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Chen H.-M.,Shanghai JiaoTong University | Chen H.-M.,Key Laboratory of Gastroenterology and Hepatology | Chen H.-M.,Shanghai Institute of Digestive Disease | Yu Y.-N.,Shanghai JiaoTong University | And 23 more authors.
American Journal of Clinical Nutrition | Year: 2013

Background: Accumulating evidence indicates that diet is one of the most important environmental factors involved in the progression from advanced colorectal adenoma (A-CRA) to colorectal cancer. Objective: We evaluated the possible effects of dietary fiber on the fecal microbiota of patients with A-CRA. Design: Patients with a diagnosis of A-CRA by pathological examination were enrolled in the A-CRA group. Patients with no obvious abnormalities or histopathological changes were enrolled in the healthy control (HC) group. Dietary fiber intake was assessed in all patients. Short-chain fatty acids (SCFAs) in feces were detected by gas chromatography. The fecal microbiota community was analyzed by 454 pyrosequencing based on 16S ribosomal RNA. Results: Lower dietary fiber patterns and consistently lower SCFA production were observed in the A-CRA group (n = 344). Principal component analysis showed distinct differences in the fecal microbiota communities of the 2 groups. Clostridium, Roseburia, and Eubacterium spp. were significantly less prevalent in the A-CRA group (n = 47) than in the HC group (n = 47), whereas Enterococcus and Streptococcus spp. were more prevalent in the A-CRA group (n = 47) (all P<0.05). Butyrate and butyrate-producing bacteria were more prevalent in a subgroup of HC subjects with a high fiber intake than in those in both the low-fiber HC subgroup and the high-fiber A-CRA subgroup (all P<0.05). Conclusion: A high-fiber dietary pattern and subsequent consistent production of SCFAs and healthy gut microbiota are associated with a reduced risk of A-CRA. This trial was registered at www.chictr. org as ChiCTR-TRC-00000123. © 2013 American Society for Nutrition.


Qian J.,Shanghai Institute of Digestive Disease | Kong X.,Shanghai Institute of Digestive Disease | Deng N.,National University of Singapore | Tan P.,National University of Singapore | And 8 more authors.
Gut | Year: 2015

Objective: Octamer transcription factor 1 (OCT1) was found to be expressed in intestinal metaplasia and gastric cancer (GC), but the exact roles of OCT1 in GC remain unclear. The objective of this study was to determine the functional and prognostic implications of OCT1 in GC.Design: Expression of OCT1 was examined in paired normal and cancerous gastric tissues and the prognostic significance of OCT1 was analysed by univariate and multivariate survival analyses. The functions of OCT1 on synbindin expression and extracellular signal-regulated kinase (ERK) phosphorylation were studied in vitro and in xenograft mouse models.Results: The OCT1 gene is recurrently amplified and upregulated in GC. OCT1 overexpression and amplification are associated with poor survival in patients with GC and the prognostic significance was confirmed by independent patient cohorts. Combining OCT1 overexpression with American Joint Committee on Cancer staging improved the prediction of survival in patients with GC. High expression of OCT1 associates with activation of the ERK mitogen-activated protein kinase signalling pathway in GC tissues. OCT1 functions by transactivating synbindin, which binds to ERK DEF domain and facilitates ERK phosphorylation by MEK. OCT1-synbindin signalling results in the activation of ERK substrates ELK1 and RSK, leading to increased cell proliferation and invasion. Immunofluorescent study of human GC tissue samples revealed strong association between OCT1 protein level and synbindin expression/ERK phosphorylation. Upregulation of OCT1 in mouse xenograft models induced synbindin expression and ERK activation, leading to accelerated tumour growth in vivo.Conclusions: OCT1 is a driver of synbindin-mediated ERK signalling and a promising marker for the prognosis and molecular subtyping of GC.


