Li J.,Hubei University |
Li J.,Hubei Clinical Center |
Wang F.,Hubei University |
Wang F.,Hubei Clinical Center |
And 18 more authors.
World Journal of Gastroenterology | Year: 2015
AIM: To evaluate clinical response to initial corticosteroid (CS) treatment in Chinese ulcerative colitis patients (UC) and identify predictors of clinical response. METHODS: Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China, and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors. Short-term outcomes within one month were classified as primary response and primary non-response. Longterm outcomes within one year were classified as prolonged CS response, CS dependence and secondary non-response. CS refractoriness included primary and secondary non-response. Multivariate analyses were performed to identify predictors associated with clinical response. RESULTS: Within one month, 95.0% and 5.0% of the cases were classified into primary response and non-response, respectively. Within one year, 41.6% of cases were assessed as prolonged CS response, while 49.5% as CS dependence and 4.0% as secondary nonresponse. The rate of CS refractoriness was 8.9%, while the cumulative rate of surgery was 6.9% within one year. After multivariate analysis of all the variables, tenesmus was found to be a negative predictor of CS dependence (OR = 0.336; 95%CI: 0.147-0.768; P = 0.013) and weight loss as a predictor of CS refractoriness (OR = 5.662; 95%CI: 1.111-28.857; P = 0.040). After one-month treatment, sustained high Sutherland score (≥ 6) also predicted CS dependence (OR = 2.347; 95%CI: 0.935-5.890; P = 0.014). CONCLUSION: Tenesmus was a negative predictor of CS dependence, while weight loss and sustained high Sutherland score were strongly associated with poor CS response. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Zhao J.,Wuhan University |
Zhao J.,General Hospital of Guangzhou Military Command |
Ng S.C.,Chinese University of Hong Kong |
Lei Y.,Hubei Clinical Center |
And 23 more authors.
Inflammatory Bowel Diseases | Year: 2013
Background: Previously a disease of the West and rarely seen in China, inflammatory bowel disease (IBD) is now increasing in incidence in China. However, its true incidence is unknown. The incidence of IBD in Wuhan, a major city in central China, was investigated using populationbased methods. Methods: A prospective, population-based IBD incidence study was conducted between January 1, 2010, and December 31, 2010. New IBD cases were identified by gastroenterologists and from hospital case records in 17 central hospitals covering the health care service of central Wuhan. Cases were confirmed by follow-up and assessed by a specialist IBD group every 3 months. The population at risk was 6,085,556. Results: Overall, 131 new cases of IBD were identified during the 1-year period, including 97 cases of ulcerative colitis (UC) and 34 cases of Crohn's disease (CD). The age-adjusted incidence for all IBD, UC, and CD were 1.96 per 100,000 (95% confidence interval [CI], 1.62-2.30 per 100,000), 1.45 (95% CI, 1.16-1.75), and 0.51 (95% CI, 0.33-0.68), respectively. CD affected the small bowel only in 15%, colon only in 24%, and ileocolonic in 61%. CD often presented with complicated phenotype: inflammatory (44%), stricturing (29%), and penetrating (24%). Among patients with UC, complications included proctitis (34.5%), left-sided colitis (44.6%), and extensive colitis (19.5%). Conclusions: There is a substantial incidence of IBD in China. Although still lower than in the West, the emergence of IBD will necessitate specific health care planning and education and offers the possibility of identifying causative factors in a population with a rapidly increasing incidence. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.
Xu S.,Wuhan University |
Zhou F.,Wuhan University |
Zhou F.,Hubei Clinical Center |
Tao J.,BGI Shenzhen |
And 10 more authors.
