[Evaluation and Early Diagnosis of Gastrointestinal Failure in Acute Pancreatitis].

Objective To investigate the application of Acute Gastrointestinal Injury(AGI) grading in evaluating gastrointestinal failure in patients with acute pancreatitis(AP). Methods In this retrospective observational study,patients presented with moderate severe AP and severe AP in our hospital from October 2013 to October 2016 were consecutively enrolled.Logistic regression analysis and receiver operating characteristic curve were used to explore and evaluate potential predictors of gastrointestinal failure. Results A total of 202 patients were included in this study,with 90 cases(44.6%) identified as gastrointestinal failure.Survival curve showed significantly increased risk of death in patients with gastrointestinal failure(P < 0.05).Logistic regression analysis showed age(OR=1.06,95%CI:1.03-1.09,P<0.001),complaint of stopping flatus and defecation(OR=7.02,95%CI:2.08-23.66,P=0.002),increased counts of white blood cells in peripheral blood(OR=1.09,95%CI:1.02-1.17,P=0.015),decreased level of serum albumin(OR=0.93,95%CI:0.86-1.00,P=0.048),and increased level of serum creatinine at admission(OR=1.02,95%CI:1.01-1.04,P=0.001) were the independent risk factors of gastrointestinal failure.The area under curves of Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and Beside Index for Severity in Acute Pancreatitis (BISAP) scores in diagnosing gastrointestinal failure were 0.999 and 0.782,respectively. Conclusions Gastrointestinal failure can remarkably increase the risk of death in patients with AP.Both APACHE Ⅱ and BISAP scores at admission are useful in diagnosing gastrointestinal failure in patients with AP.

[Effects of Vitamin D Receptor on Mucosal Barrier Proteins in Colon Cells under Hypoxic Environment].

To investigate the expressions of mucosal barrier proteins in colon cell line DLD-1 under hypoxic environment in vitro and its mechanism. Methods After DLD-1 cells were treated separately with hypoxia(l% O2),vitamin D(100 nmol/L),or vitamin D plus hypoxia for 48 hours,the expressions of vitamin D receptor(VDR),tight junction proteins zonula occludens-1(ZO-1),occludin,Claudin-1,and adherent junction protein(E-cadherin)were determined by Western blot.Stable VDR knock-down(Sh-VDR)DLD-1 cell line and control DLD-1 cell line were established by lentivirus package technology and the protein expressions after hypoxia treatment were detected. Results Compared with control group,the expressions of occludin,Claudin-1,and VDR increased significantly after hypoxia treatment(all P<0.001).In addition to the protein expressions of occludin,Claudin-1 and VDR,the expressions of ZO-1 and E-cadherin were also obviously higher in vitamin D plus hypoxia group than in single vitamin D treatment group(all P<0.001).After hypoxia treatment,Sh-VDR cell line showed significantly decreased expressions of ZO-1(P<0.001),occludin(P<0.05),Claudin-1(P<0.01)and E-cadherin(P<0.001)when compared with untreated Sh-VDR cell line. Conclusion VDR acts as a regulator for the expressions of intestinal mucosal barrier proteins under hypoxia environment in DLD-1 colon cell line,indicating that VDR pathway may be another important protective mechanism for gut barrier in low-oxygen environment.

Interaction of Th17 differentiations-related gene polymorphisms and environmental factors contributing to the disease classification, complications, and surgical risks of Crohn's disease in the Chinese Han population.

OBJECTIVES: Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals. METHODS: We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis. RESULTS: Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD. CONCLUSIONS: This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis.

Association between matrix Gla protein and ulcerative colitis according to DNA microarray data.

BACKGROUND: Matrix Gla protein (MGP) is a secreted protein contributed to the immunomodulatory functions of mesenchymal stromal cells. Microarray profiling found a significantly higher expression level of the extracellular matrix gene MGP in patients with ulcerative colitis (UC). However, little is known about the role of MGP in UC and its upstream signaling regulation. This study aimed to identify the expression of MGP in UC and its upstream regulator mechanism. METHODS: Colonic mucosa biopsies were obtained from patients with UC and healthy controls. DNA microarray profiling was used to explore underlying genes correlating with UC development. Mice were fed with water containing different concentrations of dextran sodium sulfate (DSS) to induce an experimental colitis model. Colonic tissues were collected and evaluated using immunohistochemistry, immunoblot, real-time polymerase chain reaction, and chromatin immunoprecipitation assay. Bioinformatics analysis was performed to identify candidate MGP gene-promoter sequence and transcription-initiation sites. Luciferase-reporter gene assay was conducted to examine the potential transcription factor of MGP gene expression. RESULTS: The expression of MGP was significantly increased in colonic tissues from UC patients and DSS-induced colitis models, and was positively correlated with disease severity. Bioinformatics analysis showed a conserved binding site for Egr-1 in the upstream region of human MGP gene. The significantly higher level of Egr-1 gene expression was found in UC patients than in healthy controls. The activity of luciferase was significantly enhanced in the Egr-1 expression plasmid co-transfected group than in the control group and was further inhibited when co-transfected with the Egr-1 binding-site mutated MGP promoter. CONCLUSIONS: Up-regulated expression of MGP was found in UC patients and DSS-induced colitis. The expression of MGP can be regulated by Egr-1.

Corrigendum to: Association between matrix Gla protein and ulcerative colitis according to DNA microarray data.

[This corrects the article DOI: 10.1093/gastro/goz038.][This corrects the article DOI: 10.1093/gastro/goz038.].