This study is to investigate the protective effect of rosiglitazone (RSG) against learning and memory impairment of APP/PS1/tau transgenic mice. AD mice model was replicated by using 6-month APP/PS1/tau transgenic mice. The learning and memory ability of mice was evaluated by Morris water maze and Western blotting assays was applied to measure the phosphorylation and O-glycosylation of Tau and neurofilaments (NFs) protein. The results demonstrated that RSG could reverse the learning and memory deficits of 3 x Tg mice significantly. It was also found that RSG could suppress the hyperphosphorylation of Tau and NFs protein levels and increase the glycosylation expression of Tau and NFs proteins in 3 x Tg mice brain. Together, RSG ameliorates cognitive impairments of 3 x Tg mice via the alleviation of the hyperphosphorylated Tau and NFs proteins burden in the brain.

Objective To investigate the risk factors for non-curative resection after endoscopic submucosal dissection ( ESD ) for early esophageal cancer and high-grade intraepithelial neoplasia .Methods The clinicopathological data of 427 cases of early esophageal cancer and high-grade intraepithelial neoplasia who underwent ESD was performed from January 2013 to December 2016 in the Department of Gastroenterology , First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed .According to the results of postoperative pathology and immunohistochemistry ,339 patients were defined as curative resection group and 88 patients were defined as non-curative resection group .Chi-square test , univariate analysis and multivariate logistic regression analysis were used for statistical analysis .Results A total of 427 patients were enrolled in this study, with an average age of (63.2 ±7.7) years, including 96 cases of early esophageal cancer and 331 cases of high-grade intraepithelial neoplasia .The enbloc resection rate of ESD was 94.8％(405/427), 88 of them were non-curative resected, and the non-curative resection rate was 20.6％.Univariate analysis showed that early esophageal cancer (odds ratio (OR)=3.682, 95％confidence interval (CI) 2.216 to 6.118, P<0.01), submucosal infiltration (OR=10.220, 95％CI 4.861 to 21.481, P<0.01), ESD indications (OR=6.005, 95％CI 3.545 to 10.172, P<0.01) and lifting sign after injecting at the base of lesions (OR=2.508, 95％CI 1.005 to 6.255, P=0.042) were statistically significant between non-curative resection group and curative resection group . Multivariate unconditional logistic regression analysis revealed that submucosal infiltration (OR =4.329, 95％CI 1.758 to 10.661,P =0.001), not absolute indications of ESD (OR =6.484, 95％CI 2.205 to 19.068, P=0.001) and negative lifting sign (OR=3.182, 95％CI 1.171 to 8.651, P=0.023) were independent risk factors for non-curative resection.Conclusions Patients with early esophageal cancer , submucosal infiltration , not absolute indications for ESD and negative lifting signs are prone to non-curative resection .Moreover , submucosal infiltration , not absolute indications for ESD , and negative lifting signs are the independent risk factors for non-curative resection .

AIM: To investigate the ability of quercetin to reverse acquire adriamycin (ADR) resistance and explored its probably mechanism. METHODS: The CCK-8 assay was used to detect the cytotoxicity of quercetin in MCF-7/ADR cells and the reversal effect of ADR. The colony formation assay and Hoechst 332582 staining were used to detect the cell proliferation, cell apoptosis and the accumulation of rhodamine 123 (Rh123) respectively. The RNA expression levels of GAS5 and ABCB1 were detected by qRT-PCR. The protein expression levels of GSK-3β, β-catenin, c-MYC, cyclin D1, and ABCB1 were detected by Western blot. RESULTS: Quercetin (10, 20, 40 μmol/L) significantly enhanced the sensitivity of MCF-7/ADR to ADR, inhibitd cell proliferation, and increased the intracellular accumulation of Rh123. Treatment with quercetin in MCF-7/ADR cells, the expression levels of GAS5 and GSK-3β were increased, whereas the expression levels of β-catenin, c-myc, cyclin D1 and ABCB1 were decreased. Further research revealed that reduction of GAS5 by RNA interference (si-GAS5) induced inhibitory effects on the expressions of GAS5 and GSK-3β, and enhanced the expressions of β-catenin, c-myc, cyclin D1, and ABCB1. Furthermore, treatment by quercetin combined with si-GAS5 in MCF-7/ADR cells, the expressions of these proteins were effectively reversed in comparison to quercetin combined with siRNA negative control (sncRNA). CONCLUSION: Quercetin increases the expression of GAS5by GSK-3β/β-catenin signaling pathway, which inhibits the expression of ABCB1, ultimately reversing ADR resistance in the MCF-7/ADR cells.