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Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： shuai Feng Juanji Li Tingting Liu shiqi Huang Xiangliang Chen shen Liu Junshan Zhou Hongdong Zhao Ye Hong Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

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T-cell and B-cell repertoire diversity are selectively skewed in children with idiopathic nephrotic syndrome revealed by high-throughput sequencing

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World Journal of Pediatrics 2023年第3期19卷 273-282页

作者： Qing Ye Dong-Jie Wang Bing Lan Jian-Hua Mao Department of Clinical Laboratory Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNational Children's Regional Medical CenterHangzhou 310052China Department of Nephrology Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNational Children's Regional Medical CenterHangzhou 310052China

Background Clinical studies suggest that the dysfunction of T cells and B cells may play an essential role in the pathogenesis of idiopathic nephrotic syndrome(INs),but laboratory evidence is ***,this study explored T-cell receptor(TCR)and B-cell receptor(BCR)profiling in children with idiopathic nephrotic *** High-throughput sequencing technology was used to profile the TCR and BCR repertoires in children with *** blood was collected from ten INs patients,including five vinculin autoantibody-positive patients and five vin-culin autoantibody-negative patients,before and after *** and BCR libraries were constructed by 5'-RACE and sequenced by a DNBsEQ-T7 sequencer,and sequence analyses were performed using ReseqTools,FastP,MiXCR,and *** The TRA(T-cell receptorα),TRG(T-cell receptor y),and IGH(immunoglobulin heavy chain)repertoires of the INs group were occupied by highly abundant clonotypes,whereas small clonotypes occupied the healthy group,especially TRA.A significant increase in the shannon-Weaver index was observed for the TRA and TRG repertoires after treatment in vinculin autoantibody-negative patients,but a significant increase in the IGH repertoire after treatment was observed in vinculin autoantibody-positive *** frequency of some V-J pairs was significantly enriched in steroid-sensitive nephrotic syndrome *** usage frequency of the V and J genes was skewed in patients,which seemed not related to immunosuppressive ***,after effective treatment,dynamic changes in the size of the individual clonotype were *** T-cell and B-cell immunity contribute to the pathogenesis of different INss.

关键词： B-cell receptor repertoire Complementary determining region 3 Idiopathic nephrotic syndrome T-cell receptor repertoire

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Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome(CAPs)

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science China(Life sciences) 2017年第12期60卷 1436-1444页

作者： Caifeng Li Xiaohua Tan Junmei Zhang shipeng Li Wenxiu Mo Tongxin Han Weiying Kuang Yifang Zhou Jianghong Deng Department of Rheumatology and Immunology Beijing Children's HospitalCapital Medical UniversityNational Center for Children"s HealthBeijing 100045China

The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPs patients. Fifteen confirmed patients with CAPs were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash(93.3%) with fever(100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever(100%), rash(93.3%) and myalgia(76%). Other clinical manifestations include arthritis(11 cases), lung involvement(seven cases), optical dysfunction(seven cases), nerve deafness(six cases), nervous system involvement(five cases), hepatomegaly, splenomegaly and lymphadenectasis(five cases). Also, four patients had heart involvement and one patient suffered kidney involvement. The laboratory inflammation index such as leukocyte counts, platelet counts, erythrocyte sedimentation rate(EsR), C-reactive protein(CRP), serum amyloid A(sAA) and fibrinogen(FIB) increased significantly at initial stage, but decreased after therapy. As for gene mutation detection, Twelve out of 15 patients were confirmed with mutation in NLRP3, including 11 mutant site: c1789 A>G, c.1703 T>A, c.913 G>A, c.1710 G>C, c.1057 G >T, c.2335 C>T, c.932 T>C,c.296 G>C, c.663 C>T, t.1702 T>A, 299 G>A. Mutation sites c.1703 T>A, c.2335 C>T, c.296 G>C, c.663 C>T, and 299 G>A were newly identified. The association between gene mutation and clinical manifestation shows that D305 N was highly associated with severe organs involvements, and therefore, the time of therapy and regimen were critical for the prognosis of disease. As the largest cohort study of Chinese CAPs patients, we confirmed that all patients presented typical clinical manifestations, identified five new mutation sites on NLRP3 and analyzed the correlation between the genotypes and phenotypes. We also raise concerns for one case

