Different timing for abdominal paracentesis catheter placement and drainage in severe acute pancreatitis complicated by intraabdominal fluid accumulation

BACKGROUND Non-surgical methods such as percutaneous drainage are crucial for the treatment of patients with severe acute pancreatitis(SAP).However,there is still an ongoing debate regarding the optimal timing for abdominal paracentesis catheter place-ment and drainage.AIM To explore the influence of different timing for abdominal paracentesis catheter placement and drainage in SAP complicated by intra-abdominal fluid accumu-lation.METHODS Using a retrospective approach,184 cases of SAP complicated by intra-abdominal fluid accumulation were enrolled and categorized into three groups based on the timing of catheter placement:group A(catheter placement within 2 d of symptom onset,n=89),group B(catheter placement between days 3 and 5 after symptom onset,n=55),and group C(catheter placement between days 6 and 7 after symptom onset,n=40).The differences in progression rate,mortality rate,and the number of cases with organ dysfunction were compared among the three groups.RESULTS The progression rate of group A was significantly lower than those in groups B and groups C(2.25%vs 21.82%and 32.50%,P<0.05).Further,the proportion of patients with at least one organ dysfunction in group A was significantly lower than those in groups B and groups C(41.57%vs 70.91%and 75.00%,P<0.05).The mortality rates in group A,group B,and group C were similar(P>0.05).At postoperative day 3,the levels of C-reactive protein(55.41±19.32 mg/L vs 82.25±20.41 mg/L and 88.65±19.14 mg/L,P<0.05),procalcitonin(1.36±0.51 ng/mL vs 3.20±0.97 ng/mL and 3.41±0.98 ng/mL,P<0.05),tumor necrosis factor-alpha(15.12±6.63 pg/L vs 22.26±9.96 pg/L and 23.39±9.12 pg/L,P<0.05),interleukin-6(332.14±90.16 ng/L vs 412.20±88.50 ng/L and 420.08±87.65ng/L,P<0.05),interleukin-8(415.54±68.43 ng/L vs 505.80±66.90 ng/L and 510.43±68.23ng/L,P<0.05)and serum amyloid A(270.06±78.49 mg/L vs 344.41±81.96 mg/L and 350.60±80.42 mg/L,P<0.05)were significantly lower in group A compared to those in groups B and group C.The length of hospital stay in group A was significantly lower than those in groups B and group C(24.50±4.16 d vs 35.54±6.62 d and 38.89±7.10 d,P<0.05).The hospitalization expenses in group A were also significantly lower than those in groups B and groups C[2.70(1.20,3.55)ten-thousand-yuan vs 5.50(2.98,7.12)ten-thousand-yuan and 6.00(3.10,8.05)ten-thousand-yuan,P<0.05).The incidence of complications in group A was markedly lower than that in group C(5.62%vs 25.00%,P<0.05),and similar to group B(P>0.05).CONCLUSION Percutaneous catheter drainage for the treatment of SAP complicated by intra-abdominal fluid accumulation is most effective when performed within 2 d of onset.

Computerized tomography-guided therapeutic percutaneous puncture catheter drainage-combined with somatostatin for severe acute pancreatitis: An analysis of efficacy and safety

