Impact of bariatric surgery on glucose and lipid metabolism and liver and kidney function in food-induced obese diabetic rats

BACKGROUND Obesity usually causes diabetes mellitus(DM)and is a serious danger to human health.Type 2 DM(T2DM)mostly occurs along with obesity.Foodborne obesityinduced DM is caused by an excessive long-term diet and surplus energy.Bariatric surgery can improve the symptoms of T2DM in some obese patients.But different types of bariatric surgery may have different effects.AIM To investigate the effect of bariatric surgery on glucose and lipid metabolism and liver and kidney function in rats.METHODS Male Sprague-Dawley rats aged 6-8 wk underwent Roux-en-Y gastric bypass surgery(RYGB),sleeve gastrectomy(SG),or gastric banding(GB).Glucose and insulin tolerance tests,analyses of biochemical parameters,histological examination,western blot,and quantitative real-time polymerase chain reaction were conducted.RESULTS In comparison to the sham operation group,the RYGB,SG,and GB groups had decreased body weight and food intake,reduced glucose intolerance and insulin insensitivity,downregulated biochemical parameters,alleviated morphological changes in the liver and kidneys,and decreased levels of protein kinase Cβ/P66shc.The effect in the RYGB group was better than that in the SG and GB groups.CONCLUSION These results suggest that RYGB,SG and GB may be helpful for the treatment of foodborne obesity-induced DM.

Prognostic value of number of examined lymph nodes in patients with node-negative gastric cancer

AIM:To elucidate the potential impact of examined lymph nodes(eLNs)on long-term survival of nodenegative gastric cancer patients after curative surgery.METHODS:A total of 497 node-negative gastric cancer patients who underwent curative gastrectomy between January 2000 and December 2008 in our center were enrolled in this study.Patients were divided into4 groups according to eLNs through cut-point analysis.Clinicopathological features were compared between≤15 eLNs group and>15 eLNs group and potential prognostic factors were analyzed.The Log-rank test was used to assess statistical differences between the groups.Independent prognostic factors were identifiedusing the Cox proportional hazards regression model.Stratified analysis was performed to investigate the impact of eLNs on patient survival in each stage.Overall survival was also compared among the four groups.Finally,we explored the recurrent sites associated with eLNs.RESULTS:Patients with eLNs>15 had a better survival compared with those with eLNs≤15 for the entire cohort.By the multivariate survival analysis,we found that the depth of invasion and the number of eLNs were the independent predictors of overall survival(OS)of patients with node-negative gastric cancer.According to the cut-point analysis,T2-T4 patients with 11-15 eLNs had a significantly longer mean OS than those with 4-10 eLNs or 1-3 eLNs.Patients with≤15 eLNs were more likely to experience locoregional and peritoneal recurrence than those with>15eLNs.CONCLUSION:Number of eLNs could predict the prognosis of node-negative gastric cancer,and dissection of>15 eLNs is recommended during lymphadenectomy so as to improve the long-term survival.

Prolonged overall survival in gastric cancer patients after adoptive immunotherapy

AIM:To assess the efficacy of immunotherapy with expanded activated autologous lymphocytes(EAALs) in gastric cancer.METHODS:An observational study was designed to retrospectively analyze the clinical data of 84 gastric cancer patients,of whom 42 were treated by EAAL immunotherapy plus conventional treatment and another 42 only received conventional treatment(control group).EAALs were obtained by proliferation of peripheral blood mononuclear cells from patients followed by phenotype determination.Clinical data including age,gender,clinical stage,chemotherapeutic regimens,hospitalization,surgical,radiotherapy,and survival data were collected along with EAAL therapy details and side effects.Patients were followed and the relationship between treatment and overall survival(OS) data obtained for the immunotherapy and control groups were compared retrospectively.The safety of EAAL immunotherapy was also evaluated.RESULTS:After in vitro culture and proliferation,the percentages of CD3+,CD3+CD8+,CD8+CD27+,CD8+CD28+,and CD3+CD16+/CD56+cells increased remarkably(P < 0.05),while the percentages of CD3+CD4+,CD4+CD25+,and CD3-CD16+/CD56+(natural killer cells) were overtly decreased(P < 0.05); no significant change was observed in CD4+CD25+CD127- cells(P =0.448).Interestingly,OS in the immunotherapy group was significantly higher than that in the control group,with 27.0 and 13.9 mo obtained for the two groups,respectively(P =0.028,HR =0.573,95%CI:0.347-0.945).These findings indicated a 42.7% decrease in the risk of death.In addition,we found that clinical stage and application of EAAL immunotherapy wereindependent prognostic factors for gastric cancer patients.Indeed,the OS in stage Ⅲc and Ⅳ patients that had received surgery was prolonged after EAAL immunotherapy(P < 0.05).Importantly,in vitro induction and proliferation of EAAL were easy and biologically safe.CONCLUSION:Overall,EAAL adoptive immunotherapy might prolong the OS in gastric cancer patients.

New insight of obesity-associated NAFLD: Dysregulated “crosstalk” between multi-organ and the liver?

Obesity plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanism for the pathogenesis of obesity-associated NAFLD remains largely obscure. Although the “multiple hit” theory provides a more accurate explanation of NAFLD pathogenesis, it still cannot fully explain precisely how obesity causes NAFLD. The liver is the key integrator of the body's energy needs, receiving input from multiple metabolically active organs. Thus, recent studies have advocated the “multiple crosstalk” hypothesis, highlighting that obesity-related hepatic steatosis may be the result of dysregulated “crosstalk” among multiple extra-hepatic organs and the liver in obesity. A wide variety of circulating endocrine hormones work together to orchestrate this “crosstalk”. Of note, with deepening understanding of the endocrine system, the perception of hormones has gradually risen from the narrow sense (i.e. traditional hormones) to the broad sense of hormones as organokines and exosomes. In this review, we focus on the perspective of organic endocrine hormones (organokines) and molecular endocrine hormones (exosomes), summarizing systematically how the two types of new hormones mediate the dialogue between extra-hepatic organs and liver in the pathogenesis of obesity-related NAFLD.