Pancreatic infection is an independent risk factor leading to death. Early prophylaxis, diagnosis and treat-ment are three keys to raise the survival rate. Strategies of prevention include prevention of bacteria translacation, fluid sequestration and antibiotic prophylaxis usage. The principal methods to decrease bacteria translocation are shortening of interval of intestinal iscbemia, decreasing of abdominal pressure, selective digestive decontamination and total enteral nutrition as early as possible. And strategy of controlling fluid resuscitation is the key point to decrease fluid sequestration. Early diagnostic criteria of pancreatic infection include at least 4 indexes of the following: white blood cell count, temperature, heart beat, intraabdominal pressure, procalcitonin, air bubble, blood pressure, prealbumin, total bilirubin and respiratory alkalosis, and addition of 2 weeks after the onset of the disease and exclusion of infection from other sites. If pancreatic infection has not been controlled by intensive nonoperative therapy for 48 hours, surgical intervention should be performed.

Recently, heme oxygenase-1 (HO-1) has been emphasized in the area of intensive care unit (ICU) and other domains. HO-1 can catalyze the decomposition of heine and the products of its enzymatic activity, including carbon monoxide, biliverdin, and bilirubin and ferritin can play a significant cytoprotec-tive role in antagonizing inflammation, protecting cells from oxidative injury and cellular stresses. In the re-search of severe acute pancreatitis (SAP), researchers have realized that it is of great importance to antago-nize the overflow of cytokines in order to improve the therapeutic effect of SAP. In this article, we give a re-view of the research progress of HO-1 and its relationship with SAP.

Heme oxygenase- 1 ( HO- 1 ) can catalyze the decomposition of heme and the products of its enzymatic activity,including carbon monoxide, biliverdin, bilintbin and ferritin, can play a significant cytoprotective role in antagonizing inflammation, protecting cells from oxidative injury and cellular stresses. The method of gene transfer can maintain target gene expression for a long time,can regulate the inflammatory immune response. HO- 1 gene transfer has made marked results in research of numerous diseases. In this article,we give a review of feasibility of HO-1 gene transfer therapy in acute pancreatitis.

Objective Analyse the influencing factors of early enteral nutrition support in patients of severe acute pancreatitis( SAP). Methods From April 2006 to August 2008, a total of 57 patients with SAP were analyzed in two aspects:the APACHE II scores, Ranson scores, Balthazar CT scores, and some frequent complications (shock, MODS, ACS, severe sepsis, paralytic ileus, etc.) were compared in two groups of A(≤5 d) and B( >5 d) according to the initial time of enteral nutrition:Hie initial timing of entend nutrition,the above scores and complications were also compared in two groups of nasojejunal feedingtube and jejunostomy feeding tube. Results The APACHE H scores, Ranson scores, Balthazar CT scores and the incidence of shock, MODS and ACS in group A were significant higher than those in group B; The APACHE II scores, Ranson scores and Balthazar CT scores in group of nasojejunal feeding tube were significant lower than those in group of jejunostomy feeding tube, and the initial time of enteral nutritionin nasojejunal feeding tube was significantly earlier. Conclusions Early enteral nutrition support in SAP is influenced by multiple factors, especially of pathogenetic severity, severe complications and feeding pathways.Homeostasis and intestines functions recover are the sign of enteral nutrition initiation, and to carry out enteral nutrition in ≤5 d after admission is feasible.The APACHE II scores may be helpful to guide the time of EN start.

