Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

Association between ultra-processed foods and risk of cancer: a systematic review and meta-analysis.

Background: Despite increasing evidence that has shown the association of ultra-processed foods (UPFs) with cancer risk, the results remain inconclusive. We, therefore, conducted the meta-analysis to clarify the association by including recently published studies. Methods: A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies from inception to January 2023. To pool data, fixed-effects or random-effects models were used where appropriate. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. Results: A total of 13 studies (4 cohort studies and 9 case-control studies) were included in the analysis, with a total of 625,738 participants. The highest UPFs consumption was associated with increased risk of colorectal cancer (OR = 1.23, 95% CI: 1.10-1.38), colon cancer (OR = 1.25, 95% CI: 1.14-1.36), and breast cancer (OR = 1.10, 95% CI: 1.00-1.20) but not rectal cancer (OR = 1.18, 95% CI: 0.97-1.43) and prostate cancer (OR = 1.03, 95% CI: 0.93-1.12). In addition, the subgroup analyses showed that a positive association between UPFs consumption and colorectal cancer was observed among men (OR = 1.31, 95% CI: 1.15-1.50), whereas no significant association was observed among women (OR = 1.10, 95% CI: 0.94-1.29). Conclusion: The present meta-analysis suggests that high UPFs consumption is associated with a significantly increased risk of certain site-specific cancers, especially the digestive tract and some hormone-related cancers. However, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.

Machine Learning to Dynamically Predict In-Hospital Venous Thromboembolism After Inguinal Hernia Surgery: Results From the CHAT-1 Study.

BACKGROUND: The accuracy of current prediction tools for venous thromboembolism (VTE) events following hernia surgery remains insufficient for individualized patient management strategies. To address this issue, we have developed a machine learning (ML)-based model to dynamically predict in-hospital VTE in Chinese patients after hernia surgery. METHODS: ML models for the prediction of postoperative VTE were trained on a cohort of 11 305 adult patients with hernia from the CHAT-1 trial, which included patients across 58 institutions in China. In data processing, data imputation was conducted using random forest (RF) algorithm, and balanced sampling was done by adaptive synthetic sampling algorithm. Data were split into a training cohort (80%) and internal validation cohort (20%) prior to oversampling. Clinical features available pre-operatively and postoperatively were separately selected using the Sequence Forward Selection algorithm. Nine-candidate ML models were applied to the pre-operative and combined datasets, and their performance was evaluated using various metrics, including area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using importance scores, which were calculated by transforming model features into scaled variables and representing them in radar plots. RESULTS: The modeling cohort included 2856 patients, divided into 2536 cases for derivation and 320 cases for validation. Eleven pre-operative variables and 15 combined variables were explored as predictors related to in-hospital VTE. Acceptable-performing models for pre-operative data had an AUROC ≥ 0.60, including logistic regression, support vector machine with linear kernel (SVM_Linear), attentive interpretable Tabular learning (TabNet), and RF. For combined data, logistic regression, SVM_Linear, and TabNet had better performance, with an AUROC ≥ 0.65 for each model. Based on these models, 7 pre-operative predictors and 10 combined predictors were depicted in radar plots. CONCLUSIONS: A ML-based approach for the identification of in-hospital VTE events after hernia surgery is feasible. TabNet showed acceptable performance, and might be useful to guide clinical decision making and VTE prevention. Further validated study will strengthen this finding.

Prediction Model of in-Hospital Venous Thromboembolism in Chinese Adult Patients after Hernia Surgery: The CHAT Score.

