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Unresolved Excess Accumulation of Myelin-Derived Cholesterol Contributes to Scar Formation after spinal Cord Injury

Research 2024年第1期2023卷 17-32页

作者： Bolin Zheng Yijing He Shuai Yin Xu Zhu Qing Zhao Huiyi Yang Zhaojie wang Rongrong Zhu Liming Cheng key laboratory of Spine and spinal Cord Injury Repair and Regeneration Ministry of EducationDepartment of OrthopedicsTongji HospitalSchool of MedicineTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research School of Life Science and TechnologyTongji UniversityShanghai 200092China Clinical Center for Brain and spinal Cord Research Tongji UniversityShanghai 200092China

spinal cord injury triggers complex pathological cascades,resulting in destructive tissue damage and incomplete tissue *** formation is generally considered a barrier for regeneration in the central nervous ***,the intrinsic mechanism of scar formation after spinal cord injury has not been fully ***,we report that excess cholesterol accumulates in phagocytes and is inefficiently removed from spinal cord lesions in young adult ***,we observed that excessive cholesterol also accumulates in injured peripheral nerves but is subsequently removed by reverse ***,preventing reverse cholesterol transport leads to macrophage accumulation and fibrosis in injured peripheral ***,the neonatal mouse spinal cord lesions are devoid of myelin-derived lipids and can heal without excess cholesterol *** found that transplantation of myelin into neonatal lesions disrupts healing with excessive cholesterol accumulation,persistent macrophage activation,and *** internalization suppresses macrophage apoptosis mediated by CD5L expression,indicating that myelin-derived cholesterol plays a critical role in impaired wound *** together,our data suggest that the central nervous system lacks an efficient approach for cholesterol clearance,resulting in excessive accumulation of myelin-derived cholesterol,thereby inducing scar formation after injury.

关键词： healing spinal impaired

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Incidence,prevalence,and causes of spinal injuries in China,1990-2019:Findings from the Global Burden of Disease Study 2019

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Chinese Medical Journal 2024年第6期137卷 704-710页

作者： Chenjun Liu Tingling Xu Weiwei Xia Shuai Xu Zhenqi Zhu Maigeng Zhou Haiying Liu Department of spinal Surgery Peking University People’s HospitalPeking UniversityBeijing 100044China Chinese Preventive Medicine Association Committee on Prevention and Control of Spinal DiseaseBeijing 100009China National Center for Chronic and Noncommunicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 100050China School of Public Health Xi’an Jiaotong UniversityXi’anShaanxi 710061China

Background:spinal injuries are an urgent public health priority;nevertheless,no China-wide studies of these injuries *** study measured the incidence,prevalence,causes,regional distribution,and annual trends of spinal injuries in China from 1990 to ***:We used data from the Global Burden of Diseases,Injuries,and Risk Factors Study 2019 to estimate the incidence and prevalence of spinal injuries in *** data of 33 provincial-level administrative regions(excluding Taiwan,China)provided by the National Center for Chronic and Noncommunicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention(CDC)were use to systematically analyze the provincial etiology,geographical distribution,and annual trends of spinal *** Bayesian meta-regression tool DisMod-MR 2.1 was used to ensure the consistency among incidence,prevalence,and mortality rates in each ***:From 1990 to 2019,the number of living patients with spinal injuries in China increased by 138.32%,from 2.14 million to 5.10 million,while the corresponding age-standardized prevalence increased from 0.20%(95%uncertainty interval[UI]:0.18-0.21%)to 0.27%(95%UI:0.26-0.29%).The incidence of spinal injuries in China increased by 89.91%(95%UI:72.39-107.66%),and the prevalence increased by 98.20%(95%UI:89.56-106.82%),both the most significant increases among the G20 countries;71.00%of the increase could be explained by age-specific *** 2019,the incidence was 16.47(95%UI:12.08-22.00,per 100,000 population),and the prevalence was 358.30(95%UI:333.96-386.62,per 100,000 population).Based on the data of 33 provincial-level administrative regions provided by CDC,age-standardized incidence and prevalence were both highest in developed provinces in Eastern *** primary causes were falls and road injuries;however,the prevalence and specific causes differed across ***:In China,the overall disease burden of spinal injuries increased significantl

