Roux-en-Y gastric bypass (RYGB) is a highly effective therapy for obesity and type 2 diabetes mellitus (T2DM), but its underlying mechanisms, particularly regarding adipose tissue remodeling, remain incompletely understood. This study investigated the hypothesis that RYGB induces a phenotypic shift in white adipose tissue (WAT) towards a brown-like (beige) state, which contributes to its systemic metabolic benefits. An obese T2DM model was established in C57BL/6J mice using a high-fat diet and low-dose streptozotocin. Mice were allocated to control (CON), sham-operated (SHAM), or RYGB groups. Metabolic parameters were monitored for 8 weeks post-surgery. Terminal analyses included body composition assessment via micro-CT, plasma lipid profiling, and histological evaluation of liver and multiple adipose depots (epididymal, inguinal, perirenal, and brown adipose tissue). RYGB induced sustained weight loss, normalized glycemia, improved insulin sensitivity, and corrected dyslipidemia. Body composition analysis revealed a preferential reduction in visceral and subcutaneous fat mass, with lean mass preserved. Histologically, RYGB markedly alleviated hepatic steatosis. Crucially, RYGB induced a profound remodeling of WAT, characterized by a significant reduction in adipocyte size in both epididymal and inguinal depots, indicating improved adipose tissue health. Concomitantly, brown adipose tissue exhibited a reversal of obesity-associated “whitening,” displaying a more active morphology with smaller lipid droplets. Beyond its established effects on weight and metabolism, RYGB induces morphological changes in white adipose tissue consistent with improved metabolic health. This structural and phenotypic reprogramming of fat depots likely represents a key cellular mechanism underpinning the surgery’s potent anti-diabetic and hepatoprotective effects. Our findings highlight adipose tissue plasticity as a central therapeutic target of RYGB. Not applicable.

ObjectiveTo investigate whether increased IGFBP-1 following Roux-en-Y gastric bypass (RYGB) surgery is associated with upregulation of IRS-1 and its downstream PI3K/AKT/GSK-3β signaling components, thereby contributing to the glucose-lowering mechanism of metabolic surgery.MethodsWild-type C57BL/6 mice (WT) and C57BL/6-Igfbpem1 IGFBP-1 knockout mice (KO) were used, along with an induced diabetes model (high-fat diet for 6 weeks followed by low-dose streptozotocin for 5 days prior to surgery). Preoperatively and at 1 to 8 weeks postoperatively, body weight, fasting blood glucose, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR, calculated from fasting glucose and insulin at week 8) were assessed. Plasma samples were collected and stored at -80 °C. Mice were euthanized at eight weeks postoperatively, and tissues were collected. ELISA was used to measure plasma IGFBP-1, IRS-1, PI3K, AKT, GSK-3β. Real-time PCR was performed to assess mRNA expression of these targets in multiple tissues. This work is reported in accordance with the ARRIVE guidelines.ResultsFollowing RYGB, body weight, fasting blood glucose, and HOMA-IR improved significantly. IGFBP-1 levels were significantly elevated post-surgery, along with marked upregulation of IRS-1, PI3K, and AKT, and downregulation of GSK-3β in WT mice. These changes were absent in KO mice. Histomorphometric analysis demonstrated that RYGB reversed multi-organ pathological changes (cardiomyocyte hypertrophy, hepatic steatosis, glomerular enlargement, adipocyte hypertrophy) in WT mice but only partially in KO mice.ConclusionMetabolic surgery upregulates IGFBP-1 expression. Elevated IGFBP-1 is associated with upregulation of the IRS/PI3K/AKT/GSK-3β signaling axis and improved insulin sensitivity. IGFBP-1 is necessary for achieving complete normalization of glucose homeostasis and multi-tissue repair after RYGB.

