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Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma

Cancer Innovation 2024年第2期3卷 80-95页

作者： Satoru Sasagawa Jun Kumai Toru Wakamatsu Yoshihiro Yui Molecular Biology laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Sarcoma Treatment laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Department of musculoskeletal Oncology Service Osaka International Cancer InstituteOsakaJapan

Background:Synovial sarcoma(SS)is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics,associated with a poor prognosis due to frequent metastasis to a distant organ,such as the *** deacetylase(HDAC)inhibitors(HDACis)are arising as potent molecular targeted drugs,as HDACi treatment disrupts the SS oncoprotein complex,which includes HDACs,in addition to general HDACi *** provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells,we examined cellular responses to HDACi treatment in combination with two-dimensional(2D)and 3D culture ***:Using several SS cell lines,biochemical and cell biological assays were performed with romidepsin,an HDAC1/2 selective ***38 was concomitantly used as an ameliorant drug with romidepsin ***,apoptosis induction,and MHC class I polypeptide-related sequence A/B(MICA/B)induction were monitored to evaluate the drug *** addition to the conventional 2D culture condition,spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on ***:By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells,we observed that responsiveness is diverse in each cell *** the apoptotic inducible cells,co-treatment with SN38 enhanced cell *** nonapoptotic inducible cells,cytostasis and MICA/B induction were observed,and SN38 improved MICA/B induction *** a novel efficacy of SN38,we revealed TWIST1 suppression in SS *** the spheroid(3D)condition,romidepsin efficacy was severely restricted in TWIST1-positive *** demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form,and concomitant SN38 treatment along with romidepsin reproduced the ***:The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and

关键词： HDAC inhibitor MICA/B SN38 spheroid synovial sarcoma TWIST1

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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

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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

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Design Improvements and Validation of a Novel Fully 3D Printed Analogue Lumbar Spine Motion Segment

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Journal of Bionic Engineering 2024年第3期21卷 1388-1396页

作者： Siril Teja Dukkipati Mark Driscoll musculoskeletal Biomechanics research Lab Department of Mechanical EngineeringMcGill University845 Sherbrooke St.W(163)MontréalQCH3A 0C3Canada Orthopaedic research Lab Montreal General Hospital1650 Cedar Ave(LS1.409)MontréalQCH3G 1A4Canada

Spine biomechanical testing methods in the past few decades have not evolved beyond employing either cadaveric studies or finite element modeling ***,both these approaches may have inherent cost and time *** studies are the present gold standard for spinal implant design and regulatory approval,but they introduce significant variability in measurements across patients,often requiring large sample *** element modeling demands considerable expertise and can be computationally expensive when complex geometry and material nonlinearity are *** analogue spine models could complement these traditional methods as a low-cost and high-fidelity alternative.A fully 3D printable L-S1 analogue spine model with ligaments is developed and validated in this *** stiffness of the model under pure bending loading in flexion-extension,Lateral Bending(LB)and Axial Rotation(AR)is evaluated and compared against historical ex vivo and in silico ***,the effect of interspinous,intertransverse ligaments and the Thoracolumbar Fascia(TLF)on spinal stiffness is evaluated by systematic construction of the *** flexion,model Range of Motion(ROM)was 12.92±0.11°(ex vivo:16.58°,in silico:12.96°)at *** LB,average ROM was 13.67±0.12°at 7.5 Nm(ex vivo:15.21±1.89°,in silico:15.49±0.23°).Similarly,in AR,average ROM was 17.69±2.12°at 7.5Nm(ex vivo:14.12±0.31°,in silico:15.91±0.28°).The addition of interspinous and intertransverse ligaments increased both flexion and LB stiffnesses by approximately 5%.Addition of TLF showed increase in flexion and AR stiffnesses by 29%and 24%,*** novel model can reproduce physiological ROMs with high repeatability and could be a useful open-source tool in spine biomechanics.

