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Recently, more than 10 models have been developed to predict remission of type 2 diabetes mellitus (T2DM) after metabolic surgery. The ABCD score was compared to the individualized metabolic surgery (IMS) score in terms of prediction of T2DM remission, but which of the two scoring systems is better remains controversial. Patient data from 463 obese East Asian patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or SG with duodenojejunal bypass (SG-DJB) as a primary operation and were followed for at least 3 years were retrospectively collected from 24 institutions. The correlation between the ABCD and IMS scoring systems and the discrimination power of the models was evaluated. The cut-off point for the IMS stage of T2DM severity was also revised to adjust the scoring system to obese East Asian patients. The two scoring systems were significantly well correlated. The IMS scoring system showed significant differences in T2DM remission rates between the procedures in the moderate stage, but the ABCD score showed no significant differences in each category. The discrimination power of the IMS score was comparable to that of the ABCD score at both 3 and 5 years. The revised IMS scoring system showed that SG-DJB had significantly higher T2DM remission rates in the moderate stage at 5 years than RYGB or SG. IMS score may be comparable to ABCD score to predict T2DM remission in obese East Asian patients. The revised IMS scoring system may also select candidates for SG or SG-DJB.

To clarify the function of long non-coding RNA (lncRNA) GALNT5 uaRNA in cisplatin resistant colorectal cancer and its potential mechanism. The expression levels were also detected in cisplatin resistant colorectal cancer cell lines (HCT116/DDP and HT29/DDP cells) and sensitive colorectal cancer cell lines. The effects of GALNT5 uaRNA on apoptosis of HCT116/DDP and HT29/DDP cells were examined by flow cytometry assay respectively. The protein levels of drug resistance related genes influenced by GALNT5 uaRNA were detected by Western blot. The cells of siNC, sIGALNT5 uaRNA, Vector and GALNT5 uaRNA cells groups from HCT116/DDP and HT29/DDP cells were injected into dorsal flanks of the mice repectively. Higher GALNT5 uaRNA expression was observed in HCT116/DDP and HT29/DDP cells relative to that of their parental cells. The apoptotic rate increased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA knockdown compared to the cells with control group. Furthermore, the expression levels of MDR1, MRP1 and p-NF-κB were decreased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA knockdown compared to the cells with control group. The apoptotic rate decreased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA overexpression. Furthermore, the expression levels of MDR1, MRP1 and p-NF-κB were increased in HCT116/DDP cells with GALNT5 uaRNA overexpression compared to the cells with control group. The tumors in the HCT116/DDP/siGANLNT5 uaRNAgroup were smaller and lighter than those in the HCT116/DDP/siNC. In a word GALNT5 uaRNA promotes cisplatin resistance by MDR1/MRP1/NF-κB pathway.

Background Specific tumour markers that are similar to the 21-gene assay in breast cancer, have yet to be identified in rectal cancer. The objective of this study is to identify a novel genetic signature in rectal cancer to help predict survival and provide clues for immunotherapy. Methods Differentially Expressed Genes were obtained from two GEO datasets of rectal cancer. By using data from TCGA and GSE133057, two cohorts of rectal cancer were applied to establish and evaluate the prognostic signature. Then, a nomogram was constructed to estimate survival predictability in both training and validation cohorts. Subsequently, we integrated the risk-score with clinicopathological features and assessed its interplay with immune cells and molecules. Finally, our study performed functional annotations, gene-targeted miRNAs, and single-cell analysis to reveal potential functions and relevant mechanisms. Results A total of 468 DEGs were identified between rectal cancer and normal tissues, and a signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected for further analyses in a prognostic model. According to the risk-score calculated by the model, results showed that overall survival was significantly worse in the high-risk group (P = 0.0044). The model exhibited high performance in time-dependent ROC as well as a nomogram. Notably, as an independent prognostic factor, the risk-score was associated with vascular invasion (P = 0.038). Furthermore, there was a dramatic difference in nonregulatory CD4 + and CD8 + T cells between the high and low-risk groups. Strikingly, the Heat map plot showed that genes in our model were correlated with immune inhibitors. Moreover, there was also a big difference in autophagy-, immune-, cell cycle-, infection-, and apoptosis-associated terms and pathways between high and low-risk groups by GO and KEGG enrichment. Then, hsa-miR-6887 was predicted to be a common microRNA of 5 genes, which was only correlated with GNG7 in expression. Markedly, the functional states of differentiation, apoptosis, and quiescence were highly related to the 5-gene signature in single-cell analysis. Conclusion Our results suggest that the 5-gene-based signature could serve as a novel prognostic biomarker in rectal cancer, which could be of benefit for decision-making in rectal cancer immunotherapy.

