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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

Deficiency of Trp53 and Rb1 in myeloid cell lineage spontaneously develops acute myeloid leukemia in a mouse model

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Genes & Diseases 2024年第1期11卷 4-6页

作者： Yang Li Shu-ting Yang Shuying Yang Department of Basic&Translational Sciences School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Orthopaedic surgery School of MedicineJohns Hopkins University BaltimoreMD 21205USA center for Innovation&Precision Dentistry School of Dental MedicineSchool of Engineering and Applied SciencesUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Penn center for musculoskeletal Disorders School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Acute myeloid leukemia(AML)is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic *** recent decades,AML patients are significantly *** 2019 alone,21,450 new AML cases were diagnosed in the United States,with an estimated 10,920 deaths due to ***’s worse,AML occurs with an increasing incidence with advanced age,and the survival rate remains dismal with a median overall survival of only 5e10 *** great advances in allogenic transplant and chemotherapy,the therapeutic outcomes are unfavorable due to the disease relapse and mortality *** importantly,the development of more specific and effective therapies was hampered in part by the lack of proper animal models for ***,management and elucidation of the pathological mechanism of AML remain an ongoing challenge,and the development of effective AML mouse models and treatment options are urgently needed.

关键词： myeloid Acute leukemia

The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon Lee Sowmya Ramesh Aaron W.James David Hudson Kevin N.Dalby Lin Xu Robert J.Tower Benjamin Levi center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

Biophysical-driven piezoelectric and aligned nanofibrous scaffold promotes bone regeneration by re-establishing physiological electrical microenvironment

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Nano Research 2024年第8期17卷 7376-7393页

作者： Aoao Wang Xinbo Ma Yafeng Yang Guoliang Shi Liwei Han Xiantong Hu Rui Shi Jun Yan Quanyi Guo Yantao Zhao Senior Department of Orthopedics the Fourth Medical Center of PLA General HospitalBeijing 100048China Department of Chemistry Capital Normal UniversityBeijing 100048China National center for Orthopaedics Beijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Xijing 986 Hospital Department The Fourth Military Medical UniversityXi'an 710032China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Laboratory of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing 100853China

The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events,including pathogen clearance,immunological modulation,and *** this study,we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PCL/PVDF with multiple antibacterial,immunomodulatory,and osteogenic effects using electrospinning *** scaffold’s piezoelectric signal output under ultrasound(US)control can be similar to the physiological electrical signals of healthy bone tissue,creating a truly biomimetic electrical microenvironment in the bone *** vitro studies have shown that ZnO@PCL/PVDF scaffold significantly enhances the proliferation,migration,and osteogenic differentiation of MC3T3-E1 cells under piezoelectric drive provided by ***,the scaffold exhibits inhibitory effects on the growth of *** and ***,as well as the ability to induce M2 macrophage polarization,indicating potent antibacterial and immunomodulatory *** vivo experiments demonstrated that the ZnO@PCL/PVDF scaffold can accelerate the repair of mandibular defects in rats,effectively inhibit bacterial colonization,and reduce inflammatory ***,this study confirms that the newly developed ZnO@PCL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing,thus providing a simple and effective solution for bone defects.

关键词： piezoelectricity bone defect bacterial infection ZnO nanoparticles immunomodulation osteogenesis

Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature

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Chinese Journal of Traumatology 2024年第2期27卷 114-120页

作者： Sheng-Feng Chen Bo-Yao Yang Tie-Yuan Zhang Xiang-Yu Song Zhi-Bo Jia Lei-Jia Chen Meng-Yi Cui Wen-Jing Xu Jiang Peng Guizhou Medical University Guiyang550025China Medical School of PLA Beijing100048 China Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLADepartment of OrthopedicsThe Fourth Medical CenterChinese PLA General HospitalBeijing100048China Hebei North Universiy Zhangjiakou075000Hebei ProvinceChina

Purpose:Ischemia and hypoxia are the main factors limiting limb replantation and *** cold storage(SCS),a common preservation method for tissues and organs,can only prolong limb ischemia time to 4-6 *** normothermic machine perfusion(NMP)is a promising method for the preservation of tissues and organs,which can extend the preservation time in vitro by providing continuous oxygen and *** study aimed to evaluate the difference in the efficacy of the 2 limb preservation ***:The 6 forelimbs from beagle dogs were divided into 2 *** the SCS group(n=3),the limbs were preserved in a sterile refrigerator at 4°C for 24 h,and in the NMP group(n=3),the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h,and the solution was changed every 6 *** effects of limb storage were evaluated by weight gain,perfusate biochemical analysis,enzyme-linked immunosorbent assay,and histological *** statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of *** p value of less than 0.05 was considered to indicate statistical ***:In the NMP group,the weight gained percentage was 11.72%±4.06%;the hypoxia-inducible factor-1αcontents showed no significant changes;the shape of muscle fibers was normal;the gap between muscle fibers slightly increased,showing the intercellular distance of(30.19±2.83)μm;and the vascularα-smooth muscle actin(α-SMA)contents were lower than those in the normal blood *** creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion,decreased after each perfusate change,and remained stable at the end of perfusion showing a peak level of 4097.6 U/*** lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/*** the SCS group,the percentage of weight gain was 0.18%±0.10%,a

