Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with live...Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.展开更多
Evidence suggests that exosomes can transfer genetic material between cells. However, their roles in hepatitis B virus (HBV) infection remain unclear. Here, we report that exosomes present in the sera of chronic hep...Evidence suggests that exosomes can transfer genetic material between cells. However, their roles in hepatitis B virus (HBV) infection remain unclear. Here, we report that exosomes present in the sera of chronic hepatitis B (CHB) patients contained both HBV nucleic acids and HBV proteins, and transferred HBV to hepatocytes in an active manner. Notably, HBV nucleic acids were detected in natural killer (NK) cells from both CHB patients and healthy donors after exposure to HBV-positive exosomes. Through real-time fluorescence microscopy and flow cytometry, 1, r-dioctadecyl-3,3,3',3',-tetramethylindodicarbocyanine, 4-chlorobenzenesulfnate salt (DiD)-Iabeled exosomes were observed to interact with NK cells and to be taken up by NK cells, which was enhanced by transforming growth factor-β treatment. Furthermore, HBV-positive exosomes impaired NK-cell functions, including interferon (IFN)-y production, cytolytic activity, NK-cell proliferation and survival, as well as the responsiveness of the cells to poly (I.C) stimulation. HBV infection suppressed the expression of pattern-recognition receptors, especially retinoic acid inducible gene I (RIG-I), on NK cells, resulting in the dampening of the nuclear factor KB (NF-KB) and p38 mitogen-activated protein kinase pathways. Our results highlight a previously unappreciated role of exosomes in HBV transmission and NK-cell dysfunction during CHB infection.展开更多
Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and invol...Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death.In addition,autoimmune and genetic factors are involved in the development of CAN.CAN might be subclinical for several years until the patient develops resting tachycardia,exercise intolerance,postural hypotension,cardiac dysfunction and diabetic cardiomyopathy.During its sub-clinical phase,heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic.Newer imaging techniques(such as scintigraphy)have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system.One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN;however,the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN,and also proposed screening for CAN in patients with diabetes mellitus.A major challenge,however,is the lack of specific treatment to slow the progression or prevent the development of CAN.Lifestyle changes,improved metabolic control might prevent or slow the progression of CAN.Reversal will require combination of these treatments with new targeted therapeutic approaches.The aim of this article is to review the latest evidence regarding the epidemiology,pathogenesis,manifestations,diagnosis and treatment for CAN.展开更多
AIM: To study retrospectively the influence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in patients with early acute pancreatitis (AP) (during the first week after admission) on phys...AIM: To study retrospectively the influence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in patients with early acute pancreatitis (AP) (during the first week after admission) on physiological functions, and the association of the presence of IAH/ACS and outcome. METHODS: Patients (n = 74) with AP recruited in this study were divided into two groups according to intra-abdominal pressure (IAP) determined by indirect measurement using the transvesical route via Foley bladder catheter during the first week after admission. Patients (n = 44) with IAP ≥ 12 mmHg were assigned in IAH group, and the remaining patients (n = 30) with IAP < 12 mmHg in normal IAP group. For analysis of the influence of IAH/ACS on organ function and outcome, the physiological parameters and the occurrence of organ dysfunction during intensive care unit (ICU) stay were recorded, as were the incidences of pancreatic infection and in-hospital mortality. RESULTS: IAH within the first week after admission was found in 44 patients (59.46%). Although the APACHE Ⅱ scores on admission and the Ranson scores within 48 h after hospitalization were elevated in IAH patients in early stage, they did not show the statistically significant differences from patients with normal IAP within a week after admission (16.18 ± 3.90 vs 15.70 ± 4.25, P = 0.616; 3.70 ± 0.93 vs 3.47 ± 0.94, P = 0.285, respectively). ACS in early AP was recorded in 20 patients (27.03%). During any 24-h period ofthe first week after admission, the recorded mean IAP correlated significantly with the Marshall score calculated at the same time interval in IAH group (r = 0.635, P < 0.001). Although ACS patients had obvious amelioration in physiological variables within 24 h after decompression, the incidences of pancreatitic infection, septic shock, multiple organ dysfunction syndrome (MODS) and death in the patients with ACS were significantly higher than that in other patients without ACS (pancreatitic infection: 60.0% vs 7.4%, P < 0.001; septic shoc展开更多
