Research progress of small molecule modulators targeting Toll-like receptor 2 / 药学学报

Toll like receptors (TLRs) are the earliest discovered natural immune pattern recognition receptors (PRRs). The abnormality of TLR signal transduction pathway is the key factor leading to chronic inflammatory, cancer, nervous system disease and cardiovascular diseases. The development of TLR agonists and inhibitors has attracted much attention. Currently known TLR2 agonists, such as lipopeptides or their derivatives, have certain limitations in drug development due to their difficult synthesis, easy hydrolysis, and triggering inflammatory cytokine storms, while inhibitors have been rarely reported. New small molecule TLR2 agonists or inhibitors with higher stability are more likely to be developed as tumor immunotherapy or anti-inflammatory drugs.

Clinical application of reverse puncture device(RPD) in laparascopic esophagogastrectomy (esophagojejunostomy): a report of 18 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>The authors report the newly developed reconstruction technique after laparoscopic total gastrectomy (LTG) or laparoscopic distal gastrectomy (LDG): intracorporeal circular stapling esophagojejunostomy(esophagojejunostomy) using the reverse puncture device(RPD).</p><p><b>METHODS</b>After LTG or LDG, The anvil is then transorally inserted into the esophagus by using the RPD system. Double-stapling esophagojejunostomy with a circular stapler is performed intracorporeally, and the jejunal stump is closed with an Echelon.</p><p><b>RESULTS</b>There was no intraoperative complication or conversion to open surgery, the mean operation time was 155 min and blood loss was 75 ml. Postoperative fluorography revealed no anastomosis leakage or stenosis Patients resumed an oral liquid diet on postoperative day 2, and discharged at day 8.</p><p><b>CONCLUSIONS</b>We have successfully performed LTG or LDG, reconstruction using our technique in 18 patients without any anastomosis complications. We believe that our procedure is a safe and reliable reconstruction method, which is especially useful in obese patients, in whom conventional extracorporeal anastomosis is often difficult.</p>

Impacts of laparoscopic bariatric surgery on GLP-1 and Ghrelin level in patients with type 2 diabetes mellitus / 中华外科杂志

<p><b>OBJECTIVES</b>To investigate the impacts of laparoscopic bariatric surgery on fasting glucagon-like peptide-1 (GLP-1) and Ghrelin level in patients with type 2 diabetes mellitus (T2DM), and the mechanism in surgical treatment of T2DM.</p><p><b>METHODS</b>From March 2010 to August 2011, 44 patients with T2DM underwent laparoscopic bariatric, including laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 14), laparoscopic mini-gastric bypass (LMGB, n = 11), laparoscopic sleeve gastrectomy (LSG, n = 9) and laparoscopic adjustable gastric banding (LAGB, n = 10). The curative effects, changes of metabolism and gastrointestinal hormones were analyzed respectively.</p><p><b>RESULTS</b>Within 6 months after surgery, the clinical complete remission of T2DM was 11, 8, 6, 3 cases in LRYGB, LMGB, LSG, LAGB group respectively; the clinical partial remission was 3, 3, 2, 4 cases respectively. The inefficacy was 1, 3 patients in LSG and LAGB group respectively. The effects of surgery within 6 months postoperative among 4 groups were different (χ(2) = 8.162, P < 0.05). The levels of body mass index (F = 275.29) and homeostasis model assessment of insulin resistance (F = 40.09) of 4 groups were declined in 6 months postoperatively (P < 0.01). The extents of decrease were no significance among 4 groups. Compared to preoperative level, GLP-1 in LRYGB ((116 ± 33) vs. (66 ± 20) ng/L and LMGB group ((103 ± 22) vs. (65 ± 16) ng/L) was higher in the first month after surgery (F = 21.76 and 139.21, P < 0.05). The changes in LSG and LAGB group were no significance (P > 0.05). The level of Ghrelin in LRYGB, LMGB, LSG group at the first week after surgery were (208 ± 79), (275 ± 102) and (258 ± 91) ng/L respectively, and they were lower than preoperative (there were (398 ± 114), (439 ± 96) and (446 ± 105) ng/L, F = 55.08, 49.96 and 46.47, all P < 0.01). But the level of Ghrelin in LRYGB and LMGB groups rebounded in the first postoperative month. The postoperative level of Ghrelin was higher in LAGB group (F = 29.24, P = 0.001).</p><p><b>CONCLUSIONS</b>There are difference efficacies and impacts on gastrointestinal hormones among different modes of bariatric surgery. The change of gastrointestinal hormones is plausible mechanism of T2DM remission after surgery.</p>

