Connective Tissue Research最新文献

{"title":"Impact of VX-765 and VX-740 on chondrogenesis and inflammatory cytokine release in murine micromass cultures.","authors":"Barbora Vesela, Katerina Dadakova, Katerina Holomkova, Corina Blecha, Natalia Obratilova, Susanne Grässel, Eva Matalova","doi":"10.1080/03008207.2025.2539414","DOIUrl":"https://doi.org/10.1080/03008207.2025.2539414","url":null,"abstract":"<p><strong>Aim: </strong>Caspase-1 inhibition is a promising option for degenerative joint diseases such as osteoarthritis; however, there is still a long way to go toward clinical use. One of the open challenges is associated with the non-inflammatory role of this caspase in the inflammatory environment as well as under physiological conditions. This study therefore focuses on two already pre-clinically tested caspase-1 inhibitors, VX-765 and VX-740, to specify their effects on chondrogenic cells.</p><p><strong>Material and methods: </strong>The analysis was performed on mouse micromass cultures where chondrocyte differentiation, inflammatory cytokine release, and gene expression were examined.</p><p><strong>Results: </strong>Our data indicate that the inhibitor VX-740 increases chondrogenesis, suggesting osteocalcin as a target molecule. In the inflammatory environment induced by IL-1β, there was an increase in chondrogenic nodules and partial compensation of differentiation for both investigated inhibitors. Morphological changes were not primarily due to changes in chondrogenic/osteogenic gene expression, but different levels of inflammatory molecules were found in the culture supernatant. While an increase in anti-inflammatory cytokine levels was observed with VX-765, a decrease in pro-inflammatory cytokines was recorded in the case of VX-740 treatment.</p><p><strong>Conclusion: </strong>The results demonstrate the differential effects of the caspase-1 inhibitors VX-765 and VX-740 on chondrogenic cell cultures and point to molecules that may be potential targets for use in the local treatment of osteoarthritis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microengineering the synovial membrane microenvironment for osteoarthritis research.","authors":"Hyon-U Pak, Daqing Wang, Jianhua Qin, Hongjing Li","doi":"10.1080/03008207.2025.2534723","DOIUrl":"https://doi.org/10.1080/03008207.2025.2534723","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a multifactorial joint disease characterized by cartilage degradation, subchondral bone remodeling, synovitis, and cartilage matrix degradation. The synovial membrane plays a pivotal role in the progression of OA through low-grade inflammation and secretion of catabolic enzymes under altered mechanical homeostasis. While widely used to study OA pathogenesis and therapies, in vitro models (e.g. 2D synoviocyte co-cultures) frequently lack critical aspects of the in vivo synovial microenvironment, such as cellular heterogeneity, physiologically relevant mechanical stress, and dynamic cell-matrix crosstalk. These shortcomings reduce their translational value. This translational gap indicates the need for advanced 3D microengineered platforms that integrate patient-specific cells, biomechanical elements, and real-time biosensing to bridge <i>in vitro</i> findings to clinical outcomes. Recent advances in microengineering offer innovative in vitro systems such as OA synovium-on-a-chip, 3D-printed constructs, and hydrogel-based organoids that recapitulate key features of the synovial microenvironment. These tools enable precise control over mechanical stimuli, matrix composition, and cell-cell signaling. This review summarizes the microenvironment of the OA synovium, critiques existing model systems, and highlights emerging microengineering strategies aimed at better mimicking OA pathophysiology and advancing translational research.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory mechanisms of mesenchymal stem cells in joint preservation in osteoarthritis.","authors":"Mohammed Lakrat, Pallavi Bhattaram, Hicham Drissi","doi":"10.1080/03008207.2025.2536148","DOIUrl":"https://doi.org/10.1080/03008207.2025.2536148","url":null,"abstract":"<p><p>Osteoarthritis (OA) remains a major challenge for clinicians and researchers, as current treatments predominantly focus on symptomatic relief without completely addressing the underlying pathogenesis. In this regard, intraarticular injections of mesenchymal stem cells (MSCs) are emerging as a promising choice to mitigate pain and functional impairment in knee OA patients. The strong optimism for this therapeutic modality is based on experimental evidence supporting a role for MSCs in modulating inflammation, as well as encouraging clinical trials reporting safety and significant pain mitigation outcomes. However, inconsistencies related to their therapeutic efficacy remain a key concern. Therefore, a comprehensive understanding of the mechanisms by which MSCs exert their anti-inflammatory and joint-preserving effects is critically needed to ensure wider clinical translation. Recent research underscores the significance of MSCs as biomedicines with the potential to modulate the pro-inflammatory pathobiology of the entire OA joint. Their ability to crosstalk with joint resident cells and the infiltrating immune cells to reduce the overall catabolic load on the OA joints is being recognized as a primary mechanism underlying their therapeutic benefits. In this review, we discuss the significance of intraarticular MSC injections in the field of OA clinical research and focus on the immunomodulatory mechanisms underlying the ability of MSCs to modulate inflammation within OA joints by targeting both immune and resident joint cells. We identify current limitations and highlight the need for multidisciplinary clinical and basic science research to establish innovative approaches to further develop MSC-based therapies as efficacious biomedicines to treat OA patients.