Background: The need for therapeutic endoscopy in patients with upper GI hemorrhage is important in determining the risk and disposition of these patients. Pre-endoscopic risk scores may be helpful in predicting this need. Objective: To test the Blatchford and pre-endoscopic Rockall scores with the need for therapeutic endoscopy as the primary outcome. Design: Prospective validation study. Setting: Tertiary-care university-affiliated hospital. Patients and Interventions: Between January 1, 2006 and February 28, 2007, 1087 patients with upper GI hemorrhage who had undergone an inpatient EGD within 24 hours were entered in the study. Main Outcome Measurements: Blatchford and pre-endoscopic Rockall scores were prospectively calculated for all patients, and the need for therapeutic endoscopy was determined during the EGD. Results: Of the 1087 patients, 297 (27.3%) needed therapeutic endoscopy. The mean Blatchford score for those who needed therapeutic endoscopy was significantly higher (mean [standard deviation]: 10.3 [3.5] vs 7.0 [4.4], P < .001). The area under a receiver-operating characteristic curve was 0.72 (95% CI, 0.68-0.75). A threshold of 0 (low risk) predicted the need for therapeutic endoscopy with 100% sensitivity and 6.3% specificity. Fifty (4.6%) patients were identified as low risk. The pre-endoscopic Rockall score was unable to predict this need. Limitations: The decision to perform therapeutic endoscopy is a subjective one, although endoscopists are trained to follow international consensus guidelines. Conclusions: The Blatchford score is more useful for predicting low-risk patients who do not need therapeutic endoscopy and who may be suitable for outpatient management. A threshold of 0 for low risk should be used. The Rockall score is not helpful in predicting the presence of low-risk lesions. © 2010 American Society for Gastrointestinal Endoscopy.

Pang    Jessica Ching    James Lau    沈祖堯     David yates Graham    Francis Chan   

Gastrointestinal Endoscopy

2010

Background: The interleukin-2-mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling. Methods: Using a case-control design, we tested for an association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis, and severe malaria) in blood samples from 8402 persons in Gambia, Hong Kong, Kenya, Malawi, and Vietnam. We had previously tested 20 other immune-related genes in one or more of these sample collections. Results: We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five single-nucleotide polymorphisms (SNPs) (at positions -639, -292, -163, +1320, and +3415 [all relative to CISH]) within the CISH-associated locus were considered together in a multiple-SNP score, we found an association between CISH genetic variants and susceptibility to bacteremia, malaria, and tuberculosis (P = 3.8x10 for all comparisons), with -292 accounting for most of the association signal (P = 4.58x10). Peripheral-blood mononuclear cells obtained from adult subjects carrying the -292 variant, as compared with wild-type cells, showed a muted response to the stimulation of interleukin-2 production - that is, 25 to 40% less CISH expression. Conclusions: Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signaling have a role in immunity against various infectious diseases. The overall risk of one of these infectious diseases was increased by at least 18% among persons carrying the variant CISH alleles. Copyright © 2010 Massachusetts Medical Society.

Chiea chuen Khor    Fredrik Vannberg    Jonathan Chapman    Guo Haiyan    Sunny Wong    Walley Andrew J.    Vukcevic Damjan    Anna Rautanen    Mills Tara C.    Chang Kwok-Chiu    Kaiman Kam    Crampin Amelia    Ngwira Bagrey    Leung Chi-Chiu    Tam Cheuk-ming    Chiuyeung Chan    沈祖堯     Wing wai Yew    Toh Kai Yee    Tay Stacey K. H.    Dominic Kwiatkowski    Christian Lienhardt    Hien Tran Tinh    Nicholas Day    Nobert Peshu    Kevin Marsh    Maitland    John anthony gerard Scott    Thomas Williams    Berkley James A.    Floyd Sian    Nelson Leung-Sang Tang    Paul em Fine    Goh Denise L.M.    Hil Adrian V.S.   