Objective To investigate the cause and the therapy of acute pancreatitis. Methods 994 patients of acute pancreatitis admitted in the Surgery Ward in Ruijin Hospital between Jan. 2003 to Jan. 2007 were retrospectively analyzed. They were divided into groups according to etiology and therapy. Results In these 994 patients, 825 cases were with biliary origin (83.0%); 24 cases were alcoholic origin (2.41%); 29 cases were hyperlipidemia origin (2.92%); 16 cases were pregnancy origin (1. 61% ), 71 cases were idiopathic origin (7.14%); 4 cases were traumatic origin (0.40%); 25 cases were mixed origin (2.52%).There were 767 cases (77.2%)of mild acute pancreatitis (MAP) and 227 (22.8%) cases of severe acute pancreatitis (SAP). The overall cure rate was 91.2% , 87 cases were dead with a mortality of 8.8%. The mortality of alcoholic acute pancreatitis was 37.5% , which was significantly higher than that in biliary acute pancreatitis. Non - surgical treatment, ERCP + EST, cholecystectomy and exploration of common bile duct, or laparoscopic cholecystectomy after ERCP or debridement treatment was used for biliary acute pancreatitis. All patients underwent debridement treatment were SAP patients with a post-operative mortality of 25.0% , which was significantly higher than those in other treatment group ( P ＜ 0.01 ). There was no significant difference among the other 3 groups as regard to SAP patients and mortality. Conclusions The major cause of acute pancreatitis was biliary factor. Alcoholic pancreatitis was critical with poor prognosis. For biliary acute pancreatitis, the therapeutic efficacies of multiple treatment were not significantly different.

Objective To investigate the efficacy of intravenous antioxidants therapy in treating moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP).Methods Pubmed,Embase,Cochrane library and CNKI databases for all randomized control trials published before March 18st,2016 manually was searched by computer.Data on AP associated mortality and length of stay (LOS) were collected.The quality of the trials included was assessed by the Cochrane systematic review method.Results Fifteen trials with data of 620 patients were eligible for final inclusion.Among the 15 trials,detailed randomization for grouping was clearly described in 5 studies and obvious bias was observed in 1 study.Three studies had obvious biases considering whether outcome assessment was blinded,outcome data was incomplete and outcome report was selective.No other apparent bias was found.Statistical analysis showed that compared with control group,intravenous antioxidants administration did not significantly reduce mortality (12.1 vs 9.7,RD=-0.02,95％ CI-0.08～-0.03,P=0.44;RR=0.83.95％ CI0.51～ 1.34,P=0.44),but could shorten LOS (MD=-2.02;95％ CI-4.00～-0.05;P=0.04).Conclusions Intravenous antioxidants could greatly shorten LOS of patients with MSAP and SAP.

ObjectiveTo investigate the effects of heme oxygenase- 1 ( HO- 1 ) on pancreas and liver in severe acute pancreatitis(SAP) rats, and explore its probable mechanism. MethodsA total of 40 male SD rats were randomLy divided into 4 groups: control group(n = 10) ; SAP group(n = 10) ; HO-1 stimulation group (75 μg/kg hemin was injected intraperitoneally at 30 minutes after model establishment, n = 10 ) ; HO-1 inhibition group(20 μg/kg ZnPP was injected intraperitoneally at 30 minutes after model establishment, n = 10). Sodium Cholate (3％) was retrogradedly injected into the pancreatic duct to produce the SAP model. To observe the histopathological changes of pancreas, liver tissues were observed and serum, pancrease and liver tissues concentration of HO-1, IL-10 and TNF-α in different groups were observed 24 h after the SAP model establishment. ResultsCompared with those in SAP model group, the pathological scores were lower in HO-1 stimuLation group[ (7.50 ±0.58) vs (10.50 ±0. 71) ; ( 1.20 ±0.42) vs (1.70 ±0.48) ]( P ＜ 0.05 ), and the serum, pancreas and liver tissues HO- 1 [ (0.97 ± 0.02) ng/mL, (0.78 ± 0.09) ng/mL,(0.73 ±0.05) ng/mL]and IL-10[(101.72 ±2.63) ng/mL, (63.58 +1.02) pg/mL, (169.40 ±3.06) pg/mL ]concentrations were significantly elevated in HO- 1 stimuLation group ( P ＜ 0.05 ), while the serum, pancreas and liver tissues TNF-α [ (22.85 ± 1.74) pg/mL, (26.50 ± 1.3) pg/mL, (35.88 ±0.98 ) pg/mL]concentrations were significantly decreased in HO-1 stimuLation group (P ＜ 0.05 ). Compared with those in SAP model group, the pathological scores were higher in HO-1 inhibition group (P ＜0.05 ), and the serum, pancreas and liver tissues HO-1 and IL-10 concentrations were significantly decreased( P ＜0.05 ), while the serum, pancreas and liver tissues TNF-α concentrations were significantly elevated (P ＜ 0.05 ). CondusionThe results of the study demonstrated that HO- 1 over- expression has protective effects on the pancreas and liver in SAP. UP-regulated IL-10 expression and down-reguLated TNF-α expression might be served as a potential mechanism.

