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Population pharmacokinetics of valproate in Chinese children with epilepsy

Acta Pharmacologica Sinica 2007年第10期28卷 1677-1684页

作者： De-chun JIANG~(2.3),Li WANG~4,Yu-qin WANG~(2.6),Lin LI~3,Wei LU~5,Xiang-rong BAI~2.2.department of Pharmacy,xuan-{2. hospital of Capital medical university,beijing 100053,china ~4 department of Pediatrics,Peking universityFirst hospital,beijing 100034,china ~3 department of pharmacology,xuan-{2. hospital of Capital medical university,education ministry keylaboratory for neurodegenerative diseases,beijing 100053,china ~5 School of Pharmaceutical Science,Peking university,beijing 100083,china department of Pharmacy Xuan-wu Hospital of Capital Medical University Beijing China department of pharmacology Xuan-wu Hospital of Capital Medical University Education Ministry Key Laboratory for Neurodegenerative Diseases Beijing China department of Pediatrics Peking University First Hospital Beijing China School of Pharmaceutical Science Peking University Beijing China

Aim:The aim of the present study is to establish a population pharmacokinetic（PPK） model of valproate （VPA） in Chinese epileptic children to promote thereasonable use of anti-epileptic ***:Sparse data of VPA serumconcentrations from 417 epileptic children were *** patients weredivided into 2.groups:the PPK model group （n=317） and the PPK valid group（n=100）.The PPK parameter values of VPA were calculated by NONMEM soft-ware using the data of the PPK model group.A basic model and a final modelwere set *** validate the 2.models,the concentrations of PPK valid groupwere predicted by each model,*** mean prediction error （MPE）,mean squared prediction error （MSPE）,root mean squared prediction error（RMSPE）,weight residues （WRES）,and the 95% confidence intervals （95%CI） were also ***,the values between the 2.models were ***:The PPK of VPA was determined by a 1-compartment model with afirst-order absorption *** basic model was:Ka=3.09 (h-1),V/F=2..4（L）,CL/F=0.2.6 （L/h）.The final model was:Ka=0.2.1+2.2.·（1-HS）(h-1),V/F=2.88+0.157·WT （L）,CL/F=0.1060.98·CO+0.0157·AGE （L/h）.For thebasic model,the MPE,MSPE,RMSPE,WRES,and the 95% CI were-2..53（-30.36,-16.70）,372..96 （2.72.72.4585.2.）,39.62.（34.34,44.90）,and-0.06 （-0.14,0.02.,*** the final model,the MPE,MSPE,RMSPE,WRES,and the95% CI were-1.16 （-4.85,2.53）,1002.83 （1050.64,1143.61）,2..04 （2..12.2..96）,and0.08 （-0.04,0.2.）,*** final model was more optimal than the ***:The PPK model of VPA in Chinese epileptic children wassuccessfully *** will be valuable to facilitate individualized dosageregimens.

关键词： population pharmacokinetics valproic acid epilepsy children Bayesian method NONMEM software individualized dosage regimens

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ERK pathway activation is required for amyloid-β1-40-induced neurotoxicity of THP-1 human monocytes towards SK-N-SH neuroblastoma

ERK pathway activation is required for amyloid-β1-40-induce...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Lin-Lin YIN~1,Wei LI~2.Yan-Qi CHU~1,Lin LI~(1,*) 1 department of pharmacology,{2.-wu hospital of Capital medical university,education ministry Key Laboratory for neurodegenerative Disease,45 Chang-chun Street,beijing 100053,china 2.department of Neurology,Henan Provincial People’s hospital,7 Wei-wu Road,Zhengzhou 450003,china

Alzheimer’s disease(AD) is characterized by amyloid-P peptide deposition,increased activated microglia and progressive loss of neurons in the *** Aβ can elicit inflammation in microglia,the intracellular signaling events mediating these effects are poorly *** we show that cell-free supernatant from Aβ-treated THP-1 monocytes induced cytotoxicity towards neuroblastoma SK-N-SH *** of THP-1 monocytes to Aβ leads to increased tyrosine phosphorylation and extracellular signaling-regulated kinase(ERK) and increased levels of inflammatory cytokines(IL-1β,IL-8 and TNF-α) in the supernatant of THP-1 *** of THP-1 monocytes with either a protein tyrosine kinase(PTK) inhibitor or an ERK inhibitor protects SK-N-SH cells from the cytotoxic effect of conditional supernatant from Aβ-treated THP-1 monocytes.Aβ-treated THP-1 monocytes also leads to upregulation of cyclooxygenase-2.and iNOS expression and increased of nitric oxide *** results suggest that Aβ-induced activation of PTK/MEK/ERK pathway in THP-1 monocytes leads to the release of inflammatory factors that are toxic to SK-N-SH cells and might contribute to the onset of AD.

