Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes...Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.展开更多
Necrotizing or severe pancreatitis represents approximately 10%-20%of acute pancreatitis.30%-40%of patients with acute necrotizing pancreatitis(ANP)will develop debris infection through translocation of intestinal mic...Necrotizing or severe pancreatitis represents approximately 10%-20%of acute pancreatitis.30%-40%of patients with acute necrotizing pancreatitis(ANP)will develop debris infection through translocation of intestinal microbial flora.Infected ANP constitutes a serious clinical condition and is complicated by severe sepsis with high mortality rates of up to 40%despite progress in current intensive care.The timely detection of sepsis is crucial.The Quick Sequential Organ Failure Assessment score,procalcitonin levels>1.8 ng/mL and increased lactates>2 mmol/L(>18 mg/dL),indicate the need for urgent management.The escalated step-by-step management protocol starts with broad-spectrum antibiotics,percutaneous drainage or endoscopic management,and ends with surgical management if needed.The latter includes necrosectomy(either laparoscopic or traditional open surgery),peritoneal lavage and extensive drainage.This management protocol increases the chance of survival to approximately 60%in patients with otherwise fatal cases.Any treatment choice must be individualized,and the timing is critical.展开更多
We report the case of a female patient with severe acute necrotizing pancreatitis associated with hypercalcemia as first manifestation of primary hyperparathyroidism caused by a benign parathyroid adenoma.Initially th...We report the case of a female patient with severe acute necrotizing pancreatitis associated with hypercalcemia as first manifestation of primary hyperparathyroidism caused by a benign parathyroid adenoma.Initially the acute pancreatitis was treated conservatively.The patient subsequently underwent surgical resection of the parathyroid adenoma and surgical clearance of a large infected pancreatic pseudocyst.Although the association of parathyroid adenoma-induced hypercalcemia and acute pancreatitis is a known medical entity,it is very uncommon.The pathophysiology of hypercalcemia-induced acute pancreatitis is therefore not well known,although some mechanisms have been proposed.It is important to treat the provoking factor.Therefore,the cause of hypercalcemia should be identif ied early.Surgical resection of the parathyroid adenoma is the ultimate therapy.展开更多
ObjectiFe To evaluate the changes of pancreatic acinar cell functions in the rats with acutenecrotizing pancreatitis (ANP). methods Seventy SD rats were randomized into two groups: experimental group(n=35) and control...ObjectiFe To evaluate the changes of pancreatic acinar cell functions in the rats with acutenecrotizing pancreatitis (ANP). methods Seventy SD rats were randomized into two groups: experimental group(n=35) and control group (n=35). To prepare the experimental model, the retrograde injection of 5% sodiumtaurocholate into the pancreatic duct was used for inducing ANP. Radioactive tracing by L -3H-phenylalanineand autoradiography were performed for scoring the differences of changes of amino acid uptake, enzyme-proteinsynthesis and output from acinar cells in rats between both groups. Results No changes were observed in aminoacid uptake and enzyme -protein synthesis in rats with dotted and haemorrhagic necrotizing foci as compared withcontrol group. However, accumulated zymogen granules in the interstitial of acinar cells were seen in theexperimental group. Conclusion It indicates that in experimental ANP rats, the functions of acinar cells in bothamino acid uptake and protein synthesis were essentially normal, but the pathway of enzyme output was affectedinto ectopic secretion through the bottom or lateral cellular membrane of pancreatic acinar cell.展开更多
BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to exp...BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group C); ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1β (IL-1β) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P<0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P<0.01). The level of serum IL-1β in group P increased more significantly than that in group C (P<0.01). Blood flow of the stomach in group T was significantlyhigher than that in group P after 2 hours (P<0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P<0.01). Although serum IL-1β level of group T, was higher than of group C (P<0.01), it was lower than that of group P (P<0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P<0.01), and between gastric blood flow and pathological score (r=-0.917, P<0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.展开更多
Necrosis of pancreatic parenchyma or extrapancreatic tissues is present in 10%-20% of patients with acute pancreatitis, defining the necrotizing presentation frequently associated with high morbidity and mortality rat...Necrosis of pancreatic parenchyma or extrapancreatic tissues is present in 10%-20% of patients with acute pancreatitis, defining the necrotizing presentation frequently associated with high morbidity and mortality rates. During the initial phase of acute necrotizing pancreatitis the most important pillars of medical treatment are fluid resuscitation, early enteral nutrition, endoscopic retrograde colangiopancreatography if associated cholangitis and intensive care unit support. When infection of pancreatic or extrapancreatic necrosis occurs, surgical approach constitutes the most accepted therapeutic option. In this context, we have recently assited to changes in time for surgery(delaying the indication if possible to around 4 wk to deal with "walledoff" necrosis) and type of access for necrosectomy: from a classical open approach(with closure over large-bore drains for continued postoperative lavage or semiopen techniques with scheduled relaparotomies), trends have changed to a "step-up" philosophy with initial percutaneous drainage and posterior minimally invasive or endoscopic access to the retroperitoneal cavity for necrosectomy if no improvement has been previously achieved. These approaches are progressively gaining popularity and morbidity and mortality rates have decreased significantly. Therefore, a staged, multidisciplinary, step-up approach with minimally invasive or endoscopic access for necrosectomy is widely accepted nowadays for management of pancreatic necrosis.展开更多
