Vegetable, Fruit Consumption and Risk of Biliary Cancer: Evidence from a Meta-Analysis.

BACKGROUND AND OBJECTIVE: This meta-analysis was performed to assess the association between vegetable and fruit (VF) consumption and biliary cancer risk. METHOD: Relevant studies were identified by a search of MEDLINE and Embase databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) for the highest vs. lowest consumption and dose-response analyses were assessed. RESULTS: Fourteen studies were eligible. The summary RRs associated with the risk of biliary cancer for the highest vs. lowest were 0.48 (n = 10; 95% CI: 0.22-0.74; Q = 68.27, Pheterogeneity < 0.001, I2 = 86.8%) for vegetable consumption and 0.47 (n = 13; 95% CI: 0.32-0.61; Q = 32.68, Pheterogeneity = 0.001, I2 = 63.3%) for fruit consumption. Dose-response associations were analyzed for every 100 gram/day increment: for vegetable (n = 8; RR = 0.31, 95%CI: 0.20-0.47; Pnon-linearity = 0.35) and for fruit (n = 8; RR = 0.89, 95%CI: 0.66-1.18; Pnon-linearity = 0.20). There was no publication bias among studies (PBegg = 0.53, PEgger = 0.84 for vegetable; PBegg = 0.95, PEgger = 0.64 for fruit). CONCLUSION: This meta-analysis indicated that VF consumption may significantly reduce the risk of biliary cancer. Further well-designed prospective studies are warranted to confirm our findings.

Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome With COVID-19: A Meta-Analysis.

The available literature has furnished substantial evidence indicating the favorable outcomes of prone positioning (PP) on oxygenation parameters among patients afflicted with coronavirus disease 2019 (COVID-19). However, there is a notable disparity in the reported influence of PP on the overall outcomes of COVID-19 patients undergoing venovenous extracorporeal membrane oxygenation (V-V ECMO) for acute respiratory distress syndrome (ARDS) across studies. This article has been prepared in adherence with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. MEDLINE, Embase, and Cochrane databases were utilized for data retrieval. The primary endpoint was to evaluate the cumulative survival rate among COVID-19 patients receiving V-V ECMO, comparing those who received PP to those who did not. Secondary endpoints included the duration of intensive care unit (ICU) stay, ECMO duration, and mechanical ventilation duration. A total of 15 studies involving 2286 patients were analyzed in the meta-analysis. PP significantly improved the cumulative survival rate (0.48, 95% CI: 0.40-0.55); risk ratio (RR) of 1.24 (95% CI: 1.11-1.38).PP during ECMO for COVID-19 patients yielded favorable outcomes in terms of 60-day survival, 90-day survival, ICU survival, and hospital survival. In contrast, patients who underwent PP had longer ECMO duration (8.1 days, 95% CI: 6.2-9.9, p<0.001) and mechanical ventilation duration (9.6 days, 95% CI: 8.0-11.2, p<0.001). PP demonstrated improved survival in COVID-19 patients with ARDS receiving V-V ECMO. However, additional well-designed prospective trials are warranted to further explore the effects of this combination on survival outcomes in COVID-19 patients.

Lung Ultrasound Evaluation of Aeration Changes in Response to Prone Positioning in Acute Respiratory Distress Syndrome (ARDS) Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: An Observational Study.

BACKGROUND: Prone positioning (PP) has been proven to be a beneficial approach in enhancing survival outcomes for patients with severe acute respiratory distress syndrome (ARDS) who need venovenous extracorporeal membrane oxygenation (V-V ECMO) support. The study utilized bedside lung ultrasound (LUS) to evaluate changes in lung aeration caused by PP in ARDS patients receiving V-V ECMO. METHODS: This retrospective single-center study involved adult ARDS patients requiring V-V ECMO. The assessment of LUS involved examining specific dorsal lung regions, encompassing 16 areas, during three pre-defined time points: baseline (10 minutes prior), three-hour PP positioning, and 10-minute post-supine repositioning, all within the initial three days. Based on the oxygenation response to PP, patients were categorized into responder and non-responder groups. The primary outcome was LUS score changes during the initial three-day period. Secondary outcomes examined the impact of PP on the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) (P/F) ratio, V-V ECMO weaning success, length of ICU stay, and hospital survival. RESULTS: Among the enrolled patients (27 in total), 16 were responders and 11 were non-responders. In the responder group, the global LUS score underwent a significant reduction from 26.38 ± 4.965 at baseline to 20.75 ± 3.337 (p < 0.001) after the first PP session, which further decreased to 15.94 ± 2.816 (p< 0.001) after three days. However, no significant differences were observed among PP non-responders. The oxygenation reaction yielded comparable results. There was a significant correlation between the duration of daily PP and the reduction in global LUS score among PP responders (r = -0.855, p < 0.001). In cases where the global LUS score decreased by > 7.5 after three days of PP, the area under the receiver operating characteristic curve (AUROC) for predicting ECMO weaning success was 0.815, while it was 0.761 for predicting hospital survival. CONCLUSION: LUS has the potential to predict the response to PP and evaluate the prognosis of ARDS patients with V-V ECMO, although more studies are demanded in the future.

