Hinokione: an abietene diterpene with pancreatic ß cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara.

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.

Compounds from Agathis dammara exert hypoglycaemic activity by enhancing glucose uptake: lignans, terpenes and others.

In this study, two new kaurane diterpenes (16, 17), together with 12 lignans (1-12), a triterpene (15), and two other compounds (13, 14) were isolated from the woods of Agathis dammara. The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy, and its absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. Compounds 5, 11, 14 exhibit significant hypoglycaemic activity in zebrafish, and their mechanism of action is to enhance glucose uptake in zebrafish.

Oleanolic acid derivative alleviates cardiac fibrosis through inhibiting PTP1B activity and regulating AMPK/TGF-ß/Smads pathway.

Cardiac fibrosis (CF) in response to persistent exogenous stimuli or myocardial injury results in cardiovascular diseases (CVDs). Protein tyrosine phosphatase 1B (PTP1B) can promote collagen deposition through regulating AMPK/TGF-ß/Smads signaling pathway, and PTP1B knockout improves cardiac dysfunction against overload-induced heart failure. Oleanolic acid (OA) has been proven to be an inhibitor of PTP1B, and its anti-cardiac remodeling effects have been validated in different mouse models. To improve the bioactivity of OA and to clarify whether OA derivatives with stronger inhibition of PTP1B activity have greater prevention of cardiac remodeling than OA, four new OA derivatives were synthesized and among them, we found that compound B had better effects than OA in inhibiting cardiac fibrosis both in vivo in the isoproterenol (ISO)-induced mouse cardiac fibrosis and in vitro in the TGF-ß/ISO-induced 3T3 cells. Combining with the results of molecular docking, surface plasmon resonance and PTP1B activity assay, we reported that OA and compound B directly bound to PTP1B and inhibited its activity, and that compound B showed comparable binding capability but stronger inhibitory effect on PTP1B activity than OA. Moreover, compound B presented much greater effects on AMPK activation and TGF-ß/Smads inhibition than OA. Taken together, OA derivative compound B more significantly alleviated cardiac fibrosis than OA through much greater inhibition of PTP1B activity and thus much stronger regulation of AMPK/TGF-ß/Smads signaling pathway.

Meta-analysis on comparison of long-term complications and quality of life between two digestive tract reconstruction techniques following total gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the incidence of postoperative long-term complications and quality of life between two digestive tract reconstruction techniques after total gastrectomy in order to provide evidence for clinical practice.</p><p><b>METHODS</b>A systematic literature search was carried out to obtain studies of randomized controlled trials (RCTs) of reconstruction techniques including jejunal interposition and Roux-en-Y. Data extracted from RCTs for meta-analysis were independently assessed by two reviewers. A meta-analysis was performed by RevMan5.0 software.</p><p><b>RESULTS</b>A total of 1628 gastric cancer cases undergoing total gastrectomy from 10 RCTs were eligible for inclusion, among whom 728 received jejunal interposition reconstruction and 954 Roux-en-Y anastomosis. As compared with Roux-en-Y anastomosis, jejunal interposition reconstruction significantly decreased the incidence of dumping syndrome (OR=0.19, 95%CI:0.11-0.34, P<0.01), increased the prognostic nutritional index (WMD=6.02, 95%CI:1.82-10.22, P<0.01), and improved the body weight postoperatively (WMD=-2.45, 95%CI:-3.81--1.71, P<0.01). Meanwhile, jejunal interposition reconstruction did not prolong operative time and hospital stay (both P>0.05).</p><p><b>CONCLUSION</b>Jejunal interposition has better efficacy than Roux-en-Y in dumping syndrome and quality of life, and is a reasonable and effective digestive tract reconstruction for long-term survival of gastric cancer patients.</p>

Value of nasogastric decompression tube in patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of nasogastric decompression tube after gastric cancer operation on the postoperative recovery.</p><p><b>METHODS</b>A total of 174 patients with gastric cancer were prospectively enrolled from December 2009 to March 2011 and randomly divided into non-nasogastric tube control group(n=88) and nasogastric tube group(n=86). Postoperative symptoms, complications, recovery time, and quality of life during hospital stay were compared between the two groups.</p><p><b>RESULTS</b>The incidences of nausea(14.8% vs. 47.7%, P<0.01), sore throat(6.8% vs. 38.4%, P<0.01), bucking and foreign body sensation(3.4% vs. 20.9%, P<0.01), expectoration obstruction(36.4% vs. 55.8%, P<0.05) were significantly lower in nasogastric tube group than those in the control group. The intervals to ambulation and flatus were(1.46±0.58) d and(3.11±0.77) d in the non-nasogastric tube group, significantly shorter those in nasogastric tube group[(1.68±0.61) d and(3.75±1.03) d]. There was no anastomotic leak or bowel obstruction. The difference in bleeding was not statistically significant[3.4%(3/88) vs. 5.8%(5/86), P>0.05] between the two groups. The quality of life differed between the two groups(mean score, 3.36 vs. 2.78, P<0.01).</p><p><b>CONCLUSION</b>Early removal of nasogastric decompression tube is safe and reasonable and can improve the quality of life during hospital stay.</p>

