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 ...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 展开更多
Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologica...Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (> 50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis- Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%.展开更多
The Third Universal Definition of Myocardial Infarction(MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin(cT n) with at least one cT n measurement g...The Third Universal Definition of Myocardial Infarction(MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin(cT n) with at least one cT n measurement greater than the 99 th percentile of the upper normal reference limit during:(1) symptoms of myocardialischemia;(2) new significant electrocardiogram(ECG) ST-segment/T-wave changes or left bundle branch block;(3) the development of pathological ECG Q waves;(4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or(5) identification of intracoronary thrombus by angiography or autopsy.Myocardial infarction,when diagnosed,is now classified into five types.Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI.However,high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis.The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated,especially if the initial ECG is not diagnostic of MI.There have been significant advances in adjunctive pharmacotherapy,procedural techniques and stent technology in the treatment of patients with MIs.The routine use of antiplatelet agents such as clopidogrel,prasugrel or ticagrelor,in addition to aspirin,reduces patient morbidity and mortality.Percutaneous coronary intervention(PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI.Drug eluting coronary stents are safe and beneficial with primary coronary intervention.Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein Ⅱb/Ⅲa receptor antagonists and is associated with a significant reduction in bleeding.The intra-coronary use of a glycoprotein Ⅱb/Ⅲa antagonist can reduce infarct size.Pre- and post-conditioning techniques can provide additional cardioprotection.However,the incidence and mortality due to MI continues to be high despite all these recent advances.The ini展开更多
Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of se...Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis （SAP）. An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as e^ective as multifactorial scoring systems （MFSS） at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen （BUN）, creatinine, matrix metalloproteinase-9 （MMP-9） and serum amyloid A （SAA） have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis （PN）, infected PN （IPN） and mortality.展开更多
Osteonecrosis is a phenomenon involving disruption to the vascular supply to the femoral head, resulting in articular surface collapse and eventual osteoarthritis. Although alcoholism, steroid use, and hip trauma rema...Osteonecrosis is a phenomenon involving disruption to the vascular supply to the femoral head, resulting in articular surface collapse and eventual osteoarthritis. Although alcoholism, steroid use, and hip trauma remain the most common causes, several other etiologies for osteonecrosis have been identified. Basic science research utilizing animal models and stem cell applications continue to further elucidate the pathophysiology of osteonecrosis and promise novel treatment options in the future. Clinical studies evaluating modern joint-sparing procedures have demonstrated significant improvements in outcomes, but hip arthroplasty is still the most common procedure performed in these affected younger adults. Further advances in joint-preserving procedures are required and will be widely studied in the coming decade.展开更多
Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether acti- vation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the po...Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether acti- vation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the potential role and possible signaling pathway of autophagy in neuronal survival after cerebral ischemia and proposes that autophagy has dual effects.展开更多
Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) play...Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.展开更多
Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through t...Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyI-N- methylglycine or pharmacological properties. cholylsarcosine, interest owing have also aroused to their protective展开更多
OBJECTIVE: To evaluate the influence of necrotic tissue on progressive injury in deep partial thickness burn wounds. METHODS: Tissue specimens were cultured both for estimation of IL-8, EGF, bFGF, PDGF-AB and histopat...OBJECTIVE: To evaluate the influence of necrotic tissue on progressive injury in deep partial thickness burn wounds. METHODS: Tissue specimens were cultured both for estimation of IL-8, EGF, bFGF, PDGF-AB and histopathological examination, from the pre-operation, post-operation, and non-operation wounds from seven patients with deep partial thickness burn. RESULTS: In seven specimens from the non-operation group, IL-8 release increased compared with those in the post-operation group (P展开更多
