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.

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.

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.

Resolution of diabetes mellitus by ileal transposition compared with biliopancreatic diversion in a nonobese animal model of type 2 diabetes.

BACKGROUND: It has been demonstrated that biliopancreatic diversion (BPD) and ileal transposition (IT) effectively induce weight loss and long-term control of type 2 diabetes in morbidly obese individuals. It is unknown whether the control of diabetes is better after IT or after BPD. The objective of this study was to investigate the effects of IT and BPD on the control of diabetes in an animal model. METHODS: We performed IT and BPD on 10- to 12-week-old Goto-Kakizaki rats with a spontaneous nonobese model of type 2 diabetes, and we performed a series of detection. The rats were observed for 24 weeks after surgery. RESULTS: Animals who underwent IT and BPD demonstrated improved glucose tolerance, insulin sensitivity and the secretion of glucagon-like peptide-1 compared with the sham-operated animals. Furthermore, IT resulted in a shorter duration of surgery and better postoperative recovery than BPD. CONCLUSION: This study provides strong evidence for the crucial role of the hindgut in the resolution of diabetes after duodenum-jejunum bypass or IT. We confirmed that IT was associated with better postoperative recovery than BPD and had a similar control of diabetes as BPD in nonobese animals with type 2 diabetes.

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.

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.

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).

Transumbilical single port laparoscopic cholecystectomy with a simple technique: initial experience of 33 cases.

Transumbilical single port laparoscopic cholecystectomy is a novel laparoscopic surgical technique for cholecystectomy utilizing only a transumbilical incision, which eliminates any visible abdominal scars and improves cosmesis. As the true single port laparoscopic technique, we presented an easy and feasible method for transumbilical laparoscopic cholecystectomy. A total of 33 patients were presented for transumbilical single port laparoscopic cholecystectomy. A 1.5 cm incision was made at the umbilicus. We used one sterile glove and designed a simple method for this procedure. All the operations were completed successfully. The operative time of the first case was 189 min, the average time of the following two cases was 90 min, and the mean of the latest ten cases was 50 min. Operative blood loss was <30 ml for all patients. No drainage tube was placed and no postoperative complications such as bleeding or biliary leakage occurred after three to six months of follow-up. All the patients were discharged 24h after the operation. There were no visible scars on the abdominal wall at the second weekend. Transumbilical single port laparoscopic cholecystectomy by our designed methods was technically simple, feasible and safe. Furthermore, development of newer instruments, accumulation of experience and enhancement of operative technique may facilitate this new operative approach.

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.

Endoscopic thyroidectomy by a modified anterior chest approach: a single institution's 5-year experience.

Endoscopic thyroidectomy embodies the features of both minimally invasive surgery and aesthetic surgery. However, none of the established approaches is minimally invasive and meanwhile maximally cosmetic. Here we applied a modified anterior chest approach to achieve excellent cosmesis with reduced physical invasion. Fifty-six patients with benign thyroid diseases accepted this procedure. A 10mm longitudinal incision was made about one-fourth of the distance from the xiphoid to the sternal notch. Bilateral transversal incisions (5mm and 10mm) were performed about one-third of the distance from the nipple to the sternoclavicular joint. The subfascial space was maintained with CO(2) insufflation. Endoscopic lobectomy or subtotal thyroidectomy was performed according to the diseases. Fifty-four of the 56 procedures were successfully performed endoscopically, including 41 unilateral lobectomies and 13 subtotal thyroidectomies. The mean operative time for uni- and bilateral procedures was 117.2 min and 184.5 min, respectively. Conversion occurred in two cases due to bleeding and malignant frozen section analysis, respectively. Postoperative complications included one temporary recurrent nerve palsy, one transient hypocalcemia, and one subcutaneous emphysema. 96.2%(50/52) of the patients were extremely satisfied or satisfied with the cosmetic effect. This procedure is more likely to be accepted by patients older than 30 years. Endoscopic thyroidectomy by the modified anterior chest approach is an effective procedure with both excellent aesthetic benefits and reduced physical injury.

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.

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.

Ileal transposition controls diabetes as well as modified duodenal jejunal bypass with better lipid lowering in a nonobese rat model of type II diabetes by increasing GLP-1.

OBJECTIVE: Modified duodenal jejunal bypass (MDJB) and ileal transposition (IT) were compared as surgeries for glucose control. Initial conclusions might be formed with respect to the possibility of (1) whether duodenal exclusion is essential for the control of diabetes and (2) application as a low morbid procedure. SUMMARY BACKGROUND DATA: IT, MDJB, sham-IT, and sham-MDJB procedures were performed on 10- to 12-week-old Goto-Kakizaki (GK) rats, nonobese animals who spontaneously develop type 2 diabetes. Rats were observed for 24 weeks after surgery. Glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose tolerance, insulin sensitivity, cholesterol, triglycerides, and free fatty acid levels were measured. RESULTS: MDJB and IT rats, when compared with sham-operated rats, showed reduced blood-glucose levels (P < 0.001); but IT- and MDJB did not differ from one another (P < 0.05). Compared with sham-operated rats, IT- and MDJB rats showed increased GLP-1 secretion (P < 0.01), with a more rapid and higher secretion in IT operated than in MDJB rats (P < 0.05). After 6 months, sham-operated rats weighed more than IT or MDJB rats (P < 0.01), but the weights of IT- and MDJB rats were similar to one another (P > 0.05). In terms of both operative time (P < 0.001) and postoperative recovery time (P < 0.001), MDJB took longer than did IT. CONCLUSION: In nonobese spontaneously diabetic rats, IT is equivalent to MDJB in terms of glucose control and weight secondary to significant increases of GLP-1. IT is faster to perform and yields a shorter recovery period than does MDJB.

