Short-term outcomes of totally robotic versus robotic-assisted distal gastrectomy for gastric cancer: a single-center retrospective study.

BACKGROUND: Totally robotic distal gastrectomy (TRDG) is being used more and more in gastric cancer (GC) patients. The study aims to evaluate the short-term efficacy of TRDG and robotic-assisted distal gastrectomy (RADG) in the treatment of GC. METHODS: We retrospectively collected the clinical data of patients who underwent TRDG or RADG, of which 60 patients were included in the study: 30 cases of totally robotic and 30 cases of robotic-assisted. The short-term efficacy of the two groups was compared. RESULTS: There was no significant difference in the clinicopathological data between the two groups. Compared to RADG, TRDG had less intraoperative blood loss(P = 0.019), less postoperative abdominal drainage(P = 0.031), shorter time of exhaust( P = 0.001) and liquid diet(P = 0.001), shorter length of incision(P<0.01), shorter postoperative hospital stays(P = 0.033), lower postoperative C-reactive protein(CRP)(P = 0.024) and lower postoperative Visual Analogue Scale(VAS) scores(P = 0.048). However, no significant statistical differences were found in terms of total operation time(P = 0.108), number of lymph nodes retrieved(P = 0.307), time for anastomosis(P = 0.450), proximal resection margin(P = 0.210), distal resection margin(P = 0.202), postoperative complication(P = 0.506), total hospital cost(P = 0.286) and postoperative white blood cell(WBC)(P = 0.113). CONCLUSIONS: In terms of security and technology, TRDG could serve as a better treatment method for GC.

Robotic natural orifice specimen extraction surgery I-type F method vs conventional robotic resection for lower rectal cancer.

BACKGROUND: Robotic resection using the natural orifice specimen extraction surgery I-type F method (R-NOSES I-F) is a novel minimally invasive surgical strategy for the treatment of lower rectal cancer. However, the current literature on this method is limited to case reports, and further investigation into its safety and feasibility is warranted. AIM: To evaluate the safety and feasibility of R-NOSES I-F for the treatment of low rectal cancer. METHODS: From September 2018 to February 2022, 206 patients diagnosed with low rectal cancer at First Affiliated Hospital of Nanchang University were included in this retrospective analysis. Of these patients, 22 underwent R-NOSES I-F surgery (R-NOSES I-F group) and 76 underwent conventional robotic-assisted low rectal cancer resection (RLRC group). Clinicopathological data of all patients were collected and analyzed. Postoperative outcomes and prognoses were compared between the two groups. Statistical analysis was performed using SPSS software. RESULTS: Patients in the R-NOSES I-F group had a significantly lower visual analog score for pain on postoperative day 1 (1.7 ± 0.7 vs 2.2 ± 0.6, P = 0.003) and shorter postoperative anal venting time (2.7 ± 0.6 vs 3.5 ± 0.7, P < 0.001) than those in the RLRC group. There were no significant differences between the two groups in terms of sex, age, body mass index, tumor size, TNM stage, operative time, intraoperative bleeding, postoperative complications, or inflammatory response (P > 0.05). Postoperative anal and urinary functions, as assessed by Wexner, low anterior resection syndrome, and International Prostate Symptom Scale scores, were similar in both groups (P > 0.05). Long-term follow-up revealed no significant differences in the rates of local recurrence and distant metastasis between the two groups (P > 0.05). CONCLUSION: R-NOSES I-F is a safe and effective minimally invasive procedure for the treatment of lower rectal cancer. It improves pain relief, promotes gastrointestinal function recovery, and helps avoid incision-related complications.

Enhanced glucose homeostasis via Clostridium symbiosum-mediated glucagon-like peptide 1 inhibition of hepatic gluconeogenesis in mid-intestinal bypass surgery.

BACKGROUND: The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood. AIM: To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism. METHODS: Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor. RESULTS: The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus, Clostridium symbiosum, Ruminococcus gnavus, and Bilophila. Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota. CONCLUSION: The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.

