Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic insulin-secreting beta cells, resulting in hyperglycemia and a lifelong need for exogenous insulin therapy. Regulatory T cells (Tregs) are essential for maintaining immune tolerance and preventing autoimmune reactions. It has been shown that dysfunctional Tregs participate in the pathophysiology of T1D. Therapeutic approaches designed to enhance Treg stability, survival, and function have progressively emerged as a promising treatment strategy for T1D. This narrative review explores the potential of Treg cell-based therapy as a therapeutic tool to alter the natural history of T1D. It discusses different pharmacological strategies to enhance Treg stability and function, as well as the latest advances in Treg cell-based therapies, including adoptive Treg cell therapy and genetic engineering of Tregs. It also outlines current challenges and future research directions for integrating Treg cell-based therapy into clinical practice, aiming to provide a comprehensive overview of its potential benefits and limitations as an innovative therapeutic intervention for T1D.

The discovery of the one-carbon metabolism-homocysteine-metabolic dysfunction-associated steatotic liver disease (OCM-Hcy-MASLD) axis has renewed our understanding of MASLD-related primary liver cancer (PLC). Based on Suzuki et al.’s mathematical modeling findings of diminished cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) expression in MASLD, this commentary analyzes recent findings regarding sex-specific variations in this axis and their implications for surgical management. We highlight how the integration of OCM-Hcy pathway modulation with precise surgical interventions could enhance perioperative outcomes and long-term prognosis. The emerging evidence suggests that targeted metabolic interventions, particularly those accounting for sex differences, may complement traditional surgical approaches by addressing the systemic nature of MASLD-related PLC. This paradigm shift from purely surgical resection toward comprehensive metabolic regulation marks a significant advance in precision medicine for hepatobiliary surgery, potentially improving both perioperative safety and oncological outcomes.

Aim: To evaluate the prognostic performance of the preoperative neutrophil-to-lymphocyte ratio (NLR) for early complications following sleeve gastrectomy.

Methods: A retrospective cohort study was conducted by analyzing the institutional database of a bariatric clinic from 2017 to 2020. The neutrophil-to-lymphocyte ratio was determined from the preoperative blood count. The area under the curve (AUC) was calculated to determine the performance of the preoperative NLR for early postoperative complications following sleeve gastrectomy.

Results: Among the 387 patients who underwent sleeve gastrectomy, 45 experienced complications within the first 30 postoperative days (11.6%). The AUC for NLR as a predictor of overall early complications after sleeve gastrectomy was 0.42, and for severe complications, it was 0.39.

Conclusion: The preoperative NLR does not perform well as a prognostic indicator for early complications from sleeve gastrectomy.

Aim: Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a hypo-absorptive bariatric procedure with promising weight-loss and metabolic outcomes. The impact of obstructive sleep apnea (OSA), a common obesity-related comorbidity, on surgical outcomes following SADI-S remains underexplored. This study assesses 30-day postoperative outcomes in patients with OSA who underwent SADI-S, utilizing data from the MBSAQIP database (2020-2022).

Methods: Patients undergoing primary SADI-S between January 1, 2020, and December 31, 2022, were identified from the MBSAQIP database. Comparative analyses between patients with and without OSA were conducted using 19 preoperative variables and 17 postoperative outcomes. Continuous variables were analyzed with the Student’s t-test, and categorical variables using the chi-square test. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and multivariate logistic regression models identified independent predictors of OSA. Statistical significance was set at P < 0.05.

Results: A total of 1,301 patients were analyzed, with 596 (45.8%) having OSA. OSA patients were older (45.84 ± 10.14 years vs. 40.67 ± 10.55 years, P < 0.001), had higher body mass index (BMI) (50.57 ± 9.91 kg/m² vs. 49.05 ± 8.50 kg/m², P = 0.003), and more comorbidities such as diabetes, hypertension, and hyperlipidemia. OSA was associated with longer operative times (144.30 ± 58.92 min vs. 127.41 ± 54.59 min, P < 0.001) and increased blood transfusions (1.7% vs. 0.3%, P = 0.009), but no significant differences in mortality, pulmonary embolism, or readmission rates. Multivariate analysis identified male sex (OR: 3.306, P < 0.001), age (OR: 2.077, P < 0.001), and higher American Society of Anesthesiologists (ASA) classification (OR: 2.133, P < 0.001) as independent predictors of OSA.

Conclusion: Patients with OSA undergoing SADI-S experience longer operative times and an increased risk of blood transfusions, which is primarily an intraoperative or early postoperative event. However, OSA does not significantly impact key short-term postoperative outcomes, such as mortality, pulmonary embolism, or readmission rates. These findings support the safety and efficacy of SADI-S in OSA patients, emphasizing the need for careful intraoperative management while maintaining favorable postoperative outcomes.

