Altered expression levels of occludin, claudin-1 and myosin light chain kinase in the common bile duct of pediatric patients with pancreaticobiliary maljunction.

BACKGROUND: In pancreaticobiliary maljunction (PBM), the sphincter of Oddi can not control bile and pancreatic juice flow, which may lead to two-way reflux of bile and pancreatic juice, thus causing chronic inflammation, thickening, fibrosis and metaplasia of the common bile duct wall. These pathophysiological changes have been linked to disruption of the epithelium barrier in the common bile duct. We hypothesized that the expression of tight junction-associated proteins may be dysregulated in the common bile duct in PBM. In the current study, we sought to analyze the expression of tight junction-associated proteins in the common bile duct epithelium of pediatric patients with PBM. METHODS: Specimens of the common bile duct were collected from 12 pediatric patients with PBM and 10 non-PBM controls. The expression of the tight junction-associated proteins occludin and claudin-1 in the epithelium was examined by immunohistochemistry. The Image-Pro Plus v. 6.0 image analysis software was used to calculate the mean qualifying score (MQS) of imunostained sections of common bile duct epithelium. Total protein extracts of common bile duct were analyzed by Western blotting assays to examine expression of occludin, claudin-1 and myosin light chain kinase (MLCK). Spearman correlation analysis was used to analyze the relation between MLCK and occludin, MLCK and claudin-1. RESULTS: Immunostained sections of the common bile duct epithelium showed significantly higher MQS in pediatric patients than controls for occludin (44.11 ± 13.82 vs. 11.30 ± 9.58, P = 0.0034) and claudin-1 (63.44 ± 23.59 vs. 46.10 ± 7.84, P = 0.0384). Western blotting also showed significantly higher expression of occludin, claudin-1 and MLCK in the common bile duct of patients than of controls (P = 0.0023, 0.0015, 0.0488). Spearman correlation analysis showed that MLCK expression correlated positively with the expression of occludin (r s = 0.61538, P = 0.0032) and claudin-1 (r s = 0.7972, P = 0.0019). CONCLUSIONS: Occludin and claudin-1 are up-regulated in the common bile duct epithelium of pediatric PBM patients. MLCK may be involved in the process of up-regulation of the tight junction-associated proteins in PBM.

Expression of p38 mitogen-activated protein kinase (p38MAPK) and pathological change in intussusception.

BACKGROUND: The aim of this study was to develop a mouse model and further assess the pathological changes associated with the expression of p38mitogen-activated protein kinase (p38MAPK) in intussusception. METHODS: Sixty-two adult Balb/C mice were used. A longitudinal incision was made in the middle rectus muscle in the body cavity. The ileum was intussuscepted into the colon. Measurements were taken at the onset of intussusception and at 5, 15, 30, 60, and 120 min. Mucosal impairment was assessed on microscopy. Ten of the intussuscepted mice were used as an ischemia-reperfusion (I/R) model. Immunohistochemistry was used to assess expression of p38MAPK in the I/R model and pediatric patients specimens of intussusception. RESULTS: The intussusception model was successfully established in 46 mice. After 15 min, vascular compromise became visible in these 46 mice. Over time, vascular function worsened. There were significant differences in microscopy injury score in the intestinal mucosa between the 15 min and 30 min groups (P = 0.0006), 30 min and 60 min groups (P = 0.0046), and the 60 min and 120 min groups (P = 0.0050). There was no significant difference between the 5 min and 15 min groups (P = 0.0597). p38MAPK was expressed strongly in pediatric specimens of intussusception. Immunostained sections of intestinal epithelium had significantly higher mean quick score for p38MAPK in the intussusception I/R model group than in the intussusception group and controls (P = 0.0130). On each two-group comparison there was a significant difference between groups (all P < 0.01; Fig. ). CONCLUSIONS: The present mouse model can be used to assess the dynamic pathological changes associated with intussusception. I/R is associated with upregulation of p38MAPK in intussusception.

Diagnostic accuracy of coronary angiography using 64-slice computed tomography in coronary artery disease.

OBJECTIVES: To conduct a meta-analysis and investigate the diagnostic value of 64-slice computed tomography (CT) angiography for diagnosing coronary artery disease (CAD) in patients. METHODS: A comprehensive literature search from March 2005 to August 2014 was performed on the following databases: Cochrane Library; Medline; EmBase; PubMed; and BioMed Central database. As a reference standard, studies that assessed 64-slice CT angiography in detecting coronary artery stenosis (CAS) with invasive coronary angiography were included. Coronary artery stenosis was defined as ≥50% diameter stenosis. Diagnostic value was determined by pooling sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) values at segment-level analysis. Diagnostic accuracy was undertaken using area under the curve (AUC) value and summary receiver operating characteristic (SROC) curves. Publication bias was examined by Deek's funnel plot asymmetry test. RESULTS: Eight studies were included in the analysis, enrolling a total of 579 patients (7,407 segment coronary vessels). At segment-level, pooled sensitivity value was 90% (95% confidence interval [CI]: 83-95%), specificity was 91% (95% CI: 61-98%), PLR value was 9.7 (95% CI: 1.8-53.3), and NLR value was 0.11 (95% CI: 0.05-0.22) for CAS. Optimal cut-off point of sensitivity was 90%, and specificity under the SROC curve was 91%. The AUC value was 0.94. CONCLUSION: The 64-slice CT angiography is a reliable tool for detection of CAD when using a cut-off of more than or equal to 50% diameter stenosis in elderly population.