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-7"},"PeriodicalIF":2.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of gene therapy in osteoarthritis.","authors":"You Li, Biao Li, Andras Nagy, Christopher Kim","doi":"10.1080/03008207.2025.2533332","DOIUrl":"https://doi.org/10.1080/03008207.2025.2533332","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a leading cause of pain and disability globally,characterized by progressive cartilage degeneration, subchondralbone remodeling, and synovial inflammation. Current treatmentsprimarily offer symptomatic relief without addressing the underlyingdisease mechanisms or halting progression. Gene therapy hasemerged as a promising strategy to target the molecular drivers ofOA by modulating key pathways involved in inflammation, tissuedegeneration, and pain. This review summarizes recent advancesin OA gene therapy, including anti-inflammatory approachestargeting IL-1β and IL-10, as well as regenerative strategiesleveraging TGF-β1 and FGF-18. Preclinical and early clinicalstudies have shown encouraging results in both symptom reliefand cartilage preservation. However, significant challengesremain, including vector safety, immune responses, and thecomplex, heterogeneous nature of OA that complicates treatmentresponse. The integration of precision medicine with improved genedelivery platforms and combinatorial therapeutic strategies holdsstrong potential to overcome these limitations. Collectively, theseinnovations may accelerate the development of disease-modifyingosteoarthritis drugs (DMOADs) and provide long-term, effectivetherapeutic options for patients.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-8"},"PeriodicalIF":2.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone deacetylase 4 in limb mesenchyme is essential for chondrocyte proliferation, growth plate maintenance and proper bone formation.","authors":"Yunfei Wang, Ling Wu, Sujing Zong, Pengcui Li, Lixun Chai, Li Guo, Xinping Chen, Shiping Yu, Jian Sun","doi":"10.1080/03008207.2025.2530045","DOIUrl":"https://doi.org/10.1080/03008207.2025.2530045","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of well-ordered chondrocyte proliferation and differentiation leads to distorted architecture of the growth plate, resulting in skeletal dysplasia with impaired longitudinal bone growth. Histone deacetylase 4 (HDAC4) is essential for chondrocyte hypertrophy and endochondral bone formation, but its role in postnatal bone development remains unexplored due to early lethality in Hdac4-ablated mice. Furthermore, a direct in vivo effect of Hdac4 on mesenchymal cell specification and bone development has not been investigated.</p><p><strong>Methods: </strong>We generated <i>Prx1-Cre;Hdac4^fl/fl, Sp7-Cre;Hdac4^fl/fl, Acan-CreERT2;Hdac4^fl/fl</i>, and <i>Hdac4^fl/fl</i> transgenic mice, respectively. The genotyping of transgenic mice was performed via conventional PCR. Whole-body radiographs and x-ray analyses of limbs were conducted. Trabecular and cortical bone microstructures of tibias from 21-day-old mice were evaluated using micro-computed tomography. EdU label-retention assay investigated cell proliferation, while histological analyses included H&E, TRAP, and Von Kossa staining. RT-qPCR and Immunohistochemistry to detect the pro-osteogenic function of HDAC4.</p><p><strong>Results: </strong>Hdac4 inactivation in limb mesenchyme cells resulted in limb shortening, premature growth plate closure, abnormal bone morphologies, and loss of the rounded articular surface. HDAC4 was crucial for regulating chondrocyte proliferation and secondary ossification center formation. Micro-computed tomography showed increased trabecular and cortical bone <i>Prx1-Cre;Hdac4^fl/fl</i> mice at 3 weeks, with altered microarchitecture. .</p><p><strong>Conclusion: </strong>Hdac4 in limb mesenchymal cells plays an indispensable role in chondrocyte proliferation, maintenance of the growth plate and formation of secondary ossification centers, its pro-osteogenic role was accomplished through premature differentiation of chondrocytes, along with accelerated cartilage-to-bone conversion.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-18"},"PeriodicalIF":2.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key insights and implications of cartilage degradation in osteoarthritis.","authors":"Lucienne A Vonk","doi":"10.1080/03008207.2025.2536153","DOIUrl":"https://doi.org/10.1080/03008207.2025.2536153","url":null,"abstract":"<p><strong>Background: </strong>Progressive degradation of articular cartilage is characteristic of osteoarthritis (OA), but OA is more than a wear-and-tear disease of the cartilage.