AIM: To examine the effects of anti-high mobility group box 1 (HIGB1) neutralizing antibody in experimental severe acute pancreatitis (SAP). METHODS: SAP was induced by creating closed duodenal loop inC3H/HeN mi...AIM: To examine the effects of anti-high mobility group box 1 (HIGB1) neutralizing antibody in experimental severe acute pancreatitis (SAP). METHODS: SAP was induced by creating closed duodenal loop inC3H/HeN mice. SAP was induced immediately after intrapedtoneal injection of anti-HMGB1 neutralizing antibody (200 pg). Sevedty of pancreatitis, organ injury (liver, kidney and lung), and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS: Anti-HHGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HHGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HHGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION: Blockade of HHGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HHGB1 may act as a key mediator for inflammatory response and organ injury in SAR展开更多
Sepsis-induced myocardial dysfunction is a common complication in septic patients and is associated with increased mortality.In the clinical setting,it was once believed that myocardial dysfunction was not a major pat...Sepsis-induced myocardial dysfunction is a common complication in septic patients and is associated with increased mortality.In the clinical setting,it was once believed that myocardial dysfunction was not a major pathological process in the septic patients,at least in part,due to the unavailability of suitable clinical markers to assess intrinsic myocardial function during sepsis.Although sepsis-induced myocardial dysfunction has been studied in clinical and basic research for more than 30 years,its pathophysiology is not completely understood,and no specific therapies for this disorder exist.The purpose of this review is to summarize our current knowledge of sepsis-induced myocardial dysfunction with a special focus on pathogenesis and clinical characteristics.展开更多
Acute-on-chronic liver failure(ACLF) is increasingly recognized as a complex syndrome that is reversiblein many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existin...Acute-on-chronic liver failure(ACLF) is increasingly recognized as a complex syndrome that is reversiblein many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure(OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept(Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.展开更多
Background Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent ne...Background Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP. Methods One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) 〈35%, n=56) or slow hemodilution (HCT 〉35%, n=-59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined. Results The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P 〈0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4±1.9) days) compared with the slow hemodilution group ((10.2±2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P 〈0.05). Conclusions Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.展开更多
Low frequency (≤ 1 Hz) repetitive transcranial magnetic stimulation (rTMS) can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of ce...Low frequency (≤ 1 Hz) repetitive transcranial magnetic stimulation (rTMS) can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of cerebral infarction, whether it promotes the recovery of motor function remains controversial. Twenty patients with cerebral infarction combined with hemiparalysis were equally and randomly divided into a low frequency rTMS group and a control group. The patients in the low frequency rTMS group were given 1-Hz rTMS to the contralateral primary motor cortex with a stimulus intensity of 90% motor threshold, 30 minutes/day. The patients in the control group were given sham stimulation. After 14 days of treatment, clinical function scores (National Institute of Health Stroke Scale, Barthel Index, and Fugl-Meyer Assessment) improved significantly in the low frequency rTMS group, and the effects were better than that in the control group. We conclude that low frequency (1 Hz) rTMS for 14 days can help improve motor function after cerebral infarction.展开更多
Background: Postoperative cognitive dysfunction (POCD) is a serious complication after surgery, especially in elderly patients. The anesthesia technique is a potentially modifiable risk factor for POCD. This study ass...Background: Postoperative cognitive dysfunction (POCD) is a serious complication after surgery, especially in elderly patients. The anesthesia technique is a potentially modifiable risk factor for POCD. This study assessed the effects of dexmedetomidine, propofol or midazolam sedation on POCD in elderly patients who underwent hip or knee replacement under spinal anesthesia. Methods: The present study was a prospective randomized controlled preliminary trial. From July 2013 and December 2014, a total of 164 patients aged 65 years or older who underwent hip or knee arthroplasty at China-Japan Friendship Hospital and 41 non-surgical controls were included in this study. Patients were randomized in a 1:1:1 ratio to 3 sedative groups. All the patients received combined spinal-epidural anesthesia (CSEA) with midazolam, dexmedetomidine or propofol sedation. The