Background:Obesity is strongly associated with metabolic dysfunction and steatotic liver disease (MASLD). Laparoscopic sleeve gastrectomy (LSG) effectively addresses severe obesity and its metabolic complications. Recent studies suggest that exosomes and their microRNA (miRNA) content mediate systemic metabolic improvements following bariatric surgery. Objective:This study aims to characterize plasma exosomal miRNAs before and after LSG, identify functional candidates linked to MASLD remission, and validate underlying mechanisms in vitro. Methods:Plasma exosomes from control subjects, as well as pre- and post-LSG patients, were isolated via ultracentrifugation, characterized, and subjected to high-throughput miRNA sequencing. Differential expression analysis, weighted gene co-expression network analysis, and random forest modeling were used to identify key miRNAs. Predicted targets, based on multi-database consensus, were integrated with paired liver transcriptomes from GEO (GSE106737, GSE83452). miRNA-target interactions were confirmed through dual-luciferase assays. In a free fatty acid-induced HepG2 MASLD model, miRNA mimics/inhibitors were employed to evaluate lipid accumulation (Oil Red O, intracellular triacylglycerol/total cholesterol) and target expression (qRT-PCR, Western blot). Results:LSG significantly altered circulating exosomal miRNA profiles. Six key miRNAs were identified, with miR-497-5p being the most prominent. Integrative analysis revealed GABARAPL1 as a direct target of miR-497-5p, and its upregulation in post-LSG liver tissues. Luciferase assays confirmed miR-497-5p binding to the GABARAPL1 3'UTR. In HepG2 cells, inhibition of miR-497-5p reduced lipid droplet formation and intracellular triacylglycerol/total cholesterol levels, while overexpression exacerbated steatosis. Inhibition also led to increased GABARAPL1 mRNA and protein levels. Conclusion:LSG induces significant remodeling of the circulating exosomal miRNA profile. Specifically, the downregulation of exosomal miR-497-5p post-LSG appears to alleviate hepatic lipid accumulation by derepressing its target, GABARAPL1, a key regulator of lipophagy. miR-497-5p is thus a potential biomarker and therapeutic target.

Obesity and related metabolic diseases are major global health challenges. Metabolic and bariatric surgery (MBS) is an effective treatment. Yet exploring its molecular mechanisms remains limite due to the challenge of obtaining postoperative tissue samples. While rat models are more convenient in size and operation, mouse models offer unique advantages such as lower breeding costs and easier genetic modification. However, research on mouse MBS models is still limited because of their small size and surgical complexity, highlighting the need for optimized techniques to advance the field. This study aims to establish a high-fat diet-induced (HFD) obesity combined with metabolic dysfunction-associated steatotic liver disease (MASLD) mouse model, and to evaluate the MBS models assisted by microsurgery, so as to provide a reliable tool for mechanism research. Male SPF C57BL/6J mice were randomly assigned to the normal diet (ND) group and the HFD group. The mouse in the HFD group were induced to develop obesity with MASLD through a high-fat diet for 16 weeks. The HFD group was further divided into sham operation group (Sham), sleeve gastrectomy (SG) group, and modified Roux-en-Y gastric bypass (RYGB) group (n = 6). Metabolic efficacy was evaluated by weight, metabolic parameters, and pathological staining analysis at the 4th week post-surgery. Compared with the ND group, the weight of the HFD group increased by 38.25

BACKGROUND:The triglyceride-glucose index (TyG) has shown comprehensive value in relation to numerous obesity-associated comorbidities, especially cardiovascular diseases. Although their incidence risk and severity are lowered following sleeve gastrectomy (SG), the extent of relief varies. OBJECTIVES:To analyze potential influencing factors of decrease in the TyG index (△TyG) following SG, and establish a predictive model using preoperative data. SETTING:University hospital, China. METHODS:Preoperative and 1-year postoperative data of patients with obesity who underwent SG were collected. After being randomly divided at a proportion of 70%, the patients in the modeling group were further divided into group A (decreased poorly) and group B (decreased satisfactorily) based on the degree of △TyG. After screening the variables with significant differences between the groups, we conducted logistic regression analysis to identify the influencing factors related to △TyG and those with a predictive value. Subsequently, a nomogram was established. Internal, external validations and decision curve analysis (DCA) were performed. Clinical impact curve (CIC) was drawn. RESULTS:The study included 744 patients. Four independent predictors, namely waist-hip ratio (WHR), high-density lipoprotein cholesterol (HDL-c), uric acid (UA), and TyG index were identified. The joint predictor formed by combining these four factors had an area under the curve of .838 (.803-.868) and a significantly better predictive value. The predictive accuracy and clinical net benefit of the nomogram established utilizing the joint predictor were verified. CONCLUSIONS:SG can lead to significant △TyG, with preoperative WHR, HDL-c, UA, and TyG index being independent predictors. The joint predictor can effectively predict the magnitude of the decrease.