关键词： amyloid-β1-40 inflammation THP-1 monocytes SK-N-SH neuroblastoma cells PTK/MEK/ERK pathway

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Morroniside prevents peroxide-induced apoptosis by induction of endogenous glutathione in human neuroblastoma cells

Morroniside prevents peroxide-induced apoptosis by induction...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Wen WANG~1,Wen-Ting HUANG~2.Lin Li~(1,3),Hou-Xi AI~1,Fang-Ling SUN~2.Ci LIU~1.Yi AN~2.1 department of pharmacology,{2.-wu hospital of Capital medical university,Key Laboratory for neurodegenerative diseases of ministry of education,beijing 100053,{12. 2.chool of Life Science and Technology,beijing Institute of Technology,beijing 100081,{12.

(1) Morroniside belongs to an extensive group of natural iridorid *** the present study,using human neuroblastoma SH-SY5Y cells,we have investigated the protective effects of this compound on modifications in endogenous reduced glutathione(GSH),intracellular oxygen species(ROS) and apoptotic death on HO-mediated cytoxicity. (2. Incubation of cells with morroniside led to a significant dose-dependent elevation of cellular GSH accompanied by a marked protection against H2.2.mediated *** at 1-100μmol/L inhibited the formation of ROS and the activation of caspase-3 and 9,and the upregulation of Bcl-2.whereas no significant change occurred in Bax levels.(3) Our results indicated that the anti-oxidative and anti-apoptotic properties render this natural compound potentially protective against HO-induced cytotoxicity.(4) This study suggested that intracellular GSH appeared to be an important factor in morroniside-mediated cytoprotection against HO-toxicity in SH-SY5Y cells.

关键词： morroniside antioxidant apoptosis human neuroblastoma cell iridorid glycoside neurodegenerative disorders cornus officinalis

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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan department of Neurology Peking University Third HospitalBeijingChina beijing Municipal Key Laboratory of Biomarker and Translational Research in neurodegenerative {2. BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking university Third {2. between January 2.2. and May 2.2..A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72.95%CI=0.58–0.89,P=0.002.,and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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Brain activity in Parkinson's disease patients with mild cognitive impairment

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Science Bulletin 2016年第24期61卷 1876-1883页

作者： Linlin Gao Xuemin wu Jiarong Zhang Piu Chan Tao wu department of Neurobiology Key Laboratory on Neurodegenerative Disorders of Ministry of Education Beijing Institute of Geriatrics Xuanwu Hospital Capital Medical University beijing Key Laboratory on Parkinson’s Disease Parkinson Disease Center of Beijing Institute for Brain Disorders Community Health Station China University of Mining and Technology

Mild cognitive impairment(MCI) is common in patients with Parkinson's disease(PD), yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain activity of PD patients with MCI(PD-MCI) relative to cognitively normal PD patients(PD-CN) and healthy control(HC)subjects. In this work, 13 PD-MCI patients, 16 PD-CN patients, and 16 HC subjects completed resting state functional MRI. Spontaneous brain activity was measured by calculating amplitude of low frequency fluctuation(ALFF) values across the whole brain. Between-group differences and correlations between ALFF values and cognitive test scores were analyzed. ALFF values decreased in the right superior temporal gyrus and increased in the left middle temporal gyrus and left superior frontal gyrus of PD-MCI patients compared with PD-CN patients. In the PD-MCI group, ALFF values in the left middle temporal gyrus were negatively correlated with Montreal Cognitive Assessment and vocabulary test scores,and the ALFF values in the left superior frontal gyrus were negatively correlated with vocabulary test scores. Our study demonstrates that PD-MCI is associated with abnormal spontaneous brain activity in the temporal and frontal lobes. These findings inform the underlying neural mechanism of cognitive impairment in PD.

