Background: In recent years, many clinical studies have confirmed the value of laparoscopy-assisted gastrectomy (LAG) in gastric cancer surgery, especially in early stages. But the safety and oncologic adequacy of laparoscopy-assisted D2 radical gastrectomy for advanced gastric cancer are still in debate. We conducted a prospective randomized trial to compare open versus laparoscopy-assisted D2 radical gastrectomy in advanced gastric cancer. Methods: For this study, 123 patients who had been diagnosed endoscopically with gastric cancer were randomly assigned to either LAG (n = 61) or open gastrectomy (OG) (n = 62) which ran from March 2008 to December 2009. Clinical characteristics, operative findings, postoperative recovery, morbidity, pathological report and survival rate were compared. D2 lymph node dissection was performed in 49 patients in the LAG group and 47 patients in the OG group with advanced gastric cancer. We adopt sub-group analysis in this paper. Results: The clinical characteristics of patients in the LAG and OG groups who were in the advanced stage, included age, sex, BMI and concurrent illness, and their ECOG scores were well matched. Operative findings, postoperative recovery, morbidity, pathological findings including tumor location, depth of invasion, TNM stage, histological grade and surgical extension in the two groups were also similar. Compared to the OG group, the mean operating time was significantly longer for the LAG group (267.88 ± 54.284 min in the LAG group vs. 182.02 ± 41.016 min in the OG group, p = 6.383 × 10–13); the mean number of days when body temperature exceeded 37°C was significantly shorter in the LAG group (p = 6.34 × 10–8). There were no postoperative deaths in both the groups. The postoperative morbidity rate was 12.24% in the LAG group and 19.15% in the OG group with no significant difference (p = 0.357). However, pulmonary infection was observed more frequently in the OG group (p = 0.038). After a mean follow-up of 22.1354 months (from 4 to 36 months), 14 and 15 patients died of gastric cancer in the LAG and OG groups, respectively. Two and one patient died of nongastric cancer in the LAG and OG groups, respectively. The overall survival rates were 67.1% and 53.8% in the LAG and OG groups, respectively. The estimated mean survival time was 29.387 months in the LAG group and 28.978 months in the OG group. There was no statistically significant difference in the overall survival rate for patients in both groups – LAG and OG (log-rank test, p = 0.911, Tarone Ware test, p = 0.994, and Breslow test, p = 0. 961). Conclusion: LAG with D2 lymph node dissection is a safe and feasible procedure with adequate lymphadenectomy, good curability and survival rate for the treatment of advanced gastric cancer.
As a constitutively active kinase, glycogen synthase kinase 3 (GSK3) is a kinase which regulates body metabolism by phosphorylation of glycogen synthase (GS) and other substrates. Considerable evidence suggests that GSK3 is involved in the common pathology underlying Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). The overexpression or overactivation of GSK3 could induce a series of pathological changes, most of which are hallmarks of AD and T2DM. Therefore, GSK3 could be a novel target to treat these two age-dependent diseases. The inhibition of this kinase can prevent the aggregation of β-amyloid (Aβ) and hyperphosphorylation of tau protein. GSK3 inhibition can also be a promising strategy to ameliorate neurodegenerative developments. Its potential association with memory formation has been shown in electrophysiological and behavioral experiments. The neuroprotective effects of novel drugs developed to treat T2DM, glucagon-like peptide 1 (GLP-1) and its long-lasting analogs, have a possible link to GSK3 modification. Recent investigations of the interaction between the phosphatidylinositol 3 kinase (PI3K) signaling pathway and the protective effect of novel GPL-1 receptor agonist geniposide on PC12 cells support this theory.
BackgroundAlthough laparoscopic surgery has been recommended as an optional therapy for patients with early gastric cancer, whether patients with locally advanced gastric cancer (AGC) could benefit from laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy remains elusive due to a lack of comprehensive clinical data. To evaluate the efficacy of LADG, we conducted a multi-institutional randomized controlled trial to compare laparoscopy-assisted versus open distal gastrectomy (ODG) for AGC in North China.MethodsIn this RCT, after patients were enrolled according to the eligibility criteria, they were preoperatively assigned to LADG or ODG arm randomly with a 1:1 allocation ratio. The primary endpoint was the morbidity and mortality within 30 postoperative days to evaluate the surgical safety of LADG. The secondary endpoint was 3-year disease-free survival. This trial was registered at ClinicalTrial.gov as NCT02464215.ResultsBetween March 2014 and August 2017, a total of 446 patients with cT2-4aN0-3M0 (AJCC 7th staging system) were enrolled. Of these, 222 patients underwent LADG and 220 patients underwent ODG were included in the modified intention-to-treat analysis. The compliance rate of D2 lymph node dissection was identical between the LADG and ODG arms (99.5%, P = 1.000). No significant difference was observed regarding the overall postoperative complication rate in two groups (LADG 13.1%, ODG 17.7%, P = 0.174). No operation-related death occurred in both arms.ConclusionsThis trial confirmed that LADG performed by credentialed surgeons was safe and feasible for patients with AGC compared with conventional ODG.
Intracerebral-ventricular (ICV) injection of streptozotocin (STZ) induces an insulin-resistant brain state that may underlie the neural pathogenesis of sporadic Alzheimer disease (AD). Our previous work showed that prior ICV treatment of glucagon-like peptide-1 (GLP-1) could prevent STZ-induced learning memory impairment and tau hyperphosphorylation in the rat brain. The Chinese herbal medicine geniposide is known to relieve symptoms of type 2 diabetes. Because geniposide is thought to act as a GLP-1 receptor agonist, we investigated the potential therapeutic effect of geniposide on STZ-induced AD model in rats. Our result showed that a single injection of geniposide (50 μM, 10 μL) to the lateral ventricle prevented STZ-induced spatial learning deficit by about 40% and reduced tau phosphorylation by about 30% with Morris water maze test and quantitative immunohistochemical analysis, respectively. It has been known that tau protein can be phosphorylated by glycogen synthase kinase-3 (GSK3) and STZ can increase the activity of GSK3β. Our result with Western blot analysis showed that central administration of geniposide resulted in an elevated expression of GSK3β(pS-9) but suppressed GSK3β(pY-216) indicating that geniposide reduced STZ-induced GSK3β hyperactivity. In addition, ultrastructure analysis showed that geniposide averted STZ-induced neural pathology, including paired helical filament (PHF)-like structures, accumulation of vesicles in synaptic terminal, abnormalities of endoplasmic reticulum (ER) and early stage of apoptosis. In summary, our study suggests that the water soluble and orally active monomer of Chinese herbal medicine geniposide may serve as a novel therapeutic agent for the treatment of sporadic AD.
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