Duodenal-jejunal bypass increases intraduodenal bile acids and upregulates duodenal SIRT1 expression in high-fat diet and streptozotocin-induced diabetic rats.

BACKGROUND: The mechanisms underlying diabetes remission after duodenal-jejunal bypass (DJB) remain elusive. In DJB surgery, the duodenum is excluded. However, the duodenum has emerged as an important regulator of glucose homeostasis, and elevated duodenal SIRT1 leads to improved hepatic insulin sensitivity. After DJB, bile acids (BAs) in the duodenum are not mixed and diluted by the ingested food. And activation of BA receptors promotes SIRT1 expression in many tissues. We hypothesized that BA-mediated upregulation of SIRT1 may contribute to diabetic control after DJB. AIM: To investigate the surgical effects of DJB on duodenal SIRT1 expression and uncover the potential crosslinks between BAs and SIRT1. METHODS: Twenty diabetic rats were randomly allocated to the sham (n = 10) and DJB (n = 10) groups. Body weight, food intake, fasting blood glucose (FBG), serum and intraduodenal total BA (TBA) levels were measured accordingly. Oral glucose tolerance test (OGTT) and intraperitoneal pyruvate tolerance test (ipPTT) were performed to evaluate the effects of surgeries on systemic glucose disposal and hepatic gluconeogenesis. The key genes of BA signaling pathway in the duodenal mucosa, including farnesoid X receptor (FXR), small heterodimer partner (SHP), and Takeda G-protein-coupled receptor 5 (TGR5) were evaluated by real-time quantitative polymerase chain reaction 8 wk postoperatively. The duodenal SIRT1, AMPK, and phosphorylated AMPK (p-AMPK) levels were evaluated by western blotting. Rat small intestine epithelial IEC-6 cells were treated with GW4064 and INT-777 to verify the effects of BAs on SIRT1 expression in enterocytes. RESULTS: The DJB group exhibited body weight and food intake comparable to those of the sham group at all postoperative time points. The FBG level and area under the curve for the OGTT and ipPTT were significantly lower in the DJB group. The DJB group exhibited higher fasting and postprandial serum TBA levels than the sham group at both 2 and 8 wk postoperatively. At 8 wk after surgery, the DJB group showed higher intraluminal TBA concentration, upregulated mRNA expression of FXR and SHP, and elevated protein expression of SIRT1 and p-AMPK in the descending and horizontal segments of the duodenum. Activation of FXR and TGR5 receptors by GW4064 and INT-777 increased the mRNA and protein expression of SIRT1 and promoted the phosphorylation of AMPK in IEC-6 cells. CONCLUSION: DJB elevates intraduodenal BA levels and activates the duodenal BA signaling pathway, which may upregulate duodenal SIRT1 and further contribute to improved glucose homeostasis after DJB.

Low-pressure pneumoperitoneum with abdominal wall lift in laparoscopic total mesorectal excision for rectal cancer: Initial experience.

AIM: To evaluate the safety and feasibility of a new technology combining low-pressure pneumoperitoneum (LPP) and abdominal wall lift (AWL) in laparoscopic total mesorectal excision (TME) for rectal cancer. METHODS: From November 2015 to July 2017, 26 patients underwent laparoscopic TME for rectal cancer using LPP (6-8 mmHg) with subcutaneous AWL in Qilu Hospital of Shandong University, Jinan, China. Clinical data regarding patients' demographics, intraoperative monitoring indices, operation-related indices and pathological outcomes were prospectively collected. RESULTS: Laparoscopic TME was performed in 26 cases (14 anterior resection and 12 abdominoperineal resection) successfully, without conversion to open or laparoscopic surgery with standard-pressure pneumoperitoneum. Intraoperative monitoring showed stable heart rate, blood pressure and paw airway pressure. The mean operative time was 194.29 ± 41.27 min (range: 125-270 min) and 200.41 ± 20.56 min (range: 170-230 min) for anterior resection and abdominoperineal resection, respectively. The mean number of lymph nodes harvested was 16.71 ± 5.06 (range: 7-27). There was no positive circumferential or distal resection margin. No local recurrence was observed during a median follow-up period of 11.96 ± 5.55 mo (range: 5-23 mo). CONCLUSION: LPP combined with AWL is safe and feasible for laparoscopic TME. The technique can provide satisfactory exposure of the operative field and stable operative monitoring indices.

LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway.

Pancreatic cancer (PC) remains one of the most lethal malignant tumors; early distant metastasis commonly results in poor prognosis. Recent studies confirmed the pivotal role of the long non-coding RNAs (lncRNAs) in tumorigenesis and metastasis of malignant tumors, including PC. However, little is known about the role of LincRNA-ROR (linc-ROR) in PC. In the present study, we found that linc-ROR was upregulated in PC tissues. Overexpression of linc-ROR promoted cells proliferation, migration, invasion and metastasis both in vitro and in a mouse model. Contrarily, knockdown of linc-ROR attenuated proliferation, invasion and distant metastasis. Mechanistically, we confirmed that linc-ROR up-regulates ZEB1 and then induces epithelial-mesenchymal transition (EMT), which promotes the aggressive biological behaviors of PC. Together, these results indicate that linc-ROR acts as an important regulator of ZEB1, can promote invasion and metastasis in PC, and may represent a novel therapeutic target.