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5-Fluorouracil (5-FU) is a common chemotherapy drug for patients with advanced colorectal cancer; however, many patients develop resistance to 5-FU and suffer from treatment failure. Discoidin domain receptor 1 (DDR1) is upregulated in multiple cancers and positively associated with chemoresistance. We explored the effect of DDR1a on the cytotoxicity induced by 5-FU in LoVo cells and the underlying mechanism. Therefore, DDR1a overexpression (DDR1a

To establish a prognostic nomogram based on response to bortezomib and BTK expression for treatment-experienced multiple myeloma patients.The Oncomine database was utilized to determine BTK expression, sex, age, albumin, Mayo index, response to bortezomib treatment, follow-up time and survival status in multiple myeloma(MM) patients. Cut-off point for BTK expression was calculated using R software. Univariate and multivariate analyses by Cox proportional hazards regression were then performed. Significant prognostic factors were combined to build a nomogram. The discrimination ability and predictive accuracy of the nomogram were evaluated using the index of concordance (C-index) and calibration curves.Multivariate analysis showed that response to bortezomib, BTK expression and sex were independent risk factors for prognosis. The C-index value of the nomogram made according to the independent risk factors was 0.729 (95%CI, 0.642-0.8164). The calibration curves showed good consistency between predicted and actual survivals for 1-year and 2-year overall survival.The proposed nomogram is accurate in predicting the prognosis of patients with MM.基于硼替佐米治疗反应及BTK表达水平建立非初治多发性骨髓瘤临床预测模型.基于硼替佐米治疗反应及骨髓瘤细胞BTK表达水平建立非初治多发性骨髓瘤（MM）临床预测模型的列线图（nomogram）。.运用Oncomine数据库搜索BTK基因表达水平、性别、年龄、白蛋白水平、Mayo评分、硼替佐米治疗反应、随访时间及生存状态等信息，计算影响MM临床预后的BTK表达水平截断值（cut-off值），对上述因素进行Cox多因素回归分析，并根据独立预后因素制作列线图，用一致性指数（C-index）和校正曲线确定列线图的预测精度和判别能力。.多因素分析结果显示，影响患者预后的因素有硼替佐米治疗反应、BTK表达水平及性别，根据上述指标制作的列线图一致性指数为0.729（95%CI，0.642-0.8164），患者1年及2年的生存率的校正曲线与实际观测结果吻合较好。.基于BTK表达水平及硼替佐米治疗反应的列线图能准确地预测MM患者的预后。.

We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China.A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined byThe eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) ofThe HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is an idiopathic intestinal inflammatory disease which is closely connected with host genetic factor, immune system disorder and environmental factors, would influence the ileum, rectum and colon as well. With the gradual increase of incidence, the endoscopy plays an important role in diagnosis of UC and CD and timely monitoring of anti-inflammatory treatment, mucosal healing and cancers related to inflammatory bowel diseases. Compared with traditional white light endoscopy, endocytoscopy, an advanced monitoring technique, could more precisely reflect lesion, predict mucosal inflammation, and carry out observation of living tissue cell structure similar to that under microscope, determine the location and nature of lesion, and thus increase precision of endoscopic diagnosis and reduce diagnosis steps, this could possibly pave a new way for IBD diagnosis and clinical monitoring. This paper summarizes recent advances in application of endocytoscopy in the diagnosis of IBD. DOI: 10.11855/j.issn.0577-7402.2018.11.13