关键词： spinal injuries Global Burden of Diseases,Injuries and Risk Factors Study 2019 Incidence Prevalence Falls Road injuries

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Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

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Neural Regeneration Research 2024年第3期19卷 636-641页

作者： Jiao Mu Liufang Hao Zijue Wang Xuyang Fu Yusen Li Fei Hao Hongmei Duan Zhaoyang Yang Xiaoguang Li Beijing key laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal *** investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal *** first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal *** antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time *** improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing *** this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after *** addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over ***,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian ***,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal *** conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

关键词： corticospinal tract green fluorescent protein microglia spinal anterior horn cells stroke virus trace Wallerian degeneration

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Single-cell omics:experimental workflow,data analyses and applications

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Science China Life Sciences 2024年

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biology the Institute of Biomedical Sciences and School of Life Sciences East China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Center for Quantitative Biology (CQB) Peking University Zhejiang key laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women’s Hospital Zhejiang University School of Medicine key laboratory of Advanced Theory and Application in Statistics and data Science-MOE School of Statistics East China Normal University Shanghai 200062 China Department of Clinical laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical Sciences Zhejiang University key laboratory of Spine and spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of Education Orthopaedic Department Tongji Hospital Bioinformatics Department School of Life Sciences and Technology Tongji University Frontier Science Center for Stem Cells School of Life Sciences and Technology Tongji University Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East Hospital Bioinformatics Department School of Life Sciences and Technology Tongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine National key laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River Delta Zhejiang University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial scRNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

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Mutational spectrum of syndromic genes in sporadic brain arteriovenous malformation

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Chinese Neurosurgical Journal 2022年第2期8卷 104-110页

作者： Kun Wang Mingqi Zhang Sen Zhao Zhixin Xie Yisen Zhang Jian Liu Ying Zhang Xinjian Yang Nan Wu Department of Interventional Neuroradiology Beijing Neurosurgical Institute and Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Department of Orthopedic Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Beijing key laboratory for Genetic Research of Skeletal Deformity Beijing 100730China key laboratory of big data for spinal deformities Chinese Academy of Medical SciencesBeijing 100730China

Background:Brain arteriovenous malformations(BAVMs)are abnormal vessels that are apt to rupture,causing lifethreatening intracranial hemorrhage(ICH).The estimated prevalence of BAVMs is 0.05%among otherwise healthy *** this study,we aim to investigate the mutational spectrum of syndromic genes in sporadic ***:We recruited a cohort of 150 patients with BAVM and performed whole-exome sequencing on their peripheral blood *** explore the mutational spectrum of syndromic genes in sporadic brain arteriovenous malformation,we selected six genes according to the Online Mendelian Inheritance in Man(OMIM)and *** variants in the six candidate genes were extracted and underwent filtering for qualifying ***:There are a total of four patients with rare variants in hereditary hemorrhagic telangiectasia-related *** addition,we identified two patients have the variant of RASA1 gene in our database,which are also rare mutations that are absent from population ***,we did not find any patients with GNAQ mutations in our ***:In conclusion,we demonstrated that variants in syndromic vascular malformations play important roles in the etiology of sporadic BAVM.

关键词： arteriovenous malformation spectrum

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Treatment of lumbar disc herniation with robot combined with unilateral biportal endoscopic technology:A case report

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World Journal of Clinical Cases 2024年第17期12卷 3235-3242页

作者： Yan-Dong Liu Duo-Fang Xu Qiang Deng Yan-Jun Zhang Tie-Feng Guo Ran-Dong Peng Jun-Jie Li Graduate School Gansu University of Traditional Chinese MedicineLanzhou 730030Gansu ProvinceChina spinal Disease Treatment Center Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050Gansu ProvinceChina Department of spinal Orthopedics II Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050Gansu ProvinceChina Department of Osteomyelitis Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050Gansu ProvinceChina

BACKGROUND This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion(UBE-LIF),utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment,and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw *** advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies,and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients,and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for *** SUMMARY A 44-year-old patient presented to our *** various clinical data,we diagnosed the patient with lumbar disc herniation with radiculopathy,lumbar spondylolisthesis,and lumbar spinal *** developed a surgical plan of"UBE decompression+UBE-LIF+orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation".The results were *** We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good ***,the technique is worthy of clinical promotion.