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.

Background: Metastasis-associated with colon cancer-1 (MACC1) is an important regulator that promotes colorectal cancer (CRC) cells' proliferation and distant metastasis. Therefore, MACC1 is considered as a promising therapeutic target of CRC. This work aimed to identify the microRNA (miR) targeted to MACC1, and to study the potential of using the particular miR in enhancing the antitumor effect of chemotherapy. Materials and methods: miR prediction was performed in the miR database. The effect of miR-940 on MACC1's expression was examined by Western blot, and the effect of miR-940 on the expression of genes related to the epithelial-mesenchymal transition (EMT) was identified by quantitative real-time polymerase chain reaction experiments. In vivo growth of CRC cells were analyzed in the nude mice subcutaneous tumor model and CRC liver metastasis model. Results: By using the database, miR-940 was identified to target to the 3'UTR of MACC1's mRNA. Experimentally, transfection of miR-940 decreased the expression of MACC1 in CRC cells and inhibited the EMT process of the transfected cells. MiR-940 also enhanced the inhibitory effect of Anlotinib on CRC cells' in vivo growth and invasion. Correspondingly, ectopic expression of MACC1 mutant, which does not contain miR-940 binding site, blocked the antitumor effect of miR-940 on CRC cells. Conclusion: MiR-940 restricts the proliferation and invasion of CRC cells by targeting to MACC1's mRNA, and enhances the antitumor effect of Anlotinib on CRC tumors.

To investigate prognostic factors for complete remission in type 2 diabetes mellitus (T2DM) patients who underwent gastric bypass (GBP) and to establish a prognostic model for risk stratification. We evaluated the baseline clinical features of patients with T2DM who received at Beijing Tian Tan Hospital from April 2012 to December 2015. Complete remission of T2DM was defined as meeting the following criteria: HbA1c

Background Bariatric surgery may be indicated in patients with nonalcoholic fatty liver disease (NAFLD) to achieve and maintain the degree of weight loss required to ensure therapeutic effects. However, bariatric surgery is still underrecognized in the treatment of NAFLD, including its inflammatory subtype, nonalcoholic steatohepatitis (NASH). Moreover, there is a lack of follow-up outcome data on different types of bariatric surgery in patients with NAFLD. This study aims to adequately assess the effect of bariatric surgery on NAFLD remission in obese patients. Methods This prospective multicentre observational follow-up study will include 142 obese patients with NAFLD scheduled to undergo one of the following surgical procedures: sleeve gastrostomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass. The primary outcome is the complete remission rate of NAFLD one year postoperatively, which is defined by liver fat fraction Discussion This study will provide a necessary and preliminary foundation for the early identification and targeted treatment of patients with NAFLD who can be referred for bariatric surgery, as indicated for management of obesity and metabolic disease. Trial registration: Clinicaltrials.gov: NCT04366999. Registered 21 April 2020. (https://clinicaltrials.gov/ct2/show/NCT04366999).