BACKGROUND: In approximately 20% of patients, necrotizing pancreatitis is complicated with severe acute pancreatitis, with high morbidity and mortality rates. Minimally invasive step-up approach is both safe and effec...BACKGROUND: In approximately 20% of patients, necrotizing pancreatitis is complicated with severe acute pancreatitis, with high morbidity and mortality rates. Minimally invasive step-up approach is both safe and effective, but sometimes requires multiple access sites.METHODS: A 62-year-old woman was admitted with diabetic ketoacidosis, and initial computed tomography(CT) revealed no evidence of acute pancreatitis. She was clinically improved with insulin therapy, fl uid administration, and electrolyte replacement. However, on the 14 th day of admission, she developed a high-grade fever, and CT demonstrated evidence of acute necrotizing pancreatitis with a large collection of peripancreatic fl uid. Percutaneous transgastric drainage was performed and a 14 French gauge(Fr) pigtail catheter was placed 1 week later, which drained copious pus. Because of persistent high-grade fever and poor clinical improvement, multiple 8 and 10 Fr pigtail catheters were placed via the initial drainage route, allowing the safe and effective drainage of the extensive necrotic tissue that was occupying the bilateral anterior pararenal space.RESULTS: After drainage, the patient recovered well and the last catheter was removed on day 123 of admission.CONCLUSIONS: Multiple percutaneous drainage requires both careful judgment and specialist skills. The perforation of the colon and small bowel as well as the injury of the kidney and major vessels can occur. The current technique appears to be safe and minimally invasive compared with other drainage methods in patients with extended, infected necrotic pancreatic pseudocysts.展开更多
AIM: To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 64 rats were random...AIM: To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane.Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 (P＜0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and (P＜0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20) μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07) μg/L (P＜0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P＜0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred.CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.展开更多
BACKGROUND:In experimental acute pancreatitis,a large amount of reactive oxygen species are produced,and in turn cytoskeletal changes may be induced in pancreatic tissue.These changes contribute to an imbalance of dig...BACKGROUND:In experimental acute pancreatitis,a large amount of reactive oxygen species are produced,and in turn cytoskeletal changes may be induced in pancreatic tissue.These changes contribute to an imbalance of digestive enzyme segregation,transport,exocytosis and activation, resulting in cell injury.In this study,we assessed the effects of chondroitin sulfate(CS)on attenuation of oxidative damage and protection of F-actin in rats with acute necrotizing pancreatitis(ANP). METHODS:Ninety male Wistar rats were divided randomly into three groups.Group A was infused with 5%sodium taurocholate;group B was treated with CS; and group C served as control.Rats from the three groups were killed at 1,3 or 8 hours.The levels were measured of malonyl dialdehyde(MDA),total superoxide dismutase (SOD),glutathione synthetase(GSH),serum amylase (SAM)and adenosine triphosphate(ATP).F-actin immunostained with rhodamine-phalloidin was analyzed using a confocal laser scanning system and the content of F-actin protein was determined. RESULTS:The levels of SAM increased in groups A and B,whereas the levels of GSH,SOD and ATP in group A decreased markedly during pancreatitis,and MDA increased significantly.The levels of GSH,SOD and ATP in group B were higher than those in group A,but the level of MDA was lower than in group A.At the same time, ANP resulted in early disruption of the cytoskeleton with dramatic changes and a loss of F-actin.Administration of CS moderated the damage to the actin cytoskeleton.CONCLUSIONS:Retrograde infusion of sodium taurocholate via the pancreatic duct may produce pancreatic necrosis and a marked increase in serum amylase activity,induce a severe depletion of ATP level, prime lipid peroxidation,and damage F-actin.Treatment with CS can ameliorate pancreatic cell conditions,limit cell membrane peroxidation,protect F-actin,and attenuate pancreatitis.展开更多
AIM: To evaluate the role of microcirculatory disorder (MCD) and the therapeutic effectiveness of tetramethyl- pyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP). METHODS: A t...AIM: To evaluate the role of microcirculatory disorder (MCD) and the therapeutic effectiveness of tetramethyl- pyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 192 Sprague-Dawley rats were randomly divided into three groups: normal control group (C group), ANP group not treated with TMP (P group), ANP group treated with TMP (T group). An ANP model was induced by injection of 50 g/L sodium tau- rocholate under the pancreatic membrane (4 mL/kg). C group received isovolumetric injection of 9 g/L physi- ological saline solution using the same method. T group received injection of TMP (10 mL/kg) via portal vein. Ra- dioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histol- ogy score. Intestinal tissues were also used for examina- tion of myeloperoxidase (MPO) expressed intracellularly in azurophilic granules of neutrophils. RESULTS: The blood flow was significantly lower in P group than in C group (P < 0.01). The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group (P < 0.01). The blood flow of intestine was significantly higher in T group than in P group after 2 h (P < 0.01). The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group (P < 0.01 or P < 0.05). There was a negative correlation be- tween intestinal blood flow and MPO activity (r = -0.981, P < 0.01) as well as between intestinal blood flow and pathologic scores (r = -0.922, P < 0.05).CONCLUSION: MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.展开更多
AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatit...AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatitis (ANP). METHODS:A total of 64 Sprague-Dawley (SD) rats were randomly divided into two groups:normal control group (C group), ANP group (P group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane. Normal control group received isovolumetric injection of 9 g/L physiological saline solution using the same method. The blood samples of the rats in each group were obtained via superior mesenteric vein to measure levels of IL-2, IL-10, sFas and calculate the value of IL-2/IL-10. The levels of IL-2, IL-10 and sFas were determined by ELISA. The severity of intestinal mucosal injury was evaluated by pathologic score. The expression of Fas in intestinal mucosal tissue was determined by immunohistochemistry staining. RESULTS:Levels of serum IL-2 were significantly higher in P group than those of C group (2.79 ± 0.51 vs 3.53 ± 0.62, 2.93 ± 0.89 vs 4.35 ± 1.11, 4.81 ± 1.23 vs 6.94 ± 1.55 and 3.41 ± 0.72 vs 4.80 ± 1.10, respectively, P < 0.01, for all) and its reached peak at 6 h. Levels of serum IL-10 were significantly higher in P group than those of C group at 6 h and 12 h (54.61 ± 15.81 vs 47.34 ± 14.62, 141.15 ± 40.21 vs 156.12 ± 43.10, 89.18 ± 32.52 vs 494.98 ± 11.23 and 77.15 ± 22.60 vs 93.28 ± 25.81, respectively, P < 0.01, for all). The values of IL-2/IL-10 were higher significantly in P group than those of C group at 0.5 h and 2 h (0.05 ± 0.01 vs 0.07 ± 0.02 and 0.02 ± 0.01 vs 0.03 ± 0.01, respectively, P < 0.01, for all), and it were significantly lower than those of C group at 6 h (0.05 ± 0.02 vs 0.01 ± 0.01, P < 0.01) and returned to the control level at 12 h (0.04 ± 0.01 vs 0.05 ± 0.02, P > 0.05). In sFas assay, there was no significant difference between P group and C group (3.16 ± 0.75 vs 3.31 ± 0.80, 4.05 ± 1.08 vs 4.32 ± 1.11, 5.93 ± 1.52 vs 5.41 ± 1.47 and 4.62 ± 1.23 vs 4.44 ± 1.16, respectively, P > 0.05, for all). Comparison of P group and C group, the pathological changes were aggravated significantly in P group. Immunohistochemistry staining show the expression of Fas was absent in normal intestinal tissues, however, it gradually increased after induction of pancreatitis in intestinal tissue, then reached their peaks at 12 h.CONCLUSION:Fas were involved in the pathogenesis of pancreatitis associated intestinal injury. The mechanisms of Fas may be associated to Fas mediated T helper cell apoptosis.展开更多
AIM:To investigate the effect of Chai-Qin-Cheng-Qi Decoction(CQCQD)on cefotaxime(CTX)concentration in pancreas of rats with acute necrotizing pancreatitis (ANP). METHODS:Sixty healthy male Sprague-Dawley rats were div...AIM:To investigate the effect of Chai-Qin-Cheng-Qi Decoction(CQCQD)on cefotaxime(CTX)concentration in pancreas of rats with acute necrotizing pancreatitis (ANP). METHODS:Sixty healthy male Sprague-Dawley rats were divided randomly into an ANP group(ANP model +CTX,n=20),treatment group(ANP model+CTX +CQCQD,n=20)and control group(normal rats+ CTX,n=20).ANP models were induced by retrograde intraductal injection of 3.5%sodium taurocholate (1 mL/kg),and the control group was injected intraductally with normal saline.All rats were injected introperitoneally with 0.42 g/kg CTX(at 12-h intervals for a continuous 72 h)at 6 h after intraductal injection. Meanwhile,the treatment group received CQCQD (20 mL/kg)intragastrically at 8-h intervals,and the ANP and control group were treated intragastrically with normal saline.At 15 min after the last CTX injection,blood and pancreas samples were collected for the determination of CTX concentration using validated high-performance liquid chromatography. Pathological changes and wet-to-dry-weight(W/D) ratio of pancreatic tissue were examined. RESULTS:Serum CTX concentrations in three groups were not significantly different.Pancreatic CTXconcentration and penetration ratio were lower in ANP group vs control group(4.4±0.6μg/mL vs 18.6± 1.7μg/mL,P=0.000;5%vs 19%,P=0.000),but significantly higher in treatment group vs ANP group (6.4±1.7μg/mL vs 4.4±0.6μg/mL,P=0.020;7% vs 5%,P=0.048).The histological scores and W/D ratio were significantly decreased in treatment group vs ANP and control group. CONCLUSION:CQCQD might have a promotive effect on CTX concentration in pancreatic tissues of rats with ANP.展开更多
AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of...AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS: Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg·b·m, of 50 g/L sodium taurocholate(NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mglkg·b.m.was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction.Serum activities of amylase, IL-6 and TNF-α and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-,Cu-,and Zn-SOD) in pancreatic tissue were measured.RESULTS: Serum TNF-α and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes.CONCLUSION: Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylac ticoctreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.展开更多
INTRODUCTIONAcute narcotizing pancreatitis usually takes a severe clinical course and is associated with multiple organ dysfunction .With the further understanding of pathophysiological events of acute pancreatisis an...INTRODUCTIONAcute narcotizing pancreatitis usually takes a severe clinical course and is associated with multiple organ dysfunction .With the further understanding of pathophysiological events of acute pancreatisis and the therapeutic measuses taken by the clinicians ,the patients can pass through the critical carry stages ,and then the septic complication caused by rtanslocated bacteria, mostly gram-negative microbes from the intestines ensues[1].展开更多
Acute necrotizing pancreatitis complicated with pancreatic pseudoaneurysm is a rare emergency associated with high mortality that demands immediate treatment to save the patient’s life. We treated a 64-year-old man w...Acute necrotizing pancreatitis complicated with pancreatic pseudoaneurysm is a rare emergency associated with high mortality that demands immediate treatment to save the patient’s life. We treated a 64-year-old man who presented with a bleeding pseudoaneurysm of the superior mesenteric artery caused by acute pancreatitis, using interventional embolizing therapy. In the present report we show that interventional treatment is an effective therapeutic modality for patients with acute necrotizing pancreatitis complicated with intra-abdominal bleeding.展开更多