PLoS ONE | Year: 2014
Background: Genetic variants make some contributions to inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). More than 100 susceptibility loci were identified in Western IBD studies, but susceptibility gene has not been found in Chinese IBD patients till now. Sequencing of individuals with an IBD family history is a powerful approach toward our understanding of the genetics and pathogenesis of IBD. The aim of this study, which focuses on a Han Chinese CD family, is to identify high-risk variants and potentially novel loci using whole exome sequencing technique. Methods: Exome sequence data from 4 individuals belonging to a same family were analyzed using bioinformatics methods to narrow down the variants associated with CD. The potential risk genes were further analyzed by genotyping and Sanger sequencing in family members, additional 401 healthy controls (HC), 278 sporadic CD patients, 123 UC cases, a pair of monozygotic CD twins and another Chinese CD family. Results: From the CD family in which the father and daughter were affected, we identified a novel single nucleotide variant (SNV) c.374T>C (p.I125T) in exon 4 of discs large homolog 1 (DLG1), a gene has been reported to play mutiple roles in cell proliferation, T cell polarity and T cell receptor signaling. After genotyping among case and controls, a PLINK analysis showed the variant was of significance (P<0.05). 4 CD patients of the other Chinese family bore another non-synonymous variant c.833G>A (p.R278Q) in exon 9 of DLG1. Conclusions: We have discovered novel genetic variants in the coding regions of DLG1 gene, the results support that DLG1 is a novel potential susceptibility gene for CD in Chinese patients. © 2014 Xu et al.
Wang X.,Wuhan University |
Wang X.,Hubei Clinical Center |
Wang G.,Wuhan University |
Wang G.,Hubei Clinical Center |
And 16 more authors.
European Journal of Gastroenterology and Hepatology | Year: 2014
Background Growing evidence has shown that coagulation processes play an important role in disease pathogenesis and/or disease progression in patients with inflammatory bowel disease. However, no study has ever focused on the possible influence of infliximab (IFX) therapy on the coagulation status in patients with Crohn's disease (CD). Objective To investigate the difference in the coagulation biomarkers between the CD patients and the control participants, and evaluate the impact of IFX usage on the coagulation status of CD patients. Patients and methods A retrospective study that included a case-control study and a self-control study was designed. The medical records of CD patients and control participants were evaluated according to the inclusion and exclusion criteria. The results of laboratory tests including blood routine, coagulation, D-dimer, C-reactive protein, and erythrocyte sedimentation rate were retrieved to assess the coagulation state. Results In the case-control study, almost all the parameters showed a statistically significant difference between the CD patients and the control participants, except for activated partial thromboplastin time and thrombin time (the P value ranged from 0.000 to 0.002). Most of the values of the parameters reverted to normal over time during IFX therapy in the self-control study. Moreover, the fibrinogen concentration decreased obviously after IFX infusion (P=0.000) and the D-dimer concentration also decreased obviously by about half of the start value after IFX usage (P=0.018). Conclusion IFX therapy could ameliorate the hypercoagulable state in patients with CD. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Zhu S.,Hubei University |
Zhu S.,Hubei Clinical Center |
Bing Y.,Hubei Clinical Center |
Wang X.,Hubei University |
And 13 more authors.
PLoS ONE | Year: 2014
Background: Natural killer T (NKT) cells share phenotypic and functional properties with both conventional natural killer cells and T cells. These cells might have an important role in the pathogenesis of ulcerative colitis (UC). The interaction of chemokine ligand 25 (CCL25) with chemokine receptor 9 (CCR9) is involved in gut-specific migration of leukocytes and induces regulatory T cells (Tregs) to migrate to the intestine in chronic ileitis. Methodology/Findings: In UC patients, NKT receptor CD161, CCL25, and CCR9 expression levels were evaluated by qRTPCR. A murine model of oxazolone-induced colitis was induced in BALB/c mice. The mRNA levels of NK1.1, CCL25 and CCR9, and pro-inflammatory cytokines in mice were evaluated. The CCR9 expression on Type I or invariant NKT (iNKT) cells, and the iNKT cells chemotaxis are observed according to flow cytometry. NKT receptor CD161, CCL25 and CCR9 expression levels were significantly increased in UC patients. And, the mRNA expression levels of NK1.1, CCL25 and CCR9 were increased in oxazolone-induced colitis in mice. The production of pro-inflammatory cytokines was significantly increased, especially interleukin 4 (IL-4), IL-10 and IL-13. We observed significantly increased CCR9 expression on iNKT cells. Furthermore, we found an increased iNKT population and enhanced chemotaxis during oxazolone-induced colitis. Conclusions/ Significance: Our study suggests that CCL25/CCR9 interactions may promote the induction and function of iNKT cells during oxazolone-induced colitis. These findings may have important implications for UC treatment and suggest a role for CCR9 inhibitors. © 2014 Zhu et al.