BACKGROUND: Venous thromboembolism (VTE) events after hernia surgery influence prognosis and life quality and may be preventable. This study aimed to develop a useful model for predicting in-hospital VTE in Chinese patients after hernia surgery. METHODS: Patients after hernia surgery were retrospectively recruited from 58 institutions (n = 14 322). Totally, 36 potential predictors were involved in the regression analysis. Weighted points were assigned to the predictors of in-hospital VTE identified in the multivariate logistic regression analysis and a prediction model was established. Decision curve analysis was performed to evaluate the net clinical benefit between the established and Caprini models. RESULTS: A total of 11 707 patients were included and five variables were explored as predictors related to in-hospital VTE: varicose veins of lower extremity, history of VTE, family history of thrombosis, interruption of antithrombotic agents, and reducible hernia. The prediction model (the CHAT score) revealed a good performance metrics (c-statistic, 0.81 [95% CI, 0.80 to 0.81]; Nagelkerke R2, 0.27 [95% CI, 0.26 to 0.30]; Brier score, 0.16 [95% CI, 0.13 to 0.23]). The rate of in-hospital VTE after hernia surgery at low-risk (-4 points), intermediate-risk (0-1 points), high-risk (4 points) and very high-risk (≥5 points) were 0.05%, 0.39%, 0.73% and 8.62%, respectively. The CHAT score identified a considerable variability (from 0.05% to 8.62%) for in-hospital VTE among the overall population after hernia surgery. Decision curve analysis found a superior net benefit of the established model than the Caprini score. CONCLUSIONS: The CHAT score is likely to be a practical 5-item supporting tool to identify patients at high risk of in-hospital VTE after hernia surgery that might assist in decision making and VTE prevention. Further validated study will strengthen this finding.

Rationale and design of a prospective, multicenter, randomized controlled trial of postoperative venous thromboembolism prophylaxis in Chinese adult patients with inguinal hernia (CHAT-3 trial).

BACKGROUND: Venous thromboembolism (VTE) is one of the most common causes of preventable harm for patients in hospitals. Nearly half of all VTE events was estimated to occur after surgical procedure. The Caprini risk score is the most extensively used risk assessment tool in predicting postoperative VTE, which is too complicate for surgeons to use properly in their clinical practice. METHODS: The CHAT-3 trial will be a prospective, multicenter, randomized, parallel-group trial, which is designed to identify patients at moderate or high risk of VTE after inguinal hernia surgery using the previously established three-factor model, and to use low molecular weight heparin (LMWH) for VTE prevention, in comparison to the current routine assessment and practice used in those patients. Totally, 1,008 patients planned to undergo inguinal hernia surgery will be enrolled, with cluster randomization at 1:1 ratio into intervention arm and control arm. The primary outcomes are the accordance of perioperative VTE prophylaxis based on current guidelines and the rate of pharmacological prophylaxis for VTE. The secondary outcomes are the occurrences of perioperative VTE, major bleeding, mortality of patients after inguinal hernia surgery, and trend of D-dimer during the follow-up period. DISCUSSION: This study will create evidence that whether the administration based on a simple model is of efficacy and safety for VTE prophylaxis among Chinese patients underwent inguinal hernia surgery. TRIAL REGISTRATION: The CHAT-3 trial (Trial registration number: ChiCTR2000033769).

Effect of oligofructose on resistance to postoperative high-fat diet-induced damage of metabolism in diabetic rats after sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) can induce prominent remission of type 2 diabetes mellitus. However, the long-term remission rate of diabetes usually decreases over time. Oligofructose has been verified to modulate host metabolism. The aim of this study was to explore the protective effect of oligofructose on high-fat diet (HFD)-induced metabolic dysfunction after SG. AIM: To study the effect and mechanism of oligofructose on diabetic remission in diabetic rats after SG. METHODS: SG and SHAM operation were performed on diabetes rats induced with an HFD, nicotinamide, and low-dose streptozotocin. Then the rats in the SHAM and SG groups were continuously provided with the HFD, and the rats in sleeve gastrectomy-oligofructose group were provided with a specific HFD containing 10% oligofructose. Body weight, calorie intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance, lipid profile, serum insulin, glucagon-like peptide 1 (GLP-1), total bile acids, lipopolysaccharide (LPS), and colonic microbiota levels were determined and compared at the designated time points. All statistical analyses were performed using Statistic Package for Social Science version 19.0 (IBM, United States), and the statistically significant difference was considered at P < 0.05. RESULTS: At 2 wk after surgery, rats that underwent SG exhibited improved indexes of glucose and lipid metabolism. Compared with the SG group, the rats from SG-oligofructose group exhibited better parameters of glucose and lipid metabolism, lower body weight (526.86 ± 21.51 vs 469.25 ± 21.84, P < 0.001), calorie intake (152.14 ± 9.48 vs 129.63 ± 8.99, P < 0.001), homeostasis model assessment of insulin resistance (4.32 ± 0.57 vs 3.46 ± 0.52, P < 0.05), and LPS levels (0.19 ± 0.01 vs 0.16 ± 0.01, P < 0.05), and higher levels of insulin (1.17 ± 0.17 vs 1.58 ± 0.16, P < 0.001) and GLP-1 (12.39 ± 1.67 vs 14.94 ± 1.86, P < 0.001), and relative abundances of Bifidobacterium (0.0034 ± 0.0014 vs 0.0343 ± 0.0064, P < 0.001), Lactobacillus (0.0161 ± 0.0037 vs 0.0357 ± 0.0047, P < 0.001), and Akkermansia muciniphila (0.0050 ± 0.0024 vs 0.0507 ± 0.0100, P < 0.001) at the end of the study. However, no difference in total bile acids levels was observed between the two groups. CONCLUSION: Oligofructose partially prevents HFD-induced glucose and lipid metabolism damage after SG, which may be due to the changes of calorie intake, insulin, GLP-1, LPS, and the gut microbiota in rats.