With the rising incidence of type 2 diabetes mellitus (T2DM) worldwide, the search for effective treatments has become an important direction of contemporary medical research. Bariatric metabolic surgery, as a new therapeutic approach, has made remarkable progress in improving T2DM in recent years. In this paper, we collected studies on the mechanisms by which metabolic surgery improves T2DM by altering the intestinal flora and its metabolites in the last 5 years, and systematically analysed the effects of different weight loss surgeries, such as gastric bypass and sleeve gastrectomy, on the composition of the intestinal flora. Then, the changes in the metabolites of the flora triggered by these surgeries and the possible downstream molecular mechanisms were explored. Although it has been revealed that the intestinal flora is altered by bacterial genera after metabolic surgery, the downstream mechanisms remain unclear. The aim of this review is to provide a new perspective for a deeper understanding of the microbiological mechanisms of metabolic surgery for T2DM and to provide a theoretical basis for future microbiome-based therapeutic strategies.

Bariatric surgery is an effective treatment for type 2 Diabetes Mellitus (T2DM), yet the precise mechanisms underlying its effectiveness remain incompletely understood. While previous research has emphasized the role of rearrangement of the gastrointestinal anatomy, gaps persist regarding the specific impact on the gut microbiota and barriers within the biliopancreatic, alimentary, and common limbs. This study aimed to investigate the effects of duodenal-jejunal bypass (DJB) surgery on obese T2DM mice. We performed DJB and SHAM surgery in obese T2DM mice to investigate changes in the gut microbiota and barrier across different intestinal limbs. The effects on serum metabolism and potential associations with T2DM improvement were also investigated. Following DJB surgery, there was an increased abundance of commensals across various limbs. Additionally, the surgery improved intestinal permeability and inflammation in the alimentary and common limbs, while reducing inflammation in the biliopancreatic limbs. Furthermore, DJB surgery also improved T2DM by increasing L-glutamine, short-chain fatty acids, and bile acids and decreasing branched-chain amino acids. This study underscores the role of intestinal rearrangement in reshaping gut microbiota composition and enhancing gut barrier function, thereby contributing to the amelioration of T2DM following bariatric surgery, and providing new insights for further research on bariatric surgery.

The aim of our study was to assess the impact of high body mass index (BMI) on type 2 diabetes mellitus (T2DM) in different Socio-Demographic Development Index (SDI) regions using data from the Global Burden of Disease (GBD) 2021 study. Using data from the GBD study, the burden of disease for T2DM was measured by analyzing the age-standardized disability-adjusted life year rate (ASDR) and age-standardized mortality rate (ASMR) for type 2 diabetes due to high BMI and the associated estimated annual percentage change (EAPC). Decomposition analyses, frontier analyses, and predictive models were used to analyze changes and influencing factors for each metric. The study revealed the significant global health burden of T2DM induced by high BMI, which EAPC of 1.82 with confidence intervals (CI) ranging from 1.78 to 1.87 for disability-adjusted life years (DALYs) and 0.85 with CIs ranging from 0.77 to 0.93 for mortality. The results of the analysis emphasized the geographic variability of T2DM disease burden associated with SDI Within the area covered by the study, a decreasing trend in ASMR for T2DM was observed in high SDI areas, with an EAPC value of − 1.07 and a confidence interval ranging from − 1.39 to − 0.76. At the same time, in the other SDI areas, the ASMR and ASDR for T2DM showed an increasing trend. In addition, the study noted that individuals in the 65- to 75-year-old age group accounted for a higher proportion of T2DM-related deaths and DALYs, with females affected at a greater rate than males. Projections for future trends indicate that the ASDR and ASMR for T2DM are expected to continue an upward trajectory over the next decade. This study investigates the variation in T2DM burden attributable to high BMI across regions with different SDI levels. The analysis reveals that, in high-SDI regions, the ASMR decreased from 1990 to 2021 and stabilized around 4.4 deaths per 100,000 people, while the ASDR increased, reaching approximately 416 cases per 100,000 people in 2021. Conversely, both ASDR and ASMR exhibited an upward trend in other SDI regions over the same period.

