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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National clinical Research center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-Hong Ma Department of Neurology and clinical Research center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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Sex differences in aging and injured brain

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Neural Regeneration Research 2025年第10期20卷 2901-2902页

作者： Jordan N.Williamson Yuan Yang University of Illinois Urbana-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of Illinois Urbana-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA Northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and *** higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with *** one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington prevalence traumatic

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First-episode psychiatric disorder risk from SARS-Co V-2 infection:A clinical analysis with Chinese psychiatric inpatients

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Journal of Biomedical Research 2025年第1期39卷 50-60页

作者： Ya Xie Zifeng Xu Yumin Zhang Yisheng Li Pengyu Du Chun Wang clinical Mental Health center the Affiliated Brain Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Medical School of Nanjing University NanjingJiangsu 210008China

The extensive spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)throughout China in late 2022 has underscored the correlation between this virus and severe psychiatric ***,there remains a lack of reported clinical and pathological ***,we retrospectively reviewed the electronic medical records of psychiatric inpatients for seven days from early January ***-one inpatients who developed first-episode psychiatric disorders within two weeks after SARS-CoV-2 infection were recruited,while 24 uninfected first-episode psychiatric inpatients were selected as *** analyses of clinical manifestations,routine laboratory tests,and imaging examinations were *** investigation demonstrated a 330%increase in the incidence of first-episode psychiatric inpatients after SARS-CoV-2 infection in 2023,compared with the preceding year without SARS-CoV-2 *** cases exhibited psychiatric symptoms within one week of SARS-CoV-2 infection,which resolved after approximately two weeks,with no residual symptoms after three ***-way ANOVA demonstrated a significant difference in the highest fever temperature between inpatients with and without psychotic *** inpatients displayed elevated levels of interleukin-4,interleukin-8,and interferon-α,but decreased levels of eosinophils and *** findings suggest that SARS-CoV-2 may contribute to the development of psychiatric disorders,likely mediated by the virus-induced inflammatory response and neuronal dysfunction in the context of psychological distress.

关键词： COVID-19 SARS-CoV-2 psychiatric disorders inflammation interleukins

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Predicting colorectal adenomatous polyps in patients with chronic liver disease: A novel nomogram

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World Journal of Gastroenterology 2025年第2期31卷 71-84页

作者： Yu-Qin Li Wen-Tao Kuai Lin Chen Ming-Hui Zeng Xue-Mei Tao Jia-Xin Han Yue-Kui Wang Lian-Xin Xu Li-Ying Ge Yong-Gang Liu Shuang Li Liang Xu Yu-Qiang Mi clinical School of the Second People’s Hospital Tianjin Medical UniversityTianjin 300192China Department of Hepatology Tianjin Second People’s HospitalTianjin 300192China Department of Pathology Clinical School of the Second People’s HospitalTianjin 300110China Endoscopy center Tianjin Second People’s HospitalTianjin 300192China

BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for *** To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were *** data including laboratory results,colonoscopy findings,and pathology reports were *** variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic *** performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve *** The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin *** novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation *** curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of *** The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.

关键词： Metabolic dysfunction associated steatotic liver disease Fatty liver Chronic liver disease Colorectal adenomas Hepatitis Risk factors

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Inflammatory Bowel Disease and Dementia:Evidence Triangulation from a Meta-Analysis of Observational Studies and Mendelian Randomization Study

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Biomedical and Environmental Sciences 2025年第1期38卷 56-66页

作者： Di Liu Meiling Cao Shanshan Wu Bingli Li Yiwen Jiang Tengfei Lin Fuxiao Li Weijie Cao Jinqiu Yuan Feng Sha Zhirong Yang Jinling Tang Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhen 518055GuangdongChina Beijing Key Laboratory of clinical Epidemiology School of Public HealthCapital Medical UniversityBeijing 100069China Department of Gastroenterology Beijing Friendship HospitalCapital Medical UniversityNational Clinical Research Center for Digestive DiseaseBeijing Digestive Disease CenterBeijing Key Laboratory for Precancerous Lesion of Digestive DiseaseBeijing 100050China Centre for Precision Medicine Edith Cowan UniversityPerth WA7027Australia clinical Research center The Seventh Affiliated HospitalSun Yatsen UniversityShenzhen 518107GuangdongChina

Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are *** remains unclear whether these associations are *** We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and *** randomization(MR)analysis based on summary genome-wide association studies(GWASs)was *** correlation and Bayesian colocalization analyses were used to provide robust genetic *** Ten observational studies involving 80,565,688 participants were included in this *** was significantly associated with dementia(risk ratio[RR]=1.36,95%CI=1.04-1.78;I2=84.8%)and VD(RR=2.60,95%CI=1.18-5.70;only one study),but not with AD(RR=2.00,95%CI=0.96-4.13;I^(2)=99.8%).MR analyses did not supported significant causal associations of IBD with dementia(dementia:odds ratio[OR]=1.01,95%CI=0.98-1.03;AD:OR=0.98,95%CI=0.95-1.01;VD:OR=1.02,95%CI=0.97-1.07).In addition,genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and *** Our study did not provide genetic evidence for a causal association between IBD and dementia *** increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.

关键词： Dementia Inflammatory bowel disease Meta-analysis Observational studies Mendelian randomization Genetic evidence Evidence triangulation

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Composite score of PD-1+CD8+ tumor-infiltrating lymphocytes and CD57+CD8+ tumor ascites lymphocytes is associated with prognosis and tumor immune microenvironment of patients with advanced high-grade serous ovarian cancer

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Chinese Journal of Cancer Research 2025年第01期 73-99页

作者： Tianhui He Jie Zhang Lin Zeng Zhongnan Yin Bo Yu Xi Zhang Xiaoxue Yang Chunliang Shang Lixiang Xue Hongyan Guo Department of Obstetrics and Gynecology Peking University Third Hospital center of Basic Medical Research Institute of Medical Innovation and Research Peking University Third Hospital Biobank Peking University Third Hospital Research center of clinical Epidemiology Peking University Third Hospital

Objective: The expression of programmed death 1（PD-1） on CD8+T cells is associated with their activation and exhaustion, while CD57 serves as a senescence marker. The impact of PD-1+and CD57+CD8+T cells on the prognosis of patients with advanced high-grade serous ovarian cancer（HGSOC） remain ***: We assessed the percentages of PD-1+and CD57+CD8+T cells in tumor-infiltrating lymphocytes（TILs, n=85） and tumor ascites lymphocytes（TALs, n=87） using flow cytometry. The optimal cutoffs for these markers in TILs and TALs were determined through the log-rank maximization method. Gene expression analysis elucidated the tumor immune microenvironment（TIME, n=36）.Results: Patients with higher PD-1+CD8+TILs（>87.8%） exhibited longer platinum-free interval（PFI） and overall survival（OS）. In contrast, those with elevated CD57+CD8+TALs（>28.69%） were more likely to experience chemotherapy and had lower complete remission rates, shorter PFI and OS. PD-1+CD8+TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities. Approximately 50% of CD57+CD8+TALs were terminally differentiated, exhibiting significantly impaired proliferation. Based on the proportions of PD-1+CD8+TILs and CD57+CD8+TALs, patients were categorized into good, median and poor prognosis groups, with median PFI of 47.78, 27.29 and 11.96 months, respectively（P<0.0001）. Median OS for these groups was not reach, 49.23 and 30.92 months, respectively（P<0.0001）. Patients with poor prognosis exhibit significantly reduced CD8+T cell proportion and increased M2 macrophage in the TIME, alongside downregulation of multiple T cell activation-related ***: Lower levels of PD-1+CD8+TILs and higher CD57+CD8+TALs, assessed prior to treatment,correlated with poor prognosis and suppressive TIME in advanced HGSOC.

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Association between fresh fruit intake and cardiovascular disease risk in patients with diabetes: A prospective cohort study

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中华医学杂志(英文版) 2025年第2期138卷 243-245页

作者： Fang Xin Zhang Xingyi Yang Ze Zhang Yefa Huang Shaofeng Chen Tiehui Yu Ling Zhong Wenling Department of Non-communicable Chronic Disease Control Fujian Provincial Center for Disease Control and Prevention Fuzhou Fujian China National clinical Research center of Cardiovascular Diseases NHC Key Laboratory of Clinical Research for Cardiovascular Medications State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Cardiology Fujian Provincial Hospital Fuzhou Fujian China

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Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

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Neural Regeneration Research 2025年第3期20卷 763-778页

作者： Minghuang Gao Xinyue Wang Shijie Su Weicheng Feng Yaona Lai Kongli Huang Dandan Cao Qi Wang Science and Technology Innovation center Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina Institute of clinical Pharmacology Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina The Sixth Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

关键词： central nervous system meningeal lymphatic vessels immunity myeloid cells lymphatic cells neurodegenerative disease

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National clinical Research center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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