</p><p><strong>Significant discoveries: </strong>It is a complex, multifactorial disease affecting all joint tissues, amplified by local and systemic inflammation. Chondrocytes play a crucial role in cartilage homeostasis and various molecular pathways that leading to their catabolic state have been identified. Cartilage degradation fragments and direct exposure of chondrocytes to extracellular matrix molecules provide feedback loops that further stimulate the catabolic profile. Synovial inflammation and subchondral bone changes enhance cartilage degradation by changing the joint environment, secreting pro-inflammatory cytokines and proteolytic enzymes, and attracting immune cells. The heterogeneity of the disease is underscored by the recognition on various phenotypes and endotypes, although consensus on classification of subtypes is lacking.</p><p><strong>Lessons learned: </strong>In the last 25 years, we have learned that timely treatment of joint injuries and repairing the meniscus are the best options to delay cartilage degradation and the development of post-traumatic OA. In addition, clinical studies have shown that cartilage thickness can be restored, but it does not necessarily provide clinical improvements.</p><p><strong>Knowledge gaps and barriers: </strong>So far, there is no disease modifying OA drug (DMOAD) available. The development of DMOADs is partially hindered by the requirement of long preclinical and clinical studies, as cartilage degradation is a slow process. Availability of biomarkers as surrogate endpoint could accelerate the development. Biomarker panels for early diagnosis and patient stratification could also advance the field.</p><p><strong>Outlook: </strong>Currently emerging treatment approaches, such as using regenerative medicine, promising for successful treatment.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-6"},"PeriodicalIF":2.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in understanding the role of obesity in osteoarthritis.","authors":"Isabella Y Goh, Ujjyani Ghosh, Natalia S Harasymowicz","doi":"10.1080/03008207.2025.2533330","DOIUrl":"10.1080/03008207.2025.2533330","url":null,"abstract":"<p><p>Obesity is a major risk factor for osteoarthritis (OA), yet the precise contribution to the pathogenesis of OA is still not fully known. Although traditionally viewed as a weight-induced joint deterioration, recent studies have highlighted multiple mechanisms through which obesity contributes to OA. This review summarizes the advances in our understanding of the obesity-associated impact on OA and addresses the knowledge gaps within the field. It highlights the newest findings on the role of local and systemic factors produced by adipose tissue (AT). While AT-derived adipokines, such as leptin and resistin, have been shown to promote cartilage degradation by inducing pro-inflammatory cytokines through multiple pathways, others, like adiponectin, exert both pro- and anti-inflammatory effects. Furthermore, this review focuses on recent findings regarding the reorganization of the obesity-associated immune cell landscape during OA progression, highlighting the reduced content of synovial lining macrophages and patrolling monocytes, as well as the increased content of monocyte-derived macrophages, T cells, and myeloid suppressor cells in obese subjects. Additionally, this review explores the emerging link between the gut microbiome and metabolic dysfunction in obesity-related OA and examines the influence of sex differences on the disease. By framing OA as a systemic condition in the context of obesity, this review underscores the need for multifactorial therapeutic approaches and precision medicine strategies to address this growing public health challenge. By presenting current and emerging treatment strategies, this review features the multifaceted approach to managing and researching OA in obese populations, emphasizing the need for innovative preventative measures.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Just a breath away: considerations for oxygen imbalances in osteoarthritis.","authors":"Annemarie Lang, Christophe Merceron, Jay M Patel","doi":"10.1080/03008207.2025.2530013","DOIUrl":"https://doi.org/10.1080/03008207.2025.2530013","url":null,"abstract":"<p><p>Oxygen availability plays a critical role in maintaining cartilage homeostasis and influencing the progression of osteoarthritis (OA). Articular cartilage is an avascular tissue that depends on a tightly regulated hypoxic microenvironment, with oxygen gradients shaped by diffusion from synovial fluid, cartilage thickness, and mechanical loading. Both degenerative OA, which develops gradually with age, and post-traumatic osteoarthritis (PTOA), which follows joint injury and progresses more rapidly, may involve disruption of this oxygen balance. Such dysregulation, whether through reduced or elevated oxygen tension, can impair chondrocyte metabolism, increase reactive oxygen species (ROS) production, and alter hypoxia-inducible factor 1-alpha (HIF-1α) signaling, ultimately contributing to cartilage degeneration. This mini-review explores the complex oxygen dynamics in cartilage and their potential role in OA. We highlight current knowledge gaps in oxygen level assessment and mechanistic understanding, and discuss emerging therapeutic and biomaterial-based strategies, including oxygen-sensing nanoparticles, ROS-responsive scaffolds, and oxygen-generating materials, that aim to modulate the joint oxygen environment. These approaches underscore the need for temporally controlled oxygen-related pathway modulation to support cartilage repair. Advancing our understanding of oxygen regulation in joint tissues may offer new opportunities for more effective, stage-specific OA therapies.