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Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian Chu Tinglin Zhang Tong Yin Yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang Yan Liu Jie Gao You Yin Department of neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

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Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

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Neural Regeneration Research 2024年第1期19卷 100-115页

作者： Jianjian Chu Weicong Zhang Yan Liu Baofeng Gong Wenbo Ji Tong Yin Chao Gao Danqi Liangwen Mengqi Hao Cuimin Chen Jianhua Zhuang Jie Gao You Yin Department of neurology Second Affiliated Hospital(Shanghai Changzheng Hospital)of Naval Medical UniversityShanghaiChina School of Pharmacy University College LondonLondonUK Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineClinical Pharmacy Innovation InstituteShanghai Jiao Tong University School of MedicineShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease *** re,there is an urgent need for new effective *** underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease *** inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's *** review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's *** review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

关键词： Alzheimer's disease anti-inflammation blood-brain barrier drug delivery microglia nanoparticles neuroinflammation plant extracts

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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 *** 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 *** We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect *** 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 *** analyses by aneurysm location,size and form were also *** 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 *** Our data confirmed the efficacy of PED in relieving mass *** findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial *** registration number NCT03831672.

关键词： aneurysm intracranial Irvine

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MECHANISM OF ACTION OF ARGININE VASOPRESSIN ON ACUTE ISCHEMIC BRAIN EDEMA

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中华医学杂志(英文版) 1991年第6期104卷 480-483页

作者：刘新峰史荫绵林葆城 Department of neurology Changhai Hospital Second Military Medical College Shanghai 200433

The purpose of this experiment is to study the role of arginine vasopressin （AVP） in acute cerebral ischemic edema in Mongolian gerbils. The results show that intracerebroventricular injection （ICV） of AVP exacerbates acute ischemic brain edema, while ICV of AVP antiserum significantly decreases the ischemic brain edema. Nimodipine （calcium antagonist） cannot block this role of AVP in brain edema. In addition, the cortical Na-KATPase activity is significantly decreased, while the cAMP content of ischemic cortex and hypothalamus and the cGMP content of the hypothalamus are markedly increased after AVP ICV. These suggest that AVP may play an important role in the pathophysiologic process of ischemic brain edema by inhibiting the Na-KATPase activity of the cerebral cell membrane and the AVP receptors mediated by cAMP and cGMP.

关键词： CEREBRAL EDEMA RAT

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Delayed onset of nemaline myopathy: a case report

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Chinese Medical Journal 2003年第5期116卷 798-800页

作者：韩燕郑惠民丁素菊 Department of neurology Changhai Hospital Second Military Medical University Shanghai 200433 China

Nemaline myopathy (NM), first reported by Shy et al1 in 1963, is characterized by the presence of nemaline rods in myofibers and in the nucleus in severe cases. NM is a clinically rare, heterogeneous congenital muscle disorder, displaying dominant or recessive autosomal forms, and in rare cases, sporadic as well. Its chief manifestations are proximal muscle weakness and atrophy followed by further progress to generalized weakness and weakness of facial muscles, tongue muscles and throat muscles. Below is the case of an adult onset nemaline myopathy.

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Clinical and genetic study of spinocerebellar ataxia type 7 in East Asian population

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Chinese Medical Journal 2010年第16期123卷 2274-2278页

作者： HAN Yan YU Long ZHENG Hui-min GUAN Yang-tai Department of neurology Changhai Hospital Second Military Medical University Shanghai 200433 China

