Establishing an effective three-dimensional(3D) in vitro culture system to better model human neurological diseases is desirable, since the human brain is a 3D structure. Here, we demonstrated the development of a pol...Establishing an effective three-dimensional(3D) in vitro culture system to better model human neurological diseases is desirable, since the human brain is a 3D structure. Here, we demonstrated the development of a polydimethylsiloxane(PDMS) pillar-based 3D scaffold that mimicked the 3D microenvironment of the brain. We utilized this scaffold for the growth of human cortical glutamatergic neurons that were differentiated from human pluripotent stem cells. In comparison with the 2D culture, we demonstrated that the developed 3D culture promoted the maturation of human cortical glutamatergic neurons by showing significantly more MAP2 and less Ki67 expression. Based on this 3D culture system,we further developed an in vitro disease-like model of traumatic brain injury(TBI), which showed a robust increase of glutamate-release from the neurons, in response to mechanical impacts, recapitulating the critical pathology of TBI. The increased glutamate-release from our 3D culture model was attenuated by the treatment of neural protective drugs, memantine or nimodipine. The established 3D in vitro human neural culture system and TBI-like model may be used to facilitate mechanistic studies and drug screening for neurotrauma or other neurological diseases.展开更多
Spontaneous free perforation of the small intestine is uncommon, especially if there is no prior history of visceral trauma. However, free, even recurrent, perforation may complicate a defined and established clinical...Spontaneous free perforation of the small intestine is uncommon, especially if there is no prior history of visceral trauma. However, free, even recurrent, perforation may complicate a defined and established clinical disorder, such as Crohn’s disease. In addition, free perforation may be the initial clinical presentation of an occult intestinal disorder, such as a lymphoma complicating celiac disease, causing diffuse peritonitis and an acute abdomen. Initial diagnosis of the precise cause may be difficult, but now has been aided by computerized tomographic imaging. The site of perforation may be helpful in defining a cause (e.g., ileal perforation in Crohn’s disease, jejunal perforation in celiac disease, complicated by lymphoma or collagenous sprue). Urgent surgical intervention, however, is usually required for precise diagnosis and treatment. During evaluation, an expanding list of other possible causes should be considered, even after surgery, as subsequent management may be affected. Free perforation may not only complicate an established intestinal disorder, but also a new acute process (e.g., caused by different infectious agents) or a longstanding and unrecognized disorder (e.g., congenital, metabolic and vascular causes). Moreover, new endoscopic therapeutic and medical therapies, including use of emerging novel biological agents, have been complicated by intestinal perforation. Recent studies also support the hypothesis that perforation of the small intestine may be genetically-based with different mutations causing altered connective tissue structure, synthesis and repair.展开更多
Purpose:Traumatic brain injury(TBI),currently a major global public health problem,imposes a significant economic burden on society and families.We aimed to quantify and predict the incidence and severity of TBI by an...Purpose:Traumatic brain injury(TBI),currently a major global public health problem,imposes a significant economic burden on society and families.We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence,prevalence,and years lived with disability(YLDs).The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention,treatment,and incidence-reducing measures for TBI.Methods:A secondary analysis was performed on the incidence,prevalence,and YLDs of TBI by sex,age group,and region(n=21,204 countries and territories)between 1990 and 2019 using the Global Burden of Diseases,Injuries,and Risk Factors Study 2019.Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported.Results:In 2019,there were 27.16 million(95%uncertainty intervals(UI):23.36-31.42)new cases of TBI worldwide,with age-standardized incidence and prevalence rates of 346 per 100,000 population(95%UI:298-401)and 599 per 100,000 population(95%UI:573-627),respectively.From 1990 to 2019,there were no significant trends in global age-standardized incidence(estimated annual percentage changes:-0.11%,95%UI:-0.18%--0.04%)or prevalence(estimated annual percentage changes:0.01%,95%UI:-0.04%-0.06%).TBI caused 7.08 million(95%UI:5.00-9.59)YLDs in 2019,with age-standardized rates of 86.5 per 100,000 population(95%UI:61.1-117.2).In 2019,the countries with higher incidence rates were mainly distributed in Central Europe,Eastern Europe,and Australia.The 2019 global age-standardized incidence rate was higher in males than in females.The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population,accounting for 52.8%of all TBI,with falls and road traffic injuries being the main causes in most regions.Conclusions:The incidence of moderate and severe TBI was slightly higher in 2019,and TBI still accounts for a significant portion of the global injury burden.The l展开更多
