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抗癫痫药物影响儿童骨矿物质密度及骨代谢的荟萃分析（英文）

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2015年第7期16卷 611-621页

作者： Ying ZHANG Yu-xin ZHENG Jun-ming ZHU Jian-min ZHANG Zhe ZHENG neuroscience Care Unit the Second Affiliated Hospital School of Medicine Zhejiang University department of neurosurgery the Second Affiliated Hospital School of Medicine Zhejiang University

目的:癫痫是神经系统常见病,半数以上患者儿童时期便发病,癫痫病患者常需终身服用抗癫痫药。研究表明,长期服用抗癫痫药物会影响骨代谢,加速骨矿物质的丢失,导致骨质疏松。但是,每种抗癫痫药物的具体作用还不清楚。作为典型的肝酶诱导... 详细信息

目的:癫痫是神经系统常见病,半数以上患者儿童时期便发病,癫痫病患者常需终身服用抗癫痫药。研究表明,长期服用抗癫痫药物会影响骨代谢,加速骨矿物质的丢失,导致骨质疏松。但是,每种抗癫痫药物的具体作用还不清楚。作为典型的肝酶诱导剂的抗癫痫药物,卡马西平已经公认有降低骨密度的作用,但是作为非肝酶诱导剂的丙戊酸钠,还没有定论。在新型抗癫痫药物中,奥卡西平、托吡酯和拉莫三嗪等对骨密度似乎没有影响,但目前相关的研究很少,各研究所得结果也不一致。本研究拟通过荟萃分析评估抗癫痫药对癫痫病儿童骨密度和骨代谢的影响。创新点:目前已有荟萃分析评估抗癫痫药对成人骨密度的影响,但尚无研究分析抗癫痫药对儿童的影响。方法:检索PubMed和Web of Science数据库中评估抗癫痫药与儿童骨密度及骨代谢关系的临床试验。入选标准为:(1)至少包括一项骨代谢的标志物;(2)骨密度用双能×线吸收计量法计算;(3)研究结果包括平均的骨密度和骨密度的标准差;(4)年龄小于18岁;(5)患者采用单药或多药治疗;(6)具有健康对照组;(7)必须是观察性研究或随机对照研究。采用固定效应模型和随机效应模型对22篇文献的1492例患者中的骨密度及骨代谢资料进行荟萃分析,结果用加权均数差(WMD)或标准均数差(SMD)进行评估。结论:共22篇文献符合纳入标准,共计1492例患者。荟萃分析的结果显示,抗癫痫药物的使用可以引起儿童:(1)腰椎、转子、股骨颈的骨密度和全身骨密度的下降;(2)维生素D下降和血清碱性磷酸酶的上升;(3)甲状旁腺激素、钙和磷没有显著改变。荟萃分析的结果表明,抗癫痫药的使用可能和癫痫病患儿骨密度降低相关。

关键词：抗癫痫药骨密度骨代谢荟萃分析

Neural stem cell-derived exosome as a nano-sized carrier for BDNF delivery to a rat model of ischemic stroke

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Neural Regeneration Research 2023年第2期18卷 404-409页

作者： Zhi-Han Zhu Feng Jia Waqas Ahmed Gui-Long Zhang Hong Wang Chao-Qun Lin Wang-Hao Chen Lu-Kui Chen department of neurosurgery School of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina department of neurosurgery Neuroscience CenterCancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouGuangdong ProvinceChina department of neurosurgery The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of neurosurgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Our previo us study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes(hNSC-Exo)in ischemic stroke.Here,we loaded brain-derived neurotrophic factor(BDNF)into exosomes derived from NSCs to construct engineered exosomes(BDNF-hNSC-Exo)and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in vivo.In a model of H_(2)O_(2)-induced oxidative stress in NSCs,BDNF-hNSC-Exo markedly enhanced cell survival.In a rat middle cerebral arte ry occlusion model,BDNF-hNSC-Exo not only inhibited the activation of microglia,but also promoted the differentiation of endogenous NSCs into neurons.These results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stro ke.Our research may support the clinical use of other neurotrophic factors for central nervous system diseases.

关键词： brain-derived neurotrophic factor exosome inflammation ischemic stroke neural stem cell neurogenesis neurological recovery transplantation

Seasonal variations of nonmotor symptoms in patients with Parkinson's disease in Southeast China

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Chinese Medical Journal 2023年第4期136卷 415-422页

作者： Jingyi Wang Kangping Xiong Jingyuan Chao Sheng Zhuang Jie Li Chunfeng Liu department of Neurology and Clinical Research center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China Sleep center The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China Institute of neuroscience Soochow UniversitySuzhouJiangsu 215123China