Melatonin ameliorates acute necrotizing pancreatitis by the regulation of cytosolic Ca2+ homeostasis.

OBJECTIVES: This study aims to investigate the relationship between the protective effects of melatonin in pancreas and the expression of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+)/Ca(2+) exchanger (NCX) in rats with acute necrotizing pancreatitis (ANP), to verify whether melatonin ameliorates ANP by alleviating calcium overload. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into four groups (sham operation group, ANP group, melatonin treatment group, melatonin contrast group). ANP was induced by the retrograde injection of 4% taurocholate (1 ml/kg body weight) into the biliopancreatic duct. Melatonin (50 mg/kg body weight) was administered 30 min before the induction of ANP in the melatonin treatment group. Rats in each group were euthanized at 1, 4, and 8 h after ANP induction. Pancreatic tissues were removed to measure SERCA and NCX levels and cytosolic calcium ion (Ca(2+)) concentration ([Ca(2+)](i)). RESULTS: At each time point, SERCA and NCX levels in the melatonin treatment group were significantly higher than that in the ANP group, and lower than that in the sham group and the melatonin contrast group. These levels did not differ between the 4- and 8-h time points in the ANP group. [Ca(2+)](i) in pancreatic acinar cells was higher in the melatonin treatment group than in the sham group and the melatonin contrast group, but lower than in the ANP group, at each time point. CONCLUSION: Melatonin can reduce pancreatic damage via the up-regulation of SERCA and NCX expression, which can alleviate calcium overload in pancreatic acinar cells.

Impact of prone positioning duration on the outcome of patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: A meta-analysis.

Purpose: Research has shown that prone positioning (PP) improves the survival of patients receiving venovenous extracorporeal membrane oxygenation (V-V ECMO) for acute respiratory distress syndrome (ARDS). However, the reported impact of PP duration on the outcome of V-V ECMO patients with ARDS varies across studies. Methods: A meta-analysis approach was used to identify studies that investigated the impact of PP duration on the outcome of ARDS patients who were treated with V-V ECMO; the following databases were used: MEDLINE, Embase, Wanfang, and the China National Knowledge Infrastructure. The primary outcome was cumulative survival. Secondary outcomes were length of stay in an intensive care unit, exchange of arterial blood gases, and adverse events. Results: A total of 8 studies were included in the final meta-analysis. Patients with longer duration of PP (≥12 h) had a longer survival period (risk ratio: 1.24; 95% confidence interval: 1.00, 1.54]) than those with PP < 12 h. There was no evidence of publication bias across the studies. Conclusion: Our results imply that a longer duration of PP ≥ 12 h might improve the outcome of patients with ARDS who receive V-V ECMO therapy.

Nomogram for the Prediction of Delayed Colorectal Post-Polypectomy Bleeding.