Summary Obesity is an important risk factor and a potential treatment target for hepatic steatosis. The maladaptation of hepatic mitochondrial flexibility plays a key role in the hepatic steatosis. Herein, we found that hepatocyte-like cells derived from human adipose stem cell of obese patients exhibited the characteristics of hepatic steatosis and accompanied with lower expression of the subunits of mitochondrial complex I and lower oxidative phosphorylation levels. The GSK3 inhibitor CHIR-99021 promoted the expression of NDUFB8, NDUFB9, the subunits of mitochondrial complex I, the basal oxygen consumption rate, and the fatty acid oxidation of the hepatocytes of obese patients by upregulating the expression of the transcription factor PGC-1α, TFAM, and NRF1 involved in mitochondrial biogenesis. Moreover, CHIR-99021 decreased the lipid droplets size and the triglyceride levels in hepatocytes of obese patients. The results demonstrate that GSK3 inhibition ameliorates hepatic steatosis by elevating the mitochondrial function in hepatocytes of obese patients., Graphical abstract, Highlights • Obese patients’ adipose-stem-cell-derived hepatocytes reveal hepatic steatosis • Hepatic steatosis is accompanied the mitochondrial dysfunction • The mitochondrial dysfunction is governed by the low expression PGC-1α, TFAM, and NRF1 • GSK3 inhibitor ameliorates hepatic steatosis via mitochondrial dysfunction modulation, human metabolism; molecular biology

One anastomosis gastric bypass (OAGB) and sleeve gastrectomy (SG) are popular bariatric surgeries for morbid obesity. Reports on the safety and effectiveness of SG and OAGB are inconsistent. This meta-analysis investigated the clinical outcomes of SG versus those of OAGB for morbid obesity. Based on PRISMA guidelines, we searched the published articles in English from Scopus, PubMed (Medline), Central (Cochrane), and Embase databases. Articles were retrieved from the start date of each database to February 13, 2019. Statistical analysis of this meta-analysis was conducted in Stata 14.0, and the most appropriate effect model was chosen based on heterogeneity. A total of 20 articles examining 4064 OAGB patients and 3733 SG patients were included in this meta-analysis. Compared with SG, OAGB showed a higher percentage excess weight loss (%EWL) at 6 months (weighted mean difference (WMD) = 11.32; 95% CI 6.00–16.64), 12 months (WMD = 8.22; 95% CI 3.78–12.66), 24 months (WMD = 10.19; 95% CI 0.88–21.25), 36 months (WMD = 7.93; 95% CI 3.37–12.48), 48 months (WMD = 17.22; 95% CI 7.37–27.06), and 60 months (WMD = 16.43; 95% CI 8.96–23.90). In addition, OAGB was associated with a lower rate of postoperative leak, gastroesophageal reflux disease, revisions, mortality, and dyslipidemia remission rates. However, OAGB increased the incidence of ulcers, malnutrition, and bile reflux. OAGB is more effective for %EWL and dyslipidemia remission than SG. In addition, OAGB may lower the risk of postoperative leak, gastroesophageal reflux disease, revision, and mortality. Further comparisons of the clinical outcomes of OAGB versus SG for morbid obesity would benefit from more high-quality controlled studies.

The study evaluated the predictive role of preoperative fasting C-peptide, hemoglobin (Hb)A1c, fasting plasma glucose (FPG), and body mass index (BMI) levels on diabetes remission in patients with type 2 diabetes following bariatric surgery.Medline, PubMed, Central, and Google Scholar databases of up to September 7, 2016 were searched using the following terms: type 2 diabetes mellitus, gastric bypass, Roux-en-Y, anastomosis, C-peptide, weight loss, HbA/HbA1c, predictive/predictor.Meta-analysis of the pooled data indicated that fasting C-peptide was predictive of increased chance of remission of type 2 diabetes (pooled difference in means = 0.93, 95% confidence interval [CI] = 0.61 to 1.25, p.001). The analysis also found that FPG (pooled standardized mean difference = -0.42, 95% CI: -0.64 to -0.20, p.004) and HbA1c levels (pooled difference in means = -1.05, 95% CI: -1.48 to -0.62, p.001) were associated with reduced odds of type 2 diabetes remission. BMI was not found to be associated with remission (pooled difference in means = 0.29, 95% CI: 0.30 to 0.88, p = .343). In general, subgroup analysis, which evaluated the pooled data from the retrospective and prospective studies separately, gave similar results.Preoperative fasting plasma C-peptide was associated with increased type 2 diabetes remission after bariatric surgery, whereas baseline HbA1c and FPG levels were associated with reduced chance of remission. These parameters may be used as a guideline in weighing the risks and benefits for surgical intervention in patients with type 2 diabetes.

