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Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis

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

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

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

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

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

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

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

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

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

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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

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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

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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

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Metal ion metabolism and osteoporosis:possible implications for pharmaceutical biotechnology and tissue engineering

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Science China(Life Sciences) 2024年第8期67卷 1763-1765页

作者： Huaqiang Tao Qiufei Wang Kai Chen Pengfei Zhu Ye Gu Dechun Geng department of orthopedics The First Affiliated Hospital of Soochow UniversitySuzhou 215000China department of orthopedics Changshu Hospital Affiliated to Soochow UniversityFirst People’s Hospital of Changshu CityChangshu 215506China department of orthopedics Hai’an People’s HospitalHai’an 226600China

Osteoporosis(OP)is a systemic metabolic bone disease characterized by low bone mass,damage to bone microstructure and increased bone *** imbalance of functional coupling between osteoblasts and osteoclasts contributes to the pathological progression of the disease(Rachner et al.,2011).The pathogenesis of OP is precisely controlled by the complex regulatory network of the bone *** elements,although present in small amounts in the body,are essential for their influence on the physiological activities of *** ions act as effective catalysts and have applications in all stages of cell biochemical evolution(Qian et al.,2021).Bone tissue contains various metal elements,and metal ions play indispensable roles in bone metabolism at the molecular and cellular levels(Luo et al.,2023).However,it is important to note that these metal ions can also contribute to the progression of OP by influencing multiple cellular pathways either directly or indirectly.

关键词： metabolism biotechnology indispensable

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Delayed neurological dysfunction following posterior laminectomy with lateral mass screw fixation:A case report and review of literature

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World Journal of Clinical Cases 2024年第7期12卷 1356-1364页

作者： Rui-Zhong Yan Chao Chen Chu-Ran Lin Yan-Hui Wei Zhi-Jian Guo Ya-Kun Li Quan Zhang He-Yi Shen Hao-Lin Sun department of orthopedics Taiyuan Central HospitalTaiyuan 030009Shanxi ProvinceChina department of orthopedics Graduate School Shanxi University of Traditional Chinese MedicineTaiyuan 030024Shanxi ProvinceChina department of orthopedics Peking University First HospitalBeijing 100034China

BACKGROUND While most complications of cervical surgery are reversible,some,such as symptomatic postoperative spinal epidural hematoma(SEH),which generally occurs within 24 h,are associated with increased morbidity and *** neurological dysfunction is diagnosed in cases when symptoms present>3 d *** to its rarity,the risk factors for delayed neurological dysfunction are ***,this condition can result in irreversible neurological deficits and serious *** this paper,we present a case of postoperative SEH that developed three days after hematoma *** SUMMARY A 68-year-old man with an American Spinal Injury Association(ASIA)grade C injury was admitted to our hospital with neck pain and tetraplegia following a *** C3-C7 posterior laminectomy and the lateral mass screw fixation surgery were performed on the tenth ***,the patient showed no changes in muscle strength or ASIA *** patient experienced neck pain and subcutaneous swelling on the third day postoperatively,his muscle strength decreased,and his ASIA score was grade *** resonance imaging showed hypointense signals on T1 weighted image(T1WI)and T2WI located behind the epidural space,with spinal cord *** surgical intervention for the hematoma was performed 12 h after *** hypoproteinemia and pleural effusion did not improve in the perioperative period,the patient recovered to ASIA grade C on day 30 after surgery,and was transferred to a functional rehabilitation exercise *** This case shows that amelioration of low blood albumin and pleural effusion is an important aspect of the perioperative management of cervical *** to relieve the pressure on the spinal cord should be performed as soon as possible to decrease neurological disabilities.

