Type 2 diabetes mellitus(T2DM)and its complications have significantly increased the burden of mortality and disability globally,making diabetes one of the most dangerous and prevalent chronic diseases.Acute pancreati...Type 2 diabetes mellitus(T2DM)and its complications have significantly increased the burden of mortality and disability globally,making diabetes one of the most dangerous and prevalent chronic diseases.Acute pancreatitis(AP)is one of the most frequent gastrointestinal causes for hospital admission,which is a common exocrine pancreatic inflammatory disease that can cause severe abdominal pain and multiple organ dysfunction.There is an inseparable relationship between AP and diabetes.Diabetes is a high risk factor of AP,and patients with AP can develop pancreatogenic diabetes.In T2DM patients,the incidence rate of AP is significantly higher than that of the general population,and the clinical symptoms are more severe,with the majority of cases being moderate to severe AP.This review briefly introduces the pathogenesis and clinical features of AP in T2DM patients,focusing on the magnetic resonance imaging(MRI)manifestations of AP in T2DM patients.Our aim is to evaluate the severity of AP in patients with T2DM by MRI,so as to help clinicians assess the patient's condition and prognosis.展开更多
AIM: To examine the effects of anti-high mobility group box 1 (HMGB1) neutralizing antibody in experimental se-vere acute pancreatitis (SAP).METHODS: SAP was induced by creating closed duode-nal loop in C3H/HeN mice. ...AIM: To examine the effects of anti-high mobility group box 1 (HMGB1) neutralizing antibody in experimental se-vere acute pancreatitis (SAP).METHODS: SAP was induced by creating closed duode-nal loop in C3H/HeN mice. SAP was induced immediately after intraperitoneal injection of anti-HMGB1 neutralizing antibody (200 μg). Severity of pancreatitis, organ injury (liver, kidney and lung), and bacterial translocation to pancreas was examined 12 h after induction of SAP.RESULTS: Anti-HMGB1 neutralizing antibody significant-ly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAP. Anti-HMGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and cre-atinine in SAP. However, anti-HMGB1 antibody worsened the bacterial translocation to pancreas.CONCLUSION: Blockade of HMGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HMGB1 may act as a key mediator for inflammatory response and organ injury in SAP.展开更多
AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP...AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP). METHODS: A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the in? uence of EP on survival times of SAP rats. RESULTS: Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 ±0.42 vs 9.76 ± 0.45, P < 0.01), pulmonary histological scores (7.1 ± 0.7 vs 8.4 ± 1.1, P < 0.01), serum AST (667 ± 103 vs 1 368 ± 271, P < 0.01), ALT (446 ± 91 vs 653 ± 98, P < 0.01) and Cr (1.2 ± 0.3 vs 1.8 ± 0.3, P < 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment signifi cantly prolonged median survival time to 72 h (P < 0.01). CONCLUSION: Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGB1levels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients.展开更多
BACKGROUND The incidence of hypertriglyceridemic acute pancreatitis(HTG-AP)has increased yearly,but updated population-based estimates on the incidence of HTG-AP are lacking.Reducing serum triglyceride(TG)levels quick...BACKGROUND The incidence of hypertriglyceridemic acute pancreatitis(HTG-AP)has increased yearly,but updated population-based estimates on the incidence of HTG-AP are lacking.Reducing serum triglyceride(TG)levels quickly is crucial in the early treatment of HTG-AP.Decreased serum TG levels are treated by non-invasive methods,which include anti-lipidemic agents,heparin,low-molecular weight heparin,and insulin,and invasive methods,such as blood purification including hemoperfusion(HP),plasmapheresis,and continuous renal replacement therapy.However,authoritative guidelines have not been established.Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP.AIM To evaluate the effect between patients treated with intravenous insulin(INS)and HP to guide clinical treatment.METHODS We retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021.The inpatient medical and radiologic records were reviewed to determine clinical features,severity,complications,mortality,recurrence rate,and treatment.Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP.Propensity score matching was used to compare the clinical outcomes of INS and HP.RESULTS A total of 371 patients met the HTG-AP criteria.The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years(8.4%in April 2012-March 2013 and 22.3%in April 2020-March 2021).The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years.The amylase level was elevated in 80.1%of patients but was only three times the normal value in 46.9%of patients.The frequency of severe acute pancreatitis(26.9%),organ failure(31.5%),rate of recurrence(32.9%),and mortality(3.0%)of HTG-AP was high.Improved Marshall score,modified computed tomography severity index score,baseline TG,baseline amylase,C-reactive protein(CRP),albumin,aspartate aminotransferase,low-density lipoprotein cholesterol,urea nitrogen,creatinine,calcium,hemoglobin,free triiodothyronine,admission to intensive care unit,and mortality were significantly different between patients with different grades of severity(P<0.050).Multivariate logistic regression analysis confirmed that high CRP[P=0.005,odds ratio(OR)=1.011,95%CI:1.003-1.019],low calcium(P=0.003,OR=0.016,95%CI:0.001-0.239),and low albumin(P=0.023,OR=0.821,95%CI:0.693-0.973)were risk factors of severe HTG-AP.After propensity score matching adjusted by sex,age,severity of HTG-AP,and baseline TG,the serum TG significantly decreased in patients treated with INS(P<0.000)and HP(P<0.000)within 48 h.However,the clearance rate of TG(57.24±33.70%vs 56.38±33.61%,P=0.927)and length of stay(13.04±7.92 d vs 12.35±6.40 d,P=0.730)did not differ between the two groups.CONCLUSION The incidence of HTG-AP exhibited a significant increase,remarkable severity,and recurrent trend.Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.展开更多
BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage(APD)attenuates intestinal mucosal injury in rats with severe acute pancreatitis(SAP),and improves administration of enteral nutrition in p...BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage(APD)attenuates intestinal mucosal injury in rats with severe acute pancreatitis(SAP),and improves administration of enteral nutrition in patients with acute pancreatitis(AP).However,the underlying mechanisms of the beneficial effects of APD remain poorly understood.AIM To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats,and its potential mechanisms.METHODS SAP was induced in male adult Sprague-Dawley rats by 5%sodium taurocholate.Mild AP was induced by intraperitoneal injections of cerulein(20μg/kg body weight,six consecutive injections).Following SAP induction,a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD.Morphological changes,serum inflammatory mediators,serum and ascites high mobility group box protein 1(HMGB1),intestinal barrier function indices,apoptosis and associated proteins,and toll-like receptor 4(TLR4)signaling molecules in intestinal tissue were assessed.RESULTS APD significantly alleviated intestinal mucosal injury induced by SAP,as demonstrated by decreased pathological scores,serum levels of D-lactate,diamine oxidase and endotoxin.APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells,and normalized the expression of apoptosis-associated proteins in intestinal tissues.APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1,thus exerting protective effects against SAP-associated intestinal injury.CONCLUSION APD improved intestinal barrier function,intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats.The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.展开更多
