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Microinjection of preformed alpha-synuclein fibrils into the sublaterodorsal tegmental nucleus mimicked REM sleep behavior disorder and Parkinsonian behaviors in mice

Microinjection of preformed alpha-synuclein fibrils into the...

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中国睡眠研究会第十一届全国学术年会

作者： Yan Shen Zhili Huang Jian Wang Department of Neurology and National Research Center for Aging and Medicine Huashan Hospital Fudan University Department of Pharmacology State Key Laboratory of Medical Neurobiology School of Basic Medical SciencesInstitutes of Brain Science and Collaborative Innovation Center for Brain Science Fudan University

Idiopathic rapid eye movement(REM) sleep behavior disorder(RBD), characterized by the loss of normal skeletal muscle atonia and enactment of violent dream during REM sleep(also coined paradoxical sleep), has been considered as a prodromal biomarker of synucleinopathies such as Parkinson’s disease(PD), multiple system atrophy(MSA) and dementia with Lewy body(DLB). Accumulating clinical and experimental evidence suggests that neurodegeneration or incapacitation of the sublaterodorsal tegmental nucleus(SLD), located within pontine tegmentum and beneath the locus coeruleus(LC), could give rise to the typical phenotype of REM sleep without atonia(RWA) and RBD. Nonetheless, the manipulative incapacitation of the SLD fails to mirror the synucleinopathic essence of idiopathic RBD. To solve this conundrum, we performed stereotaxic inoculation of preformed alpha-synuclein fibrils(PFFs) into mouse SLD and conducted regular polysomnographic recording and Parkinsonian behavior tests. As a result, the PFFs-inoculated mice displayed a loss of normal skeletal muscle atonia and even enactment of violent dream scenarios during REM sleep. Moreover, these mice also exhibited a time-gradient dependent Parkinsonian motor and non-motor deficits, which had been corroborated by the deposition of pathologic alpha-synuclein in corresponding mouse and human brain subregions and nuclei. Given these findings, our study may pave a way for further clarification of the RBD-to-synucleinopathy transition process and provide a potential animal model basis for future blocking target *** rapid eye movement(REM) sleep behavior disorder(RBD), characterized by the loss of normal skeletal muscle atonia and enactment of violent dream during REM sleep(also coined paradoxical sleep), has been considered as a prodromal biomarker of synucleinopathies such as Parkinson’s disease(PD), multiple system atrophy(MSA) and dementia with Lewy body(DLB). Accumulating clinical and experimental evidence su

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Quantitative evaluation of severity of behavioral and psychological symptoms of dementia in patients with vascular dementia

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Translational Neurodegeneration 2013年第1期2卷 52-58页

作者： Wei-Dong Pan Sohei Yoshida Qian Liu Chun-Lan Wu Jun Wang Jin Zhu Ding-Fang Cai Department of Neurology Shuguang Hospital Affiliated to Shanghai University of TCM185Pu-An RoadShanghai 200021China Department of Neurology Kansai University ClinicKansai University of Health Sciences1-11-2 WakabaKumatori-ChoSennan-GunOsaka 590-0482Japan Department of Cardiology Shuguang Hospital Affiliated to Shanghai University of TCM185Pu-An RoadShanghai 200021China laboratory of Neurology Institute of Integrative MedicineZhongshan HospitalFudan University180Fenglin RoadShanghai 200032China

To quantitatively evaluate severity of behavioral and psychological symptoms of dementia(BPSD)for vascular dementia(VD).Changes of 51 patients with VD in BPSD between the first and 24th week were assessed using the Neuropsychiatric Inventory(NPI)and the behavioral pathology in Alzheimer’s disease(BEHAVE-AD)rating scale,in detrended fluctuation analysis(DFA)represented by diurnal activity(DA),evening activity(EA),and nocturnal activity(NA),and the relationships were *** subscores of activity disturbances,diurnal rhythm disturbances,and anxieties and phobias in the BEHAVE-AD score,and that of agitation,irritability,and sleep disorder in the NPI score were significantly increased compared with the first week,as was for the changes for EA in the DFA value.A linear correlation was observed between the changes of activity disturbances plus anxieties and phobias,and those of DA,and between the development of diurnal rhythm and those of EA,the vehement and autism scores and those of DA,and the difference in sleep disorder scores and those of EA,*** of DA,NA,and EA may reflect the fluctuational degrees of VD-BPSD,can provide a useful assessment of VD-BPSD accompanied by clinical scores for VD.