New England Journal of Medicine

2010

Kaion Ng    Yu Jun    Ava Kwong    沈祖堯    

Gut

2010

Background Dyspepsia and irritable bowel syndrome (IBS) are common in Western populations. Aim To determine the epidemiology of dyspepsia and IBS in China. Methods A representative sample of 18 000 adults from five regions of China were asked to complete the modified Rome II questionnaire; 20% were asked to complete the 36-item Short Form Health Survey (SF-36). Participants from Shanghai were invited to provide blood samples and undergo oesophagogastroduodenoscopy. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using a multivariate logistic regression model. Results The survey was completed by 16 091 individuals (response rate: 89.4%). Overall, 387 participants (2.4%) had dyspepsia and 735 (4.6%) had IBS. All SF-36 dimension scores were at least five points lower in individuals with than without dyspepsia or IBS (P ≤ 0.001). In Shanghai, 1030 (32.7%) of the 3153 respondents agreed to endoscopy; neither dyspepsia nor IBS was found to be associated with reflux oesophagitis, peptic ulcer disease or Helicobacter pylori infection. Conclusions Prevalence estimates for dyspepsia and IBS in China are lower than in Western populations. In China, dyspepsia or IBS symptoms are generally not associated with underlying organic disease. © 2010 Blackwell Publishing Ltd.

Yanfang Zhao    Duowu Zou    王瑞    马修强    Xiaoyan Yan    Xiaohua Man    Li Gao    Jiqian Fang    Hong Yan    Kang Xiaoping    Yin Ping    郝元涛    Li Qiang    Dent John    沈祖堯     Halling Katarina    Wernersson    Johansson Saga    Jia He   

Alimentary Pharmacology and Therapeutics

2010

Background: The epidemiology of gastroesophageal reflux disease (GERD) has yet to be investigated using the symptomatic threshold criteria recommended by the Montreal Definition. This study aimed to determine the prevalence of symptom-defined GERD across five regions of China, and to investigate variables associated with GERD.Methods: A representative sample of 18 000 adults (aged 18-80 years) were selected equally from rural and urban areas in each region (n = 1800). According to the Montreal Definition, GERD is present when mild symptoms of heartburn and/or regurgitation occur on ≥2 days a week, or moderate-to-severe symptoms of heartburn and/or regurgitation occur on ≥1 day a week.Results: In total, 16 091 participants completed the survey (response rate: 89.4%) and 16 078 responses were suitable for analysis. Applying the Montreal criteria, the prevalence of symptom-defined GERD was 3.1% and varied significantly (p < 0.001) among the five regions (from 1.7% in Guangzhou to 5.1% in Wuhan) and between rural and urban populations (3.8% vs 2.4%). Factors significantly associated with GERD included living in a rural area and a family history of gastrointestinal diseases.Conclusions: This population-based survey found that the prevalence of symptom-defined GERD in China was 3.1%, which is lower than that found in Western countries. © 2010 He et al; licensee BioMed Central Ltd.

Jia He    马修强    Yanfang Zhao    Wang Rui    Xiaoyan Yan    Hong Yan    Yin Ping    Kang Xiaoping    Jiqian Fang    郝元涛    Li Qiang    Dent John    沈祖堯     Duowu Zou    Wallander Mari-Ann    Johansson Saga    Wenbin Liu    李兆申   