BACKGROUND:Colorectal cancer (CRC) is one of the malignancies with high morbidity and mortality rates worldwide, and its disease burden continues to increase with population aging and changes in lifestyle and dietary habits. Based on the Global Burden of Disease database (GBD), this study analyzed trends in global CRC incidence, deaths, and disability-adjusted life years (DALYs) from 1990 to 2021, and explored health inequalities across countries and regions. METHODS:This study used data from the GBD Database 2021 to quantify the contribution of population aging, population growth, and epidemiological changes to the burden of CRC. Health inequalities were assessed on a global scale through the Slope index (SII) and concentration index (CI), and the potential room for improvement in the control of DALYs burden in CRC was assessed by countries using frontier analysis. The future disease burden of CRC was predicted based on a Bayesian Age-Period-cohort model (BAPC). RESULTS:Worldwide, the incidence, death and DALYs burden of CRC increased significantly, mainly driven by population aging and population growth. Areas with high socio-demographic index (SDI) have significantly reduced the burden of disease through epidemiological changes, while the burden remains higher in areas with low SDI. Health inequalities have improved, but areas with low SDI still face a higher burden of disease. Frontier analysis shows that there is still much room for improvement in CRC prevention and control in countries with high SDI. Projections show that despite the decline in CRC deaths, the number of cases of CRC is expected to continue to increase due to the impact of population aging and population growth. CONCLUSIONS:Population aging and growth drive the global CRC burden increase. Low - SDI regions' epidemiological changes have limited impact. Future policies should focus on low - SDI areas' early prevention and screening and optimize resource allocation.

Introduction: As the most common postoperative complication, intestinal adhesions can cause intestinal obstruction, female infertility, and even endanger life. The currently developed materials for preventing intestinal adhesions mainly focus on physical barriers and reducing inflammatory reactions, while neglecting the importance of effectively promoting rapid repair of the peritoneum. We previously found that platelet-rich fibrin (PRF) can prevent postoperative intestinal adhesions. The proliferation of mesothelial cells may play a significant role in reducing intestinal adhesions, but the mechanism remains unclear. A study found a positive correlation between calretinin (CR) and mesothelial cell proliferation. Does CR play an important role in PRF promoting mesothelial cell proliferation? This study aims to further explore the mechanism of PRF in preventing intestinal adhesions. Methods: Primary mouse peritoneal mesothelial cells and mouse peritoneal fibroblasts were used in this study. The effects of PRF on the proliferation and attachment of mesothelial cells and fibroblasts were observed and compared using the CCK-8 assay, Edu assay, and laser scanning confocal microscope. The effects of PRF on the migration of mesothelial cells were examined using scratch and transwell migration assays. The effects of PRF on the mesothelial-mesenchymal transition (MMT) of mesothelial cells were examined using western blot. The expression level of CR in mesothelial cells was detected through immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot. Results: PRF promotes mesothelial cell proliferation from 1st day and significantly promotes fibroblast proliferation from 7th day. Meanwhile, PRF tends to promote the proliferation and attachment of mesothelial cells rather than fibroblasts. However, PRF had a limited regulatory effect on the MMT of mesothelial cells. In addition, PRF can promote mesothelial cell migration and upregulate the expression level of CR. Conclusion: PRF promotes mesothelial cell proliferation and migration, as well as peritoneal repair, by up-regulating CR in the early stages of peritoneal injury to prevent postoperative intestinal adhesion. Its mechanism is obviously different from that of traditional anti-adhesion materials, which will provide new strategies for the prevention of intestinal adhesions.

Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern due to its increasing prevalence and potential to cause serious liver complications. NAFLD is rising among people aged 15 to 49 years, a critical age group for workforce and reproduction, yet its burden and trends in this population remain insufficiently studied. This study aimed to evaluate the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with NAFLD in this age group across 204 countries and territories from 1990 to 2021, using data from the global burden of disease (GBD) 2021 database. Trends in disease burden were assessed using average annual percentage change (AAPC), with stratified analyses by sex, age, and socio-demographic index (SDI). Bayesian age-period-cohort (BAPC) models were employed to project future trends and quantify the contributions of major risk factors. By 2021, the global incidence, prevalence, mortality, and DALY rates of NAFLD in people aged 15 to 49 years were 909.48 per 100,000 persons (95% UI: 647.19-1216.77), 16,580.43 per 100,000 persons (95% UI: 12,851.14-20,866.60), 0.45 per 100,000 persons (95% UI: 0.27-0.72), and 22.77 per 100,000 person-years (95% UI: 13.74-35.81), respectively. Between 1990 and 2021, both incidence and prevalence increased, whereas mortality and DALYs remained relatively stable. NAFLD burden declined as SDI increased, peaking at an SDI of approximately 0.6 before gradually decreasing. Males consistently exhibited higher burden than females. The leading contributors to age-standardized mortality were tobacco use and elevated fasting glucose, with the impact of metabolic risk factors rising over time. Burden increased with age, with incidence peaking at age 22.5 and subsequently declining. By 2050, the number of new NAFLD cases among people aged 15 to 49 years is projected to reach 48.29 million globally, with the number of deaths expected to rise to 23,396.5. The substantial increase in NAFLD burden over the past 3 decades highlights the urgent need for early screening and diagnosis. These findings may inform future public health planning aimed at reducing the disease burden among people aged 15 to 49 years.

Obesity is a chronic low-grade inflammatory condition. Laparoscopic sleeve gastrectomy (LSG) is a widely recognized intervention for weight management; however, the percentage of total weight loss (

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis and limited response to gemcitabine-based chemotherapy. Chemoresistance in PDAC arises from both cancer-intrinsic mechanisms and extrinsic factors like stromal fibrosis. This study investigates the role of mesothelin (MSLN) and the YAP1 inhibitor TED-347 in modulating gemcitabine resistance. Elevated MSLN expression in PDAC correlates with advanced disease stages and poor prognosis. Mechanistically, MSLN promotes gemcitabine resistance by counteracting drug-induced apoptosis and upregulating ABCC1, a key drug efflux transporter. YAP1 transcriptionally activates MSLN by binding to its promoter, independent of the Canscript sequence. The YAP1 inhibitor TED-347 disrupts this interaction, reducing MSLN expression and suppressing PDAC cell migration, invasion, and epithelial-mesenchymal transition (EMT). In a mouse model, TED-347 combined with gemcitabine enhanced antitumor efficacy, reduced fibrosis, and increased gemcitabine sensitivity. Notably, TED-347 alleviated stromal fibrosis by inhibiting pancreatic stellate cell (PSC) activation, addressing a critical barrier to drug delivery. While gemcitabine itself induces fibrosis, TED-347 mitigates this effect, offering a dual therapeutic strategy. These findings highlight the YAP1-MSLN axis as a key driver of chemoresistance and fibrosis in PDAC, with TED-347 demonstrating potential to improve clinical outcomes by targeting both malignant and stromal components. This study provides a translational research framework for combining YAP1 inhibitors with chemotherapy to overcome resistance in PDAC.

Background: The global prevalence of non-alcoholic fatty liver disease (NAFLD) is approximately 30%, and the condition can progress to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Metabolic and bariatric surgery (MBS) has been shown to be effective in treating obesity and related disorders, including NAFLD. Objective: In this study, comprehensive machine learning was used to identify biomarkers for precise treatment of NAFLD from the perspective of MBS. Methods: Differential expression and univariate logistic regression analyses were performed on lipid metabolism-related genes in a training dataset (GSE83452) and two validation datasets (GSE106737 and GSE48452) to identify consensus-predicted genes (CPGs). Subsequently, 13 machine learning algorithms were integrated into 99 combinations; among which the optimal combination was selected based on the total score of the area under the curve, accuracy, F-score, and recall in the two validation datasets. Hub genes were selected based on their importance ranking in the algorithms and the frequency of their occurrence. Finally, a mouse model of MBS was established, and the mRNA expression of the hub genes was validated via quantitative PCR. Results: A total of 12 CPGs were identified after intersecting the results of differential expression and logistic regression analyses on a Venn diagram. Four machine learning algorithms with the highest total scores were identified as optimal models. Additionally, PPARA, PLIN2, MED13, INSIG1, CPT1A, and ALOX5AP were identified as hub genes. The mRNA expression patterns of these genes in mice subjected to MBS were consistent with those observed in the three datasets. Conclusion: Altogether, the six hub genes identified in this study are important for the treatment of NAFLD via MBS and hold substantial promise in guiding personalized treatment of NAFLD in clinical settings.