Sleeve gastrectomy ameliorates endothelial function and prevents lung cancer by normalizing endothelin-1 axis in obese and diabetic rats.

BACKGROUND: Previous evidence has implied that obesity is an independent risk factor for developing cancer. Being closely related to obesity, type 2 diabetes mellitus provides a suitable environment for the formation and metastasis of tumors through multiple pathways. Although bariatric surgeries are effective in preventing and lowering the risk of various types of cancer, the underlying mechanisms of this effect are not clearly elucidated. AIM: To uncover the role and effect of sleeve gastrectomy (SG) in preventing lung cancer in obese and diabetic rats. METHODS: SG was performed on obese and diabetic Wistar rats, and the postoperative transcriptional and translational alterations of the endothelin-1 (ET-1) axis in the lungs were compared to sham-operated obese and diabetic rats and age-matched healthy controls to assess the improvements in endothelial function and risk of developing lung cancer at the postoperative 4th, 8th, and 12th weeks. The risk was also evaluated using nuclear phosphorylation of H2A histone family member X as a marker of DNA damage (double-strand break). RESULTS: Compared to obese and diabetic sham-operated rats, SG brought a significant reduction to body weight, food intake, and fasting blood glucose while improving oral glucose tolerance and insulin sensitivity. In addition, ameliorated levels of gene and protein expression in the ET-1 axis as well as reduced DNA damage indicated improved endothelial function and a lower risk of developing lung cancer after the surgery. CONCLUSION: Apart from eliminating metabolic disorders, SG improves endothelial function and plays a protective role in preventing lung cancer via normalized ET-1 axis and reduced DNA damage.

Warshaw Technique in Laparoscopic Spleen-Preserving Distal Pancreatectomy: Surgical Strategy and Late Outcomes of Splenic Preservation.

Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) can be accomplished with either the preservation or the resection of splenic vessels; the latter is also known as Warshaw technique. Our study is designed to investigate the operation selection strategy when proceeding LSPDP and to evaluate the long-term outcomes of patients undergoing Warshaw surgery. The medical records and follow-up data of patients who underwent LSPDP in Qilu Hospital, Shandong University, were reviewed retrospectively. A total of thirty-five patients were involved in this study, including 17 cases of patients who were treated with Warshaw procedure (WT) while the other 18 cases had splenic vessels preserved (SVP). Compared with the SVP group, the operative time and intraoperative blood loss in WT group were improved significantly. The incidence of early postoperative splenic infarction was higher in WT group. However, there was no report of splenic abscess or second operation. Follow-up data confirmed that there was no significant difference in spleen phagocytosis and immune function compared with normal healthy population. Our study confirms that LSPDP-Warshaw procedure is a safe and efficient treatment for the benign or low grade malignant tumors in distal pancreas in selected patients. The long-term spleen function is normal after Warshaw procedure. Preoperative assessment and intraoperative exploration are recommended for the selection of operation approaches.

Khubchandani's procedure combined with stapled posterior rectal wall resection for rectocele.

