Frontiers in Endocrinology

Aims: Sarcopenia and sarcopenic obesity are associated with increased risks of cardiovascular (CV) disease and mortality. This study examined the associations of body composition and daily physical activity with mortality, CV events and cancer in patients with diabetes. Methods: This prospective cohort study included patients with diabetes treated at a specialised clinic in Japan between January 2018 and March 2023. Body composition, including visceral adipose tissue (VAT), was assessed by bioelectrical impedance analysis. Daily physical activity was evaluated using the non-exercise activity thermogenesis (NEAT) questionnaire, and handgrip strength (HGS) was measured by dynamometry. Cox proportional hazards models were used to assess associations with mortality, CV events, and cancer. Results: Among 2,024 patients (mean age 63.0 years, BMI 24.6 kg/m^2, HbA1c 7.8%), NEAT, HGS, and VAT were not independently associated with all-cause mortality. Higher VAT was associated with increased cancer risk (HR 1.485; 95% CI 1.101-2.003; p = 0.009). Higher HGS was inversely associated with CV event risk (HR 0.951; 95% CI 0.919-0.984; p = 0.004). NEAT was not associated with any outcome. Conclusions: Higher VAT was associated with increased cancer risk, whereas higher HGS was protective against CV events. Incorporating body composition and HGS assessments into clinical practice may improve risk stratification and management in patients with diabetes.

Objective: Patients and physicians frequently focus on HbA1c and weight alone. We hypothesized that individuals with similar HbA1c and BMI may present markedly distinct metabolic backgrounds. We investigated whether the adipo-B index- composite of adipose insulin resistance (adipo-IR) and beta-cell function (HOMA-B)-can uncover hidden heterogeneity in this clinically homogeneous population. Methods: A total of 399 newly diagnosed, drug-naive Japanese subjects with T2DM were analyzed. Histograms of HbA1c and BMI demonstrated peak distributions within HbA1c 8-10% and BMI 24-26. Based on these distributions, a clinically homogeneous subgroup was defined to minimize confounding by glycemic severity and adiposity. Metabolic parameters including FBG, insulin, FFA, HOMA-R, HOMA-B, adipo-IR, adipo-B, T-C, TG, HDL-C and non-HDL-C were analyzed. Simple regression, multivariable linear regression, and subgroup stratification analyses were performed. Results: Despite comparable HbA1c and BMI by design, adipo-B stratification revealed significant differences in HOMA-B, FFA, non-HDL-C, and TG, whereas HOMA-R stratification identified only higher insulin and adipo-IR without differences in lipids or HOMA-B. Thus, adipo-B-but not HOMA-R-identified a lipotoxic, beta-cell-stressed phenotype invisible to conventional markers. Simple regression showed significant positive correlations between adipo-B and HbA1c, FBG, FFA, T-C, TG, and non-HDL-C, and negative correlations with insulin and HOMA-B. Multivariable linear regression confirmed that adipo-B was independently associated with non-HDL cholesterol, TG, and FFA after adjustment for HbA1c and BMI. Conclusion: Even among patients with identical HbA1c and BMI, the adipo-B index uncovers clinically relevant metabolic heterogeneity, supporting its role as a functional marker of the adipose-pancreas axis and a potential tool for precision phenotyping in early T2DM.

