisms of DHB. Key pharmacological targets identified in cell and animal models included the activation of AMP-activated protein kinase (AMPK) and glucokinase (GCK), modulation of lipid metabolism, and attenuation of inflammatory and oxidative stress pathways. Furthermore, DHB interacted extensively with the gut microbiota, acting both as a microbial metabolite of BBR and a modulator of microbial composition. Toxicological assessments indicated a favorable safety profile, although potential risks such as hERG channel inhibition required careful evaluation. Importantly, while in vitro and animal studies demonstrated significant metabolic benefits, human clinical trials assessing direct disease outcomes remained highly limited. This review highlighted the pharmacokinetic advantages of DHB and outlined the critical translational gaps that must be addressed in future research.

Pancreatic ductal adenocarcinoma (PDAC) in patients with diabetes mellitus (DM) represents a clinically heterogeneous subgroup, yet biomarkers that reflect diabetes-associated tumor biology and chemotherapy response remain limited. In particular, the influence of diabetes duration on treatment resistance in PDAC is poorly understood.

We performed an integrated translational analysis combining reanalysis of public single-cell RNA sequencing (scRNA-seq) datasets, clinical serum biomarker profiling, and functional validation using pancreatic cancer cell lines and patient-derived organoids. Circulating REG4 concentrations were measured in independent PDAC cohorts and correlated with diabetes duration, overall survival, and response to FOLFIRINOX. Functional relevance was assessed under diabetes-mimicking hyperglycemic conditions.

Single-cell transcriptomic analysis demonstrated enrichment of REG4-expressing tumor cells within the classical PDAC subtype specifically in diabetic patients. Clinically, circulating REG4 concentrations were significantly elevated in PDAC patients with long-standing diabetes, and high REG4 levels were associated with poor overall survival and resistance to FOLFIRINOX exclusively in this subgroup. In contrast, no prognostic association was observed in non-diabetic or new-onset diabetic patients. In patient-derived organoids and pancreatic cancer cell lines, chronic glucose exposure induced REG4 expression, activation of WNT/β-catenin signaling, suppression of apoptotic pathways, and increased resistance to FOLFIRINOX, recapitulating key clinical features of long-standing diabetes-associated PDAC.

These findings suggest REG4 as a candidate diabetes duration-dependent prognostic and predictive biomarker in pancreatic cancer, warranting validation in larger prospective cohorts. By linking metabolic context to chemotherapy resistance through REG4-associated signaling, this study provides a translational framework for patient stratification and treatment optimization in diabetes-associated PDAC.

People hospitalized for heart failure (HF) often have coexisting diabetes mellitus (DM). However, the balance between HF- and DM-related inpatient care in specialized cardiovascular wards remains unclear.

In this study, our aim was to compare HF- and DM-related inpatient care processes in people hospitalized for HF with coexisting DM and identify nurse-led opportunities for integrated management.

This retrospective observational study was conducted in the specialized cardiovascular ward of a 400-bed Japanese hospital (April 2023-March 2024). Among 274 consecutive HF admissions, clinical characteristics were compared by DM status and, within the HF+DM subgroup (n = 79), HF versus DM care processes were assessed: specialist involvement, medication adjustments, and nursing documentation. Effect sizes (Cohen's d, risk difference, and risk ratio [RR]) were calculated.

The prevalence of DM was 28.8%. Compared with people in the non-DM group, those in the HF+DM subgroup were younger (79.2 vs. 82.8 years; d = -0.31), had higher body mass index (23.5 vs. 20.9 kg/m2 at discharge; d = 0.52), and lower left ventricular ejection fraction (40.3% vs. 47.0%; d = -0.44). In the HF+DM subgroup, HF care practices were more frequently documented compared with DM care practices: specialist nurse involvement 45.6% versus 3.8% (RR = 12.00), medication adjustment 89.9% versus 22.8% (RR = 3.94), and nursing documentation 53.2% versus 5.1% (RR = 10.43). Some process gaps exceeded 10-fold differences.

Diabetes mellitus care was markedly under-addressed during HF admission. This is the first Japanese study to quantify HF-DM care disparities using effect sizes and highlight targets for nurse-led integrated pathways and stronger collaboration with endocrinologists.