Objective To investigate changes in number of endothelial progenitor cells(EPCs)from bone marrow and circulation in mice with acute pancreatitis.Methods BALB/c mice were assigned randomly to saline group and cerulein group.Animals were sacrificed at 12, 24 and 48 hours after injection.Bone marrow and circulating EPCs were detected by flow cyzometric analysis.Plasma VEGF, TNF-α and ET-1 were determined by enzyme-linked immunosorbent assay.The expression of VEGF in the pancreas was assessed by Western blotting.Apoptosis in situ was detected by TUNEL.Results The amounts of EPCs in bone marrow and circulation increased remarkably after cerulein injection(P < 0.05), also the levels of plasma VEGF TNF-α and ET-1(P < 0.05), the EPCs levels in bone marrow and circulation seen in the study closely mirrors the levels of VEGF detected in the circulation(r = 0.77, 0.67 individually).VEGF expression in pancreas was up-regulated after 12 h of cerulein injection compared with that of control group.Apoptosis of endothelial cells also increased in the cerulein group.Conclusion EPCs were mobilized by acute pancreatitis, which may be due to the mobilizing effect of increased levels of VEGF, EPCs may participate in the repair process of injured endothelium induced by acute pancreatitis.

Objective To evaluate the serum trough concentration and the pharmacokinetics/pharmacodynamics (PK/PD)of vancomycin in patients with severe acute pancreatitis (SAP), and analyze the effect of vancomycin continuous infusion for optimizing the characteristics of its PK/PD.Methods The inhospital patients with SAP received vancomycin treatment and admitted to emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2011 to December 2016 were enrolled. Steady-state trough concentrations of vancomycin from patients were collected retrospectively. The SAP patients were divided into augmented renal clearance (ARC) and non-ARC groups, as well as systemic inflammatory response syndrome (SIRS) and non-SIRS groups according to the patients with or without symptom above. Adjustments of increased dosage or 24-hour continuous infusion or increase vancomycin dose were made for patients if the steady-state trough concentrations fell below the target level. Steady state trough concentration for vancomycin intermittent infusion or steady state concentration for vancomycin continuous infusion was determined by the fluorescence polarization immunoassay method. PK parameters of vancomycin were calculated using the Bayesian estimator and the area under the serum drug concentration-time curve (AUCc-t), the minimum inhibitory concentration (MIC) and AUCc-t/MIC was recorded and calculated.Results The steady state trough concentration or steady state concentration from 61 patients with SAP were collected with mean steady state trough concentration of vancomycin of (7.7±4.4) mg/L, which was significantly lower than standard concentration (15 mg/L,P < 0.001). Apparent volume of distribution (Vd) and clearance of vancomycin was (1.06±0.26) L/kg and (8.9±2.8) L/h. The serum steady state trough concentration of vancomycin in ARC group (n = 33) was significantly lower than that in non-ARC group (n = 28; mg/L: 6.7±3.5 vs. 8.2±4.1, P < 0.01), clearance was significantly increased (L/h: 9.8±2.9 vs. 7.7±2.2,P < 0.01). Compared with non-SIRS group (n = 31), the serum steady state trough concentration of vancomycin in SIRS group (n= 30) was significantly lowered (mg/L: 6.1±3.2 vs. 13.0±4.2,P < 0.01), and clearance was significantly increased (L/h: 9.4±2.0 vs. 7.1±2.1,P < 0.05). Compared with the only increasing vancomycin dose group (n = 29), vancomycin continuous infusion for 24 hours (n = 21) could significantly reduce daily dosage (mg/kg: 13.6±3.9 vs. 19.1±3.5,P < 0.01), increase the serum trough concentration (mg/L: 18.1±7.0 vs. 12.6±5.3,P < 0.01), and improve the AUCc-t/MIC.Conclusions The serum trough concentration of vancomycin was significantly reduced in SAP patients with ARC. The more serious of the SIRS is, the lower the vancomycin trough concentration is. Vancomycin 24-hour continuous infusion could optimize the PK/PD parameters, decrease the daily dose, increase the clinical effect, and reduce the bacterial resistance.