Differences in metabolic improvement after metabolic surgery are linked to the gut microbiota in non-obese diabetic rats.

BACKGROUND: Different metabolic/bariatric surgery approaches vary in their effect on weight loss and glucose levels, although the underlying mechanism is unclear. Studies have demonstrated that the gut microbiota might be an important mechanism of improved metabolism after metabolic/bariatric surgery. AIM: To investigate the relationship between the improvement in metabolic disturbances and the changes in gut microbiota after gastric or intestinal bypass. METHODS: We performed sleeve gastrectomy (SG), distal small intestine bypass (DSIB) or sham surgery in nonobese rats with diabetes induced by 60 mg/kg streptozotocin (STZ-DM). RESULTS: The group comparisons revealed that both SG and DSIB induced a reduction in body weight and significant improvements in glucose and lipid metabolism in the STZ-DM rats. Furthermore, DSIB exhibited a stronger glucose-lowering and lipid-reducing effect on STZ-DM rats than SG. 16S ribosomal RNA gene sequencing revealed the gut abundance of some Lactobacillus spp. increased in both the SG and DSIB groups after surgery. However, the DSIB group exhibited a more pronounced increase in the gut abundance of Lactobacillus spp. compared to the SG group, with more Lactobacillus spp. types increased in the gut. CONCLUSION: The gut abundance of Lactobacillus was significantly correlated with the improvement in glycolipid metabolism and the change in serum fibroblast growth factor 21 levels.

The Role of Bile Acid in Improving Glucose Tolerance of Non-Obese Diabetic Rats After Proximal Small Bowel Bypass.

An increase in bile acid (BA) levels after metabolic surgery is an important mechanism for improving glucose metabolism. However, the mechanisms underlying elevated BA levels and the regulatory mechanism of glucose metabolism remain unclear. In this study, we used the Goto-Kakizaki rat model to investigate the mechanism of BA elevation by comparing side-to-side jejunoileal bypass plus proximal loop ligation (SSJIBL) and bile ileum diversion (BID) as well as to explore the mechanism of BA metabolism in regulating blood glucose. The results showed that the fed blood glucose of rats in both the SSJIBL and BID groups was significantly lower than that of the SHAM group on days 2 and 14 after the operation. The oral glucose tolerance test (OGTT) improved in the SSJIBL and BID groups at day 14 postoperatively. The expression of CYP27A1 in the livers of the SSJIBL and BID groups was significantly increased. In addition, total serum BA levels in the SSJIBL and BID groups were significantly increased. Moreover, serum levels of lithocholic acid (LCA) and deoxycholic acid (DCA) were significantly higher in the SSJIBL group than in the SHAM group and negatively correlated with the area under the glucose tolerance curve (AUC-OGTT). In conclusion, increased BA synthesis may be an important cause of elevated total serum BA levels, and LCA and DCA are closely associated with improved glucose metabolism.

Bypassing Different Parts of the Small Intestine Determines Different Metabolic Effects in Streptozotocin-Induced Diabetic Rats.

PURPOSE: Side-to-side jejunoileal bypass with proximal loop ligation (SSJIBL) has significant glucose-lowering and weight-control effects; however, no study has elucidated which segment is most effective in SSJIBL. This study investigated the effect of proximal small intestinal bypass (PSIB), middle small intestinal bypass (MSIB), and distal small intestinal bypass (DSIB) on metabolic improvement in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: STZ-induced diabetic rats were divided into four groups: PSIB, MSIB, DSIB, and sham-operated. The primary outcome measures were body weight, food intake, fasting blood glucose (FBG) levels, oral glucose tolerance (OGTT), insulin tolerance (ITT), serum insulin, gut hormones, serum lipid profile, and liver function levels. RESULTS: Global body weight in the DSIB group was lower than that in the PSIB group. The global food intake in the PSIB group was lower than that in the MSIB group. The PSIB group had a slightly better glucose-lowering effect than the MSIB and DSIB groups. The PSIB, MSIB, and DSIB groups all had improvement in insulin sensitivity at postoperative week 6. The MSIB group exhibited the best improvement in lipid homeostasis. Serum insulin and leptin levels were higher, and serum ghrelin levels were lower in the operated groups than in the sham group. CONCLUSIONS: This study provides experimental evidence that PSIB surgery induces a better glucose-lowering effect than DSIB surgery, and MSIB induced the best improvement in lipid homeostasis, whereas DSIB was even more advantageous in terms of weight control in the STZ-induced diabetic rat model.