Administration of ciliary neurotrophic factor (CNTF) reduces food intake and body weight in both humans and experimental animals, where it also ameliorates hyperglycemia, hyperinsulinemia, and dyslipidemia. To exert its anti-obesogenic and anti-diabetogenic effects, CNTF targets brain feeding centers as well as multiple peripheral organs inducing the phosphorylation of the transcription factor signal transducer and activator of transcription 3 (p-STAT3). However, data showing which peripheral cytotypes are specifically targeted by exogenous CNTF in vivo in metabolically relevant organs are currently lacking. Here, we first evaluated the gene expression levels of the subunits of the tripartite CNTF receptor (Cntfr) complex, i.e., the Cntfr, the leukemia inhibitory factor receptor {beta} (Lifr{beta}) and the glycoprotein 130 (gp130), by quantitative real-time PCR in metabolically relevant organs of adult male mice: gastrointestinal (GI) tract, pancreas, liver, visceral and subcutaneous white (WAT) and interscapular brown adipose tissue (iBAT), skeletal muscle and the sciatic nerve. We then quantified p-STAT3 by Western blotting in these organs after intraperitoneal administration of CNTF (0.3 mg/kg) or saline. Finally, we mapped CNTF-responsive cells by immunohistochemistry, followed by morphometric quantification and confocal microscopy in both CNTF- and saline-treated mice. Lifr{beta} and gp130 were ubiquitously detected across all the investigated organs; the Cntfr showed the highest expression levels in the skeletal muscle, sciatic nerve, and iBAT, whereas it was found to be expressed to a lesser extent in the other sites. Administration of CNTF led to a significant increase of p-STAT3/STAT3 protein ratio in all organs examined, except the duodenum, and induced a distinctive pattern of cell nuclear p-STAT3 immunoreactivity. Notably, along the analyzed GI tract CNTF induced nuclear STAT3 phosphorylation in neurons of the submucosal and myenteric plexuses of the enteric nervous system and in contractile cells of the muscularis externa, where the response peaked in the mesenteric gut and colon. In the pancreas, CNTF triggered a higher activation within the endocrine component compared to the exocrine parenchyma. In the liver, CNTF induced STAT3 phosphorylation not only in parenchymal cells but also in sinusoids and resident macrophages. The cytokine activated p-STAT3 in subcutaneous and visceral white adipocytes, but also in brown adipocytes, with a prominent response observed in the beige subcutaneous adipocytes; adipose resident macrophages and endothelial cells of numerous blood vessels were also CNTF-responsive. Lastly, in skeletal muscle, a major site for glucose/lipid utilization, CNTF induced widespread nuclear p-STAT3 immunoreactivity in muscle fibers and in connective and Schwann cells of the peripheral nerves, including the sciatic nerve, supplying the gastrocnemius. In conclusion, our data indicate that CNTF acts across diverse cytotypes within metabolically relevant organs and tissues, likely fostering its peripheral metabolic effects through this cellular heterogeneity.

BackgroundVertical sleeve gastrectomy (VSG) improves glycaemic control in type 2 diabetes (T2D) through mechanisms that extend beyond weight loss. The interaction between glucocorticoid metabolism and inflammation in this context remains unclear. MethodsWe investigated the role of 11{beta}-hydroxysteroid dehydrogenase type 1 (11{beta}HSD1) in mediating the metabolic effects of VSG in humans and mice. Subcutaneous adipose tissue biopsies were collected before and 6 months after VSG. Parallel studies were conducted in lean and high-fat diet-fed mice undergoing VSG or sham surgery, alongside 11{beta}HSD1 knockout models. Glucose tolerance and expression of 11{beta}HSD1 and interleukin-6 (IL6) were assessed. Mechanistic interactions were examined in IL6-treated human hepatocytes. ResultsVSG reduced 11{beta}HSD1 and IL6 expression in human adipose tissue and improved insulin resistance. In lean mice, VSG improved glucose tolerance and downregulated both markers independently of weight loss. 11{beta}HSD1 knockout mice exhibited improved glucose tolerance despite increased adiposity, partially recapitulating the VSG phenotype. Both interventions reduced circulating and tissue IL6 levels. IL6 stimulation increased HSD11B1 expression in hepatocytes. Conclusions11{beta}HSD1 links glucocorticoid metabolism, inflammation, and glucose homeostasis following VSG. Targeting this pathway may offer a strategy to replicate key metabolic benefits of metabolic bariatric surgery.