The expression of micro RNA-19b(mi R-19b) in acute necrotizing pancreatitis(ANP) and its functional role in acinar cell necrosis of SD rats were investigated. Twelve SD rats were divided into two groups randomly, incl...The expression of micro RNA-19b(mi R-19b) in acute necrotizing pancreatitis(ANP) and its functional role in acinar cell necrosis of SD rats were investigated. Twelve SD rats were divided into two groups randomly, including control group and ANP group. The rat ANP models were established by intraperitoneal injection of L-arginine(2400 mg/kg body weight), and equal volume of 0.9% Na Cl was injected in the control group. Mi RNA chip assay was performed to examine the expression of mi RNAs in the pancreas in two different groups. Besides, to further explore the role of mi R-19 b in ANP in vitro, taurolithocholic acid 3-sulfate disodium salt(TLC-S)(200 μmol/L) was administrated to treat the rat pancreatic acinar cell line, AR42 J, for establishing the ANP cells model. The quantitative real-time PCR(q RT-PCR) was adopted to measure the mi R-19 b expression. Moreover, the mimic mi RNA, mi RNA antisense oligonucleotide(AMO) and control vector were used to transfect AR42 J cells, the expression of mi R-19 b was confirmed by q RT-PCR and the necrotizing rate of AR42 J cells was detected with AO/EB method. The expression of mi R-19 b was significantly higher in ANP group than in control group as displayed by the mi RNA chip assay. Furthermore, after inducing necrosis of AR42 J cells in vitro, the expression of mi R-19 b was significantly increased by 2.51±0.14 times in comparison with the control group. As revealed by q RT-PCR assay, the expression of mi R-19 b was 5.94±0.95 times higher in the mimic mi RNA group than in the control vector group, companied with an obviously increased acinar cell necrotizing rate(50.3%±1.5% vs. 39.6%±2.3%, P<0.05). Moreover, the expression of mi R-19 b in the mi RNA AMO group was 0.38±0.15 times lower than in the control vector group, and the cell necrosis rate was much lower accordingly(23.1%±3.3% vs. 39.6%±2.3%, P<0.05). Besides, there was no significant difference between the control vector cells and the cells without treatment(P>0.05). The expression of mi R-19 b was significantly induced in ANP. In addition, up-regulation of mi R-19 b could promote the necrosis of pancreatic acinar cells and mi R-19 b deficiency could decrease the rate of pancreatic acinar cell necrosis.展开更多
AIM:To establish a one-stage model of experimental acute necrotizing pancreatitis(ANP)in rats characterized by the simplicity of performance and a high degree of repeatability.METHODS:ANP modeling in rats was performe...AIM:To establish a one-stage model of experimental acute necrotizing pancreatitis(ANP)in rats characterized by the simplicity of performance and a high degree of repeatability.METHODS:ANP modeling in rats was performed based on modification of the ligation model as follows:synthetic material ligature using an atraumatic needle was performed to capture pancreatic gland ducts and marginal duodenum vessels.Ligature tips were exteriorized to the abdominal wall,and the ligature was skinned over to avoid catching intestine loops.Pancreatic macroscopic appearance and histological changes were observed.Blood biochemical and hemostatic indicators were also determined.RESULTS:Laboratory analysis of rats with experimental ANP showed a pattern of disturbances similar to that observed during pancreatic necrosis in humans as soon as the first day.General blood analysis revealed enhanced leukocytosis and alterations in leukogram characteristics,indicating acute inflammation.Serum levels of amylase,aspartate aminotransferase and creatinine significantly increased(P<0.05).Hemostatic indicators showed alterations indicating formation of disseminated intravascular coagulation,and signs of endotoxicosis were observed.These typical pancreatic necrosis patterns of disturbances were validated by the results of histological investigation.CONCLUSION:Histological changes and laboratory indicators confirm the development of a suitable model of ANP.展开更多
BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancre...BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.展开更多
BACKGROUND Early initiation of enteral feeding is recognized to play a crucial role in improving the outcomes of treatment of acute pancreatitis.However,the method of adminis-tration of enteral nutrition remains debat...BACKGROUND Early initiation of enteral feeding is recognized to play a crucial role in improving the outcomes of treatment of acute pancreatitis.However,the method of adminis-tration of enteral nutrition remains debatable.We present the experience of treating a patient with moderate-severe acute pancreatitis,at high risk of progressing to a severe or fatal condition,using a novel method of selective feeding with duodenal isolation.CASE SUMMARY A 27-year-old female patient presented to the emergency unit of the hospital with a typical manifestation of acute pancreatitis.Despite a conventional treatment,the patient’s condition deteriorated by day 2 of hospitalization.Using an endoscopic approach,a novel catheter PandiCathffwas placed to the duodenum of the patient,isolating its segment between the duodenal bulb and the ligament of Treitz.In the isolated area created,a negative pressure was applied,followed by introduction of early selective enteral feeding.The patient’s condition subsequently improved in a rapid manner,and no complications often associated with moderate-to-severe acute pancreatitis developed.CONCLUSION Within 48 h of starting treatment with the novel method,it can prevent the development of multiple organ failure and,when combined with minimally invasive drainage methods,help prevent infection.展开更多
基金supported by grants from the National Natural Science Foundation of China (82070665 and 81900592)
文摘Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.