Conserved Mitotic Phosphorylation of a Proteasome Subunit Regulates Cell Proliferation.

Reversible phosphorylation has emerged as an important mechanism for regulating proteasome function in various physiological processes. Essentially all proteasome phosphorylations characterized thus far occur on proteasome holoenzyme or subcomplexes to regulate substrate degradation. Here, we report a highly conserved phosphorylation that only exists on the unassembled α5 subunit of the proteasome. The modified residue, α5-Ser16, is within a SP motif typically recognized by cyclin-dependent kinases (CDKs). Using a phospho-specific antibody generated against this site, we found that α5-S16 phosphorylation is mitosis-specific in both yeast and mammalian cells. Blocking this site with a S16A mutation caused growth defect and G2/M arrest of the cell cycle. α5-S16 phosphorylation depends on CDK1 activity and is highly abundant in some but not all mitotic cells. Immunoprecipitation and mass spectrometry (IP-MS) studies identified numerous proteins that could interact with phosphorylated α5, including PLK1, a key regulator of mitosis. α5-PLK1 interaction increased upon mitosis and could be facilitated by S16 phosphorylation. CDK1 activation downstream of PLK1 activity was delayed in S16A mutant cells, suggesting an important role of α5-S16 phosphorylation in regulating PLK1 and mitosis. These data have revealed an unappreciated function of "exo-proteasome" phosphorylation of a proteasome subunit and may bring new insights to our understanding of cell cycle control.

The role of gut microbiota and amino metabolism in the effects of improvement of islet ß-cell function after modified jejunoileal bypass.

The change in gut microbiota is an important mechanism of the amelioration of type 2 diabetes mellitus (T2DM) after bariatric surgery. Here, we observe that the modified jejunoileal bypass effectively decreases body weight gain, fasting blood glucose, and lipids level in serum; additionally, islet ß-cell function, glucose tolerance, and insulin resistance were markedly ameliorated. The hypoglycemic effect and the improvement in islet ß-cell function depend on the changes in gut microbiota structure. modified jejunoileal bypass increases the abundance of gut Escherichia coli and Ruminococcus gnavus and the levels of serum glycine, histidine, and glutamine in T2DM rats; and decreases the abundance of Prevotella copri and the levels of serum branched chain amino acids, which are significantly related to the improvement of islet ß-cell function in T2DM rats. Our results suggest that amino acid metabolism may contribute to the islet ß-cell function in T2DM rats after modified jejunoileal bypass and that improving gut microbiota composition is a potential therapeutic strategy for T2DM.

CRL4DCAF2 is required for mature T-cell expansion via Aurora B-regulated proteasome activity.

The proliferation of T cells in peripheral lymphoid tissues requires T cell receptor (TCR)-mediated cell cycle entry. However, the underlying mechanism regulating cell cycle progression in mature T cells is incompletely understood. Here, we have identified an E3 ubiquitin ligase, CRL4DCAF2, as a critical mediator controlling M phase exit in activated T cells. DCAF2 expression is induced upon TCR stimulation and its deficiency attenuates T cell expansion. Additionally, DCAF2 T cell-specific knockout mice display impaired peripheral T cell maintenance and reduced severity of various autoimmune diseases. Continuous H4K20me1 modification caused by DCAF2 deficiency inhibits the induction of Aurkb expression, which regulates 26S proteasome activity during G2/M phase. CRL4DCAF2 deficiency causes M phase arrest through proteasome-dependent mechanisms in peripheral T cells. Our findings establish DCAF2 as a novel target for T cell-mediated autoimmunity or inflammatory diseases.

