19 颅内出血史
根据最初的 FDA 标签和2013年AHA/ASA指南,颅内出血史是静脉阿替普酶治疗缺血性卒中的一项额外禁忌证或排除标准。最近修订后的标签仅将近期 ICH 列为一项警告,并且在禁忌证中删除了ICH史。与前面讨论的静脉阿替普酶治...19 颅内出血史
根据最初的 FDA 标签和2013年AHA/ASA指南,颅内出血史是静脉阿替普酶治疗缺血性卒中的一项额外禁忌证或排除标准。最近修订后的标签仅将近期 ICH 列为一项警告,并且在禁忌证中删除了ICH史。与前面讨论的静脉阿替普酶治疗排除标准相似,文献回顾仅在大样本回顾性研究中发现了少量这类病例。缺乏相关数据可能是修订后的FDA 标签不再将 ICH 史作为禁忌证而仅将近期ICH 列为一项警告的原因。在这种情况下,FDA 如何定义“近期”一词尚不清楚。有趣的是,对在静脉阿替普酶治疗前通过 MRI 检测脑微出血（ cerebral microbleed, CMBs）存在情况进行的研究可为这个卒中亚组患者提供更多的见解。从病理生理学角度,这种微出血的原因尚不清楚,可能反映再灌注损伤或脑血管自动调节功能破坏。因此,在静脉阿替普酶治疗后出现这些损害可能没有意义或是人为信号。展开更多
Death-mediating proteases such as caspases and caspase-3 in particular, have been implicated in neurodegenerative processes, aging and Alzheimer＇s disease. However, emerging evidence suggests that in addition to thei...Death-mediating proteases such as caspases and caspase-3 in particular, have been implicated in neurodegenerative processes, aging and Alzheimer＇s disease. However, emerging evidence suggests that in addition to their classical role in cell death, caspases play a key role in modulating synaptic function. It is remarkable that active caspases-3, which can trigger widespread damage and degeneration, aggregates in structures as delicate as synapses and persists in neurons without causing acute cell death. Here, we evaluate this dichotomy, and discuss the hypothesis that caspase-3 may be a bifurcation point in cellular signaling, able to orient the neuronal response to stress down either pathological/apoptotic pathways or towards physiological cellular remodeling. We propose that temporal, spatial and other regulators of caspase activity are key determinants of the ultimate effect of caspase-3 activation in neurons. This concept has implications for differential roles of caspase-3 activation across the lifespan. Specifically, we propose that limited caspase-3 activation is critical for synaptic function in the healthy adult brain while chronic activation is involved in degenerative processes in the aging brain.展开更多
One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to ...One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane. The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high leve｜s of superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to respond to such an attack because they only possess the first enzyme in the base excision repair （BER） pathway, 8-oxoguanine glycosylase 1 （OGG1）. The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further because they lack the downstream proteins （APE1, XRCC1） needed to complete the repair process. It is the responsibility of the oocyte to continue the BER pathway prior to initiation of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the spermatozoa of male infertility patients may have implications for the health of children conceived in vitro and serves as a driver for current research into the origins of free radical generation in the germ line.展开更多
AIM:To describe our own experience with pyogenic liver abscesses over the past 10 years and investigate the risk factors associated with failure of initial percutaneous therapy.METHODS:A retrospective study of records...AIM:To describe our own experience with pyogenic liver abscesses over the past 10 years and investigate the risk factors associated with failure of initial percutaneous therapy.METHODS:A retrospective study of records of 63 PLA patients presenting between 1998 and 2008 to Australian tertiary referral centre,were reviewed.Amoebic and hydatid abscesses were excluded.Demographic,clinical,radiological,and microbiological characteristics,as well as surgical/radiological interventions,were recorded.RESULTS:Sixty-three patients(42 males,21 females) aged 65(±14) years[mean±(SD) ]had prodromal symptoms for a median(interquartile range;IQR) of 7(5-14) d.Only 59%of patients were febrile at presentation;however,the serum C-reactive protein was elevated in all 47 in whom it was measured.Liver function tests were non-specifically abnormal.67%of patients had a solitary abscess,while 32%had>3 abscesses with a median(IQR) diameter of 6.3(4-9) cm.Causative organisms were:Streptococcus milleri 25%,Klebsiella pneumoniae 21%,and Escherichia coli 16%.A presumptive cryptogenic cause was most common (34%).Four patients died in this series:one from sepsis,two from advanced cancer,and one from acute myocardial infarction.The initial procedure was radiological aspiration±drainage in 54 and surgery in two patients.17%underwent surgical management during their hospitalization.Serum hypoalbuminaemia[mean (95%CI) :32(29-35) g/L vs 28(25-31) g/L,P=0.045] on presentation was found to be the only factor related to failure of initial percutaneous therapy on univariate analysis.CONCLUSION:PLA is a diagnostic challenge,because the presentation of this condition is non-specific.Intravenous antibiotics and radiological drainage in the first instance allows resolution of most PLAs;However,a small proportion of patients still require surgical drainage.展开更多
