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Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

Neural Regeneration Research 2025年第9期20卷 2598-2610页

作者： Yi Wang Yuning Li Yakun Gu Wei Ma Yuying Guan Mengyuan Guo Qianqian Shao Xunming Ji Jia Liu Department of Clinical Laboratory Beijing Bo’ai HospitalChina Rehabilitation Research CenterCapital Medical UniversityBeijingChina Beijing Institute of brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersBeijing Advanced Innovation Center for Big Data-based Precision MedicineCapital Medical UniversityBeijingChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this *** aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive *** found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic *** addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic *** phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic ***,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein *** ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein *** together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

关键词： biomarker high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment

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Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

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Chinese Journal of Cancer Research 2024年第1期36卷 55-65页

作者： Yaping Yang Liang Jin Yudong Li Nanyan Rao Chang Gong Shunrong Li Jiannan Wu Jinghua Zhao Linxiaoxiao Ding Fengxia Gan Jun Zhang Ruifa Feng Zhenzhen Liu Qiang Liu Breast tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationGuangzhou 510120China Department of Thyroid and Breast Surgery Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518000China Breast and Thyroid Surgery Guilin Medical College Second Affiliated HospitalGuilin 541199China Department of Breast Disease Henan Breast Cancer Centerthe Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008China

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity ***: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety

关键词： Breast cancer HER2-positive breast cancer dual HER2 blockade neoadjuvant therapy sequential therapy

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STON2风险变异通过影响Syt1转运和突触功能导致精神分裂症样行为

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Science Bulletin 2024年第10期69卷 1458-1471页

作者：马远林高凯孙晓璇王金鑫杨扬武建荧柴安平姚立刘楠郁昊苏怡卢天兰王力芳岳伟华章晓辉徐林张岱李俊 Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Key Laboratory of Mental HealthChinese Academy of Medical SciencesBeijing 100191China The First Affiliated Hospital Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China Changping Laboratory Beijing 102206China d Chinese Institute for brain Research Beijing 102206China Laboratory of Learning and Memory Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China Shenzhen Key Laboratory of Translational Research for brain Diseases The Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China State Key Laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing 100875China PKU-IDG/McGovern Institute for brain Research Peking UniversityBeijing 100871China

Synaptic dysfunction is a core component of the pathophysiology of ***,the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully *** Stonin 2(STON2)gene encodes a major adaptor for clathrin-mediated endocytosis(CME)of synaptic *** this study,we showed that the C-C(307Pro-851Ala)haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of *** found that schizophrenia-related STON2 variations led to protein dephosphorylation,which affected its interaction with synaptotagmin 1(Syt1),a calcium sensor protein located in the presynaptic membrane that is critical for ***2307Pro851Ala knockin mice exhibited deficits in synaptic transmission,short-term plasticity,and schizophrenia-like ***,among seven antipsychotic drugs,patients with the C-C(307Pro-851Ala)haplotype responded better to haloperidol than did the T-A(307Ser-851Ser)*** recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin *** findings demonstrated the effect of schizophreniarelated STON2 variations on synaptic dysfunction through the regulation of CME,which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.

关键词： STON2 variations Schizophrenia Synaptic dysfunction Syt1 Haloperidol

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Sirolimus can promote the disappearance of renal angiomyolipoma associated with tuberous sclerosis complex:a prospective cohort study

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World Journal of Pediatrics 2024年第6期20卷 602-610页

作者： Shuo Dun Yang-Yang Wang Lin Wan Qiu-Hong Wang Qian Lu Xiao-Yan Yang Qi Zhang Hui-Min Chen Lu-Peng Qiu Li-Ping Zou Medical School of Chinese PLA Beijing 100853China Department of Pediatrics The First Medical CenterChinese PLA General HospitalBeijing 100853China Center of Epilepsy Beijing Institute for Brain DisordersBeijing 100069China