Rapid Improvement in Diabetes After Simple Side-to-side Jejunoileal Bypass Surgery: Does It Need a Ligation or Not?

BACKGROUND: Dual-path side-to-side jejunoileal bypass (SSJIB) can markedly ameliorate diabetes and obesity. However, whether SSJIB requires the ligation of the bypassed loop (single-path) and what is the most appropriate length of the bypassed small bowel remain unknown. The aim of this study was to evaluate the role of ligation and the length of the bypassed small bowel in mediating changes in glucose homeostasis after SSJIB in streptozotocin (STZ)-induced diabetic rats. METHODS: Fourteen STZ-induced diabetic rats were randomized into two groups: one group was subjected to 50% SSJIB (SSJIB-50 group) and one group was subjected to sham surgery (sham group). Three weeks later, the SSJIB-50 group was re-operated, and the bypassed segment was ligated (SSJIBL-50 group). Three weeks later, the SSJIBL-50 group was operated again, and 60% of the length of the proximal small intestine was bypassed (SSJIBL-60 group). The measured primary outcomes were body weight, food intake, fasting blood glucose (FBG), and oral glucose tolerance test (OGTT). RESULTS: Body weight in the SSJIBL-60 group was lower than that in the sham group. Food intakes in the SSJIBL-50 and SSJIBL-60 groups were lower than that in the sham group. FBG and OGTT were not improved in the SSJIB-50 group compared with the sham group. However, FBG and OGTT were improved in the SSJIBL-50 group and were further improved in the SSJIBL-60 group. CONCLUSIONS: Ligation of the first portion of the bypassed loop is essential to SSJIB, and bypassing approximately 60% of the small intestine length may be appropriate in SSJIBL.

A rational approach to enhancing antibody Fc homodimer formation for robust production of antibody mixture in a single cell line.

Combinations of different antibodies have been shown to be more effective for managing certain diseases than monotherapy. Co-expression of the antibody mixture in a single cell line is key to reducing complexity during antibody development and manufacturing. However, co-transfection of multiple light and heavy chains into cells often leads to production of mismatched, heterodimeric by-products that are inactive, making the development of co-expression systems that robustly and efficiently produce highly active antibody mixtures a high priority. In this study, we modified the CH3 domain interface of the antibody fragment crystallizable (Fc) region by changing several charge pairs to create electrostatic interactions favoring Fc homodimer formation and disfavoring Fc heterodimer formation. When co-expressed, these modified antibodies with altered charge polarity across the Fc dimer interface preferentially formed homodimers that fully preserved the functions of each component, rather than inactive heterodimers whose formation was reduced because of rationally designed repulsive interactions. We designed eight different combinations and experimentally screened the best one, which enabled us to produce a binary antibody mixture against the EGF receptor with a minimal heterodimer contaminant. We further determined the crystal structure of a triple-mutated Fc variant in the best combination, and we elucidated the molecular interactions favoring Fc homodimer over heterodimer formation, which provided a structural basis for further optimization. The approach presented here demonstrates the feasibility of rational antibody modification for efficient and consistent production of monoclonal antibody mixtures in a single cell line and thus broadens our options for manufacturing more effective antibody-based therapeutic agents.

Small Intestinal Bypass Induces a Persistent Weight-Loss Effect and Improves Glucose Tolerance in Obese Rats.