Aim: While cardiometabolic disorders and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist, the genetic connections and causes are not clearly understood. This study aimed to explore their shared genetic architecture to elucidate the mechanisms driving their comorbidity.

Methods: Using summary statistics from genome-wide association studies (GWASs) on MASLD and 29 cardiometabolic traits (CMTs), we assessed their genetic correlation and causality, and identified shared genetic loci, genes, pathways, cell types, and tissues. Additionally, shared biological mechanisms were uncovered using single-cell RNA sequencing data.

Results: Significant genetic correlations were detected between MASLD and 17 CMTs, encompassing cardiometabolic diseases, glucose, lipids, adiposity, and inflammatory markers, after adjusting for multiple testing (p.adjust < 0.05). Cross-trait analysis yielded a total of 166 shared risk SNPs (including those located in or near TRIB1, LPL, PNPLA3, GCKR, and PPARG). Subsequent colocalization highlighted 73 genetic loci associated with both MASLD and CMTs, with rs429358 (APOE) consistently prioritized in HyPrColoc. Common genes were identified (such as NPC1, MST1R, TMBIM1, IRAK1BP1, L3MBTL3, RBM6, and RGS19), with significant enrichment in cholesterol metabolism, glucose metabolism, immune inflammation, and long-term depression. Shared tissue-specific heritability enrichment was identified in the liver, adipose, artery, adrenal gland, and brain tissue. Moreover, shared enrichment was observed in specific cell types (epicardial adipocytes, erythroid progenitor cells, hepatocytes, glial cells, macrophages, monocytes, and myeloid cells). The expressions of APOE and LPL, which showed colocalization between MASLD and CMTs, were significantly altered in the macrophages of patients with MASLD compared to those of controls. Causality and potential medications were also explored.

Conclusion: Multiple biological pathways contribute to the comorbidity between MASLD and cardiometabolic disorders, with lipid metabolism emerging as a critical factor. This study provides valuable insight into the possible mechanisms underlying their comorbidity and offers potential directions for future therapeutic innovations.

This review focuses on the evolution in the nomenclature of fatty liver disease in the pediatric population, from the initial definition non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD), and more recently to metabolic dysfunction-associated steatotic liver disease (MASLD). These changes in the nomenclature aim to more accurately reflect the relation between the disease and the underlying metabolic alterations, while also seeking to reduce the stigma associated with earlier definitions. Epidemiological data indicate an increase in the global burden of NAFLD in the pediatric population, with a prevalence of 5%-10%, more commonly affecting males. The condition is strongly associated with obesity, type 2 diabetes mellitus (T2DM), and genetic factors, including the PNPLA3 polymorphism. Prevalence rates are significantly higher in Latin America (24%-68%), which is linked to the growing epidemic of metabolic syndrome. In terms of pathophysiology, pediatric NAFLD differs from the adult form in the histological patterns and has a strong link to insulin resistance. Each definition of the disease has pros and cons. NAFLD is a simple definition but exclusionary, while MAFLD incorporates metabolic factors to better characterize the disease. The most recent term, MASLD, aims to reduce the stigma of this disease and emphasize the metabolic factor of this pathology. Various scientific societies consistently recommend lifestyle changes as the first-line treatment, although adherence to this intervention remains a challenge in the pediatric population. In addition, there is a strong consensus on the need for noninvasive tools and longitudinal studies to better understand this disease in children.

This review aims to identify and map the extent and nature of published research investigating multidisciplinary teamworking in surgical services and evaluate the relevance of the evidence base to bariatric surgery. A systematic search of CINAHL, Embase, and Scopus databases was conducted from inception to June 2022, focusing on observational studies that examined multidisciplinary teamworking in surgical services. Data were synthesized narratively. Of the 483 articles screened, eight studies met the inclusion criteria. Most studies focused on oncology teams (n = 4), were conducted in the context of multidisciplinary team (MDT) meetings (n = 4), and employed quantitative methodologies (n = 5). Sample sizes for qualitative studies ranged from 11 to 88 participants, while quantitative studies involved 47 to 1,636 participants; where patient cases were the unit of analysis instead, sample sizes ranged from 50 to 298 cases. The composition of professional groups varied across studies, though all included nurses. Despite the widespread recommendation and adoption of multidisciplinary teamworking in surgical care, only eight relevant studies were identified, and none addressed bariatric surgery specifically. These findings highlight a significant gap and underscore the need for further research on multidisciplinary teamworking in surgical services, particularly in the field of bariatric surgery.