Excessive visceral adipose tissue (VAT) accumulation is strongly associated with numerous metabolic disorders. Laparoscopic sleeve gastrectomy (LSG) reduces VAT, leading to improved metabolic conditions. However, considerable individual variability results in suboptimal metabolic improvements in certain patients post-LSG. Currently, no predictive model for postoperative VAT content exists, and reliance on macroscopic anthropometric or basic metabolic parameters alone fails to accurately predict postoperative metabolic outcomes. This study aims to evaluate the long-term effects of LSG on VAT reduction, identify factors influencing VAT loss, and develop a clinically applicable risk assessment model. This study included 177 patients, randomly divided into a modeling group (132 patients) and a validation group (45 patients). Demographic, metabolic, and imaging data were collected, and patients were categorized based on the median ΔVAT change at 12 months post-LSG. Independent predictors were identified via univariate and multivariate logistic regression, and a nomogram model was developed, followed by external validation. In the modeling group, significant differences in gender, waist-to-hip ratio (WHR), VAT, high-density lipoprotein cholesterol (HDL-c), and hypertension were observed between the high-change and low-change groups. Multivariate logistic regression identified preoperative VAT and HDL-c as independent predictors of weight loss outcomes. The nomogram model demonstrated excellent discriminatory power, with an AUC of 0.7 in the training set and 0.88 in the validation group. The calibration curve confirmed high predictive accuracy, and decision curve analysis (DCA) and clinical impact curve (CIC) analyses underscored the model’s strong clinical applicability. The combination of preoperative HDL-c and VAT serves as an effective predictor of VAT reduction post-LSG, offering a theoretical basis for improving preoperative assessment and facilitating personalized patient management.

Objective:Quantify global high body mass index (BMI)-linked colorectal cancer death and disability-adjusted life years (DALYs) (1990-2021) using the Global Burden of Disease (GBD) 2021 data, assessing spatiotemporal trends to inform prevention strategies. Methods:Geographic analysis, age-sex stratification, and sociodemographic index (SDI) quintiles evaluated disease distribution. Calculated estimated annual percentage change (EAPC) for trends. Demographic decomposition models quantified the contributions of population aging, epidemiological changes, and growth. Assessed health inequality via the slope inequality index (SII) and concentration index and prevention efficiency with SDI-age-standardized DALYs rate frontier. Results:Globally from 1990 to 2021, deaths from high BMI-associated colorectal cancer rose from 41,536 to 99,268, with the age-standardized death rate increasing from 1.14 to 1.17. The age-standardized death rate significantly increased in low- and middle-SDI regions while declining in high SDI regions. Disease burden growth was prominent in East and Southeast Asia. Death rates and rates of DALYs were higher in men than in women, and the burden was highest in people aged 60 years or older. Population growth was the primary driver of the increased burden (contributing >60 % to deaths and DALYs), followed by population aging. While health inequality (as measured by the SII) slightly decreased from 42.12 to 39.76, significant socio-demographic disparities persisted. Conclusion:High BMI-associated colorectal cancer burden escalates in low-middle SDI regions and elderly males. Targeted prevention and healthcare efficiency in low SDI areas are critical.