BACKGROUND: This study investigated the role of proximal small intestinal bypass (PSIB) and distal small intestinal bypass (DSIB) as well as their long-term effects on weight loss and glucose metabolism in high-sugar and high-fat diet-induced obese rats. METHODS: Sprague-Dawley rats were divided into four groups: PSIB, bypassing 60% of the proximal small intestine length; DSIB, bypassing 60% of the distal small intestine length; sham-operated (Sham) animals; and control animals. All rats were fed a high-sugar and high-fat diet after surgery. The primary outcome measures were body weight, food intake, fasting blood glucose (FBG) levels, oral glucose tolerance test (OGTT), and the insulin tolerance test (ITT). RESULTS: Global body weight (BW) and food intake in the PSIB and DSIB groups were lower than those in the Sham group at postoperative week 2. BW and food intake in the PSIB group were lower than those in the DSIB group at postoperative week 24. The PSIB and DSIB groups exhibited improvement in glucose tolerance at postoperative weeks 4, 8, and 24. The PSIB and DSIB groups exhibited improvement in FBG at postoperative week 24, and only the DSIB group exhibited improvement in insulin sensitivity. CONCLUSIONS: This study provides experimental evidence that PSIB surgery induced a better and more persistent weight loss effect than DSIB surgery and that the two types of intestinal bypass surgeries yielded equivalent and stable long-term improvement in glucose tolerance in an obese rat model.

Side-to-Side Jejunoileal Bypass Induces Better Glucose-Lowering Effect than End-to-Side Jejunoileal Bypass on Nonobese Diabetic Rats.

BACKGROUND: Jejunoileal bypass (JIB) can markedly ameliorate diabetes in obese patients and rodents. The aim of this study is to systematically evaluate the role of the operational manner and the retained distal small bowel length in mediating changes in glucose homeostasis after intestinal bypass surgeries in nonobese diabetic rats. METHODS: Streptozotocin-induced diabetic rats underwent side-to-side jejunoileal bypass plus proximal loop ligation (SSJIBL), end-to-side jejunoileal bypass (ESJIB), proximal small bowel resection (PBR), and sham operation. Each operational manner included two subgroups, in which 30 cm (L-30) or 40 cm (L-40) distal small bowel was retained. Main outcome measures were fasting blood glucose levels (FBG), insulin sensitivity, serum insulin, glucagon-like peptide-1 (GLP-1), bilirubin (BIL), and total bile acids (TBA) levels. RESULTS: Global food intake in the sham group was higher than in the operation groups, and global body weight and food intake in the SSJIBL group were higher than in the ESJIB and PBR groups. Global body weight and food intake in L-40 group were higher than in L-30 group. The SSJIBL procedure induced better improvement in glucose homeostasis and insulin sensitivity than the ESJIB and PBR procedures, and L-30 group showed better antidiabetic effects than L-40 group. Serum GLP-1, BIL, and TBA levels in SSJIBL group were higher than in ESJIB and PBR groups. CONCLUSIONS: This study shows that side-to-side jejunoileal bypass induced better glucose-lowering effects than end-to-side jejunoileal bypass and proximal small bowel resection, and intestinal bypass surgery that retained shorter distal small bowel yielded better antidiabetic effects.

Mid to distal small bowel resection with the preservation of the terminal ileum improves glucose homeostasis in diabetic rats by activating the hindgut-dependent mechanism.

BACKGROUND: The aim of this study was to develop a novel surgical model to test the "hindgut hypothesis" and thereby study the role of the gut in glucose homeostasis and the mechanism of action of bariatric surgery. METHOD: Sprague-Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid to distal small bowel resection with the preservation of the terminal ileum (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation only) groups. Rats were observed for 12 weeks after the operation. The main outcome measures were weight, food intake, non-fasting glucose, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum bile acids, and lipid profile. RESULT: The DBRPI and sham groups exhibited no difference in weight and food intake after surgery. When compared to the sham controls, the DBRPI group displayed an improvement in non-fasting glucose, oral glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks postoperation; furthermore, DBRPI resulted in higher serum levels of triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and lower free fatty acid level at 12 weeks. CONCLUSIONS: This study provides strong evidences for the key role of hindgut in the amelioration of diabetes after bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and effective surgical model for testing the "hindgut hypothesis" and focused study of biliary enterohepatic recycling in the context of bariatric operations.