Pub Date : 2025-05-01DOI: 10.1016/j.jot.2025.03.018
Yang Zhao , Qianhua Ou , Hong Huang , Delong Li , Jianmao Chen , Song Xue , Zuoqing Zhou , Guangfeng Ruan , Changhai Ding
Objective
The effects of vitamins D and K on osteoarthritis (OA) progression remain ambiguous, particularly in its subtype, osteoporotic OA (OPOA), where aberrant activation of osteoclasts exacerbates subchondral bone remodeling. This study aimed to investigate the effect of 1,25-dihydroxyvitamin D3 (calcitriol) and menaquinone-4 (MK4) on OA and OPOA progression and explore their combined mechanisms in osteoclastogenesis inhibition.
Methods
Therapeutic effects of calcitriol and MK4 were evaluated in OA and OPOA models induced by medial meniscus destabilization (DMM) and bilateral ovariectomy (OVX). In vitro analyses assessed their impact on chondrocyte degradation and osteoclastogenesis. RNA sequencing of preosteoclasts elucidated the vitamins' anti-osteoclastogenic mechanisms.
Results
Combined administration of calcitriol and MK4 significantly attenuated cartilage degradation in OA and OPOA mouse models, though direct effects on chondrocyte degradation were limited. Importantly, calcitriol and MK4 jointly suppressed osteoclastogenesis in vivo and in vitro, ameliorating subchondral remodeling and reducing pain levels in OPOA mice. Mechanistically, osteoclast-associated receptor (OSCAR) mediated their anti-osteoclastogenic effects.
Conclusions
Calcitriol and MK4 confer enhanced benefits on OA and OPOA progression through OSCAR-mediated osteoclastogenesis inhibition in preosteoclasts.
The Translational potential of this article
This study demonstrates vitamins D and K as dual-action agents inhibiting osteoclastogenesis and normalizing subchondral bone remodeling both in OA and OPOA models, making it a potential therapeutic alternative for the disease.
{"title":"Vitamins D and K jointly protect against osteoarthritis via regulating OSCAR during osteoclastogenesis","authors":"Yang Zhao , Qianhua Ou , Hong Huang , Delong Li , Jianmao Chen , Song Xue , Zuoqing Zhou , Guangfeng Ruan , Changhai Ding","doi":"10.1016/j.jot.2025.03.018","DOIUrl":"10.1016/j.jot.2025.03.018","url":null,"abstract":"<div><h3>Objective</h3><div>The effects of vitamins D and K on osteoarthritis (OA) progression remain ambiguous, particularly in its subtype, osteoporotic OA (OPOA), where aberrant activation of osteoclasts exacerbates subchondral bone remodeling. This study aimed to investigate the effect of 1,25-dihydroxyvitamin D3 (calcitriol) and menaquinone-4 (MK4) on OA and OPOA progression and explore their combined mechanisms in osteoclastogenesis inhibition.</div></div><div><h3>Methods</h3><div>Therapeutic effects of calcitriol and MK4 were evaluated in OA and OPOA models induced by medial meniscus destabilization (DMM) and bilateral ovariectomy (OVX). In vitro analyses assessed their impact on chondrocyte degradation and osteoclastogenesis. RNA sequencing of preosteoclasts elucidated the vitamins' anti-osteoclastogenic mechanisms.</div></div><div><h3>Results</h3><div>Combined administration of calcitriol and MK4 significantly attenuated cartilage degradation in OA and OPOA mouse models, though direct effects on chondrocyte degradation were limited. Importantly, calcitriol and MK4 jointly suppressed osteoclastogenesis in vivo and in vitro, ameliorating subchondral remodeling and reducing pain levels in OPOA mice. Mechanistically, osteoclast-associated receptor (OSCAR) mediated their anti-osteoclastogenic effects.</div></div><div><h3>Conclusions</h3><div>Calcitriol and MK4 confer enhanced benefits on OA and OPOA progression through OSCAR-mediated osteoclastogenesis inhibition in preosteoclasts.</div></div><div><h3>The Translational potential of this article</h3><div>This study demonstrates vitamins D and K as dual-action agents inhibiting osteoclastogenesis and normalizing subchondral bone remodeling both in OA and OPOA models, making it a potential therapeutic alternative for the disease.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 387-403"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1016/j.jot.2025.03.006
Tianwu Chen , Yongtao Mao , Lunhao Bai , Xizhuang Bai , Qing Bi , Chen Chen , Liaobin Chen , Shiyi Chen , Wai Sin Chan , Guofeng Dai , Xuesong Dai , Lin Guo , Yang Guo , Yaohua He , Ning Hu , Yong Hu , Jingmin Huang , Xuan Huang , Xunwu Huang , Chang-Ming Huang , Jingbin Zhou
<div><h3>Background</h3><div>With the recent rise in anterior cruciate ligament (ACL) reconstruction surgeries in China, a corresponding increase in surgical failures has been observed. Variability in primary surgical techniques and the intricacies of failure mechanisms have introduced significant challenges in diagnosing failures, planning procedures, and conducting revision surgeries.</div></div><div><h3>Methods</h3><div>In response to these challenges, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) initiated the development of an expert consensus on ACL reconstruction failure and revision. Utilizing a modified Delphi method, 67 domestic experts from relevant fields were invited for consensus formulation and review.</div></div><div><h3>Results</h3><div>The expert panel achieved a high degree of consensus on twelve key aspects. The consensus clearly defines ACL reconstruction failure and outlines multiple contributing factors, with surgical errors, especially incorrect bone tunnel placement, identified as primary causes. It also emphasizes the significant impact of patient-specific variables on the likelihood of failure. Recommendations for revision surgeries include careful determination of revision indications, preserving meniscal integrity to reduce the risk of joint degeneration, and a preference for single-stage or two-stage surgeries based on individual patient evaluations. A unified approach for managing bone defects remains absent, necessitating comprehensive assessments. Graft selection should be tailored to each patient, with autografts, allografts, or synthetic ligaments as viable options. For patients with a highly positive pivot shift test or those engaged in high-demand athletic activities, anterolateral structure augmentation or reconstruction is recommended.