Background Renal angiomyolipoma(RAML)is the most common kidney lesion in patients with tuberous sclerosis complex(TSC),affecting about 80%of *** is a benign tumor that grows over time,usually bilaterally,and can easily lead to kidney complications such as acute ***,we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup *** A prospective cohort study was *** was initiated at 1 mg/(m^(2)×day),and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5-10 ng/*** disappearance of RAML in chil-dren after sirolimus treatment was observed,and Cox regression was used to screen the factors affecting tumor *** One hundred and twenty-six patients who met the criteria were *** 3 months,6 months,12 months,and 24 months of follow-up,tumors disappeared in 18(14.3%),30(23.8%),39(31.0%),and 42(33.3%)children,*** disappeared in 50(39.7%)children by the last visit of each individual,and 30(60%)of them occurred within 6 *** multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance ***-six(29%)patients had stomatitis during the entire treatment period,and no serious *** Sirolimus could promote the disappearance of TSC-related *** disappearance rate was correlated with the maximum diameter at baseline,and the smaller the tumor was,the higher the disappearance *** is well tolerated in the treatment of RAML associated with TSC.

关键词： Angiomyolipoma mTOR inhibitor Sirolimus Tuberous sclerosis

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The marriage of immunomodulatory,angiogenic,and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scafold for military medicine

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Military Medical Research 2024年第3期11卷 323-344页

作者： Ping Wu Lin Shen Hui-Fan Liu Xiang-Hui Zou Juan Zhao Yu Huang Yu-Fan Zhu Zhao-Yu Li Chao Xu Li-Hua Luo Zhi-Qiang Luo Min-Hao Wu Lin Cai Xiao-Kun Li Zhou-Guang Wang Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research the Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000ZhejiangChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhou 325000ZhejiangChina Department of Spine Surgery and Musculoskeletal tumor Zhongnan Hospital of Wuhan UniversityWuhan 430071China National Engineering Research Center for Nanomedicine College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Department of Overseas Education College Jimei UniversityXiamen 361021FujianChina School and Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325035ZhejiangChina

Background:Most bone-related injuries to grassroots troops are caused by training or accidental *** establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone ***:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)*** physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were *** and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in ***:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated *** to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 *** in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury *** underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 ***:The piezoelectric Cs/Gel/PHA/PBT hy

关键词： Piezoelectric hydrogel Tissue engineering scafold Immunomodulation Angiogenesis Osteogenic differentiation

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Timing of biomarker changes preceding Alzheimer's disease:for diagnosis, treatment or prevention?

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Science China Life Sciences 2024年

作者： Meina Quan Innovation Center for Neurological Disorders and Department of Neurology Xuanwu Hospital Capital Medical University National Medical Center for Neurological Diseases and National Clinical Research Center for Geriatric Diseases Center of Alzheimer's Disease Beijing Institute of Brain Disorders Collaborative Innovation Center for Brain Disorders

The pathophysiological and behavioural features of Alzheimer’s disease (AD) have been extensively investigated in transgenic mouse models, including the temporal sequence of each pathophysiological change and behavioural abnormality, a summary of which was recently presented by our team in this Journal (Li et al.,2023). Nevertheless, studying such features and timings directly in human patients before symptoms occur is challenging. Starting from familial AD, then gradually shifting to sporadic AD, growing evidence from longitudinal studies indicates that biomarkers change at least10 to 20 years before the onset of symptoms in AD (Bateman et al., 2012;Villemagne et al., 2013; Gordon et al.,2018; Vermunt et al., 2019).

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Molecular biomarkers for vascular cognitive impairment and dementia:the current status and directions for the future

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Neural Regeneration Research 2024年第12期19卷 2579-2580页

作者： Satoshi Hosoki Perminder SSachdev Centre for Healthy brain Ageing Discipline of Psychiatry and Mental HealthSchool of Clinical MedicineFaculty of Medicine and HealthUniversity of New South WalesSydneyAustralia Department of Neurology National Cerebral and Cardiovascular CenterOsakaJapan

Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive *** development of disease-specific treatments and targeted prevention strategies requires precise clinical sub-typing via etiology and pathophysiological ***,recent research advances in biomarkers,especially for Alzheimer's disease(AD)diagnosis,have improved diagnostic precision for dementia.