Triglycerides have traditionally occupied an uncertain role in atherosclerotic cardiovascular disease (ASCVD) prevention, often considered secondary to low-density lipoprotein cholesterol (LDL-C). Emerging evidence indicates that triglycerides are best viewed not as a direct cause of atherosclerosis, but as a clinical marker of triglyceride-rich lipoprotein (TGRL) and remnant particle burden. These apolipoprotein B-containing particles can enter the arterial wall, promote lipid deposition, and amplify vascular inflammation. Genetic and Mendelian randomization studies support a causal link between remnant lipoproteins and ASCVD that is independent of LDL-C levels and proportional to atherogenic particle number. Despite effective LDL-C lowering, substantial residual ASCVD risk persists, particularly in patients with diabetes mellitus, obesity, and metabolic dysfunction. However, reducing triglyceride concentrations alone does not consistently translate into fewer cardiovascular events. Clinical benefit appears to depend on whether therapy meaningfully reduces atherogenic particle burden or modifies causal pathways. Icosapent ethyl has demonstrated reductions in major adverse cardiovascular events, although the mechanism of benefit remains incompletely understood and is not explained entirely by triglyceride lowering. Fibrates have shown modest benefit in selected populations, whereas mixed omega-3 formulations have not consistently demonstrated cardiovascular risk reduction. Emerging therapies targeting key regulators of remnant metabolism, including apolipoprotein C-III and angiopoietin-like protein 3, offer more direct approaches to modifying causal pathways. In contemporary practice, triglycerides should be interpreted longitudinally within a framework of remnant lipoprotein biology and residual cardiovascular risk rather than pursued as an isolated therapeutic target.

Background and objectives This systematic review seeks to assess the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM) within the Indian population. Methods A comprehensive search of SCOPUS, Web of Science and PubMed was performed for studies published from January 2000 to March 2025, using search terms such as MASLD, T2DM, NAFLD, steatohepatitis and India. This systematic review considered eligible Indian studies that included patients (≥18 years old) with T2DM and reported the prevalence of MASLD/NAFLD. The study excluded reviews, case reports, conference abstracts, editorials, and studies that did not have full texts. Pooled MASLD prevalence determined by liver biopsy, transient elastography, ultrasound, or biochemical markers was the main result. Prevalence estimates were combined using a random-effects model, and quality was evaluated using the Joanna Briggs Institute approach. Results Across the 18 selected studies, the pooled prevalence of MASLD was estimated from 81,364 adult diabetic participants. In diabetic adults, the estimated pooled prevalence of MASLD was 56.9% [95% Confidence interval (CI), 39.1-74.8]. Among these studies, the prevalence by biochemical marker was 50.4% (95% CI 38.6 - 62.2), the prevalence by ultrasonography was 55.6% (95% CI 37.1 - 74.1), and the prevalence by Fibroscan as an imaging modality was 64.3% (95% CI 31 - 97.7). Several limitations were noted; many studies provided insufficient information regarding cohort representativeness, selection criteria for non-exposed groups, and the adequacy of follow up. Interpretation and conclusions While awareness of MASLD is increasing among diabetic populations globally, data concerning its prevalence and clinical characteristics in the Indian population-especially within regional demographics-remains limited. The variability in reported prevalence rates, ranging from 34 to 94%, among individuals with T2DM indicates a pressing need for region-specific research that considers the diverse ethnic backgrounds, diets, and lifestyles throughout India.

Lysophosphatidylcholine acyltransferase 3 (LPCAT3), a membrane-bound O-acyltransferase, is well known for enriching phospholipids (PLs) with polyunsaturated fatty acids (PUFAs) and thereby driving ferroptosis. However, accumulating evidence indicates that LPCAT3 is not merely a ferroptosis effector but a broader integrator of non-ferroptotic functions, such as autophagy, endoplasmic reticulum homeostasis, and inflammatory signaling. Herein, we provide an overview of LPCAT3 functions that explicitly extend beyond ferroptosis. We first provide a comprehensive review of the structural and enzymatic characteristics of LPCAT3, along with its diverse regulatory mechanisms of expression. Subsequently, we summarize how LPCAT3-mediated PL remodeling modulates membrane biophysical properties and further elucidate the downstream effects of this remodeling on the regulation of autophagy, endoplasmic reticulum homeostasis, and inflammatory signaling pathways. Finally, we systematically review the pivotal roles of LPCAT3 in the pathogenesis of multiple human diseases, including neurodegenerative diseases, stroke, atherosclerosis (AS), diabetes mellitus, obesity (OB), non-alcoholic fatty liver disease (NAFLD), and cancer. This review aims to elucidate the functions of LPCAT3 beyond its role in regulating ferroptosis and may provide new insights into its involvement in human diseases.

Observational studies have repeatedly reported lower cancer incidence among metformin users than nonusers, but findings are inconsistent and often affected by issues such as immortal time, unclear comparators, and use of total cancer as a composite outcome, which precludes adequate adjustment for site-specific confounding. These limitations can be mitigated by explicitly emulating a target trial with a suitable active comparator.