</div></div><div><h3>Conclusion</h3><div>The consensus emphasizes the critical need for individualized approaches in ACL revision surgery. By clearly defining failure criteria and outlining strategies for surgical revisions, these statements are expected to serve as a guide for refining clinical practice, reducing complications, and improving surgical outcomes.</div></div><div><h3>The translational potential of this article</h3><div><ul><li><span>1)</span><span><div><strong>Establishment of Evidence-Based Clinical Guidelines:</strong> This article presents a rigorously developed expert consensus on ACL reconstruction failure and revision, providing evidence-based clinical guidelines that are directly applicable in surgical practice. The standardization of these protocols across medical institutions has the potential to reduce variability in patient care and improve surgical outcomes on a national scale.</div></span></li><li><span>2)</span><span><div><strong>Advancement of Precision Medicine in ACL Surgery:</strong> By emphasizing the need for patient-specific approaches in the management of ACL reconstruction failure, t
{"title":"Chinese expert consensus on failure and revision after anterior cruciate ligament reconstruction","authors":"Tianwu Chen , Yongtao Mao , Lunhao Bai , Xizhuang Bai , Qing Bi , Chen Chen , Liaobin Chen , Shiyi Chen , Wai Sin Chan , Guofeng Dai , Xuesong Dai , Lin Guo , Yang Guo , Yaohua He , Ning Hu , Yong Hu , Jingmin Huang , Xuan Huang , Xunwu Huang , Chang-Ming Huang , Jingbin Zhou","doi":"10.1016/j.jot.2025.03.006","DOIUrl":"10.1016/j.jot.2025.03.006","url":null,"abstract":"<div><h3>Background</h3><div>With the recent rise in anterior cruciate ligament (ACL) reconstruction surgeries in China, a corresponding increase in surgical failures has been observed. Variability in primary surgical techniques and the intricacies of failure mechanisms have introduced significant challenges in diagnosing failures, planning procedures, and conducting revision surgeries.</div></div><div><h3>Methods</h3><div>In response to these challenges, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) initiated the development of an expert consensus on ACL reconstruction failure and revision. Utilizing a modified Delphi method, 67 domestic experts from relevant fields were invited for consensus formulation and review.</div></div><div><h3>Results</h3><div>The expert panel achieved a high degree of consensus on twelve key aspects. The consensus clearly defines ACL reconstruction failure and outlines multiple contributing factors, with surgical errors, especially incorrect bone tunnel placement, identified as primary causes. It also emphasizes the significant impact of patient-specific variables on the likelihood of failure. Recommendations for revision surgeries include careful determination of revision indications, preserving meniscal integrity to reduce the risk of joint degeneration, and a preference for single-stage or two-stage surgeries based on individual patient evaluations. A unified approach for managing bone defects remains absent, necessitating comprehensive assessments. Graft selection should be tailored to each patient, with autografts, allografts, or synthetic ligaments as viable options. For patients with a highly positive pivot shift test or those engaged in high-demand athletic activities, anterolateral structure augmentation or reconstruction is recommended.</div></div><div><h3>Conclusion</h3><div>The consensus emphasizes the critical need for individualized approaches in ACL revision surgery. By clearly defining failure criteria and outlining strategies for surgical revisions, these statements are expected to serve as a guide for refining clinical practice, reducing complications, and improving surgical outcomes.</div></div><div><h3>The translational potential of this article</h3><div><ul><li><span>1)</span><span><div><strong>Establishment of Evidence-Based Clinical Guidelines:</strong> This article presents a rigorously developed expert consensus on ACL reconstruction failure and revision, providing evidence-based clinical guidelines that are directly applicable in surgical practice. The standardization of these protocols across medical institutions has the potential to reduce variability in patient care and improve surgical outcomes on a national scale.</div></span></li><li><span>2)</span><span><div><strong>Advancement of Precision Medicine in ACL Surgery:</strong> By emphasizing the need for patient-specific approaches in the management of ACL reconstruction failure, t","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 451-463"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1016/j.jot.2025.04.012
Mengcun Chen , Yanmei Yang , Mingshu Cui , Bin Wang
Objective
This study aims to (1) identify a simplified method to preserve sample integrity and maintain original fluorescence distribution; (2) assess the diffusivity of small and large molecules within articular cartilage (AC), calcified cartilage (CC), and subchondral bone (SB); and (3) investigate the changes in solute transport at various stages of osteoarthritis (OA) in a destabilization of the medial meniscus (DMM) murine model.
Methods
Fluorescent dyes of small and large molecules were injected into the knee joints of live mice. Joints were harvested and rapidly frozen immediately post-euthanasia. Optimal dye concentrations and dwelling times were determined through exploratory studies. Mice underwent either DMM or sham surgery and were evaluated at 2 and 8 weeks postoperatively. Relative fluorescence intensity was quantified within the AC, CC and SB, complemented by micro-CT, safranin O staining, and collagen II immunohistochemistry staining.