Background:Studies suggest seasonal fluctuations of symptoms in Parkinson’s disease(PD)patients in Western countries.However,the association between seasonal change and variation in nonmotor symptoms(NMS)in Chinese PD patients is unclear.Here,we studied whether there is a change rule with annual cycle with severity of NMS for patients with PD in Southeast China.Methods:We studied 1005 PD patients between April 2008 and October 2020.Patients were classified into four seasons according to the 24 Chinese solar terms,based on assessment date.We compared comprehensive NMS scales and polysomnography parameters among groups and conducted further analysis of disease severity.Results:Among the 1005 patients studied,the mean age was 64.2±9.7 years and 569(56.6%)of them were men.Relative to the summer group,patients assessed during winter had higher Scales for Outcomes in Parkinson’s disease-Autonomic Dysfunction(SCOPA-AUT)scores(P=0.045).The sleep efficiency factor scores of Pittsburgh Sleep Quality Index in patients were higher during spring than summer(P=0.009).Among patients who completed polysomnography during the same period(n=135),compared with summer follow-ups,we observed a higher percentage of NREMS1 in winter and spring follow-ups(P=0.042,P=0.011),a higher NREMS1 time in spring follow-ups(P=0.0024),a lower NREMS2 time in winter follow-ups(P=0.007),and a higher percentage of phasic rapid eye movement(REM)-sleep without atonia in autumn and winter follow-ups(P=0.026 and P=0.020,respectively).In a subset of patients with PD and REM sleep behavior disorder(RBD;n=182),those visited during winter had higher scores for RBD questionnaire-Hong Kong and its factor 1(dream-related sub-score)than those visited during summer(P=0.034,P=0.020).We observed similar findings for SCOPA-AUT and sleep efficiency factor scores in early stage patients in subgroup analysis.Conclusions:PD patients assessed for follow-up during summer showed less severe symptoms of autonomic dysfunction and RBD symptoms than those assessed in winter,and l

关键词： Nonmotor symptoms Parkinson’s disease Seasonal variations

Clinical Significance of REM Sleep Behavior Disorders and Other Non-motor Symptoms of Parkinsonism

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neuroscience Bulletin 2017年第5期33卷 576-584页

作者： Hong Jin Jin-Ru Zhang Yun Shen Chun-Feng Liu department of Neurology and Sleep center The Second Affiliated Hospital of Soochow University Institute of neuroscience Soochow University

Rapid eye movement sleep behavior disorder （RBD） is one of the most common non-motor symptoms of parkinsonism, and it may serve as a prodromal marker of neurodegenerative disease. The mechanism underlying RBD is unclear. Several prospective studies have reported that specific non-motor symptoms predict a conversion risk of developing a neurodegenerative disease, including olfactory dysfunction, abnormal color vision, autonomic dysfunction, excessive daytime sleepiness, depression, and cognitive impairment. Parkinson＇s disease （PD） with RBD exhibits clinical heterogeneity with respect to motor and non-motor symptoms compared with PD without RBD. In this review, we describe the main clinical and pathogenic features of RBD, focusing on its association with other non-motor symptoms of parkinsonism.

关键词： Parkinson＇s disease · Rapid eye movement sleep behavior disorder · Risk factors ·Parkinsonism

Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage

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neuroscience Bulletin 2021年第4期37卷 535-549页

作者： Yang Cao Yin Li Chao He Feng Yan Jian-Ru Li Hang-Zhe Xu Jian-Feng Zhuang Hang Zhou Yu-Cong Peng Xiong-Jie Fu Xiao-Yang Lu Yuan Yao Yu-Yu Wei Yun Tong Yi-Fu Zhou Lin Wang department of neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou310009China

Ferroptosis is a form of iron-dependent regulated cell death.Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage(SAH)is still lacking.In the present study,we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation.In in vivo experiments,we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH.Moreover,liproxstatin-1 attenuated the neurological deficits and brain edema,reduced neuronal cell death,and restored the redox equilibrium after SAH.The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acylCoA synthetase long-chain family member 4 as well as cyclooxygenase 2.In addition,liproxstatin-1 decreased the activation of microglia and the release of IL-6,IL-1 b,and TNF-a.These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.

关键词： Subarachnoid hemorrhage Ferroptosis Inflammation Liproxstatin-1

HLY78 Attenuates Neuronal Apoptosis via the LRP6/GSK3β/β-Catenin Signaling Pathway After Subarachnoid Hemorrhage in Rats

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neuroscience Bulletin 2020年第10期36卷 1171-1181页

作者： Xu Luo Lina Li Weilin Xu Yuan Cheng Zongyi Xie department of neurosurgery The Second Affiliated HospitalChongqing Medical UniversityChongqing 400010China department of Nephrology The Third Affiliated HospitalChongqing Medical UniversityChongqing 401120China department of neurosurgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Neuronal apoptosis is one of the essential mechanisms of early brain injury after subarachnoid hemorrhage(SAH).Recently,HLY78 has been shown to inhibit apoptosis in tumor cells and embryonic cells c aused by carbon ion radiation through activation of the Wnt/β-catenin pathway.This study was designed to explore the anti-apoptotic role of HLY78 in experimental SAH.The results demonstrated that HLY78 attenuated neuronal apoptosis and the neurological deficits after SAH through the activation of low-density lipoprotein receptor-related protein 6(LRP6),which subsequently increased the level of phosphorylated glycogen synthesis kinase 3 beta(p-GSK3β)(Ser9),β-catenin,and Bcl-2,accompanied by a decrease of p-β-catenin,Bax,and cleaved caspase 3.An LRP6 small-interfering ribonucleic acid reversed the effects of HLY78.In conclusion,HLY78 attenuates neuronal apoptosis and improves neurological deficits through the LRP6/GSK3β/β-catenin signaling pathway after SAH in rats.HLY78 is a promising therapeutic agent to attenuate early brain injury after SAH.

