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A"messenger zone hypothesis"based on the visual three-dimensional spatial distribution of motoneurons innervating deep limb muscles

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Neural Regeneration Research 2024年第7期19卷 1559-1567页

作者： Chen Huang Shen Wang Jin Deng Xinyi Gu Shuhang Guo Xiaofeng Yin MoE Key Laboratory for trauma Treatment and Nerve Regeneration Peking UniversityBeijingChina department of orthopedics and trauma Peking University People’s HospitalBeijingChina

Coordinated contraction of skeletal muscles relies on selective connections between the muscles and multiple classes of the spinal motoneuro *** r,current research on the spatial location of the spinal motoneurons innervating differe nt muscles is *** this study,we investigated the spatial distribution and relative position of different motoneurons that control the deep muscles of the mouse hindlimbs,which were innervated by the obturator nerve,femoral nerve,inferior gluteal nerve,deep pe roneal nerve,and tibial *** were visualized by combining a multiplex retrograde tracking technique compatible with three-dimensional imaging of solvent-cleared o rgans(3DISCO)and 3-D imaging technology based on lightsheet fluorescence microscopy(LSFM).Additionally,we propose the hypothesis that"messenger zones"exist as interlaced areas between the motoneuron pools that dominate the synergistic or antagonist muscle *** hypothesize that these interlaced neurons may participate in muscle coordination as messenger *** revealed the precise mutual positional relationships among the many motoneurons that innervate different deep muscles of the *** only do these findings update and supplement our knowledge regarding the overall spatial layout of spinal motoneurons that control mouse limb muscles,but they also provide insights into the mechanisms through which muscle activity is coordinated and the architecture of motor circuits.

关键词： 3-D imaging motoneurons multiple retrograde tracing muscle coordination skeletal muscle spatial distribution optical tissue clearing

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Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

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Neural Regeneration Research 2024年第8期19卷 1822-1827页

作者： Yuhui Kou Yusong Yuan Qicheng Li Wenyong Xie Hailin Xu Na Han department of trauma and orthopedics Peking University People’s HospitalBeijingChina National Center for trauma Medicine BeijingChina Key Laboratory of trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina department of orthopedics China-Japan Friendship HospitalBeijingChina department of Central Laboratory and Institute of Clinical Molecular Biology Peking University People’s HospitalBeijingChina

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still *** preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve ***,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains *** study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush *** functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent *** debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian *** inflammatory factor expression in different polarization states was detected using a protein *** results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 *** axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 *** peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in ***,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

关键词： axonal debris inflammatory factors macrophages neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration RAW 264.7 cells sciatic nerve Wallerian degeneration

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Ruxolitinib improves the inflammatory microenvironment,restores glutamate homeostasis,and promotes functional recovery after spinal cord injury

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Neural Regeneration Research 2024年第11期19卷 2499-2512页

作者： Jiang Cao Xiao Yu Jingcheng Liu Jiaju Fu Binyu Wang Chaoqin Wu Sheng Zhang Hongtao Chen Zi Wang Yinyang Xu Tao Sui Jie Chang Xiaojian Cao department of orthopedics The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina department of trauma surgery Subei People’s Hospital of JiangsuClinical Medical College of Yangzhou UniversityYangzhouJiangsu ProvinceChina department of orthopedics Zhongda HospitalSoutheast UniversityNanjingJiangsu ProvinceChina department of Orthopedic surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord ***,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine *** studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains *** address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord *** sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory ***,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic ***,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.

关键词： astrocytes EAAT2 excitotoxicity glutamate homeostasis JAK-STAT pathway locomotor function neurotoxicity ruxolitinib spinal cord injury transcriptome analysis

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The emerging role of tranexamic acid and its principal target,plasminogen,in skeletal health

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2869-2884页

作者： Weixin Xie Antonia Donat Shan Jiang Anke Baranowsky Johannes Keller department of trauma and Orthopedic surgery University Medical Center Hamburg-EppendorfHamburg 20246Germany

The worldwide burden of skeletal diseases such as osteoporosis,degenerative joint disease and impaired fracture healing is steadily *** acid(TXA),a plasminogen inhibitor and anti-fibrinolytic agent,is used to reduce bleeding with high effectiveness and safety in major surgical *** its widespread clinical application,the effects of TXA beyond anti-fibrinolysis have been noticed and prompted renewed interest in its *** clinical trials have characterized the effects of TXA on reducing postoperative infection rates and regulating immune responses in patients undergoing ***,several animal studies suggest potential therapeutic effects of TXA on skeletal diseases such as osteoporosis and fracture *** a direct effect of TXA on the differentiation and function of bone cells in vitro was shown,few mechanisms of action have been ***,we summarize recent findings of the effects of TXA on skeletal diseases and discuss the underlying plasminogen-dependent and-independent mechanisms related to bone metabolism and the immune *** furthermore discuss potential novel indications for TXA application as a treatment strategy for skeletal diseases.