BACKGROUND Abdominal paracentesis drainage(APD)is a safe and effective strategy for severe acute pancreatitis(SAP)patients.However,the effects of APD treatment on SAPassociated cardiac injury remain unknown.AIM To inv...BACKGROUND Abdominal paracentesis drainage(APD)is a safe and effective strategy for severe acute pancreatitis(SAP)patients.However,the effects of APD treatment on SAPassociated cardiac injury remain unknown.AIM To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms.METHODS SAP was induced by 5%sodium 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 SAP induction.Morphological staining,serum amylase and inflammatory mediators,serum and ascites high mobility group box(HMGB)1,cardiac-related enzymes indexes and cardiac function,oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats.Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined.RESULTS APD treatment improved cardiac morphological changes,inhibited cardiac dysfunction,decreased cardiac enzymes and reduced cardiomyocyte apoptosis,proapoptotic Bax and cleaved caspase-3 protein levels.APD significantly decreased serum levels of HMGB1,inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury.Furthermore,the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis.CONCLUSION APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress,which may be a novel mechanism behind the effectiveness of APD on SAP.展开更多
文摘Type 2 diabetes mellitus(T2DM)and its complications have significantly increased the burden of mortality and disability globally,making diabetes one of the most dangerous and prevalent chronic diseases.Acute pancreatitis(AP)is one of the most frequent gastrointestinal causes for hospital admission,which is a common exocrine pancreatic inflammatory disease that can cause severe abdominal pain and multiple organ dysfunction.There is an inseparable relationship between AP and diabetes.Diabetes is a high risk factor of AP,and patients with AP can develop pancreatogenic diabetes.In T2DM patients,the incidence rate of AP is significantly higher than that of the general population,and the clinical symptoms are more severe,with the majority of cases being moderate to severe AP.This review briefly introduces the pathogenesis and clinical features of AP in T2DM patients,focusing on the magnetic resonance imaging(MRI)manifestations of AP in T2DM patients.Our aim is to evaluate the severity of AP in patients with T2DM by MRI,so as to help clinicians assess the patient's condition and prognosis.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and from the Ministry of Health, Labor and Welfare of Japan
文摘AIM: To examine the effects of anti-high mobility group box 1 (HMGB1) neutralizing antibody in experimental se-vere acute pancreatitis (SAP).METHODS: SAP was induced by creating closed duode-nal loop in C3H/HeN mice. SAP was induced immediately after intraperitoneal injection of anti-HMGB1 neutralizing antibody (200 μg). Severity of pancreatitis, organ injury (liver, kidney and lung), and bacterial translocation to pancreas was examined 12 h after induction of SAP.RESULTS: Anti-HMGB1 neutralizing antibody significant-ly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAP. Anti-HMGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and cre-atinine in SAP. However, anti-HMGB1 antibody worsened the bacterial translocation to pancreas.CONCLUSION: Blockade of HMGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HMGB1 may act as a key mediator for inflammatory response and organ injury in SAP.
基金The National Natural Science Foundation of China, No. 30600593
文摘AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP). METHODS: A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the in? uence of EP on survival times of SAP rats. RESULTS: Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 ±0.42 vs 9.76 ± 0.45, P < 0.01), pulmonary histological scores (7.1 ± 0.7 vs 8.4 ± 1.1, P < 0.01), serum AST (667 ± 103 vs 1 368 ± 271, P < 0.01), ALT (446 ± 91 vs 653 ± 98, P < 0.01) and Cr (1.2 ± 0.3 vs 1.8 ± 0.3, P < 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment signifi cantly prolonged median survival time to 72 h (P < 0.01). CONCLUSION: Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGB1levels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients.