Outcomes after laparoscopic surgery for 219 patients with obesity / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the outcomes after laparoscopic gastrointestinal surgery for patients with obesity and type 2 diabetes mellitus(T2DM).</p><p><b>METHODS</b>From June 2003 to June 2010, 219 patients underwent laparoscopic gastrointestinal surgery for obesity and T2DM, including laparoscopic adjustable gastric banding(LAGB, n=201), laparoscopic mini gastric bypass(LMGB, n=13), and laparoscopic sleeve gastrectomy(LSG, n=5). Clinical data were analyzed retrospectively.</p><p><b>RESULTS</b>The mean body mass index(BMI) of patients who received LAGB was 37.9 kg/m(2), and decreased to 32.4 kg/m(2) at 6 months and to 29.7 kg/m(2) at 12 months. In 43 patients who had concurrent T2DM, 11(25.6%) showed clinical partial remission(CPR) and 16(37.2%) clinical complete remission (CCR). Postoperative complications occurred in 26 patients(12.9%). The mean BMI of patients undergoing LMGB was 34.7 kg/m(2), and decreased to 31.6 kg/m(2) at 6 months and 26.9 kg/m(2) at 12 months after surgery. Ten patients had T2DM before operation, of whom 2(20.0%) had CPR and 7(70.0%) CCR postoperatively. Postoperative complications occurred in 2 patients(15.4%). The mean BMI of patients who underwent LSG was 43.8 kg/m(2), and was reduced to 38.1 kg/m(2) at 6 months and 34.3 kg/m(2) at 12 months after operation. Three patients were diagnosed with T2DM before operation. One patient (33.3%) had CPR and 1(33.3%) reached CCR after operation. There was 1(20.0%) patient who developed complication. No perioperative death occurred.</p><p><b>CONCLUSION</b>Laparoscopic gastrointestinal surgery may result in satisfactory weight loss and clinical remission of T2DM with few complications.</p>

A new technique for esophagojejunostomy or esophagogastrostomy after laparoscopic gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To report the newly developed reconstruction technique after laparoscopic total gastrectomy: intracorporeal circular stapling esophagojejunostomy using the transorally inserted anvil (OrVil; Covidien), and evaluate its feasibility, safety, and clinical outcomes.</p><p><b>METHODS</b>After LTG (3 patients with gastric carcinoma in the body) or LPG (2 patients with gastric carcinoma in the cardiac and fundus, respectively, and 1 with cardiac stromal tumor), the anvil was then inserted transorally into the esophagus by using the OrVil system. Double-stapling esophagojejunostomy or esophagogastrostomy with a circular stapler was performed intracorporeally.</p><p><b>RESULTS</b>The operations were uneventful. The operative time was (183.3+/-25.8) min, and blood loss was (128.3+/-90.2) ml. Postoperative fluorography revealed no anastomotic leakage or stenosis. Patients resumed an oral liquid diet on postoperative day (4.0+/-1.1), and were discharged on day (9.0+/-2.6). Patients were followed at 28 days and no complications were reported.</p><p><b>CONCLUSIONS</b>LTG with Roux-en-Y reconstruction or LPG with esophagogastrostomy using the OrVil system appear to be safe and reliable with satisfactory short-term outcomes.</p>