To the Editor: Obesity and type 2 diabetes (T2D) present significant health issues in China. Despite generally having lower body mass index (BMI) thresholds than Western populations, Chinese individuals often experience higher rates of central obesity, leading to increased metabolic risks even at lower BMI levels. The prevalence of T2D among adults in China is estimated to be 11.2%. Traditional treatments, including lifestyle interventions and medications, often fail to achieve sustained weight loss and effective glycemic control in the long term in patients with obesity and T2D. This prospective multicenter observational study aimed to evaluate the 2-year and 5-year treatment effects of laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on T2D patients in China (Clinical Trials identifier: NCT02217943). All subjects from six high-volume tertiary hospitals were recruited between August 2014 and January 2016 [Supplementary Table 1, https://links.lww.com/CM9/C282]. The study protocol was reviewed and approved by the Independent Ethics Committee or the Institutional Review Committee at each center (Ethical approval number of the leading research institution is 2014-32 [Supplementary Material 1, https://links.lww.com/CM9/C282]), and all subjects provided written informed consent before enrollment. Participants were between 20 years old and 60 years old, with a BMI ranging from 28 kg/m2 to 50 kg/m2 and a diagnosis of T2D for at least six months. Subjects were required to have a C-peptide level greater than 1 ng/mL. Exclusions also applied to individuals with certain medical conditions [Supplementary Material 2, https://links.lww.com/CM9/C282]. At baseline, comprehensive data on demographics, medical history, physical exams, and various laboratory tests were collected. Participants underwent either RYGB or SG. The choice of procedure was determined by the attending surgeons. Outpatient follow-up visits were scheduled at 1-month, 3-, 6-, 12-, 24-, 36-, 48-, and 60-months post-surgery and focused on evaluating subjects' glycemic control, weight loss, and other health metrics. Safety was documented through investigator-observed and subject-reported adverse events (AEs). The outcome of T2D status, defined by the American Society for Metabolic and Bariatric Surgery (ASMBS), was evaluated at 2 years and 5 years. T2D status was classified as complete remission, partial remission, improvement, no change, or recurrence using a composite metric of glycemic control combining HbA1c and FPG (see definition in Supplementary Material 3, https://links.lww.com/CM9/C282). The percentage of subjects achieving HbA1c <7.0% regardless of medication usage, changes in body weight, BMI, blood pressure, lipid profile, and liver enzymes were also evaluated. Predefined procedure-related complications were recorded (see definition in Supplementary Material 4, https://links.lww.com/CM9/C282). The full analysis set was used as the primary analysis set and safety set. The number and percentage of subjects achieving each of the five components of the composite measure of glycemic control were summarized, and 95% confidence intervals (CIs) were provided using the Clopper–Pearson method. The change from baseline for HbA1c and cardiometabolic markers were summarized at each postoperative measurement time point, and 95% CIs were provided using the t distribution. No adjustments for covariates were performed for outcome analysis. All analyses were performed using SAS 9.4 (SAS Institute Inc. Cary, NC, USA). A two-sided P <0.05 was considered statistically significant. A total of 101 subjects were enrolled (76 in RYGB and 25 in SG). The mean age was 37.1 ± 9.7 years and 52.5% were women. The mean baseline BMI was 35.1 ± 5.2 kg/m2 and the mean baseline HbA1c was 8.1 ± 1.7%. Baseline clinical characteristics are summarized in Supplementary Table 2, https://links.lww.com/CM9/C282. No subject switched to open surgery. A total of 79 subjects (78.2%, 79/101; 62 RYGB, 17 SG) completed the 2-year follow-up, while 63 subjects (62.4%; 63/101; 51 RYGB, 12 SG) completed the 5-year follow-up. The T2D status of these subjects are presented in Figure 1A. Bivariate analyses comparing subjects with and without complete or partial remission showed that subjects without complete or partial remission had higher mean (Standard Deviation, SD) FPG at baseline mean (Standard Deviation, SD) (9.8 [3.6] mmol/L vs. 8.3 [2.4] mmol/L; P = 0.0432) and a longer duration of T2D (5.0 [2.8] years vs. 3.1 [2.4] years; P <0.05).Figure 1: Five-year outcomes of glycemic control and weight loss after metabolic surgery (RYGB, SG) in Chinese obese population with T2D. (A) The percentage of subjects achieving each of the five components of the composite measure of glycemic control (definition in Supplementary Material 2,https://links.lww.com/CM9/C282) was summarized for each treatment group (RYGB, SG, Total) at two and five years after bariatric/metabolic surgery. (B) Mean BMI and TWL% in the RYGB and SG groups over a 60-months period compared with baseline metric. BMI: Body mass index; RYGB: Roux-en-Y gastric bypass; SG: Sleeve gastrectomy; TWL: Total weight loss; T2D: Type 2 diabetes. (Note: Denominator and percentages are based on subjects with non-missing data)HbA1c decreased rapidly within the first three months after surgery. The percentages of subjects with HbA1c <7.0% regardless of medication status were 93.3% (91.5% for RYGB and 93.8% for SG) at 2 years and 78.3% (78.0% for RYGB and 80.0% for SG) at 5 years [Supplementary Figure 1, https://links.lww.com/CM9/C282]. Improvement in glycemic control was paralleled by an improvement in homeostasis model assessment of insulin resistance (HOMA-IR) [Supplementary Table 2, https://links.lww.com/CM9/C282]. The percentage of subjects receiving oral anti-hyperglycemic medication and/or insulin decreased rapidly after bariatric/metabolic surgery, although there was a slight rebound in medication use over time [Supplementary Figure 2, https://links.lww.com/CM9/C282]. Significant reductions occurred in body weight and mean BMI at 2 years (total weight loss [TWL%] −22.8%, −22.6% for RYGB and −23.5% for SG; BMI −7.9 ± 3.6, −7.9 ± 3.8 kg/m2 for RYGB and −8.1 ± 2.3 kg/m2 for SG; all P <0.001) and at 5 years (TWL% −20.8%, −20.6% for RYGB and −21.8% for SG; BMI −7.2 ± 2.9, −7.1 ± 3.1 kg/m2 for RYGB and −7.7 ± 2.1 kg/m2 for SG; all P <0.001) [Figure 1B]. Hypertension, dyslipidemia, and elevated ALT, AST, and GGT levels improved from baseline to 5 years in both RYGB and SG, consistent with previous studies.[1] Common AEs included deficiencies in iron (49.5%, 50/101), vitamin D (34.7%, 35/101), and vitamin B12 (32.7%, 33/101), along with incision site pain (26.7%, 27/101), anemia (25.7%, 26/101), abdominal pain (17.8%, 18/101), and vomiting (13.9%, 14/101) [Supplementary Table 3, https://links.lww.com/CM9/C282]. Procedure-related AEs and serious adverse events (SAEs) classified according to the Clavien-Dindo (CD) classification of surgical complications are summarized in Supplementary Table 4, https://links.lww.com/CM9/C282. Most AEs were classified as Grade I (overall 77%, 341/443; RYGB 76.3%, 277/363; and SG 80%, 64/80) or II (overall 21.4%, 95/443; RYGB 21.8%, 79/363; and SG 20%, 16/80) according to the Clavien–Dindo classification of surgical complications. SAEs were reported in 10.5% (8/76) of the RYGB group over five years (four gastrointestinal disorders, two anemia, and two metabolism and nutrition disorders), but in none of the SG group [Supplementary Table 4, https://links.lww.com/CM9/C282]. This study demonstrates that both RYGB and SG have substantial long-term benefits for glycemic control and weight loss in Chinese subjects with T2D. Two previous 5-year studies[2,3] evaluating metabolic surgery for T2D subjects in China showed slightly higher complete remission rates of T2DM compared with our study, possibly due to the absence of rigorous FPG criteria. A meta-analysis[1] of RCTs involving 381 Caucasians with T2D who underwent metabolic surgery showed a 27.5% remission rate at 5 years. The inclusion of adjustable gastric banding (AGB) data may be related to the poorer long-term efficacy. Another meta-analysis[4] with 240 non-severely obese subjects (60% Chinese) showed similar T2D remission rates for RYGB and SG (54.0% and 56.7%, respectively), comparable to our findings. Moriconi et al[5] reported that short T2DM duration and good glycemic control before surgery were the best predictors for 10-year remission in Caucasians, consistent with our findings. This study had some limitations. It was a prospective observational study rather than a randomized controlled study. The choice of surgical procedure was not randomized, which prevents direct comparison between RYGB and SG. Additionally, the dropout rate was relatively high (21.8% at 2 years and 37.6% at 5 years), partly due to data collection challenges during the Coronavirus disease (COVID-19) pandemic. These factors could introduce biases and affect the generalizability of the results. The mean duration of diabetes was greater for the cohort that completed the 5-year visit. Mean age, BMI, body weight, waist circumference, systolic blood pressure (SBP), and the proportion of male subjects were somewhat greater for the cohort that did not complete the 5-year visit. In conclusion, this is a prospective, multicenter, 5-year study of metabolic surgery in subjects with T2DM in China. The results of this study provide evidence that metabolic surgery, including RYGB and SG, offers significant long-term benefits for glycemic control and weight loss in Chinese subjects with T2D. These procedures can lead to partial or complete remission of T2D, improving overall metabolic health. Conflicts of interest The authors thank Olivia Mathis of Ethicon, Inc. for editorial assistance. Financial support for this study was provided by Ethicon Endo-Surgery, Inc.