BACKGROUND: Delayed colorectal post-polypectomy bleeding (PPB) is a fairly common complication after polypectomy. The present study aimed to build a novel nomogram-based model of delayed PPB. METHODS: A cohort of 2494 patients who had undergone colonoscopic polypectomy between January 2016 and April 2020 were consecutively enrolled. The patient demographics, polyp characteristics, laboratory factors, and pathological parameters were collected. The least absolute shrinkage and selection operator (LASSO) regression was applied for selecting potential variables. Multivariate logistic regression was used to develop the nomogram. A bootstrapping method was employed for internal validation. The performance of the nomogram was evaluated on the basis of its calibration, discrimination, and clinical usefulness. RESULTS: Of 2494 patients undergoing colonoscopic polypectomy, 40 (1.6%) developed delayed PPB. The LASSO regression identified 6 variables (age, gender, polyp location, polyp morphology, antithrombotic medication use, and modality of polypectomy), and a predictive model was subsequently established. The area under the curve (AUC) of the predictive model and the internal validation were 0.838 (95% CI: 0.775-0.900) and 0.824 (95% CI: 0.759-0.889), respectively. The predictive model provided acceptable calibration, and a decision curve analysis (DCA) showed its clinical utility. CONCLUSION: This predictive model may enable clinicians to predict the risk of delayed PPB and optimize preoperative decision-making, for effective treatment.

Diagnostic accuracy of fecal calprotectin for screening patients with colorectal cancer: A meta-analysis.

BACKGROUND/AIMS: Fecal calprotectin (FC) is reported to have a broad diagnostic accuracy for colorectal cancer (CRC). Therefore, we explored the diagnostic value of FC for CRC using meta-analytical techniques to substantiate the assertion. MATERIALS AND METHODS: An electronic search of the MEDLINE and Embase databases was conducted to identify studies that assessed the diagnostic accuracy of FC for CRC. The sensitivities and specificities of the eligible studies were summarized using a bivariable random-effects model. RESULTS: In total, 20 studies were included in the final analysis. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FC for CRC detection were 0.83 (95% confidence interval CI, 0.77-0.88), 0.61 (95% CI, 0.54-0.68), 2.15 (95% CI, 1.82-2.55), and 0.28 (95% CI, 0.21-0.37), respectively. The overall diagnostic odds ratio of FC for CRC was 7.76 (95% CI, 5.41-11.12) with an area under the curve of 0.81 (95% CI, 0.77-0.84), whereas the diagnostic value of FC for colorectal adenoma was relatively inferior (area under the curve, 0.55; 95% CI, 0.51-0.59; diagnostic odds ratio, 1.27; 95% CI, 0.91-1.78). CONCLUSION: The results imply that the FC test, as currently implemented, cannot be recommended for CRC detection.

Effectiveness and safety of biliary stenting in the management of difficult common bile duct stones in elderly patients.

BACKGROUND/AIMS: To investigate the efficacy and safety of endoscopic biliary stenting for difficult common bile duct (CBD) stones in elderly patients. MATERIALS AND METHODS: Elderly patients (≥65 years) with large (≥20 mm) or multiple (≥3) CBD stones were studied. The patients underwent placement of single (n=34, group A) or double (n=30, group B) plastic stents at the time of initial endoscopic retrograde cholangiopancreatography (ERCP). Approximately 3 months later, stone removal was attempted at the second ERCP. The reduction of stone size and number before and after biliary stenting, complete stone removal, 3-month stent patency rate, and complications were compared. RESULTS: The mean size (longitudinal/transverse diameter) of the CBD stones was significantly reduced after biliary stenting in both groups (p<0.001). Complete stone removal at the second ERCP was 94.1% in group A and 100% in group B (p=0.494). Kaplan-Meier analysis indicated that group B had a higher 3-month stent patency rate than group A (p=0.008). CONCLUSION: Endoscopic biliary stenting is safe and feasible for the management of difficult CBD stones in elderly patients, while double biliary stenting is superior to single stenting in maintaining higher stent patency rates.

Impact of smoking on the risk of pancreatitis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Cigarette smoking may increase the risk of developing pancreatic cancer, although its impact on pancreatitis has only been discerned in recent years. However, the results of previous studies differ. We performed a meta-analysis to provide a quantitative pooled risk estimate of the association of cigarette smoking with pancreatitis. METHOD: A literature search of the MEDLINE and Embase databases was conducted, and studies were selected that investigated the association of cigarette smoking with pancreatitis. Summary relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. RESULTS: Twenty-two studies were included. The summary RRs (95% CI) associated with ever, current and former smokers for acute and chronic pancreatitis (AP/CP) were as follows: 1.51 (1.10, 2.07)/3.00 (1.46, 6.17), 1.42 (1.08, 1.87)/2.72 (1.74, 4.24), and 1.22 (0.99, 1.52)/1.27 (1.00, 1.62), respectively. Moreover, studies that analyzed both AP and CP were also summarized: 1.73 (1.18, 2.54) for ever smokers, 1.67 (1.03, 2.68) for current smokers and 1.56 (1.16, 2.11) for former smokers, respectively. There was no evidence of publication bias across the studies. CONCLUSION: The evidence suggests a positive association of cigarette smoking with the development of pancreatitis. It is possible that smoking cessation may be a useful strategy for the management of pancreatitis.