关键词：帕金森病认知障碍脑活动患者功能磁共振成像认知功能障碍神经机制 ALF

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The study of brain functional connectivity in Parkinson’s disease

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Translational Neurodegeneration 2016年第1期5卷 145-151页

作者： Lin-lin Gao Tao wu department of Neurobiology Key Laboratory on Neurodegenerative Disorders of Ministry of EducationBeijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityBeijing 100053China beijing Key Laboratory on Parkinson’s Disease Parkinson Disease Center of Beijing Institute for Brain DisordersBeijingChina

Parkinson’s disease(PD)is a neurodegenerative disorder primarily affecting the aging *** neurophysiological mechanisms underlying parkinsonian symptoms remain *** affects extensive neural networks and a more thorough understanding of network disruption will help bridge the gap between known pathological changes and observed clinical presentations in *** of neuroimaging techniques,especially functional magnetic resonance imaging,allows for detection of the functional connectivity of neural networks in patients with *** review aims to provide an overview of current research involving functional network disruption in PD relating to motor and non-motor *** into functional network connectivity will further our understanding of the mechanisms underlying the effectiveness of clinical interventions,such as levodopa and deep brain stimulation *** addition,identification of PD-specific neural network patterns has the potential to aid in the development of a definitive diagnosis of PD.

关键词： Parkinson’s disease Functional connectivity fMRI

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Advances of nanoparticles as drug delivery systems for disease diagnosis and treatment

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Chinese Chemical Letters 2023年第2期34卷 65-88页

作者： Rui Liu Cong Luo Zhiqing Pang Jinming Zhang Shaobo Ruan Meiying wu Lei Wang Tao Sun Nan Li Liang Han Jinjin Shi Yuanyu Huang Weisheng Guo Shaojun Peng Wenhu Zhou Huile Gao Key Laboratory of Drug-Targeting and Drug Delivery System of the education ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China department of Pharmaceutics School of PharmacyFudan UniversityKey Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 200433China State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130China Advanced Research Institute of Multidisciplinary Science Beijing Institute of TechnologyBeijing 100081China School of Pharmaceutical Sciences(Shenzhen) Sun Yat-sen UniversityShenzhen 518107China School of Pharmaceutical Sciences Zhengzhou UniversityKey Laboratory of Targeting Therapy and Diagnosis for Critical DiseasesZhengzhou 450001China Tianjin Key Laboratory of Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China Jiangsu Key Laboratory of Neuropsychiatric diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China Advanced Research Institute of Multidisciplinary Science School of Life ScienceKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Radiology Center Key Laboratory of Molecular Target&Clinical PharmacologySchool of Pharmaceutical Sciences&The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China Zhuhai Institute of Translational Medicine Zhuhai People's Hospital(Zhuhai hospital affiliated with Jinan University)Zhuhai 519000China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China

Decades have passed since the first nanoparticles-base medicine was approved for human cancer treatment, and the research and development of nanoparticles for drug delivery are always ***, the significant advances complicate nanoparticles’ branches, including liposomes, solid lipid nanoparticles, inorganic nanoparticles, micelles, nanovaccines and nano-antibodies, etc. These nanoparticles show numerous capabilities in treatment and diagnosis of stubborn diseases like cancer and neurodegenerative diseases, emerging as novel drug carriers or therapeutic agents in future. In this review, the complicated branches of nanoparticles are classified and summarized, with their property and functions concluded. Besides, there are also some delivery strategies that make nanoparticles smarter and more efficient in drug delivery, and frontiers in these strategies are also summarized in this review. Except these excellent works in newly-produced drug delivery nanoparticles, some points of view and future expectations are made in the end.

关键词： Nanoparticles Drug delivery Nanomaterials Delivery strategies Specific delivery Disease diagnosis Disease treatment

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Abnormal white matter microstructure in Parkinson's disease revealed by diffusion tensor imaging A non-randomized concurrent control observation

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Neural Regeneration Research 2010年第2期5卷 98-101页

作者： Jiangtao Liu Kuncheng Li Jinglin Zhang Xiaoli wu Biao Chen department of Radiology Xuanwu Hospital Capital Medical University Beijing 100053 China Key Laboratory of ministry of education on {2. diseases Xuanwu Hospital Capital Medical University Beijing 100053 China