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The utility of animal models in understanding osteoarthritis (OA) pathogenesis - an update on the impact of genetically modified mice.","authors":"Carina L Blaker, Cindy C Shu, Jamie Soul, Sanaa Zaki, Christopher B Little","doi":"10.1080/03008207.2025.2523517","DOIUrl":"https://doi.org/10.1080/03008207.2025.2523517","url":null,"abstract":"<p><p>Osteoarthritis (OA) is one of the most common health conditions worldwide leading to immense individual and societal burden. Current treatments for OA are inadequate with no approved structural disease modifying therapies, and existing options for chronic pain only moderately successful long-term. Improving this bleak picture requires a better understanding of OA molecular pathophysiology, how this differs between individuals and over time. Critical in this goal are animal models. There have been four key advancements in this field that have dramatically improved OA pathophysiology discovery research: (1) initial studies showing mouse OA-risk is modified by the same factors as humans-age, sex/sex-hormones, diet and genetics (1952-65); (2) first studies of naturally-occurring OA in mice with spontaneous (1972-81) and induced (1993) genetic mutations (GMs); (3) developing reproducible inducible models with good structural and symptomatic fidelity to human OA (1990-2005); and (4) using inducible and spontaneous OA-models in GM-mice to show disease and symptom modification and define molecular causality (1999-present). These milestones revolutionized OA pathophysiology research, such that there are now >500 unique genes/gene-products identified as having significant effects on OA (beneficial or detrimental). Studies in different mouse OA-models have underpinned the concept of OA-phenotypes, and more particularly endotypes and theratypes, with ~35% of tested molecular targets having different effects on post-traumatic (pt)OA versus spontaneous/age-associated-OA. Deciphering and translating the enormous and growing data from animal-models into effective therapeutics for people remains challenging. This will require better identification and stratification of patients with different OA pheno/endotypes, and improved collaboration between clinical and pre-clinical researchers.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-8"},"PeriodicalIF":2.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetics in osteoarthritis: emerging mechanistic and translational landscape.","authors":"Yaniet T Ghezai, Nada M Farhat, Saleh M S Ibrahim, Muhammad Farooq Rai","doi":"10.1080/03008207.2025.2523520","DOIUrl":"https://doi.org/10.1080/03008207.2025.2523520","url":null,"abstract":"<p><p>Epigenetic mechanisms are implicated in osteoarthritis (OA) as they regulate the expression of several key genes involved in OA disease progression. This mini-review highlights major epigenetic studies in OA from the past 25 years, focusing on mechanistic and therapeutic perspectives. We discuss how DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) impact OA, highlighting preclinical studies targeting epigenetic mechanisms in mouse models. Indeed, existing studies demonstrate that DNA methylation regulates the expression of OA-related genes through DNA methyltransferases, and targeting their activity has shown promise in restoring cartilage homeostasis. EZH2 and DOT1L are key methyltransferases involved in histone methylation with opposing roles in OA: high EZH2 promotes disease progression and is a potential therapeutic target, whereas DOT1L exerts protective effects, partly by suppressing Wnt signaling. Additionally, targeting enzymes that catalyze histone acetylation (PCAF, BRD4) and deacetylation (HDAC1/2) has demonstrated therapeutic potential in preclinical OA models. ncRNAs-including miRNAs, circRNAs, and lncRNAs-regulate gene expression in OA tissues at multiple levels. Several miRNAs (e.g. miR-17, miR-27b-3p) influence cartilage homeostasis and OA pathogenesis, while circRNAs (e.g. circPDE4B) and lncRNAs (e.g. ELDR) have emerged as important disease regulators, offering new therapeutic avenues. Despite significant advancements in OA-related epigenetic mechanisms, clinical translation remains challenging due to the complexity of epigenetic regulation, patient heterogeneity, and limited success of preclinical studies. Importantly, epigenetic alterations are often context-specific, necessitating nuanced interpretation to accurately discern their role in OA. Future research should prioritize identifying specific epigenetic markers linked to clinical outcomes (e.g. structural changes, functional impairment, pain) and developing more selective and potent epigenetic modulators for therapeutic use.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-10"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}