Purpose: To compare the short-term outcomes between self-expandable metallic stent (SEMS) and decompression tubes (DT) for malignant colorectal obstruction. Methods: A comprehensive literature search was performed from inception to 2018/12/6 covering Pubmed, Embase, and Cochrane library. Methodological assessments of eligible studies were performed by using Newcastle-Ottawa Scale (NOS). The Revman software (version 5.3) was used in our statistical analysis. Results: Totally 7 cohort studies were enrolled in our meta-analysis. All the 7 eligible studies proved to be high quality according to the NOS scale. Patients receiving SEMS had higher clinical success rates, higher laparoscopic surgery rates, and higher primary anastomosis rates compared with patients receiving DT. Conclusions: Based on evidence from eastern countries, SEMS placement is an effective procedure that treats malignant colorectal obstruction. Compared with DT placement, patients receiving SEMS may benefit from higher clinical success rates, higher laparoscopic surgery rates, and higher primary anastomosis rates.

The aim of the present study was to identify potential therapeutic targets for colorectal cancer (CRC). The gene expression profile GSE32323, containing 34 samples, including 17 specimens of CRC tissues and 17 of paired normal tissues from CRC patients, was downloaded from the Gene Expression Omnibus database. Following data preprocessing using the Affy and preprocessCore packages, the differentially-expressed genes (DEGs) between the two types of samples were identified with the Linear Models for Microarray Analysis package. Next, functional and pathway enrichment analysis of the DEGs was performed using the Database for Annotation Visualization and Integrated Discovery. The protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes database. Utilizing WebGestalt, the potential microRNAs (miRNAs/miRs) of the DEGs were screened and the integrated miRNA-target network was built. A cohort of 1,347 DEGs was identified, the majority of which were mainly enriched in cell cycle-related biological processes and pathways. Cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), MAD2 mitotic arrest deficient-like 1 (MAD2L1) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) were prominent in the PPI network, while the over-represented genes in the integrated miRNA-target network were SRY (sex determining region Y)-box 4 (SOX4; targeted by hsa-mir-129), v-myc avian myelocytomatosis viral oncogene homolog (MYC; targeted by hsa-let-7c and hsa-mir-145) and cyclin D1 (CCND1; targeted by hsa-let-7b). CDK1, CCNB1 and CCND1 were also associated with the p53 signaling pathway. Overall, several genes associated with the cell cycle and p53 pathway were identified as biomarkers for CRC. CDK1, CCNB1, MAD2L1, BUB1B, SOX4, collagen type I α2 chain and MYC may play significant roles in CRC progression by affecting the cell cycle-related pathways, while CDK1, CCNB1 and CCND1 may serve as crucial regulators in the p53 signaling pathway. Furthermore, SOX4, MYC and CCND1 may be targets of miR-129, hsa-mir-145 and hsa-let-7c, respectively. However, further validation of these data is required.

Trefoil factor 1 (TFF1) is a tumor suppressor gene that encodes a peptide belonging to the trefoil factor family of protease‑resistant peptides. Although TFF1 expression is frequently lost in gastric carcinomas (GCs), the tumorigenic pathways that are affected have yet to be determined. The aim of the current study was to identify the mechanism(s) by which the TFF1 gene is regulated in gastric carcinogenesis. In this study, TFF1 was shown to be silenced or downregulated in gastric tumor tissue compared with matched non‑cancerous tissue. In addition, human gastric cells weakly expressed TFF1. The hypermethylation status in the promoter CpG islands appeared to be correlated with TFF1 expression levels in gastric cell lines or specimen tissue. Further molecular analysis indicated that the CpG islands play a role in the promoter activity of the TFF1 gene. The expression of TFF1 and DNA methylation of its promoter affected cell proliferation and apoptosis. The expression of TFF1 in gastric cell lines was restored with a demethylating agent, 5‑azacytidine. Low expression of TFF1 in gastric cell lines and cancer tissue is associated with TP 53. In conclusion, the current study demonstrates that DNA methylation is a key mechanism of silencing TFF1 expression in human gastric cells and TFF1 gene hypermethylation of the CpG islands is a potential biomarker for GC.