BACKGROUND: Obstructed defecation syndrome (ODS) is a widespread disease in the world. Rectocele is the most common cause of ODS in females. Multiple procedures have been performed to treat rectocele and no procedure has been accepted as the gold-standard procedure. Stapled transanal rectal resection (STARR) has been widely used. However, there are still some disadvantages in this procedure and its effectiveness in anterior wall repair is doubtful. Therefore, new procedures are expected to further improve the treatment of rectocele. AIM: To evaluate the efficacy and safety of a novel rectocele repair combining Khubchandani's procedure with stapled posterior rectal wall resection. METHODS: A cohort of 93 patients were recruited in our randomized clinical trial and were divided into two different groups in a randomized manner. Forty-two patients (group A) underwent Khubchandani's procedure with stapled posterior rectal wall resection and 51 patients (group B) underwent the STARR procedure. Follow-up was performed at 1, 3, 6, and 12 mo after the operation. Preoperative and postoperative ODS scores and depth of rectocele, postoperative complications, blood loss, and hospital stay of each patient were documented. All data were analyzed statistically to evaluate the efficiency and safety of our procedure. RESULTS: In group A, 42 patients underwent Khubchandani's procedure with stapled posterior rectal wall resection and 34 were followed until the final analysis. In group B, 51 patients underwent the STARR procedure and 37 were followed until the final analysis. Mean operative duration was 41.47 ± 6.43 min (group A) vs 39.24 ± 6.53 min (group B). Mean hospital stay was 3.15 ± 0.70 d (group A) vs 3.14 ± 0.54 d (group B). Mean blood loss was 10.91 ± 2.52 mL (group A) vs 10.14 ± 1.86 mL (group B). Mean ODS score in group A declined from 16.50 ± 2.06 before operation to 5.06 ± 1.07 one year after the operation, whereas in group B it was 17.11 ± 2.57 before operation and 6.03 ± 2.63 one year after the operation. Mean depth of rectocele decreased from 4.32 ± 0.96 cm (group A) vs 4.18 ± 0.95 cm (group B) preoperatively to 1.19 ± 0.43 cm (group A) vs 1.54 ± 0.82 cm (group B) one year after operation. No other serious complications, such as rectovaginal fistula, perianal sepsis, or deaths, were recorded. After 12 mo of follow-up, 30 patients' (30/34, 88.2%) final outcomes were judged as effective and 4 (4/34, 11.8%) as moderate in group A, whereas in group B, 30 (30/37, 81.1%) patients' outcomes were judged as effective, 5 (5/37, 13.5%) as moderate, and 2 (2/37, 5.4%) as poor. CONCLUSION: Khubchandani's procedure combined with stapled posterior rectal wall resection is an effective, feasible, and safe procedure with minor trauma to rectocele.

Immunotherapy for pancreatic cancer: A long and hopeful journey.

Multiple therapeutic strategies have been developed to treat pancreatic cancer. However, the outcomes of these approaches are disappointing. Due to deeper understandings of the pivotal roles of the immune system in pancreatic cancer tumorigenesis and progression, novel therapeutic strategies based on immune cells and the tumor microenvironment are being investigated. Some of these approaches, such as checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and BiTE antibodies, have achieved exciting outcomes in preclinical and clinical trials. The current review describes the roles of immune cells and the immunosuppressive microenvironment in the development of pancreatic cancer, as well as the preclinical and clinical outcomes and benefits of recent immunotherapeutic approaches, which may help us further disclose the mechanisms of pancreatic cancer progression and the dialectical views of feasibility and effectiveness of immunotherapy in treatment of pancreatic cancer.

Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries.

Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.

Deactivation of the NLRP3 inflammasome in infiltrating macrophages by duodenal-jejunal bypass surgery mediates improvement of beta cell function in type 2 diabetes.

OBJECTIVE: Bariatric surgery could improve pancreatic beta cell function, thereby leading to the remission of the type 2 diabetes mellitus (T2DM). However, the specific mechanism underlying this phenomenon is yet to be revealed. The aim of this study is to test the hypothesis that Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in infiltrating macrophages plays an important role in the modulation of beta cell function after duodenal-jejunal bypass (DJB) surgery. METHODS: DJB and sham surgery were performed in diabetic Sprague-Dawley (SD) rats induced by high-fat diet (HFD) and streptozotocin (STZ). Body weight, food intake, and glucose tolerance test (GTT) were measured at indicated time points. Apoptosis of the beta cells was measured by Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) assay. We also assessed the macrophage content and NLRP3 expression in the rat model. Furthermore, macrophage reconstitution was performed after DJB surgery. Beta cell function and NLRP3 inflammasome pathway were re-evaluated in wild-type macrophage reconstitution group and NLRP3-knockdown macrophage reconstitution group. RESULTS: DJB surgery group rats displayed rapid and sustained improvement in glucose tolerance. Decreased apoptosis and improved secretion function of the beta cells were observed in DJB surgery group. NLRP3 inflammasome pathway in infiltrating macrophages was also suppressed after DJB surgery. Moreover, diabetic remission acquired by DJB sustained in NLRP3-knockdown macrophage reconstitution group, while extinguished in group reconstituted with wild-type macrophage. CONCLUSIONS: NLRP3 inflammasome deactivation in infiltrating macrophages is involved in marked beta cell function improvement after DJB surgery.

Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies.

There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this study, a systematic review and meta-analysis of prospective studies were performed in order to evaluate safety and effectiveness of neoadjuvant therapy in PC. Thirty-nine studies were selected (n = 1458 patients), with 14 studies focusing on patients with resectable disease (group 1), and 19 studies focusing on patients with borderline resectable and locally advanced disease (group 2). Neoadjuvant chemotherapy was administered in 97.4% of the studies, in which 76.9% was given radiotherapy and 74.4% administered with chemoradiation. The complete and partial response rate was 3.8% and 20.9%. The incidence of grade 3/4 toxicity was 11.3%. The overall resection rate after neoadjuvant therapy was 57.7% (group 1: 73.0%, group 2: 40.2%). The R0 resection rate was 84.2% (group 1: 88.2%, group 2: 79.4%). The overall survival for all patients was 16.79 months (resected 24.24, unresected 9.81; group 1: 17.76, group 2: 16.20). Our results demonstrate that neoadjuvant therapy has not been proven to be beneficial and should be considered with caution in patients with resectable PC. Patients with borderline resectable or locally advanced disease may benefit from neoadjuvant therapy, but further research is needed.

Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology.

Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide. Increasing evidence has confirmed the pivotal role of stromal components in the regulation of carcinogenesis, invasion, metastasis, and therapeutic resistance in PC. Interaction between neoplastic cells and stromal cells builds a specific microenvironment, which further modulates the malignant properties of cancer cells. Instead of being a "passive bystander", stroma may play a role as a "partner in crime" in PC. However, the role of stromal components in PC is complex and requires further investigation. In this article, we review recent advances regarding the regulatory roles and mechanisms of stroma biology, especially the cellular components such as pancreatic stellate cells, macrophages, neutrophils, adipocytes, epithelial cells, pericytes, mast cells, and lymphocytes, in PC. Crosstalk between stromal cells and cancer cells is thoroughly investigated. We also review the prognostic value and molecular therapeutic targets of stroma in PC. This review may help us further understand the molecular mechanisms of stromal biology and its role in PC development and therapeutic resistance. Moreover, targeting stroma components may provide new therapeutic strategies for this stubborn disease.

Effects of sleeve gastrectomy with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats.

AIM: To explore the effect of sleeve gastrectomy (SG) with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats. METHODS: Diabetic rats, which were induced by high-fat diet (HFD), nicotinamide and low-dose streptozotocin, underwent sham operations, SG, SG with jejuno-ileal loop (SG-JI) and SG with jejuno-jejunal loop (SG-JJ) followed by postoperative HFD. Then, at the time points of baseline and 2, 12 and 24 wk postoperatively, we determined and compared several variables, including the area under the curve for the results of oral glucose tolerance test (AUCOGTT), serum levels of triglyceride, cholesterol and ghrelin in fasting state, homeostasis model assessment of insulin resistance (HOMA-IR), body weight, calorie intake, glucagon-like peptide (GLP)-1 and insulin secretions after glucose gavage at dose of 1 g/kg. RESULTS: At 2 wk postoperatively, rats that underwent SG, SG-JJ and SG-JI, compared with sham-operated (SHAM) rats, demonstrated lower body weight, calorie intake and ghrelin (P < 0.05 vs SHAM), enhanced secretion of insulin and GLP-1 after glucose gavage (P < 0.05 vs SHAM), improved AUCOGTT, HOMA-IR, fasting serum triglyceride and cholesterol (AUCOGTT: 1616.9 ± 83.2, 837.4 ± 83.7, 874.9 ± 97.2 and 812.6 ± 81.9, P < 0.05 vs SHAM; HOMA-IR: 4.31 ± 0.54, 2.94 ± 0.22, 3.17 ± 0.37 and 3.41 ± 0.22, P < 0.05 vs SHAM; Triglyceride: 2.35 ± 0.17, 1.87 ± 0.23, 1.98 ± 0.30 and 2.04 ± 0.21 mmol/L, P < 0.05 vs SHAM; Cholesterol: 1.84 ± 0.21, 1.53 ± 0.20, 1.52 ± 0.20 and 1.46 ± 0.23 mmol/L). At 12 wk postoperatively, rats receiving SG-JJ and SG-JI had lower body weight, reduced levels of triglyceride and cholesterol and elevated level of GLP-1 compared to those receiving SG (P < 0.05 vs SG). At 24 wk after surgery, compared with SG, the advantage of SG-JJ and SG-JI for glucolipid metabolism was still evident (P < 0.05 vs SG). SG-JI had a better performance in lipid metabolism and GLP-1 secretion of rats than did SG-JJ. CONCLUSION: SG combined with intestinal loop induces better glycolipid metabolism than simple SG, with the lipid metabolism being more improved with SG-JI compared to SG-JJ.

