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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 *** 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 *** first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward *** effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using ***,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated ***,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 *** 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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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 *** membership characteristics,however,are poorly *** study delineates orthopedic surgeon LLRS members’demographic traits,academic achievement,leadership attainment,and geographical distribution across the United *** To inform aspiring orthopedic professionals,as well as to promote growth and diversity in both the LLRS organization and overarching *** This cross-sectional study examined United States LLRS members’academic,leadership,demographic,and geographical *** reviewing the 2023 LLRS member directory,Google search results were matched to the listings and appended to the compiled *** and ethnicity were evaluated visually utilizing retrieved *** 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 *** members per state and capita determined geographic *** 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 *** The study included 101 orthopedic surgeons,78(77.23%)Caucasian and 23(22.77%)non-Caucasian,79(78.22%)male and 22(21.78%)*** 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 *** those professionals who occupied leadership positions,14%were women,while 86%were ***,19(37.25%)United States regions and the District of Columbia lacked an LLRS-member orthopedic *** per capita rate across the United States was 0.30 LLRS orthopedic

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

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Evidence-based orthobiologic practice:Current evidence review and future directions

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World Journal of orthopedics 2024年第10期15卷 908-917页

作者： Madhan Jeyaraman Naveen Jeyaraman Swaminathan Ramasubramanian Sangeetha Balaji Sathish Muthu Department of orthopedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennai 600077Tamil NaduIndia Department of Research Methods Orthopedic Research GroupCoimbatore 641045Tamil NaduIndia Department of Orthopedic Government Medical CollegeOmandurar Government EstateChennai 600002Tamil NaduIndia Department of orthopedics Government Medical College and HospitalKarur 639004Tamil NaduIndia Department of Biotechnology Faculty of EngineeringKarpagam Academy of Higher EducationCoimbatore 641021Tamil NaduIndia

The field of orthopedic and regenerative medicine is rapidly evolving with the increasing utilization of *** biologically derived therapies,inc-luding platelet-rich plasma,mesenchymal stem cells,bone marrow aspirate con-centrate,stromal vascular fraction(SVF),and autologous chondrocyte implanta-tion,are gaining traction for their potential to enhance the body's natural healing *** offer a promising alternative to traditional surgical interventions for musculoskeletal injuries and degenerative *** evidence su-ggests significant benefits of orthobiologics in treating conditions like osteoarth-ritis,tendon injuries,and spinal disorders,yet inconsistencies in treatment pro-tocols and outcomes *** global market for orthobiologics is projected to grow substantially,driven by advancements in biologic therapies such as adipose-derived stem cells and SVF,and the demand for minimally invasive *** their promise,regulatory and ethical challenges,as well as the need for high-quality,standardized research,remain significant *** dire-ctions in the field include advancements in delivery systems,personalized medi-cine approaches,and the exploration of novel sources like induced pluripotent stem cells,aiming for more targeted and effective *** efforts are crucial to overcoming these challenges and ensuring the safe and effective application of orthobiologics in clinical practice.

关键词： Orthobiologics Platelet-rich plasma Stem cells Musculoskeletal regeneration Regenerative medicine Evidence-based medicine

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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 *** secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue *** previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal *** three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)***,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains *** 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 *** 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 *** 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 *** 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 ***,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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The future path to sutureless surgery:Self–adhesive tough hydrogel

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Science Bulletin 2024年第15期69卷 2307-2310页

作者： Lei Xiang Ding Zhao Yihan Li Qimanguli Saiding Wenguo Cui Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Surgical sutures serve as foundational elements in surgical procedures,facilitating wound closure,exudation minimization,infection prevention,structural support maintenance,and healing *** classification of traditional surgical suturing methods is intricate,and contingent upon variables such as tissue type,wound morphology,and desired healing outcomes.

关键词： healing wound prevention

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pH-Responsive Theranostic Colloidosome Drug Carriers Enable Real-Time Imaging of Targeted Thrombolytic Process with Near-Infrared-II for Deep Venous Thrombosis

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Research 2024年第3期2024卷 17-33页

作者： Yaxin Ye Zhechang Chen Shengzhang Zhang Paul Slezak Fei Lu Ruiqi Xie Dongwon Lee Guangqian Lan Enling Hu State Key Laboratory of Resource Insects College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing 400715China Department of Cardiovascular Medicine Yueqing People's Hospital.Wenzhou 325699China Ludwig Boltzmann institute for traumatology AUVA Research Center1200 ViennaAustria Department of Bionanotechnology and Bioconvergence Engineering and Department of Polymer-Nano Science and Technology Jeonbuk National UniversityJeonjuChonbuk 54896Republic of Korea School of Fashion and Textiles The Hong Kong Polytechnic UniversityHong KongChina

