Objective Alzheimer’s disease(AD)is the most common age-related neurodegenerative disorder.Emerging evidence suggests that synaptic dysfunction is associated with the onset and progression of AD.Interestingly,Ginkgo ...Objective Alzheimer’s disease(AD)is the most common age-related neurodegenerative disorder.Emerging evidence suggests that synaptic dysfunction is associated with the onset and progression of AD.Interestingly,Ginkgo biloba extract(EGb)is one of the most frequently investigated herbal medicines for enhancing cognition and alleviating neurodegenerative dementia.This study aimed to investigate the effect and the mechanism of EGb on AD-like synaptic disorders.Methods Scopolamine(SCO)-induced rats were used to mimic AD-like memory deficits.Morris water maze test and fear conditioning test were conducted to evaluate the memory status of rats in response to different treatments.Then,the synapse alterations were assessed by Golgi staining,and Western blotting was conducted to assess the protein expression of PSD95,GluN2B,synapsin-1,and synaptophysin.Reverse transcription quantitative polymerase chain reaction was applied to detect the mRNA expression of PSD95 and the levels of miR-1-3p/miR-206-3p.Results EGb supplement alleviated the learning and memory deficits induced by SCO in behavioral experiments.Moreover,EGb treatment attenuated synaptic damage elicited by SCO,manifested as increased dendritic spine density and the proportion of mushroom-type spines in hippocampal neurons.Further investigation indicated that EGb rescued the expression of synaptic-related proteins,especially PSD95,and decreased the levels of miR-1-3p/miR-206-3p in the rat hippocampus.Conclusion The application of EGb effectively treats SCO-induced memory impairments probably by suppressing miR-1-3p/miR-206-3p and elevating the expression of PSD95.展开更多
患者,男,49岁,2022年1月至温州医科大学附属舟山医院就诊,自诉1月余前无明显诱因下出现行走不稳,后症状持续存在。该患者既往有血栓性静脉炎,无动脉或静脉血栓家族史;有2次急性脑梗死发作史,于上海交通大学医学院附属瑞金医院行易栓症...患者,男,49岁,2022年1月至温州医科大学附属舟山医院就诊,自诉1月余前无明显诱因下出现行走不稳,后症状持续存在。该患者既往有血栓性静脉炎,无动脉或静脉血栓家族史;有2次急性脑梗死发作史,于上海交通大学医学院附属瑞金医院行易栓症相关检测,发现蛋白S总量为26.7%,基因检测结果为蛋白S的编码基因PROS1第15号外显子发生c.1955A>T,p.Asp652Val杂合突变。该患者被诊断为遗传性蛋白S缺乏症(protein S deficiency,PSD),之后长期口服利伐沙班片抗凝。此次查体除行走稍不稳外,其余无明显异常;静脉血栓栓塞症(venous thromboembolism,VTE)风险评估量表(Padua模型)评分为6分,判定为VTE高危患者。动态心电图显示窦性心律,偶发房性早搏、室性早搏;四肢血管B超显示双侧腘动脉、胫后动脉多发血栓形成伴局部狭窄,右侧桡动脉闭塞;心脏超声及颈动脉超声未见明显异常;颅脑MRI结果显示左侧基底节区脑梗死陈旧性病灶。CT血管造影联合三维重建显示左侧大脑中动脉M1段重度狭窄、闭塞可能,两侧颈内动脉虹吸段狭窄、硬化。该患者最终被诊断为PSD合并脑梗死及外周动脉阻塞。治疗采用瑞舒伐他汀钙片调脂稳定斑块,利伐沙班片抗凝,琥珀酸美托洛尔缓释片控制心室率,叶酸片改善代谢;治疗10 d后,患者症状好转。展开更多
Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefor...Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefore, agent(s) capable of inhibiting brain amyloid deposition might delay the occurrence or retard the progress forwards of AD and related neurobehavioral symptoms. Here, we report whether, chronic oral administration of Syzygium cumini (locally known as Jam)-seed extract exerts protection against the progressive cognitive decline in the Aβ1-40-infused AD model rats. After 12 weeks of feeding with S. cumini seed extract (at 300 mg/kg BW), we evaluated the learning-related memory of the rats by 8-arm radial maze task, where we determined two types of memory errors, namely reference memory errors (RMEs) and working memory errors (WMEs). After completion of memory tests, rats were sacrificed and the levels of lipid peroxide (LPO), the Aβ1-40-burden, Aβ1-40-oligomers, proinflammatory TNFα, brain derived neurotrophic factor (BDNF), Tyrosine-kinase B (TrkB), postsynaptic-density protein 95 (PSD-95) and Synapse-associated protein (SNAP-25) were determined in the corticohippocampal tissues of the brain. In addition, in vitro antioxidative effects of S. cumini seed extract were evaluated. The oral administration of S. cumini extract significantly increased the memory-related