Hubei Clinical Center

Wuhan, China

Hubei Clinical Center

Wuhan, China
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Chen P.,Wuhan University | Chen P.,Hubei Clinical Center | Chen P.,The Central Hospital of Enshi Autonomous Prefecture | Wang F.,Wuhan University | And 11 more authors.
Oncotarget | Year: 2017

Hepatocellular carcinoma (HCC) has a high incidence and mortality worldwide, and its carcinogenesis and progression are influenced by a complex network of gene interactions. A weighted gene co-expression network was constructed to identify gene modules associated with the clinical traits in HCC (n = 214). Among the 13 modules, high correlation was only found between the red module and metastasis risk (classified by the HCC metastasis gene signature) (R2 = -0.74). Moreover, in the red module, 34 network hub genes for metastasis risk were identified, six of which (ABAT, AGXT, ALDH6A1, CYP4A11, DAO and EHHADH) were also hub nodes in the protein-protein interaction network of the module genes. Thus, a total of six hub genes were identified. In validation, all hub genes showed a negative correlation with the four-stage HCC progression (P for trend < 0.05) in the test set. Furthermore, in the training set, HCC samples with any hub gene lowly expressed demonstrated a higher recurrence rate and poorer survival rate (hazard ratios with 95% confidence intervals > 1). RNA-sequencing data of 142 HCC samples showed consistent results in the prognosis. Gene set enrichment analysis (GSEA) demonstrated that in the samples with any hub gene highly expressed, a total of 24 functional gene sets were enriched, most of which focused on amino acid metabolism and oxidation. In conclusion, co-expression network analysis identified six hub genes in association with HCC metastasis risk and prognosis, which might improve the prognosis by influencing amino acid metabolism and oxidation. © Chen et al.


Feng J.-R.,Wuhan University | Feng J.-R.,Hubei Clinical Center | Qiu X.,Wuhan University | Qiu X.,Hubei Clinical Center | And 18 more authors.
Gastroenterology Research and Practice | Year: 2017

The aim of this study is to investigate the diagnostic efficacy of neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-monocyte ratio (NMR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with Crohn's disease (CD) and non-CD controls. These ratios were all derived from complete blood counts. Two hundred and six participants including CD inpatients and non-CD controls were retrospectively enrolled. We found statistically higher NLR and PLR and lower LMR in CD patients than in non-CD controls (all P<0.01). However, NMR was not different between the two groups (P=0.18). In addition, NLR, PLR, and LMR were associated with CRP and ESR. Optimal cutoffs for NLR and PLR were 2.72 (sensitivity: 68.3%, specificity: 75.9%, and overall accuracy: 70.1%) and 132.88 (sensitivity: 76.7%, specificity: 84.8%, and overall accuracy: 80.8%), respectively. In conclusion, the NLR and PLR might be effective, readily available, and low-cost biomarkers for differentiating CD patients from non-CD controls. © 2017 Jue-Rong Feng et al.


Qiu X.,Wuhan University | Qiu X.,Hubei Clinical Center | Feng J.-R.,Wuhan University | Feng J.-R.,Hubei Clinical Center | And 12 more authors.
Medicine (United States) | Year: 2017

Background: Autologous hematopoietic stem cell transplantation (HSCT) has been proposed for patients with refractory Crohn's disease (CD), but it is associated with mortality and adverse events; the balance between risks and benefits becomes significantly important in the therapy. The aim of the study was to assess the efficacy and safety of autologous HSCT therapy for refractory CD. Methods: We conducted a comprehensive search of PubMed, Embase, the Cochrane library, and Web of Science from inception to February 2017. The pooled estimate rates for efficacy and safety of refractory CD was performed by meta-analysis and reported according to the standard Cochrane guidelines and the PRISMA statement. Results: Four prospective uncontrolled cohort studies, 4 prospective case series, and 1 randomized controlled trial (RCT) were included. Autologous HSCT had a high rate of clinical and endoscopic remission in refractory CD [79.4%, 95% confidence interval (95% CI): 0.550-0.924; 81.9%, 95% CI: 0.603-0.931, respectively]. In the case of safety, it had a relatively high incidence rate of transplant-related mortality (6.4%, 95% CI: 0.028-0.140). A significant association was observed between autologous HSCT and the incidence of febrile neutropenia (83.2%, 95% CI: 0.632-0.934). About 18.5% (95% CI: 0.061-0.442) of patients with refractory CD reached clinical remission at mobilization phase. Besides, 82.1% (95% CI: 0.692-0.903) and 54.1% (95% CI: 0.261-0.797) patients with refractory CD could achieve immunosuppressive-free and steroid-free remission for at least 12 months after the therapy. Conclusion: Autologous HSCT could be a complicated treatment with relatively high mortality and significantly high efficacy for refractory CD, which should be used with caution. However, more RCTs of larger samples using refined and standardized protocols and longer period of follow-up time are needed to further assess the outcomes of autologous HSCT therapy. Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.


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.


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.

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