Alterations in gut microbiota during remission and recurrence of diabetes after duodenal-jejunal bypass in rats.

AIM: To observe the alterations in gut microbiota in high-fat diet (HFD)-induced diabetes recurrence after duodenal-jejunal bypass (DJB) in rats. METHODS: We assigned HDF- and low-dose streptozotocin-induced diabetic rats into two major groups to receive DJB and sham operation respectively. When the DJB was completed, we used HFD to induce diabetes recurrence. Then, we grouped the DJB-operated rats by blood glucose level into the DJB-remission (DJB-RM) group and the DJB-recurrence (DJB-RC) group. At a sequence of time points after operations, we compared calorie content in the food intake (calorie intake), oral glucose tolerance test, homeostasis model assessment of insulin resistance (HOMA-IR), concentrations of glucagon-like peptide 1 (GLP-1), serum insulin, total bile acids (TBAs) and lipopolysaccharide (LPS) and alterations in colonic microbiota. RESULTS: The relative abundance of Firmicutes in the control (58.06% ± 11.12%; P < 0.05 vs sham; P < 0.05 vs DJB-RC) and DJB-RM (55.58% ± 6.16%; P < 0.05 vs sham; P < 0.05 vs DJB-RC) groups was higher than that in the sham (29.04% ± 1.36%) and DJB-RC (27.44% ± 2.17%) groups; but the relative abundance of Bacteroidetes was lower (control group: 33.46% ± 10.52%, P < 0.05 vs sham 46.88% ± 2.34%, P < 0.05 vs DJB-RC 47.41% ± 5.67%. DJB-RM group: 34.63% ± 3.37%, P < 0.05 vs sham; P < 0.05 vs DJB-RC). Escherichia coli was higher in the sham (15.72% ± 1.67%, P < 0.05 vs control, P < 0.05 vs DJB-RM) and DJB-RC (16.42% ± 3.00%; P < 0.05 vs control; P < 0.05 vs DJB-RM) groups than in the control (3.58% ± 3.67%) and DJB-RM (4.15% ± 2.76%) groups. Improved HOMA-IR (2.82 ± 0.73, P < 0.05 vs DJB-RC 4.23 ± 0.72), increased TBAs (27803.17 ± 4673.42 ng/mL; P < 0.05 vs DJB-RC 18744.00 ± 3047.26 ng/mL) and decreased LPS (0.12 ± 0.04 ng/mL, P < 0.05 vs DJB-RC 0.19 ± 0.03 ng/mL) were observed the in DJB-RM group; however, these improvements were reversed in the DJB-RC group, with the exception of GLP-1 (DJB-RM vs DJB-RC P > 0.05). CONCLUSION: Alterations in gut microbiota may be responsible for the diabetes remission and recurrence after DJB, possibly by influencing serum LPS and TBAs.

Lymph node ratio is an independent prognostic factor for patients after resection of pancreatic cancer.