Aim: Despite the well-documented pathogenic role of insulin resistance (IR) and hypertension in nephropathy progression, the prognostic value of the estimated glucose disposal rate (eGDR) for incident renal dysfunction remains unclear. This population-based longitudinal analysis specifically examined the eGDR-renal dysfunction relationship in middle-aged and elderly populations, with a particular focus on the potential mediating role of systolic blood pressure (SBP) based on a nationwide longitudinal study.

Methods: Utilizing data from 8,136 participants in the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015), we conducted multivariable-adjusted logistic regression analyses combined with a restricted cubic spline model to assess the association between eGDR and incident renal dysfunction. Mediation analysis was employed to assess the proportion of the association mediated by SBP in this relationship.

Results: Over a median follow-up period of 4 years, 2,223 participants developed renal dysfunction. Both eGDR and SBP were significantly and independently associated with incident renal dysfunction. The odds ratio (OR) for eGDR was 0.73 (95%CI: 0.58-0.92), while the OR for SBP was 1.20 (95%CI: 1.05-1.38). Restricted cubic spline analysis identified critical thresholds, with eGDR levels below 11.6 mg/kg/min and SBP levels above 125 mmHg being associated with a higher risk of renal dysfunction. Mediation analysis further demonstrated that SBP acted as a significant mediator in the relationship between eGDR and renal dysfunction, accounting for 42.6% of the total effect (95%CI: 19.9%-86.7%).

Conclusion: This prospective cohort study identifies eGDR as an independent predictor of renal dysfunction, with nearly half of its effect mediated by SBP. These findings highlight the potential benefit of integrated management strategies targeting both insulin sensitivity and blood pressure control to reduce the risk of renal dysfunction in aging populations.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with any one of five principal traits of the metabolic syndrome. MASLD is characterised by multimorbidity with liver-related and extrahepatic complications including cardiovascular and cardiac disease, chronic kidney disease and certain extrahepatic cancers. While increasing liver fibrosis severity is well-established as a major contributor to the hepatic complications of MASLD, emerging evidence demonstrates that the severity of associated metabolic dysfunction significantly influences adverse extrahepatic clinical outcomes and all-cause mortality. Changing models of care are needed for patients with MASLD, extending the focus beyond that of liver health and optimising the inherent (heterogeneous) cardiometabolic dysfunction. Such an approach requires multi-stakeholder and community-based engagement with improved identification and diagnosis, and better patient and healthcare provider education that also focuses on type 2 diabetes, hypertension, and obesity, to ameliorate the consequences of this highly prevalent global multisystem disease.

In the past 20 years, liver transplantation has become one of the few effective treatments for various end-stage liver diseases. With the development of surgical methods and equipment, ischemia/reperfusion injury (IRI) and rejection have become the main factors affecting prognosis. Due to the use of detection methods such as metabolomics, surprising findings revealed that some significant lipid metabolism disorders are associated with liver transplantation. Moreover, the fatty liver, as an important part of the marginal donor organ, is severely affected by imbalances derived from the preexisting lipid metabolism turbulence. In other words, the lipid metabolism remodeling present in conventional liver transplantation is more severe and intricate in nonalcoholic fatty liver. This paper aims to review the recent 20 years of research on lipid metabolism in liver transplantation, especially the different molecular targets and signaling pathways involved in IRI, acute rejection, and chronic rejection. Through a comprehensive review and analysis of the literature, we outline the research status and forward motion, which provides both a valuable reference substance for future research and a theoretical summary for the prevention and treatment of lipid metabolism disorders during liver transplantation.

Aim: Sterol regulatory element-binding proteins (SREBPs) are key transcription factors driving de novo lipid synthesis (DNL) and associated metabolic disorders. This study aims to investigate whether bilirubin, a potential SREBP inhibitor, alleviates lipid accumulation and insulin resistance by targeting the HSP90β/SREBP pathway.

Methods:In vitro, HL-7702 cells were treated with bilirubin to assess lipid-lowering effects and SREBP-related gene expression. In vivo, high-fat diet (HFD)-induced obese mice received bilirubin intervention for 6 weeks. Lipid profiles, insulin sensitivity, hepatic SREBP protein levels, and downstream gene expression were analyzed. Mechanistic studies focused on HSP90β activity modulation by bilirubin.

Results: Bilirubin significantly reduced lipid accumulation in HL-7702 cells and downregulated SREBPs and their target genes. In HFD-fed mice, bilirubin attenuated obesity, hepatic steatosis, and insulin resistance, accompanied by suppressed SREBP protein levels and expression of target genes. Mechanistically, bilirubin inhibited SREBP activation by targeting HSP90β.

Conclusion: Bilirubin ameliorates metabolic syndrome via the HSP90β/SREBP axis, providing a novel therapeutic strategy for lipid metabolism disorders and insulin resistance. These findings highlight bilirubin’s potential as a pharmacological agent against metabolic diseases.