Results
The methodology successfully preserved sample integrity and original dye distribution. Fluorescent imaging revealed that small solute was mainly restricted by the tidemark, while large solute showed limited permeability in AC. Permeability of AC remained elevated in the DMM group at both time points. Increased permeability in CC and SB was observed only at 8 weeks post-DMM surgery, accompanied by reduced collagen II amount.
Conclusions
In live mice, the tidemark serves as a barrier to small molecule diffusion, while the cartilage surface restricts larger molecules; however, both structures exhibit increased permeability in OA. These findings advance the understanding of OA pathogenesis and suggest potential therapeutic targets related to cartilage permeability.
Translational Potential
The findings of this study advance the understanding of osteoarthritis pathogenesis by elucidating the role of solute transport alterations in cartilage and subchondral bone, thereby suggesting potential therapeutic targets aimed at modulating cartilage permeability to improve joint health in osteoarthritis.
{"title":"Solute transport from synovial fluid to articular cartilage and subchondral bone at different stages of osteoarthritis in a live mouse model","authors":"Mengcun Chen , Yanmei Yang , Mingshu Cui , Bin Wang","doi":"10.1016/j.jot.2025.04.012","DOIUrl":"10.1016/j.jot.2025.04.012","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to (1) identify a simplified method to preserve sample integrity and maintain original fluorescence distribution; (2) assess the diffusivity of small and large molecules within articular cartilage (AC), calcified cartilage (CC), and subchondral bone (SB); and (3) investigate the changes in solute transport at various stages of osteoarthritis (OA) in a destabilization of the medial meniscus (DMM) murine model.</div></div><div><h3>Methods</h3><div>Fluorescent dyes of small and large molecules were injected into the knee joints of live mice. Joints were harvested and rapidly frozen immediately post-euthanasia. Optimal dye concentrations and dwelling times were determined through exploratory studies. Mice underwent either DMM or sham surgery and were evaluated at 2 and 8 weeks postoperatively. Relative fluorescence intensity was quantified within the AC, CC and SB, complemented by micro-CT, safranin O staining, and collagen II immunohistochemistry staining.</div></div><div><h3>Results</h3><div>The methodology successfully preserved sample integrity and original dye distribution. Fluorescent imaging revealed that small solute was mainly restricted by the tidemark, while large solute showed limited permeability in AC. Permeability of AC remained elevated in the DMM group at both time points. Increased permeability in CC and SB was observed only at 8 weeks post-DMM surgery, accompanied by reduced collagen II amount.</div></div><div><h3>Conclusions</h3><div>In live mice, the tidemark serves as a barrier to small molecule diffusion, while the cartilage surface restricts larger molecules; however, both structures exhibit increased permeability in OA. These findings advance the understanding of OA pathogenesis and suggest potential therapeutic targets related to cartilage permeability.</div></div><div><h3>Translational Potential</h3><div>The findings of this study advance the understanding of osteoarthritis pathogenesis by elucidating the role of solute transport alterations in cartilage and subchondral bone, thereby suggesting potential therapeutic targets aimed at modulating cartilage permeability to improve joint health in osteoarthritis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 291-300"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1016/j.jot.2025.03.005
Bo Chen , Xu Liu , Min Hu , Jingwen Liao
Musculoskeletal disorders are age-related illnesses that substantially impact the locomotor system. These problems can lead to serious complications, such as fractures, which can severely compromise the quality of life of patients. With the aging of the global population, the incidence and prevalence of musculoskeletal disorders are gradually increasing. Proliferation, differentiation, and cellular fate are extensively regulated by the BMP signaling pathway, which is expressed in approximately all organ systems. Musculoskeletal diseases are generally influenced by BMP signaling, which impedes the degeneration of musculoskeletal diseases. In this review, the pathophysiological functions of BMP signaling in four main musculoskeletal disorders (osteoporosis, osteoarthritis, rheumatoid arthritis, and sarcopenia) are summarized, and the role of cross talk between BMP signaling and other signaling pathways in the development of musculoskeletal disorders is reviewed. Finally, a conclusion regarding research on the role of BMP signaling in musculoskeletal disorders is formulated. Targeting the BMP signaling pathway is a promising therapeutic approach, and related studies have offered insights into the pathophysiological mechanism of musculoskeletal disorders.