Early dumping syndrome (DS) is a common complication after Roux-en-Y gastric bypass (RYGB), with refractory cases posing significant therapeutic challenges. A 38-year-old male developed severe refractory early DS 2 years post-RYGB, confirmed by modified oral glucose tolerance test meeting Scarpellini 2020 criteria. Symptoms persisted despite maximal dietary and pharmacotherapy (acarbose, somatostatin analogues). The patient underwent laparoscopic gastrogastric anastomosis combined with sleeve gastrectomy -the first reported application for this indication. The Sigstad score decreased from 16 to 6 at 180-day follow-up, indicating complete symptom resolution. Endoscopy and imaging confirmed patent anastomosis without stenosis/leakage, and no complications occurred. This novel combined procedure is a safe and effective solution for refractory early DS post-RYGB, restoring physiological gastric emptying. Long-term outcomes require validation in larger studies.

AIM:The purpose of this study was to quantify the global burden of ischemic heart disease associated with lead exposure, utilizing data from the Global Burden of Disease (GBD) Study, 2021. METHODS:Data on the burden of ischemic heart disease (IHD) associated with lead exposure were compiled globally from 1990 to 2021. These data were further stratified by dimensions including gender, age, GBD regions, and countries. Utilizing the Joinpoint regression model, we analyzed long-term trends in the burden of IHD disease associated with lead exposure and derived estimated annual percentage changes (EAPC). For future projections, we used an ARIMA model to predict potential trends in the burden of IHD disease associated with lead exposure over the next decade. RESULTS:The study's findings reveal that in 2021, there were 590,370 deaths attributed to IHD (95% UI (Uncertainty interval (UI) is derived from the Bayesian school of statistical analysis used in the GBD studies. Unlike the frequency school of thought, which constructs confidence intervals (CI), the Bayesian school of thought views probability as a measure of confidence in an event, and in this approach the actual mean is viewed as a random variable dependent on the data and prior knowledge, with UI indicating that there is a specific probability (e.g., 95%) that the actual mean will fall within the interval.): -83,778 to 1,233,628) and 11,854,661 disability-adjusted life years (DALYs) (95% UI: -1,668,553 to 24,791,275) globally due to lead exposure, reflecting an increasing and then stabilizing trend from 1990 to 2021. Comparative analysis across study regions indicated a higher disease burden for IHD in regions with lower Socio-Demographic Index (SDI) values, contrasting with the lower burden in regions with higher SDI values. Furthermore, IHD mortality and DALYs peak in the 70-80 age cohort, with males exhibiting higher rates compared to females. Decadal projections indicate a downward trend in IHD mortality and DALYs for regions with higher SDI, in contrast to an anticipated upward trend in regions with lower SDI. CONCLUSION:The global burden of ischemic heart disease associated with lead exposure is increasing, particularly in regions with low SDI values and within the elderly population. Considering the profound threat posed by lead exposure to the global burden of IHD, there is an imperative to consistently reinforce and execute robust prevention strategies to mitigate environmental lead exposure.

To investigate the effectiveness of different bariatric metabolic surgeries in improving metabolic syndrome indicators in patients. A retrospective analysis was conducted on obese patients who underwent laparoscopic sleeve gastrectomy (LSG), laparoscopic sleeve gastrectomy + jejunojejunal bypass (LSG + JJB), and laparoscopic Roux-en-Y gastric bypass (LRYGB). Patients were categorized into groups based on their surgical procedure: LSG (N = 199), LSG + JJB (N = 242), and LRYGB (N = 288). Successful laparoscopic bariatric metabolic surgery was achieved in 729 patients. Indicators related to body mass, glucose metabolism, insulin resistance, lipid metabolism, and kidney function showed significant improvement compared to the preoperative period. LSG, LSG + JJB, and LRYGB all demonstrate significant effectiveness in promoting weight loss and improving glycolipid metabolism in the short term. Post-surgery, symptoms of metabolic syndrome improved compared to the preoperative period, with LRYGB showing superior effectiveness over LSG + JJB and LSG.