AIMS:Pancreatic ductal adenocarcinoma (PDAC) develops therapy resistance primarily through its fibrotic stroma generated by activated pancreatic stellate cells (PSCs). While the lipid droplet protein perilipin 5 (PLIN5) may be associated with PSC quiescence, its precise role in PDAC pathogenesis remains unclear. This study aims to investigate PLIN5 role in regulating PSC function and tumor progression. METHODS:PLIN5 expression was analyzed in human PDAC tissue using immunohistochemistry and immunofluorescence. Primary and immortalized PSCs were used, and PLIN5 overexpression PSCs were created using lentiviral transfection. Subcutaneous and orthotopic pancreatic cancer models in nude mice were developed by using these PSCs and pancreatic cancer cells. Cytological assays, PCR, Western blotting and histological and immunofluorescence analysis, were performed to investigate PLIN5 expression in PSCs and its effects on PSC activation, fibrosis, and cancer progression. KEY FINDINGS:PLIN5 expression was markedly reduced in human PDAC tissues compared to normal adjacent pancreas and was specifically co-localized with α-SMA-positive stromal PSCs. PLIN5 expression is high in quiescent PSCs but is rapidly lost upon activation. PLIN5 inhibited PSC proliferation and migration, reduced extracellular matrix protein secretion, and restored lipid droplets formation. In vitro, PLIN5 overexpression PSCs significantly constrained the growth and invasive capacity of pancreatic cancer cells, while in vivo, they markedly reduced tumor growth and fibrosis, and prevented splenic metastasis. SIGNIFICANCE:These findings suggest that PLIN5 is a core regulatory protein that inhibits the activation of PSCs and alleviates pancreatic fibrosis, as well as a key protein in hindering pancreatic cancer progression.