文摘BACKGROUND The incidence of hypertriglyceridemic acute pancreatitis(HTG-AP)has increased yearly,but updated population-based estimates on the incidence of HTG-AP are lacking.Reducing serum triglyceride(TG)levels quickly is crucial in the early treatment of HTG-AP.Decreased serum TG levels are treated by non-invasive methods,which include anti-lipidemic agents,heparin,low-molecular weight heparin,and insulin,and invasive methods,such as blood purification including hemoperfusion(HP),plasmapheresis,and continuous renal replacement therapy.However,authoritative guidelines have not been established.Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP.AIM To evaluate the effect between patients treated with intravenous insulin(INS)and HP to guide clinical treatment.METHODS We retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021.The inpatient medical and radiologic records were reviewed to determine clinical features,severity,complications,mortality,recurrence rate,and treatment.Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP.Propensity score matching was used to compare the clinical outcomes of INS and HP.RESULTS A total of 371 patients met the HTG-AP criteria.The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years(8.4%in April 2012-March 2013 and 22.3%in April 2020-March 2021).The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years.The amylase level was elevated in 80.1%of patients but was only three times the normal value in 46.9%of patients.The frequency of severe acute pancreatitis(26.9%),organ failure(31.5%),rate of recurrence(32.9%),and mortality(3.0%)of HTG-AP was high.Improved Marshall score,modified computed tomography severity index score,baseline TG,baseline amylase,C-reactive protein(CRP),albumin,aspartate aminotransferase,low-density lipoprotein cholesterol,urea nitrogen,creatinine,calcium,hemoglobin,free triiodothyronine,admission to intensive care unit,and mortality were significantly different between patients with different grades of severity(P<0.050).Multivariate logistic regression analysis confirmed that high CRP[P=0.005,odds ratio(OR)=1.011,95%CI:1.003-1.019],low calcium(P=0.003,OR=0.016,95%CI:0.001-0.239),and low albumin(P=0.023,OR=0.821,95%CI:0.693-0.973)were risk factors of severe HTG-AP.After propensity score matching adjusted by sex,age,severity of HTG-AP,and baseline TG,the serum TG significantly decreased in patients treated with INS(P<0.000)and HP(P<0.000)within 48 h.However,the clearance rate of TG(57.24±33.70%vs 56.38±33.61%,P=0.927)and length of stay(13.04±7.92 d vs 12.35±6.40 d,P=0.730)did not differ between the two groups.CONCLUSION The incidence of HTG-AP exhibited a significant increase,remarkable severity,and recurrent trend.Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.
基金Supported by The National Natural Science Foundation of China,No.81772001the National Clinical Key Subject of China,No.41732113
文摘BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage(APD)attenuates intestinal mucosal injury in rats with severe acute pancreatitis(SAP),and improves administration of enteral nutrition in patients with acute pancreatitis(AP).However,the underlying mechanisms of the beneficial effects of APD remain poorly understood.AIM To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats,and its potential mechanisms.METHODS SAP was induced in male adult Sprague-Dawley rats by 5%sodium taurocholate.Mild AP was induced by intraperitoneal injections of cerulein(20μg/kg body weight,six consecutive injections).Following SAP induction,a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD.Morphological changes,serum inflammatory mediators,serum and ascites high mobility group box protein 1(HMGB1),intestinal barrier function indices,apoptosis and associated proteins,and toll-like receptor 4(TLR4)signaling molecules in intestinal tissue were assessed.RESULTS APD significantly alleviated intestinal mucosal injury induced by SAP,as demonstrated by decreased pathological scores,serum levels of D-lactate,diamine oxidase and endotoxin.APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells,and normalized the expression of apoptosis-associated proteins in intestinal tissues.APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1,thus exerting protective effects against SAP-associated intestinal injury.CONCLUSION APD improved intestinal barrier function,intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats.The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.
基金Supported by National Natural Science Foundation of China,No.81772001National Clinical Key Subject of China,No.41792113Technology Plan Program of Sichuan Provence,No.2015SZ0229,No.2016HH0067,No.2018JY0041and No.2019YJ0277
文摘BACKGROUND Abdominal paracentesis drainage(APD)is a safe and effective strategy for severe acute pancreatitis(SAP)patients.However,the effects of APD treatment on SAPassociated cardiac injury remain unknown.AIM To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms.METHODS SAP was induced by 5%sodium 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 SAP induction.Morphological staining,serum amylase and inflammatory mediators,serum and ascites high mobility group box(HMGB)1,cardiac-related enzymes indexes and cardiac function,oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats.Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined.RESULTS APD treatment improved cardiac morphological changes,inhibited cardiac dysfunction,decreased cardiac enzymes and reduced cardiomyocyte apoptosis,proapoptotic Bax and cleaved caspase-3 protein levels.APD significantly decreased serum levels of HMGB1,inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury.Furthermore,the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis.CONCLUSION APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress,which may be a novel mechanism behind the effectiveness of APD on SAP.