Shang J.,Wuhan University |
Shang J.,Hubei Clinical Center |
Li L.,Wuhan University |
Li L.,Hubei Clinical Center |
And 12 more authors.
Mediators of Inflammation | Year: 2016
Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a key mediator of TNF receptor superfamily members and is important in both T helper (Th) cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5's influence on inflammatory bowel diseases (IBDs), we investigated TRAF5 deficiency's effect on dextran sulfate sodium- (DSS-) induced colitis. Colitis was induced in TRAF5 knockout (KO) mice and their wild-type (WT) littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4+ T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-B in CD4+ T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation. © 2016 Jian Shang et al.
Yi F.,Wuhan University |
Zhao J.,Hubei Clinical Center |
Luckheeram R.V.,Hubei Clinical Center |
Lei Y.,Hubei Clinical Center |
And 6 more authors.
Virology Journal | Year: 2013
Background: The etiology of inflammatory bowel disease (IBD) is not clear and cytomegalovirus (CMV) infection is often associated with IBD patients. The etiologic link between IBD and CMV infection needs to be studied. The objective of the present study is to investigate the prevalence and risk factors of CMV in a cohort of IBD patients from Central China. Methods. Two hundred and twenty six IBD patients (189 ulcerative colitis (UC) and 37 patients with Crohn's disease (CD)), and 290 age and sex matched healthy controls were recruited. CMV DNA was detected by nested PCR, while serum anti-CMV IgG and anti-CMV IgM was determined by ELISAs. Colonoscopy/enteroscopy with biopsy of diseased tissues and subsequent H&E stain were then conducted in IBD patients with positive anti-CMV IgM. Finally, we analyzed the prevalence and clinical risk factors of CMV infection in IBD patients. Results: The prevalence of CMV DNA and anti-CMV IgG positive rate in IBD patients were 84.07% and 76.11%, respectively, higher than those in healthy controls (59.66% and 50.69%, respectively, P < 0.05), However, anti-CMV IgM positive rate was no different with healthy controls (1.77% vs 0.34%, P = 0.235). In univariate analysis of risk factors, the recent use of corticosteroid was associated with increase of CMV DNA and IgM positive rate in UC (P = 0.035 and P = 0.015, respectively), aminosalicylic acid drug therapy was correlated with positivity of CMV DNA and IgG in UC and CMV DNA in CD (P = 0.041, P < 0.001 and P = 0.014, respectively), the treatment of immunosuppresent was correlated with CMV IgM (P < 0.001). Furthermore, patients with severe UC were significantly associated with CMV DNA and IgM (P = 0.048 and P = 0.031, respectively). Malnutrition (albumin < 35 G/L) was also found to be related with CMV recent infection (P = 0.031). In multivariate analysis of risk factors in UC, pancolitis was significantly associated with CMV DNA positivity (P = 0.001). Severe UC and pancolitis seemed to be related with IgG positivity. For CD, there was just single factor associated with CMV positive in each group, multivariate analysis was unnecessary. Conclusions: CMV positive rate in IBD patients was significantly higher, than in healthy controls. The use of aminosalicylic acid, corticosteroid, immunosuppressants, pancolitis and severe IBD patients seemed to be more susceptible to CMV infection in univariate analysis of risk factors. However, no risk factor was found to be significantly correlated with CMV infection in multivariate analysis of risk factors. © 2013 Yi et al.; licensee BioMed Central Ltd.
Wang W.,Wuhan University |
Chen L.,Wuhan University |
Zhou R.,Wuhan University |
Zhou R.,Hubei Clinical Center |
And 6 more authors.