The relationship of prognosis to surgery and pathologic characteristics of stage IV (M0) gastric cancer patients / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The proportion of stage IV gastric cancer in the whole gastric cancer population in China is still high. This study was to investigate the surgery and pathologic characteristic and prognostic factors of stage IV (M0) gastric cancer.</p><p><b>METHODS</b>Clinical data of 630 patients with pathologically confirmed stage IV (M0) gastric cancer treated at the affiliated Tumor Hospital of Harbin Medical University between January 1993 and August 2004 were analyzed using Cox proportional hazard model. Of the 630 patients, 338 received radical excision and 292 received palliative resection.</p><p><b>RESULTS</b>The overall 1-, 3-, 5-year survival rates were 63.8%, 31.4% and 14.3%, respectively. Univariate analysis showed that Borrmann type, lymphatic metastasis, organ involvement, tumor location, tumor size, pathologic type, radical excision and other organ excision were significant prognostic factors affecting 1-year survival rate (P < 0.05); Borrmann type, lymphatic metastasis, organ involvement, pathologic type and radical excision affected 3-year survival rate (P < 0.05); only organ involvement and pathologic type affected 5-year survival rate (P < 0.05). Multivariate analysis showed that pathologic type was independent prognostic factor for poor survival.</p><p><b>CONCLUSIONS</b>Radical resection and combined organ resection could prolong the survival of stage IV (M0) gastric cancer patients. Chemotherapy, radiotherapy and targeted therapy should be considered for individual therapeutic regimen.</p>

Expression of hepatocyte growth factor, transcription factor SP1, vascular endothelial growth factor and CD34 in serosa-infiltrative gastric cancer and their relations with defluxion of gastric cancer cell and prognosis / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the expression of hepatocyte growth factor (HGF), transcription factor SP1, vascular endothelial growth factor (VEGF) and CD34 (demonstrating by microvessel density, MVD) in serosa-infiltrative gastric cancer (T3) and their relations with the pathobiological behavior of the tumor, and to investigate the molecular basis of the defluxion of gastric cancer cells in abdominal cavity and its influence on prognosis.</p><p><b>METHODS</b>Selective collection of peritoneal lavage was obtained from 80 patients with serosa-infiltrative gastric cancer received operation from April to December in 2007. The cancer cells were detected by using peritoneal lavage cytology (PLC) and immunochemistry of cytokeratin 18 (CK18). Immunohistochemistry was applied to detect the HGF, SP1, VEGF and CD34 in serosa-infiltrative gastric cancer tissues. The rigorous follow-up was carried out for the patients.</p><p><b>RESULTS</b>The positive rate of PLC was 63.8% (51/80), and the positive rate of immunochemistry of CK18 was 75.0% (60/80). The positive cases in PLC were positive in immunochemistry of CK18 also, while 9 negative cases in PLC were positive with CK18, and of them 6 cases were determined positive with exfoliated cancer cells through pathological consulting. So the positive rate of exfoliated cells of this group was 71.3% (57/80). The positive rates of HGF, SP1 and VEGF in gastric cancer tissues were 57.5%, 52.5% and 55.0%, respectively, and were all significantly correlated with the MVD (P < 0.05). HGF, SP1, VEGF and MVD were correlated with the positive rate of exfoliated cells (P < 0.05). HGF, SP1, VEGF and MVD were found significantly related to prognosis on univariate analysis (P < 0.05), and it was demonstrated that HGF, SP1 and VEGF were independent prognostic influential factors on Logistic regression analysis (P < 0.05).</p><p><b>CONCLUSIONS</b>The expression of HGF, SP1, VEGF and MVD are related with the biological behaviour of serosa-infiltrative gastric cancer. The detection of these factors might be helpful in predicting the defluxion of gastric cancer cells and postoperative recurrence.</p>

Expression of transcription factor SP1, vascular endothelial growth factor and CD34 in serosa-infiltrating gastric cancer and their relationship with biological behavior and prognosis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of transcription factor SP1, vascular endothelial growth factor(VEGF) and CD34 in serosa-infiltrating gastric cancer and their relationship with biological behavior and survival rate.</p><p><b>METHODS</b>Immunohistochemical technique was used to detect the expression of SP1, VEGF and CD34(described by microvessel density, MVD) in 68 specimens with serosa-infiltrating gastric cancer.</p><p><b>RESULTS</b>The positive expression rates of SP1 and VEGF in serosa-infiltrating gastric cancer were 50.0% and 52.9% respectively. In positive SP1 specimens, the positive rate of VEGF(73.5%) was significantly higher than that of negative SP1 specimens (32.4%, chi(2)=11.57, P=0.01). The mean tumor MVD was correlated with the expression levels of SP1 and VEGF(P<0.01). There was a significant correlation of the SP1 expression with tumor size and growth pattern(P =0.01). The expression levels of VEGF and MVD were correlated with Borrmann types, cell differentiation, metastatic lymph nodes and growth pattern(P<0.01). Univariate analysis revealed that SP1 and VEGF expression, MVD, Borrmann types, lymph node metastasis, tumor size and growth pattern were significant prognostic factors related to survival time. Multivariate analysis showed that SP1 expression, MVD and growth pattern were independently prognostic factors of poor survival.</p><p><b>CONCLUSIONS</b>The activation of SP1 contributes to angiogenesis and metastasis in gastric cancer through the up-regulation of VEGF. SP1, VEGF and MVD may serve as valuable indicators of biological behavior of gastric cancer. SP1 protein expression is not related with the number of metastatic lymph nodes. SP1 expression and MVD may serve as valuable indicators of prognosis in gastric carcinoma.</p>