关键词： Vascular dementia Behavioral and psychological symptoms of dementia Rating scale of the behavioral pathology in Alzheimer’s disease Neuropsychiatric inventory Actigraph

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Progress research on non-drug therapy in cancer-related fatigue

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TMR Non-Drug Therapy 2020年第4期3卷 192-198页

作者： Kai Zhou Jia-Yu Zhang Xi-Wei Yang Da Shen Jun-Jin Li Yan-Fang Cheng Xiao-ling Qian Pei-Xian Zhang The First Clinical Medical College of Yunnan University of Traditional Chinese Medicine Kunming 650051China Department of Oncology Yan’an Hospital Affiliated to Kunming Medical UniversityKunming 650051China The People’s Hospital of Shilin Shilin 652200China Key laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province Kunming 650051China

Cancer-related fatigue is the most prevalent and persistently symptom in cancer survivors than any other symptom,which is caused by both the disease and its *** with cancer show a severe symptom of fatigue,which cannot be relieved by general rest or ***-related fatigue negatively impacts a patient's physical and emotional function,social ability and even patients’*** present,the mechanism of cancer-related fatigue remain unclear despite much research,and a variety of mechanisms may contribute to its occurrence and development,including inflammatory reaction,metabolism dysregulation,immune activation,hormonal changes,central nervous system dysfunction,*** a broad variety of drugs and non-drugs interventions are used against cancer-related *** intervention of conventional western medicine mainly contains hematopoietic stimulants,hormones,mental stimulants,and antidepressants,but their widely clinical application is limited by their effectiveness and possible side effects to a certain *** are also many forms of non-drug interventions for managing cancer-related fatigue,such as exercise intervention,psychological intervention,sleep intervention,nutrition intervention,bright white light therapy,*** aim of this review is to provide recommendations of non-drug interventions for patients with CRF during and after cancer treatment,in order to provide an evidence-based guideline for clinicians.

关键词： Cancer-related fatigue Mechanism Non-drug therapy Exercise intervention Psychological intervention sleep intervention

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Hidden Genetic Regulation of Human Complex Traits via Brain Isoforms

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Phenomics 2023年第3期3卷 217-227页

作者： Lu Pan Chenqing Zheng Zhijian Yang Yudi Pawitan Trung Nghia Vu Xia Shen Biostatistics Group School of Life SciencesSun Yat-Sen UniversityGuangzhou 510006China Department of Medical Epidemiology and Biostatistics Karolinska InstitutetStockholm 17177Sweden State Key laboratory of Genetic Engineering School of Life SciencesFudan UniversityShanghai 200433China Center for Intelligent Medicine Research Greater Bay Area Institute of Precision Medicine(Guangzhou)Fudan UniversityGuangzhou 511458China Centre for Global Health Research Usher InstituteUniversity of EdinburghEdinburgh EH89AGUK

