Correlation between Simplified Endoscopic Score for Crohn's Disease (SES-CD) and Clinical and Laboratory Markers in Patients with Crohn's Disease / 胃肠病学

Endoscopic activity has been used as an endpoint in treatment of Crohn's disease (CD).Simplified Endoscopic Score for Crohn's Disease (SES-CD) is a simple and easy-to-use endoscopic scoring system for CD, however, studies evaluating the correlation between SES-CD and noninvasive inflammatory markers are scarce.Aims: To investigate the correlation between SES-CD and clinical and laboratory inflammatory markers for identifying a noninvasive surrogate marker for endoscopic activity of CD.Methods: Forty-two patients with CD were enrolled for detecting laboratory inflammatory markers including leukocyte and platelet count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), albumin (Alb) and fecal calprotectin (FC);SES-CD and Crohn' disease activity index (CDAI) were assessed.Predictive performance of these markers for endoscopic activity of CD was analyzed by ROC curve, and the correlation of SES-CD with all these markers was evaluated.Results: The platelet count, CRP, ESR, FC and SES-CD were significantly higher in active CD than in inactive CD, while Hb and Alb were significantly lower in active CD (P all <0.05).In all the noninvasive markers, only CDAI and FC had an area under the curve (AUC) greater than 0.9 for predicting CD endoscopic activity.Taken 150 as the cut-off value of CDAI and 50 μg/g (the upper limit of normal, ULN) as the cut-off value of FC, the sensitivity of CDAI and FC were 58.8% and 100%, and the specificity were 100% and 60.0%, respectively.SES-CD had moderate correlation with CDAI, platelet count, CRP, ESR, Alb and FC, respectively (P all <0.05).Conclusions: SES-CD is correlated moderately with the clinical and laboratory inflammatory markers, however, when taken the ULN as cut-off value the conventional inflammatory markers such as CDAI, CRP and ESR are hard to predict sensitively and accurately the endoscopic activity of CD;while FC has fairly high accuracy and sensitivity and can be used as a noninvasive surrogate marker for evaluating endoscopic activity of CD.

Expression and Significance of MicroRNA-595 in Inflammatory Bowel Disease / 胃肠病学

Background:Dysregulation of microRNAs is associated with intestinal mucosal barrier injury,intestinal inflammation and intestinal dysfunction. Abnormal expression of microRNAs occurs in patients with inflammatory bowel disease(IBD). Aims:To investigate the expression and significance of microRNA-595( miR-595)in IBD. Methods:A total of 100 patients with IBD at Nanjing General Hospital of Nanjing Military Command of PLA from July 2012 to July 2014 were enrolled,in which 63 cases were ulcerative colitis(UC)and 37 cases were Crohn’s disease(CD). According to disease activity,patients were divided into active UC(aUC)group,remissive UC(rUC)group,active CD(aCD)group and remissive CD(rCD)group. A total of 42 healthy subjects were served as normal control(NC)group. Specimens of serum and intestinal tissue were collected. Expression of miR-595 in serum and intestinal tissue was determined by fluorescence quantitative PCR. Luciferase report gene plasmid containing the 3’UTR of neural cell adhesion molecule 1(NCAM1)or fibroblast growth factor receptor 2(FGFR2)and plasmid containing miR-595 were co-transfected into human colon cancer cell line HCT116 to detect the effect of miR-595 on transcriptional activities of NCAM1 and FGFR2. Results:Expression of miR-595 in serum and intestinal tissue in UC and CD groups was significantly higher than that in NC group(P < 0. 05), and that in aUC and aCD groups was significantly higher than that in rUC and rCD groups,respectively(P < 0. 05). MiR-595 could down-regulate the transcriptional activities of NCAM1 and FGFR2 through directly binding to the 3’UTR of NCAM1 and FGFR2. Conclusions:Expression of miR-595 in serum and intestinal tissue is increased in patients with IBD and correlates with disease activity. MiR-595 inhibits the expressions of tight junction protein NCAM1 and FGFR2,thereby inducing injury of intestinal mucosal barrier and promoting intestinal inflammation. MiR-595 can serve as a serum biomarker for diagnosis of IBD and disease activity evaluation.