Aims/Hypothesis: Behavioral and phenotypic characteristics do not fully explain variability in African Americans with youth-onset type 2 diabetes (Y-T2D) treated with metformin with or without liraglutide. We hypothesized that biological heterogeneity, including genetic variation in the metformin transporter OCT1, influences metformin pharmacokinetics and hepatic glucose flux. Therefore, we sought to characterize metformin pharmacokinetics in Y-T2D and evaluate genetic variants known to modulate metformin efficacy in adults to determine the mechanisms underlying variation in treatment response. Methods: We evaluated genetic variants related to metformin transport and mechanisms of action in 30 Y-T2D using a candidate-gene approach to evaluate the association of pharmacogenetic variants with fasting glucose and gluconeogenesis. In a subset of Y-T2D randomized to 3 months of metformin (n=11) or metformin and liraglutide (n=8), we constructed a metformin population pharmacokinetic model and evaluated gene variant associations. Results: A one-compartment first-order absorption and elimination pharmacokinetic model provided the optimal fit. Metformin pharmacokinetic parameters were similar by group and not related to glycemia. The rs628031_OCT1 A allele was associated with greater metformin clearance. The rs622342_OCT1 C allele was associated with lower post-treatment fractional gluconeogenesis ({beta} [95% CI] = -8.8 [-14.13, -3.47] %, Adjusted R2 = 0.56, P = 0.003). The rs7903146_TCF7L2 T allele was associated with greater reductions in fasting glucose among those treated with metformin + liraglutide ({beta} = -1.32 [-2.42, -0.22] mmol/L, Adjusted R2 = 0.8, P<0.002), but baseline glucose and gluconeogenesis (P<0.0001) were the strongest predictors of post-treatment glycemia. Conclusion/interpretation: In Y-T2D, OCT1 gene variants rs628031 and rs622342 were associated with metformin clearance and gluconeogenesis, respectively. TCF7L2 variant rs7903146 may contribute to differences in glycemic response in youth treated with metformin and liraglutide. These findings suggest genetic variants may be important for understanding variable metformin response in Y-T2D.

Background: Repeated metabolic-bariatric surgery (MBS, r-BS) represents 10-25% of all MBS procedures and is commonly performed for recurrent weight gain after initial weight loss. How weight loss followed by regain reshapes adipose tissue biology remains unclear. We hypothesized that women undergoing r-BS exhibit a distinct adipose tissue signature compared with those undergoing primary bariatric surgery (p-BS). Methods: We analyzed subcutaneous and visceral adipose tissues (SAT, VAT, respectively) from women undergoing either p-BS, or r-BS with documented >15% weight loss after prior MBS. Tissues were assessed histologically, molecularly, and functionally (activation of human microglia cells (HMC3) by SAT secretome). Results: Consistent with other cohorts, women undergoing r-BS (n=21) trended to be older (47.2 vs. 40.5 y, p=0.06) than those undergoing p-BS (n=35), with a lower BMI (42.3 vs. 45.6 kg/m2, respectively, p=0.103), and a trend for improved cardiometabolic risk parameters such as fasting insulin, CRP and HDL-c. Adipose tissue histological features (adipocyte size, fibrosis, macrophage and crown-like structure abundance) were similar, while adipose mast cells were slightly (though insignificantly) more prevalent in r-BS. A single-nucleus RNA-seq-based deconvolution algorithm applied to bulk RNA-seq confirmed the absence of a major shift in adipose tissue cell-type composition. Yet, it uncovered a unique SAT transcriptome, with activation of inflammatory pathways in r-BS. Consistently, SAT explants from r-BS secreted higher protein concentrations of NFkB-regulated cytokines IL6 and IL8. Biological impact of the more inflammatory secretome was demonstrated by its increased ability to activate human microglia cells. Conclusions: Prior BS with significant weight loss-regain in women is associated with an inflammatory SAT transcriptome and secretome, possibly reflecting altered adipose-brain endocrine communication.

