Alzheimer's disease(AD)is a multifactorial neurodegenerative disorder characterized by the presence of senile plaques and neurofibrillary tangles.Research attempts to identify characteristic factors that are assoc...Alzheimer's disease(AD)is a multifactorial neurodegenerative disorder characterized by the presence of senile plaques and neurofibrillary tangles.Research attempts to identify characteristic factors that are associated with the presence of the AD pathology on the one hand and that increase the risk of developing AD on the other.Changes in non-rapid eye movement(NREM)sleep may meet both requirements for various reasons.First,NREM-sleep is important for optimal memory function.In addition,studies report that the presence of AD pathology is associated with NREM-sleep changes.Finally,more and more results appear to suggest that sleep problems are not only a symptom of AD but can also increase the risk of AD.Several of these studies suggest that it is primarily a lack of NREM-sleep that is responsible for this increased risk.However,the majority investigated sleep only through subjective reporting,as a result of which NREMsleep could not be analyzed separately.The aim of this literature study is therefore to present the results of the studies that relate the AD pathology and NREM-sleep(registered by electroencephalography).Furthermore,we try to evaluate whether NREM-sleep analysis could be used to support the diagnosis of AD and whether NREM-sleep deficiency could be a causal factor in the development of AD.展开更多
Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intrap...Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to100 mg/kg.Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles.Further,orexin neurons in the lateral hypothalamus(LH)and corticotropin-releasing hormone(CRH)neurons in the paraventricular hypothalamic nucleus(PVH)were ablated using viral vector surgery and electrode embedding.The excitability of LH^(orexin)and PVH^(CRH)neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog(c-Fos)expression.Results:Rg1(12.5–100 mg/kg)augmented the duration of non-rapid eye movement(NREM)sleep phases,while reducing the duration of wakefulness,in a dose dependent manner.The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time.We found that these sleep-promoting effects were weakened in the LH^(orexin)and PVH^(CRH)neuron ablation groups,and disappeared in the orexin and CRH double-ablation group.Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons.Conclusion:Rg1 increases the duration of NREM sleep,underscoring the essential roles of LH^(orexin)and PVH^(CRH)neurons in facilitating the sleep-promoting effects of Rg1.Please cite this article as:Wang YY,Wu Y,Yu KW,Xie HY,Gui Y,Chen CR,Wang NH.Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus.J Integr Med.2024;22(6):719–728.展开更多
目的:采用快速卫生技术评估(HTA)的方法,评估恩沙替尼与其他5种已上市的间变性淋巴瘤激酶酪氨酸激酶抑制剂(ALK-TKI)治疗间变性淋巴瘤激酶(ALK)阳性的非小细胞肺癌(NSCLC)的有效性、安全性和经济性差异。方法:计算机检索PubMed、Embase...目的:采用快速卫生技术评估(HTA)的方法,评估恩沙替尼与其他5种已上市的间变性淋巴瘤激酶酪氨酸激酶抑制剂(ALK-TKI)治疗间变性淋巴瘤激酶(ALK)阳性的非小细胞肺癌(NSCLC)的有效性、安全性和经济性差异。方法:计算机检索PubMed、Embase、the Cochrane Library、Web of Science、中国知网、万方数据库、中国生物医学文献服务系统等数据库,以及国际卫生技术评估机构协作网、加拿大药物卫生技术局等卫生技术评估机构官方数据库网站,查找恩沙替尼对比其他5种ALK-TKI(克唑替尼、塞瑞替尼、阿来替尼、布格替尼、洛拉替尼)治疗ALK阳性的NSCLC的HTA报告、系统评价/Meta分析、药物经济学研究,检索时间为建库至2024年9月14日。根据纳入与排除标准筛选文献后,提取资料并进行方法学质量评价,对有效性、安全性和经济性进行对比和描述性分析。结果:共纳入25篇文献,其中系统评价/Meta分析19篇,经济学研究6篇。有效性方面,恩沙替尼在延长中位无进展生存期、提高客观应答率和总生存率方面比第1代ALK-TKI克唑替尼有疗效优势,与其他4种ALK-TKI效果相近;恩沙替尼在未发生脑转移的患者、亚洲患者和不吸烟患者群体中的疗效相比其他ALK-TKI具有非劣性。安全性方面,恩沙替尼发生严重不良反应的概率不低于其他5种ALK-TKI,尤其是发生呼吸系统和皮肤系统的不良反应。经济性方面,在我国医疗卫生体系内,恩沙替尼比克唑替尼、阿来替尼和洛拉替尼更具经济性,与塞瑞替尼和布格替尼的经济性对比仍需更多研究结果支持。结论:恩沙替尼治疗ALK阳性的NSCLC的有效性和经济性均较好,但安全性较差,尤其需要注意呼吸系统和皮肤系统不良反应的发生。展开更多
