Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced ...Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.展开更多
Numerical simulations based on a high-resolution three-dimensional MIT general circulation model(MITgcm)using realistic topography and tidal forcing are conducted to investigate the generation and propagation of the s...Numerical simulations based on a high-resolution three-dimensional MIT general circulation model(MITgcm)using realistic topography and tidal forcing are conducted to investigate the generation and propagation of the so-called type-a waves(large-amplitude rank-ordered wave packets)and type-b waves(isolated wave packets)in the northern South China Sea.At first,we summarized and analyzed the generation and propagation characteristics of these waves.Then,energy budget at the Luzon Strait is calculated.Energy generation has three local maxima every day,of which the largest one corresponds to the emergence of the type-a wave.Energy flux at the west boundary of the Luzon Strait shows two local maxima each day.The larger one is consistent with the generation of the type-a wave and the smaller one is in correspondence with the generation of the type-b wave.Sensitivity experiments are designed to explore the role of the east and west ridge of the Luzon Strait on the generation and propagation of the type-a and type-b waves.It is found that the east ridge is indispensable on the generation of the type-a wave while the west ridge has little contribution.The west ridge diminishes the type-a waves'amplitude but hardly changes their propagation speed.The type-b waves also come from perturbation signals which originate from the east ridge and are enhanced in amplitude and reduced in propagation speed by the west ridge.展开更多
目的 评价2020—2022年吉林省适龄儿童接种含无细胞百白破成分疫苗的安全性,以期为后续预防接种工作中疫苗的安全使用提供参考。方法 通过吉林省免疫规划信息管理系统和国家免疫规划信息管理系统疑似预防接种异常反应(adverse event fol...目的 评价2020—2022年吉林省适龄儿童接种含无细胞百白破成分疫苗的安全性,以期为后续预防接种工作中疫苗的安全使用提供参考。方法 通过吉林省免疫规划信息管理系统和国家免疫规划信息管理系统疑似预防接种异常反应(adverse event following immunization,AEFI)功能管理模块,收集2020年1月1日—2022年12月31日吉林省适龄儿童接种吸附无细胞百白破联合疫苗(diphtheria,tetanus and acellular pertussis combined vaccine,DTaP)、无细胞百白破-b型流感嗜血杆菌联合疫苗(diphtheria,tetanus,acellular pertussis and Haemophilus influenzae type b combined vaccine,DTaP-Hib)和无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗[diphtheria,tetanus,pertussis(acellular,component),poliomyelitis(inactivated)vaccine and Haemophilus type b conjugate vaccine,adsorbed,DTaP-IPV/Hib]后发生AEFI的个案报告信息,采用描述性流行病学方法进行分析,并应用统计学方法比较组间差异。结果 2020—2022年吉林省适龄儿童接种DTaP、DTaP-Hib和DTaP-IPV/Hib共1 301 812剂次,共计报告AEFI个案3 132例(240.59/10万剂次),其中一般反应3 122例(99.68%,239.82/10万剂次),异常反应7例(0.22%,0.54/10万剂次),偶合症3例(0.1%,0.23/10万剂次)。3种含DTaP成分疫苗的AEFI报告发生率分别为257.00/10万剂次(3 025例)、175.61/10万剂次(34例)、69.26/10万剂次(73例),差异有统计学意义(χ^(2)=145.53,P<0.001);3种含DTaP成分疫苗加强免疫AEFI报告发生率高于基础免疫,差异有统计学意义(χ^(2)分别为254.98、18.03、20.39,P均<0.05);报告的AEFI病例以一般反应为主,包括发热、局部红肿、局部硬结等,主要发生于接种疫苗后0~1 d内。结论 2020—2022年吉林省适龄儿童接种DTaP、DTaP-Hib和DTaP-IPV/Hib的AEFI以一般反应为主,总体安全性良好。建议持续加强接种后AEFI监测,并优化被动监测系统以减少漏报偏倚。展开更多
文摘Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.