BACKGROUND: The prognostic value of lymph node ratio (LNR) in pancreatic cancer remains controversial. In the current retrospective study, we assessed the value of LNR on predicting the survival of postoperative patients with pancreatic cancer. METHODS: Medical records of patients who underwent pancreatic resection for pancreatic cancer in the department of general surgery, Qilu Hospital, Shandong University were reviewed retrospectively. Demographic, clinicopathological, tumor-specific data, and histopathological reports were collected. Univariate and multivariate survival analyses were performed. RESULTS: A total of 83 patients with pancreatic cancer were collected. The mean number of examined LN was 8.2 ± 6.1 (0 to 26). Differential degree (low) (P = 0.019, hazard ratio (HR) = 2.276, 95% confidence interval (CI): 1.171 to 4.424) and LNR >0.2 (P = 0.018, HR = 2.685, 95% CI: 1.253 to 5.756) were independent adverse prognostic factors according to the multivariate survival analysis. CONCLUSIONS: Our study indicated that LNR >0.2 was an independent adverse prognostic factor for pancreatic cancer, which may provide important information for prognostic assessment.

Overexpression of nuclear ß-catenin in rectal adenocarcinoma is associated with radioresistance.

AIM: To investigate the association between nuclear ß-catenin overexpression in rectal adenocarcinoma and radioresistance. METHODS: A retrospective analysis was conducted. The analysis involved 136 patients with locally advanced rectal adenocarcinoma who underwent short-course preoperative radiotherapy and radical resection. The expression of ß-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry. The correlation of ß-catenin expression with radioresistance was evaluated using the tumor regression grading (TRG) system. The relationship between ß-catenin expression and clinicopathological characteristics was also analyzed. Univariate and logistic multivariate regression analyses were adopted to determine the independent factors of radioresistance. RESULTS: Nuclear ß-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma (57.6% vs 16.7%, P < 0.001). Nuclear ß-catenin was overexpressed in favor of poor TRG (≤ 2), whereas membrane ß-catenin was expressed in favor of good TRG (≥ 3). Nuclear ß-catenin expression in tumor cell differentiation (P = 0.018), lymph node metastasis (P = 0.022), and TRG (P < 0.001) showed significant differences. Univariate analyses demonstrated that radioresistance is associated with nuclear ß-catenin overexpression (P < 0.001). In addition, logistic multivariate regression analysis indicated that only three factors, namely, tumor size (P < 0.001), tumor cell differentiation (P < 0.001), and nuclear ß-catenin overexpression (P < 0.001), are associated with radioresistance. By using radioresistance as a prediction target, nuclear ß-catenin-based prediction alone achieved 83% accuracy, 65% sensitivity, and 88% specificity. CONCLUSION: Nuclear ß-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.

Expression of farnesyltransferase in primary liver cancer.

BACKGROUND: Primary liver cancer (PLC) is a common malignant tumor. Over the past decade, although farnesyltransferase (FTase) has emerged as a significant target for anticancer therapies and has become a hotspot of cancer research, its exact mechanism of action remains unknown. The aim of this study was to investigate the expression of FTase in PLC and its role in the development of PLC. METHODS: Expression of FTase was detected by real-time fluorescent quantitative-polymerase chain reaction (FQ-PCR) in cancer and surrounding normal tissues from 32 patients with PLC. RESULTS: Expression of FTase mRNA in PLC was significantly higher than that in normal hepatic tissues (P < 0.001). Overexpression of FTase was as high as 87.5%. The positive rate for FTase mRNA in the high tendency to metastatic recurrence group was obviously higher than that in the low tendency to metastatic recurrence group (P = 0.02). The positive rate for FTase mRNA in patients with metastatic recurrence during postoperative follow-up was also significantly higher than that in those without metastatic recurrence (P = 0.01). CONCLUSIONS: The level of FTase mRNA expression in cancer tissues is much higher than in normal tissues. FTase may play an important role in the genesis and development of PLC and may be one of the reliable markers for the metastatic activity gained by liver tumor cells. FTase could be used clinically in predicting metastatic recurrence of PLC.

Loss of membranous carcinoembryonic antigen-related cell adhesion molecule 1 expression is related to decreased relapse-free survival of hepatocellular carcinoma following liver transplantation.

BACKGROUND: Loss of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression is an adverse prognostic factor in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival (RFS) following liver transplantation (LT) for HCC. METHODS: Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed. RESULTS: Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum α-fetoprotein levels (all P < 0.05). Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis (P = 0.027). Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation (P = 0.037). CONCLUSION: Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.