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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal key laboratory of Biomarker and translational research in Neurodegenerative Diseases BeijingChina key laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第01期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing key laboratory of carcinogenesis and translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University key laboratory of carcinogenesis and Cancer Invasion Ministry of Education State key laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Iron-handling solute carrier SLC22A17 as a blood-brain barrier target after stroke

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Neural Regeneration research 2025年第11期20卷 3207-3208页

作者： Xueqi Ren Wenlu Li key laboratory of Neuropharmacology and translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Neuroprotection research Laboratories Departments of Radiology and NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

The pathophysiology of ischemic stroke is complex and multifactorial,involving various forms of cell death such as apoptosis,autophagy,and necrosis.A recent study suggests that oxidative and inflammatory stress can induce ferroptosis,a specialized form of cell death characterized by the accumulation of lipid peroxides dependent on intracellular iron overload(Li and Jia,2023).

关键词： death specialized barrier

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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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Retrospective analysis of interventional treatment of hepatic metastasis from gastroenteropancreatic neuroendocrine tumors

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Chinese Journal of Cancer research 2017年第6期29卷 581-586页

作者： Peng Liu Xu Zhu Jie Li Ming Lu Jiahua Leng Ying Li Jiangyuan Yu key laboratory of carcinogenesis and translational research(Ministry of Education/Beijing) Department of Interventional Therapy key laboratory of carcinogenesis and translational research(Ministry of Education/Beijing)Department of Gastroenterological Oncology key laboratory of carcinogenesis and translational research(Ministry of Education/Beijing)Center of Gastrointestinal Surgery Unit III key laboratory of carcinogenesis and translational research(Ministry of Education/Beijing)Department of Radiolog key laboratory of carcinogenesis and translational research(Ministry of Education/Beijing)Department of NuclearMedicine Peking University Cancer Hospital&InstituteB eijing 100142China

Objective： To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors （GEP-NETs）, and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases. Methods： Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016, and received transarterial embolization （TAE） in the hepatic tumor or hepatic arterial infusion chemotherapy （HAIC）. All patients received 179 times of the intervention therapy in total. Results： Blood supplies were identified in the 50 eases with angiography, which showed that 35 cases had abundant vessels, while 15 eases had poor blood supply. Twenty-two cases were found either collateral blood supply, or portal vein invasion or arterial-portal vein fistula. The best curative efficacy was complete remission （CR） in 4 cases, partial remission （PR） in 28 cases and stable disease （SD） in 18 eases during the process of treatment. The angiography （P=0.047） and the frequency of intervention （P=0.037） showed significantly statistical difference with Kaplan-Meier analysis. The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor. Conclusions： Interventional treatment is safe and effective for GEP-NETs, and is beneficial to patients with main hepatic metastases after endocrine therapy.

关键词： Gastroenteropancreatic neuroendocrine tumors hepatic metastasis angiography interventionaltreatment retrospective analysis

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Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease

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Neural Regeneration research 2025年第10期20卷 2823-2837页

作者： Qiuquan Cai Lianghui Meng Meina Quan Ling Wang Jing Ren Chenguang Zheng Jiajia Yang Dong Ming Academy of Medical Engineering and translational Medicine Tianjin UniversityTianjinChina Innovation Center for Neurological Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Brain-Computer Interaction and Human-Machine Fusion Haihe laboratory Tianjin UniversityTianjinChina Tianjin key laboratory of Brain Science and Neural Engineering Tianjin UniversityTianjinChina

Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive *** presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s *** use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent *** a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive *** article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound *** is placed on the benefits of introducing these treatment methods and their potential *** found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque *** believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.