Objective To observe the change of the serum trough concentration and its pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP), and to analyze the factors influencing vancomycin concentration. Methods A retrospective analysis was conducted. Steady-state trough concentrations of vancomycin from patients (18-80 years old) with SAP concomitantly with G+ infection admitted to Intensive Care Unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2010 to December 2016 were enrolled. According to the usage time of vancomycin, the patients with SAP were divided into early group (onset within 21 days), middle group (onset between 21-28 days) and late group (onset over 28 days). The gender, age, body weight, clinical diagnosis, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ ) score, renal function, and the pharmacokinetic parameters were recorded. Influencing factors of vancomycin was analyzed by multiple linear regression and stepwise regression. Results Fifty-eight patients were enrolled who contained 134 times trough concentrations of vancomycin. There were 41 patients enrolled and 61 times of trough concentrations in the early group, 24 patients enrolled and 33 times of trough concentrations in the middle group, and 28 patients enrolled and 40 times of trough concentrations in the late group. There was no significant difference in gender, age, body weight, serum creatinine, creatinine clearance (CCr), albumin, APACHE Ⅱ score among the three groups. There was significantly difference in the duration from the onset time to vancomycin administration between early, middle groups and late group (days:15.9±3.2, 23.3±2.2 vs. 35.0±6.7, both P < 0.05). The positive liquid balance in early group was lower than that of late group (mL: 1565.2±3132.1 vs. 3675.1±3411.5, P < 0.01), while it was increased in the middle group as compared with that of late group (mL: 5078.7±3892.4 vs. 3675.1±3411.5, P < 0.05). The average daily dose of vancomycin in the early, middle and late groups were (14.7±5.0), (15.0±2.8), (17.0±4.2) mg/kg, respectively, and there was no significant difference (P > 0.05). Compared with the standard concentration (15 mg/L) of vancomycin, the serum trough concentration of vancomycin was significantly reduced in SAP patients [(7.5±4.3) mg/L, P < 0.01]. Apparent volume of distribution (Vd) was (72.4±15.4) L, and clearance rate (CL) was (9.0±2.8) L/h. According to the Bayesian, the serum trough concentration of vancomycin was significantly reduced in early group and middle group compared with late group (mg/L: 5.0±2.1, 7.3±2.5 vs. 11.5±5.1, both P < 0.01), CL was significantly increased (L/h: 10.5±3.0, 8.1±1.9 vs. 7.4±1.9, both P < 0.05), and Vd was significantly increased in early group compared with late group (L: 73.7±15.5 vs. 71.0±12.6, P < 0.05). It was shown by multiple linear regression analysis that there was strong relationship between serum trough concentration and the serum creatinine, CCr, average daily dose and the starting time of vancomycin treatment (r value were 0.449, -0.318, 0.373, 0.763, respectively, all P < 0.05). Conclusions The serum trough concentration of vancomycin was significantly reduced in SAP patients. And the earlier usage of vancomycin, the lower of the trough concentration is. Therefore, higher dosage regimen was needed to ensure the clinical effect, and reduce the bacterial resistance.