The Translational Potential of This Article
The identification of the BMP signaling pathway involved in the development of musculoskeletal disorders and the investigation of their signaling cross talk can pave the way for effective treatments and management strategies for patients with musculoskeletal disorders
{"title":"Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk","authors":"Bo Chen , Xu Liu , Min Hu , Jingwen Liao","doi":"10.1016/j.jot.2025.03.005","DOIUrl":"10.1016/j.jot.2025.03.005","url":null,"abstract":"<div><div>Musculoskeletal disorders are age-related illnesses that substantially impact the locomotor system. These problems can lead to serious complications, such as fractures, which can severely compromise the quality of life of patients. With the aging of the global population, the incidence and prevalence of musculoskeletal disorders are gradually increasing. Proliferation, differentiation, and cellular fate are extensively regulated by the BMP signaling pathway, which is expressed in approximately all organ systems. Musculoskeletal diseases are generally influenced by BMP signaling, which impedes the degeneration of musculoskeletal diseases. In this review, the pathophysiological functions of BMP signaling in four main musculoskeletal disorders (osteoporosis, osteoarthritis, rheumatoid arthritis, and sarcopenia) are summarized, and the role of cross talk between BMP signaling and other signaling pathways in the development of musculoskeletal disorders is reviewed. Finally, a conclusion regarding research on the role of BMP signaling in musculoskeletal disorders is formulated. Targeting the BMP signaling pathway is a promising therapeutic approach, and related studies have offered insights into the pathophysiological mechanism of musculoskeletal disorders.</div></div><div><h3>The Translational Potential of This Article</h3><div>The identification of the BMP signaling pathway involved in the development of musculoskeletal disorders and the investigation of their signaling cross talk can pave the way for effective treatments and management strategies for patients with musculoskeletal disorders</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 419-440"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1016/j.jot.2025.04.009
Hongtao Jia , Shuqin Chen , Xuye Hu , Jiajun Wang , Jinlong Suo , Sheng-Ming Dai , Weiguo Zou , Heng Feng
Background
Annulus fibrosus (AF) is an important part of the intervertebral disc (IVD) and its injury leads to back pain and impaired mobility. The stem/progenitor cells are essential for the maturation and repair of the AF, however, the identity of AF stem/progenitor cells remain elusive.
Methods
In this study, we sorted cells from the murine IVDs and performed the single-cell RNA sequencing. Using single-cell transcriptomics, genetic lineage tracing, in vitro stem cell experiment, ablation models and cell transplantation, we elucidate the role of AF progenitor cells in maturation and injury.
Results
On the basis of single-cell RNA-sequencing (scRNA-seq) analysis of the intervertebral disc, we found that the transcription factor Scleraxis (Scx) can specifically label a progenitor cell population of the outer AF. By lineage tracing assay, Scx-lineage AF cells proliferate mainly prior to sexual maturity, but barely proliferate after age of 8 weeks. The Scx-expressing AF cells are enriched for stem/progenitor cell markers and show a higher proliferative capacity and differentiation potential than the Scx− cells. The ablation of Scx-expressing AF cells impairs the maturation of AF. The Scx+ AF cells are enriched for TGFβ signaling. Transplantation of Scx-lineage cells to injured AF with Connective tissue growth factor (CTGF) improved the AF healing.
Conclusions
Scleraxis-expressing progenitor cells are critical for the maturation of AF and demonstrate therapeutic potential for AF regeneration.
The translational potential of this article
These findings expand the important role of stem cells in maturation and repair and provide new strategy for cellular therapy of AF repair.
{"title":"Scleraxis-expressing progenitor cells are critical for the maturation of the annulus fibrosus and demonstrate therapeutic potential","authors":"Hongtao Jia , Shuqin Chen , Xuye Hu , Jiajun Wang , Jinlong Suo , Sheng-Ming Dai , Weiguo Zou , Heng Feng","doi":"10.1016/j.jot.2025.04.009","DOIUrl":"10.1016/j.jot.2025.04.009","url":null,"abstract":"<div><h3>Background</h3><div>Annulus fibrosus (AF) is an important part of the intervertebral disc (IVD) and its injury leads to back pain and impaired mobility. The stem/progenitor cells are essential for the maturation and repair of the AF, however, the identity of AF stem/progenitor cells remain elusive.</div></div><div><h3>Methods</h3><div>In this study, we sorted cells from the murine IVDs and performed the single-cell RNA sequencing. Using single-cell transcriptomics, genetic lineage tracing, <em>in vitro</em> stem cell experiment, ablation models and cell transplantation, we elucidate the role of AF progenitor cells in maturation and injury.</div></div><div><h3>Results</h3><div>On the basis of single-cell RNA-sequencing (scRNA-seq) analysis of the intervertebral disc, we found that the transcription factor <em>Scleraxis</em> (<em>Scx</em>) can specifically label a progenitor cell population of the outer AF. By lineage tracing assay, <em>Scx</em>-lineage AF cells proliferate mainly prior to sexual maturity, but barely proliferate after age of 8 weeks. The <em>Scx</em>-expressing AF cells are enriched for stem/progenitor cell markers and show a higher proliferative capacity and differentiation potential than the <em>Scx</em><sup>−</sup> cells. The ablation of <em>Scx</em>-expressing AF cells impairs the maturation of AF. The <em>Scx</em><sup>+</sup> AF cells are enriched for TGFβ signaling. Transplantation of <em>Scx</em>-lineage cells to injured AF with Connective tissue growth factor (CTGF) improved the AF healing.</div></div><div><h3>Conclusions</h3><div><em>Scleraxis</em>-expressing progenitor cells are critical for the maturation of AF and demonstrate therapeutic potential for AF regeneration.</div></div><div><h3>The translational potential of this article</h3><div>These findings expand the important role of stem cells in maturation and repair and provide new strategy for cellular therapy of AF repair.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 301-312"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-01DOI: 10.1016/j.jot.2025.03.004
Xiaoyang Ge , Yesheng Jin , Jingyuan He , Zhihao Jia , Ying Liu , Yong Xu
Extracellular matrix (ECM) is an intricate, dynamic network that is essential for structural and biochemical support of skeletal muscle cells. Upon skeletal muscle injury, ECM undergoes rapid remodeling to clear damaged tissue and provides a scaffold to support muscle regeneration. Disruptions in the structure and composition of ECM lead to fibrosis and impaired muscle function, consequently hindering the regenerative capability of skeletal muscle following acute injury. Besides, dysregulation of ECM can also affect muscle mass and cross-sectional area, contributing to the onset of muscle atrophy. Thus, understanding the physiological and mechanical roles of ECM in skeletal muscle injury and atrophy is crucial for developing strategies to treat muscle-related diseases. This review focuses on the complex interactions between the ECM and skeletal muscle, aiming to summarize the regulatory function and mechanism of ECM in muscle development, injury repair, and atrophy. Additionally, it covers recent advances in the treatment of skeletal muscle diseases via the utilization or modulation of ECM components. We will discuss the potential benefits of ECM-based therapies and the current challenges in this area, including producing standardized ECM, minimizing graft-versus-host disease (GVHD), and ensuring that scaffolds have the appropriate biological function. In sum, this comprehensive review will provide a foundation and insights into the relationship between ECM and skeletal muscle, shedding light on the development of ECM-based therapies in the treatment of muscle injury and atrophy.