Effects of Gastric bypass surgery on the apoptosis of islet β-cells in type 2 nonobese diabetic (NOD) rats and its mechanism / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of Gastric bypass surgery on the apoptosis of islet β-cells in type 2 nonobese diabetic (NOD) rats and its mechanisms.</p><p><b>METHODS</b>Seventy-two 8-week-old GK rats were randomly divided into four groups:operation group (group O, n = 18), sham operation group (group S, n = 18), diet control group (group F, n = 18) and control group (group C, n = 18). The levels of fasting, postprandial blood glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured and compared among the 4 groups before the operation and at 1, 2, 4 and 8 weeks following the operation. The blood samples were collected at 2, 4 and 8 weeks after the operation for the measurement of postprandial blood glucose, and then the rats in batches (6 rats in each group) were decapitated to retrieve the pancreas. The apoptosis of the islet β-cells was detected by using TUNEL assay, and the expression of apoptosis-related proteins Bcl-2, Bax was measured with immunohistochemistry.</p><p><b>RESULTS</b>As for group O, the fasting blood glucose level decreased from (16.2 ± 0.8) mmol/L before the operation to respectively (9.2 ± 0.6) mmol/L and (9.7 ± 0.7) mmol/L at 4 and 8 weeks after the operation; postprandial blood glucose decreased from (31.1 ± 1.1) mmol/L before the operation to respectively (13.1 ± 0.7) mmol/L and (12.3 ± 0.7) mmol/L at 4 and 8 weeks after the operation. Fasting insulin level increased from (28.0 ± 1.2) mU/L before the operation to respectively (62.8 ± 1.9) mU/L and (61.7 ± 1.4) mU/L at 4 and 8 weeks after the operation; and at 4 and 8 weeks after the operation postprandial insulin level was (77.4 ± 1.1) mU/L and (77.1 ± 1.0) mU/L. At 2 weeks from the operation, the fasting GLP-1 in group O increased from (10.7 ± 1.0) pmol/L to (13.5 ± 0.8) pmol/L, and respectively to (26.1 ± 0.9) pmol/L and (25.3 ± 1.2) pmol/L at 4 and 8 weeks after the operation. The differences in the above-mentioned items before and after the operation were all significant in group O (P < 0.05), and the differences in the items among group O and the other three groups (P < 0.05) were all significant as well. In group O, the apoptosis rate of pancreatic islet cell decreased to (5.9 ± 0.7)% at 4 weeks from the operation, and (6.3 ± 1.1)% at 8 weeks from the operation (P < 0.05). The expression of Bcl-2 protein in group O was 31.3 ± 1.5, 35.7 ± 1.0 and 35.8 ± 0.8 at 2, 4 and 8 weeks post operation, which was significantly higher in statistics than those of the same time point in the other three groups (P < 0.05). The expression of Bax protein in group O was 13.3 ± 0.9, 10.8 ± 0.9 and 10.9 ± 1.1 at 2, 4 and 8 weeks from the operation, which was significantly lower in statistics than those of the same time point in the other three groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Gastric bypass surgery can significantly reduce the blood glucose level and promote the secretion of GLP-1, and therefore inhibit the apoptosis of the islet β cells in diabetic rats through the Bcl-2 pathway.</p>

Laparoscopic adjustable gastric banding in the treatment of obesity: analysis of 172 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the outcome of weight loss by laparoscopic adjustable gastric banding (LAGB) on obesity patients and the improvement of comorbidity.</p><p><b>METHODS</b>From June 2003 to June 2009, the data 172 obesity patients(119 women, 53 men, mean age 28.5 years, mean body mass index 38.5 kg/m(2)) were analyzed. Comorbidities included 28 cases with diabetes, 36 with hypertension, 85 with dyslipidemia, 56 with sleep apnea and 138 with fatty liver.</p><p><b>RESULTS</b>Mean body mass index(BMI) at 1,3,6,12, 24, 36 and 48 months was 37.2 kg/m(2),35.9 kg/m(2), 34.5 kg/m(2), 32.9 kg/m(2), 30.7 kg/m(2), 29.2 kg/m(2) and 28.1 kg/m(2), respectively. The percentage of excess weight loss(% EWL) at 1, 3, 6, 12, 24, 36, and 48 months was 10.1%, 16.2%, 25.1%, 37.4%, 51.3%, 59.0% and 62.1%, respectively. At 24, 36 and 48 months, respectively, 50.7%, 63.6% and 70.0% of patients had more than 50% excess weight loss. Complications included 6 cases of port infection, 3 of other port problem, 7 of gastric pouch dilatations, 4 of slippage and 1 of chronic intestinal obstruction. Bands of 5 patients were explanted. No death occurred. Blood glucose of 60.7% patients with diabetes was controlled well without any drug. The blood pressure of 22 hypertensive patients became normal. The blood fat of 49 hyperlipidemia cases returned to normal. The symptom of 29 patients with sleep apnea disappeared. All the patients with fatty liver were improved in different degree.</p><p><b>CONCLUSION</b>Gastric banding provides good weight loss and significant reduction in comorbidities with few and minor complications.</p>