BACKGROUND Severe acute pancreatitis(SAP),a condition with rapid onset,critical condition and unsatisfactory prognosis,poses a certain threat to human health,warranting optimization of relevant treatment plans to improve treatment efficacy.AIM To evaluate the efficacy and safety of computerized tomography-guided the-rapeutic percutaneous puncture catheter drainage(CT-TPPCD)combined with somatostatin(SS)in the treatment of SAP.METHODS Forty-two SAP patients admitted to The Second Affiliated Hospital of Fujian Medical University from June 2020 to June 2023 were selected.On the basis of routine treatment,20 patients received SS therapy(control group)and 22 patients were given CT-TPPCD plus SS intervention(research group).The efficacy,safety(pancreatic fistula,intra-abdominal hemorrhage,sepsis,and organ dysfunction syndrome),abdominal bloating and pain relief time,bowel recovery time,hospital stay,inflammatory indicators(C-reactive protein,interleukin-6,and pro-calcitonin),and Acute Physiology and Chronic Health Evaluation(APACHE)II score of both groups were evaluated for comparison.RESULTS Compared with the control group,the research group had a markedly higher total effective rate,faster abdominal bloating and pain relief and bowel recovery,INTRODUCTION Pancreatitis,an inflammatory disease occurring in the pancreatic tissue,is classified as either acute or chronic and is associated with high morbidity and mortality,imposing a socioeconomic burden[1,2].The pathogenesis of this disease involves early protease activation,activation of nuclear factor kappa-B-related inflammatory reactions,and infiltration of immune cells[3].Severe acute pancreatitis(SAP)is a serious condition involving systemic injury and subsequent possible organ failure,accounting for 20%of all acute pancreatitis cases[4].SAP is also characterized by rapid onset,critical illness and unsatisfactory prognosis and is correlated with serious adverse events such as systemic inflammatory response syn-drome and acute lung injury,threatening the health of patients[5,6].Therefore,timely and effective therapeutic inter-ventions are of great significance for improving patient prognosis and ensuring therapeutic effects.Somatostatin(SS),a peptide hormone that can be secreted by endocrine cells and the central nervous system,is in-volved in the regulatory mechanism of glucagon and insulin synthesis in the pancreas[7].It has complex and pleiotropic effects on the gastrointestinal tract,which can inhibit the release of gastrointestinal hormones and negatively modulate the exocrine function of the stomach,pancreas and bile,while exerting a certain influence on the absorption of the di-gestive system[8,9].SS has shown certain clinical effectiveness when applied to SAP patients and can regulate the severity of SAP and immune inflammatory responses,and this regulation is related to its influence on leukocyte apoptosis and adhesion[10,11].Computerized tomography-guided therapeutic percutaneous puncture catheter drainage(CT-TPPCD)is a surgical procedure to collect lesion fluid and pus samples from necrotic lesions and perform puncture and drainage by means of CT image examination and precise positioning[12].In the research of Liu et al[13],CT-TPPCD applied to pa-tients undergoing pancreatic surgery contributes to not only good curative effects but also a low surgical risk.Baudin et al[14]also reported that CT-TPPCD has a clinical success rate of 64.6%in patients with acute infectious necrotizing pan-creatitis,with nonfatal surgery-related complications found in only two cases,suggesting that this procedure is clinically effective and safe in the treatment of the disease.In light of the limited studies on the efficacy and safety of SS plus CT-TPPCD in SAP treatment,this study performed a relevant analysis to improve clinical outcomes in SAP patients.

Application of psychological intervention in intensive care unit nursing for patients with severe acute pancreatitis

BACKGROUND Severe acute pancreatitis(SAP)is a familiar critical disease in the intensive care unit(ICU)patients.Nursing staff are important spiritual pillars during the treatment of patients,and in addition to routine nursing,more attention needs be paid to the patient’s psychological changes.AIM To investigate the effects of psychological intervention in ICU patients with SAP.METHODS One hundred ICU patients with SAP were hospitalized in the authors’hospital between 2020 and 2023 were selected,and divided into observation and control groups per the hospitalization order.The control and observation groups received routine nursing and psychological interventions,respectively.Two groups are being compared,using the Self-rating Anxiety Scale(SAS),Self-Determination Scale(SDS),Acute Physiology and Chronic Health Evaluation(APACHE)Ⅱ,and 36-item Short Form Health Survey(SF-36)scores;nursing satisfaction of patients;ICU care duration;length of stay;hospitalization expenses;and the incidence of complications.RESULTS After nursing,the SDS,SAS,and APACHEⅡ scores in the experimental group were significantly lower than in the control group(P<0.05).The SF-36 scores in the observation group were significantly higher than those in the control group(P<0.05).The nursing satisfaction of patients in the experimental group was 94.5%,considerably higher than that of 75.6% in the control group(P<0.05).The ICU care duration,length of stay,and hospitalization expenses in the observation group were significantly lower than those in the control group,and the incidence of complications was lower(P<0.05).CONCLUSION For patients with SAP,the implementation of standardized psychological intervention measures can effectively alleviate adverse psychological conditions.