We emulated a target trial using a Japanese claims database (April 2014-March 2024) to assess whether metformin reduces colorectal cancer (CRC) risk compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes. DPP-4is served as an active comparator because they are widely used as first-line alternatives in Japan and have no clear evidence of affecting CRC risk. We estimated the observational analogue of the per-protocol effect using pooled logistic regression with inverse probability weighting to adjust for baseline and time-varying confounders.

Among 26 273 metformin users and 108 299 DPP-4i users, the 5-year risk of CRC was 1.55% (95% confidence interval, 1.16 to 2.04) versus 1.26% (1.13 to 1.41), yielding a risk difference of 0.29% (-0.12 to 0.79) and a risk ratio of 1.23 (0.91 to 1.66).

Metformin use did not reduce the 5-year risk of CRC compared with DPP-4is. This finding is consistent with meta-analyses of randomized trials and contrasts with earlier observational reports of substantial benefit, which were likely inflated by methodological flaws. Explicitly emulating a target trial minimized design-related biases and provided estimates that support causal interpretation.

The differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in patients with pleural effusion (PE) continues to pose significant clinical challenges. While conventional pleural fluid cytology has limited sensitivity, invasive diagnostic procedures are often costly or inaccessible, particularly in resource-limited settings. In this study, we investigated the diagnostic contribution of ratios derived from pleural fluid adenosine deaminase (ADA), total protein, serum lactate dehydrogenase (S-LDH), and pleural effusion lactate dehydrogenase (PE-LDH) levels in patients with histopathological confirmed pleural effusion etiology. Specifically, the diagnostic performance of biochemical and hematological parameters, particularly the ADA/serum protein, S-LDH/ADA and PE-LDH/ADA ratios were evaluated for their ability to discriminate between TPE and MPE.

This retrospective cross-sectional study was conducted among patients who underwent diagnostic evaluation and treatment for pleural effusion at a tertiary referral hospital between 1 November 2014 and 1 November 2024. A total of 1,003 patients with pleural effusion (397 TPE and 606 MPE: 409 primary, 133 metastatic, and 64 mesothelioma) were included, whose etiologies were determined using a composite reference standard based on clinical, radiological, microbiological, and histopathological findings, with multidisciplinary team (MDT) evaluation applied in selected cases where appropriate. Receiver operating characteristic (ROC) curve analyses were performed to determine diagnostic accuracy, sensitivity, specificity, and optimal cut-off values.

Patients with TPE were significantly younger than those with MPE (median age: 32 vs. 65 years, p < .001). Overall, 62.9% of the study population were male. ADA levels were significantly higher in the TPE group, whereas S-LDH levels were higher in the malignant effusion group. When ratio-based parameters were evaluated, the S-LDH/ADA ratio was markedly higher in patients with malignant pleural effusion and emerged as the most powerful discriminatory marker, with an area under the curve (AUC) of 0.938, sensitivity of 89.5%, and specificity of 91.3%. The ADA/serum protein ratio also demonstrated high diagnostic accuracy for differentiating TPE, with an AUC of 0.929, sensitivity of 89.9%, and specificity of 93.3%. In multivariate analysis, the S-LDH/ADA ratio, ADA/serum protein ratio, and PE-LDH/ADA ratio remained independently associated with diagnostic discrimination between TPE and MPE.

Biochemical ratios particularly the S-LDH/ADA and PE-ADA/serum protein ratios are reliable, minimally invasive diagnostic tools for distinguishing TPE from MPE. These ratios are especially useful in guiding clinical decision-making in settings where access to invasive diagnostic procedures is limited.

To assess the effectiveness of photobiomodulation, compared to standard care, to prevent oral mucositis and functional impairment, and improve quality of life in adults who underwent hematopoietic cell transplantation (HCT).

Randomized, controlled clinical trial with 30 patients with hematologic malignancies.

InGaIP diode laser treatment, starting on the first day of conditioning until day + 3, three times a week.

wavelengths of 660 nm and 808 nm, 100 mW, 2 J, 20 points.

oral mucositis (WHO scale), functional capacity (2-min step test), handgrip strength (Jamar dynamometer), lower limb strength (Sit-to-Stand test), quality of life (FACT-BMT), and acceptance (0-10 numerical scale).

Participants fully adhered to the intervention (n = 15; 100%). Acceptance was rated 10/10 by 93.3% of participants. Severe oral mucositis occurred in 26.6% of the control group and 0% of the photobiomodulation group (p = 0.032). No significant differences were found between the groups in hospitalization days, handgrip strength, aerobic capacity, or lower-limb strength.

Photobiomodulation was associated with a lower occurrence of severe oral mucositis but did not affect physical function or quality of life at discharge. Acceptance in the Chilean context was very high.

ClinicalTrials.gov: NCT06260111.