文摘Necrotizing or severe pancreatitis represents approximately 10%-20%of acute pancreatitis.30%-40%of patients with acute necrotizing pancreatitis(ANP)will develop debris infection through translocation of intestinal microbial flora.Infected ANP constitutes a serious clinical condition and is complicated by severe sepsis with high mortality rates of up to 40%despite progress in current intensive care.The timely detection of sepsis is crucial.The Quick Sequential Organ Failure Assessment score,procalcitonin levels>1.8 ng/mL and increased lactates>2 mmol/L(>18 mg/dL),indicate the need for urgent management.The escalated step-by-step management protocol starts with broad-spectrum antibiotics,percutaneous drainage or endoscopic management,and ends with surgical management if needed.The latter includes necrosectomy(either laparoscopic or traditional open surgery),peritoneal lavage and extensive drainage.This management protocol increases the chance of survival to approximately 60%in patients with otherwise fatal cases.Any treatment choice must be individualized,and the timing is critical.
文摘We report the case of a female patient with severe acute necrotizing pancreatitis associated with hypercalcemia as first manifestation of primary hyperparathyroidism caused by a benign parathyroid adenoma.Initially the acute pancreatitis was treated conservatively.The patient subsequently underwent surgical resection of the parathyroid adenoma and surgical clearance of a large infected pancreatic pseudocyst.Although the association of parathyroid adenoma-induced hypercalcemia and acute pancreatitis is a known medical entity,it is very uncommon.The pathophysiology of hypercalcemia-induced acute pancreatitis is therefore not well known,although some mechanisms have been proposed.It is important to treat the provoking factor.Therefore,the cause of hypercalcemia should be identif ied early.Surgical resection of the parathyroid adenoma is the ultimate therapy.
文摘ObjectiFe To evaluate the changes of pancreatic acinar cell functions in the rats with acutenecrotizing pancreatitis (ANP). methods Seventy SD rats were randomized into two groups: experimental group(n=35) and control group (n=35). To prepare the experimental model, the retrograde injection of 5% sodiumtaurocholate into the pancreatic duct was used for inducing ANP. Radioactive tracing by L -3H-phenylalanineand autoradiography were performed for scoring the differences of changes of amino acid uptake, enzyme-proteinsynthesis and output from acinar cells in rats between both groups. Results No changes were observed in aminoacid uptake and enzyme -protein synthesis in rats with dotted and haemorrhagic necrotizing foci as compared withcontrol group. However, accumulated zymogen granules in the interstitial of acinar cells were seen in theexperimental group. Conclusion It indicates that in experimental ANP rats, the functions of acinar cells in bothamino acid uptake and protein synthesis were essentially normal, but the pathway of enzyme output was affectedinto ectopic secretion through the bottom or lateral cellular membrane of pancreatic acinar cell.
基金This study was supported by grants from the Zhenjiang Science and Technology Committee(No.SH2002015and No.SH2005044).
文摘BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group C); ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1β (IL-1β) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P<0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P<0.01). The level of serum IL-1β in group P increased more significantly than that in group C (P<0.01). Blood flow of the stomach in group T was significantlyhigher than that in group P after 2 hours (P<0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P<0.01). Although serum IL-1β level of group T, was higher than of group C (P<0.01), it was lower than that of group P (P<0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P<0.01), and between gastric blood flow and pathological score (r=-0.917, P<0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.
文摘Necrosis of pancreatic parenchyma or extrapancreatic tissues is present in 10%-20% of patients with acute pancreatitis, defining the necrotizing presentation frequently associated with high morbidity and mortality rates. During the initial phase of acute necrotizing pancreatitis the most important pillars of medical treatment are fluid resuscitation, early enteral nutrition, endoscopic retrograde colangiopancreatography if associated cholangitis and intensive care unit support. When infection of pancreatic or extrapancreatic necrosis occurs, surgical approach constitutes the most accepted therapeutic option. In this context, we have recently assited to changes in time for surgery(delaying the indication if possible to around 4 wk to deal with "walledoff" necrosis) and type of access for necrosectomy: from a classical open approach(with closure over large-bore drains for continued postoperative lavage or semiopen techniques with scheduled relaparotomies), trends have changed to a "step-up" philosophy with initial percutaneous drainage and posterior minimally invasive or endoscopic access to the retroperitoneal cavity for necrosectomy if no improvement has been previously achieved. These approaches are progressively gaining popularity and morbidity and mortality rates have decreased significantly. Therefore, a staged, multidisciplinary, step-up approach with minimally invasive or endoscopic access for necrosectomy is widely accepted nowadays for management of pancreatic necrosis.