The aim of this study was to investigate the effects of ileal interposition (IT) on glucose and insulin resistance (IR) in type 2 diabetic mellitus (T2DM), and the role of T-cell factor 7-like 2 (TCF7L2), formerly known as TCF4, in the downregulation of hyperglycemia following IT. Goto-Kakizaki (GK) rats subjected to IT surgery (GK-IT group), GK rats subjected to sham surgery (GK-Sham group) and Wistar (WS) rats subjected to sham surgery (WS-Sham group) were investigated in this study. Fasting plasma glucose, body weight, food intake per 1 kg body weight, insulin and a homeostasis model assessment of insulin resistance (HOMA-IR) were measured pre- and post-surgery. The rats were euthanized 28 days post-surgery and the pancreas of each rat was dissected. The expression levels of TCF7L2 mRNA and protein were analyzed by quantitative RT-PCR and western blotting, respectively. Our results revealed that IT improved both fasting plasma glucose levels and IR in GK rats by upregulating the expression of the TCF7L2 protein. IT provides a valuable therapeutic option for patients with T2DM. Upregulation of TCF7L2 protein expression may be a possible mechanism underlying the improvement of T2DM following IT.

To investigated changes in intestinal Akkermansia muciniphila (A. muciniphila) and explored the mechanism underlying the therapeutic effects of Roux-en-Y gastric bypass (RYGB) surgery on type 2 diabetes in diabetic Goto-Kakizaki (GK) rats.Male diabetic GK rats (n = 12) aged 8 wk were randomly assigned to the surgery group (GK-RYGB) or sham surgery group (GK-Sham) (n = 6 per group), and another 6 male Wistar rats aged 8 wk served as controls (WS-Sham). In the surgery group, RYGB surgery was conducted, and a sham operation was performed in both sham groups. Fasting blood glucose (FBG) levels before and after surgery, fasting levels of serum insulin and serum glucagon-like peptide-1 (GLP-1) and levels 30 min after intragastric injection of glucose, and the amount of A. muciniphila in the stool were determined. Insulin and GLP-1 were measured by enzyme-linked immunosorbent assay, and A. muciniphila were detected by fluorescence-based quantitative polymerase chain reaction.The FBG was improved, and serum GLP-1 and insulin increased significantly (P0.05) in the GK-RYGB group after surgery compared to levels before surgery and to levels in the GK-Sham group. Before surgery, the amounts of A. muciniphila in the GK-RYGB and GK-Sham groups were significantly lower than in the WS-Sham group (P0.05). After surgery, the amount of A. muciniphila in the GK-RYGB group increased markedly compared to that before surgery and to that in the GK-Sham and WS-Sham groups (P0.05). In addition, the A. muciniphila amount was positively related to GLP-1 (r = 0.86, P0.05).Our results demonstrated RYGB surgery may increase GLP-1 secretion, elevate serum insulin after intragastric injection of glucose, and improve insulin resistance in diabetic GK rats, thereby contributing to a significant reduction in blood glucose. The increased amount of A. muciniphila after RYGB surgery may be related to elevated GLP-1 secretion.

AIM To evaluate the feasibility of side-to-side anastomosis of the lesser curvature of stomach and jejunum in laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS Seventy-seven patients received side-to-side anastomosis of the lesser curvature of stomach and jejunum by utilization of linear stapler in LRYGB from April 2012 to July 2015 were retrospectively analyzed. RESULTS All patients were successfully completed laparoscopic gastric bypass with the side-to-side anastomosis of the lesser curvature of stomach and jejunum. No patient was switched to laparotomy during operation. No early complications including gastrointestinal anastomotic bleeding, fistula, obstruction, deep vein thrombosis, incision infections, intra-abdominal hernia complications were found. One patient complicated with stricture of gastrojejunal anastomosis (1.3%) and six patients complicated with incomplete intestinal obstruction (7.8%). BMI and HbA1c determined at 3, 6, 12, 24 mo during follow up period were significantly reduced compared with preoperative baselines respectively. The percentage of patients who maintain HbA1c (%) < 6.5% without taking antidiabetic drugs reached to 61.0%, 63.6%, 75.0%, and 63.6% respectively. The outcome parameters of concomitant diseases were significantly improved too. CONCLUSION Present surgery is a safety and feasibility procedure. It is effective to lighten the body weight of patients and improve type 2 diabetes and related complications.