关键词： Tranexamic acid Osteoporosis Osteoarthritis Fracture healing Bone metabolism Inflammation Plasminogen Fibrinolysis

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In vivo imaging of the neuronal response to spinal cord injury:a narrative review

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Neural Regeneration Research 2024年第4期19卷 811-817页

作者： Junhao Deng Chang Sun Ying Zheng Jianpeng Gao Xiang Cui Yu Wang Licheng Zhang Peifu Tang department of orthopedics The Fourth Medical Center of Chinese PLA General Hospital National Clinical Research Center for orthopedics Sports Medicine and Rehabilitation School of Life Sciences Tsinghua University department of orthopedics Air Force Medical CenterPLA Medical School of Chinese PLA Institute of orthopedics The First Medical CenterChinese PLA General Hospital Key Lab of Regenerative Medicine in orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLA

Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are *** in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and *** review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to *** then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience ***,we identify the challenges and possible solutions for spinal cord neuron imaging.

关键词： anterior horn neurons calcium imaging central nervous system dorsal horn neurons dorsal root ganglion in vivo imaging neuronal response spinal cord injury spinal cord two-photon microscopy

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Addressing metallosis in knee arthroplasty:From diagnostic challenges to innovative treatments

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World Journal of orthopedics 2024年第5期15卷 386-389页

作者： Yvon Maurice Bogdonoff Farid Amirouche department of orthopedics surgery University of Illinois at ChicagoChicagoIL 60612United States department of orthopedics surgery Northshore University Health SystemSkokieIL 60076United States

In this editorial,we comment on the article by Toro et al published in the recent issue of World Journal of *** editorial review provides a comprehensive exploration of the landscape surrounding knee arthroplasty metallosis,focusing on key aspects ranging from the mechanisms influencing susceptibility to clinical implications and advanced treatment *** elucidate the complex interplay of implant design,patient-specific variables,and wear-related processes contributing to ***,we seek to shed light on diagnostic challenges,the necessity of a multidisciplinary approach,and the imperative for vigilant implant ***-on-uni revision,as a targeted treatment modality,is discussed,highlighting its potential to address metallosis in unicompartmental knee arthroplasty(UKA).There is a need for heightened awareness among clinicians regarding the subtle presentations of metallosis,coupled with the limitations of traditional imaging *** metallosis requires a collaborative,multidisciplinary approach to effectively navigate the complexities associated with this ***,the review emphasizes the evolving paradigm of personalized care,with uni-on-uni revision emerging as a promising surgical *** conclusion,the editorial outlines the dynamic nature of knee arthroplasty metallosis and its multifaceted impact on clinical *** calls for ongoing collaboration,education,and integration of innovative solutions to enhance diagnostic accuracy,proactive management,and overall patient outcomes in the realm of UKA.

关键词： Ultrasound X-ray Total knee arthroplasty Case report Review Editorial

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Adipose-derived regenerative therapies for the treatment of knee osteoarthritis

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World Journal of Stem Cells 2024年第4期16卷 324-333页

作者： Ilias E Epanomeritakis Wasim S Khan Division of trauma and Orthopaedic surgery Addenbrooke’s HospitalCambridge University Hospitals NHS Foundation TrustCambridge CB20QQUnited Kingdom Division of trauma and Orthopaedic surgery Department of SurgeryUniversity of CambridgeCambridge CB20QQUnited Kingdom

Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying *** treatment ultimately requires joint *** capable of regenerating cartilage could significantly reduce financial and clinical *** regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee *** has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to ***-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative *** vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,*** avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of *** this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee *** discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative *** underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.

关键词： Knee osteoarthritis Mesenchymal stromal cells Adipose tissue Stromal vascular fraction Micro-fragmented adipose tissue Regeneration

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Biochanin A attenuates spinal cord injury in rats during early stages by inhibiting oxidative stress and inflammasome activation

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Neural Regeneration Research 2024年第9期19卷 2050-2056页

作者： Xigong Li Jing Fu Ming Guan Haifei Shi Wenming Pan Xianfeng Lou department of orthopedics The First Affiliated Hospital of Zhejiang UniversityHangzhouZhejiang ProvinceChina department of Stomatology Xixi HospitalHangzhouZhejiang ProvinceChina department of orthopedics and Spine Surgerythe Affiliated Hospital of Xuzhou Medical Schoolthe Second People’s Hospital of ChangshuChangshuJiangsu ProvinceChina