关键词： Subarachnoid hemorrhage HLY78 LRP6 Neuronal apoptosis

Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis

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Cancer Biology & Medicine 2020年第1期17卷 154-168页

作者： Caijun Zha Xiangqi Meng Lulu Li Shan Mi Da Qian Ziwei Li Pengfei Wu Shaoshan Hu Shihong Zhao Jinquan Cai Yanhong Liu department of Laboratory Diagnosis The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China department of neurosurgery The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China neuroscience Institute Heilongjiang Academy of Medical SciencesHarbin 150086China

Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown.This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment.Methods:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically evaluated.The effects of NETs on glioma cell progression were studied in a co-culture system.In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of gliomas.Results:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma.NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion.NETs overproduction promoted glioma cell proliferation,migration,and invasion.Furthermore,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro.In addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in glioblastoma.Subsequently,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in TINs.Conclusions:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis.Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.

关键词： Neutrophil extracellular traps HMGB1 IL-8 NF-κB glioma microenvironment

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect:a large Chinese cohort

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Stroke & Vascular Neurology 2024年第1期9卷 50-58页

作者： Yang Zhao Junlin Lu Hongqi Zhang Tianxiao LI Donglei Song Sheng Guan Aisha Maimaitili Yunyan Wang Wenfeng Feng Yang Wang Jieqing Wan Guohua Mao Huaizhang Shi Xinjian Yang Jianmin Liu Yuanli Zhao department of neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of neurosurgery Peking University International HospitalBeijingChina department of neurosurgery West China HospitalSichuan UniversityChengduSichuanChina department of neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina department of Interventional Neuroradiology Zhengzhou University People's HospitalZhengzhouHenanChina department of neurosurgery Shanghai Donglei Brain HospitalShanghaiChina department of Interventional Neuroradiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina department of neurosurgery The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiangChina department of neurosurgery Qilu Hospital of Shandong University QingdaoJinanShandongChina department of neurosurgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina department of neurosurgery The First Affiliated Hospital of Nanchang UniversityNanchangJiangxiChina department of neurosurgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina department of neurosurgery The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxiChina department of neurosurgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina department of neurosurgery Changhai HospitalNaval Medical UniversityShanghaiChina

Background Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding,relieves symptoms and improve the quality of life for patients.This study aimed to assess the safety and efficacy of Pipeline Embolization Device(PED,Covidien/Medtronic,Irvine,CA)treatment for intracranial aneurysms presenting with mass effect in real-world settings.Methods We selected patients from the PED in China Post-Market Multi-center Registry Study with mass effect presentation.The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up(3–36 months).We conducted multivariate analysis to identify factors associated with mass effect relief.Subgroup analyses by aneurysm location,size and form were also performed.Results This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0%(162/218).The postoperative mass effect deterioration rate was 9.6%(21/218).During a median follow-up period of 8.4 months,the mass effect relief rate was 71.6%(156/218).Notably,immediate aneurysm occlusion following treatment was significantly associated with mass effect relief(OR 0.392,95%CI,0.170 to 0.907,p=0.029).Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms,while dense embolism impeded symptom relief in aneurysms<10mm and saccular aneurysms.Conclusions Our data confirmed the efficacy of PED in relieving mass effect.The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms.Trial registration number NCT03831672.

关键词： aneurysm intracranial Irvine

Characteristics of diffusion-tensor imaging for healthy adult rhesus monkey brains

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Neural Regeneration Research 2013年第31期8卷 2951-2961页

作者： Xinxiang Zhao Jun Pu Yaodong Fan Xiaoqun Niu Danping Yu Yanglin Zhang department of Radiology Second Affiliated Hospital of Kunming Medical University department of neurosurgery Second Affiliated Hospital of Kunming Medical University department of neurosurgery Third Affiliated Hospital of Kunming Medical University department of Pneumology Second Affiliated Hospital of Kunming Medical University Yiwu hospital affiliated to Zhejiang University School of Medicine

Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional ani- sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum （splenium and genu） as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4-8 years. Results showed no laterality dif- ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of cau- date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the sple- nium of corpus callosum in the white matter, followed by genu of the corpus callosum and the pos- terior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4-8-year-old rhesus monkeys are similar to those of healthy young people.

关键词： neural regeneration neuroimaging rhesus monkey fractional anisotropy brain white matter graymatter MRI diffusion-tensor imaging grants-supported paper neuroregeneration