Background: C-terminal binding protein 2 (CtBP2) has been implicated in metabolic regulation, but its association with specific measures of adiposity and lipid profiles in humans remains unclear. This study examined the relationship between circulating CtBP2 levels and key components of metabolic syndrome, focusing on body fat distribution and lipid markers. Methods: Data from 508 participants (259 men, 249 women) from a publicly available dataset were analyzed. Serum CtBP2 concentrations were measured using ELISA. Associations with obesity markers (BMI, waist circumference, waist-to-hip ratio) and lipid profiles (triglycerides, HDL cholesterol) were assessed using Spearman correlation and linear regression, adjusting for age and sex. Results: CtBP2 levels showed weak but statistically significant positive correlations with all measures of adiposity, with the strongest association observed for waist circumference ({rho} = 0.150, p < 0.001), followed by BMI ({rho} = 0.120, p = 0.007) and waist-to-hip ratio ({rho} = 0.098, p = 0.027). No significant correlations were found with triglycerides or HDL cholesterol. In the regression model predicting BMI, age, and sex were significant predictors, while CtBP2 demonstrated a trend toward association ({beta} = 0.080, p = 0.052). Conclusion: Circulating CtBP2 appears to be modestly associated with measures of adiposity, particularly abdominal fat, but not with lipid abnormalities. These findings suggest a potential role for CtBP2 in obesity-related metabolic dysregulation and underscore the need for further mechanistic studies to clarify its clinical relevance.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries, with granulosa cell dysfunction being a key pathological feature. This study aimed to investigate the role of microRNA-6818-5p in PCOS pathogenesis. Quantitative PCR revealed a significant upregulation of circulating miR-6818-5p in PCOS patients compared to healthy controls. In vitro, functional assays in the human granulosa cell line KGN demonstrated that miR-6818-5p overexpression markedly inhibited cell proliferation (assessed by CCK-8 assay) and promoted apoptosis (measured by Annexin V/PI flow cytometry). Mechanistically, dual-luciferase reporter assay and Western blotting identified HSD17B2 as a direct target of miR-6818-5p, with miR-6818-5p mimics significantly suppressing HSD17B2 protein expression. In conclusion, our findings reveal that elevated miR-6818-5p in PCOS may contribute to follicular development dysfunction by targeting HSD17B2 to disrupt granulosa cell proliferation and apoptosis balance, offering novel insights into PCOS pathology and highlighting miR-6818-5p as a potential diagnostic biomarker and therapeutic target.

Gestational diabetes mellitus (GDM) is a major metabolic complication of pregnancy with significant maternal and fetal adverse consequences. Beyond classical mechanisms, emerging evidence suggests that gut-derived metabolic endotoxemia may contribute to dysglycemia. Intestinal alkaline phosphatase (IAP), a key enzyme involved in maintaining gut barrier integrity and detoxifying lipopolysaccharides, has been linked to type 2 diabetes mellitus; however, its role in GDM remains largely unexplored. This hospital-based cross-sectional analytical study evaluated fecal IAP levels and their association with GDM among 198 pregnant women recruited from three antenatal care clinics representing three tiers of ANC services. Participants were screened for GDM using a 75-g oral glucose tolerance test and classified as having GDM (n=55) or normal glucose tolerance (NGT; n=143) according to WHO 2013 criteria. Stool samples were collected, and fecal IAP levels were measured using an enzymatic colorimetric assay. Fecal IAP level was significantly lower in women with GDM than in those with NGT (median 23.59 vs 46.48 U/g stool; p<0.001). Lower IAP level remained independently associated with GDM after adjustment for body mass index and previous GDM (adjusted OR 0.98 per unit increase; 95% CI 0.97-0.99; p<0.001). A graded relationship was observed between declining IAP level and GDM. Receiver operating characteristic analysis demonstrated modest discrimination (AUC 0.676), while a threshold of approximately 65 U/g stool yielded high sensitivity (89.1%) but lower specificity. Reduced fecal IAP is independently associated with GDM, supporting a potential role of gut-derived metabolic dysregulation in gestational glucose intolerance. While not suitable as a standalone diagnostic tool, fecal IAP may serve as a complementary biomarker for risk stratification during pregnancy. Prospective studies are warranted to determine its predictive value and explore its potential as a therapeutic target.