Alternative splicing exists in most multi-exonic genes,and exploring these complex alternative splicing events and their resultant isoform expressions is ***,it has become conventional that RNA sequencing results have often been summarized into gene-level expression counts mainly due to the multiple ambiguous mapping of reads at highly similar ***-level quantification and interpretation are often overlooked,and biological interpretations are often deduced based on combined transcript information at the gene ***,for the most variable tissue of alternative splicing,the brain,we estimate isoform expressions in 1,191 samples collected by the Genotype-Tissue Expression(GTEx)Consortium using a powerful method that we previously *** perform genome-wide association scans on the isoform ratios per gene and identify isoform-ratio quantitative trait loci(irQTL),which could not be detected by studying gene-level expressions *** analyzing the genetic architecture of the irQTL,we show that isoform ratios regulate edu-cational attainment via multiple tissues including the frontal cortex(BA9),cortex,cervical spinal cord,and *** tissues are also associated with different neuro-related traits,including Alzheimer’s or dementia,mood swings,sleep duration,alcohol intake,intelligence,anxiety or depression,*** randomization(MR)analysis revealed 1,139 pairs of isoforms and neuro-related traits with plausible causal relationships,showing much stronger causal effects than on general diseases measured in the UK Biobank(UKB).Our results highlight essential transcript-level biomarkers in the human brain for neuro-related complex traits and diseases,which could be missed by merely investigating overall gene expressions.

关键词： Alternative splicing Isoform-ratio quantitative trait loci(irQTL) Expression quantitative trait loci(eQTL) Genome-wide Association Studies Neuro-related human complex traits

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Effects of Additional Glycine in Outpatients Being Treated for Urine Storage Disorders

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Open Journal of Urology 2021年第11期11卷 381-392页

作者： Kimio Sugaya Hitoshi Oh-Oka Tetsuo Yamada Masanobu Miyata Katsuhiro Ashitomi Katsumi Kadekawa Saori Nishijima Department of Urology Kitakami Central Hospital Okinawa Japan Southern Knights’ laboratory Okinawa Japan Kobe Medical Center Kobe Japan Yamada Urological Clinic Sagamihara Japan Kitanodai Clinic Kitahiroshima Japan Department of Urology Okinawa Hokubu Hospital Okinawa Japan Department of Urology Okinawa Kyodo Hospital Okinawa Japan

Objectives: This study aimed to determine whether additional glycine can improve urine storage symptoms in outpatients. Methods: We recruited 50 outpatients (15 females, 35 males) with an Overactive Bladder Symptom Score (OABSS) of 3 or more. Participants being treated for urine storage disorders took additional glycine for 8 weeks at a dose of 3 g twice a day. Outcome measures included blood pressure, the International Prostate Symptom Score (IPSS), OABSS, Nocturia Quality of Life (N-QOL) score, urination frequency, sleep latency, time until the first void at night, bladder pain, improvement in urinary symptoms assessed with the Global Self-Assessment (GSA), and adverse events. Results: In the OABSS, the number of nighttime voids, urgency to urinate, urgent incontinence, and total score were improved. Improvements were also found in the IPSS total score for urine storage items, blood pressure, IPSS-QOL, time to first void, bladder pain, and GSA score, but no changes were seen in the frequency of urination at night, sleep latency or N-QOL score. No adverse events were recorded. Conclusion: Oral glycine improves objective and self-assessed urine storage symptoms, blood pressure, and bladder pain.

关键词： Chronic Prostatitis Glycine Interstitial Cystitis Overactive Bladder Urine Storage Symptoms

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原发性帕金森患者血清铁蛋白水平的研究

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国际检验医学杂志 2011年第18期32卷 2069-2071页

作者：詹晓燕林玉蓓刘卫国李晓荣王瑶王莉 Department of Clinical laboratory Tradition Chinese Medicine Hospital of Jiangu Province Hospital Department of Neurology Nanjing Brain Hospital Affiliated to Nanjing Medical University

目的探讨原发性帕金森病(PD)血清铁蛋白水平与临床症状的关系。方法将101例PD患者分为PD组、男性PD和女性PD组,检测血清铁蛋白水平,同时收集性别、年龄、发病年龄、病程等一般资料,应用临床量表进行评估,并与血清铁蛋白水平进行相关性... 详细信息