A meta-analysis of critically ill patients reveals several potential risk factors for delirium.

OBJECTIVE: To investigate potential risk factors for delirium in critically ill patients through a meta-analysis of clinical observational studies. METHOD: A literature search was conducted of MEDLINE and Embase databases. Studies that reported risk factors for delirium in a critical care setting were included. Data were independently extracted by two reviewers and pooled using a fixed-effect or random effects model according to the result of a heterogeneity test. RESULTS: Twenty-five studies were included. The combined odds ratio (95% confidence interval) for each potential risk factor estimated by meta-analysis was as follows (univariate/multivariate): alcohol use, 1.47 (0.79-2.72)/2.34 (1.56-3.49); smoking, 1.01 (0.81-1.25)/1.61 (0.83-3.10); hypertension, 1.64 (1.30-2.06)/1.98 (1.44-2.72); age (per year), 1.03 (1.001-1.05)/1.04 (1.02-1.05); age >65 years, 2.52 (1.55-4.10)/2.59 (1.93-3.47); mechanical ventilation, 3.09 (1.43-6.66)/4.51 (1.41-14.39); and Acute Physiology and Chronic Health Evaluation (APACHE) II score (per point), 1.13 (1.06-1.21) (multivariate only). There was no evidence of publication bias except for APACHE II score. CONCLUSION: Age, history of hypertension, clinical use of mechanical ventilation and higher APACHE II score are associated with increased risk of delirium in critically ill patients.

Cyanoacrylate injection compared with band ligation for acute gastric variceal hemorrhage: a meta-analysis of randomized controlled trials and observational studies.

Background. Cyanoacrylate injection (GVO) and band ligation (GVL) are effective treatments for gastric variceal hemorrhage. However, data on the optimal treatment are still controversial. Methods. For our overall analysis, relevant studies were identified from several databases. For each outcome, data were pooled using a fixed-effect or random-effects model according to the result of a heterogeneity test. Results. Seven studies were included. Compared with GVL, GVO was associated with increased likelihood of hemostasis of active bleeding (odds ratio [OR] = 2.32; 95% confidence interval [CI] = 1.19-4.51) and a longer gastric variceal rebleeding-free period (hazard ratio = 0.37; 95% CI = 0.24-0.56). No significant differences were observed between GVL and GVO for mortality (hazard ratio = 0.66; 95% CI = 0.43-1.02), likelihood of variceal obliteration (OR = 0.89; 95% CI = 0.52-1.54), number of treatment sessions required for complete variceal eradication (weighted mean difference = -0.45; 95% CI = -1.14-0.23), or complications (OR = 1.02; 95% CI = 0.48-2.19). Conclusion. GVO may be superior to GVL for achieving hemostasis and preventing recurrence of gastric variceal rebleeding but has no advantage over GVL for mortality and complications. Additional studies are warranted to enable definitive conclusions.

Inflammatory bowel disease and risk of cholangiocarcinoma: evidence from a meta-analysis of population-based studies.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) have an increased risk of extra-intestinal cancer, whereas its impact on cholangiocarcinoma (CC) remains unknown. The aim of this study was to obtain a reliable estimate of the risk of CC in IBD patients through a meta-analysis of clinical observational studies. METHODS: Relevant studies were retrieved by searching PUBMED, EMBASE and Web of Science Databases up to Dec 2013. Four population-based case-control and two cohort studies with IBD were identified. Summary relative risk (RR) and its corresponding 95% confidence interval (CI) were calculated using a random-effects model. Potential sources of heterogeneity were detected using subgroup analyses. RESULTS: The pooled risk estimate indicated IBD patients were at increased risk of CC (RR = 2.63, 95%CI = 1.47-4.72). Moreover, the increased risk of CC was also associated with Crohn's disease (RR = 2.69, 95%CI = 1.59-4.55) and ulcerative colitis (RR = 3.40, 95%CI = 2.50-4.62). In addition, site-specific analyses revealed that IBD patients had an increased risk of intrahepatic CC (ICC) (RR = 2.61, 95%CI = 1.72-3.95) and extrahepatic CC (ECC) (RR = 1.47, 95%CI = 1.10- 1.97). CONCLUSIONS: This study suggests the risk of CC is significantly increased among IBD patients, especially in ICC cases. Further studies are warranted to enable definite conclusions to be drawn.