Short-term outcome of laparoscopic gastric bypass and minigastric bypass on obesity patients with type 2 diabetes mellitus / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the short-term outcome of laparoscopic gastric bypass on obesity patients with type 2 diabetes mellitus.</p><p><b>METHODS</b>Seven obesity patients with type 2 diabetes mellitus received laparoscopic gastric bypass(n=1) or laparoscopic minigastric bypass(n=6), and their data of treatment outcomes were analyzed.</p><p><b>RESULTS</b>The operations were all successfully performed without any complications. The average operation time was 125 minutes(range: 100 to 170 minutes). The patients underwent 1-18 months follow-up after operation. Diabetic indicators returned to normal without any medication and body weight reduced by on average of 24.3 kg.</p><p><b>CONCLUSION</b>Laparoscopic gastric bypass and minigastric bypass have good short-term outcome in the treatment of obesity patients with type 2 diabetes mellitus.</p>

Effects of duodenal-jejunal bypass and sleeve gastrectomy on the expression of liver glucokinase in diabetic rats / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of duodenal-jejunal bypass(DJB) and sleeve gastrectomy(SG) on the expression of liver glucokinase(GCK) in diabetic rats.</p><p><b>METHODS</b>Animal models of Goto-Kakizaki rats and Sprague-Dawley rats were established by DJB and SG. Results of fasting glycemia and insulin were compared. Liver tissue was harvested 8 weeks postoperatively.Quantitative real-time PCR and Western blot were used to detect liver GCK mRNA and protein expression after operation.</p><p><b>RESULTS</b>Fasting plasma glucose levels of DJB group and SG group in GK rats were markedly declined 3 day and 1, 2, 4, 6, 8 weeks postoperatively(all P <0.01), while Sham group only dropped 3 day and 1 week postoperatively, and there were no significant differences 2 weeks postoperatively(P >0.05). Fasting plasma glucose levels of each group in SD rats did not change after operation. In GK rats, GCK mRNA level (1.45 +/-0.29) and protein expression (494.25 +/-30.25) after DJB were higher than Sham group (1.05 +/-0.19 and 409.13 +/-26.86) and control group (1.04 +/-0.17 and 404.75 +/-30.90). GCK mRNA level and protein expression after SG were 0.65 +/-0.25 and 345.25 +/-28.13 respectively, which were significantly lower than those in control group(all P <0.01). All the groups in SD rats experienced similar GCK expression change.</p><p><b>CONCLUSION</b>Both DJB and SG can decrease the plasma glucose levels of GK rats, while there are different effects on the expression of liver GCK.</p>

Application of neoadjuvant chemotherapy in laparoscopic gastrectomy for advanced gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the benefit of neoadjuvant chemotherapy in advanced gastric cancer patients treated by laparoscopy.</p><p><b>METHODS</b>Fifteen patients with histologically proved gastric adenocarcinomas (stages II(, III(, IIII(M(0)) were treated with FOLFOX7 neoadjuvant chemotherapy followed by laparoscopy between June 2005 and March 2007( trial group). Thirty patients were assigned to the control group with only laparoscopic treatment in the same period. The clinicopathological data were compared between two groups.</p><p><b>RESULTS</b>All the patients in trial group accepted four cycles of preoperative chemotherapy and the toxicity was less than grade 3. Two of them achieved complete response, 10 achieved partial response and 3 kept stable disease. Ten patients of trial group underwent laparoscopic-assisted radical gastrectomy. The rates of R(0)-resection(80.0%) and pN(0) (60.0%) in trial group were significantly higher than those in control group(46.7% and 20.0%), while the rate of positive lymph node 11.0%(34/309) was significantly lower than that of control group 23.8%(142/596). The operation time and postoperative complication were similar in two groups.</p><p><b>CONCLUSIONS</b>Advanced gastric cancer after neoadjuvant chemotherapy can be down-regulated in the stage, increase the rate of R(0)-resection, diminish the infiltration extent of tumor, decrease the metastasis of lymph node, and increase the possibility of laparoscopic radical gastrectomy.</p>