目的探讨原发性帕金森病(PD)血清铁蛋白水平与临床症状的关系。方法将101例PD患者分为PD组、男性PD和女性PD组,检测血清铁蛋白水平,同时收集性别、年龄、发病年龄、病程等一般资料,应用临床量表进行评估,并与血清铁蛋白水平进行相关性分析。结果男性PD组的血清铁蛋白水平为(139.76±77.44)ng/mL,低于男性健康对照组[(177.97±97.29ng/mL,P<0.05)];PD组的血清铁蛋白水平与患者年龄(r=0.244,P<0.05)、发病年龄(r=0.208,P<0.05)、教育年限(r=0.243,P<0.05)相关;男性PD患者血清铁蛋白水平与性功能障碍症状(r=0.270,P<0.05)相关;女性PD患者血清铁蛋白水平与年龄(r=0.417,P<0.05)、非运动症状的睡眠/疲劳感(r=-0.337,P<0.05)负相关。结论低血清铁蛋白水平很可能为男性PD患者发病的危险因素之一,血清铁蛋白水平和一些临床症状具有一定的相关性,值得进一步研究。

关键词：帕金森障碍铁蛋白质类运动症状非运动症状

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Infectious Microbes & Diseases 2023年第3期5卷 120-126页

作者： Fei-Xiang Liu Zi-Bei Dong Min Zhao Ya-Hui Gao Xiang Li Ya-Nan Jiang Yi-Ming Li Yu-Xin Zheng Zhen Wang Yan-Chen Feng Ya-Li Liu Cerebropathy Hospital The First Affiliated Hospital of Henan University of Chinese MedicineZhengzhouChina The First Clinical Medical School Henan University of Chinese MedicineZhengzhouChina State Key laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Research Units of Infectious Disease and Microecology Chinese Academy ofMedical SciencesHangzhouChina Traditional ChineseMedicine(Zhong Jing)School Henan University of Chinese MedicineZhengzhouChina.

Coronavirus disease 2019(COVID-19)has affected the quality of sleep for various populations,causing anxiety and depression ***-19–related insomnia(COVIDRI)appears to be more common in certain populations,including females,urban residents and other individuals who reside in high-risk COVID-19–related areas,lack higher socioeconomic and educational levels,have a history of underlying mental illness,have no access to social support and work,or have been mandated for *** vulnerable pop-ulations,pregnant women,adolescents and children are more likely to suffer from anxiety and depression,which leads to irregular sleep-wake cycles and significantly poor sleep *** in COVID-19 patients is associated with decreased immune levels,ex-cessive psychological stress and severe *** COVIDRI incidence and severity among frontline healthcare workers is high,espe-cially among females and those working in isolation wards and intensive care *** factors related to COVIDRI for college students during home study are stress from upcoming graduation,disharmonious family relationships and inadaptability to online *** military personnel,anxiety and depression are the main causes of poor sleep *** on the characteristics of different popula-tions,active Chinese and Western medications,non-drug therapy,psychological counseling and suitable sleep management are vital measures to strengthen immunity,alleviate insomnia and limit recurrence.

关键词： COVID-19 insomnia anxiety depression.

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LIM kinase 1 in hippocampo-cortical circuit is required for spatial memory stabilization

LIM kinase 1 in hippocampo-cortical circuit is required for ...

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中国神经科学学会第十二届全国学术会议

作者： Xiangyu Yang Chuntao Luo Yan Wei Chunfeng Yang Zikai Zhou The Key laboratory of Developmental Genes and Human Disease Ministry of Education Institute of Life Sciences Southeast University Centre de Recherche en Information Biomédicale sino-fran?ais (CRIBs) Rennes France and LIST School of Computer Science and Engineering Southeast University