Lung protective ventilation in patients undergoing major surgery: a systematic review protocol.

INTRODUCTION: There is growing interest in the use of low tidal volume ventilation in patients undergoing general anaesthesia. However, its potential benefit has long been debated and conflicting results have been reported. We describe here the protocol of a systematic review and meta-analysis for investigating the beneficial effects of low tidal volume ventilation in patients undergoing general anaesthesia. METHODS AND ANALYSIS: Data sources include PubMed, Scopus, Embase and EBSCO. Patients undergoing general anaesthesia will be included irrespective of type of surgery. The intervention is low tidal volume ventilation or protective ventilation, and the control is conventional ventilation. The quality of included trials will be assessed by using Delphi consensus. Outcomes include new onset lung injury, atelectasis, arrhythmia, levels of inflammatory biomarkers, arterial oxygenation, partial pressure of carbon dioxide and alveolar-arterial oxygen gradient. Conventional approaches for meta-analysis will be used, and heterogeneity will be investigated by using subgroup analysis and meta-regression if appropriate. The Bayesian method will be used for the synthesis of binary outcome data. ETHICS AND DISSEMINATION: The systematic review was approved by the ethics committee of Jinhua hospital of Zhejiang university and will be published in a peer-reviewed journal and will be disseminated electronically and in print. REGISTRATION DETAILS: The study protocol has been registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42013006416.

Correlation of fibrinogen-like protein 2 with disease progression in patients with severe acute pancreatitis.

It has recently been demonstrated that fibrinogen-like protein 2 (fgl2) is expressed on the surface of macrophages, T cells and endothelial cells and directly cleaves prothrombin to thrombin. The present study was designed to examine fgl2 expression in patients with severe acute pancreatitis (SAP) and its correlation with disease progression. Peripheral blood mononuclear cells (PBMCs) were isolated from 25 patients with SAP, 37 patients with mild acute pancreatitis (MAP) and 20 healthy volunteers as controls. Paraffin sections of pancreas were obtained from 18 postoperative patients with SAP between 2003 and 2012. Human fgl2 (hfgl2) gene expression was determined in the PBMCs by real-time PCR. A monoclonal antibody against hfgl2 was applied to detect hfgl2 protein expression in the pancreatic tissues as well as in the PBMCs by immunohistochemical staining. The levels of hfgl2 expression in the PBMCs from the 25 patients with SAP were markedly upregulated compared with the other groups, whereas no significant difference between the MAP group and healthy controls was observed. hfgl2 expression in the PBMCs and pancreatic tissues was detectable through using immunohistochemistry and was demonstrated to be specifically localized to the endothelium of microvessels and inflammatory infiltrative cells in the areas of acute focal, confluent necrosis. There were positive correlations between hfgl2 expression in the PBMCs and the severity of SAP, as indicated by scores of Ranson and Acute Physiology and Chronic Health Evaluation II. The results suggest that hfgl2 is involved in the pathogenesis of SAP and hfgl2 levels may serve as a biomarker during disease progression.

Melatonin reduces bacterial translocation by preventing damage to the intestinal mucosa in an experimental severe acute pancreatitis rat model.