BMC Gastroenterology

2010

This study aimed to clarify the relationship between TRPV1 activation-induced visceral pain and the serotonin pathway in the colon of rats. The effects of para-chlorophenylalanine (pCPA) on visceral pain threshold pressure were assessed in capsaicin -induced visceral pain of rats. The expression of TRPV1 in the colon was examined by immunohistochemistry and Western blot analysis, and TRPV1 excitability in dorsal root ganglion (DRG) neurons was examined by whole-cell patch-clamp recording in pCPA-treated rats. Calcineurin and Ca-calmodulin-dependent kinase II (CaMKII), the important proteins in maintaining TRPV1 function in the colon, were also tested by Western blot analysis and immunofluorescence staining. Results showed that pCPA significantly increased the capsaicin-induced visceral pain threshold by 2.3-fold, and the enhanced visceral pain threshold corresponded with decreased 5-HT content (58% depleted) and enterochromaffin cell number (80% reduced). The reduced excitability of TRPV1 in DRG neurons, instead of changed TRPV1 expression, is responsible for the enhanced visceral pain threshold in 5-HT-depleted rats, and the mechanism may be related to the decreased expression of pCaMKII. These results indicate that visceral hypersensitivity induced by TRPV1 activation is modulated through 5-HT pathways and the attenuated function of TRPV1 and decreased protein expression of pCaMKII may play an important role in capsaicin-induced TRPV1 desensitization under 5-HT-depleted condition. The important role of TRPV1 and 5-HT in generating and maintaining visceral hypersensitivity may provide insights for the treatment of visceral hypersensitivity. © 2010 Elsevier B.V.

Hongyan Qin    Luo Jialie    Qi Sheng-Da    徐宏喜    沈祖堯     Zhaoxiang Bian   

European Journal of Pharmacology

2010

Background: Gastroesophageal reflux disease imposes a significant burden of illness in Western populations. However, data on the impact of reflux symptoms on daily life in Asian populations are scarce. The current study aimed to evaluate the impact of GERD (defined on the basis of symptoms) on health-related quality-of-life (HRQoL) in individuals from five regions in China, as part of the Systematic Investigation of Gastrointestinal Diseases in China (SILC) study.Methods: In total, 18 000 residents were randomly selected from across five regions of China and asked to complete a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire (RDQ). A randomly selected subsample of one-fifth of subjects (20% from each region) completed Chinese versions of the 36-item self-administered (SF-36) questionnaire and Epworth Sleepiness Scale (ESS) questionnaire. Reflux symptoms were defined as the presence of heartburn and/or regurgitation. Symptom-defined GERD was diagnosed as mild heartburn and/or regurgitation ≥2 days per week, or moderate/severe heartburn and/or regurgitation ≥1 day a week, based on the Montreal Definition of GERD for population-based studies.Results: The response rate was 89.4% for the total sample (16 091/18 000), and for the 20% subsample (3219/3600). Meaningful impairment was observed in all 8 SF-36 dimensions in participants with symptom-defined GERD, in 7 of the 8 SF-36 dimensions in participants with troublesome reflux symptoms, and in 6 of the 8 SF-36 dimensions in participants with reflux symptoms below the threshold for symptom-defined GERD. Meaningful daytime sleepiness was also observed in each of these groups. The proportion of individuals reporting troublesome symptoms increased as reflux symptom frequency and severity approached the threshold for symptom-defined GERD, and this was associated with concomitant decreases in all HRQoL measures. Troublesome symptoms were reported by 68.2% (75/110) of individuals with symptom-defined GERD.Conclusions: GERD diagnosed using symptom/frequency criteria (recommended for population-based studies), or based on troublesome reflux symptoms (recommended for the clinic), is associated with significantly impaired HRQoL in Chinese individuals. However, patient groups identified using these definitions do not overlap completely, suggesting that they capture slightly different, though clinically relevant, GERD populations. © 2010 Wang et al; licensee BioMed Central Ltd.

王瑞    Duowu Zou    马修强    Yanfang Zhao    Xiaoyan Yan    Hong Yan    Jiqian Fang    Yin Ping    Kang Xiaoping    Qiang Li    Dent John    沈祖堯     Halling Katarina    Johansson Saga    Wenbin Liu    Jia He   