Memories are stabilized by consolidation after learning experience. In particular, hippocampo-cortical dialog during non-rapid eye movement（NREM） sleep promotes spatial information transformation for long-term memory（LTM） storage. It is well known that synapses are the building blocks of neuronal circuits and synaptic reorganization plays critical role in memory consolidation. However, the mechanism of how the dialog between these two brain regions regulating synapse remodelingdependent memory consolidation is still unclear. By simultaneously recording neural activities and local field potentials（LFPs） in the hippocampus and medial prefrontal cortex（m PFC）, we found that hippocampal sharp wave ripple（SWR） induce long-term synaptic plasticity that contribute to memory retention in m PFC. In LIMK1 knockout（Limk1-/-） mice, which show abnormal spine morphology and LTM impairments, we found that the hippocampo-cortical interactions were abnormal which lead to impaired long-term spatial memory. Furthermore, restricted synaptic remodeling in m PFC by pharmacologically inhibiting LIMK1 activity reduce LTM retention. Together, these findings indicate that activation of LIMK1 are important for hippocampo-cortical interactions-induced synapse remodeling-dependent memory consolidation.

关键词： LIM kinase 1 Hippocampo-cortical circuits memory consolidation synaptic plasticity

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Transcranial Direct Current Stimulation: Effects on Motor and Non-Motor Symptoms of Parkinson’s Disease

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Journal of Behavioral and Brain Science 2024年第5期14卷 135-160页

作者： Fayda Protásio Carlos Alberto Bezerra Tomaz Joaquim Brasil-Neto Pedro Brandão Nasser Allam Maria Clotilde Henriques Tavares laboratory of Neuroscience and Behavior Department of Physiological Sciences Institute of Biology University of Braslia Braslia Brazil Master Program in Environment University CEUMA So Lus MA and Faculty of Medicine Euro-American University Center-UNIEURO Braslia Brazil Faculty of Medicine Euro-American University Center-UNIEURO Braslia Brazil NA Neurologistas Associados Braslia Brazil

Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson’s disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2 mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg

关键词： Parkinson’s Disease Neuromodulation Transcranial Direct Current Stimulation—tDCS Movement Disorders Mood sleep Cognition

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Understanding Patients’ Symptoms Management Using Objective and Subjective Indicators among Patients with Systemic Lupus Erythematosus

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Open Journal of Nursing 2023年第5期13卷 314-328页

作者： Kiyoko Makimoto Kazuko Shiozawa Yoshihito Shima Toru Hirano Mitsuyo Inoue Osaka University Osaka Japan Rheumatology & Collagen Disease Center Hyogo Prefectural Kakogawa Medical Center Kakogawa Japan laboratory of Thermo-Therapeutics for Vascular Dysfunction Osaka University Graduate School of Medicine Osaka Japan Division of Rheumatology Nishinomiya Municipal Central Hospital Nishinomiya Japan School of Nursing Hyogo Medical University Kobe Japan

Background: Descriptive statistics have been used to document the high prevalence of sleep disorders, fatigue, and pain in patients with systemic lupus erythematosus (SLE). Objectives: To describe day-to-day variations in sleep indicators, physical activity level, pain, and fatigue measured using objective and subjective indicators in lupus patients with sleep disorders. Methods: We selected three patients with sleep disorders, measured by the Pittsburgh sleep Quality Index score (≥9), out of 20 participants followed up for 4 weeks. We compared the self-rated quality of life (QoL) measured using the Pittsburgh sleep Quality Index (PSQI) with that of objectively measured sleep indicators monitored using the Nemuri scan. The detailed data collection methods have been previously published. Results: The sleep status generated by the Nemuri scan revealed that Case A with a flare and Case B without a flare required frequent daytime rest. The PSQI sleep duration and sleep latency were generally in agreement with the monitored data, although the PSQI failed to capture the complexity of sleep disorders, particularly the fluctuations in the quality of sleep indicators. Patient C approximately 4 hours on weekdays and 10 hours on Saturday nights. All three cases had high fatigue levels, and their moderate-to-vigorous physical activity duration was less than one-half of duration that recommended by the World Health Association. Conclusion: Visual display for objective monitoring of sleep quality is an excellent tool for understanding patients who require frequent resting and irregular sleep indicators. Objective monitoring of sleep quality, along with self-rated pain and fatigue, promotes an understanding of how patients with SLE cope with severe symptoms.

关键词： Symptoms Management sleep Indicator Physical Activity Pain Fatigue QoL

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