文摘BACKGROUND: In approximately 20% of patients, necrotizing pancreatitis is complicated with severe acute pancreatitis, with high morbidity and mortality rates. Minimally invasive step-up approach is both safe and effective, but sometimes requires multiple access sites.METHODS: A 62-year-old woman was admitted with diabetic ketoacidosis, and initial computed tomography(CT) revealed no evidence of acute pancreatitis. She was clinically improved with insulin therapy, fl uid administration, and electrolyte replacement. However, on the 14 th day of admission, she developed a high-grade fever, and CT demonstrated evidence of acute necrotizing pancreatitis with a large collection of peripancreatic fl uid. Percutaneous transgastric drainage was performed and a 14 French gauge(Fr) pigtail catheter was placed 1 week later, which drained copious pus. Because of persistent high-grade fever and poor clinical improvement, multiple 8 and 10 Fr pigtail catheters were placed via the initial drainage route, allowing the safe and effective drainage of the extensive necrotic tissue that was occupying the bilateral anterior pararenal space.RESULTS: After drainage, the patient recovered well and the last catheter was removed on day 123 of admission.CONCLUSIONS: Multiple percutaneous drainage requires both careful judgment and specialist skills. The perforation of the colon and small bowel as well as the injury of the kidney and major vessels can occur. The current technique appears to be safe and minimally invasive compared with other drainage methods in patients with extended, infected necrotic pancreatic pseudocysts.
基金Supported by the Traditional Chinese Medicine Administration Bureau Foundation of Jiangsu Province,No.9965the Applied Basic Research Program of Science and Technology Commission Foundation of Jiangsu Province,No.BJ2000327
文摘AIM: To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane.Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 (P＜0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and (P＜0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20) μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07) μg/L (P＜0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P＜0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred.CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.
文摘BACKGROUND:In experimental acute pancreatitis,a large amount of reactive oxygen species are produced,and in turn cytoskeletal changes may be induced in pancreatic tissue.These changes contribute to an imbalance of digestive enzyme segregation,transport,exocytosis and activation, resulting in cell injury.In this study,we assessed the effects of chondroitin sulfate(CS)on attenuation of oxidative damage and protection of F-actin in rats with acute necrotizing pancreatitis(ANP). METHODS:Ninety male Wistar rats were divided randomly into three groups.Group A was infused with 5%sodium taurocholate;group B was treated with CS; and group C served as control.Rats from the three groups were killed at 1,3 or 8 hours.The levels were measured of malonyl dialdehyde(MDA),total superoxide dismutase (SOD),glutathione synthetase(GSH),serum amylase (SAM)and adenosine triphosphate(ATP).F-actin immunostained with rhodamine-phalloidin was analyzed using a confocal laser scanning system and the content of F-actin protein was determined. RESULTS:The levels of SAM increased in groups A and B,whereas the levels of GSH,SOD and ATP in group A decreased markedly during pancreatitis,and MDA increased significantly.The levels of GSH,SOD and ATP in group B were higher than those in group A,but the level of MDA was lower than in group A.At the same time, ANP resulted in early disruption of the cytoskeleton with dramatic changes and a loss of F-actin.Administration of CS moderated the damage to the actin cytoskeleton.CONCLUSIONS:Retrograde infusion of sodium taurocholate via the pancreatic duct may produce pancreatic necrosis and a marked increase in serum amylase activity,induce a severe depletion of ATP level, prime lipid peroxidation,and damage F-actin.Treatment with CS can ameliorate pancreatic cell conditions,limit cell membrane peroxidation,protect F-actin,and attenuate pancreatitis.
基金Supported by Zhenjiang Science and Technology Committee, No. SH2002015
文摘AIM: To evaluate the role of microcirculatory disorder (MCD) and the therapeutic effectiveness of tetramethyl- pyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 192 Sprague-Dawley rats were randomly divided into three groups: normal control group (C group), ANP group not treated with TMP (P group), ANP group treated with TMP (T group). An ANP model was induced by injection of 50 g/L sodium tau- rocholate under the pancreatic membrane (4 mL/kg). C group received isovolumetric injection of 9 g/L physi- ological saline solution using the same method. T group received injection of TMP (10 mL/kg) via portal vein. Ra- dioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histol- ogy score. Intestinal tissues were also used for examina- tion of myeloperoxidase (MPO) expressed intracellularly in azurophilic granules of neutrophils. RESULTS: The blood flow was significantly lower in P group than in C group (P < 0.01). The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group (P < 0.01). The blood flow of intestine was significantly higher in T group than in P group after 2 h (P < 0.01). The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group (P < 0.01 or P < 0.05). There was a negative correlation be- tween intestinal blood flow and MPO activity (r = -0.981, P < 0.01) as well as between intestinal blood flow and pathologic scores (r = -0.922, P < 0.05).CONCLUSION: MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.