Wang Y.Y.,Shanghai JiaoTong University | Liu J.,Jinling Hospital | Zheng Q.,Shanghai JiaoTong University | Ran Z.H.,Shanghai JiaoTong University | And 5 more authors.
Journal of Digestive Diseases | Year: 2012

OBJECTIVE: To investigate the in vivo oncosuppressive effect of the non-structural protein NS1 of parvovirus H-1 on human gastric cancer cell lines. METHODS: Recombinant plasmid pcDNA3.1-NS1 containing the complete NS1 gene of parvovirus H-1 was constructed and characterized by restriction enzyme digestion and sequence analysis. The human gastric cancer cell lines MKN28, SGC7901 and MKN45 were stably transfected with empty or recombinant plasmids. NS1 gene transcription and protein expression in the latter transfectants were verified by reverse transcriptase polymerase chain reaction and Western blot, respectively. The oncosuppressive effect of the parvoviral protein NS1 on the gastric cancer cell lines was tested by comparing the tumorigenicity of empty and recombinant vector-transfected cells in nude mice. RESULTS: Well differentiated gastric cancer cells (MKN28) transfected with either empty plasmid or pcDNA3.1-NS1 were tumorigenic in nude mice. Moderately (SGC7901) and poorly (MKN45) differentiated gastric cancer cells transfected with empty plasmid were also tumorigenic, but no tumor resulted from the injection when they were transfected with pcDNA3.1-NS1. This NS1-associated suppression of SGC7901 and MKN45 tumors correlated with the decreased percentage of CD44 positive cells. CONCLUSIONS: NS1 expression in poorly differentiated gastric cancer cells prevents them from forming tumors, perhaps by impairing the stem-like phenotype. The parvoviral NS1 protein warrants further investigation for its therapeutic potential against cancer. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.


Gu L.-Y.,Shanghai JiaoTong University | Lin W.-W.,Shanghai JiaoTong University | Lu H.,Shanghai JiaoTong University | Lu H.,Shanghai Institute of Digestive Disease | And 5 more authors.
Helicobacter | Year: 2011

Background: The eradication rates of first-line treatment for Helicobacter pylori infection are not satisfactory. Various regimens including quadruple therapies have been recommended as rescue therapies after the first H. pylori eradication attempt failed. Aims: To compare the efficacy and safety between quadruple therapies with medications containing either rufloxacin or levofloxacin in the Chinese nonulcer dyspepsia patients infected with H. pylori. Methods: One hundred and thirty-eight patients after an unsuccessful 10-day standard triple therapy were enrolled in this study. They were randomized to receive a 14-day quadruple therapy with pantoprazole, bismuth citrate, and furazolidone in combination with either rufloxacin (Group Ruf, n=70) or levofloxacin (Group Lev, n=68). The H. pylori eradication was evaluated by 13C-urea breath test 4 and 12weeks after therapy was completed. Results: One hundred and twenty-seven patients (65 in Group Ruf and 62 in Group Lev) completed the study. The H. pylori eradication rates in Group Ruf were 81.4% for intention-to-treat (ITT) analysis and 87.7% for per-protocol (PP) analysis. The rates were statistically significantly higher than those in Group Lev (66.2% and 72.6%) (p<0.05). There were no severe adverse effects found in these two groups. Conclusions: Fourteen-day quadruple therapy with a combination of proton-pump inhibitor, bismuth citrate, furazolidone, and rufloxacin is considered an effective and safe rescue therapy for H. pylori eradication after failure of standard triple treatment. © 2011 Blackwell Publishing Ltd.


Hu Y.,Shanghai JiaoTong University | Wang J.,Shanghai JiaoTong University | Qian J.,Shanghai Institute of Digestive Disease | Kong X.,Shanghai JiaoTong University | And 8 more authors.
Cancer Research | Year: 2014

It is increasingly evident that long noncoding RNAs (lncRNA) have causative roles in carcinogenesis. In this study, we report findings implicating a novel lncRNA in gastric cancer, termed GAPLINC (gastric adenocarcinoma predictive long intergenic noncoding RNA), based on the use of global microarray and in situ hybridization (ISH) analyses to identify aberrantly expressed lncRNA in human gastric cancer specimens. GAPLINC is a 924-bp-long lncRNA that is highly expressed in gastric cancer tissues. GAPLINC suppression and with gene expression pro filing in gastric cancer cells revealed alterations in cell migration pathways, with CD44 expression the most highly correlated. Manipulating GAPLINC expression altered CD44 mRNA abundance and the effects of GAPLINC on cell migration and proliferation were neutralized by suppressing CD44 expression. Mechanistic investigations revealed that GAPLINC regulates CD44 as a molecular decoy for miR211-3p, a microRNA that targets both CD44 and GAPLINC. Tissue ISH analysis suggested that GAPLINC overexpression defines a subgroup of patients with gastric cancer with very poor survival. Taken together, our results identify a noncoding regulatory pathway for the CD44 oncogene, shedding new light on the basis for gastric cancer cell invasiveness. © 2014 American Association for Cancer Research.