关键词： Orthopedic robot Unilateral biportal endoscopy Unilateral biportal endoscopic lumbar interbody fusion Lumbar disc herniation Decompression fusion Case report

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Transfer force perception skills to robot‐assisted laminectomy via imitation learning from human demonstrations

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CAAI Transactions on Intelligence Technology 2024年第4期9卷 903-916页

作者： Meng Li Xiaozhi Qi Xiaoguang Han Ying Hu Bing Li Yu Zhao Jianwei Zhang Harbin Institute of Technology ShenzhenChina Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhenChina Shenzhen key laboratory of Minimally Invasive Surgical Robotics and System Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina Beijing Jishuitan Hospital Capital Medical UniversityBeijingChina Department of Orthopedics Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina University of Hamburg Hamburg22527Germany

A comparative study of two force perception skill learning approaches for robot‐assisted spinal surgery,the impedance model method and the imitation learning(IL)method,is *** impedance model method develops separate models for the surgeon and patient,incorporating spring‐damper and bone‐grinding *** surgeons'feature parameters are collected and mapped using support vector regression and image navi-gation *** imitation learning approach utilises long short‐term memory networks(LSTM)and addresses accurate data labelling challenges with custom *** results demonstrate skill recognition rates of 63.61%-74.62%for the impedance model approach,relying on manual feature ***,the imitation learning approach achieves a force perception recognition rate of 91.06%,outperforming the impedance model on curved bone *** findings demonstrate the potential of imitation learning to enhance skill acquisition in robot‐assisted spinal surgery by eliminating the laborious process of manual feature extraction.

关键词： learning(artificial intelligence) medical applications medical signal processing robotics

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Reduced non-CpG methylation is a potential epigenetic target after spinal cord injury

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Neural Regeneration Research 2023年第11期18卷 2489-2496页

作者： Zhourui Wu Chen Li Ran Zhu Yiqiu Cao Thomas C.Chen Liming Cheng key laboratory of Spine and spinal cord Injury Repair and Regeneration(Tongji University) Ministry of EducationShanghaiChina Division of Spine Department of OrthopedicsTongji HospitalTongji University School of MedicineShanghaiChina Institute of spinal and spinal Cord Injury Tongji University School of MedicineShanghaiChina Department of Neurosurgery Keck School of MedicalUniversity of Southern CaliforniaLos AngelesCAUSA

DNA methylation is a critical epigenetic regulator in the occurrence and development of diseases and is closely related to various functional responses in relation to spinal cord *** investigate the role of DNA methylation in spinal cord injury,we constructed a library with reduced-representation bisulfite sequencing data obtained at various time points(day 0-42)after spinal cord injury in *** DNA methylation levels,specifically non-CpG(CHG and CHH)methylation levels,decreased modestly following spinal cord *** post-spinal cord injury were classified as early(day 0-3),intermediate(day7-14),and late(day 28-42)based on similarity and hie rarchical cluste ring of global DNA methylation *** non-CpG methylation level,which included CHG and CHH methylation levels,was markedly reduced despite accounting for a minor proportion of total methylation *** multiple genomic sites,including the 5’untranslated regions,promoter,exon,intron,and 3’untranslated regions,the non-CpG methylation level was markedly decreased following spinal cord injury,whereas the CpG methylation level remained unchanged at these *** one-half of the differentially methylated regions were located in intergenic areas;the other differentially methylated regions in both CpG and non-CpG regions were cluste red in intron regions,where the DNA methylation level was *** function of genes associated with differentially methylated regions in promoter regions was also *** Gene Ontology analysis results,DNA methylation was implicated in a number of essential functional responses to spinal cord injury,including neuronal synaptic connection creation and axon ***,neither CpG methylation nor non-CpG methylation was implicated in the functional response of glial or inflammatory *** summary,our work elucidated the dynamic pattern of DNA methylation in the spinal co rd following injury and identified reduced nonCpG meth