BACKGROUND： Imaging has been used to determine gray matter volume and metabolism in subjects with depressed Parkinson＇s disease （DPD）. OBJECTIVE： To reveal abnormalities in orbitofrontal white matter and the anterior cingulate bundle in depressed and non-depressed Parkinson＇s disease （NDPD） patients using diffusion tensor imaging. DESIGN, TIME AND SETTING： A non-randomized, concurrent, control, neuroimaging study was performed at the Laboratory of neurodegenerative diseases and Center of Neuroimage, {2.wu hospital of Capital medical university from July 2.08 to January 2.09. PARTICIPANTS： A total of 30 Parkinson＇s disease patients, including 14 males and 16 females, were included in the present study. All patients met Brain Bank criteria for idiopathic Parkinson＇s disease formulated by the United Kingdom Parkinson＇s Disease Society. Patients, who underwent previous head surgery, exhibited abnormal density on T2.weighted images, or Mini-Mental State Examination scores 〈 corresponding education level, were excluded from the study. METHODS： All 35 patients underwent MRI scans, including traditional T2.weighted and DTI scans. The patients were assigned to DPD （n = 16） and NDPD （n = 14） groups according to the Diagnostic and Statistical Manual of Mental Disorders-IV （DSM-IV） criteria. The fractional anisotropy values of regions of interest were compared between the NDPD and DPD groups. MAIN OUTCOME MEASURES： Abnormalities in the orbitofrontal white matter and anterior cingulate bundle. RESULTS： Compared with the NDPD group, the DPD group exhibited significantly lower fractional anisotropy values in orbitofrontal white matter and anterior cingulate bundle （P 〈 0.05）. CONCLUSION： Microstructure abnormalities existed in the orbitofrontal and anterior cingulate regions in DPD patients. This is the first report of abnormalities in the orbitofrontal white matter region in DPD patients.

关键词： Parkinson's disease depression diffusion tensor imaging fractional anisotropy

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Seropositivity rates of water channel protein 4 antibodies compared between a cell-based immunofluorescence assay and an enzyme-linked immunosorbent assay in neuromyelitis optica patients

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Neural Regeneration Research 2011年第32期6卷 2490-2494页

作者： Xiaoli wu Zhangyuan Liao Jing Ye Huiqing Dong ChaodongWang Piu Chan department of Neurology and Key Laboratory ministry of {2. on neurodegenerative diseases Xuanwu Hospital of Capital MedicalUniversity Beijing 100053 China department of Neurology Xuanwu Hospital of Capital Medical University Beijing 100053 China

A total of 66 samples （from 2. cases with neuromyelitis optica, 2. cases with multiple sclerosis, aa 13 cases with optic neuritis） were tested for aquaporin-4 antibody by a cell-based immunofluorescence assay and an enzyme-linked immunosorbent assay. The sensitivities and specificities of the two assays were similar. We further analyzed an additional 68 patients and 93 healthy controls using the enzyme-linked immunosorbent assay. A Kappa test showed good consistency between the two methods in terms of detection of anti-aquaporin-4 antibody in the se of neuromyelitis optica patients. No significant correlations were identified with onset age or disea duration, suggesting that aquaporin-4 antibody is a good marker for neuromyelitis optica. The enzyme-linked immunosorbent assay can be used for quantifying aquaporin-4 antibody concentrations and may be useful to dynamically monitor changes in the levels of aquaporin-4 antibody during disease duration.

关键词： neuromyelitis optica cell-based immunofluorescence assay anti-aquaporin 4 antibody enzyme-linked immunosorbent assay long and extended spinal cord lesions neural regeneration

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DYT1 MUTATIONS AMONGST EARLY ONSET PRIMARY DYSTONIA PATIENTS IN china

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Chinese medical Sciences Journal 2008年第1期23卷 38-43页

作者： Jing-fang Yang Jian-yu Li Yong-jie Li Tao wu Yan-li Zhang Biao Chen department of Neurobiology Beijing 100053 department of Functional Neurosurgery Key Laboratory for Neurodegenerative Disease of Ministry of Education Xuanwu Hospital of Capital Medical University Beijing 100053

Objective To investigate the frequency of GAG deletion in the DYT1 gene among early onset primary dystonia patients in *** Thirteen patients with early onset primary torsion dystonia were screened for mutation in exon 5 of the DYT1 gene using denaturing high-performance liquid chromatography(DHPLC)and DNA sequencing,and the results were confirmed with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results The GAG deletion mutation which results in Glu302.el in exon 5 of the DYT1 gene was found in 5 *** detecting results were consistent between with DHPLC and *** did not find any other mutations in the DYT1 *** The GAG deletion in the DYT1 gene is common amongst early onset primary torsion dystonia patients in *** frequency of DYT1 mutation is not significantly different between European and Asian patients with early onset primary dystonia.

关键词：肌张力障碍 DYT1基因高效液相色谱法基因突变

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