Background: Tandem mass tag (TMT) labeling technology in labeled quantitative proteomics has been widely used in studying differentially expressed proteins (DEPs).Objectives: The purpose of the research was to explore DEPs closely associated with optimal initial clinical response.Methods: Optimal initial clinical response was defined as a percentage of excess weight loss (%EWL) >= 50%. Using TMT technology and bioinformatics, we screened DEPs to identify those associated with weight-loss outcomes 1 year after surgery. Key DEPs were validated using western blotting and immunohistochemistry in tissue samples from patients with optimal and suboptimal clinical responses.Results: We enrolled 26 patients, including 13 with optimal initial clinical response and 13 with suboptimal initial clinical response. Of the 267 DEPs screened, only heat shock protein beta 2 (HSP beta 2) best evaluated the weight loss, with an optimal cutoff of 0.8206 (area under the curve, 1.000; 95% confidence interval: 0.868-1.000; sensitivity, 100.00%; specificity, 100.00%). In an external validation cohort, the HSP beta 2 expression was significantly lower in the optimal initial clinical response group than in the suboptimal initial clinical response group.Conclusions: HSP beta 2 is closely associated with the weight-loss outcome of laparoscopic sleeve gastrectomy.

Background:A significant proportion of patients with obesity have comorbid hyperuricemia (HUA). However, the curative effect of sleeve gastrectomy (SG) on HUA remains debated. Objective:To clarify the remission effect of SG on HUA, analyze potential influencing factors, and establish a predictive model using preoperative data. Methods:Pre- and post-operative data from 130 patients with obesity and HUA who underwent SG in our hospital were collected and evaluated for the therapeutic effect on HUA. Binary logistic regression analysis was employed to screen the influencing factors and the ones with predictive value. Predictive model was constructed, then evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) and internal and external validations. Complete remission of HUA was defined as a follow-up SUA level that no longer met the reference value for diagnosing HUA, i.e., an SUA concentration of <428 μmol/L (in males) or <357 μmol/L (in females), according to the reference value in our hospital's laboratory. Results:The mean follow-up duration is 20.4 months. After ≥ one year post SG, the complete remission rate of HUA was 58%. Preoperative hip circumference (HC) and preoperative serum uric acid (SUA) level were found to be predictive variables, the AUC values of which, along with their combination in predicting this outcome, were 0.696, 0.731, 0.738, respectively, p >0.05. The joint predictive model was found to have a sensitivity and specificity of 0.776 and 0.738, respectively, and its reliability was confirmed by internal and external validations. Conclusion:Some patients can achieve HUA complete remission following SG after 1 year. Preoperative SUA concentration and HC can be utilized to predict this outcome in Chinese patients with obesity. The joint predictive model offers potentially better clinical value.