Journal of Clinical Microbiology | Year: 2014
Dysbiosis in the intestinal microbiota of persons with inflammatory bowel disease (IBD) has been described, but there are still varied reports on changes in the abundance of Bifidobacterium and Lactobacillus organisms in patients with IBD. The aim of this investigation was to compare the compositions of mucosa-associated and fecal bacteria in patients with IBD and in healthy controls (HCs). Fecal and biopsy samples from 21 HCs, 21 and 15 Crohn's disease (CD) patients, and 34 and 29 ulcerative colitis (UC) patients, respectively, were analyzed by quantitative real-time PCR targeting the 16S rRNA gene. The bacterial numbers were transformed into relative percentages for statistical analysis. The proportions of bacteria were uniformly distributed along the colon regardless of the disease state. Bifidobacterium was significantly increased in the biopsy specimens of active UC patients compared to those in the HCs (4.6% versus 2.1%, P=0.001), and the proportion of Bifidobacterium was significantly higher in the biopsy specimens than in the fecal samples in active CD patients (2.7% versus 2.0%, P=0.012). The Lactobacillus group was significantly increased in the biopsy specimens of active CD patients compared to those in the HCs (3.4% versus 2.3%, P= 0.036). Compared to the HCs, Faecalibacterium prausnitzii was sharply decreased in both the fecal and biopsy specimens of the active CD patients (0.3% versus 14.0%, P<0.0001 for fecal samples; 0.8% versus 11.4%, P<0.0001 for biopsy specimens) and the active UC patients (4.3% versus 14.0%, P=0.001 for fecal samples; 2.8% versus 11.4%, P<0.0001 for biopsy specimens). In conclusion, Bifidobacterium and the Lactobacillus group were increased in active IBD patients and should be used more cautiously as probiotics during the active phase of IBD. Butyrate-producing bacteria might be important to gut homeostasis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Wang F.,Hubei University |
Wang F.,Hubei Clinical Center |
Lin X.,Hubei University |
Lin X.,Hubei Clinical Center |
And 4 more authors.
European Journal of Clinical Pharmacology | Year: 2015
Background: Anti-tumor necrosis factor-alpha (TNF-α) agents have considerable advances in treating inflammatory bowel disease (IBD). These drugs carry possible risk of adverse symptoms, and no meta-analysis has examined this issue and the potential duration-response relationship. Purpose: The purpose of this study was to assess duration-response relationship between anti-TNF-α agents and risk of adverse symptoms from all available randomized control trials (RCTs) with placebo arms in IBD. Methods: PubMed, OVID, and Cochrane Library were searched to January 2015. The RCTs comparing anti-TNF-α therapy with placebo in adults with IBD were eligible. We estimated pooled relative risks (RRs) of adverse symptoms for anti-TNF-α therapy and examined both non-linear and linear duration-response relations between therapy duration and significant related adverse symptoms. Results: Twenty-three RCTs with 7325 patients were included. Adverse symptoms of headache, nausea/vomit, abdominal pain, fever, and arthralgia showed no significant relationship with anti-TNF-α therapy, respectively. Fatigue was significantly associated with anti-TNF-α therapy (RR 1.35, 95 % confidence interval (CI) 1.01-1.81), and subgroup analysis indicated that long therapy duration (>30 weeks) and combination without azathioprine (AZA) were two risk factors for the occurrence of fatigue (RR 1.74, 95 % CI 1.03-2.93; RR 1.65, 95 % CI 1.13-2.40). In the trials without AZA combination, there was a linear duration-response relationship between therapy duration and risk of fatigue (P∈=∈0.0217), and duration of 35 weeks increased the risk of fatigue by 50 %. Conclusion: This meta-analysis suggested a promotive effect of anti-TNF-α therapy to the occurrence of fatigue, and for the anti-TNF-α therapy without AZA combination, a linear duration-response relationship existed between therapy duration and risk of fatigue. © 2015 Springer-Verlag Berlin Heidelberg.