关键词： CAPs genetic mutation clinical phenotTpe NLRP3

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Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus

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World Journal of Pediatrics 2020年第3期16卷 240-246页

作者： Zhi-Min Chen Jun-Fen Fu Qiang shu Ying-Hu Chen Chun-Zhen Hua Fu-Bang Li Ru Lin Lan-Fang Tang Tian-Lin Wang Wei Wang Ying-shuo Wang Wei-Ze Xu Zi-Hao Yang sheng Ye Tian-Ming Yuan Chen-Mei Zhang Yuan-Yuan Zhang children's hospital Zhejiang University School of MedicineNational Clinical Research Center for Child HealthNational Children's Regional Medical CenterHangzhou 310052China

since December 2019,an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in *** of 8 pm,31 January 2020,more than 20 pediatric cases have been reported in *** these cases,ten patients were identified in Zhejiang Province,with an age of onset ranging from 112 days to 17 *** the latest national recommendations for diagnosis and treatment of pneumonia caused by 2019-nCo V (the 4th edition) and current status of clinical practice in Zhejiang Province,recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the national Clinical Research Center for Child Health,the national children's Regional Medical Center,children's hospital,Zhejiang University school of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.

关键词： New coronavirus Respiratory infection Child Diagnosis Treatment Recommendation

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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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Genome-wide analysis of differential DNA methylation in silver-Russell syndrome

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science China(Life sciences) 2017年第7期60卷 692-699页

作者： Di Wu Chunxiu Gong Chang su Department of Endocrinology Genetics and Metabolism Beijing Children's Hospital Capital Medical University National Center for Children's Health MOE Key Laboratory of Major Diseases in Children Beijing 100045 China

silver-Russell syndrome(sRs) is clinically heterogeneous disorder characterized by low birth weight, postnatal growth restriction, and variable dysmorphic features. Current evidence strongly implicates imprinted genes as an important etiology of sRs. Although almost half of the patients showed DNA hypomethylation at the H19/IGF2 imprinted domain, and approximately7%–10% of sRs patients have maternal uniparental disomy of chromosome 7(UPD(7) mat); the rest of the sRs patients shows unknown etiology. In this study, we investigate whether there are further DNA methylation defects in sRs patients. We measured DNA methylation in seven sRs patients and five controls at more than 485,000 CpG sites using DNA methylation microarrays. We analyzed methylation changes genome-wide and identified the differentially methylated regions(DMRs) using bisulfite sequencing and digital PCR. Our analysis identifies epimutations at the previously characterized domains of H19/IGF2,providing proof of principle that our methodology can detect the changes in DNA methylation at imprinted loci. In addition,our results showed a novel sRs associated imprinted gene OsBPL5 located on chromosome 11p14 with the probe cg25963939,which is hypomethylated in 4/7 patients(P=0.023, β=.0.243). We also report DMRs in other genes including TGFβ3, HsF1,GAP43, NOTCH4 and MYH14. These DMRs were found to be associated with sRs using GO pathway analysis. In this study,we identified the probe cg25963939, located at the 5′UTR of imprinted gene OsBPL5, as a novel DMR that is associated with sRs. This finding provides new insights into the mechanism of sRs etiology and aid the further stratification of sRs patients by molecular phenotypes.