Efficacy of sleeve gastrectomy plus gastric remnant banding on weight reduction and remnant gastric dilatation: an animal experimental study / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of sleeve gastrectomy plus gastric remnant banding on weight reduction and remnant gastric dilatation in SD rat model.</p><p><b>METHODS</b>Sleeve gastrectomy plus gastric remnant banding was performed in 20 male SD rats as the study group; sleeve gastrectomy was performed in 20 SD male rats as the control group, and laparotomy was performed in 10 SD male rats as the blank control group. Body weight was measured before the experiment, at day 1 and at 2-week intervals within 16 weeks after operation.</p><p><b>RESULTS</b>The number of survival rats was 15 in the study group (15/20), 13 in the control group (13/20), and 10 in the blank control group (10/10). Postoperative body weight increased markedly in the blank control group, returned to the pre-operative level two weeks after operation in the control group, and four weeks after operation in the study group. Weight increase of the study group was significantly slower than that of the other two groups (P<0.01). Postoperative gastric dilation of the control group was more obvious as compared to the study group.</p><p><b>CONCLUSION</b>Sleeve gastrectomy plus gastric remnant banding is safe and effective because of the restriction of postoperative gastric dilation.</p>

Laparoscopic resection of submucosal tumors in gastric fundus / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and safety of extraluminal laparoscopic wedge resection (ELWR) in treating submucosal tumors in the gastric fundus.</p><p><b>METHODS</b>Clinical data of 84 patients underwent ELWR for submucosal tumors in the gastric fundus between September 2000 and December 2006 were reviewed and analyzed retrospectively. The four-portal operation procedures were carried out as follows: localization of the tumor, dissection of the omentum, mobilization of the gastric fundus and the upper polar of spleen, exposure of ECJ, and resection of the gastric fundus with Endo GIA.</p><p><b>RESULTS</b>The patients included 53 males and 31 females, age ranged from 32 to 78 years (mean, 59 years). The mean tumor diameter was (4.2 +/- 1.3) cm. The distance from the tumor edge to the ECJ was 1.1 - 3.0 cm. The operations were successful in all the 84 patients, with a mean operation time of (62.6 +/- 8.9) min and mean operative blood loss of (86.2 +/- 8.1) ml. No apparent tumor focus was left. No operation was converted to open surgery, and no significant postoperative complications occurred. The mean post-operative hospital stay was (5.6 +/- 0.5) days. The gastrointestinal function recovered within 36 h after operation in 66 cases (78.6%), and the patients returned to normal activity and restored oral feeding. The distance between the tumor and the resection margin was 0.7 - 2.5 cm from the ECJ [mean, (1.4 +/- 0.5) cm], and 2.5 - 6.0 cm from the other three sides [mean, (4.1 +/- 1.0) cm]. Of the 84 cases, 29 cases were diagnosed with leiomyoma, 51 cases different types of stromal tumor and 4 cases neurofibroma. The mean follow-up duration was (51.0 +/- 4.3) months, no recurrence or metastasis was found in the mean time.</p><p><b>CONCLUSIONS</b>ELWR is a safe, simple and beneficial procedure for submucosal tumors in the gastric fundus, especially in the posterior wall near the ECJ. It avoids intraperitoneal infection, possible splenic injury and postoperative esophageal stenosis. In addition, the resection scope is not limited.</p>

Diagnosis and treatment of postoperative complications after laparoscopic adjustable gastric banding procedure / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis and treatment of the complications in patients after laparoscopic adjustable gastric banding (LAGB) procedure.</p><p><b>METHODS</b>Retrospectively analyze the data of the 23 patients who received the LAGB procedure from June 2003 to November 2004.</p><p><b>RESULTS</b>Of the 23 LAGB operations, 3 (13%) cases of vomiting and nausea, 1 (4.3%) case of access-port infection and 5 (21.4%) cases of food intolerance occurred. One band (4.3%) and one injection reservoir (4.3%) displaced and were removed by laparoscopy. No death and thrombo-embolism occurred.</p><p><b>CONCLUSIONS</b>The diagnosis and treatment of complications after LAGB in morbid obesity was special, if managed properly, the result would be satisfactory.</p>