Previous studies have shown that Biochanin A,a flavonoid compound with estrogenic effects,can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury;howeve r,its effect on spinal cord injury is still unclea r. In this study,a rat model of spinal cord injury was established using the heavy o bject impact method,and the rats were then treated with Biochanin A(40 mg/kg) via intrape ritoneal injection for 14 consecutive *** res ults showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal co rd tissue injury,reduced inflammation and oxidative stress in spinal cord neuro ns,and reduced apoptosis and *** addition,Biochanin A inhibited the expression of inflammasome-related proteins(ASC,NLRP3,and GSDMD)and the Toll-like receptor 4/nuclear factor-κB pathway,activated the Nrf2/heme oxygenase 1 signaling pathway,and increased the expression of the autophagy markers LC3 Ⅱ,Beclin-1,and *** r,the therapeutic effects of Biochanin A on early post-s pinal cord injury were similar to those of *** findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling *** findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

关键词： apoptosis autophagy Biochanin A heme oxygenase 1 inflammation Nrf2 protein nuclear factor kappa-B oxidative stress spinal cord injury Toll-like receptor 4

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Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 513-528页

作者： Miao CHU Guangdong CHEN Kai CHEN Pengfei ZHU Zhen WANG Zhonglai QIAN Huaqiang TAO Yaozeng XU Dechun GENG department of orthopedics the First Affiliated Hospital of Soochow UniversitySuzhou 215006China department of orthopedics Yixing People’s HospitalYixing 214200China department of orthopedics Hai’an People’s HospitalHai’an 226600China department of orthopedics Suzhou Kowloon HospitalShanghai Jiao Tong University School of MedicineSuzhou 215028China

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the *** activation plays a crucial role in the occurrence of subchondral bone loss in early ***,the specific mechanism of osteoclast differentiation in OA remains *** our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)***2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral ***,fourteen DEGs that are associated with oxidative stress were *** first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further *** results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of *** was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in ***,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in *** research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of *** HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

关键词： Osteoclast Oxidative stress Osteoarthritis(OA) Heme oxygenase 1(HMOX1) Carnosol

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Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

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Neural Regeneration Research 2024年第5期19卷 1126-1132页

作者： Hengxing Zhou Yongfu Lou Lingxiao Chen Yi Kang Lu Liu Zhiwei Cai David BAnderson Wei Wang Chi Zhang Jinghua Wang Guangzhi Ning Yanzheng Gao Baorong He Wenyuan Ding Yisheng Wang Wei Mei Yueming Song Yue Zhou Maosheng Xia Huan Wang Jie Zhao Guoyong Yin Tao Zhang Feng Jing Rusen Zhu Bin Meng Li Duan Zhongmin Zhang Desheng Wu Zhengdong Cai Lin Huang Zhanhai Yin Kainan Li Shibao Lu Shiqing Feng department of orthopedics The Second HospitalCheeloo College of MedicineShandong UniversityShandongChina department of orthopedics Shandong University Center for OrthopedicsQilu HospitalCheeloo College of MedicineShandong UniversityShandongChina department of orthopedics Tianjin Medical University General HospitalInternational Science and Technology Cooperation Base of Spinal Cord InjuryTianjin Key Laboratory of Spine and Spinal CordTianjinChina Faculty of Medicine and Health The Back Pain Research TeamSydney Musculoskeletal HealthThe Kolling InstituteUniversity of SydneySydneyNSWAustralia department of Spine surgery Honghui HospitalXi’an Jiaotong UniversityXi’anShaanxi ProvinceChina department of Burns and Plastic surgery The Fourth Medical Center of Chinese PLA General HospitalBeijingChina Faculty of Medicine and Health School of Health SciencesUniversity of SydneyNSWAustralia Sydney Spine Institute BurwoodSydneyNSWAustralia Laboratory of Epidemiology Tianjin Neurological InstituteDepartment of NeurologyTianjin Medical University General Hospital&Tianjin Neurological InstituteKey Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjinChina department of orthopedics Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina department of Spinal surgery The Third Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina department of orthopedics The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Spine surgery Zhengzhou Orthopedics HospitalZhengzhouHenan ProvinceChina department of Orthopedic surgery and Orthopedic Research Institute West China HospitalSichuan UniversityChengduSichuan ProvinceChina department of orthopedics Xinqiao HospitalArmy Medical UniversityChongqingChina department of orthopedics The First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina department of Spinal surgery Shengj

traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even *** has the largest population of patients with traumatic spinal cord *** studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been *** the best of our knowledge,no national-level study of treatment status and economic burden has been *** retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national *** included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of *** epidemiological and clinical features,treatment status,and total and daily costs were *** in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression *** percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent *** 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 *** total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 ho

关键词： China clinical features costs epidemiology methylprednisolone sodium succinate methylprednisolone retrospective study traumatic spinal cord injury treatment

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