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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

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

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

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

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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Military Medical Research 2024年第2期11卷 287-307页

作者： Pan Luo Fu-Qiang Gao Wei Sun Jun-You Li Cheng Wang Qing-Yu Zhang Zhi-Zhuo Li Peng Xu department of Joint surgery Honghui HospitalXi'an Jiaotong UniversityXi'an 710054China department of orthopedics China-Japan Friendship HospitalBeijing 100029China department of Orthopaedic surgery of the Perelman School of Medicine University of PennsylvaniaPhiladelphiaPA 19104USA School of Mechanical Engineering Sungkyunkwan UniversitySuwon 16419South Korea department of Orthopaedic surgery Peking University Third HospitalPeking UniversityBeijing 100191China department of orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life ***,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of *** fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo ***,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

关键词： Rheumatoid arthritis Fluorescent probe Imaging Diagnosis Biomarker

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

Advances in the application of hydrogel-based scaffolds for tendon repair

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Genes & Diseases 2024年第4期11卷 296-313页

作者： Renqiang Chen Fanglin Chen Kenian Chen Jian Xu department of orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China department of orthopedics The Fourth Affiliated Hospital of Guangxi Medical UniversityLiuzhou Guangxi 545005China

Tendon injuries often lead to joint dysfunction due to the limited self-regeneration capacity of *** tendons is a major challenge for surgeons and imposes a signif-icant financial burden on ***,there is an urgent need to develop effective stra-tegies for repairing injured *** tissue engineering using hydrogels has emerged as a promising approach that has attracted considerable *** possess excellent biocompatibility and biodegradability,enabling them to create an extracellular matrix-like growth environment for *** can also serve as a carrier for cells or other substances to accelerate tendon *** the past decade,numerous studies have made significant prog-ress in the preparation of hydrogel scaffolds for tendon *** review aims to provide an overview of recent research on the materials of hydrogel-based scaffolds used for tendon tis-sue engineering and discusses the delivery systems based on them.

关键词： Application Hydrogel-based Repairscaffolds Review Tendon injury Tissue engineering

Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52

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Journal of Pharmaceutical Analysis 2024年第1期14卷 86-99页

作者： Shengyou Li Xue Gao Yi Zheng Yujie Yang Jianbo Gao Dan Geng Lingli Guo Teng Ma Yiming Hao Bin Wei Liangliang Huang Yitao Wei Bing Xia Zhuojing Luo Jinghui Huang department of orthopedics Xijing HospitalFourth Military Medical UniversityXi'an710032China

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

关键词： Ferroptosis UBA52 Ferroportin Ubiquitination Hydralazine Peripheral nerve injury

Neurophysiological, histological, and behavioral characterization of animal models of distraction spinal cord injury: a systematic review

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Neural Regeneration Research 2024年第3期19卷 563-570页

作者： Bo Han Weishi Liang Yong Hai Duan Sun Hongtao Ding Yihan Yang Peng Yin department of orthopedics Beijing Chao-Yang HospitalCapital Medical UniversityBeijingChina

Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal *** the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and *** few studies have been published on the specific characteristics of distraction spinal cord *** this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this *** addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord *** provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.

关键词： animal models behavior distraction heterogeneity histology mechanism neurophysiology spinal cord injury systematic review tension