Background: Consensus continuous glucose monitoring (CGM) metrics, including time in range (TIR), time above range (TAR), time below range (TBR), mean glucose, glucose management indicator, and glycemic variability, are essential for modern glucose assessment. However, these whole-day summaries do not explicitly partition nocturnal basal from daytime ambulatory glycemic burden. Objective: To develop and evaluate a complementary domain-based CGM framework that quantifies basal and daytime ambulatory glycemic exposure across oral glucose tolerance test (OGTT)-derived dysglycemia phenotypes. Methods: In this observational, clinic-based study, 253 individuals underwent OGTT with insulin measurement and CGM. Participants were classified using a prespecified OGTT-derived phenotyping algorithm, implemented through a deterministic rules-based web calculator, and collapsed into five groups: NoDM, Increased insulin resistance, Midzone Glycemia, Prediabetes, and Diabetes. CGM files were uniformly reprocessed by selecting the latest contiguous episode and retaining the most recent 15 calendar days with data. The 24-hour profile was partitioned into nocturnal basal (00:00 to <06:00) and daytime ambulatory (06:00 to <24:00) domains. Derived indices included Area of Basal Glycemia (ABG), Area of Prandial/Daytime Ambulatory Glycemia (APG), incremental ABG (iABG), incremental APG (iAPG), and exploratory deficit indices dABG and dAPG. Results: The final dataset contributed 3,647 analyzable CGM days. APG remained higher than ABG across all groups. Mean ABG/APG increased from 80.45/86.38 mg/dL in NoDM to 111.96/124.70 mg/dL in Diabetes. Mean iABG/iAPG increased from 5.65/6.60 to 34.12/38.91 mg/dL, whereas dABG/dAPG declined as dysglycemia worsened. Conclusions: The ABG/APG framework provides interpretable, domain-resolved CGM burden metrics that separate basal from daytime ambulatory exposure and distinguish total burden from above-threshold excess. These indices are proposed as adjunctive metrics to support dysglycemia phenotyping, early risk recognition, and treatment monitoring, but are not intended to replace established consensus CGM metrics or diagnostic criteria. External, prospective validation is required.

Background Chronic gastritis and duodenitis (CGD) are highly prevalent among patients with type 2 diabetes (T2D). However, the prognostic impact of their comorbidity and the potential role of MRI-derived phenotype-tailored dietary strategies remain unclear. Methods This prospective cohort study included 453,768 UK Biobank participants. Primary endpoints were myocardial infarction, stroke, end-stage renal disease (ESRD), dementia, Parkinson's disease, and all-cause mortality. Time-dependent multivariable Cox regression assessed outcome associations, while additive interaction analyses evaluated synergistic effects between T2D and CGD. Eight healthy dietary pattern scores were analyzed. Latent profile analysis classified MRI-derived body composition phenotypes based on fat distribution and organ volume. Results T2D and CGD were positively associated, and their comorbidity increased risks of cardiovascular events, ESRD, dementia, and all-cause mortality. Additive interaction analyses demonstrated synergistic effects on myocardial infarction and all-cause mortality. The comorbidity was further associated with aggravated lipid metabolic abnormalities and multiorgan atrophy. Higher adherence to the Healthful Plant-Based Diet Index (HPDI) and Dietary Approaches to Stop Hypertension (DASH) diets attenuated the excess mortality risk related to this synergy. Dietary associations varied across T2D, CGD, and comorbid populations, while MRI-based latent profiles modified diet-outcome relationships. A nomogram integrating demographic, dietary, and body composition data demonstrated reliable long-term predictive performance for myocardial infarction, stroke, and all-cause mortality. Conclusions Comorbid T2D and CGD substantially increase adverse clinical risks and exhibit synergistic effects on myocardial infarction and all-cause mortality. These findings support routine CGD screening in T2D care and provide population-based evidence for MRI-derived phenotype-tailored dietary strategies.

Introduction Knee pain is a highly prevalent condition in the general population and is more common than knee osteoarthritis. Population-based evidence linking metabolic dysfunction to knee pain remains limited, and data on sex-specific effects are scarce. Therefore, we examined sex-specific associations between metabolic dysregulation and knee pain in a population-based cohort. Method We analyzed data from a population-based cohort of 1,512 adults (mean age 37.2 years at baseline), of whom 250 completed follow-up after a mean of 9.4 years. Metabolic dysfunction was assessed using a continuous MetS severity score (cMetS) derived from waist circumference, triglycerides, HDL cholesterol, fasting glucose, and systolic blood pressure. Knee pain at follow-up was defined using a combined measure based on a standardized question and a body manikin. Logistic regression models were used to examine associations between baseline cMetS and knee pain, including interaction analyses by sex. Results At follow-up, 28.5% of participants reported knee pain. Higher baseline cMetS was associated with increased odds of knee pain in males (odds ratio [OR] 1.41, 95% confidence interval [CI] 1.17-1.69) but not in females (OR 0.94, 95% CI 0.84-1.07), with evidence of interaction by sex (interaction P < 0.001). Findings were consistent across sensitivity analyses. Conclusions These results indicate that metabolic dysfunction is associated with knee pain in males but not in females, suggesting sex-specific mechanisms linking metabolic dysfunction and knee pain.