BACKGROUND:Distinguishing bariatric surgical effects on reversing nonalcoholic fatty liver disease (NAFLD) remain unclear. To assess discrepancies in histological response and changes in magnetic resonance imaging-proton density fat fraction (MRI-PDFF) after bariatric surgery. METHODS:This prospective multicenter cohort included 138 NAFLD patients who underwent bariatric surgery and were followed up for 1 year. We obtained paired liver biopsy samples (n = 40), paired proteomic data (n = 23), and sequential MRI-PDFF at 3-, 6-, and 12-month (n = 80, 65, 52, respectively) follow-ups. RESULTS:At 1 year, a ≥2-point improvement in NAFLD activity score (NAS) was observed in 80.0% of patients; nonalcoholic steatohepatitis (NASH) improved without fibrosis worsening in 42.1%; fibrosis improved without NASH worsening in 78.8% (95% confidence interval [CI]: 66.0-91.2, 26.8-58.2, and 63.0-91.3) (all P <0.001). MRI-PDFF discriminated the presence and grading of hepatic steatosis (area under the curve [AUC], 0.94 and 0.95, respectively), indicating liver fat remission (<3.3% or 5.0% at 1 year) in 72.2% or 90.4% of patients (95% CI: 58.4%-83.5% or 78.9%-95.5%; all P <0.001). A ≥78.8% relative decline in MRI-PDFF within 1 year differentiated NAS improvement from non-NAS improvement (AUC, 0.912; 95% CI: 0.79-1.00). Compared to non-NASH remission, NASH remission was associated with significant pre- or postoperative regulation of protein expression levels. CONCLUSIONS:These findings can help evaluate the expected histological response, and aid in understanding the proteomic features resulting from the beneficial surgical effects on NAFLD and its advanced stages in patients with obesity.

Background:Laparoscopic sleeve gastrectomy (LSG) is associated with sustained and substantial weight loss. However, suboptimal results are observed in certain patients. Objective:Drawing from body composition data at our center, clinically accessible predictive factors for weight loss outcomes were identified, leading to the development and validation of a preoperative predictive model for weight loss following LSG. Methods and Materials:A retrospective analysis was conducted on the general clinical baseline and body composition data of obese patients (body mass index [BMI] ≥ 32.5 kg/m2) who underwent LSG between December 2016 and December 2022. Independent predictors for weight loss outcomes were selected through univariate logistic regression, random forest analysis, and multivariate logistic regression. Subsequently, a nomogram was developed to predict weight loss outcomes and was evaluated for discrimination, accuracy, and clinical utility, with validation performed in a separate cohort. Results:A total of 473 patients with mean BMI were included. The preoperative resting energy expenditure to body weight ratio (REE/BW), fat-free mass index (FFMI), and waist circumference (WC) emerged as independent predictive factors for weight loss outcomes at one year post-LSG. These body composition parameters were incorporated into the construction of an Inbody predictive nomogram, which yielded area under the curve (AUC) values of 0.868 (95% CI: 0.826-0.902) for the modeling cohort and 0.829 (95% CI: 0.756-0.887) for the validation cohort. Calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC) from both groups demonstrated the model's robust discrimination, accuracy, and clinical utility. Conclusion:In obese Chinese patients with a BMI ≥ 32.5 kg/m2, the Inbody-based nomogram integrating REE/BW, FFMI, and WC offers an effective preoperative tool for predicting weight loss outcomes one year after LSG, facilitating surgical planning and postoperative management.

Purpose:Obesity and related complications are managed by One Anastomosis Gastric Bypass (OAGB) and Single Anastomosis Duodeno-Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG), both of which are adapted from traditional gastric bypass procedures. However, there are no current comparative studies on the safety and efficacy of these two surgical procedures. Patients and Methods:Preoperative baseline data of patients who had undergone OAGB and SADJB-SG surgeries from June 2019 to June 2021 were retrospectively analyzed at our bariatric facility. Postoperative data, including weight changes, improvement in type 2 diabetes (T2DM), and complication rates were collected over 2 years. This was followed by a comprehensive evaluation of the safety and efficacy of the two surgical procedures. Results:A total of 63 patients completed the follow-up in this study. At the 24-month follow-up, excess weight loss percentage (EWL%) for the OAGB and SADJB-SG was 73.970±5.005 and 75.652±7.953, respectively (P-value = 0.310); total weight loss percentage (TWL%) was 24.006±8.231 and 23.171±6.600, respectively (P-value = 0.665). The diabetes remission rates for the two groups were 71.429% and 69.048%, respectively (P-value = 0.846). The cost for OAGB was 55088.208±1508.220 yuan, which was significantly lower than the 57538.195±1374.994 yuan for SADJB-SG (P-value< 0.001). Conclusion:The two surgical procedures are reliable in terms of safety and efficacy, and each has distinct advantages. While OAGB has reduced operational expenses, SADJB-SG offers a broader range of applicability.