Background Spinocerebellar ataxia type 7 （SCA7） is known as an autosomal dominant cerebellar ataxia; patients with genetically confirmed diagnoses of SCA7 have increased rapidly in recent ***, SCA7 is a rare subtype of SCA, and most data available about SCA7 are those of white *** aim of the present study was to systematically review the prevalence and clinical and genetic aspects of SCA7 patients in East Asian *** A search for publications on SCA7 was performed by using the ＂PubMed＂ database with the published language limited in *** mainly focusing on the prevalence of SCA7 in patients with SCA and the clinical and genetic features of SCA7 patients were fully reviewed and *** The prevalence of SCA7 in SCA patients ranged from 0 to 7.7%, which was similar to those reported *** clinical manifestations were typically present at the 30＇s of its victims （median, 29 years; interquartile range （IQR）,19.5-36.5 years）, and the symptoms appeared 15 years （（15.17±4.22） years） earlier on average in the offspring than in the *** ataxia and visual impairment were both found in all patients of whom the clinical features were *** SCA7 alleles contained 40-100 CAG repeats, with a median of 47 repeats （IQR, 44.5-50.0）; and the offspring had 13 more repeats on average compared with their parents （12.62±19.03）.A strong negative correlation was found between CAG repeat size and the onset age of patients （r=-0.739, P=0.000）.In addition, no significant difference was found in CAG repeat sizes between patients with visual impairment as the initial symptom and those with gait disturbance as their initial symptom （P=0.476）.Conclusions The prevalence of SCA7 in SCA patients, the age at onset and CAG repeats of SCA7 patients in East Asia are consistent with those of white ***, larger population study is needed to assess the correlation between the CAG repeat size and initial symptoms of

关键词： spinocerebellar ataxia type 7 East Asia clinical features genetics

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Novel drug-delivery approaches to the blood-brain barrier

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Neuroscience Bulletin 2015年第2期31卷 257-264页

作者： Xiaoqing Wang Xiaowen Yu William Vaughan Mingyuan Liu Yangtai Guan Department of neurology Changhai Hospital Second Military Medical University Stem Cells and Medical Research Center Second Military Medical University Department of Gerontology Changhai Hospital Second Military Medical University Department of Genetics Yale University

The blood-brain barrier （BBB） maintains homeostasis by blocking toxic molecules from the circulation, but drugs are blocked at the same time. When the dose is increased to enhance the drug concentration in the central nervous system, there are side-effects on peripheral organs. In recent years, genetic therapeutic agents and small molecules have been used in various strategies to penetrate the BBB while minimizing the damage to systemic organs. In this review, we describe several representative methods to circumvent or cross the BBB, including chemical and physical strategies.

关键词： drug delivery blood-brain barrier nanoparticles focused ultrasound

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Comparative Study of Chuanxiong and Dextran 40 in the Treatment of Acute Cerebral Infuriction

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Chinese Journal of Integrative Medicine 1995年第2期1卷 17-20页

作者： Chen Da-ren(陈达仁) Shi Yin-mian (史荫绵) Tian Gui-qin (田桂琴) and Gong Jie (宫杰) (Department of neurology, changhai hospital, Second Military Medical University, Shanghai) (200433) Department of neurology Changhai Hospital Second Military Medical University Shanghai

This paper reports the results of a double-blind trial in 220 patients with acute cerebral in-farction evidenced by computerized tomography, who were randomly divided into a Chuanxiong group(134 cases) and a low molecular weight dextran group (86 cases) . A weighted scoring system was adopt-ed to evaluate the neurological function and living capability. The results showed that the total therapeuticefficacy rate in the Chuanxiong group and in the dextran 40 group were 86. 6% and 62. 8% *** effects of Chuanxiong on the treatment of acute cerebral infarction was superior to the low molecularweight dextran, and the difference between the two groups was statistically significant (P

关键词： Chuanxiong dextran 40 acute cerebral infarction

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Recombinant-activated factorⅦand neuronal apoptosis in a rat model of intracerebral hemorrhage

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Neural Regeneration Research 2009年第10期4卷 791-795页

作者： Qiang Li Wei Li Suju Ding Jianping Tang Jing Fang Benqiang Deng Tao Wu Department of neurology Ninth People's Hospital of Shanghai Jiao Tong University Shanghai 200011 China Department of neurology Changhai Hospital Second Military Medical University of Chinese PLA Shanghai 200043 China