关键词： Lumbar spine 3D printing Intervertebral disc Biomechanical testing Spine mechanics

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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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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

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Ultrasmall copper-based clusterzymes ameliorate Achilles tendinopathy by inhibiting acute oxidative stress

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Nano research 2024年第6期17卷 5374-5389页

作者： Xuzhuo Chen Yi Du Yazi Huang Xianhao Zhou Xinru Xie Chang Li Chen Zhao Fengrong Dai Xijiao Yu Shanyong Zhang Department of Oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai 200011China Department of Endodontics Central LaboratoryJinan Stomatological HospitalJinan Key Laboratory of Oral Tissue RegenerationShandong Provincial Health Commission Key Laboratory of Oral Diseases and Tissue RegenerationJinan 250001China State Key laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China Department of Chemistry College of Chemistry and EnvironmentGuangdong Ocean UniversityZhanjiang 524088China Department of Orthopedics Shanghai Key Laboratory of Orthopedic ImplantShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

Tendinopathy is a prevalent musculoskeletal disorder,accounting for over 30%of musculoskeletal ***,current therapeutic strategies for tendinopathy are limited and often yield unsatisfactory clinical ***,there is a critical need to explore novel therapeutic approaches with minimal side effects for tendinopathy and its early *** this study,we successfully designed and synthesized a copper(I)-based nanocluster,named Cu_(11),which possesses remarkable enzyme-like and ROS-scavenging *** unique combination of properties qualifies Cu_(11)as an attractive anti-inflammatory and anti-ROS *** Cu_(11)clusterzymes specifically target mitochondria,effectively scavenging excessive reactive oxygen species(ROS)and reducing oxidative ***,Cu_(11)clusterzymes inhibit the activation of key signaling pathways involved in inflammation,namely tumor necrosis factor(TNF),mitogen-activated protein kinase(MAPK),and nuclear factor(NF)-κB,leading to a decrease in the release of proinflammatory ***,our in vivo experiments using a collagenase-induced acute Achilles tendinopathy model demonstrated that Cu_(11)clusterzymes effectively alleviate inflammation and oxidative stress,without causing systemic *** study highlights the potential of copper-based clusterzymes as therapeutic agents for the treatment of Achilles tendinopathy and other inflammatory *** unique enzyme-like and ROS-scavenging activities of Cu_(11)make it a promising candidate for further development and clinical translation.

关键词： nanoclusters clusterzymes oxidative stress tendinopathy reactive oxygen species(ROS)

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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

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Management and classification of the fracture of lateral process of talus:An overview and literature update

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World Journal of Clinical Cases 2024年第15期12卷 2487-2498页

作者： Chao-Qun Wang Ulrich Stockle Sheng-Nan Dong Xu-Gui Li Ze-Xi Ling Department of Traumatic Orthopedics The Affiliated Hospital of Wuhan Sports UniversityWuhan 430079Hubei ProvinceChina Center of musculoskeletal Surgery Berlin CharitéMedical University HospitalBerlin 13353Germany

Fracture of the lateral process of the talus(FLPT)is uncommon in clinical practice and can be easily missed or *** recent years,as researchers from all over the world have further deepened their research on FLPT,there has been a breakthrough in the classification,and the methods and principles of clinical management have changed accordingly;however,there is still no standardized guideline for the diagnosis and management of FLPT,and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 *** this article,we review the clinical classification,classification-based therapeutic recommendations,and prognosis of FLPT,with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.

关键词： Fracture of the lateral process of the talus Fracture of the talus Hindfoot injuries Intraarticular fracture Subtalar joint

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Flexible assistance strategy of lower limb rehabilitation exoskeleton based on admittance model

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Science China(Technological Sciences) 2024年第3期67卷 823-834页

作者： KOU JianGe WANG YiXuan CHEN ZhenLei SHI Yan GUO Qing XU Meng School of Automation Science and Electrical Engineering Beihang UniversityBeijing 100191China School of Aeronautics and Astronautics University of Electronic Science and Technology of ChinaChengdu 611731China Department of musculoskeletal Tumor Senior Department of Orthopedicsthe Fourth Medical Centerof PLA GeneralHospitalBeijing 100853China

Exercise training based on exoskeleton is an effective rehabilitation method for stroke patients. However, some rehabilitation exoskeletons still have poor wearable performance and obvious human-robot impedance during training, which easily cause secondary injuries to the patients. In this study, a variable admittance control strategy is proposed to improve the operator's wearable comfort, which can adapt to different operators by regulating admittance parameters. The admittance controller has two feedback loops: the position inner-loop and the admittance outer-loop. Meanwhile, the exoskeleton Lagrange model is constructed with unknown friction disturbance. By using Lyapunov technique and backstepping with state observer, the joint position error of exoskeleton is convergence into a zero neighborhood. The effectiveness of the proposed admittance controller is verified by both simulation and experiment. The tracking error of hip and knee joint is less than 4 degrees while the human-robot interaction torque is constrained in a tolerable range of the operator.

关键词： human-robot interaction exoskeleton backstepping admittance control

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