基金Zhenjiang Science and Technology Committee, No. SH2005044
文摘AIM:To investigate dynamic changes of serum IL-2, IL-10, IL-2/IL-10 and sFas in rats with acute necrotizing pancreatitis. To explore the expression of Fas in intestinal mucosa of rats with acute necrotizing pancreatitis (ANP). METHODS:A total of 64 Sprague-Dawley (SD) rats were randomly divided into two groups:normal control group (C group), ANP group (P group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane. Normal control group received isovolumetric injection of 9 g/L physiological saline solution using the same method. The blood samples of the rats in each group were obtained via superior mesenteric vein to measure levels of IL-2, IL-10, sFas and calculate the value of IL-2/IL-10. The levels of IL-2, IL-10 and sFas were determined by ELISA. The severity of intestinal mucosal injury was evaluated by pathologic score. The expression of Fas in intestinal mucosal tissue was determined by immunohistochemistry staining. RESULTS:Levels of serum IL-2 were significantly higher in P group than those of C group (2.79 ± 0.51 vs 3.53 ± 0.62, 2.93 ± 0.89 vs 4.35 ± 1.11, 4.81 ± 1.23 vs 6.94 ± 1.55 and 3.41 ± 0.72 vs 4.80 ± 1.10, respectively, P < 0.01, for all) and its reached peak at 6 h. Levels of serum IL-10 were significantly higher in P group than those of C group at 6 h and 12 h (54.61 ± 15.81 vs 47.34 ± 14.62, 141.15 ± 40.21 vs 156.12 ± 43.10, 89.18 ± 32.52 vs 494.98 ± 11.23 and 77.15 ± 22.60 vs 93.28 ± 25.81, respectively, P < 0.01, for all). The values of IL-2/IL-10 were higher significantly in P group than those of C group at 0.5 h and 2 h (0.05 ± 0.01 vs 0.07 ± 0.02 and 0.02 ± 0.01 vs 0.03 ± 0.01, respectively, P < 0.01, for all), and it were significantly lower than those of C group at 6 h (0.05 ± 0.02 vs 0.01 ± 0.01, P < 0.01) and returned to the control level at 12 h (0.04 ± 0.01 vs 0.05 ± 0.02, P > 0.05). In sFas assay, there was no significant difference between P group and C group (3.16 ± 0.75 vs 3.31 ± 0.80, 4.05 ± 1.08 vs 4.32 ± 1.11, 5.93 ± 1.52 vs 5.41 ± 1.47 and 4.62 ± 1.23 vs 4.44 ± 1.16, respectively, P > 0.05, for all). Comparison of P group and C group, the pathological changes were aggravated significantly in P group. Immunohistochemistry staining show the expression of Fas was absent in normal intestinal tissues, however, it gradually increased after induction of pancreatitis in intestinal tissue, then reached their peaks at 12 h.CONCLUSION:Fas were involved in the pathogenesis of pancreatitis associated intestinal injury. The mechanisms of Fas may be associated to Fas mediated T helper cell apoptosis.
基金Supported by National Key Technology R&D Program of China,No.2006BAI04A15Major Diseases Fund of Sichuan Province Administration of Traditional Chinese Medicine,No.2007B03
文摘AIM:To investigate the effect of Chai-Qin-Cheng-Qi Decoction(CQCQD)on cefotaxime(CTX)concentration in pancreas of rats with acute necrotizing pancreatitis (ANP). METHODS:Sixty healthy male Sprague-Dawley rats were divided randomly into an ANP group(ANP model +CTX,n=20),treatment group(ANP model+CTX +CQCQD,n=20)and control group(normal rats+ CTX,n=20).ANP models were induced by retrograde intraductal injection of 3.5%sodium taurocholate (1 mL/kg),and the control group was injected intraductally with normal saline.All rats were injected introperitoneally with 0.42 g/kg CTX(at 12-h intervals for a continuous 72 h)at 6 h after intraductal injection. Meanwhile,the treatment group received CQCQD (20 mL/kg)intragastrically at 8-h intervals,and the ANP and control group were treated intragastrically with normal saline.At 15 min after the last CTX injection,blood and pancreas samples were collected for the determination of CTX concentration using validated high-performance liquid chromatography. Pathological changes and wet-to-dry-weight(W/D) ratio of pancreatic tissue were examined. RESULTS:Serum CTX concentrations in three groups were not significantly different.Pancreatic CTXconcentration and penetration ratio were lower in ANP group vs control group(4.4±0.6μg/mL vs 18.6± 1.7μg/mL,P=0.000;5%vs 19%,P=0.000),but significantly higher in treatment group vs ANP group (6.4±1.7μg/mL vs 4.4±0.6μg/mL,P=0.020;7% vs 5%,P=0.048).The histological scores and W/D ratio were significantly decreased in treatment group vs ANP and control group. CONCLUSION:CQCQD might have a promotive effect on CTX concentration in pancreatic tissues of rats with ANP.
基金Supported by the grant from the Hungarian Scieutigic Research Found (OTKA No.D34004) the Hungarian Academy of Sciences (B0 5/2003) and ETT SK503
文摘AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS: Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg·b·m, of 50 g/L sodium taurocholate(NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mglkg·b.m.was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction.Serum activities of amylase, IL-6 and TNF-α and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-,Cu-,and Zn-SOD) in pancreatic tissue were measured.RESULTS: Serum TNF-α and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes.CONCLUSION: Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylac ticoctreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.
文摘INTRODUCTIONAcute narcotizing pancreatitis usually takes a severe clinical course and is associated with multiple organ dysfunction .With the further understanding of pathophysiological events of acute pancreatisis and the therapeutic measuses taken by the clinicians ,the patients can pass through the critical carry stages ,and then the septic complication caused by rtanslocated bacteria, mostly gram-negative microbes from the intestines ensues[1].
