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PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis ina Temporal Manner

research 2024年第1期2023卷 33-48页

作者： Fangqian Wang Yuxiao Ye Zengjie Zhang Wangsiyuan Teng Hangxiang Sun Xupeng Chai Xingzhi Zhou Jiayu Chen Haochen Mou Yinwang Eloy Xiaoqiang Jin Liang Chen Zhenxuan Shao Yan Wu Yue Shen An Liu Peng Lin Jianwei Wang Xiaohua Yu Zhaoming Ye Department of Orthopedic Surgery the Second Affiliated HospitalZhejang University School of MedicineHangzhou CityZhejiang ProvincePR China orthopedics research institute of zhejang university Hangzhou CityZhejiang ProvincePR China Key Laboratory of Motor System Disease research and Precision Therapy of Zhejiang Province Hangzhou CityZhejiang ProvincePR China School of Material Science and Engineering University of New South WalesSydney 2052Australia

Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.

关键词： healing sized implantation

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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

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Structures and ion transport mechanisms of plant high-affinity potassium transporters

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Molecular Plant 2024年第3期17卷 409-422页

作者： Jiangqin Wang Yanping Luo Fan Ye Zhong Jie Ding Shao Jian Zheng Shuai Qiao Yong Wang Jiangtao Guo Wei Yang Nannan Su international institutes of Medicine the Fourth Affiliated HospitalZhejang University School of MedicineYiwuZhejiang 322000China Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital Zhejiang University School of MedicineHangzhouZhejang 310058China State Key Laboratory of Plant Environmental Resilience College of Life SciencesZhejang UniversityHangzhouZhejang 310058China College of Life Sciences Zhejiang UniversityHangzhouZhejiang 310058China NHC and CAMS Key Laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Science and Brain-machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310058China Nanhu Brain-computer Interface institute Hangzhou.Zheiang 311100.China

Plant high-affinity K^(+) transporters(HKTs)mediate Na^(+) and K^(+) uptake,maintain Na^(+)/K^(+) homeostasis,and therefore play crucial roles in plant salt tolerance.In this study,we present cryoelectron microscopy structures of HKTs from two classes,classI HKT1;1 from Arabidopsis thaliana(AtHKT1;1)and class II HKT2;1 from Triticum aestivum(TaHKT2;1),in both Na^(+) -and K^(+) -bound states at 2.6-to 3.0-A resolutions.BothAtHKT1;1and TaHKT2;1function ashomodimers.Each HKT subunit consists of four tan-dem domain units(D1-D4)with a repeated K^(+) -channel-like M-P-M topology.In each subunit,D1-D4 assemble into an ion conduction pore with a pseudo-four-fold symmetry.Although both TaHKT2;1and AtHKT1;1 have only one putative Na^(+) ion bound in the selectivity filter with a similar coordination pattern,the two HKTs display different K^(+) binding modes in the filter.TaHKT2;1 has three K^(+) ions bound in the selec-tivity filter,but AtHKT1;1 has only two K^(+) ions bound in the filter,which has a narrowed external entrance due to the presence of a Ser residue in the first filter motif.These structures,along with compu-tational,mutational,and electrophysiological analyses,enable us to pinpoint key residues that are critical for the ion selectivity of HKTs.The findings provide new insights into the ion selectivity and ion transport mechanisms of plant HKTs and improve our understanding about how HKTs mediate plant salt tolerance and enhance crop growth.

关键词： HKTs structure ion selectivity mechanism salt tolerance

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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

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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

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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

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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

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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 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

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Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

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Neural Regeneration research 2024年第4期19卷 900-907页

作者： Haoshuai Tang Junjin Li Hongda Wang Jie Ren Han Ding Jun Shang Min Wang Zhijian Wei Shiqing Feng Department of Othopaedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General Hospital Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General Hospital Department of Othopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OthopedicsAdvanced Medical Research InstituteShandong University Orthopedic research Center of Shandong university&Advanced Medical research institute Cheeloo College of MedicineShandong University

Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

关键词： axon growth collagen exosome human umbilical cord mesenchymal stem cells hyaluronic acid muscular atrophy nerve guidance conduits peripheral nerve regeneration

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Limb Lengthening and Reconstruction Society orthopedic surgeons in the United States:An analysis of geographical distribution,academic,leadership,and demographic characteristics

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World Journal of orthopedics 2024年第2期15卷 147-155页

作者： Amir Human Hoveidaei Reza Niakan Seyed Hossein Hosseini-Asl Abijith Annasamudram Janet D Conway International Center for Limb Lengthening Rubin Institute for Advanced OrthopedicsSinai Hospital of BaltimoreBaltimoreMD 21215United States Student research Committee Shiraz University of Medical SciencesShiraz 73Iran Students’Scientific research Center Tehran University of Medical SciencesTehran ***Iran

BACKGROUND The Limb Lengthening and Reconstruction Society(LLRS)is a premier orthopedic specialty organization that promotes limb reconstruction for all ages.LLRS membership characteristics,however,are poorly reported.This study delineates orthopedic surgeon LLRS members’demographic traits,academic achievement,leadership attainment,and geographical distribution across the United States.AIM To inform aspiring orthopedic professionals,as well as to promote growth and diversity in both the LLRS organization and overarching field.METHODS This cross-sectional study examined United States LLRS members’academic,leadership,demographic,and geographical attributes.After reviewing the 2023 LLRS member directory,Google search results were matched to the listings and appended to the compiled data.Sex and ethnicity were evaluated visually utilizing retrieved images.The Hirsch index(H-index)of academic activity,residency and fellowship training,other graduate degrees,leadership positions,practice type(academic or non-academic),and spoken languages were categorized.LLRS members per state and capita determined geographic distribution.The Mann Whitney U test was applied to compare H-index between males and females,as well as to assess member differences pertaining to affiliation with academic vs non-academic practice facilities.RESULTS The study included 101 orthopedic surgeons,78(77.23%)Caucasian and 23(22.77%)non-Caucasian,79(78.22%)male and 22(21.78%)female.Surgeons with DO degrees comprised only 3.96%(4)of the cohort,while the vast majority held MDs[96.04%(97)].Mean H-index was 10.55,with male surgeons having a significantly higher score(P=0.002).Most orthopedic surgeons(88.12%,)practiced in academic centers.Of those professionals who occupied leadership positions,14%were women,while 86%were men.Additionally,19(37.25%)United States regions and the District of Columbia lacked an LLRS-member orthopedic surgeon.Total per capita rate across the United States was 0.30 LLRS orthopedic surgeons per 1 million people.CONCLUSION Over 21

关键词： Limb lengthening and reconstruction Orthopedic surgeon demographics Orthopedic surgeon societal membership Orthopedic fellowships

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