为探究非高密度脂蛋白胆固醇(non-high density lipoprotein cholesterol, Non-HDL-C)与高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)比值NHHR与肾功能快速下降风险之间的关系。通过使用2011年和2015年中国健康与...为探究非高密度脂蛋白胆固醇(non-high density lipoprotein cholesterol, Non-HDL-C)与高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)比值NHHR与肾功能快速下降风险之间的关系。通过使用2011年和2015年中国健康与养老追踪调查(China health and retirement longitudinal study, CHARLS)数据,分析了4 055名年龄≥40岁并且基线估计肾小球滤过率(estimated glomerular filtration rate, eGFR)≥60 mL/(min·1.73m^(2))的参与者(根据血清肌酐和胱抑素C生成估计肾小球滤过率)。肾功能快速下降定义为eGFR下降≥3 mL/(min·1.73m^(2)·a)。采用多因素logistic回归模型探究NHHR与肾功能快速下降的风险的相关性,同时采用限制性立方样条和阈值效应分析评估二者的剂量-效应关系。结果表明:在4年的随访期间,447名(11.02%)参与者肾功能快速下降。在完全调整的多因素Logistic回归模型中,NHHR最高组(T3)肾功能快速下降风险是NHHR最低组(T1)的1.94倍(OR=1.94,95%CI:1.46~2.61)。当NHHR作为连续变量时,NHHR每升高一个单位,肾功能快速下降风险增加1.21倍(OR=1.21,95%CI:1.08~1.36)。限制性立方样条结果显示,NHHR与肾功能快速下降呈现近似对数曲线的饱和效应关系(P_(nonlinearity)<0.05),拐点分析显示NHHR≤3.52时,随着NHHR升高,肾功能快速下降风险增加。当NHHR>3.52,肾功能快速下降风险趋于饱和。可见在中老年人中,较高的NHHR与纵向肾功能快速下降相关且存在非线性关系。展开更多
药品杂质研究是保证药品质量、安全性的一项关键环节,杂质含量的高低关系着药品质量水平的好坏。当下,药品安全仍然是人们十分关注的公共卫生问题,因此采用高效、准确的检测技术对药品杂质进行系统性分析,可以进一步确保药品的质量安全...药品杂质研究是保证药品质量、安全性的一项关键环节,杂质含量的高低关系着药品质量水平的好坏。当下,药品安全仍然是人们十分关注的公共卫生问题,因此采用高效、准确的检测技术对药品杂质进行系统性分析,可以进一步确保药品的质量安全,为人民群众的健康安全保驾护航。本文结合液相色谱-四级杆/静电场轨道阱高分辨质谱技术(Liquid Chromatography-Quadrupole-Electrostatic Field Orbitrap High Resolution Mass Spectrometry,LC-Q-Orbitrap HRMS)的相关原理,阐明LC-Q-Orbitrap HRMS技术具有高分辨率和高灵敏度的特点。依据LC-Q-Orbitrap HRMS技术优势,介绍LC-Q-Orbitrap HRMS技术在药品杂质研究中的应用,有效解决传统分析方法在杂质检测中所存在的灵敏度不足、选择性差等问题。并重点介绍该技术应用于基因毒性杂质研究方面的进展,实现药品杂质研究的高通量、非靶向快速筛查和结构鉴定,为药品质量控制和安全性评价提供有力的技术支撑,为有关研究学者和监管部门采用准确的检测技术和手段提供理论基础和现实依据。展开更多
基金Supported by the Funds Malou Malou,Perano,Georgette Paulus,JMJS Breugelmans and Gabrielle,François and Christian,Managed by the King Baudouin Foundation of Belgium,No.2021-J1990130-222081.
文摘Alzheimer's disease(AD)is a multifactorial neurodegenerative disorder characterized by the presence of senile plaques and neurofibrillary tangles.Research attempts to identify characteristic factors that are associated with the presence of the AD pathology on the one hand and that increase the risk of developing AD on the other.Changes in non-rapid eye movement(NREM)sleep may meet both requirements for various reasons.First,NREM-sleep is important for optimal memory function.In addition,studies report that the presence of AD pathology is associated with NREM-sleep changes.Finally,more and more results appear to suggest that sleep problems are not only a symptom of AD but can also increase the risk of AD.Several of these studies suggest that it is primarily a lack of NREM-sleep that is responsible for this increased risk.However,the majority investigated sleep only through subjective reporting,as a result of which NREMsleep could not be analyzed separately.The aim of this literature study is therefore to present the results of the studies that relate the AD pathology and NREM-sleep(registered by electroencephalography).Furthermore,we try to evaluate whether NREM-sleep analysis could be used to support the diagnosis of AD and whether NREM-sleep deficiency could be a causal factor in the development of AD.