Ulinastatin in the treatment of severe acute pancreatitis:A singlecenter randomized controlled trial

BACKGROUND Severe acute pancreatitis(AP)is one of the most common diseases of the gastrointestinal tract and carries a significant financial burden with high disability and mortality.There are no effective drugs in the clinical management of severe AP,and there is an absence of evidence-based medicine concerning the treatment of severe AP.AIM To explore whether ulinastatin(UTI)can improve the outcome of severe AP.METHODS The present research included patients who were hospitalized in intensive critical care units(ICUs)after being diagnosed with severe AP.Patients received UTI(400000 IU)or placebos utilizing computer-based random sequencing(in a 1:1 ratio).The primary outcome measures were 7-d mortality,clinical efficacy,inflammatory response,coagulation function,infection,liver function,renal function,and drug-related adverse effects were evaluated.RESULTS A total of 181 individuals were classified into two groups,namely,the placebo group(n=90)and the UTI group(n=91).There were no statistically significant differences in baseline clinical data between the two groups.The 7-d mortality and clinical efficacy in the UTI group were remarkably improved compared with those in the placebo group.UTI can protect against hyperinflammation and improve coagulation dysfunction,infection,liver function,and renal function.UTI patients had markedly decreased hospital stays and hospitalization expenditures compared with the placebo group.CONCLUSION The findings from the present research indicated that UTI can improve the clinical outcomes of patients with severe AP and has fewer adverse reactions.

Risk factors and their interactive effects on severe acute pancreatitis complicated with acute gastrointestinal injury

BACKGROUND There are many risk factors for severe acute pancreatitis(SAP)complicated with acute gastrointestinal injury(AGI),but few reports on the interaction between these risk factors.AIM To analyze the risk factors for SAP complicated with AGI and their interactive effects.METHODS We selected 168 SAP patients admitted to our hospital between December 2019 and June 2022.They were divided into AGI group and non-AGI group according to whether AGI was present.Demographic data and laboratory test data were compared between the two groups.The risk factors for SAP with concomitant AGI were analyzed using multifactorial logistic regression,and an analysis of the interaction of the risk factors was performed.RESULTS The percentage of patients with multiple organ dysfunction syndrome,acute physiological and chronic health scoring system II(APACHE II)score,white blood cell count and creatinine(CRE)level was higher in the AGI group than in the non-AGI group.There was a statistically significant difference between the two groups(P<0.05).Logistic regression analysis indicated that an APACHE II score>15 and CRE>100μmol/L were risk factors for SAP complicating AGI.The interaction index of APACHE II score and CRE level was 3.123.CONCLUSION An APACHE II score>15 and CRE level>100μmol/L are independent risk factors for SAP complicated with AGI,and there is a positive interaction between them.

Acute pancreatitis:A review of diagnosis,severity prediction and prognosis assessment from imaging technology,scoring system and artificial intelligence