Health and Quality of Life Outcomes

2010

OBJECTIVES:Complications of peptic ulcer disease (PUD) are common in China. Population-based estimates of the prevalence of PUD are needed to quantify and characterize the population at risk of these complications.METHODS:As part of a large epidemiological study, 3,600 randomly selected residents of Shanghai (aged 18-80 years) were asked to undergo endoscopy and to provide blood samples for Helicobacter pylori serology. All participants also completed a general information questionnaire and Chinese versions of the reflux disease questionnaire (RDQ) and Rome II questionnaire. Associations between PUD and other factors were analyzed using a multiple logistic regression model.RESULTS:In total, 3,153 individuals (87.6%) completed the survey. All underwent blood tests, and 1,030 patients (32.7%) agreed to undergo endoscopy. Results from 1,022 patients were suitable for analysis. In all, 176 participants (17.2%) had PUD (62 with gastric ulcer; 136 with duodenal ulcer). The prevalence of H. pylori infection was 73.3% in the total population and 92.6% among those with PUD. H. pylori infection was associated with the presence of PUD (odds ratio (OR), 6.77; 95% confidence interval (CI), 2.85-16.10). The majority (72.2%) of individuals with PUD had none of the upper gastrointestinal symptoms assessed by the RDQ. PUD was not significantly associated with symptom-defined gastroesophageal reflux disease (GERD) (OR, 0.80; 95% CI, 0.32-2.03), reflux esophagitis (OR, 1.46; 95% CI, 0.76-2.79) or dyspepsia (OR, 1.69; 95% CI, 0.94-3.04).CONCLUSIONS:The prevalence of endoscopically confirmed PUD in this Shanghai population (17.2%) is substantially higher than in Western populations (4.1%). The majority of individuals with PUD were asymptomatic. © 2010 by the American College of Gastroenterology.

李兆申    Duowu Zou    马修强    陈洁    Xingang Shi    Yanfang Gong    Xiaohua Man    Li Gao    Yanfang Zhao    王瑞    Xiaoyan Yan    Dent John    沈祖堯     Wernersson    Johansson Saga    Wenbin Liu    Jia He   

American Journal of Gastroenterology

2010

T-box transcription factor 5 (TBX5) is a member of a phylogenetically conserved family of genes involved in the regulation of developmental processes. The function of TBX5 in cancer development is largely unclear. We identified that TBX5 was preferentially methylated in cancer using methylation-sensitive arbitrarily primed PCR. We aim to clarify the epigenetic inactivation, biological function and clinical significance of TBX5 in colon cancer. Promoter methylation was evaluated by combined bisulfite restriction analysis and bisulfite genomic sequencing. Cell proliferation was examined by cell viability assay and colony formation assay, apoptosis by flow cytometry and cell migration by wound-healing assay. TBX5 target genes were identified by cDNA microarray analysis. Cox regression model and log-rank test were used to identify independent predictors of prognosis. TBX5 was silenced or downregulated in 88% (7/8) colon cancer cell lines, but was expressed in normal colon tissues. Loss of gene expression was associated with promoter methylation. The biological function of TBX5 in human colon cancer cells was examined. Re-expression of TBX5 in silenced colon cancer cell lines suppressed colony formation (P<0.001), proliferation (P<0.001), migration and induced apoptosis (P<0.01). Induction of apoptosis was mediated through cross-talk of extrinsic apoptosis pathway, apoptotic BCL2-associated X protein and Granzyme A signaling cascades. TBX5 suppressed tumor cell proliferation and metastasis through the upregulation of cyclin-dependent kinase inhibitor 2A, metastasis suppressor 1 and downregulation of synuclein gamma and metastasis-associated protein 1 family member 2. TBX5 methylation was detected in 68% (71/105) of primary colon tumors. Multivariate analysis showed that patients with TBX5 methylation had a significantly poor overall survival (P=0.0007). In conclusion, we identified a novel functional tumor suppressor gene TBX5 inactivated by promoter methylation in colon cancer. Detection of methylated TBX5 may serve as a potential biomarker for the prognosis of this malignancy. © 2010 Macmillan Publishers Limited All rights reserved.

Jun Yu    Ma    Kinfai Cheung    Xiangchun Li    Linwei Tian    Shiyan Wang    Wu    William ka kei Wu    何明亮    王明伟    Simon siu man Ng    沈祖堯    

Oncogene

2010

Wai keung Leung    Henry lik yuen Chan    Raymond Lai    沈祖堯    

Hong Kong Medical Journal

2010