Recent studies have demonstrated that melatonin significantly decreased all studied acute pancreatitis-associated inflammatory parameters, in addition to reducing apoptosis and necrosis associated with pancreatic injury. However, the effect of melatonin on gut barrier dysfunction and bacterial translocation has not been fully elucidated. This study aimed to investigate the protective effects of melatonin on intestinal integrity in a rat model of severe acute pancreatitis (SAP) to evaluate whether melatonin prevented intestine barrier dysfunction and reduced bacterial translocation. Forty male Sprague Dawley (SD) rats were randomly divided into three groups, with 8 rats in the sham operation (SO) group, 18 rats in the SAP group and 14 SAP rats in the melatonin treatment (MT) group. SAP was induced by retrograde injection of 4% taurocholate into the biliopancreatic duct. Melatonin was administered 30 min prior to taurocholate injection in the melatonin-treated rats. All rats were sacrificed 24 h subsequent to pancreatitis induction. Real-time fluorescence quantitative polymerase chain reaction was used to detect and quantify Escherichia coli (E. coli) O157 in postcava blood. The microvilli structure was also analyzed with transmission electron microscopy. The level of E. coli DNA in the MT group was significantly lower than in rats in the SAP group. No E. coli DNA was detected in the control group. Villus height and crypt depth in the ileum were significantly higher in the MT and control groups compared to the SAP group, and were significantly higher in the MT group than in the SAP group. These results suggested that melatonin prevented gut barrier dysfunction and reduced bacterial translocation, resulting in reduced pancreatic-associated infections and decreased early mortality rates.

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 31 May 2013 without language limitations, and by manually searching the references of retrieved articles. Case-control 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 corresponding 95%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.

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.

Melatonin attenuates acute pancreatitis-associated lung injury in rats by modulating interleukin 22.

AIM: To investigate whether therapeutic treatment with melatonin could protect rats against acute pancreatitis and its associated lung injury. METHODS: Seventy-two male Sprague-Dawley rats were randomly divided into three groups: the sham operation (SO), severe acute pancreatitis (SAP), and melatonin treatment (MT) groups. Acute pancreatitis was induced by infusion of 1 mL/kg of sodium taurocholate (4% solution) into the biliopancreatic duct. Melatonin (50 mg/kg) was administered 30 min before pancreatitis was induced, and the severity of pancreatic and pulmonary injuries was evaluated 1, 4 and 8 h after induction. Serum samples were collected to measure amylase activities, and lung tissues were removed to measure levels of mRNAs encoding interleukin 22 (IL-22) and T helper cell 22 (Th22), as well as levels of IL-22. RESULTS: At each time point, levels of mRNAs encoding IL-22 and Th22 were significantly higher (P < 0.001) in the MT group than in the SAP group (0.526 ± 0.143 vs 0.156 ± 0.027, respectively, here and throughout, after 1 h; 0.489 ± 0.150 vs 0.113 ± 0.014 after 4 h; 0.524 ± 0.168 vs 0.069 ± 0.013 after 8 h, 0.378 ± 0.134 vs 0.122 ± 0.015 after 1 h; 0.205 ± 0.041 vs 0.076 ± 0.019 after 4 h; 0.302 ± 0.108 vs 0.045 ± 0.013 after 8 h, respectively) and significantly lower (P < 0.001) in the SAP group than in the SO group (0.156 ± 0.027 vs 1.000 ± 0.010 after 1 h; 0.113 ± 0.014 vs 1.041 ± 0.235 after 4 h; 0.069 ± 0.013 vs 1.110 ± 0.213 after 8 h, 0.122 ± 0.015 vs 1.000 ± 0.188 after 1 h; 0.076 ± 0.019 vs 0.899 ± 0.125 after 4 h; 0.045 ± 0.013 vs 0.991 ± 0.222 after 8 h, respectively). The mean pathological scores for pancreatic tissues in the MT group were significantly higher (P < 0.01) than those for samples in the SO group (1.088 ± 0.187 vs 0.488 ± 0.183 after 1 h; 2.450 ± 0.212 vs 0.469 ± 0.242 after 4 h; 4.994 ± 0.184 vs 0.513 ± 0.210 after 8 h), but were significantly lower (P < 0.01) than those for samples in the SAP group at each time point (1.088 ± 0.187 vs 1.969 ± 0.290 after 1 h; 2.450 ± 0.212 vs 3.344 ± 0.386 after 4 h; 4.994 ± 0.184 vs 6.981 ± 0.301 after 8 h). The severity of SAP increased significantly (P < 0.01) over time in the SAP group (1.088 ± 0.187 vs 2.450 ± 0.212 between 1 h and 4 h after inducing pancreatitis; and 2.450 ± 0.212 vs 4.994 ± 0.184 between 4 and 8 h after inducing pancreatitis). CONCLUSION: Melatonin protects rats against acute pancreatitis-associated lung injury, probably through the upregulation of IL-22 and Th22, which increases the innate immunity of tissue cells and enhances their regeneration.