Traumatic brain injury is among the most common causes of death and disability in youth and young adults.In addition to the acute risk of morbidity with moderate to severe injuries,traumatic brain injury is associated...Traumatic brain injury is among the most common causes of death and disability in youth and young adults.In addition to the acute risk of morbidity with moderate to severe injuries,traumatic brain injury is associated with a number of chronic neurological and neuropsychiatric sequelae including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.However,despite the high incidence of traumatic brain injuries and the established clinical correlation with neurodegeneration,the causative factors linking these processes have not yet been fully elucidated.Apart from removal from activity,few,if any prophylactic treatments against post-traumatic brain injury neurodegeneration exist.Therefore,it is imperative to understand the pathophysiological mechanisms of traumatic brain injury and neurodegeneration in order to identify potential factors that initiate neurodegenerative processes.Oxidative stress,neuroinflammation,and glutamatergic excitotoxicity have previously been implicated in both secondary brain injury and neurodegeneration.In particular,reactive oxygen species appear to be key in mediating molecular insult in neuroinflammation and excitotoxicity.As such,it is likely that post injury oxidative stress is a key mechanism which links traumatic brain injury to increased risk of neurodegeneration.Consequently,reactive oxygen species and their subsequent byproducts may serve as novel fluid markers for identification and monitoring of cellular damage.Furthermore,these reactive species may further serve as a suitable therapeutic target to reduce the risk of post-injury neurodegeneration and provide long term quality of life improvements for those suffering from traumatic brain injury.展开更多
A mathematical model has been developed to numerically model the risk of developing Alzheimer’s disease and Chronic Traumatic Encephalopathy (CTE) as a person ages. The model was programmed in Excel to provide a work...A mathematical model has been developed to numerically model the risk of developing Alzheimer’s disease and Chronic Traumatic Encephalopathy (CTE) as a person ages. The model was programmed in Excel to provide a working prototype computer simulation model. The model provides estimates of the cumulative risk of developing Alzheimer’s disease and CTE as age increases. A one-year step size was used. The model has two major parts: one predicts changes in slow-wave sleep as a person ages and the second component adjusts the flushing efficiency of waste products from the brain. The two components work together and interact to lower the flushing of waste components as age increases. The development of the model provides an overview of how the various factors work together that lead to the onset of Alzheimer’s disease and the associated CTE. Calibration of the coefficients in the model is based on published data sets presented in the literature. Further research and refinement of calibration coefficients should be explored.展开更多
目的:比较真实世界中创伤性疾病患者口服脉血康胶囊与未口服脉血康胶囊的疗效。方法:从25家三级甲等医院信息管理系统(Hospital Information System,HIS)提取患者信息,选取口服脉血康胶囊的创伤性疾病患者656例为观察组和未使用脉血康...目的:比较真实世界中创伤性疾病患者口服脉血康胶囊与未口服脉血康胶囊的疗效。方法:从25家三级甲等医院信息管理系统(Hospital Information System,HIS)提取患者信息,选取口服脉血康胶囊的创伤性疾病患者656例为观察组和未使用脉血康胶囊的创伤性疾病患者656例为对照组。运用广义Boosted模型(Generalized Boosted Models,GBM)倾向性评分法平衡混杂因素,分别采用Logistic回归、倾向性评分加权的Logistic回归和带协变量调整的倾向性评分加权Logistic回归比较2组间的疗效差异。结果:3种Logistic回归方法结果均显示观察组疗效优于与对照组,差异有统计学意义(P<0.05)。结论:对于创伤性疾病患者的治疗服用脉血康胶囊疗效优于未使用该药。展开更多
Extensive research is ongoing in the use of Photobiomodulation (PBM, often referred to as low-level or cold laser therapy) to treat Alzheimer’s disease as well as other debilitating diseases. The following case studi...Extensive research is ongoing in the use of Photobiomodulation (PBM, often referred to as low-level or cold laser therapy) to treat Alzheimer’s disease as well as other debilitating diseases. The following case studies further confirm that PBM could be a breakthrough approach to limit the progression of insidious diseases. We present four cases, two with mild to moderate dementia and two with more advanced symptoms. Several publications have shown beneficial results, however, several weeks of daily treatments were necessary. The cases described here suggest that moderate and advanced dementia cases can be significantly improved with three or four eight-minute treatments over a 5 - 7-day period when using super-pulsing technology on Monday-Wednesday-Friday schedule (Figure 1). Gives a brief visual explanation of super-pulsing versus continuous wave technology.展开更多