Ductal carcinoma in situ (DCIS) is a noninvasive precursor of breast cancer with a high potential for progression. Aberrant DNA methylation plays a pivotal role in early tumorigenesis, yet the regulatory mechanisms remain incompletely defined. Integrated bioinformatic analysis of methylation and transcriptomic datasets identified miR-217 as a candidate regulator of DNA methyltransferase 1 (DNMT1). Functional validation was conducted through RT-qPCR, dual-luciferase reporter assays, methylation-specific PCR, chromatin immunoprecipitation, and phenotypic assays in ZR-75-1 cells. An in vivo xenograft model using nude mice was employed to verify the regulatory axis. Expression of miR-217 was significantly reduced in DCIS tissues and inversely correlated with DNMT1 levels. Direct binding between miR-217 and the 3' untranslated region of DNMT1 was confirmed. Overexpression of miR-217 suppressed DNMT1, resulting in hypomethylation of the teashirt zinc finger homeobox 2 (TSHZ2) promoter and restoration of TSHZ2 expression. Elevated TSHZ2 inhibited Hedgehog-GLI signaling, thereby reducing cell proliferation, migration, invasion, and tumorigenic potential. Reintroduction of DNMT1 or activation of Hedgehog-GLI signaling reversed these effects. In vivo, miR-217 overexpression suppressed tumor growth, downregulated DNMT1 and GLI1, and increased apoptosis. The miR-217/DNMT1/TSHZ2/Hedgehog-GLI signaling axis modulates DCIS progression by epigenetically reprogramming oncogenic pathways. Targeting this axis may offer a promising strategy for DCIS treatment.

With global warming, extreme environmental heat is becoming a social issue of concern, which can cause adverse health results including heatstroke (HS). Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. However, the significant pathophysiological mechanism and treatment of HS are still not fully clear. Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. In this review, we summarized molecular mechanism, key transcriptional regulation as for HSF1, NRF2, NF-κB and PARP-1, and potential therapies of cell death resulting in CNS, liver, intestine, reproductive system and kidney injury induced by heat stress. Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.

The prevalence of obesity and type 2 diabetes is a serious global health concern. Obesity is a major pathogenic factor in type 2 diabetes, cardiovascular disease, and some cancers. Bariatric surgery offers a long-term and effective treatment option for both obesity and diabetes. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are widely recognized as the most popular bariatric surgeries. Additionally, several exploratory bariatric surgeries have demonstrated promising therapeutic effects. Duodenal-jejunal bypass (DJB), specifically tailored for diabetics with low body mass index, has shown beneficial metabolic outcomes. However, its weightindependent metabolic benefits are not fully understood due to limited animal models. In this article, we describe the optimized care protocols and surgical techniques for performing DJB surgery in diet-induced obese (DIO) diabetic mice. Using a mouse model contributes to a better understanding of the nature of changes induced by DJB surgery while facilitating related clinical practice.

Aim: The aims of this study were to better understand the outcomes of Roux-en-Y gastric bypass (RYGB) surgery in patients across multiple hospitals in China along with patients with type 2 diabetes mellitus (T2DM) and to explore the potential preoperative predictors of diabetes outcomes after RYGB. Methods: This was a retrospective cohort study in Chinese patients who underwent laparoscopic RYGB at five Chinese hospitals from April 2009 to December 2014 and returned for follow-up approximately one-year post-surgery. The STROCSS guideline checklist was applied. Results: In total, 130 patients underwent RYGB: 85 males and 45 females; age, 43.4 ± 11.3 years; and preoperative body mass index (BMI), 33.1 ± 9.0 kg/m2. Of those, 103 (79.2%) had T2DM duration of 6.6 ± 4.7 years and pre-RYGB HbA1c of 8.1 ± 1.9%. Among the patients with T2DM, glycemic control (HbA1c < 7.0%) increased from 28.7% before surgery to 79.3% at 12 months post-procedure, with a concurrent reduction in the use of anti-hyperglycemic agents, including a reduction in insulin requirement from 55.4% to 27.0%. The percentage of excess weight loss was -42.8 ± 44.2%. Among 71 patients with T2DM and data about remission status, 14 (19.7%) achieved T2DM remission at 12 months post-surgery. Age and duration of T2DM were lower in the remission group, while baseline BMI and weight were higher compared with the non-remission group. Conclusion: RYGB may be effective for weight loss and T2DM control in Chinese patients, and outcomes are consistent with the literature in Western populations. Younger patients with T2DM and with a higher BMI pre-surgery and shorter duration of T2DM were more likely to achieve T2DM remission.