Background Many cytokines have been found to increase the insulin resistance during pregnancy complicated by glucose metabolism disorder. This study aimed to investigate which comes first, the changes of some cytokine...Background Many cytokines have been found to increase the insulin resistance during pregnancy complicated by glucose metabolism disorder. This study aimed to investigate which comes first, the changes of some cytokines or the abnormal glucose metabolism. Methods This nested case-control study was undertaken from January 2004 to March 2005. Twenty-two women with gestational diabetes mellitus （GDM）, 10 with gestational impaired glucose tolerance （GIGT）, and 20 healthy pregnant women were chosen from the women who had visited the antenatal clinics and had blood samples prospectively taken and kept during their visit. The levels of tumor necrosis factor-α （TNF-α）, leptin and adiponectin were determined. One-way ANOVA analysis and bivariate correlation analysis were used to assess the laboratory results and their relationship with body mass index （BMI）. Results Women with GDM have the highest values of TNF-α and leptin and the lowest value of adiponectin compared with those with GIGT and the healthy controls （P 〈0.01） at 14-20 weeks of gestation. This was also found when these women progressed to 24-32 weeks. The significantly increased levels of TNF-α and leptin and the decreased level of adiponectin were found at the different periods of gestation within the same group. Positive correlation was shown between the levels of TNF-α and leptin at the two periods of gestation with the BMI at 14-20 weeks, while adiponectin was negatively correlated （P 〈0.05）. Conclusions The concentrations of TNF-α, leptin and adiponectin may change before the appearance of the abnormal glucose level during pregnancy. Further studies are required to verify the mechanism of this alteration and whether the three cytokines can be predictors for GDM at an early staqe of preqnancy.展开更多
Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Methods The recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head. The...Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Methods The recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head. The expression of vascular endothelial growth factor (VEGF) was examined by RNA dot hybridization and immunohistochemical techniques. Repair of the femoral head was observed by histological and histomorphometric analysis.Results The expression of VEGF was detected in the femoral head transfected with the VEGF gene. The femoral head transfected with the VEGF gene showed a significant increase in angiogenesis 2 and 4 weeks after gene transfection and a significant increase in bone formation 6 and 8 weeks after gene transfection on histomorphometric analysis ( P <0.01).Conclusions Transfection of the VEGF gene enhances bone tissue angiogenesis. Repair of osteonecrosis could be accelerated accordingly,thus providing a potential method for therapy of osteonecrosis.展开更多
Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of N...Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.展开更多
Background Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to est...Background Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin （STZ）-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor （TNF）-α, interleukin-1β （IL-1β） and interleukin-6 （IL-6）. Methods Twenty-two male Chinese Guizhou minipigs （age, 4 to 6 months; weight, 20 kg to 30 kg） were divided into STZ-induced diabetic group （n=-12） and control group （n=-10）. STZ （125 mg/kg） was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test （OGTT） was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparegine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet 13 cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-β and IL-6 mFINA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction （FIT-PCR）. Results Significant elevation in serum glucose levels was observed one month and six months after STZ induction （P〈0.001） and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β ceils almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Westem blot demonstrated dramatica展开更多
AIM:To report the results of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in cirrhotic patients and to describe the treatment related complications (mainly the rapid intrahepatic neoplastic progress...AIM:To report the results of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in cirrhotic patients and to describe the treatment related complications (mainly the rapid intrahepatic neoplastic progression). METHODS:Eighty-seven consecutive cirrhotic patients with 104 HCC (mean diameter 3.9 cm,1.3 SD) were submitted to RFA between January 1998 and June 2003.In all cases RFA was performed with percutaneous approach under ultrasound guidance using expandable electrode needles. Treatment efficacy (necrosis and recurrence) was estimated with dual phase computed tomography (CT) and alpha- fetoprotein (AFP)level. RESULTS:Complete necrosis rate after single or multiple treatment was 100%,87.7% and 57.1% in HCC smaller than 3 cm,between 3 and 5 cm and larger than 5 cm respectively (P=0.02).Seventeen lesions of 88(19.3%) developed local recurrence after complete necrosis during a mean follow up of 19.2 mo.There were no treatment-related deaths in 130 procedures and major complications occurred in 8 patients (6.1%).In 4 patients,although complete local necrosis was achieved,we observed rapid intrahepatic neoplastic progression after treatment.Risk factors for rapid neoplastic progression were high preoperative AFP values and location of the tumor near segmental portal branches. CONCLUSION:RFA is an effective treatment for hepatocellular carcinoma smaller than 5 cm with complete necrosis in more than 80% of lesions.Patients with elevated AFP levels and tumors located near the main portal branch are at risk for rapid neoplastic progression after RFA.Further studies are necessary to evaluate the incidence and pathogenesis of this underestimated complication.展开更多
Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health p...Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.展开更多
BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and postt...BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood. METHODS: We collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: All Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (P<0.05). Except for Enterococcus spp., other bacteria showed a tendency to restore to normal level along with the time after liver transplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic patients.CONCLUSIONS: Our study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency for these gut bacteria to restore to normal levels展开更多
文摘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
文摘Severe acute pancreatitis (SAP) develops in about 25% of patients with acute pancreatitis (AP). Severity of AP is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis pathomorphologically. Risk factors determining independently the outcome of SAP are early multi-organ failure, infection of necrosis and extended necrosis (> 50%). Up to one third of patients with necrotizing pancreatitis develop in the late course infection of necroses. Morbidity of SAP is biphasic, in the first week strongly related to early and persistence of organ or multi-organ dysfunction. Clinical sepsis caused by infected necrosis leading to multi-organ failure syndrome (MOFS) occurs in the later course after the first week. To predict sepsis, MOFS or deaths in the first 48-72 h, the highest predictive accuracy has been objectified for procalcitonin and IL-8; the Sepsis- Related Organ Failure Assessment (SOFA)-score predicts the outcome in the first 48 h, and provides a daily assessment of treatment response with a high positive predictive value. Contrast-enhanced CT provides the highest diagnostic accuracy for necrotizing pancreatitis when performed after the first week of disease. Patients who suffer early organ dysfunctions or at risk of developing a severe disease require early intensive care treatment. Early vigorous intravenous fluid replacement is of foremost importance. The goal is to decrease the hematocrit or restore normal cardiocirculatory functions. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and systemic infection. Patients suffering infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. Hospital mortality of SAP after interventional or surgical debridement has decreased in high volume centers to below 20%.
基金Supported by Research facilities at the James A Haley VA Hospitalin part+3 种基金Grants from the Florida King Biomedical Research Programthe Muscular Dystrophy Associationthe Robert O Law Foundationthe Cornelius Foundation
文摘The Third Universal Definition of Myocardial Infarction(MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin(cT n) with at least one cT n measurement greater than the 99 th percentile of the upper normal reference limit during:(1) symptoms of myocardialischemia;(2) new significant electrocardiogram(ECG) ST-segment/T-wave changes or left bundle branch block;(3) the development of pathological ECG Q waves;(4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or(5) identification of intracoronary thrombus by angiography or autopsy.Myocardial infarction,when diagnosed,is now classified into five types.Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI.However,high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis.The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated,especially if the initial ECG is not diagnostic of MI.There have been significant advances in adjunctive pharmacotherapy,procedural techniques and stent technology in the treatment of patients with MIs.The routine use of antiplatelet agents such as clopidogrel,prasugrel or ticagrelor,in addition to aspirin,reduces patient morbidity and mortality.Percutaneous coronary intervention(PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI.Drug eluting coronary stents are safe and beneficial with primary coronary intervention.Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein Ⅱb/Ⅲa receptor antagonists and is associated with a significant reduction in bleeding.The intra-coronary use of a glycoprotein Ⅱb/Ⅲa antagonist can reduce infarct size.Pre- and post-conditioning techniques can provide additional cardioprotection.However,the incidence and mortality due to MI continues to be high despite all these recent advances.The ini
文摘Approximately 20% of patients with acute pancreatitis develop a severe disease associated with complications and high risk of mortality. The purpose of this study is to review pathogenesis and prognostic factors of severe acute pancreatitis （SAP）. An extensive medline search was undertaken with focusing on pathogenesis, complications and prognostic evaluation of SAP. Cytokines and other inflammatory markers play a major role in the pathogenesis and course of SAP and can be used as prognostic markers in its early phase. Other markers such as simple prognostic scores have been found to be as e^ective as multifactorial scoring systems （MFSS） at 48 h with the advantage of simplicity, efficacy, low cost, accuracy and early prediction of SAP. Recently, several laboratory markers including hematocrit, blood urea nitrogen （BUN）, creatinine, matrix metalloproteinase-9 （MMP-9） and serum amyloid A （SAA） have been used as early predictors of severity within the first 24 h. The last few years have witnessed a tremendous progress in understanding the pathogenesis and predicting the outcome of SAP. In this review we classified the prognostic markers into predictors of severity, pancreatic necrosis （PN）, infected PN （IPN） and mortality.