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDA16010306)the National Natural Science Foundation of China Grants (91849117 and 81471301)+3 种基金Key Research and Development Program of China (2016YFC1306703)The National Jiangsu Outstanding Young Investigator Program (BK20160044, China)Jiangsu Province’s Innovation Person (China)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China Project (Grant No. 17KJB180010)
文摘Establishing an effective three-dimensional(3D) in vitro culture system to better model human neurological diseases is desirable, since the human brain is a 3D structure. Here, we demonstrated the development of a polydimethylsiloxane(PDMS) pillar-based 3D scaffold that mimicked the 3D microenvironment of the brain. We utilized this scaffold for the growth of human cortical glutamatergic neurons that were differentiated from human pluripotent stem cells. In comparison with the 2D culture, we demonstrated that the developed 3D culture promoted the maturation of human cortical glutamatergic neurons by showing significantly more MAP2 and less Ki67 expression. Based on this 3D culture system,we further developed an in vitro disease-like model of traumatic brain injury(TBI), which showed a robust increase of glutamate-release from the neurons, in response to mechanical impacts, recapitulating the critical pathology of TBI. The increased glutamate-release from our 3D culture model was attenuated by the treatment of neural protective drugs, memantine or nimodipine. The established 3D in vitro human neural culture system and TBI-like model may be used to facilitate mechanistic studies and drug screening for neurotrauma or other neurological diseases.
文摘Spontaneous free perforation of the small intestine is uncommon, especially if there is no prior history of visceral trauma. However, free, even recurrent, perforation may complicate a defined and established clinical disorder, such as Crohn’s disease. In addition, free perforation may be the initial clinical presentation of an occult intestinal disorder, such as a lymphoma complicating celiac disease, causing diffuse peritonitis and an acute abdomen. Initial diagnosis of the precise cause may be difficult, but now has been aided by computerized tomographic imaging. The site of perforation may be helpful in defining a cause (e.g., ileal perforation in Crohn’s disease, jejunal perforation in celiac disease, complicated by lymphoma or collagenous sprue). Urgent surgical intervention, however, is usually required for precise diagnosis and treatment. During evaluation, an expanding list of other possible causes should be considered, even after surgery, as subsequent management may be affected. Free perforation may not only complicate an established intestinal disorder, but also a new acute process (e.g., caused by different infectious agents) or a longstanding and unrecognized disorder (e.g., congenital, metabolic and vascular causes). Moreover, new endoscopic therapeutic and medical therapies, including use of emerging novel biological agents, have been complicated by intestinal perforation. Recent studies also support the hypothesis that perforation of the small intestine may be genetically-based with different mutations causing altered connective tissue structure, synthesis and repair.
基金funded by the National Natural Science Foundation of China(82260254,82060245)the Technology Project of Guizhou Province(20204Y149)+2 种基金the Technology Project of Guizhou Province(2021047)the Excellent Young Talents Training Program of the Affiliated Hospital of Zunyi Medical University(rc220220923)the High-level innovative talents of Guizhou Province(GCC 2023081)。
文摘Purpose:Traumatic brain injury(TBI),currently a major global public health problem,imposes a significant economic burden on society and families.We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence,prevalence,and years lived with disability(YLDs).The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention,treatment,and incidence-reducing measures for TBI.Methods:A secondary analysis was performed on the incidence,prevalence,and YLDs of TBI by sex,age group,and region(n=21,204 countries and territories)between 1990 and 2019 using the Global Burden of Diseases,Injuries,and Risk Factors Study 2019.Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported.Results:In 2019,there were 27.16 million(95%uncertainty intervals(UI):23.36-31.42)new cases of TBI worldwide,with age-standardized incidence and prevalence rates of 346 per 100,000 population(95%UI:298-401)and 599 per 100,000 population(95%UI:573-627),respectively.From 1990 to 2019,there were no significant trends in global age-standardized incidence(estimated annual percentage changes:-0.11%,95%UI:-0.18%--0.04%)or prevalence(estimated annual percentage changes:0.01%,95%UI:-0.04%-0.06%).TBI caused 7.08 million(95%UI:5.00-9.59)YLDs in 2019,with age-standardized rates of 86.5 per 100,000 population(95%UI:61.1-117.2).In 2019,the countries with higher incidence rates were mainly distributed in Central Europe,Eastern Europe,and Australia.The 2019 global age-standardized incidence rate was higher in males than in females.The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population,accounting for 52.8%of all TBI,with falls and road traffic injuries being the main causes in most regions.Conclusions:The incidence of moderate and severe TBI was slightly higher in 2019,and TBI still accounts for a significant portion of the global injury burden.The l
文摘Traumatic brain injury is among the most common causes of death and disability in youth and young adults.In addition to the acute risk of morbidity with moderate to severe injuries,traumatic brain injury is associated with a number of chronic neurological and neuropsychiatric sequelae including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.However,despite the high incidence of traumatic brain injuries and the established clinical correlation with neurodegeneration,the causative factors linking these processes have not yet been fully elucidated.Apart from removal from activity,few,if any prophylactic treatments against post-traumatic brain injury neurodegeneration exist.Therefore,it is imperative to understand the pathophysiological mechanisms of traumatic brain injury and neurodegeneration in order to identify potential factors that initiate neurodegenerative processes.Oxidative stress,neuroinflammation,and glutamatergic excitotoxicity have previously been implicated in both secondary brain injury and neurodegeneration.In particular,reactive oxygen species appear to be key in mediating molecular insult in neuroinflammation and excitotoxicity.As such,it is likely that post injury oxidative stress is a key mechanism which links traumatic brain injury to increased risk of neurodegeneration.Consequently,reactive oxygen species and their subsequent byproducts may serve as novel fluid markers for identification and monitoring of cellular damage.Furthermore,these reactive species may further serve as a suitable therapeutic target to reduce the risk of post-injury neurodegeneration and provide long term quality of life improvements for those suffering from traumatic brain injury.
文摘A mathematical model has been developed to numerically model the risk of developing Alzheimer’s disease and Chronic Traumatic Encephalopathy (CTE) as a person ages. The model was programmed in Excel to provide a working prototype computer simulation model. The model provides estimates of the cumulative risk of developing Alzheimer’s disease and CTE as age increases. A one-year step size was used. The model has two major parts: one predicts changes in slow-wave sleep as a person ages and the second component adjusts the flushing efficiency of waste products from the brain. The two components work together and interact to lower the flushing of waste components as age increases. The development of the model provides an overview of how the various factors work together that lead to the onset of Alzheimer’s disease and the associated CTE. Calibration of the coefficients in the model is based on published data sets presented in the literature. Further research and refinement of calibration coefficients should be explored.
文摘目的:比较真实世界中创伤性疾病患者口服脉血康胶囊与未口服脉血康胶囊的疗效。方法:从25家三级甲等医院信息管理系统(Hospital Information System,HIS)提取患者信息,选取口服脉血康胶囊的创伤性疾病患者656例为观察组和未使用脉血康胶囊的创伤性疾病患者656例为对照组。运用广义Boosted模型(Generalized Boosted Models,GBM)倾向性评分法平衡混杂因素,分别采用Logistic回归、倾向性评分加权的Logistic回归和带协变量调整的倾向性评分加权Logistic回归比较2组间的疗效差异。结果:3种Logistic回归方法结果均显示观察组疗效优于与对照组,差异有统计学意义(P<0.05)。结论:对于创伤性疾病患者的治疗服用脉血康胶囊疗效优于未使用该药。
文摘Extensive research is ongoing in the use of Photobiomodulation (PBM, often referred to as low-level or cold laser therapy) to treat Alzheimer’s disease as well as other debilitating diseases. The following case studies further confirm that PBM could be a breakthrough approach to limit the progression of insidious diseases. We present four cases, two with mild to moderate dementia and two with more advanced symptoms. Several publications have shown beneficial results, however, several weeks of daily treatments were necessary. The cases described here suggest that moderate and advanced dementia cases can be significantly improved with three or four eight-minute treatments over a 5 - 7-day period when using super-pulsing technology on Monday-Wednesday-Friday schedule (Figure 1). Gives a brief visual explanation of super-pulsing versus continuous wave technology.