Acute pancreatitis(AP)is a potentially life-threatening inflammatory disease of the pancreas,with clinical management determined by the severity of the disease.Diagnosis,severity prediction,and prognosis assessment of AP typically involve the use of imaging technologies,such as computed tomography,magnetic resonance imaging,and ultrasound,and scoring systems,including Ranson,Acute Physiology and Chronic Health Evaluation II,and Bedside Index for Severity in AP scores.Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity,while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications.Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild,moderate,or severe categories,guiding treatment decisions,such as intensive care unit admission,early enteral feeding,and antibiotic use.Despite the central role of imaging technologies and scoring systems in AP management,these methods have limitations in terms of accuracy,reproducibility,practicality and economics.Recent advancements of artificial intelligence(AI)provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data.AI algorithms can analyze large amounts of clinical and imaging data,identify scoring system patterns,and predict the clinical course of disease.AI-based models have shown promising results in predicting the severity and mortality of AP,but further validation and standardization are required before widespread clinical application.In addition,understanding the correlation between these three technologies will aid in developing new methods that can accurately,sensitively,and specifically be used in the diagnosis,severity prediction,and prognosis assessment of AP through complementary advantages.

Severe acute pancreatitis： pathogenesis, diagnosis and surgical management

BACKGROUND： Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology.DATA SOURCES： Studies published between 1st January 1991 and 31st December 2015 were identified with Pub Med, MEDLINE, EMBASE and Google Scholar online search engines using the following Medical Subject Headings： “acute pancreatitis, necrosis, mortality, pathogenesis, incidence” and the terms “open necrosectomy and minimally invasive necrosectomy”.The National Institute of Clinical Excellence（NICE） Guidelines were also included in our study. Inclusion criteria for our clinical review included established guidelines, randomized controlled trials and non-randomized controlled trials with a follow-up duration of more than 6 weeks.RESULTS： The incidence of severe acute pancreatitis within the UK is significantly rising and pathogenetic theories are still controversial. In developed countries, the most common cause is biliary calculi. The British Society of Gastroenterology,acknowledges the Revised Atlanta criteria for prediction of severity. A newer Determinant-based system has been developed.The principle of surgical management of acute necrotizing pancreatitis requires intensive care management, identifying infection and if indicated, debridement of any infected necrotic area. The current procedures opted for include standard surgical open necrosectomy, endoscopic necrosectomy and minimally invasive necrosectomy. The current paradigm is shifting towards a step-up approach.CONCLUSIONS： Severe acute pancreatitis is still a subject of grey areas in its surgical management even though new studies have been recorded since the origin of the latest UK guidelines for management of severe acute pancreatitis.

Effects of early enteral nutrition on immune function of severe acute pancreatitis patients

AIM:To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP).METHODS:Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN).Enteral nutrition was started within 48 h after admission in EEN group,whereas from the 8 th day in DEN group.All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1,3,7 and 14 after admission.The clinical outcome variables were also recorded.RESULTS:Sixty SAP patients were enrolled to this study.The CD4+ T-lymphocyte percentage,CD4+/CD8+ ratio,and the CRP levels in EEN group became significantly lower than in DEN group from the 7 th day after admission.In contrast,the immunoglobulin G(IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7 th day after admission.No difference of CD8+ T-lymphocyte percentage,IgM and IgA levels was found between the two groups.The incidences of multiple organ dysfunction syndrome,systemic inflammatory response syndrome,and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group.However,there was no difference of hospital mortality between the two groups.CONCLUSION:EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression.EEN can improve the clinical outcome,but not decrease the hospital mortality of SAP patients.

Sequential blood purification therapy for critical patients with hyperlipidemic severe acute pancreatitis