The Translational Potential of This Article
This article systematically explores the regulatory function and mechanism of ECM in muscle development, injury repair, and atrophy. It also summarizes recent advances in therapeutic strategies for skeletal muscle injury and atrophy from the ECM perspective. Insights from this review contribute to the development of therapeutic strategies for skeletal muscle injury and atrophy by modulating or utilizing ECM components, thus providing novel therapeutic avenues for tissue engineering and regenerative medicine approaches to muscle-related disorders.
{"title":"Extracellular matrix in skeletal muscle injury and atrophy: mechanisms and therapeutic implications","authors":"Xiaoyang Ge , Yesheng Jin , Jingyuan He , Zhihao Jia , Ying Liu , Yong Xu","doi":"10.1016/j.jot.2025.03.004","DOIUrl":"10.1016/j.jot.2025.03.004","url":null,"abstract":"<div><div>Extracellular matrix (ECM) is an intricate, dynamic network that is essential for structural and biochemical support of skeletal muscle cells. Upon skeletal muscle injury, ECM undergoes rapid remodeling to clear damaged tissue and provides a scaffold to support muscle regeneration. Disruptions in the structure and composition of ECM lead to fibrosis and impaired muscle function, consequently hindering the regenerative capability of skeletal muscle following acute injury. Besides, dysregulation of ECM can also affect muscle mass and cross-sectional area, contributing to the onset of muscle atrophy. Thus, understanding the physiological and mechanical roles of ECM in skeletal muscle injury and atrophy is crucial for developing strategies to treat muscle-related diseases. This review focuses on the complex interactions between the ECM and skeletal muscle, aiming to summarize the regulatory function and mechanism of ECM in muscle development, injury repair, and atrophy. Additionally, it covers recent advances in the treatment of skeletal muscle diseases via the utilization or modulation of ECM components. We will discuss the potential benefits of ECM-based therapies and the current challenges in this area, including producing standardized ECM, minimizing graft-versus-host disease (GVHD), and ensuring that scaffolds have the appropriate biological function. In sum, this comprehensive review will provide a foundation and insights into the relationship between ECM and skeletal muscle, shedding light on the development of ECM-based therapies in the treatment of muscle injury and atrophy.</div></div><div><h3>The Translational Potential of This Article</h3><div>This article systematically explores the regulatory function and mechanism of ECM in muscle development, injury repair, and atrophy. It also summarizes recent advances in therapeutic strategies for skeletal muscle injury and atrophy from the ECM perspective. Insights from this review contribute to the development of therapeutic strategies for skeletal muscle injury and atrophy by modulating or utilizing ECM components, thus providing novel therapeutic avenues for tissue engineering and regenerative medicine approaches to muscle-related disorders.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 404-418"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-29DOI: 10.1016/j.jot.2025.04.001
Yechao Shen , Boren Tan , Jiahao Zhang , Ning Zhang , Zhan Wang
<div><h3>Background</h3><div>Fractures are a significant global public health concern, imposing a substantial economic burden, particularly among the elderly. However, research on the fracture burden in Asia remains limited, highlighting the need for comprehensive and up-to-date studies to support the effective planning and allocation of healthcare resources across the region.</div></div><div><h3>Methods</h3><div>Using the Global Burden of Disease (GBD) 2021 database, we analyzed the age-standardized rates (ASRs) of incidence (ASIR), prevalence (ASPR), and years lived with disability (YLDs) (ASYR) associated with fracture burden across Asia. Our study explored trends over time, variations by age, sex, and country, and examined the correlation between fracture burden and the sociodemographic index (SDI).</div></div><div><h3>Results</h3><div>In 2021, fractures in Asia caused 91.3 million (95 % uncertainty interval, 83.65–99.47) incident cases, 232.71 million (95 % UI, (215.57–250.39) prevalent cases, and 12.97 million (95 % UI, 8.89–17.82) YLDs, with age-standardized rates of 1968.49 (95 % UI, 1799.15–2147.14) for incidence (ASIR), 4683.96 (95 % UI, 4347.58–5036.61) for prevalence (ASPR), and 261.72 (95 % UI, 179.43–358.94) for YLDs (ASYR) per 100,000 population. Despite a higher absolute burden, Asian age-standardized rates of fracture were slightly lower than the global average. For ASYR, the most burdensome fractures were those of the patella, tibia/fibula/ankle, hip, and pelvis. Between 1990 and 2021, fracture incident cases, prevalent cases, and YLDs in Asia increased markedly. Age and sex differences were observed, with the elderly experiencing the highest fracture burden, particularly for hip fractures in women. While men had a higher overall fracture burden, women faced a greater fracture disease burden in the elderly population. Geographically, High-income Asia Pacific and Central Asia exhibited the highest age-standardized YLD rates, while South and East Asia had the largest number of fractures and YLDs.