Background: Recent primary aldosteronism (PA) guidelines proposed probability-based stratifications, and use of aldosterone suppression testing, to predict lateralizing PA subtype. This guideline framework was based on very low-quality evidence. Methods: The discriminatory capacity of guideline-endorsed probability frameworks for PA subtyping were evaluated in this retrospective study of 319 PA patients, from two large tertiary centers in Bangkok, Thailand, who underwent subtyping assessments regardless of probability status. PA subtypes were determined by adrenal venous sampling (AVS) and/or post-adrenalectomy outcomes using PASO criteria. The main objectives were to evaluate the accuracy of predicting PA subtype using: 1) guideline-endorsed classification to high, intermediate, and low probabilities of lateralization; and 2) the seated saline suppression test (SST). Results: The majority of PA patients were characterized as having intermediate probability for lateralizing PA (75%); however, lateralizing PA was ultimately confirmed in 61-78% of all patients, regardless of guideline-based probability classification. The vast majority of SST results were positive using guideline-derived criteria, regardless of probability stratification or ultimate subtype: 89.3% of patients with lateralizing PA and 80.6% of those with bilateral PA had a positive SST. Among patients with intermediate probability of lateralizing PA, where guidelines specifically endorse the value of SST, the SST had a sensitivity of 89.4% and specificity of 22.0% for detecting lateralizing PA, with 78.0% false-positive and 10.6% false-negative rates. Consistently, post-SST aldosterone concentrations exhibited near-complete overlap between those with and without lateralizing PA. Conclusion: Guideline-endorsed probability frameworks, and the use of SST, lacked discriminatory capacity to predict PA subtype.

Introduction: Menstrual cycle phase has been proposed as a source of intra-individual variability in resting energy expenditure and the thermic effect of food in premenopausal females, yet studies examining the thermic effect of food across menstrual cycle phases report conflicting findings. Methods: This protocol describes a secondary analysis of prespecified outcomes from a non-randomized, two-period crossover trial primarily designed to assess postprandial plasma triglyceride concentrations across menstrual cycle phases (ClinicalTrials.gov: NCT07459465) in 12 premenopausal females aged 18-30 years, free of chronic disease and hormonal contraceptive use, recruited in Ottawa, Canada. Participants complete two experimental sessions: one in the early follicular phase and one in the mid-luteal phase, each involving consumption of a high-fat meal. Eleven secondary outcomes will be reported: fasting resting energy expenditure, thermic effect of food, respiratory exchange ratio, carbohydrate oxidation rate, lipid oxidation rate, desire to eat, hunger, fullness, prospective food consumption, serum beta-estradiol, and serum progesterone. Masked outcome analyses are performed using linear mixed-effects models. Results: Recruitment began on 26 March 2026; results will be reported in the Stage 2 manuscript. Discussion: Findings from this trial may help clarify whether menstrual cycle phase constitutes a meaningful source of intra-individual variability in energy metabolism, with implications for the design of metabolic research in premenopausal females.

We performed a new set of experiments to confirm findings reported in our previous publication regarding the role of Sulf-1 and Sulf-2 in regulating BMP-7 and FGF-2 signaling in human articular chondrocytes. Using primary chondrocytes from five independent human donors, we examined the effects of Sulf knockdown on Smad1/5 and Erk1/2 phosphorylation. Sulf-1 and Sulf-2 knockdown consistently reduced BMP-7-induced Smad1/5 phosphorylation and enhanced FGF-2-induced Erk1/2 phosphorylation. Although the magnitude of Erk1/2 activation was somewhat lower than originally reported, the direction and statistical significance of the effects were preserved. These results confirm the original conclusions and support the role of Sulfs as dual regulators of BMP-7 and FGF-2 signaling pathways in human chondrocytes.