The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of...The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.展开更多
Frozen shoulder is a common disease which causes significant morbidity. Despite over a hundred years of treating this condition the definition, diagnosis, pathology and most efficacious treatments are still largely un...Frozen shoulder is a common disease which causes significant morbidity. Despite over a hundred years of treating this condition the definition, diagnosis, pathology and most efficacious treatments are still largely unclear. This systematic review of current treatments for frozen shoulder reviews the evidence base behind physiotherapy, both oral and intra articular steroid, hydrodilatation, manipulation under anaesthesia and arthroscopic capsular release. Key areas in which future research could be directed are identified, in particular with regard to the increasing role of arthroscopic capsular release as a treatment.展开更多
Gastric cancer remains a global killer with a shifting burden from the developed to the developing world. The cancer develops along a multistage process that is defined by distinct histological and pathophysiological ...Gastric cancer remains a global killer with a shifting burden from the developed to the developing world. The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori （H pylori） as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie Hpyloriinduced gastric cancer.展开更多
Soil carbon stocks and sequestration have been given a lot of attention recently in the study of terrestrial ecosystems and global climate change.This review focuses on the progress made on the estimation of the soil ...Soil carbon stocks and sequestration have been given a lot of attention recently in the study of terrestrial ecosystems and global climate change.This review focuses on the progress made on the estimation of the soil carbon stocks of China,and the characterization of carbon dynamics of croplands with regard to climate change,and addresses issues on the mineralization of soil organic carbon in relation to greenhouse gas emissions.By integrating existing research data,China's total soil organic carbon(SOC) stock is estimated to be 90 Pg and its inorganic carbon(SIC) stock as 60 Pg,with SOC sequestration rates in the range of 20-25 Tg/a for the last two decades.An estimation of the biophysical potential of SOC sequestration has been generally agreed as being 2 Pg over the long term,of which only 1/3 could be attainable using contemporary agricultural technologies in all of China's croplands.Thus,it is critical to enhance SOC sequestration and mitigate climate change to improve agricultural and land use management in China.There have been many instances where SOC accumulation may not induce an increased amount of decomposition under a warming scenario but instead favor improved cropland productivity and ecosystem functioning.Furthermore,unchanged or even decreased net global warming potential(GWP) from croplands with enhanced SOC has been reported by a number of case studies using life cycle analysis.Future studies on soil carbon stocks and the sequestration potential of China are expected to focus on:(1) Carbon stocks and the sequestration capacity of the earths' surface systems at scales ranging from the plot to the watershed and(2) multiple interface processes and the synergies between carbon sequestration and ecosystem productivity and ecosystem functioning at scales from the molecular level to agro-ecosystems.Soil carbon science in China faces new challenges and opportunities to undertake integrated research applicable to many areas.展开更多
基金supported by a grant (AG012694-16) from the National Institue of Aging,USA
文摘Death-mediating proteases such as caspases and caspase-3 in particular, have been implicated in neurodegenerative processes, aging and Alzheimer＇s disease. However, emerging evidence suggests that in addition to their classical role in cell death, caspases play a key role in modulating synaptic function. It is remarkable that active caspases-3, which can trigger widespread damage and degeneration, aggregates in structures as delicate as synapses and persists in neurons without causing acute cell death. Here, we evaluate this dichotomy, and discuss the hypothesis that caspase-3 may be a bifurcation point in cellular signaling, able to orient the neuronal response to stress down either pathological/apoptotic pathways or towards physiological cellular remodeling. We propose that temporal, spatial and other regulators of caspase activity are key determinants of the ultimate effect of caspase-3 activation in neurons. This concept has implications for differential roles of caspase-3 activation across the lifespan. Specifically, we propose that limited caspase-3 activation is critical for synaptic function in the healthy adult brain while chronic activation is involved in degenerative processes in the aging brain.