关键词： Traumatic amputation Machine perfusion Static cold storage Limb replantation

The marriage of immunomodulatory,angiogenic,and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scafold for military medicine

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Military Medical Research 2024年第3期11卷 323-344页

作者： Ping Wu Lin Shen Hui-Fan Liu Xiang-Hui Zou Juan Zhao Yu Huang Yu-Fan Zhu Zhao-Yu Li Chao Xu Li-Hua Luo Zhi-Qiang Luo Min-Hao Wu Lin Cai Xiao-Kun Li Zhou-Guang Wang Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research the Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000ZhejiangChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhou 325000ZhejiangChina Department of Spine surgery and musculoskeletal Tumor Zhongnan Hospital of Wuhan UniversityWuhan 430071China National Engineering Research center for Nanomedicine College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Department of Overseas Education College Jimei UniversityXiamen 361021FujianChina School and Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325035ZhejiangChina

Background:Most bone-related injuries to grassroots troops are caused by training or accidental *** establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone ***:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)*** physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were *** and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in ***:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated *** to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 *** in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury *** underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 ***:The piezoelectric Cs/Gel/PHA/PBT hy

关键词： Piezoelectric hydrogel Tissue engineering scafold Immunomodulation Angiogenesis Osteogenic differentiation

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

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 *** 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 *** shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after *** Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to *** 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 *** 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 *** 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 *** vivo degradation of the magnesium alloy wire was completed within 12 *** 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

High formability Mg-Zn-Gd wire facilitates ACL reconstruction via its swift degradation to accelerate intra-tunnel endochondral ossification

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Journal of Magnesium and Alloys 2024年第1期12卷 295-315页

作者： Xuan He Ye Li Hongwei Miao Jiankun Xu Michael Tim-yun Ong Chenmin Wang Lizhen Zheng Jiali Wang Le Huang Haiyue Zu Zhi Yao Jie Mi Bingyang Dai Xu Li Patrick Shu-hang Yung Guangyin Yuan Ling Qin musculoskeletal Research Laboratory of Department of Orthopaedics&Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongHong KongChina National Engineering Research center of Light Alloy Net Forming School of Materials Science&EngineeringShanghai Jiao Tong UniversityShanghaiChina Department of Orthopaedics and Traumatology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Orthopaedic Department Peking University Third HospitalBeijingChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong KongChina

After reconstructing the anterior cruciate ligament(ACL),unsatisfactory bone tendon interface healing may often induce tunnel enlargement at the early healing *** good biological features and high formability,Magnesium-Zinc-Gadolinium(ZG21)wires are developed to bunch the tendon graft for matching the bone tunnel during ***,tensile strength,degradation,and cytotoxicity of ZG21 wire are *** rabbit model is used for assessing the biological effects of ZG21 wire by Micro-CT,histology,and mechanical *** SEM/EDS,immunochemistry,and in vitro assessments are performed to investigate the underlying *** tests demonstrate the high formability of ZG21 wire as surgical ***-CT shows ZG21 wire degradation accelerates tunnel bone formation,and histologically with earlier and more fibrocartilage regeneration at the healing *** mechanical test shows higher ultimate load in the ZG21 *** SEM/EDS presents ZG21 wire degradation triggered calcium phosphate(Ca-P)*** results demonstrate upregulation of Wnt3a,BMP2,and VEGF at the early phase and TGFβ3 and Type II collagen at the late phase of *** vitro tests also confirmed the Ca-P in the metal extract could elevate the expression of Wnt3a,βcatenin,ocn and opn to stimulate *** vivo tests of clinical samples indicated suturing with ZG21 wire did not weaken the ultimate loading of human tendon *** conclusion,the ZG21 wire is feasible for tendon graft *** degradation products accelerated intra-tunnel endochondral ossification at the early healing stage and therefore enhanced bone-tendon interface healing in ACL reconstruction.

关键词： Magnesium wire ACL reconstruction Magnesium alloy Biomaterials Endochondral ossification