AIM: To evaluate the efficacy of sequential blood purification therapy in the treatment of critical patients with hyperlipidemic severe acute pancreatitis.METHODS: Thirty-one intensive care unit(ICU) patients with hyperlipidemic severe acute pancreatitis treated at the Second Affiliated Hospital of Harbin Medical University were divided into either a study group(n = 15; July 1, 2012 to June 30, 2014) or a control group(n = 16; July 1, 2010 to June 30, 2012) based on the implementation of sequential blood purification therapy. The control group received continuous venous-venous hemofiltration(CVVH) on the basis of conventional treatments, and the therapeutic dose of CVVH was 30 m L/kg per hour. The study group received sequential plasma exchange and CVVH on the basis of conventional treatments. The anticoagulation regimen of CVVH is the regional citrate anticoagulation. Mortality rate on day 28, rates of systemic and local complications, duration of ICU, and time to target serum lipid level, as well as physiologic and laboratory indices were compared between the two groups.RESULTS: The mortality rate on day 28 was significantly lower in the study group than in the control group(13.33% vs 37.50%; P < 0.05). The duration of ICU stay was significantly shorter in the study group than in the control group(7.4 ± 1.35 d vs 9.19 ± 2.99 d, P < 0.05). The time to target serum lipid level was significantly shorter in the study group than in the control group(3.47 ± 0.52 d vs 7.90 ± 1.14 d, P < 0.01). There were no significant differences in the rates of systemic complications and local complications between the two groups(60% vs 50% and 80% vs 81%, respectively). In the comparisons of physiologic and laboratory indices, serum albumin and C-reactive protein were significantly better in the study group than in the control group after treatment(37.8 ± 4.6 g/L vs 38.9 ± 5.7 g/L, and 20.5 ± 6.4 mg/L vs 28.5 ± 7.1 mg/L, respectively, both P < 0.05). With the exception of plateletcrit, no other indices showed significant differences between the two groups.CONCLUSION: Sequential blood purification therapy is effective in the treatment of ICU patients with hyperlipidemic severe acute pancreatitis and can improve patient prognosis.

Tissue factor in predicted severe acute pancreatitis

AIM: To study tissue factor (TF) in acute pancreatitis and evaluate the role of TF as a predictive marker of severity. METHODS: Forty-nine consecutive patients admitted to Lund University Hospital, fulfilling the criteria of predicted severe acute pancreatitis (AP), were recruited prospectively between 2002 and 2004. Blood samples for TF analyses were drawn at inclusion in the study and 12 h, 1 d and 3 d later. RESULTS: Twenty-seven patients developed mild AP, and 22 patients severe AP. At inclusion in the study, the groups were comparable with respect to gender, aetiology, Acute Physiology and Chronic Health Evaluation Ⅱ score, and duration of pain. At inclusion in the study and at 12 h, TF was higher in the severe AP group (P = 0.035 and P = 0.049, respectively). After 1 and 3 d, no differences in TF levels were noted. Interleukin (IL)-6 was significantly higher in the severe AP group at all of the studied time points. C-reactive protein (CRP) was significantly higher in the AP group at 1 and 3 d. In receiver operating characteristic-curves, the area under the curve (AUC) for TF was 0.679 (P = 0.035) at inclusion in the study, and a cut off level for TF of 40 pg/mL showed a sensitivity of 71% and a specificity of 67%, whereas corresponding AUC for IL-6 was 0.775, P = 0.001, and for CRP was 0.653. IL-6 showed better AUC-values than TF at all time points studied. CONCLUSION: TF-levels are raised early in severe AP. TF as an early predictive marker of severe AP is superior to CRP, but inferior to IL-6.

Prognostic value of red blood cell distribution width for severe acute pancreatitis