文摘One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane. The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high leve｜s of superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to respond to such an attack because they only possess the first enzyme in the base excision repair （BER） pathway, 8-oxoguanine glycosylase 1 （OGG1）. The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further because they lack the downstream proteins （APE1, XRCC1） needed to complete the repair process. It is the responsibility of the oocyte to continue the BER pathway prior to initiation of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the spermatozoa of male infertility patients may have implications for the health of children conceived in vitro and serves as a driver for current research into the origins of free radical generation in the germ line.
文摘AIM:To describe our own experience with pyogenic liver abscesses over the past 10 years and investigate the risk factors associated with failure of initial percutaneous therapy.METHODS:A retrospective study of records of 63 PLA patients presenting between 1998 and 2008 to Australian tertiary referral centre,were reviewed.Amoebic and hydatid abscesses were excluded.Demographic,clinical,radiological,and microbiological characteristics,as well as surgical/radiological interventions,were recorded.RESULTS:Sixty-three patients(42 males,21 females) aged 65(±14) years[mean±(SD) ]had prodromal symptoms for a median(interquartile range;IQR) of 7(5-14) d.Only 59%of patients were febrile at presentation;however,the serum C-reactive protein was elevated in all 47 in whom it was measured.Liver function tests were non-specifically abnormal.67%of patients had a solitary abscess,while 32%had>3 abscesses with a median(IQR) diameter of 6.3(4-9) cm.Causative organisms were:Streptococcus milleri 25%,Klebsiella pneumoniae 21%,and Escherichia coli 16%.A presumptive cryptogenic cause was most common (34%).Four patients died in this series:one from sepsis,two from advanced cancer,and one from acute myocardial infarction.The initial procedure was radiological aspiration±drainage in 54 and surgery in two patients.17%underwent surgical management during their hospitalization.Serum hypoalbuminaemia[mean (95%CI) :32(29-35) g/L vs 28(25-31) g/L,P=0.045] on presentation was found to be the only factor related to failure of initial percutaneous therapy on univariate analysis.CONCLUSION:PLA is a diagnostic challenge,because the presentation of this condition is non-specific.Intravenous antibiotics and radiological drainage in the first instance allows resolution of most PLAs;However,a small proportion of patients still require surgical drainage.
文摘The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.
文摘Frozen shoulder is a common disease which causes significant morbidity. Despite over a hundred years of treating this condition the definition, diagnosis, pathology and most efficacious treatments are still largely unclear. This systematic review of current treatments for frozen shoulder reviews the evidence base behind physiotherapy, both oral and intra articular steroid, hydrodilatation, manipulation under anaesthesia and arthroscopic capsular release. Key areas in which future research could be directed are identified, in particular with regard to the increasing role of arthroscopic capsular release as a treatment.
文摘Gastric cancer remains a global killer with a shifting burden from the developed to the developing world. The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori （H pylori） as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie Hpyloriinduced gastric cancer.
基金supported by the National Natural Science Foundation of China (40830528 and 40270010092)supported by travel funds from a UK BBSRC China Partnership Award. PS is a Royal Society-Wolfson Research Merit Award holder
文摘Soil carbon stocks and sequestration have been given a lot of attention recently in the study of terrestrial ecosystems and global climate change.This review focuses on the progress made on the estimation of the soil carbon stocks of China,and the characterization of carbon dynamics of croplands with regard to climate change,and addresses issues on the mineralization of soil organic carbon in relation to greenhouse gas emissions.By integrating existing research data,China's total soil organic carbon(SOC) stock is estimated to be 90 Pg and its inorganic carbon(SIC) stock as 60 Pg,with SOC sequestration rates in the range of 20-25 Tg/a for the last two decades.An estimation of the biophysical potential of SOC sequestration has been generally agreed as being 2 Pg over the long term,of which only 1/3 could be attainable using contemporary agricultural technologies in all of China's croplands.Thus,it is critical to enhance SOC sequestration and mitigate climate change to improve agricultural and land use management in China.There have been many instances where SOC accumulation may not induce an increased amount of decomposition under a warming scenario but instead favor improved cropland productivity and ecosystem functioning.Furthermore,unchanged or even decreased net global warming potential(GWP) from croplands with enhanced SOC has been reported by a number of case studies using life cycle analysis.Future studies on soil carbon stocks and the sequestration potential of China are expected to focus on:(1) Carbon stocks and the sequestration capacity of the earths' surface systems at scales ranging from the plot to the watershed and(2) multiple interface processes and the synergies between carbon sequestration and ecosystem productivity and ecosystem functioning at scales from the molecular level to agro-ecosystems.Soil carbon science in China faces new challenges and opportunities to undertake integrated research applicable to many areas.