</div></div><div><h3>Conclusions</h3><div>Our study provides an in-depth analysis of the fracture burden in Asia. From 1990 to 2021, the overall age-standardized fracture burden in Asia showed a gradual decline, yet the burden of hip fractures continued to increase. Asia holds the highest absolute number of fracture burden globally, with East Asia and South Asia being the primary regions contributing to this burden. The fracture burden increases with age in Asia, and women experience a higher fracture burden than men in older age groups. Strengthening surveillance and targeted prevention is essential to reduce the future fracture burden.</div></div><div><h3>The translational potential of this article</h3><div>Fracture is a kind of health problem with high incidence and serious disease burden in Asia. Although overall burden of disease for fractures in Asia from 1990 to 2021 was decreasing, the burden of hip fracture disease in Asia has con
{"title":"Epidemiology and disease burden of fractures in Asia, 1990–2021: An analysis for the Global Burden of Disease Study 2021","authors":"Yechao Shen , Boren Tan , Jiahao Zhang , Ning Zhang , Zhan Wang","doi":"10.1016/j.jot.2025.04.001","DOIUrl":"10.1016/j.jot.2025.04.001","url":null,"abstract":"<div><h3>Background</h3><div>Fractures are a significant global public health concern, imposing a substantial economic burden, particularly among the elderly. However, research on the fracture burden in Asia remains limited, highlighting the need for comprehensive and up-to-date studies to support the effective planning and allocation of healthcare resources across the region.</div></div><div><h3>Methods</h3><div>Using the Global Burden of Disease (GBD) 2021 database, we analyzed the age-standardized rates (ASRs) of incidence (ASIR), prevalence (ASPR), and years lived with disability (YLDs) (ASYR) associated with fracture burden across Asia. Our study explored trends over time, variations by age, sex, and country, and examined the correlation between fracture burden and the sociodemographic index (SDI).</div></div><div><h3>Results</h3><div>In 2021, fractures in Asia caused 91.3 million (95 % uncertainty interval, 83.65–99.47) incident cases, 232.71 million (95 % UI, (215.57–250.39) prevalent cases, and 12.97 million (95 % UI, 8.89–17.82) YLDs, with age-standardized rates of 1968.49 (95 % UI, 1799.15–2147.14) for incidence (ASIR), 4683.96 (95 % UI, 4347.58–5036.61) for prevalence (ASPR), and 261.72 (95 % UI, 179.43–358.94) for YLDs (ASYR) per 100,000 population. Despite a higher absolute burden, Asian age-standardized rates of fracture were slightly lower than the global average. For ASYR, the most burdensome fractures were those of the patella, tibia/fibula/ankle, hip, and pelvis. Between 1990 and 2021, fracture incident cases, prevalent cases, and YLDs in Asia increased markedly. Age and sex differences were observed, with the elderly experiencing the highest fracture burden, particularly for hip fractures in women. While men had a higher overall fracture burden, women faced a greater fracture disease burden in the elderly population. Geographically, High-income Asia Pacific and Central Asia exhibited the highest age-standardized YLD rates, while South and East Asia had the largest number of fractures and YLDs.</div></div><div><h3>Conclusions</h3><div>Our study provides an in-depth analysis of the fracture burden in Asia. From 1990 to 2021, the overall age-standardized fracture burden in Asia showed a gradual decline, yet the burden of hip fractures continued to increase. Asia holds the highest absolute number of fracture burden globally, with East Asia and South Asia being the primary regions contributing to this burden. The fracture burden increases with age in Asia, and women experience a higher fracture burden than men in older age groups. Strengthening surveillance and targeted prevention is essential to reduce the future fracture burden.</div></div><div><h3>The translational potential of this article</h3><div>Fracture is a kind of health problem with high incidence and serious disease burden in Asia. Although overall burden of disease for fractures in Asia from 1990 to 2021 was decreasing, the burden of hip fracture disease in Asia has con","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 281-290"},"PeriodicalIF":5.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-29DOI: 10.1016/j.jot.2025.03.016
Cheng-Kung Cheng , Chengyan Lin , Yichao Luan
For Asia–Pacific countries used to long-term medical device manufacturing, developing innovative medical devices must be rooted in our profound research strength and mature medical productivity. Here, we developed a new model for achieving efficient translation through cooperation among local hospitals, universities, and industries and introduced the project manager system and Key Opinion Leader training. This “From SCI to FDA” model is a pivot for transferring cutting-edge research into valuable medical devices.
Translational potential of this article
This article presents a novel model for translating scientific research into innovative medical devices by fostering collaboration among hospitals, universities, and industries. By integrating clinical insights with academic expertise and industrial capabilities, this model addresses unmet clinical needs and bridges the gap between research and commercialization. Its potential lies in accelerating the translation of cutting-edge research into officially approved products, enhancing medical device innovation, and improving healthcare outcomes globally, particularly in Asia–Pacific countries.