sedative dose was adjusted to achieve light sedation (bispectral index[BIS] score between 70 and 85). All study participants and controls completed a battery of 5 neuropsychological tests before and 7 days after surgery. One year postoperatively, the patients and controls were interviewed over the telephone using the Montreal cognitive assessment 5-minute protocol. Results: In all, 60 of 164 patients (36.6%) were diagnosed with POCD 7 days postoperatively, POCD incidence in propofol group was significantly lower than that in dexmedetomidine and midazolam groups (18.2% vs. 40.0%, 51.9%, χ^2 6.342 and 13.603, P= 0.012 and < 0.001). When the patients were re-tested 1 year postoperatively, the incidence of POCD was not significantly different among the 3 groups (14.0%, 10.6% vs. 14.9%, χ^2 0.016 and 0.382, P= 0.899 and 0.536). Conclusion: Among dexmedetomidine, propofol and midazolam sedation in elderly patients, propofol sedation shows a significant advantage in term of short-term POCD incidence.展开更多
Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features ...Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.展开更多
Blood loss during liver transplantation (OLTx) is a common consequence of pre-existing abnormalities of the hemostatic system,portal hypertension with multiple collateral vessels,portal vein thrombosis,previous abdomi...Blood loss during liver transplantation (OLTx) is a common consequence of pre-existing abnormalities of the hemostatic system,portal hypertension with multiple collateral vessels,portal vein thrombosis,previous abdominal surgery,splenomegaly,and poor "functional" recovery of the new liver.The intrinsic coagulopathic features of end stage cirrhosis along with surgical technical difficulties make transfusion-free liver transplantation a major challenge,and,despite the improvements in understanding of intraoperative coagulation profiles and strategies to control blood loss,the requirements for blood or blood products remains high.The impact of blood transfusion has been shown to be significant and independent of other well-known predictors of posttransplant-outcome.Negative effects on immunomodulation and an increased risk of postoperative complications and mortality have been repeatedly demonstrated.Isovolemic hemodilution,the extensive utilization of thromboelastogram and the use of autotransfusion devices are among the commonly adopted procedures to limit the amount of blood transfusion.The use of intraoperative blood salvage and autologous blood transfusion should still be considered an important method to reduce the need for allogenic blood and the associated complications.In this article we report on the common preoperative and intraoperative factors contributing to blood loss,intraoperative transfusion practices,anesthesiologic and surgical strategies to prevent blood loss,and on intraoperative blood salvaging techniques and autologous blood transfusion.Even though the advances in surgical technique and anesthetic management,as well as a better understanding of the risk factors,have resulted in a steady decrease in intraoperative bleeding,most patients still bleed extensively.Blood transfusion therapy is still a critical feature during OLTx and various studies have shown a large variability in the use of blood products among different centers and even among individual anesthesiologists within the same center.展开更多
基金Supported by(in part)the Southampton National Institute for Health Research Biomedical Research Centre(Byrne CD)grants from the School of Medicine of the Verona University(Targher GT)
文摘Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.
基金This work was supported by grants from the National Basic Research Program of China (No. 2013CB531503), the Natural Science Foundation of China (Nos. 81172789 and 30972692).
文摘Evidence suggests that exosomes can transfer genetic material between cells. However, their roles in hepatitis B virus (HBV) infection remain unclear. Here, we report that exosomes present in the sera of chronic hepatitis B (CHB) patients contained both HBV nucleic acids and HBV proteins, and transferred HBV to hepatocytes in an active manner. Notably, HBV nucleic acids were detected in natural killer (NK) cells from both CHB patients and healthy donors after exposure to HBV-positive exosomes. Through real-time fluorescence microscopy and flow cytometry, 1, r-dioctadecyl-3,3,3',3',-tetramethylindodicarbocyanine, 4-chlorobenzenesulfnate salt (DiD)-Iabeled exosomes were observed to interact with NK cells and to be taken up by NK cells, which was enhanced by transforming growth factor-β treatment. Furthermore, HBV-positive exosomes impaired NK-cell functions, including interferon (IFN)-y production, cytolytic activity, NK-cell proliferation and survival, as well as the responsiveness of the cells to poly (I.C) stimulation. HBV infection suppressed the expression of pattern-recognition receptors, especially retinoic acid inducible gene I (RIG-I), on NK cells, resulting in the dampening of the nuclear factor KB (NF-KB) and p38 mitogen-activated protein kinase pathways. Our results highlight a previously unappreciated role of exosomes in HBV transmission and NK-cell dysfunction during CHB infection.