基金The National Key Research and Development Plan of China under contract No.2016YFC1401300the National Natural Science Foundation of China under contract No.41276008the Taishan Scholars Program
文摘Numerical simulations based on a high-resolution three-dimensional MIT general circulation model(MITgcm)using realistic topography and tidal forcing are conducted to investigate the generation and propagation of the so-called type-a waves(large-amplitude rank-ordered wave packets)and type-b waves(isolated wave packets)in the northern South China Sea.At first,we summarized and analyzed the generation and propagation characteristics of these waves.Then,energy budget at the Luzon Strait is calculated.Energy generation has three local maxima every day,of which the largest one corresponds to the emergence of the type-a wave.Energy flux at the west boundary of the Luzon Strait shows two local maxima each day.The larger one is consistent with the generation of the type-a wave and the smaller one is in correspondence with the generation of the type-b wave.Sensitivity experiments are designed to explore the role of the east and west ridge of the Luzon Strait on the generation and propagation of the type-a and type-b waves.It is found that the east ridge is indispensable on the generation of the type-a wave while the west ridge has little contribution.The west ridge diminishes the type-a waves'amplitude but hardly changes their propagation speed.The type-b waves also come from perturbation signals which originate from the east ridge and are enhanced in amplitude and reduced in propagation speed by the west ridge.
文摘目的了解终末期肾病维持性血透(maintained hemodialysis,MHD)患者血浆B型利钠肽(B-type natriuretic peptide,BNP)水平以及营养状况与BNP水平的关系。方法采用横断面研究,纳入符合观察条件的MHD患者116例。测量身高、体质量、上臂围、小腿围、握力等,免疫发光法检测血浆BNP水平,生物电阻抗分析法测量骨骼肌质量指数(skeletal muscle mass index,SMI),多元线性回归分析血浆BNP水平的影响因素。结果MHD患者中位血浆BNP水平为250.5(107.3,491.5)pg/mL。血浆BNP水平与年龄呈正相关(P<0.05);与细胞内水分、体质量指数(body mass index,BMI)、上臂围、小腿围、握力、骨骼肌质量指数、血红蛋白、血清总胆固醇呈负相关(P<0.05)。多元线性回归分析显示,BMI、血红蛋白、年龄、血清总胆固醇水平是MHD患者血浆BNP水平的独立影响因素(β=-0.299,P<0.001;β=-0.283,P=0.001;β=0.242,P=0.005;β=-0.187,P=0.030)。结论MHD患者血浆BNP水平高于普通人群,较低的BMI、血红蛋白和血清总胆固醇水平与较高的血浆BNP水平有关。
文摘目的 评价2020—2022年吉林省适龄儿童接种含无细胞百白破成分疫苗的安全性,以期为后续预防接种工作中疫苗的安全使用提供参考。方法 通过吉林省免疫规划信息管理系统和国家免疫规划信息管理系统疑似预防接种异常反应(adverse event following immunization,AEFI)功能管理模块,收集2020年1月1日—2022年12月31日吉林省适龄儿童接种吸附无细胞百白破联合疫苗(diphtheria,tetanus and acellular pertussis combined vaccine,DTaP)、无细胞百白破-b型流感嗜血杆菌联合疫苗(diphtheria,tetanus,acellular pertussis and Haemophilus influenzae type b combined vaccine,DTaP-Hib)和无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗[diphtheria,tetanus,pertussis(acellular,component),poliomyelitis(inactivated)vaccine and Haemophilus type b conjugate vaccine,adsorbed,DTaP-IPV/Hib]后发生AEFI的个案报告信息,采用描述性流行病学方法进行分析,并应用统计学方法比较组间差异。结果 2020—2022年吉林省适龄儿童接种DTaP、DTaP-Hib和DTaP-IPV/Hib共1 301 812剂次,共计报告AEFI个案3 132例(240.59/10万剂次),其中一般反应3 122例(99.68%,239.82/10万剂次),异常反应7例(0.22%,0.54/10万剂次),偶合症3例(0.1%,0.23/10万剂次)。3种含DTaP成分疫苗的AEFI报告发生率分别为257.00/10万剂次(3 025例)、175.61/10万剂次(34例)、69.26/10万剂次(73例),差异有统计学意义(χ^(2)=145.53,P<0.001);3种含DTaP成分疫苗加强免疫AEFI报告发生率高于基础免疫,差异有统计学意义(χ^(2)分别为254.98、18.03、20.39,P均<0.05);报告的AEFI病例以一般反应为主,包括发热、局部红肿、局部硬结等,主要发生于接种疫苗后0~1 d内。结论 2020—2022年吉林省适龄儿童接种DTaP、DTaP-Hib和DTaP-IPV/Hib的AEFI以一般反应为主,总体安全性良好。建议持续加强接种后AEFI监测,并优化被动监测系统以减少漏报偏倚。