{"title":"From “academic success” to “commercial success” —The model of medical device translation driven by SCI articles","authors":"Cheng-Kung Cheng , Chengyan Lin , Yichao Luan","doi":"10.1016/j.jot.2025.03.016","DOIUrl":"10.1016/j.jot.2025.03.016","url":null,"abstract":"<div><div>For Asia–Pacific countries used to long-term medical device manufacturing, developing innovative medical devices must be rooted in our profound research strength and mature medical productivity. Here, we developed a new model for achieving efficient translation through cooperation among local hospitals, universities, and industries and introduced the project manager system and Key Opinion Leader training. This “From SCI to FDA” model is a pivot for transferring cutting-edge research into valuable medical devices.</div></div><div><h3>Translational potential of this article</h3><div>This article presents a novel model for translating scientific research into innovative medical devices by fostering collaboration among hospitals, universities, and industries. By integrating clinical insights with academic expertise and industrial capabilities, this model addresses unmet clinical needs and bridges the gap between research and commercialization. Its potential lies in accelerating the translation of cutting-edge research into officially approved products, enhancing medical device innovation, and improving healthcare outcomes globally, particularly in Asia–Pacific countries.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 276-280"},"PeriodicalIF":5.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-26DOI: 10.1016/j.jot.2025.03.021
Xingdong Xiang , Lei Huang , Wenchen Luo , Lieyang Qin , Mengxuan Bian , Weisin Chen , Guanjie Han , Ning Wang , Guokang Mo , Cheng Zhang , Yongxing Zhang , Huilin Yang , Shunyi Lu , Jian Zhang , Tengfei Fu
Background
Stroke-related sarcopenia can result in muscle mass loss and muscle fibers abnormality, significantly affecting muscle function. The clinical management of stroke-related sarcopenia still requires further research and investigation. This study aims to explore a promising therapy to restore muscle function and promote muscle regeneration in stroke-related sarcopenia, providing a new theory for stroke-related sarcopenia treatment.
Methods
Stroke-related sarcopenia rat model was established by using permanent middle cerebral artery occlusion (pMCAO) rat and treated with neuromuscular electrical stimulation (NMES). Electrical stimulation (ES) treatment in vitro was mimicked to test the effect of NMES on muscle regeneration in rat skeletal muscle satellite cells (MuSCs). Catwalk, H&E and Masson's trichrome staining, immunofluorescence, transcriptomic analysis, transmission electron microscopy, MuSCs transfection, autophagy flux detection, quantitative real-time PCR analysis, Co-Immunoprecipitation and Western Blot were used to investigate the role of NMES and its mechanism in stroke-related sarcopenia in vivo.
Results
After NMES treatment, muscle mass and myogenic differentiation were significantly increased in stroke-related sarcopenia rats. The NMES group had more stable gait, neater footprints, higher muscle wet weight, more voluminous morphology and more regenerated muscle fibers. Additionally, ES treatment induced myogenic differentiation in rat MuSCs in vitro. Transcriptomic analysis also showed that “AMPK signaling pathway” was enriched and genes upregulated in ES-treated cells, revealing ES treatment could activate the autophagy in an AMPK-ULK1-dependent mechanism in MuSCs. Besides, it was also founded that infusion of AMPK or ULK1 inhibitor, knockdown of AMPK or ULK1 in MuSCs could block the effect of myotube formation of ES.
Conclusion
NMES not only restores muscle function but also enhances myogenic activity and muscle regeneration via AMPK-ULK1 autophagy in stroke-related sarcopenia rats. Our study provides a promising strategy for the treatment of stroke-related sarcopenia.
The translational potential of this article
This study first demonstrates that NMES alleviates stroke-related sarcopenia by promoting MuSCs differentiation through AMPK-ULK1-autophagy axis. The findings reveal a novel therapeutic mechanism, suggesting that NMES can restore muscle function and enhance regeneration in stroke patients. By combining NMES with MuSCs-based therapies, this approach offers a promising strategy for clinical rehabilitation, potentially improving muscle mass and function in stroke survivors. The translational potential lies in its applicability to non-invasive, cost-effective treatments for sarcopenia, enhancing patients' quality of life.