关键词： Alzheimer’s disease blood-brain barrier drugs magnetic resonance imaging-guided focused ultrasound microbubbles scanning ultrasound ultrasound ultrasound stimulation

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Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai Xu Zhen Gu Hua Yan Dingding Shen Xiaosong Gu Academy of Medical Engineering and translational Medicine Tianjin UniversityTianjinChina key laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological *** regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of *** pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota *** results are lacking for conventional treatments for *** resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with ***-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research *** review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of *** also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current *** studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic ***,many new technologies for the diagnosis and treatment of epilepsy are being ***,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

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Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration research 2025年第11期20卷 3259-3272页

作者： Huidong Li Faqin Li Zhaoyi Chen Erwen Wu Xiaoxi Dai Danni Li Haojie An Shiyi Zeng Chunyan Wang Li Yang Cheng Long School of Life Sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of Life Sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial key laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint laboratory of translational Medical research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission

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Depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis

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Chinese Journal of Cancer research 2017年第2期29卷 109-117页

作者： Ziyu Li Zhemin Li Shuqin Jia Zhaode Bu Lianhai Zhang Xiaojiang Wu Shuangxi Li Fei Shan Xin Ji Jiafu Ji key laboratory of carcinogenesis and translational research (Ministry of Education/Beijing) Center of Gastrointestinal Surgery key laboratory of carcinogenesis and translational research (Ministry of Education/Beijing) Center for Molecular Diagnostics Peking University Cancer Hospital & Institute Beijing 100142 China

Objective： Diagnostic laparoscopy is recommended for the pretherapeutic staging of gastric cancer to detect any unexpected or unconfirmed intra-abdominal metastasis. The aim of this study was to evaluate the role and indications of diagnostic laparoscopy in the detection of intra-abdominal metastasis. Methods： Standard diagnostic laparoscopy with peritoneal cytology examination was performed prospectively on patients who were clinically diagnosed with primary local advanced gastric cancer （CT≥2M0）. We calculated the rate of intra-abdominal metastases identified by diagnostic laparoscopy, and examined the relationship between peritoneal dissemination （P） and cytology results （CY）. Split-sample method was applied to find clinical risk factors for intra-abdominal metastasis. Multivariate logistic regression analysis and receiver-operator characteristic （ROC） analysis were performed in training set to find out risk factors ofintra-abdominal metastasis, and then validate it in testing set. Results： Out of 249 cM0 patients, 51 （20.5%） patients with intra-abdominal metastasis were identified by diagnostic laparoscopy, including 20 （8.0%） P1CY1, 17 （6.8%） POCY1 and 14 （5.6%） P1CY0 patients. In the training set, multivariate logistic regression analysis and ROC analysis showed that the depth of tumor invasion on computer tomography （CT） scan ≥21 mm and tumor-occupied 〉2 portions of stomach are predictive factors of metastasis. In the testing set, when diagnostic laparoscopy was performed on patients who had one or two of these risk factors, the sensitivity and positive predictive value for detecting intra-abdominal metastasis were 90.0% and 32.1%, respectively. Conclusions： According to our results, depth of tumor invasion and tumor-occupied portions of stomach are predictive factors ofintra-abdominal metastasis.

关键词： Gastric cancer diagnostic laparoscopy peritoneal dissemination intra-peritoneal free cancer cells pretherapeutic staging

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Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

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World Journal of Gastroenterology 2013年第46期19卷 8714-8721页

作者： Zhi-Xue Zheng Yu Sun Zhao-De Bu Lian-Hai Zhang Zi-Yu Li Ai-Wen Wu Xiao-Jiang Wu Xiao-Hong Wang Xiao-Jing Cheng Xiao-Fang Xing Hong Du Jia-Fu Ji Department of Gastrointestinal Surgery Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital and Institute Department of Pathology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital and Institute Clinical Gastric Cancer research laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital and Institute Tissue Bank Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital and Institute

AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and ***:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records *** specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker *** intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact ***:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa *** of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue

关键词： Leucine-rich repeat-containing G protein-coupled receptor 5 Cancer stem cell Gastric cancer Intestinal metaplasia Tumorigenesis

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