Correlation of fibrinogen-like protein 2 with progression of acute pancreatitis in rats

AIM: To examine fibrinogen-like protein 2 (fgl2) expression during taurocholate-induced acute pancreatitis progression in rats and its correlation with pancreatic injury severity. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into the severe acute pancreatitis (SAP) group (n = 24) and the sham operation (SO) group (n = 24). Sodium taurocholate (4% at doses of 1 mL/kg body weight) was retrogradely injected into the biliopancreatic ducts of the rats to induce SAP. Pancreatic tissues were prepared immediately after sacrifice. At the time of sacrifice, blood was obtained for determination of serum amylase activity and isolation of peripheral blood mononuclear cells (PBMCs). Pancreatic tissue specimens were obtained for routine light microscopy including hematoxylin and eosin staining, and the severity of pancreatic injury was evaluated 1, 4 and 8 h after induction. Expression of fgl2 mRNA was measured in the pancreas and PBMCs using reverse transcription polymerase chain reaction. Expression of fgl2 protein was evaluated in pancreatic tissues using Western blotting and immunohistochemical staining. Masson staining was also performed to observe microthrombosis. RESULTS: At each time point, levels of fgl2 mRNAs in pancreatic tissues and PBMCs were higher (P < 0.05) in the SAP group than in the SO group. For pancreatic tissue in SAP vs SO, the levels were: after 1 h, 3.911 ± 1.277 vs 1.000 ± 0.673; after 4 h, 9.850 ± 3.095 vs 1.136 ± 0.609; and after 8 h, 12.870 ± 3.046 vs 1.177 ± 0.458. For PBMCs in SAP vs SO, the levels were: after 1 h, 2.678 ± 1.509 vs 1.000 ± 0.965; after 4 h, 6.922 ± 1.984 vs 1.051 ± 0.781; and after 8 h, 13.533 ± 6.575 vs 1.306 ± 1.179. Levels of fgl2 protein expression as determined by Western blotting and immunohistochemical staining were markedly up-regulated (P < 0.001) in the SAP group compared with those in the SO group. For Western blotting in SAP vs SO, the results were: after 1 h, 2.183 ± 0.115 vs 1.110 ± 0.158; after 4 h, 2.697 ± 0.090 vs 0.947 ± 0.361; and after 8 h, 3.258 ± 0.094 vs 1.208 ± 0.082. For immunohistochemical staining in SAP vs SO, the results were: after 1 h, 1.793 ± 0.463 vs 0.808 ± 0.252; after 4 h, 4.535 ± 0.550 vs 0.871 ± 0.318; and after 8 h, 6.071 ± 0.941 vs 1.020 ± 0.406. Moreover, we observed a positive correlation in the pancreas (r = 0.852, P < 0.001) and PBMCs (r = 0.735, P < 0.001) between fgl2 expression and the severity of pancreatic injury. Masson staining showed that microthrombosis (%) in rats with SAP was increased (P < 0.001) compared with that in the SO group and it was closely correlated with fgl2 expression in the pancreas (r = 0.842, P < 0.001). For Masson staining in SAP vs SO, the results were: after 1 h, 26.880 ± 9.031 vs 8.630 ± 3.739; after 4 h, 53.750 ± 19.039 vs 8.500 ± 4.472; and after 8 h, 80.250 ± 12.915 vs 10.630 ± 7.003.CONCLUSION: Microthrombosis due to fgl2 overexpression contributes to pancreatic impairment in rats with SAP, and fgl2 level may serve as a biomarker during early stages of disease.

Smoking, alcohol consumption, and the risk of extrahepatic cholangiocarcinoma:A meta-analysis

AIM:To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma(ECC)through a meta-analysis of clinical observational studies.METHODS:A literature search was conducted using Embase and MEDLINE databases from inception to 31May 2013 without language limitations,and by manually searching the references of retrieved articles.Casecontrol and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included.The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale.Summary relative risks and corresponding95%CI were calculated using a random-effects model.Publication bias was assessed by Begg’s funnel plot and Egger’s test.RESULTS:A total of 12 eligible articles(11 case-control studies and one cohort study)were included in this meta-analysis.Eleven studies reported the association between smoking and ECC.Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers(summary RR=1.23;95%CI:1.01-1.50).This correlation was present in population-based studies(n=5;summary RR=1.47;95%CI:1.06-2.05)but not in hospital-based studies(n=6;summary RR=1.10;95%CI:0.88-1.37)and in non-Asian regions(n=7;summary RR=1.39;95%CI:1.03-1.87)but not in Asia(n=4;summary RR=1.08;95%CI:0.85-1.38).Seven studies reported an association between consuming alcohol and ECC.Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol(summary RR=1.09;95%CI:0.87-1.37).There was moderate heterogeneity among the studies and no evidence of publication bias.CONCLUSION:Smoking is associated with an increased risk of ECC,but alcohol consumption is not.Further population-based studies,particularly cohort studies,are warranted to enable definitive conclusions.