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.

Correlation of Sugar Molecular Probes with Inflammatory Factors and Claudin-8 in Intestinal Permeability in Colitis Rats / 胃肠病学

Background:Intestinal permeability plays an important role in the development of ulcerative colitis. Sugar molecular probes is a safe and non-invasive method to measure intestinal permeability,and its correlation with inflammatory factors and claudin-8 is not clear. Aims:To explore the correlation of sugar molecular probes with TNF-α,CRP and claudin-8 in intestinal permeability in colitis rats. Methods:Twenty-four rats were assigned randomly to model group and normal control group. Colitis model was induced by DSS solution. Expressions of TNF-α,CRP were determined by ELISA,and expression of claudin-8 was determined by immunohistochemistry. Sugar molecular probes were determined by high performance liquid chromatography. Correlations of inflammatory factors and claudin-8 with sugar molecular probes were analyzed. Results:Compared with normal control group,expressions of colonic tissue TNF-α and CRP were significantly increased while expression of claudin-8 was significantly decreased in model group(P < 0. 01);secretion of lactulose and sucrolose,ratio of lactulose/ mannitol( L/ M)were significantly increased( P < 0. 01)while mannitol secretion was significantly decreased(P < 0. 01). Secretion of lactulose and sucrolose were positively correlated with expressions of TNF-α and CRP(P < 0. 01),but negatively with expression of claudin-8(P < 0. 01). L/ M ratio and mannitol secretion were negatively correlated with expressions of TNF-α and CRP(P < 0. 01),but positively with expression of claudin-8(P <0. 01). Conclusions:Sugar molecular probes and expressions of TNF-α,CRP,claudin-8 have similar results in predicting intestinal permeability in rats. Sugar molecular probes can be used as a potential method to measure intestinal permeability.

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.

Safety and efficacy of endoscopic multiband mucosectomy for early esophageal carcinoma and intraepithelial neoplasia / 中华消化内镜杂志

Objective To study the effectiveness of endoscopic multiband mucosectomy ( EMBM ) for early cancer and precancerous lesions of the esophagus. Methods From August 2007 to December 2011,EMBM was performed on 46 patients (25 males and 21 females) with the average age of 59.0 (35-82) yr.All lesions were margined under NBI,with 2 to 13 cm in diameter (median 4 cm),and occupying at most two-third of the circumference of the esophagus.Of 46 patients,41 (89.1％ ) accepted deep sedation by intravenous injection of propofol.All patients were followed up with endoscopy at 1,6,12 months after the operation.Results A total of 48 lesions were resected completely by EMBM with 1-11 processes.During the procedure,controllable bleeding occurred in 3 cases and micro-perforation occurred in 1,which was cured by metal clip.Histopathological diagnoses revealed 3 cases of intramucosal squamous carcinoma,19 high grade intraepithelial neoplasia,17 low grade intraepithelial neoplasia,and 7 inflammatory hyperplasia.No recurrence was found during the follow-up of 1 to 53 months.Conclusion EMBM is effective and safe for the treatment of early cancer and precancerous lesions of the esophagus.Appropriate indication and manipulation can decrease complication occurrence.

Endoscopic measurement by virtual internal standard:Feasibility and accuracy / 医学研究生学报

Objective: Endoscopic measurement mainly depends on visual estimation or open biopsy forceps,which have been proved lacking in accuracy due to the image barrel distortion caused by wide-angle lens in endoscope.This study aimed to validate a new concept of "virtual internal standard" proposed by ourselves and develop a new method for endoscopic measurement based on the concept.Methods: We photographed planar grid graphs printed with standard calibrations with an electronic endoscope at different object distances,obtained the information on the virtual internal standard from each photo at the corresponding object distance,and analyzed the digital characteristics of the barrel distortion photos,including the size of the visual field,the image compression ratio,and the credible area for measurement with the virtual internal standard.Based on the analyses,the method of endoscopic measurement by the virtual internal standard was established and experiments both in vivo and in vitro were conducted.Results: The ratio of the object distance to the visual field was 1 ∶ 2 when the former was between 10 mm and 40 mm.Calculation of the compression ratio showed that the credible area of measurement in the central area was 10 mm at the object distance of 10-15 mm,20 mm at 20-30 mm,and 30 mm at 30-50 mm.The credible area of measurement on various planes accounted for 2/5 to 3/5 of the total image width.There was a tendency of double-curve change in the arrangement of pixel values of the central grids on different planes.The differences between the pixel values per centimeter became slight at the object distance of 35-50 mm.Conclusion: Endoscopic measurement by the virtual internal standard is a objective,accurate,simple and practical method.