Relationship between Peripheral Blood CD3 +,CD4 + and CD8 + T Cells and Inflammation Markers in Patients with Crohn’s Disease / 胃肠病学

Background:Abnormal immune response is involved in the pathogenesis of Crohn’s disease( CD),and T lymphocytes are the main players in the immune response. Aims:To investigate the relationship between peripheral blood CD3 + ,CD4 + and CD8 + T cells and inflammation-related markers in patients with CD. Methods:Proportions of peripheral blood CD3 + ,CD4 + and CD8 + T cells were measured by flow cytometry in 26 CD patients( including 14 patients in active stage and 12 in remission stage )and 8 healthy volunteers(control group),and their correlation with inflammation-related markers(including white blood cell count,platelet count,ESR,CRP,albumin and hemoglobin) were analyzed. Results:Proportions of CD3 + ,CD4 + and CD8 + T cells were significantly increased in patients with active CD than those with remission CD and controls( P ﹤ 0. 05),however,no significant differences were found between remission CD patients and controls(P ﹥ 0. 05). ESR and CRP in active CD patients were significantly higher than those in controls(P ﹤ 0. 05),while albumin and hemoglobin levels were significantly decreased(P ﹤ 0. 05);albumin in remission CD patients was significantly lower than that in controls(P ﹤ 0. 05). No significant differences in white blood cell count and platelet count were found between active,remission CD patients and controls(P ﹥ 0. 05). Proportions of CD3 + , CD4 + and CD8 + T cells were positively correlated with CRP,and negatively correlated with hemoglobin( P ﹤ 0. 05);CD3 + and CD4 + T cells were positively correlated with ESR(P ﹤ 0. 05). However,CD3 + ,CD4 + and CD8 + T cells were not correlated with white blood cell count,platelet count and albumin level( P ﹥ 0. 05). Conclusions:Proportions of peripheral blood CD3 + ,CD4 + and CD8 + T cells are increased with the increase of disease activity in CD,and are positively correlated with CRP,and negatively correlated with hemoglobin.

Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis

BACKGROUND/AIMS: This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. METHODS: Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. RESULTS: The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%+/-1.2% in controls and was significantly increased to 7.2%+/-1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. CONCLUSIONS: There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.

The role of IL-18 in acute pancreatitis-associated liver injury / 医学研究生学报

IL-18 participates in the morbility and exacerbation of acute pancreatitis,and induces the organ-injury of extra-pancreas.The aim of this review is to explore the source of and the regulation of activation and secretion of IL-18,as well as the pathogenesis of acute pancreatitis-associated liver injury induced by IL-18.

Role of Kupffer cell-expressed Fas ligand on acute pancreatitis-associated liver injury / 解放军医学杂志

Objective To explore the role of Kupffer cell-expressed Fas ligand(FasL) on acute pancreatitis(AP),and the protective effect of gadolinium chloride(GdCl3),a Kupffer cell inhibitor,on liver injury during AP.Methods Fifty-four ICR mice were randomly assigned into three groups: healthy control group(n=6);AP group(four time points for observation,6 mice each);Gd+AP group(GdCl3 pretreatment group,four time points for observation,6 mice each).AP was induced in mice using cerulein.Liver parenchymal enzymes(AST,ALT and LDH) and amylase(AMY) were assayed using an automatic analyzer.Serum FasL was assayed with ELISA and FasL protein expression in liver was assayed by Western blotting.Results After induction of AP in mice,the serum levels of AST,ALT,LDH,AMY and liver FasL expression were significantly elevated.Serum FasL levels at 4,8,16 and 24h after AP induction were 505.94?36.21,496.60?33.65,476.64?22.66 and 450.75?38.21,respectively,which were significantly higher than those in healthy control group(83.60?7.75,P