文摘Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death.In addition,autoimmune and genetic factors are involved in the development of CAN.CAN might be subclinical for several years until the patient develops resting tachycardia,exercise intolerance,postural hypotension,cardiac dysfunction and diabetic cardiomyopathy.During its sub-clinical phase,heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic.Newer imaging techniques(such as scintigraphy)have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system.One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN;however,the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN,and also proposed screening for CAN in patients with diabetes mellitus.A major challenge,however,is the lack of specific treatment to slow the progression or prevent the development of CAN.Lifestyle changes,improved metabolic control might prevent or slow the progression of CAN.Reversal will require combination of these treatments with new targeted therapeutic approaches.The aim of this article is to review the latest evidence regarding the epidemiology,pathogenesis,manifestations,diagnosis and treatment for CAN.
文摘AIM: To study retrospectively the influence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in patients with early acute pancreatitis (AP) (during the first week after admission) on physiological functions, and the association of the presence of IAH/ACS and outcome. METHODS: Patients (n = 74) with AP recruited in this study were divided into two groups according to intra-abdominal pressure (IAP) determined by indirect measurement using the transvesical route via Foley bladder catheter during the first week after admission. Patients (n = 44) with IAP ≥ 12 mmHg were assigned in IAH group, and the remaining patients (n = 30) with IAP < 12 mmHg in normal IAP group. For analysis of the influence of IAH/ACS on organ function and outcome, the physiological parameters and the occurrence of organ dysfunction during intensive care unit (ICU) stay were recorded, as were the incidences of pancreatic infection and in-hospital mortality. RESULTS: IAH within the first week after admission was found in 44 patients (59.46%). Although the APACHE Ⅱ scores on admission and the Ranson scores within 48 h after hospitalization were elevated in IAH patients in early stage, they did not show the statistically significant differences from patients with normal IAP within a week after admission (16.18 ± 3.90 vs 15.70 ± 4.25, P = 0.616; 3.70 ± 0.93 vs 3.47 ± 0.94, P = 0.285, respectively). ACS in early AP was recorded in 20 patients (27.03%). During any 24-h period ofthe first week after admission, the recorded mean IAP correlated significantly with the Marshall score calculated at the same time interval in IAH group (r = 0.635, P < 0.001). Although ACS patients had obvious amelioration in physiological variables within 24 h after decompression, the incidences of pancreatitic infection, septic shock, multiple organ dysfunction syndrome (MODS) and death in the patients with ACS were significantly higher than that in other patients without ACS (pancreatitic infection: 60.0% vs 7.4%, P < 0.001; septic shoc
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 (HIGB1) neutralizing antibody in experimental severe acute pancreatitis (SAP). METHODS: SAP was induced by creating closed duodenal loop inC3H/HeN mice. SAP was induced immediately after intrapedtoneal injection of anti-HMGB1 neutralizing antibody (200 pg). Sevedty of pancreatitis, organ injury (liver, kidney and lung), and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS: Anti-HHGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HHGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HHGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION: Blockade of HHGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HHGB1 may act as a key mediator for inflammatory response and organ injury in SAR
基金supported by grants from the National Natural Science Foundation of China(81372028,81170222)the Guangzhou S cience and Technology Projec ts(201508020005)the Project of the Department of Education of Guangdong Province(No.2013KJCX0019)
文摘Sepsis-induced myocardial dysfunction is a common complication in septic patients and is associated with increased mortality.In the clinical setting,it was once believed that myocardial dysfunction was not a major pathological process in the septic patients,at least in part,due to the unavailability of suitable clinical markers to assess intrinsic myocardial function during sepsis.Although sepsis-induced myocardial dysfunction has been studied in clinical and basic research for more than 30 years,its pathophysiology is not completely understood,and no specific therapies for this disorder exist.The purpose of this review is to summarize our current knowledge of sepsis-induced myocardial dysfunction with a special focus on pathogenesis and clinical characteristics.
文摘Acute-on-chronic liver failure(ACLF) is increasingly recognized as a complex syndrome that is reversiblein many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure(OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept(Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.
文摘Background Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP. Methods One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) 〈35%, n=56) or slow hemodilution (HCT 〉35%, n=-59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined. Results The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P 〈0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4±1.9) days) compared with the slow hemodilution group ((10.2±2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P 〈0.05). Conclusions Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.