关键词： silver-Russell syndrome methylation differences imprinted gene

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Thoracoabdominal duplication with hematochezia as an onset symptom in a baby:A case report

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World Journal of Clinical Cases 2021年第24期9卷 7261-7268页

作者： shao-Bo Yang Hong Yang shan Zheng Gong Chen Department of surgery Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghai 201102China

BACKGROUND Alimentary tract duplication is a rare congenital disease that may occur in any part of the alimentary tract,whereas thoracoabdominal duplications only account for approximately 2%of all alimentary tract duplication *** symptoms,including abdominal pain,abdominal distension,vomiting,gastrointestinal bleeding,chest discomfort,chest pain,and shortness of breath,may be present in patients with abdominal or thoracic *** sUMMARY A 10-mo-old infant,with a free previous medical history,was admitted to our hospital with melena three times in 6 *** magnetic resonance imaging of the thoracic vertebrae revealed multiple cervicothoracic vertebral deformities,spina bifida,meningomyelocele towards the posterior mediastinum,and possible concurrent *** gastroenterography indicated intestinal malrotation.A laparoscopic abdominal examination was performed,and the operation was intraoperatively converted to *** case was diagnosed intraoperatively as thoracoabdominal intestinal *** intestinal duplications in the abdomen and large part of the thorax were *** results of postoperative pathological examination confirmed that this case was alimentary tract duplication and that part of the duplication contained gastric *** infant recovered well and was discharged 1 wk after the surgery.A follow-up computed tomography scan 3 mo after operation showed myelomeningocele while the posterior mediastinal cyst was significantly *** Thoracoabdominal duplication should be considered if a child has suspected abdominal intestinal duplication with hematochezia as an onset symptom.

关键词： Thoracoabdominal duplication Thoracoabdominal Hematochezia Alimentary tract Case report

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EZH2-dependent myelination following sciatic nerve injury

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Neural Regeneration Research 2025年第8期20卷 2382-2394页

作者： Hui Zhu Li Mu Xi Xu Tianyi Huang Ying Wang siyuan Xu Yiting Wang Wencong Wang Zhiping Wang Hongkui Wang Chengbin Xue Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityKey Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationCo-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Medical school of Nantong University NantongJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Rehabilitation Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Critical Care Medicine Nantong Fourth People’s HospitalNantongJiangsu ProvinceChina

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve ***,the gene regulatory network of regenerated myelin differs from that of native *** of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of schwann cells in *** further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were *** results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain *** highlights the crucial role of Ezh2 in initiating schwann cell ***,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type *** suggests that the absence of Ezh2 in schwann cells impairs myelin formation and *** conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve *** EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

关键词： demyelination EZH2 myelination peripheral nerve injury PRC2 remyelination schwann cells sciatic nerve crush sciatic nerve transection

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Insufficient application of estimation equations of glomerular filtration rate:a survey of 1009 Chinese pediatricians

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World Journal of Pediatrics 2022年第5期18卷 368-372页

作者： Zi-Mo sun Nan Zhou Xiao-Xia Peng Hui Wang Ying shen Center for Clinical Epidemiology and Evidence-Based Medicine Beijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Nephrology Beijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China

The cur re nt high prevalence of kidney disease and kidney injury in children represents a significant public health *** incidence of chronic kidney disease(CKD)is 3.0-17.5 per million children,and the prevalence is 14.9-118.8 per million children,with an increasing trend[1].CKD can progress to end-stage renal disease and cause complications,including dysplasia and cardiovascular disease,thus causing more significant health problems[2].

关键词： kidney prevalence cardiovascular

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Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

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World Journal of Clinical Oncology 2025年第1期16卷 43-52页

作者： Zhi-Jian Tang Yuan-Ming Pan Wei Li Rui-Qiong Ma Jian-Liu Wang Department of Obstetrics and Gynecology Peking University People’s HospitalBeijing 100044China Cancer Research Center Beijing Chest HospitalBeijing 101149China Department of Thoracic surgery Sichuan Provincial People's HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment *** To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural *** Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression *** genes were sourced from the MitoCarta3.0 *** discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation *** the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were *** In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy *** average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation *** average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation *** The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

关键词： Ovarian cancer Mitochondria Prognosis Immunotherapy Neural network

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