文摘Osteonecrosis is a phenomenon involving disruption to the vascular supply to the femoral head, resulting in articular surface collapse and eventual osteoarthritis. Although alcoholism, steroid use, and hip trauma remain the most common causes, several other etiologies for osteonecrosis have been identified. Basic science research utilizing animal models and stem cell applications continue to further elucidate the pathophysiology of osteonecrosis and promise novel treatment options in the future. Clinical studies evaluating modern joint-sparing procedures have demonstrated significant improvements in outcomes, but hip arthroplasty is still the most common procedure performed in these affected younger adults. Further advances in joint-preserving procedures are required and will be widely studied in the coming decade.
基金supported by grants from the project of National Natural Science Foundation of China,No.31171014 and 31371065the project of Science and Technology Commission of Board of Health of Shanghai,China,No.20134125the Key Specialty(disease) Declaration of Pudong New Area’s Health System
文摘Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether acti- vation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the potential role and possible signaling pathway of autophagy in neuronal survival after cerebral ischemia and proposes that autophagy has dual effects.
基金Supported by NIAAA Grants No. AA017729Supported by NIAAA Grants No. AA011576
文摘Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.
基金Supported by Instituto de Salud CarlosTM,FIS, Spain (GrantsPI070517 and PI080151)Fundacion Investigacion Medica Mutua Madrilea, Spain (Conv-TM,, 2006)+3 种基金Junta de Castillay Leon, Spain (Grants GR75-2008, SA033A08, SA03508 and SA03608)Ministerio de Ciencia y Tecnologia, Plan Nacional de Investigacion Cientifi ca, Desarrollo e Innovacion Tecnologica, Spain (Grant BFU2006-12577)The group is member of the Network for Cooperative Research on Membrane Transport Proteins (REIT), co-funded by the Ministerio de Educacion y Ciencia, Spain, and the European Regional Development Fund (ERDF) (Grant BFU2007-30688-E/BFI)belongs to the CIBERehd (Centro de Investigacion Biomedica en Red para el Estudio de Enfermedades Hepaticas y Digestivas), Instituto de Salud CarlosTM
文摘Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyI-N- methylglycine or pharmacological properties. cholylsarcosine, interest owing have also aroused to their protective
基金supported by the Major State Basic Research Development Program of China(No．Gl999054205)．
文摘OBJECTIVE: To evaluate the influence of necrotic tissue on progressive injury in deep partial thickness burn wounds. METHODS: Tissue specimens were cultured both for estimation of IL-8, EGF, bFGF, PDGF-AB and histopathological examination, from the pre-operation, post-operation, and non-operation wounds from seven patients with deep partial thickness burn. RESULTS: In seven specimens from the non-operation group, IL-8 release increased compared with those in the post-operation group (P
文摘Background Many cytokines have been found to increase the insulin resistance during pregnancy complicated by glucose metabolism disorder. This study aimed to investigate which comes first, the changes of some cytokines or the abnormal glucose metabolism. Methods This nested case-control study was undertaken from January 2004 to March 2005. Twenty-two women with gestational diabetes mellitus （GDM）, 10 with gestational impaired glucose tolerance （GIGT）, and 20 healthy pregnant women were chosen from the women who had visited the antenatal clinics and had blood samples prospectively taken and kept during their visit. The levels of tumor necrosis factor-α （TNF-α）, leptin and adiponectin were determined. One-way ANOVA analysis and bivariate correlation analysis were used to assess the laboratory results and their relationship with body mass index （BMI）. Results Women with GDM have the highest values of TNF-α and leptin and the lowest value of adiponectin compared with those with GIGT and the healthy controls （P 〈0.01） at 14-20 weeks of gestation. This was also found when these women progressed to 24-32 weeks. The significantly increased levels of TNF-α and leptin and the decreased level of adiponectin were found at the different periods of gestation within the same group. Positive correlation was shown between the levels of TNF-α and leptin at the two periods of gestation with the BMI at 14-20 weeks, while adiponectin was negatively correlated （P 〈0.05）. Conclusions The concentrations of TNF-α, leptin and adiponectin may change before the appearance of the abnormal glucose level during pregnancy. Further studies are required to verify the mechanism of this alteration and whether the three cytokines can be predictors for GDM at an early staqe of preqnancy.