基金supported by the National Natural Science Foundation of China,No.30540058,30770714the Natural Science Foundation of Beijing of China,No.7052030+2 种基金the Talents Foundation of Organization Department of the Beijing Municipal Committee in Chinathe Beijing Science Plan Project Fund of China,No.Z0005187040191-1the Research Foundation of Capital Medical Development of China,No.2007-2068
文摘Low frequency (≤ 1 Hz) repetitive transcranial magnetic stimulation (rTMS) can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of cerebral infarction, whether it promotes the recovery of motor function remains controversial. Twenty patients with cerebral infarction combined with hemiparalysis were equally and randomly divided into a low frequency rTMS group and a control group. The patients in the low frequency rTMS group were given 1-Hz rTMS to the contralateral primary motor cortex with a stimulus intensity of 90% motor threshold, 30 minutes/day. The patients in the control group were given sham stimulation. After 14 days of treatment, clinical function scores (National Institute of Health Stroke Scale, Barthel Index, and Fugl-Meyer Assessment) improved significantly in the low frequency rTMS group, and the effects were better than that in the control group. We conclude that low frequency (1 Hz) rTMS for 14 days can help improve motor function after cerebral infarction.
文摘Background: Postoperative cognitive dysfunction (POCD) is a serious complication after surgery, especially in elderly patients. The anesthesia technique is a potentially modifiable risk factor for POCD. This study assessed the effects of dexmedetomidine, propofol or midazolam sedation on POCD in elderly patients who underwent hip or knee replacement under spinal anesthesia. Methods: The present study was a prospective randomized controlled preliminary trial. From July 2013 and December 2014, a total of 164 patients aged 65 years or older who underwent hip or knee arthroplasty at China-Japan Friendship Hospital and 41 non-surgical controls were included in this study. Patients were randomized in a 1:1:1 ratio to 3 sedative groups. All the patients received combined spinal-epidural anesthesia (CSEA) with midazolam, dexmedetomidine or propofol sedation. The sedative dose was adjusted to achieve light sedation (bispectral index[BIS] score between 70 and 85). All study participants and controls completed a battery of 5 neuropsychological tests before and 7 days after surgery. One year postoperatively, the patients and controls were interviewed over the telephone using the Montreal cognitive assessment 5-minute protocol. Results: In all, 60 of 164 patients (36.6%) were diagnosed with POCD 7 days postoperatively, POCD incidence in propofol group was significantly lower than that in dexmedetomidine and midazolam groups (18.2% vs. 40.0%, 51.9%, χ^2 6.342 and 13.603, P= 0.012 and < 0.001). When the patients were re-tested 1 year postoperatively, the incidence of POCD was not significantly different among the 3 groups (14.0%, 10.6% vs. 14.9%, χ^2 0.016 and 0.382, P= 0.899 and 0.536). Conclusion: Among dexmedetomidine, propofol and midazolam sedation in elderly patients, propofol sedation shows a significant advantage in term of short-term POCD incidence.
基金Supported by Department of Science and Technology,Government of India to Iqra Hameed,No.Wos-A LS 509/2012
文摘Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.
文摘Blood loss during liver transplantation (OLTx) is a common consequence of pre-existing abnormalities of the hemostatic system,portal hypertension with multiple collateral vessels,portal vein thrombosis,previous abdominal surgery,splenomegaly,and poor "functional" recovery of the new liver.The intrinsic coagulopathic features of end stage cirrhosis along with surgical technical difficulties make transfusion-free liver transplantation a major challenge,and,despite the improvements in understanding of intraoperative coagulation profiles and strategies to control blood loss,the requirements for blood or blood products remains high.The impact of blood transfusion has been shown to be significant and independent of other well-known predictors of posttransplant-outcome.Negative effects on immunomodulation and an increased risk of postoperative complications and mortality have been repeatedly demonstrated.Isovolemic hemodilution,the extensive utilization of thromboelastogram and the use of autotransfusion devices are among the commonly adopted procedures to limit the amount of blood transfusion.The use of intraoperative blood salvage and autologous blood transfusion should still be considered an important method to reduce the need for allogenic blood and the associated complications.In this article we report on the common preoperative and intraoperative factors contributing to blood loss,intraoperative transfusion practices,anesthesiologic and surgical strategies to prevent blood loss,and on intraoperative blood salvaging techniques and autologous blood transfusion.Even though the advances in surgical technique and anesthetic management,as well as a better understanding of the risk factors,have resulted in a steady decrease in intraoperative bleeding,most patients still bleed extensively.Blood transfusion therapy is still a critical feature during OLTx and various studies have shown a large variability in the use of blood products among different centers and even among individual anesthesiologists within the same center.