关键词： Delayed postoperative spinal epidural hematoma Complications Spinal surgery Hypoproteinemia Risk factor Case report

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Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn

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Current Medical Science 2024年第2期44卷 369-379页

作者： Ji LUO Jin ZHOU Jing-zeng LUO Hai-long WANG Xue-ling ZHAO Ru-dan ZHOU department of Intensive Care Unit The First People's Hospital of ZiyangZiyang 641300China department of orthopedics Kunming Medical University Second Affiliated HospitalKunming 650033China department of orthopedics Kunming Medical University First Affiliated HospitalKunming 650032China department of orthopedics The Third People's Hospital of Yunnan ProvinceKunming 650200China

Objective:Matrix metalloproteinase 13(MMP13)is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens,modifying protein structures and regulating inflammatory responses,but its role in deep vein thrombosis(DVT)has not been *** purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of ***:We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of *** screening genes possibly related to MMP13 in DVT mice,the expression levels of candidate genes in human umbilical vein endothelial cells(HUVECs)and the venous wall were *** effect of MMP13 on platelet aggregation in HUVECs was investigated in ***:Among the differentially expressed genes,interleukin 1 beta,podoplanin(Pdpn),and factor VIII von Willebrand factor(F8VWF)were selected for analysis in *** MMP13 was inhibited,the expression level of PDPN decreased significantly in *** HUVECs,overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation,while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet ***:Inhibiting the expression of MMP13 could reduce the burden of DVT in *** mechanism involves downregulating the expression of Pdpn through MMP13,which could provide a novel gene target for DVT diagnosis and treatment.

关键词： deep vein thrombosis matrix metalloproteinase 13 podoplanin

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Argatroban promotes recovery of spinal cord injury by inhibiting the PAR1/JAK2/STAT3 signaling pathway

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Neural Regeneration Research 2024年第2期19卷 434-439页

作者： Chenxi Zhao Tiangang Zhou Ming Li Jie Liu Xiaoqing Zhao Yilin Pang Xinjie Liu Jiawei Zhang Lei Ma Wenxiang Li Xue Yao Shiqing Feng department of orthopedics Tianjin Medical University General HospitalTianjinChina International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina Orthopedic Research Center of Shandong University Cheeloo College of MedicineDepartment of OrthopedicsQilu Hospital of Shandong UniversityJinanShandong ProvinceChina

Argatroban is a synthetic thrombin inhibitor approved by *** and Drug Administration for the treatment of ***,whether it plays a role in the repair of spinal cord injury is *** this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive *** results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal *** sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar *** blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal *** also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal *** together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.

关键词： argatroban astrogliosis JAK/STAT signaling pathway protease-activated receptor-1 spinal cord injury thrombin vimentin

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Cemented vertebra and adjacent vertebra refractured in a chronic kidney disease-mineral and bone disorder patient: A case report

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World Journal of Clinical Cases 2024年第10期12卷 1804-1809页

作者： Ti-Dong Zhang Shuai Cao Hui-Yong Ren Yu-Min Li Yi-Ming Yuan department of orthopedics Civil Aviation General HospitalBeijing 100123China

BACKGROUND Although percutaneous vertebral augmentation(PVA)is a commonly used procedure for treating vertebral compression fracture(VCF),the risk of vertebral refracture should be *** kidney disease-mineral and bone disorder(CKD-MBD)is a systemic disease of mineral and bone *** is associated with an increased risk of *** studies have reported the use of PVA in patients with *** herein report a rare case wherein the cemented vertebra and the adjacent vertebra refractured simultaneously in a CKD-MBD patient after *** SUMMARY A 74-year-old man suffered from low back pain after taking a fall about 3 wk *** to physical examination,imaging and laboratory findings,diagnoses of T12 VCF,CKD-MBD,and chronic kidney disease stage 5 were *** then received percutaneous vertebroplasty at T12 *** weeks later,he presented with T12 and L1 vertebral refractures caused by lumbar *** again,he was given PVA which was optimized for the refractured *** the short-term postoperative effect was satisfactory,he reported chronic low back pain again at the 3-month *** It is necessary that patients with CKD-MBD who have received PVA are aware of the adverse effects of *** may increase the risk of vertebral ***,the PVA surgical technique needs to be optimized according to the condition of the *** medium-and long-term effects of PVA remain uncertain in patients with CKD-MBD.

关键词： Chronic kidney disease-mineral and bone disorder Percutaneous vertebral augmentation Vertebral compression fracture Vertebral refracture Cemented vertebra Adjacent vertebra Case report

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