BACKGROUND Severe acute pancreatitis(SAP)is a common condition in the intensive care unit(ICU)and has a high mortality.Early evaluation of the severity and prognosis is very important for SAP therapy.Recently,red blood cell distribution(RDW)was associated with mortality of sepsis patients and could be used as a predictor of prognosis.Similarly,RDW may be associated with the prognosis of SAP patients and be used as a prognostic indicator for SAP patients.AIM To investigate the prognostic value of RDW for SAP patients.METHODS We retrospectively enrolled SAP patients admitted to the ICU of the First Affiliated Hospital of China Medical University from June 2015 to June 2017.According to the prognosis at 90 d,SAP patients were divided into a survival group and a non-survival group.RDW was extracted from a routine blood test.Demographic parameters and RDW were recorded and compared between the two groups.The receiver operator characteristic(ROC)curve was constructed and Cox regression analysis was performed to investigate the prognostic value of RDW for SAP patients.RESULTS In this retrospective cohort study,42 SAP patients were enrolled,of whom 22 survived(survival group)and 20 died(non-survival group).The baseline parameters were comparable between the two groups.The coefficient of variation of RDW(RDW-CV),standard deviation of RDW(RDW-SD),Acute Physiology and Chronic Health Evaluation II(APACHE II)score,and Sequential Organ Failure Assessment(SOFA)score were significantly higher in the non-survival group than in the survival group(P<0.05).The RDW-CV and RDW-SD were significantly correlated with the APACHE II score and SOFA score,respectively.The areas under the ROC curves(AUCs)of RDW-CV and RDW-SD were all greater than those of the APACHE II score and SOFA score,among which,the AUC of RDW-SD was the greatest.The results demonstrated that RDW had better prognostic value for predicting the mortality of SAP patients.When the RDW-SD was greater than 45.5,the sensitivity for predicting prognosis was 77.8%and the specificity was 70.8%.Both RDW-CV and RDW-SD could be used as independent risk factors to predict the mortality of SAP patients in multivariate logistic regression analysis and univariate Cox proportional hazards regression analysis,similar to the APACHE II and SOFA scores.CONCLUSION The RDW is greater in the non-surviving SAP patients than in the surviving patients.RDW is significantly correlated with the APACHE II and SOFA scores.RDW has better prognostic value for SAP patients than the APACHE II and SOFA scores and could easily be used by clinicians for the treatment of SAP patients.

Arpin contributes to bacterial translocation and development of severe acute pancreatitis

AIM: To assess the impact of Arpin protein and tight junction(TJ) proteins in the intestinal mucosa onbacterial translocation in patients with severe acute pancreatitis(SAP).METHODS: Fifty SAP patients were identified as study objects and then classified into two groups according to the presence of bacterial translocation(BT) in the blood [i.e., BT(+) and BT(-)].Twenty healthy individuals were included in the control group.BT was analyzed by polymerase chain reaction, colonic mucosal tissue was obtained by endoscopy and the expression of TJ proteins and Arpin protein was determined using immunofluorescence and western blotting.RESULTS: Bacterial DNA was detected in the peripheral blood of 62.0% of patients(31/50) with SAP.The expression of TJ proteins in SAP patients was lower than that in healthy controls.In contrast, Arpin protein expression in SAP patients was higher than in healthy controls(0.38 ± 0.19 vs 0.28 ± 0.16, P < 0.05).Among SAP patients, those positive for BT showed a higher level of claudin-2 expression(0.64 ± 0.27 vs 0.32 ± 0.21, P < 0.05) and a lower level of occludin(OC)(0.61 ± 0.28 vs 0.73 ± 0.32, P < 0.05) and zonula occludens-1(0.42 ± 0.26 vs 0.58 ± 0.17, P = 0.038) expression in comparison with BT(-) patients.Moreover, the level of Arpin expression in BT(+) patients was higher than in BT(-) patients(0.61 ± 0.28 vs 0.31 ± 0.24, P < 0.05).CONCLUSION: Arpin protein affects the expression of tight junction proteins and may have an impact on BT.These results contribute to a better understanding of the factors involved in bacterial translocation during acute pancreatitis.

Overexpressed miRNA-155 dysregulates intestinal epithelial apical junctional complex in severe acute pancreatitis

AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.

Abdominal paracentesis drainage ameliorates severe acute pancreatitis in rats by regulating the polarization of peritoneal macrophages

AIM To investigate the role of peritoneal macrophage(PM) polarization in the therapeutic effect of abdominal paracentesis drainage(APD) on severe acute pancreatitis(SAP).METHODS SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot.RESULTS APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin(IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of proinflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats.CONCLUSION These findings suggest that APD treatment exerts antiinflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanism underlying its therapeutic effect.