Background: A high-dose proton pump inhibitor (PPI)-amoxicillin dual therapy has been investigated for treatment of patients with Helicobacter pylori ( H. pylori) infection. Currently, the efficacy of this dual therapy remains inconclusive, with controversial findings from various single-center clinical trials. Objectives: To assess the efficacy and safety of high-dose dual therapy (HDDT) compared with the bismuth-containing quadruple therapy (BQT) in treatment-naive patients with H. pylori infection. Design: A multicenter, open-label, randomized controlled clinical trial. Methods: Three hundred and forty treatment-naïve patients with H. pylori infection were prospectively recruited from seven participating hospitals. The enrolled patients were randomized into one of two treatment groups: the HDDT group (esomeprazole, 20 mg four times daily; amoxicillin, 750 mg four times daily) and the BQT group (esomeprazole, 20 mg, twice daily; bismuth potassium citrate, 600 mg, twice daily; amoxicillin, 1 g, twice daily; metronidazole, 400 mg, four times daily). The primary outcome was eradication rate, and secondary outcomes were safety and patient compliance. Results: The eradication rates in the HDDT group versus the BQT group were 86.47% versus 87.06% on intention-to-treat (ITT) analysis, 91.88% versus 92.50% on modified ITT (MITT) analysis, and 91.77% versus 93.04% on per-protocol (PP) analysis, with no significant differences between the two groups. The patient compliance rates in the HDDT group versus the BQT group were 97.02% versus 95.86%, and no significant difference was found between the two groups. Notably, the HDDT group exhibited significantly lower incidence in the drug-induced adverse events (AEs) compared to the BQT group (16.67% versus 47.94%). Conclusion: HDDT is equally efficacious in eradicating H. pylori infection and resulted in good patient compliance and safety compared with BQT. These findings provide evidence in support of HDDT as a first-line treatment for H. pylori infection. Registration: This clinical trial was registered at The Chinese Clinical Trial Registry (trial registration number: ChiCTR2000039096).

MicroRNA-592 (miR-592) has been reported to play a significant role in mediating neuronal activity, but its possible link with Alzheimer's disease (AD) remains unclear. We aimed to explore the mechanism of miR-592 in oxidative stress (OS) injury of astrocytes (ASTs) from AD rat models induced by D-galactose or Aβ25-35 injection. Bioinformatics website and dual-luciferase reporter gene assay clarified the binding affinity between miR-592 and KIAA0319. KIAA0319 was identified as a target gene of miR-592. The mechanism of miR-592, KIAA0319 and the Keap1/Nrf2/ARE signaling pathway in AD was examined after transducing miR-592 mimic, miR-592 inhibitor and siRNA-KIAA0319 into ASTs to query cell viability, OS injury and reactive oxygen species (ROS). The rat models of AD Exhibited highly expressed miR-592 and poorly expressed KIAA0319. Furthermore, inhibition of miR-592 diminished C-Keap1 expression and enhanced N-Nrf2 and NQO1 expression, thus promoting cell viability and reducing OS injury of ASTs. Taken together, these findings suggested that the downregulation of miR-592 inhibited OS injury of ASTs in rat models of AD by up-regulating KIAA0319 through the activation of the Keap1/Nrf2/ARE signaling pathway.

Helicobacter pylori (Hp),a proven pathogen of digestive disease,is closely associated with gastrointestinal diseases including peptic ulcer,chronic active gastritis,stomach cancer,and stomach-associated lymphoid tissue lymphoma. Thus,precise and timely diagnosis of Hp is of great significance. In addition to

Background: In the general population, selective cyclooxygenase (COX)-2 inhibitors have been associated with fewer gastrointestinal adverse effects (AEs) than NSAIDs, but whether they are associated with exacerbations in patients with inflammatory bowel disease (IBD) remains controversial. Objective: The aim of this study was to review published and unpublished findings to determine whether the use of COX-2 inhibitors increased the risk for IBD exacerbations relative to placebo in the treatment of IBD. Methods: A systematic search of MEDLINE (1966-July 2007), EMBASE (1980-July 2007), the Cochrane Library (2007 Issue 4), US Food and Drug Administration records, and data on file at Novartis Pharmaceuticals Corporation, Pfizer US Pharmaceutical Group, and Merck & Co., Inc., using the search terms celecoxib, rofecoxib, valdecoxib, etoricoxib, lumiracoxib, cyclooxygenase 2 inhibitor, Crohn's disease, ulcerative colitis, and inflammatory bowel disease, was performed to identify randomized, placebo-controlled clinical trials of 5 COX-2 inhibitors in patients with IBD. The publications were fully reviewed for quality. Data on trial design, patient characteristics, intervention drugs, dosages, and outcomes were collected using a predetermined data-extraction form. A meta-analysis was performed based on the publications that met the inclusion/exclusion criteria. Results: Of 588 studies identified in the electronic search, 574 were excluded after screening the titles and abstracts. Fourteen related to the use of COX-2 inhibitors in patients with IBD were reviewed. Two randomized, controlled trials comparing COX-2 inhibitors with placebo were identified. In the first trial, 82 patients were randomized to receive etoricoxib (60–120 mg/d) and 77 to receive placebo. The exacerbation rates were 10.5% (8/76) in the active-treatment group and 11.4% (8/70) in the placebo group (relative risk [RR], 0.92; 95% CI, 0.37–2.32). In the second trial, 112 patients were treated with celecoxib (200 mg BID) and 110 received placebo. The exacerbation rates were 3.7% (4/107) in the celecoxib group and 2.7% (3/110) in the placebo group (RR, 0.73; 95% CI, 0.17–3.18). Of these patients, 5 were lost to follow-up because of AEs. In the meta-analysis comparing COX-2 inhibitors and placebo, the RR was 0.86 (95% CI, 0.39–1.88). No statistically significant differences in IBD relapse rates were found between COX-2 inhibitors and placebo. Conclusions: The results from this meta-analysis suggest that insufficient data were available to determine the impact of COX-2 inhibitors on IBD exacerbations. The relatively smaller risk for AEs makes the short-term use of COX-2 inhibitors potentially attractive, but the long-term benefits remain unclear. Further studies with sound methodology and large sample sizes are needed to evaluate the tolerability of COX-2 inhibitors in the treatment of IBD.