关键词： prevention diagnosis impairment

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Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

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Neural Regeneration Research 2024年第7期19卷 1499-1508页

作者： Yiran Xu Yifei Li Seidu A.Richard Yanyan Sun Changlian Zhu Henan Key Laboratory of Child brain Injury and Henan Pediatric Clinical Research Center Institute of Neuroscience and The Third Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina National Health Council(NHC)Key Laboratory of Birth Defects Prevention Henan Key Laboratory of Population Defects PreventionZhengzhouHenan ProvinceChina Department of Human Anatomy School of Basic Medicine and Institute of NeuroscienceZhengzhou UniversityZhengzhouHenan ProvinceChina Center for brain Repair and Rehabilitation Institute of Neuroscience and PhysiologyUniversity of GothenburgGothenburgSweden

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and *** with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal *** disturbances severely impact the child’s daily life and impose a substantial economic burden on the *** cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and *** review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy *** is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa *** pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still ***,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy *** r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular ***,exploring targeted genotypes holds potential for precision *** conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral *** breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical *** investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management *** elucidating the underlying cellular mechanisms,w

关键词： cerebral palsy environmental factors etiology genetic factors genetic mutation movement disorder spastic diplegia

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Dopamine Switches Affective States Under Acute Sleep Deprivation

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Neuroscience Bulletin 2024年第8期40卷 1205-1208页

作者： Zhou-Cai Luo Tian-Ming Gao State Key Laboratory of Organ Failure Research Key Laboratory of Mental Health of the Ministry of EducationGuangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceGuangdong-Hong Kong Joint Laboratory for Psychiatric DisordersGuangdong Province Key Laboratory of Psychiatric DisordersGuangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi DiseasesDepartment of NeurobiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

The transition of affective states manifests affective regulation,wherein individuals adaptively adjust their emotional states to cope with changes in the external environment,reflecting their sensitivity and adaptability to environmental *** process of affective state transition is complex,involving both instantaneous and persistent changes influenced by environmental,behavioral,and pharmacological *** underlying neural mechanisms encompass alterations in neurotransmitter release,neural circuit activity,and the plasticity of brain structures[1].

关键词： alterations Dopamine neural

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A novel dual serotonin transporter and M-channel inhibitor D01 for antidepression and cognitive improvement

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1457-1466页

作者： Yaqin Wei Xiangqing Xu Qiang Guo Song Zhao Yinli Qiu Dongli Wang Wenwen Yu Yani Liu KeWei Wang School of Pharmacy Xuzhou Medical UniversityXuzhou 221004China Institute of Pharmaceutical Research Jiangsu Nhwa Pharmaceutical Co.Ltd.&Jiangsu Key Laboratory of Central Nervous System Drug Research and DevelopmentXuzhou 221116China Department of Pharmacology School of PharmacyQingdao University Medical CollegeQingdao 266073China Institute of Innovative Drug Qingdao UniversityQingdao 266021China Center for brain Science and brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhou 510515China

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving *** this study,we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01(a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative)that exhibits both anti-depression effects and improvements in cognition.D01 inhibits serotonin transporters(K_(i)=30.1±6.9 nmol/L)and M channels(IC_(50)=10.1±2.4μmol/L).D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on *** administrations of D01(20 and 40 mg/kg)can significantly shorten the immobility time in a mouse model of chronic restraint stress(CRS)-induced depression-like ***,D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice,but not ***,D01 reverses the long-term potentiation(LTP)inhibition induced by *** together,our findings demonstrate that D01,a dual-target serotonin reuptake and M channel inhibitor,is highly effective in the treatment-resistant depression and cognitive deficits,thus holding potential for development as therapy of depression with cognitive deficits.

关键词： SERT 5-HT Kv7/KCNQ/M current D01 Depression Cognition

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