Pathological changes at early stage of multiple organ injury in a rat model of severe acute pancreatitis

BACKGROUND: Severe acute pancreatitis (SAP) is a commonly seen acute abdominal syndrome characterized by sudden onset, rapid progression and high mortality rate. The damage in peripheral organs may be more severe than that in the pancreas, and can even lead to multiple organ dysfunction. It is critical to recognize early pathological changes in multiple organs. This study aimed to assess the early pathological features of damaged organs in a rat model of SAP. METHODS: Thirty clean grade healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into a model control group (n=15) and a sham-operated group (n=15). The SAP rat model was induced by sodium taurocholate. Samples of blood and from multiple organs were collected 3 hours after operation. We assessed the levels of IL-6, TNF-alpha, PLA2, NO, ET-1, MDA, amylases and endotoxin in blood and observed the early pathological changes in multiple damaged organs. RESULTS: Levels of IL-6, TNF-alpha, PLA2, NO, ET-1 and MDA in serum and of amylase and endotoxin in plasma of the model control group rats were significantly higher than those of the sham-operated group (P<0.01). Different degrees of pathological change were observed in multiple damaged organs. CONCLUSION: Multiple organ injury may occur at the early stage of SAP in rats.

Circulating miRNAs as biomarkers for severe acute pancreatitis associated with acute lung injury

AIM To identify circulating micro(mi)RNAs as biological markers for prediction of severe acute pancreatitis(SAP) with acute lung injury(ALI).METHODS Twenty-four serum samples were respectively collected and classified as SAP associated with ALI and SAP without ALI, and the mi RNA expression profiles were determined by microarray analysis. These mi RNAs were validated by quantitative reverse transcriptionpolymerase chain reaction, and their putative targets were predicted by the online software Target Scan, mi Randa and Pic Tar database. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(commonly known as KEGG) were used to predict their possible functions and pathways involved.RESULTS We investigated 287 mi RNAs based on microarray data analysis. Twelve mi RNAs were differentially expressed in the patients with SAP with ALI and those with SAP without ALI. Hsa-mi R-1260 b, 762, 22-3 p, 23 b and 23 a were differently up-regulated and hsa-mi R-550 a*, 324-5 p, 484, 331-3 p, 140-3 p, 342-3 p and 150 were differently down-regulated in patients with SAP with ALI compared to those with SAP without ALI. In addition, 85 putative target genes of the significantly dysregulated mi RNAs were found by Target Scan, mi Randa and Pic Tar. Finally, GO and pathway network analysis showed that they were mainly enriched in signal transduction, metabolic processes, cytoplasm and cell membranes.CONCLUSION This is the first study to identify 12 circulating mi RNAs in patients with SAP with ALI, which may be biomarkers for prediction of ALI after SAP.

Pathogenesis of pancreatic encephalopathy in severe acute pancreatitis

BACKGROUND: Pancreatic encephalopathy (PE) is a serious complication of severe acute pancreatitis (SAP). In recent years, more and more PE cases have been reported worldwide, and the onset PE in the early stage was regarded as a poor prognosis sign of SAP, but the pathogenesis of PE in SAP still has not been clarified in the past decade. The purpose of this review is to elucidate the possible pathogenesis of PE in SAP. DATA SOURCES: The English-language literature concerning PE in this review came from the Database of MEDLINE (period of 1991-2005), and the keywords of severe acute pancreatitis and pancreatic encephalopathy were used in the searching. RESULTS: Many factors were involved in the pathogenesis of PE in SAP. Pancreatin activation, excessive release of cytokines and oxygen free radicals, microcirculation abnormalities of hemodynamic disturbance, ET-1/NO ratio, hypoxemia, bacterial infection, water and electrolyte imbalance, and vitamin B1 deficiency participated in the development of PE in SAP. CONCLUSIONS: The pathogenesis of PE in SAP has not yet been fully understood. The development of PE in SAP may be a multi-factor process. To find out the possible inducing factor is essential to the clinical management of PE in SAP.