learning ability of the AD model rats, concomitantly with reductions in the levels of corticohippocampal Aβ1-40-burden and Aβ1-40-oligomers. Furthermore, the extract suppressed the levels of TNFα and LPO in the corticohippocampal tissues of the AD rats and also the later in the plasma, suggesting an anti-oxidative and anti-inflammatory activities of the S. cumini extract in the brains of AD model rats. S. cumini extract also increased the levels of brain cognition and memory-related proteins, including BDNF, TrKB, PSD-95 and SNAP-25. We thus suggest that S. cumini-seed extract could be used in neurobehavioral deficits and associated pathogenesis of Alzheimer’s disease.展开更多
This paper is the second step of our work. The first step presents a set of parametric studies performed on automotive radiators by designing different heat exchanger models. The analysis focuses on the cooling perfor...This paper is the second step of our work. The first step presents a set of parametric studies performed on automotive radiators by designing different heat exchanger models. The analysis focuses on the cooling performance for automobile radiator by changing several dimensions of the radiator fin phase (P2.5, P2.4, P2.3, P2.2, and P2.1) as well as the importance of coolant flow lay-out on the radiator global performance [1]. The second step consists on the study of the vibration fatigue of the sample with the best heat dissipation performance we design (radiator P2.1). We use Hyper Mesh to proceed with the finite element model. Frequency response analysis is solved by using MSC. Nastran (MSC. MD. Nastran. v2010.1.3-MAGNiTUDE), fatigue durability ana-lysis by using MSC Fatigue. In this experiment, the frequency response of the unit load (the unit load is 1 g) is analyzed. Based on the analysis of the frequency response of the unit load, the fatigue life of the radiator is analyzed by the PSD (power spectral density) curve and the S-N curve. From our experiments results, we observe that the radiator we design meets the international requirements of fatigue vibration under automobile normal working condition.展开更多
基金the National Key Research and Development Project of China(No.2017YFC1309601).
文摘Objective Alzheimer’s disease(AD)is the most common age-related neurodegenerative disorder.Emerging evidence suggests that synaptic dysfunction is associated with the onset and progression of AD.Interestingly,Ginkgo biloba extract(EGb)is one of the most frequently investigated herbal medicines for enhancing cognition and alleviating neurodegenerative dementia.This study aimed to investigate the effect and the mechanism of EGb on AD-like synaptic disorders.Methods Scopolamine(SCO)-induced rats were used to mimic AD-like memory deficits.Morris water maze test and fear conditioning test were conducted to evaluate the memory status of rats in response to different treatments.Then,the synapse alterations were assessed by Golgi staining,and Western blotting was conducted to assess the protein expression of PSD95,GluN2B,synapsin-1,and synaptophysin.Reverse transcription quantitative polymerase chain reaction was applied to detect the mRNA expression of PSD95 and the levels of miR-1-3p/miR-206-3p.Results EGb supplement alleviated the learning and memory deficits induced by SCO in behavioral experiments.Moreover,EGb treatment attenuated synaptic damage elicited by SCO,manifested as increased dendritic spine density and the proportion of mushroom-type spines in hippocampal neurons.Further investigation indicated that EGb rescued the expression of synaptic-related proteins,especially PSD95,and decreased the levels of miR-1-3p/miR-206-3p in the rat hippocampus.Conclusion The application of EGb effectively treats SCO-induced memory impairments probably by suppressing miR-1-3p/miR-206-3p and elevating the expression of PSD95.