Background Depression and anxiety are prevalent among cardiovascular disease (CVD) patients and significantly worsen clinical outcomes, increasing complications, recurrent events, and healthcare costs. Evidence shows that psychological stress, depression, and anxiety elevate CVD risk, while post-discharge nurse-led telephone follow-up has demonstrated benefits in patient support and symptom management. Little is known about its impact on mental health. Objective The aim of this study was to evaluate the effects of implementing the "nurse telephone follow-up" project on depression, anxiety and stress levels among cardiovascular patients. Methods An experimental study was conducted with 60 randomly selected patients from the Coronary Care Unit (CCU) department of a hospital in Iran, who were divided into two groups: an intervention group and a control group. The educational intervention was administered within two weeks after discharge. Data were collected via the Depression Anxiety Stress Scale (DASS-21). Descriptive analysis, Mann?Whitney and Wilcoxon tests, Generalized Estimating Equations (GEE) regression, and Spearmans correlation were used for data analysis. Results The mean age of the patients was 57.43 {+/-} 15.33 years. While no significant difference was found between the intervention and control groups in terms of depression, anxiety, or stress (p>0.05), the depression score decreased by 1.53 points, and the anxiety score decreased by 1.18 points after the intervention. Furthermore, an increase in patients ejection fraction (EF) score was associated with a 0.1 decrease in both depression and anxiety levels. No significant relationship was found between stress and any variables. Conclusions The results of this study suggest that psychological and therapeutic interventions may help reduce depression and anxiety in patients with cardiovascular diseases. However, this requires further detailed evaluation and additional studies. The potential link between improved cardiac function and reduced psychological symptoms could be effective in designing more comprehensive treatments for these patients.

Background: Obesity is a global health crisis, contributing to chronic diseases such as diabetes, cardiovascular disease, and metabolic syndrome. Traditional Chinese Medicine (TCM) has been used in East Asia to manage obesity, but evidence on its efficacy and safety remains limited. This systematic review and meta-analysis assess clinical evidence from randomized controlled trials (RCTs) on TCM for obesity treatment. Methods: We systematically searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to April 2026. Eligible RCTs compared TCM interventions with placebo or conventional treatments in obese patients. Two reviewers independently conducted screening, data extraction, and quality assessment. Meta-analysis was conducted using a random-effects model to calculate pooled weighted mean differences (WMD) and odds ratios (OR) for body weight, BMI, waist-to-hip ratio (WHR), lipid profiles, and adverse events. Results: A total of 33 randomized controlled trials (RCTs) involving 3,053 participants were included in the analysis. TCM significantly reduced body weight (WMD = -5.86 kg, 95% CI: -7.51 to -4.21), BMI (WMD = -2.82 kg/m{superscript 2}, 95% CI: -3.38 to -2.25), and WHR (WMD = -0.04, 95% CI: -0.06 to -0.02). Lipid profiles improved, with reductions in total cholesterol (WMD = -0.82 mmol/L), triglycerides (WMD = -0.65 mmol/L), LDL-C (WMD = -0.39 mmol/L), and increased HDL-C (WMD = 0.29 mmol/L) (all p < 0.001). Adverse events were infrequent, with no significant difference observed between TCM and control groups (OR = 0.51, 95% CI: 0.24 to 1.08). Funnel plots indicated no publication bias. Conclusion: TCM appears effective in reducing body weight and improving lipid profiles in obese patients, with a low incidence of adverse events. It may serve as a complementary treatment for obesity, though further high-quality RCTs are needed to confirm these findings and assess long-term outcomes.