BACKGROUND： Activated clotting factor VII has been demonstrated to exhibit obvious anti-apoptosis effects. OBJECTIVE： To observe the effect of activated clotting factor VII on neuronal apoptosis at different time points following rat intracerebral hemorrhage （ICH）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Neurobiological Laboratory of Second Military Medical University from October 2005 to April 2006. MATERIALS： Recombinant-activated clotting factor Vlla （rFVtla） was purchased from Danish Novo Nordisk, Denmark. In situ cell death detection kit-POD kit was purchased from Roche, Switzerland. Caspase-3 activity determination kit from Biovision, USA. METHODS： A total of 72 healthy, male, Sprague Dawley rats, aged 5-8 months, were randomly assigned to three groups （n = 24）： sham-operated, ICH model, and rFVIla. In the ICH model and rFVIla groups, 80.0μL autologous non-clotting blood from rat tails was injected into the right caudate putamen to establish the ICH. The empty microinjector was inserted into the caudate putamen in the sham-operated group. The ICH model and rFVIla groups were subdivided into four subsets separately： 6, 24, 72 hours and 7 days following ICH. The rats in the rFVIla group were injected with 160 μg/kg rFVIla via the dorsal vein of the penis. MAIN OUTCOME MEASURES： Apoptotic cells were detected in the right caudate putamen by TUNEL; caspase-3 activity by spectrophotometry; and rat neurological function was evaluated by neurological functional impairment scales. RESULTS： Rat neurological function was deteriorated at 24, 72 hours, and 7 days following ICH. The TUNEL-positive cells and caspase-3 activity in the right caudate putamen was significantly increased in the ICH rats （P 〈 0.05）; rFVlla treatment reduced the number of TUNEL-positive cells and caspase-3 activity in the right caudate putamen （P 〈 0.05）, and neurological function was significantly improved （P 〈 0.05）. CONCLUSION： rFVIla was applie

关键词： intracerebral hemorrhage apoptosis activated clotting factor VII caspase-3 in situ nick-end labeling

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Duration of hypertension is associated with cognitive function： a cross-sectional study in Chinese adults

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Chinese Medical Journal 2014年第11期127卷 2105-2110页

作者： Li Tuo Bai Yu Xiang Junwu Wang Rui Bai Jie Tuo Xiping Zhao Zhongxin Department of Endocrinology Changzheng Hospital Shanghai 200001 China Department of Gastroenterology Changhai Hospital Shanghai 200433 China Department of General Surgery 208 Hospital Shengyang Liaoning 130000 China Department of Health Statistics Second Military Medical University Shanhgai 200433 China Department of Geriatrics Changhai Hospital Shanghai 200433 China Department of neurology Changzheng Hospital Shanghai 200001 China

Background Hypertension （HTN） is a very prevalent public health problem and as the population ages,cognitive impairment （CI） is also going to be a public health ***,the relationship between hypertension duration and cognitive function declination worldwide is still *** aim of the study was to investigate the effects of HTN duration on CI in Chinese *** At baseline,1 386 HTN patients and 293 normotensive （NT） people were *** HTN patients were further divided into four subgroups （duration of HTN 〈6 years,6-10 years,11-20 years,and 〉20 years） according to the HTN duration and were screened for cognitive function with neuropsychological tests including mini-mental-state-examination （MMSE） and clock-drawing-test （CDT） in comparison with the NT *** More HTN patients had CI （45.3%） than NT subjects （30.4%）,and increased with HTN duration （P〈0.000 1）.Compared with the scores of MMSE and CDT in the NT group,the declines were higher in the HTN patients （P 〈0.000 1）,and in the four HTN subgroups,both MMSE and CDT scores fall when the HTN duration increased （P 〈0.05）.Furthermore,in the HTN population without CI,the trend in alteration of CI was relatively mild but still existed （P 〈0.05）.Conclusion People with HTN are more likely to have CI and the possibility and aggravation increases the prolongation of HTN duration,both in amnesic and nonamnesic function.

关键词： cognition impairment hypertension duration mini-mental-state-examination clock-drawing-test epidemiology

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