Thrombosis can cause life-threatening disorders. Unfortunately, current therapeutic methods for thrombosis using injecting thrombolytic medicines systemically resulted in unexpected bleeding complications. Moreover, the absence of practical imaging tools for thrombi raised dangers of undertreatment and overtreatment. This study develops a theranostic drug carrier, Pkr(IR-Ca/Pda-uPA)-cRGD, that enables real-time monitoring of the targeted thrombolytic process of deep vein thrombosis (DVT). Pkr(IR-Ca/Pda-uPA)-cRGD, which is prepared from a Pickering-emulsion-like system, encapsulates both near-infrared-II (NIR-II) contrast agent (IR-1048 dye, loading capacity: 28%) and urokinase plasminogen activators (uPAs, encapsulation efficiency: 89%), pioneering the loading of multiple drugs with contrasting hydrophilicity into one single-drug carrier. Upon intravenous injection, Pkr(IR-Ca/Pda-uPA)-cRGD considerably targets to thrombi selectively (targeting rate: 91%) and disintegrates in response to acidic thrombi to release IR-1048 dye and uPA for imaging and thrombolysis, respectively. Investigations indicate that Pkr(IR-Ca/Pda-uPA)-cRGD enabled real-time visualization of targeted thrombolysis using NIR-II imaging in DVT models, in which thrombi were eliminated (120 min after drug injection) without bleeding complications. This may be the first study using convenient NIR-II imaging for real-time visualization of targeted thrombolysis. It represents the precision medicine that enables rapid response to acquire instantaneous medical images and make necessary real-time adjustments to diagnostic and therapeutic protocols during treatment.

关键词： Infrared enable eliminated

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of traumatology and orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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Aging impairs the osteocytic regulation of collagen integrity and bone quality

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Bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya Neha Dole Nadja M.Maldonado Luna Natalia Castillo Ryan Potter Jacob P.Rose Joanna Bons Christina D.King Jordan B.Burton Birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley/UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Buck institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly *** molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by *** hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material *** examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses *** control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)*** relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical *** effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

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Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties

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Military Medical Research 2024年第4期11卷 543-566页

作者： Ying Chen Xing Wang Sheng Tao Qi Wang Pan-Qin Ma Zi-Biao Li Yun-Long Wu Da-Wei Li Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiamen 361102FujianChina Beijing National Laboratory for Molecular Sciences Institute of ChemistryChinese Academy of SciencesBeijing 100090China University of Chinese Academy of Sciences Beijing 100049China Senior Department of orthopedics the Fourth Medical Center of Chinese PLA General HospitalBeijing 100091China institute of Materials Research and Engineering A*STAR(Agency for ScienceTechnology and Research)Singapore 138634Singapore

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical *** reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity,good drug-loading ability and sustained drug release *** a typical example,hyaluronic acid dressing(Healoderm)has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ***,the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound *** to the intricacy of diabetic wounds,antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice,although these medications are easily hindered by the hostile *** this case,scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds(such as high glucose and low pH)or combined with external stimuli(such as light or magnetic field)to achieve controllable drug release,gel degradation,and microenvironment improvements in order to overcome these clinical *** responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound ***,we review recent advances on responsive-hydrogel dressings towards diabetic wound healing,with focus on hydrogel structure design,the principle of responsiveness,and the behavior of *** but not least,the advantages and limitations of these responsive-hydrogels in clinical applications will also be *** hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

关键词： Responsive-hydrogel Diabetic wound Anti-inflammation Tissue remodeling

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Evolution of chemistry and selection technology for DNA-encoded library

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Acta Pharmaceutica Sinica B 2024年第2期14卷 492-516页

作者： Peixiang Ma Shuning Zhang Qianping Huang Yuang Gu Zhi Zhou Wei Hou Wei Yi Hongtao Xu Shanghai Key Laboratory of Orthopedic Implants Department of OrthopedicsShanghai Ninth People’s HospitalShanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China Shanghai institute for Advanced Immunochemical Studies ShanghaiTech UniversityShanghai 201210China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory DiseaseGuangzhou Medical UniversityGuangzhou 511436China College of Pharmaceutical Science and institute of Drug Development&Chemical Biology Zhejiang University of TechnologyHangzhou 310014China

DNA-encoded chemical library(DEL)links the power of amplifiable genetics and the nonself-replicating chemical phenotypes,generating a diverse chemical *** analogy with the biological world,the DEL world can evolve by using a chemical central dogma,wherein DNA replicates using the PCR reactions to amplify the genetic codes,DNA sequencing transcripts the genetic information,and DNA-compatible synthesis translates into chemical ***,DNA-compatible synthesis is the key to expanding the DEL chemical ***,the evolution-driven selection system pushes the chemicals to evolve under the selective pressure,i.e.,desired selection *** this perspective,we summarized recent advances in expanding DEL synthetic toolbox and panning strategies,which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

关键词： DNA-encoded library Drug discovery High-throughput selection DNA-compatible synthesis In vitro evolution Chemical central dogma

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