关键词： CpG methylation cytosine fraction differentially methylated regions DNA methylation DNA methyltransferases dynamic signatures Gene Ontology non-CpG methylation single-cell RNA-Seq spinal cord injury

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Effect of decompression range on decompression limit of cervical laminoplasty

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Chinese Medical Journal 2020年第8期133卷 909-918页

作者： Yin-Ze Diao Miao Yu Feng-Shan Zhang Yu Sun Shao-Bo Wang Li Zhang Sheng-Fa Pan Zhong-Jun Liu Wei-Shi Li Department of Orthopedics Institute of Spinal SurgeryPeking University Third HospitalBeijing Key Laboratory of Spinal DiseaseBeijing 100191China

Backgrounds:Cervical posterior decompression surgery is used to relieve ventral compression indirectly by incorporating a backward shift of the spinal cord, and this indirect decompression is bound to be limited. This study aimed to determine the decompression limit of posterior surgery and the effect of the decompression ***:We retrospectively reviewed the data of 129 patients who underwent cervical open-door laminoplasty through 2008 to 2012 and were grouped as follows: C4-C7 ( n = 11), C3-C6 ( n = 61), C3-C7 ( n = 32), and C2-C7 ( n = 25). According to the relative location of spinal levels within a decompression range, the type of decompression at a given level was categorized as external decompression (ED;achieved at the levels located immediately external to the decompression range margin), internal decompression (ID;achieved at the levels located immediately internal to the decompression range margin), and central decompression (CD;achieved at the levels located in the center, far from the decompression range margin). The vertebral-cord distance (VCD) was used to evaluate the decompression limit. The C2-C7 angle and VCD on post-operative magnetic resonance images were analyzed and compared between groups. The relationship between VCD and decompression type was analyzed. Moreover, the relationship between the magnitude of the ventral compressive factor and the probability of post-operative residual compression at each level for different decompression ranges was studied. Results:There was no significant kyphosis in cervical curvature (>-5°), and there was no significant difference among the groups ( F = 2.091, P = 0.105). The VCD of a specific level depended on the decompression type of the level and followed this pattern: ED < ID < CD ( P < 0.05). The decompression type of a level was sometimes affected by the decompression range. For a given magnitude of the ventral compressive factor, the probability of residual compression was lower for the group

关键词： Cervical spondylosis Ossification of posterior longitudinal ligament Magnetic resonance imaging Laminoplasty

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The identification of PAX7 variants and a potential role of muscle development dysfunction in congenital scoliosis

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Cell Regeneration 2022年第1期11卷 163-166页

作者： Muchuan Wang Ziquan Li Sen Zhao Zhifa Zheng Yipeng Wang Guixing Qiu Zhihong Wu Nan Wu Terry Jianguo Zhang Siyi Cai Department of Orthopedic Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Beijing key laboratory for Genetic Research of Skeletal Deformity Beijing 100730China key laboratory of big data for spinal deformities Chinese Academy of Medical SciencesBeijing 100730China Medical Research Center Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesNo.1 ShuaifuyuanBeijing 100730China Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA

Dear Editor,Congenital scoliosis(CS)is a spinal malformation charac-terized by failure of vertebral formation or segmentation,or a mix of these deformities,resulting in longitudinal and rotational imbalance,and affects 0.05-0.1%of new-borns(Wu et al.2015).It is generally understood that the development of CS has an underlying genetic ***,genes related to somite regulation or osteo-genesis during embryonic development are believed to be responsible for the vertebral malformations observed in CS patients(Pourquie 2011).

关键词： vertebral scoliosis

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