文摘Acute necrotizing pancreatitis complicated with pancreatic pseudoaneurysm is a rare emergency associated with high mortality that demands immediate treatment to save the patient’s life. We treated a 64-year-old man who presented with a bleeding pseudoaneurysm of the superior mesenteric artery caused by acute pancreatitis, using interventional embolizing therapy. In the present report we show that interventional treatment is an effective therapeutic modality for patients with acute necrotizing pancreatitis complicated with intra-abdominal bleeding.
文摘The expression of micro RNA-19b(mi R-19b) in acute necrotizing pancreatitis(ANP) and its functional role in acinar cell necrosis of SD rats were investigated. Twelve SD rats were divided into two groups randomly, including control group and ANP group. The rat ANP models were established by intraperitoneal injection of L-arginine(2400 mg/kg body weight), and equal volume of 0.9% Na Cl was injected in the control group. Mi RNA chip assay was performed to examine the expression of mi RNAs in the pancreas in two different groups. Besides, to further explore the role of mi R-19 b in ANP in vitro, taurolithocholic acid 3-sulfate disodium salt(TLC-S)(200 μmol/L) was administrated to treat the rat pancreatic acinar cell line, AR42 J, for establishing the ANP cells model. The quantitative real-time PCR(q RT-PCR) was adopted to measure the mi R-19 b expression. Moreover, the mimic mi RNA, mi RNA antisense oligonucleotide(AMO) and control vector were used to transfect AR42 J cells, the expression of mi R-19 b was confirmed by q RT-PCR and the necrotizing rate of AR42 J cells was detected with AO/EB method. The expression of mi R-19 b was significantly higher in ANP group than in control group as displayed by the mi RNA chip assay. Furthermore, after inducing necrosis of AR42 J cells in vitro, the expression of mi R-19 b was significantly increased by 2.51±0.14 times in comparison with the control group. As revealed by q RT-PCR assay, the expression of mi R-19 b was 5.94±0.95 times higher in the mimic mi RNA group than in the control vector group, companied with an obviously increased acinar cell necrotizing rate(50.3%±1.5% vs. 39.6%±2.3%, P<0.05). Moreover, the expression of mi R-19 b in the mi RNA AMO group was 0.38±0.15 times lower than in the control vector group, and the cell necrosis rate was much lower accordingly(23.1%±3.3% vs. 39.6%±2.3%, P<0.05). Besides, there was no significant difference between the control vector cells and the cells without treatment(P>0.05). The expression of mi R-19 b was significantly induced in ANP. In addition, up-regulation of mi R-19 b could promote the necrosis of pancreatic acinar cells and mi R-19 b deficiency could decrease the rate of pancreatic acinar cell necrosis.
基金Supported by a Special Research Grant for interdisciplinary projects between the Institute of Immunology and Physiology and the Institute of Organic Synthesis,the Ural Branch of Russian Academy of Sciences(2009-2012)
文摘AIM:To establish a one-stage model of experimental acute necrotizing pancreatitis(ANP)in rats characterized by the simplicity of performance and a high degree of repeatability.METHODS:ANP modeling in rats was performed based on modification of the ligation model as follows:synthetic material ligature using an atraumatic needle was performed to capture pancreatic gland ducts and marginal duodenum vessels.Ligature tips were exteriorized to the abdominal wall,and the ligature was skinned over to avoid catching intestine loops.Pancreatic macroscopic appearance and histological changes were observed.Blood biochemical and hemostatic indicators were also determined.RESULTS:Laboratory analysis of rats with experimental ANP showed a pattern of disturbances similar to that observed during pancreatic necrosis in humans as soon as the first day.General blood analysis revealed enhanced leukocytosis and alterations in leukogram characteristics,indicating acute inflammation.Serum levels of amylase,aspartate aminotransferase and creatinine significantly increased(P<0.05).Hemostatic indicators showed alterations indicating formation of disseminated intravascular coagulation,and signs of endotoxicosis were observed.These typical pancreatic necrosis patterns of disturbances were validated by the results of histological investigation.CONCLUSION:Histological changes and laboratory indicators confirm the development of a suitable model of ANP.
基金Supported by National Natural Science Foundation of China,No.81802450and Natural Science Foundation of Hunan Province,No.2020JJ4133 and No.2021JJ31135.
文摘BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.
文摘BACKGROUND Early initiation of enteral feeding is recognized to play a crucial role in improving the outcomes of treatment of acute pancreatitis.However,the method of adminis-tration of enteral nutrition remains debatable.We present the experience of treating a patient with moderate-severe acute pancreatitis,at high risk of progressing to a severe or fatal condition,using a novel method of selective feeding with duodenal isolation.CASE SUMMARY A 27-year-old female patient presented to the emergency unit of the hospital with a typical manifestation of acute pancreatitis.Despite a conventional treatment,the patient’s condition deteriorated by day 2 of hospitalization.Using an endoscopic approach,a novel catheter PandiCathffwas placed to the duodenum of the patient,isolating its segment between the duodenal bulb and the ligament of Treitz.In the isolated area created,a negative pressure was applied,followed by introduction of early selective enteral feeding.The patient’s condition subsequently improved in a rapid manner,and no complications often associated with moderate-to-severe acute pancreatitis developed.CONCLUSION Within 48 h of starting treatment with the novel method,it can prevent the development of multiple organ failure and,when combined with minimally invasive drainage methods,help prevent infection.