Polyendocrine metabolic ovarian syndrome (PMOS), previously called polycystic ovary syndrome (PCOS) - the most common reproductive endocrinopathy in women of reproductive age, is frequently associated with chronic low-grade inflammation and immune dysregulation. Beyond hyperandrogenism and ovulatory dysfunction, women with PMOS exhibit reduced regulatory T cell (Treg) levels and impaired STAT5 phosphorylation. This study investigates the molecular basis of the defective STAT5 signalling in PMOS. No significant difference in plasma IL2 levels is observed in PMOS women versus normal subjects. Analysis of 102 PMOS patients and 102 controls reveals significantly decreased JAK2 expression alongside increased expression and activity of the phosphatases PTP1B (Protein Tyrosine Phosphatase 1B), TCPTP (T cell Protein Tyrosine Phosphatase), and DUSP4 (Dual Specificity Protein Phosphatase), in leukocytes of PMOS women. In isolated Tregs, only PTP1B and DUSP4 were significantly upregulated. DUSP4 expression positively correlates with serum testosterone and luteinizing hormone levels, linking hormonal imbalance with immune defects. Functional experiments show that silencing PTP1B and DUSP4 enhances IL2-induced Treg generation. Our collective findings identify phosphatase-mediated inhibition of STAT5 signalling as a key mechanism underlying Treg deficiency in PMOS and highlight PTP1B and DUSP4 as potential therapeutic targets to restore immune tolerance and improve reproductive outcomes.

BackgroundHypertension is a highly heritable cardiovascular disorder and a major determinant of cardiometabolic disease, including diabetes. However, the regulatory genes and tissue-specific mechanisms underlying blood pressure variations remain incompletely understood. MethodsLeveraging a well-characterized prospective population-based cohort comprised of 27,308 participants from the Singapore Chinese Health Study (SCHS), we evaluated genome-wide genetic associations for five blood pressure traits: hypertension status, systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP) and pulse pressure (PP). Additionally, we conducted a transcriptome-wide association study (TWAS), integrating gene expression data from 49 tissues, followed by colocalization and fine-mapping to prioritize regulatory genes. Association of identified variants with incident diabetes was additionally evaluated in the longitudinal data. ResultsWe validated 10 blood pressure loci (P between 1.64 x 10-20 - 4.10 x 10-8) and identified an East-Asian specific splice donor variant at the COL21A1 gene associated with PP (rs149344559, P = 6.78 x 10-10). Integrative analyses prioritized FGF5 in kidney cortex and ENPEP in pituitary tissue as candidate regulatory genes. The blood pressure-lowering allele at ENPEP (T allele, rs1879056) was associated with reduced risk of incident diabetes. Mediation analysis demonstrated that approximately 21% of the genetic association with diabetes was mediated through MAP (Pindirect-effect = 2 x 10-16). ConclusionThis study refines genetic predispositions for blood pressure among East-Asians. We further delineate tissue-specific regulatory pathways underlying blood pressure variations and identify ENPEP-mediated dysfunctions linking blood pressure genetics to diabetes risk, underscoring integrated disease mechanisms.

ObjectivesLow serum testosterone (T) in men with obesity suggesting T deficiency may be misinterpreted by confounding changes in serum SHBG, Ts circulating carrier protein. Measuring or calculating "free" testosterone (FT) concentrations to define a low T is problematic as cFT is not a valid analytical variable lacking certified standard, quality control or reference range. We developed a novel metric, Scaled Testosterone (ST), comparing standardized serum T (LCMS) and SHBG without invoking hypothetical serum T fractions. MethodsSerum T and SHBG in men (n=10,027) pooled from three population-based studies in Australia were expressed as standardized (Z) scores (ZT, ZSHBG) and their difference ST = ZT-ZSHBG. ST was evaluated in a clinical trial of 51 men with severe obesity undergoing 1 year of diet-induced weight loss. ResultsZT and ZSHBG displayed linear correlation (r=0.44, 10-11) with ST approximating zero (-0.33 {+/-}2.14 SD). In non-obese men with low serum T suggestive of organic hypogonadism displayed very low ST indicating ST can evaluate whether a low serum T is proportionate to a concomitant serum SHBG. In men with obesity, low pre-treatment serum T and SHBG both increased during diet-induced weight loss with no change in serum LH while ST which remained within standard limits at each time. ConclusionsThe low serum T in men with obesity may better be considered as the pseudo-hypogonadism of obesity comprising low serum T with proportionately low serum SHBG in the presence of normal serum LH {+/-} FSH serving as a tissue androgen sensor.