基金ThisstudywassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 3 0 170 945 )
文摘Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Methods The recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head. The expression of vascular endothelial growth factor (VEGF) was examined by RNA dot hybridization and immunohistochemical techniques. Repair of the femoral head was observed by histological and histomorphometric analysis.Results The expression of VEGF was detected in the femoral head transfected with the VEGF gene. The femoral head transfected with the VEGF gene showed a significant increase in angiogenesis 2 and 4 weeks after gene transfection and a significant increase in bone formation 6 and 8 weeks after gene transfection on histomorphometric analysis ( P <0.01).Conclusions Transfection of the VEGF gene enhances bone tissue angiogenesis. Repair of osteonecrosis could be accelerated accordingly,thus providing a potential method for therapy of osteonecrosis.
文摘Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.
基金The study was supported by the grant from the Shanghai Natural Science Foundation(No.028610)
文摘Background Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin （STZ）-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor （TNF）-α, interleukin-1β （IL-1β） and interleukin-6 （IL-6）. Methods Twenty-two male Chinese Guizhou minipigs （age, 4 to 6 months; weight, 20 kg to 30 kg） were divided into STZ-induced diabetic group （n=-12） and control group （n=-10）. STZ （125 mg/kg） was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test （OGTT） was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparegine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet 13 cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-β and IL-6 mFINA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction （FIT-PCR）. Results Significant elevation in serum glucose levels was observed one month and six months after STZ induction （P〈0.001） and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β ceils almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Westem blot demonstrated dramatica
文摘AIM:To report the results of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in cirrhotic patients and to describe the treatment related complications (mainly the rapid intrahepatic neoplastic progression). METHODS:Eighty-seven consecutive cirrhotic patients with 104 HCC (mean diameter 3.9 cm,1.3 SD) were submitted to RFA between January 1998 and June 2003.In all cases RFA was performed with percutaneous approach under ultrasound guidance using expandable electrode needles. Treatment efficacy (necrosis and recurrence) was estimated with dual phase computed tomography (CT) and alpha- fetoprotein (AFP)level. RESULTS:Complete necrosis rate after single or multiple treatment was 100%,87.7% and 57.1% in HCC smaller than 3 cm,between 3 and 5 cm and larger than 5 cm respectively (P=0.02).Seventeen lesions of 88(19.3%) developed local recurrence after complete necrosis during a mean follow up of 19.2 mo.There were no treatment-related deaths in 130 procedures and major complications occurred in 8 patients (6.1%).In 4 patients,although complete local necrosis was achieved,we observed rapid intrahepatic neoplastic progression after treatment.Risk factors for rapid neoplastic progression were high preoperative AFP values and location of the tumor near segmental portal branches. CONCLUSION:RFA is an effective treatment for hepatocellular carcinoma smaller than 5 cm with complete necrosis in more than 80% of lesions.Patients with elevated AFP levels and tumors located near the main portal branch are at risk for rapid neoplastic progression after RFA.Further studies are necessary to evaluate the incidence and pathogenesis of this underestimated complication.
文摘Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.
基金supported by the grants from the National Basic Research Program of China (973 program) (2007CB513003)Zhejiang Provincial Science and Technology Bureau Project(2006C23017)
文摘BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood. METHODS: We collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: All Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (P<0.05). Except for Enterococcus spp., other bacteria showed a tendency to restore to normal level along with the time after liver transplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic patients.CONCLUSIONS: Our study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency for these gut bacteria to restore to normal levels