{"title":"Neuromuscular electrical stimulation alleviates stroke-related sarcopenia by promoting satellite cells myogenic differentiation via AMPK-ULK1-Autophagy axis","authors":"Xingdong Xiang , Lei Huang , Wenchen Luo , Lieyang Qin , Mengxuan Bian , Weisin Chen , Guanjie Han , Ning Wang , Guokang Mo , Cheng Zhang , Yongxing Zhang , Huilin Yang , Shunyi Lu , Jian Zhang , Tengfei Fu","doi":"10.1016/j.jot.2025.03.021","DOIUrl":"10.1016/j.jot.2025.03.021","url":null,"abstract":"<div><h3>Background</h3><div>Stroke-related sarcopenia can result in muscle mass loss and muscle fibers abnormality, significantly affecting muscle function. The clinical management of stroke-related sarcopenia still requires further research and investigation. This study aims to explore a promising therapy to restore muscle function and promote muscle regeneration in stroke-related sarcopenia, providing a new theory for stroke-related sarcopenia treatment.</div></div><div><h3>Methods</h3><div>Stroke-related sarcopenia rat model was established by using permanent middle cerebral artery occlusion (pMCAO) rat and treated with neuromuscular electrical stimulation (NMES). Electrical stimulation (ES) treatment <em>in vitro</em> was mimicked to test the effect of NMES on muscle regeneration in rat skeletal muscle satellite cells (MuSCs). Catwalk, H&E and Masson's trichrome staining, immunofluorescence, transcriptomic analysis, transmission electron microscopy, MuSCs transfection, autophagy flux detection, quantitative real-time PCR analysis, Co-Immunoprecipitation and Western Blot were used to investigate the role of NMES and its mechanism in stroke-related sarcopenia <em>in vivo</em>.</div></div><div><h3>Results</h3><div>After NMES treatment, muscle mass and myogenic differentiation were significantly increased in stroke-related sarcopenia rats. The NMES group had more stable gait, neater footprints, higher muscle wet weight, more voluminous morphology and more regenerated muscle fibers. Additionally, ES treatment induced myogenic differentiation in rat MuSCs <em>in vitro</em>. Transcriptomic analysis also showed that “AMPK signaling pathway” was enriched and genes upregulated in ES-treated cells, revealing ES treatment could activate the autophagy in an AMPK-ULK1-dependent mechanism in MuSCs. Besides, it was also founded that infusion of AMPK or ULK1 inhibitor, knockdown of AMPK or ULK1 in MuSCs could block the effect of myotube formation of ES.</div></div><div><h3>Conclusion</h3><div>NMES not only restores muscle function but also enhances myogenic activity and muscle regeneration via AMPK-ULK1 autophagy in stroke-related sarcopenia rats. Our study provides a promising strategy for the treatment of stroke-related sarcopenia.</div></div><div><h3>The translational potential of this article</h3><div>This study first demonstrates that NMES alleviates stroke-related sarcopenia by promoting MuSCs differentiation through AMPK-ULK1-autophagy axis. The findings reveal a novel therapeutic mechanism, suggesting that NMES can restore muscle function and enhance regeneration in stroke patients. By combining NMES with MuSCs-based therapies, this approach offers a promising strategy for clinical rehabilitation, potentially improving muscle mass and function in stroke survivors. The translational potential lies in its applicability to non-invasive, cost-effective treatments for sarcopenia, enhancing patients' quality of life.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 249-264"},"PeriodicalIF":5.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/Objective: This study evaluated the impact of adipose tissue-derived mesenchymal stromal cells (ADSCs) on bone-tendon healing in rabbit anterior cruciate ligament (ACL) reconstruction.
Methods
Nineteen mature male Japanese White rabbits underwent bilateral ACL reconstruction. ADSC constructs were implanted in the right femoral bone tunnel of each rabbit (implant group), while the left knee served as the control group without implantation. Nine rabbits were sacrificed at 3 and 6 weeks post-surgery, while the remaining were sacrificed immediately post-surgery. Biomechanical and micro computed tomography evaluations were conducted on six rabbits, while histological observation was performed on the remaining three.
Results
showed: (1) The implant group exhibited a significantly greater failure load than the control group at 3 weeks post-surgery. (2) Initially, the amount of new bone in the femoral tunnel was lower in the implant group at 3 weeks but surpassed that of the control group by 6 weeks. (3) Histological analysis indicated faster bone-tendon healing in the implant group than that of the control.
Conclusion
These findings suggest a positive effect of ADSC constructs on bone-tendon healing post-ACL reconstruction in rabbits. However, further studies using larger animal models must confirm these effects comprehensively.
The translational potential of this article
The method of transplanting a scaffold-free autologous ADSC construct is a technique that can safely and reliably transplant ADSCs to the tendon-bone tunnel interface without using foreign substances. It can be applied to bone-tendon healing in ACL reconstruction surgery and other areas, such as the rotator cuff and Achilles tendon attachment site.
{"title":"Promotion of bone-tendon healing after ACL reconstruction using scaffold-free constructs comprising ADSCs produced by a bio-3D printer in rabbit models","authors":"Kotaro Higa , Daiki Murata , Chinatsu Azuma , Kotaro Nishida , Koichi Nakayama","doi":"10.1016/j.jot.2025.03.019","DOIUrl":"10.1016/j.jot.2025.03.019","url":null,"abstract":"<div><div>Background/Objective: This study evaluated the impact of adipose tissue-derived mesenchymal stromal cells (ADSCs) on bone-tendon healing in rabbit anterior cruciate ligament (ACL) reconstruction.</div></div><div><h3>Methods</h3><div>Nineteen mature male Japanese White rabbits underwent bilateral ACL reconstruction. ADSC constructs were implanted in the right femoral bone tunnel of each rabbit (implant group), while the left knee served as the control group without implantation. Nine rabbits were sacrificed at 3 and 6 weeks post-surgery, while the remaining were sacrificed immediately post-surgery. Biomechanical and micro computed tomography evaluations were conducted on six rabbits, while histological observation was performed on the remaining three.</div></div><div><h3>Results</h3><div>showed: (1) The implant group exhibited a significantly greater failure load than the control group at 3 weeks post-surgery. (2) Initially, the amount of new bone in the femoral tunnel was lower in the implant group at 3 weeks but surpassed that of the control group by 6 weeks. (3) Histological analysis indicated faster bone-tendon healing in the implant group than that of the control.</div></div><div><h3>Conclusion</h3><div>These findings suggest a positive effect of ADSC constructs on bone-tendon healing post-ACL reconstruction in rabbits. However, further studies using larger animal models must confirm these effects comprehensively.</div></div><div><h3>The translational potential of this article</h3><div>The method of transplanting a scaffold-free autologous ADSC construct is a technique that can safely and reliably transplant ADSCs to the tendon-bone tunnel interface without using foreign substances. It can be applied to bone-tendon healing in ACL reconstruction surgery and other areas, such as the rotator cuff and Achilles tendon attachment site.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 265-275"},"PeriodicalIF":5.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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