Suboptimal response is one of the major problems for bariatric surgery, and constructing an individualized model for predicting outcomes of bariatric surgery is essential. Thus, the aim of this study is to develop a nomogram to predict the response to bariatric surgery. 509 patients who underwent bariatric surgery between 2019 to 2020 from 6 centers were retrieved and assessed. Multiple Imputation was used to replace missing data. Patients with

Insulin resistance (IR) is closely associated with lipid accumulation. Here, we investigated the temporal relationship between the two conditions after bariatric surgery. In total, 409 participants were enrolled from three bariatric centers in China from 2009 to 2018. We evaluated whether baseline IR (proxied by homeostasis model assessment of insulin resistance (HOMA-IR)) and lipid accumulation (proxied by visceral adiposity index (VAI) and lipid accumulation product (LAP)) were associated with follow-up IR and lipid accumulation (3 months postoperatively) using linear regression models. We then conducted a cross-lagged panel analysis model to simultaneously examine the bidirectional relationship between IR and lipid accumulation. Multivariable linear regression analyses showed that baseline HOMA-IR was associated with follow-up VAI (β = 0.430, 95

1单吻合口胃旁路术 单吻合口 胃旁路术(one anastomosis gastric bypass,OAGB)是在 Roux-en-Y 胃旁路术(Roux-en-Y gastric by-pass,RYGB)基础上简化的术式,通过建立狭长的胃囊及旷置十二指肠与部分空肠达到减重目的.此术式仅建立一个胃空肠吻合口,手术时间与学习曲线短,操作简捷易于掌握.

Current bariatric surgery models primarily utilize mice with obesity, overlooking those with type 2 diabetes (T2DM). These models have limitations in replicating clinical procedures accurately and achieving broad applicability. This study aimed to develop novel mouse models of Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) surgeries specifically designed for T2DM research, utilizing simplified surgical techniques closely resembling clinical procedures. Eight-week-old C57/Bl6 mice, except for the Blank-Control group, were induced with T2DM by combining a high-fat diet and streptozotocin injection. RYGB involved creating a 10

IntroductionPrevious studies have demonstrated that one anastomosis gastric bypass (OAGB) is not inferior to Roux-en-Y gastric bypass (RYGB) in treating obesity. However, high level evidence comparing the efficacy and safety of both procedures in type 2 diabetes (T2D) treatment is still lacking, which is another main aim of bariatric surgery. The presented trial has been designed to aim at investigating the superiority of OAGB over the reference procedure RYGB in treating T2D as primary endpoint. And diabetes-related microvascular and macrovascular complications, cardiovascular comorbidities, weight loss, postoperative nutritional status, quality of life and overall complications will be followed up for 5 years as secondary endpoints.Methods and analysisThis prospective, multicentre, randomised superiority open-label trial will be conducted in patients of Asian descent. A total of 248 patients (BMI≥27.5 kg/m2) who are diagnosed with T2D will be randomly assigned (1:1) to OAGB or RYGB with blocks of four. The primary endpoint is the complete diabetes remission rate defined as HbA1c≤6.0% and fasting plasma glucose≤5.6 mmol/L without any antidiabetic medications at 1 year after surgery. All secondary endpoints will be measured at different follow-up visit points, which will start at least 3 months after enrolment, with a continuous annual follow-up for five postoperative years in order to provide solid evidence on the efficacy and safety of OAGB in patients with T2D.Ethics and disseminationThe study has been approved by the ethics committee of leading centre (Beijing Friendship Hospital, Capital Medical University, no. 2021-P2-037-03). The results generated from this work will be disseminated to academic audiences and the public via publications in international peer-reviewed journals and conferences. The data presented will be imported into a national data registry. Findings are expected to be available in 2025, which will facilitate clinical decision-making in the field.Trial registration numberNCT05015283.