Background. Free radicals and proinflammatory cytokines have been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). Picroliv, aPicrorhiza kurroaderivative, has been demonstrated to have antioxidant and anti-inflammatory effect. The purpose of the study was to investigate the effects of picroliv on experimental model of UC in mice.Materials and Methods. Picroliv was administrated orally by gavage to mice with colitis induced by dextran sulfate sodium (DSS). Disease activity index (DAI), colon length, and histology score were observed. Myeloperoxidase (MPO) activity, and SOD, MDA concentrations were measured by enzyme-linked immunosorbent assay (ELISA) while the expression of cytokine mRNAs was studied by real-time-quantitative polymerase chain reaction and also ELISA. The expression of NF-κB p65 was observed by immunohistochemistry staining and western blotting.Results. A significant improvement was observed in DAI and histological score in mice treated with picroliv, and incerased MPO activity, MDA concentrations, and the expression of IL-1β, TNF-α, and NF-κB p65 in mice with DSS-induced colitis were significantly reduced while decreased SOD level increased following administration of picroliv.Conclusion. The administration of picroliv leads to an amelioration of DSS-induced colitis, suggesting administration of picroliv may provide a therapeutic approach for UC.

To detect the changes of expression of PTEN protein and AKT protein in patients with Ulcerative Colitis (UC) in the pathway from inflammation to carcinoma.A total of 110 paraffin colorectal sections were examined, which included 65 cases with UC, 25 cases with colorectal cancer and 25 cases with normal tissues. The expression of PTEN protein and AKT protein was detected with immunohistochemistry.(1) The patients with UC had lower expression of PTEN protein and higher expression of AKT than those with normal tissues (P0.01). (2) The patients with UC had higher expression of PTEN protein and lower expression of AKT protein than those with colorectal cancer (P0.01). (3) With the progress of UC, the expression of PTEN protein decreased while the expression of AKT protein increased (P0.01). (4) The expression of PTEN protein was negatively correlated with the expression with AKT protein in patients with UC and colorectal cancer (r = -0. 542 and -0. 674, respectively P0.01).The change of expressions of PTEN protein and AKT protein might play an important role in the development of UC and colorectal cancer. Decreased PTEN protein and increased AKT protein might be a marker for the early detection of the occurrence of colorectal cancer in patients with UC.

In recent years, many research works have focused on vertical handoff (VHO) decision algorithms. However, evaluation scenarios in different papers are often quite different and there is no consensus on how to evaluate performance of VHO algorithms. In this paper, we address this important issue by proposing an approach for systematic and thorough performance evaluation of VHO algorithms. Firstly we define the evaluation criteria for VHO with two metrics: matching ratio and average ping-pong number. Subsequently we analyze the general movement characteristics of mobile hosts and identify a set of novel performance evaluation models for VHO algorithms. Equipped with these models and evaluation criteria, we evaluate and analyze two types of decision algorithms: hysteresis based and dwelling-timer based algorithms. The results show a good match between simulation and analytical results.