基金supported by grants from the National Natural Science Foundation of China(No.82174496,No.82374574)Shanghai Key Discipline of Traditional Chinese Medicine Construction Project(No.shzyyzdxk–2024113)。
文摘Objective:This study investigates the sleep-modulating effects of ginsenoside Rg1(Rg1,C_(42)H_(72)O_(14)),a key bioactive component of ginseng,and elucidates its underlying mechanisms.Methods:C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to100 mg/kg.Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles.Further,orexin neurons in the lateral hypothalamus(LH)and corticotropin-releasing hormone(CRH)neurons in the paraventricular hypothalamic nucleus(PVH)were ablated using viral vector surgery and electrode embedding.The excitability of LH^(orexin)and PVH^(CRH)neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog(c-Fos)expression.Results:Rg1(12.5–100 mg/kg)augmented the duration of non-rapid eye movement(NREM)sleep phases,while reducing the duration of wakefulness,in a dose dependent manner.The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time.We found that these sleep-promoting effects were weakened in the LH^(orexin)and PVH^(CRH)neuron ablation groups,and disappeared in the orexin and CRH double-ablation group.Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons.Conclusion:Rg1 increases the duration of NREM sleep,underscoring the essential roles of LH^(orexin)and PVH^(CRH)neurons in facilitating the sleep-promoting effects of Rg1.Please cite this article as:Wang YY,Wu Y,Yu KW,Xie HY,Gui Y,Chen CR,Wang NH.Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus.J Integr Med.2024;22(6):719–728.
文摘目的:采用快速卫生技术评估(HTA)的方法,评估恩沙替尼与其他5种已上市的间变性淋巴瘤激酶酪氨酸激酶抑制剂(ALK-TKI)治疗间变性淋巴瘤激酶(ALK)阳性的非小细胞肺癌(NSCLC)的有效性、安全性和经济性差异。方法:计算机检索PubMed、Embase、the Cochrane Library、Web of Science、中国知网、万方数据库、中国生物医学文献服务系统等数据库,以及国际卫生技术评估机构协作网、加拿大药物卫生技术局等卫生技术评估机构官方数据库网站,查找恩沙替尼对比其他5种ALK-TKI(克唑替尼、塞瑞替尼、阿来替尼、布格替尼、洛拉替尼)治疗ALK阳性的NSCLC的HTA报告、系统评价/Meta分析、药物经济学研究,检索时间为建库至2024年9月14日。根据纳入与排除标准筛选文献后,提取资料并进行方法学质量评价,对有效性、安全性和经济性进行对比和描述性分析。结果:共纳入25篇文献,其中系统评价/Meta分析19篇,经济学研究6篇。有效性方面,恩沙替尼在延长中位无进展生存期、提高客观应答率和总生存率方面比第1代ALK-TKI克唑替尼有疗效优势,与其他4种ALK-TKI效果相近;恩沙替尼在未发生脑转移的患者、亚洲患者和不吸烟患者群体中的疗效相比其他ALK-TKI具有非劣性。安全性方面,恩沙替尼发生严重不良反应的概率不低于其他5种ALK-TKI,尤其是发生呼吸系统和皮肤系统的不良反应。经济性方面,在我国医疗卫生体系内,恩沙替尼比克唑替尼、阿来替尼和洛拉替尼更具经济性,与塞瑞替尼和布格替尼的经济性对比仍需更多研究结果支持。结论:恩沙替尼治疗ALK阳性的NSCLC的有效性和经济性均较好,但安全性较差,尤其需要注意呼吸系统和皮肤系统不良反应的发生。
文摘药品杂质研究是保证药品质量、安全性的一项关键环节,杂质含量的高低关系着药品质量水平的好坏。当下,药品安全仍然是人们十分关注的公共卫生问题,因此采用高效、准确的检测技术对药品杂质进行系统性分析,可以进一步确保药品的质量安全,为人民群众的健康安全保驾护航。本文结合液相色谱-四级杆/静电场轨道阱高分辨质谱技术(Liquid Chromatography-Quadrupole-Electrostatic Field Orbitrap High Resolution Mass Spectrometry,LC-Q-Orbitrap HRMS)的相关原理,阐明LC-Q-Orbitrap HRMS技术具有高分辨率和高灵敏度的特点。依据LC-Q-Orbitrap HRMS技术优势,介绍LC-Q-Orbitrap HRMS技术在药品杂质研究中的应用,有效解决传统分析方法在杂质检测中所存在的灵敏度不足、选择性差等问题。并重点介绍该技术应用于基因毒性杂质研究方面的进展,实现药品杂质研究的高通量、非靶向快速筛查和结构鉴定,为药品质量控制和安全性评价提供有力的技术支撑,为有关研究学者和监管部门采用准确的检测技术和手段提供理论基础和现实依据。