Protective effects of ischaemic postconditioning on warm/cold ischaemic reperfusion injury in rat liver: a comparative study with ischaemic preconditioning.

BACKGROUND: Ischaemic reperfusion injury (IRI) is inevitable during major liver surgery. Ischaemic preconditioning (IPC) has been proven an effective intervention against hepatic IRI. Recently, it was demonstrated that ischaemic postconditioning (IPO) provided effective cardioprotection on IRI. We evaluated the protective effects of IPO on warm/cold IRI in rat liver by a comparison with IPC and assessed the role of apoptosis in the process. METHODS: Warm IRI model (clamping hepatic pedicle for 30 minutes) and cold IRI model (orthotopic liver transplantation with 2 hours cold storage) were established. Each model consisted of 3 groups: (1) control group, normal warm/cold IRI; (2) IPC group, 5 minutes of ischaemia followed by 5 minutes of reperfusion twice prior to warm/cold IRI; (3) IPO group, 30 seconds of reperfusion followed by 30 seconds of reocclusion for three times after warm/cold ischaemia. The levels of serum transaminase, glucose, and gamma glutamyltransferase (GGT) in bile, histopathological examination, apoptotic activity of hepatocyte, and apoptosis related protein Fas, at 3 hours after operation were compared. Survival rates one week after intervention were also compared. RESULTS: IPO and IPC protected the functions of hepatocytes and biliary epithelial cells, inhibited the hepatocellular apoptosis by preventing expression of Fas gene, and elevated the one week survival rate compared with control group in both models (P < 0.05). IPO and IPC groups were comparable in levels of serum transaminase levels, glucose, and GGT in bile, Fas positive expression index, and one week survival. In cold ischaemic models, IPO had lower apoptotic index than IPC (P < 0.05). CONCLUSION: Compared with ischaemic preconditioning, ischaemic postconditioning is associated with comparable protections of rat liver from warm or cold ischaemic reperfusion injury.

Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities.

BACKGROUND: WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present. METHODS: Reverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma. RESULTS: Compared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis). CONCLUSION: Expression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.

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.

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.

Hand-assisted laparoscopic splenectomy for splenomegaly: a comparative study with conventional laparoscopic splenectomy.

BACKGROUND: Laparoscopic splenectomy (LS) has been considered as the standard approach to remove a normal-sized spleen, but it is facing technical challenges when applied to splenomegaly. Hand-assisted laparoscopic technique was designed to facilitate the performance of difficult laparoscopic procedure. This study was aimed to evaluate the efficacy and superiority of hand-assisted laparoscopic splenectomy (HALS) for splenomegaly. METHODS: From November 1994 to January 2006, 36 patients with splenomegaly (final spleen weight > 700 g) were treated with laparoscopic operations for splenectomy in our hospital. Conventional LS was performed in 16 patients (7 men and 9 women, group 1) and HALS in the other 20 patients (12 men and 8 women, group 2). The patients' features, intraoperative details and the postoperative outcomes in the both groups were compared. RESULTS: The both groups were comparable in the terms of patient's age ((38 +/- 12) years vs (43 +/- 14)years, P > 0.05), the greatest splenic diameter ((24 +/- 5)cm vs (27 +/- 7)cm, P > 0.05), preoperative platelet count ((118 +/- 94) x 10(9)/L vs (97 +/- 81) x 10(9)/L, P > 0.05) and diagnosis. Compared with LS group, operation time ((195 +/- 71) minutes vs (141 +/- 64) minutes, P < 0.05) was shorter, intraoperative blood loss ((138 +/- 80)ml vs (86 +/- 45)ml, P < 0.05) and conversion rate (4/16 vs 0/20, P < 0.05) were lower, but hospital stay ((5.3 +/- 3.8) days vs (7.4 +/- 1.6) days, P < 0.05) was longer in HALS group. There was no significant difference in the aspects of intraoperative and postoperative complication rate (2/16 vs 0/20, P > 0.05) or recovery time of gastrointestinal function ((16.3 +/- 11.6) hours vs (18.7 +/- 8.1) hours, P > 0.05) between the two groups. CONCLUSIONS: In the cases of splenomegaly, HALS significantly facilitates the surgical procedure and reduces the operational risk, while maintaining the advantages of conventional LS. HALS is more feasible and more effective than conventional LS for the removal of splenomegaly.