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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 lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This 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 SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,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

Bacteria-responsive programmed self-activating antibacterial hydrogel to remodel regeneration microenvironment for infected wound healing

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National Science Review 2024年第4期11卷 254-270页

作者： Yutong Yang Jiaxin Wang Shengfei Huang Meng Li Jueying Chen Dandan Pei Zhen Tang Baolin Guo State Key Laboratory for Mechanical Behavior of Materials and Frontier institute of Science and Technology and Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of Stomatology Xi'an Jiaotong University Department of orthopedics Tangdu Hospital Fourth Military Medical University Department of orthopedics The First Affiliated Hospital of Xi'an Jiaotong University

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, p H-responsive H2O2self-supplying composite nanozyme（MSCO） and p H/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase（PPEL） were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan（CA） and phenylboronic acid-modified oxidized dextran（ODP） to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide（NO） release. The composite hydrogel showed 'self-diagnostic' treatment for changes in the wound microenvironment.Through self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings.

关键词： bacterial response hydrogel dressing multiple nanozyme activity biofilm elimination infected motion wound healing

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

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Acta Pharmaceutica Sinica B 2024年第2期14卷 579-601页

作者： Jing Yan Hao Zhang Guangfeng Li Jiacan Su Yan Wei Can Xu institute of Translational Medicine Shanghai UniversityShanghai 200444China institute of Medicine Shanghai UniversityShanghai 200444China Department of orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of orthopedics Shanghai Zhongye HospitalShanghai 200941China Organoid Research Center Shanghai UniversityShanghai 200444China Department of Gastroenterology Changhai HospitalShanghai 200433China

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in 2018.To illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle preparation.Then,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery.Finally,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed.Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.

关键词： Lipid nanovehicles RNAtherapeutics Barriers to systemicRNA delivery Lipid components Fabricationmethods Lipid nanovehicledesign Extrahepatictissue targeting Organ tropism

Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes

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Neural Regeneration Research 2024年第12期19卷 2760-2772页

作者： Xiaowen Xu Xinxin Wang Li Zhang Yiming Jin Lili Li Meifang Jin Lianyong Li Hong Ni Division of Brain Science Institute of Pediatric ResearchChildren’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Pediatric orthopedics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

关键词： brain injury cerebral palsy hypoxia hypoxic-ischemic brain injury inflammation neuroprotection nicotinamide adenine dinucleotide neonate nicotinamide adenine dinucleotide proteomics

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 unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The 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 assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The 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 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,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

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 death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This 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 level.We 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 China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends 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 Program.The 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 surgery.Only 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 hours.The 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 hours,which is associated with improved sensorimot

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

Engineered plant extracellular vesicles for autoimmune diseases therapy

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Nano Research 2024年第4期17卷 2857-2873页

作者： Ruina Han Yan Wu Yafei Han Xiangfei Liu Han Liu Jiacan Su institute of Translational Medicine Shanghai UniversityShanghai 200444China Organoid Research Center Shanghai UniversityShanghai 200444China National Center for Translational Medicine(Shanghai)SHU Branch Shanghai UniversityShanghai 200444China Department of orthopedics Shanghai Zhongye HospitalShanghai 200941China Department of orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy tissues.Plant extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive molecules.Due to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of AID.This review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in AID.Additionally,we propose engineering approaches and administration methods for PEVs.Finally,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of AID.By gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for AID.Natural and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

关键词： autoimmune diseases plant extracellular vesicles extracellular vesicles engineering modification

Understanding host-graft crosstalk for predicting the outcome of stem cell transplantation

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World Journal of Stem Cells 2024年第3期16卷 232-236页

作者： Luminita Labusca Florin Zugun-Eloae Magnetic Materials and Sensors National Institute of Research and Development for Technical PhysicsIasi 700050Romania orthopedics and Trauma Emergency County Hospital Saint SpiridonIasi 700000Romania Transcend Regional Oncology InstituteIasi 7000000Romania

Mesenchymal stromal cells(MSCs)hold great promise for tissue regeneration in debilitating disorders.Despite reported improvements,the short-term outcomes of MSC transplantation,which is possibly linked to poor cell survival,demand extensive investigation.Disease-associated stress microenvironments further complicate outcomes.This debate underscores the need for a deeper understanding of the phenotypes of transplanted MSCs and their environment-induced fluctuations.Additionally,questions arise about how to predict,track,and comprehend cell fate post-transplantation.In vivo cellular imaging has emerged as a critical requirement for both short-and long-term safety and efficacy studies.However,translating preclinical imaging methods to clinical settings remains challenging.The fate and function of transplanted cells within the host environment present intricate challenges,including MSC engraftment,variability,and inconsistencies between preclinical and clinical data.The study explored the impact of high glucose concentrations on MSC survival in diabetic environments,emphasizing mitochondrial factors.Preserving these factors may enhance MSC survival,suggesting potential strategies involving genetic modification,biomaterials,and nanoparticles.Understanding stressors in diabetic patients is crucial for predicting the effects of MSC-based therapies.These multifaceted challenges call for a holistic approach involving the incorporation of large-scale data,computational disease modeling,and possibly artificial intelligence to enable deterministic insights.

关键词： Mesenchymal stem cells Phenotype Transplantation Host Microenvironment Cellular imaging Diabetes mellitus

Degradable magnesium alloy suture promotes fibrocartilaginous interface regeneration in a rat rotator cuff transosseous repair model

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Journal of Magnesium and Alloys 2024年第1期12卷 384-393页

作者： Baoxiang Zhang Wen Zhang Fei Zhang Chao Ning Mingyang An Ke Yang Lili Tan Qiang Zhang Department of Sports Medicine Chinese PLA General HospitalBeijing 100853China Shi-changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China Medical School of PLA Beijing 100853China institute of orthopedics Chinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Lab of Musculoskeletal Trauma&War Injuries of Chinese PLABeijing 100853China

Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures.In the present work,degradable magnesium(Mg)alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4±0 absorbable suture as control.The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after operation.The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure.Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups.In the histological analysis,for Mg alloy suture groups,chondrocytes appear to proliferate at 4 weeks postoperatively,and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively.The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed,where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis.In vivo degradation of the magnesium alloy wire was completed within 12 weeks.The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.

关键词： Rotator cuff repair Mg alloy wire Tendon-bone healing Fibrocartilaginous interface