Portosplenomesenteric vein thrombosis in patients with early-stage severe acute pancreatitis

AIM To investigate the incidence and risk factors of portosplenomesenteric vein thrombosis(PSMVT) in the early stage of severe acute pancreatitis(SAP).METHODS Patients with SAP in a tertiary care setting from January 2014 to December 2016 were retrospectively reviewed. All contrast-enhanced computed tomography(CT) studies were reassessed and reviewed. Clinical outcome measures were compared between SAP patients with and without PSMVT in the early stage of the disease. Univariate and multivariate logistic regression analyses were sequentially performed to assess potential risk factors for the development of PSMVT in SAP patients. A receiver operating characteristic(ROC) curve was generated for the qualifying independent risk factors.RESULTS Twenty-five of the one hundred and forty(17.86%) SAP patients developed PSMVT 6.19 ± 2.43 d after acute pancreatitis(AP) onset. PSMVT was confirmed by contrast-enhanced CT. Multivariate stepwise logistic regression analyses showed that Balthazar's CT severity index(CTSI) scores [odds ratio(OR): 2.742; 95% confidence interval(CI): 1.664-4.519; P = 0.000], hypoalbuminemia(serum albumin level < 25 g/L)(OR: 32.573; 95%CI: 2.711-391.353; P = 0.006) and gastrointestinal wall thickening(OR: 4.367, 95%CI: 1.218-15.658; P = 0.024) were independent risk factors for PSMVT developed in patients with SAP. The area under the ROC curve for Balthazar's CTSI scores was 0.777(P = 0.000), the sensitivity was 52%, and the specificity was 93% at a cut-off value of 5.5.CONCLUSION High Balthazar's CTSI scores, hypoalbuminemia and gastrointestinal wall thickening are independent risk factors for PSMVT developed in the early stage of SAP.

Involvement of interstitial cells of Cajal in experimental severe acute pancreatitis in rats

AIM:To observe the changes in interstitial cells of Cajal(ICC) in rats with experimental severe acute pancreatitis(SAP).METHODS:A total of twenty-four SD rats were randomly divided into two groups(n = 12),namely the sham(S) group and the SAP group;the SAP rat model was established by retrograde injection of 5% sodium taurocholate(1.0 mL/kg) into the pancreatic duct.Twenty-four hours later intestinal motility was assessed by testing small intestinal propulsion rate,and then the rats were sacrificed.The pancreas and jejunum were resected and underwent routine pathologic examination.Immunohistochemical staining was used to detect c-kit-positive cells in the jejunum.Expression of c-kit mRNA was detected by real-time polymerase chain reaction,and the expression of c-kit protein was evaluated by Western blotting.Ultrastructure of ICC was evaluated by transmission electron microscopy.RESULTS:There was bleeding,necrosis and a largeamount of inflammatory cell infiltration in pancreatic tissue in the SAP group,while in jejunal tissue we observed a markedly denuded mucosal layer,loss of villous tissue and a slightly dilated muscular layer.The small intestinal propulsion rate was 68.66% ± 2.66% in the S group and 41.55% ± 3.85% in the SAP group.Compared with the S group,the rate of the SAP group decreased sharply.The density of c-kit-positive cells in the SAP group was significantly lower than in the S group;the respective mean densities were 88.47 ± 10.49 in the S group and 56.11 ± 7.09 in the SAP group.The levels of c-kit protein and mRNA were 0.36 ± 0.04 and 1.29 ± 0.91 in the SAP group,respectively,which were significantly lower than those in the S group(0.53 ± 0.06,0.64 ± 0.33,respectively).In the SAP group,ICC profiles showed the same change tendency,such as vacuolation of mitochondria,irregular vacuoles and loosened desmosome-like junctions.CONCLUSION:Decreased c-kit-positive cells and ultrastructural changes in ICC resulting from blockade of the c-kit signaling pathway are involved in the intestinal dysmotility associated with SAP.

Interleukin-22 ameliorates acute severe pancreatitisassociated lung injury in mice

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P < 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.