Mao Y.,Shanghai JiaoTong University | Mao Y.,Shanghai Institute of Digestive Disease
Chinese Journal of Gastroenterology | Year: 2014

Frequently, there is a lack of safety data about diagnostic method and drug therapy of digestive diseases during pregnancy. It is profitable to understand the limited evidences of safety data about diagnosis and drug therapy of digestive diseases during pregnancy, which will allow the accurate evaluation and risk assessment on diagnostic method and treatment during pregnancy. High-quality clinical study on patients with pregnancy is helpful for the management of common digestive diseases among this special population. ©, 2014, Shanghai Institute of Digestive Diseases. All right reserved.


Chen X.,Shanghai Institute of Digestive Disease
Chinese Journal of Gastroenterology | Year: 2012

Recently endoscopic biopsy and operative specimens are sharply increasing, however, standardized pathological examination formulation is still lacking. This article detailed the pathological examination highlights of gastrointestinal biopsy specimens, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and surgical operation, with the aim of standardizing the digestive system pathological diagnosis.


Yanming Y.,Shanghai Institute of Digestive Disease
Zhongguo yi liao qi xie za zhi = Chinese journal of medical instrumentation | Year: 2010

The mechanism and principles of autofluorescence imaging based on autofluorescence technique are reported. The threshold value of fluorescence spectrum ratio applied can be quantitative and objective and the reliable measurement method that may provide intuitive method of autofluorescence imaging in the gut mucosa. The suspected lesion may be found rapidly according to the imaging color difference, therefore the results of clinical study of the digestive tract cancer diagnosis indicated that the sensitivity, specificity, and diagnostic accuracy were 94%, 95.5% and 94.8% respectively, and it has very high value in clinical application.


Jiang Y.-X.,Tongji University | Chen Y.,Tongji University | Kong X.,Shanghai Institute of Digestive Disease | Tong Y.-L.,Tongji University | Xu S.-C.,Tongji University
Hepato-Gastroenterology | Year: 2013

Background/Aims: To evaluate the efficacy of on-demand strategy with proton pump inhibitors (PPIs) in mild gastroesophageal reflux disease (GERD). Methodology: A literature search was conducted to identify randomized controlled clinical trials which investigating on-demand treatment with PPIs in mild GERD. The control group should be placebo or once-daily treatment. Comparison of treatment effect was performed. Results: Eight studies met the inclusion criteria, of which six were compared with placebo, two others with once-daily treatment. The percentage of patients unwilling to continue the study was 12.1% in the on-demand group while 39.6% in the placebo group. The meta-analysis revealed a statistically significant difference between the two groups (RR: 0.32; 95% CI: 0.23, 0.43). We obtained a similar result when compared with once-daily treatment (RR: 0.52; 95% CI: 0.34, 0.79). Conclusions: This meta-analysis indicates that on-demand therapy with PPIs is superior to placebo or once-daily treatment in terms of mild GERD. © H.G.E. Update Medical Publishing S.A.


Li H.,Shanghai Institute of Digestive Disease
Chinese Journal of Gastroenterology | Year: 2013

There are two defined diagnostic criteria for acute-on-chronic liver failure (ACLF): Asia-Pacific Association for the Study of Liver (APASL) and European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) consortium criteria. APASL criteria emphasized on hepatic function failure patient with involvement of extrahepatic organs. EASL-CLIF criteria placed emphasis on multi-organ failure of ACLF patient. Neither of them can distinguish ACLF from decompensated cirrhotic patients completely. Future perspective studying of ACLF should include identifying the disease's pathological features, making a comprehensive definition of ACLF and the mechanisms how hepatic insults triggering acute deterioration of liver function.

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