文摘患者,男,49岁,2022年1月至温州医科大学附属舟山医院就诊,自诉1月余前无明显诱因下出现行走不稳,后症状持续存在。该患者既往有血栓性静脉炎,无动脉或静脉血栓家族史;有2次急性脑梗死发作史,于上海交通大学医学院附属瑞金医院行易栓症相关检测,发现蛋白S总量为26.7%,基因检测结果为蛋白S的编码基因PROS1第15号外显子发生c.1955A>T,p.Asp652Val杂合突变。该患者被诊断为遗传性蛋白S缺乏症(protein S deficiency,PSD),之后长期口服利伐沙班片抗凝。此次查体除行走稍不稳外,其余无明显异常;静脉血栓栓塞症(venous thromboembolism,VTE)风险评估量表(Padua模型)评分为6分,判定为VTE高危患者。动态心电图显示窦性心律,偶发房性早搏、室性早搏;四肢血管B超显示双侧腘动脉、胫后动脉多发血栓形成伴局部狭窄,右侧桡动脉闭塞;心脏超声及颈动脉超声未见明显异常;颅脑MRI结果显示左侧基底节区脑梗死陈旧性病灶。CT血管造影联合三维重建显示左侧大脑中动脉M1段重度狭窄、闭塞可能,两侧颈内动脉虹吸段狭窄、硬化。该患者最终被诊断为PSD合并脑梗死及外周动脉阻塞。治疗采用瑞舒伐他汀钙片调脂稳定斑块,利伐沙班片抗凝,琥珀酸美托洛尔缓释片控制心室率,叶酸片改善代谢;治疗10 d后,患者症状好转。
文摘Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefore, agent(s) capable of inhibiting brain amyloid deposition might delay the occurrence or retard the progress forwards of AD and related neurobehavioral symptoms. Here, we report whether, chronic oral administration of Syzygium cumini (locally known as Jam)-seed extract exerts protection against the progressive cognitive decline in the Aβ1-40-infused AD model rats. After 12 weeks of feeding with S. cumini seed extract (at 300 mg/kg BW), we evaluated the learning-related memory of the rats by 8-arm radial maze task, where we determined two types of memory errors, namely reference memory errors (RMEs) and working memory errors (WMEs). After completion of memory tests, rats were sacrificed and the levels of lipid peroxide (LPO), the Aβ1-40-burden, Aβ1-40-oligomers, proinflammatory TNFα, brain derived neurotrophic factor (BDNF), Tyrosine-kinase B (TrkB), postsynaptic-density protein 95 (PSD-95) and Synapse-associated protein (SNAP-25) were determined in the corticohippocampal tissues of the brain. In addition, in vitro antioxidative effects of S. cumini seed extract were evaluated. The oral administration of S. cumini extract significantly increased the memory-related learning ability of the AD model rats, concomitantly with reductions in the levels of corticohippocampal Aβ1-40-burden and Aβ1-40-oligomers. Furthermore, the extract suppressed the levels of TNFα and LPO in the corticohippocampal tissues of the AD rats and also the later in the plasma, suggesting an anti-oxidative and anti-inflammatory activities of the S. cumini extract in the brains of AD model rats. S. cumini extract also increased the levels of brain cognition and memory-related proteins, including BDNF, TrKB, PSD-95 and SNAP-25. We thus suggest that S. cumini-seed extract could be used in neurobehavioral deficits and associated pathogenesis of Alzheimer’s disease.
文摘This paper is the second step of our work. The first step presents a set of parametric studies performed on automotive radiators by designing different heat exchanger models. The analysis focuses on the cooling performance for automobile radiator by changing several dimensions of the radiator fin phase (P2.5, P2.4, P2.3, P2.2, and P2.1) as well as the importance of coolant flow lay-out on the radiator global performance [1]. The second step consists on the study of the vibration fatigue of the sample with the best heat dissipation performance we design (radiator P2.1). We use Hyper Mesh to proceed with the finite element model. Frequency response analysis is solved by using MSC. Nastran (MSC. MD. Nastran. v2010.1.3-MAGNiTUDE), fatigue durability ana-lysis by using MSC Fatigue. In this experiment, the frequency response of the unit load (the unit load is 1 g) is analyzed. Based on the analysis of the frequency response of the unit load, the fatigue life of the radiator is analyzed by the PSD (power spectral density) curve and the S-N curve. From our experiments results, we observe that the radiator we design meets the international requirements of fatigue vibration under automobile normal working condition.