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Toward a clear relationship between mechanical signals and bone adaptation
Pub Date : 2025-02-01 DOI: 10.1016/j.mbm.2025.100115
Chenlu Wang, Ruisen Fu, Haisheng Yang
Bone adapts according to the mechanical environment, and this adaptation can be visualized by altering its shape, size, and microarchitecture. Bone adaptation was recognized more than a century ago, with a description presented in The Law of Bone Remodeling. Furthermore, the conceptual model of “The Mechanostat” provides a quantitative relationship between the magnitude of bone tissue deformation (strain) and bone adaptive responses. However, upon maintaining a constant strain magnitude, various bone responses were observed experimentally under different loading parameters (e.g., frequency, rate, number of load cycles, rest insertion, and waveform). Nevertheless, the precise relationship between mechanical signals and bone adaptation remains unclear. Accordingly, we reviewed in vivo loading studies to determine the quantitative relationships between various mechanical signals and bone adaptive responses in various animal loading models. Additionally, we explored how these relationships are influenced by pathophysiological factors, such as age, sex, and estrogen deficiency. Moreover, mechanistic studies that consider cellular mechanical microenvironments to explain these quantitative relationships are discussed. A general formula that considers the bone adaptive response as a function of different loading parameters was proposed. This review may enhance our understanding of bone adaptation and offer guidance for clinicians to develop effective mechanotherapies to prevent bone loss.
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引用次数: 0
Angiogenesis within atherosclerotic plaques: Mechanical regulation, molecular mechanism and clinical diagnosis
Pub Date : 2025-02-01 DOI: 10.1016/j.mbm.2025.100114
Hanxiao Chen , Chengxiu Peng , Fei Fang , Yuhao Li , Xiaran Liu , Ying Hu , Guixue Wang , Xiaoheng Liu , Yang Shen
Atherosclerosis (AS) is a disease characterized by focal cholesterol accumulation and insoluble inflammation in arterial intima, leading to the formation of an atherosclerotic plaque consisting of lipids, cells, and fibrous matrix. The presence of plaque can restrict or obstruct blood flow, resulting in arterial stenosis and local mechanical microenvironment changes including flow shear stress, vascular matrix stiffness, and plaque structural stress. Neovascularization within the atherosclerotic plaque plays a crucial role in both plaque growth and destabilization, potentially leading to plaque rupture and fatal embolism. However, the exact interactions between neovessels and plaque remain unclear. In this review, we provide a comprehensive analysis of the origin of intraplaque neovessels, the contributing factors, underlying molecular mechanisms, and associated signaling pathways. We specifically emphasize the role of mechanical factors contributing to angiogenesis in atherosclerotic plaques. Additionally, we summarize the imaging techniques and therapeutic strategies for intraplaque neovessels to enhance our understanding of this field.
{"title":"Angiogenesis within atherosclerotic plaques: Mechanical regulation, molecular mechanism and clinical diagnosis","authors":"Hanxiao Chen ,&nbsp;Chengxiu Peng ,&nbsp;Fei Fang ,&nbsp;Yuhao Li ,&nbsp;Xiaran Liu ,&nbsp;Ying Hu ,&nbsp;Guixue Wang ,&nbsp;Xiaoheng Liu ,&nbsp;Yang Shen","doi":"10.1016/j.mbm.2025.100114","DOIUrl":"10.1016/j.mbm.2025.100114","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a disease characterized by focal cholesterol accumulation and insoluble inflammation in arterial intima, leading to the formation of an atherosclerotic plaque consisting of lipids, cells, and fibrous matrix. The presence of plaque can restrict or obstruct blood flow, resulting in arterial stenosis and local mechanical microenvironment changes including flow shear stress, vascular matrix stiffness, and plaque structural stress. Neovascularization within the atherosclerotic plaque plays a crucial role in both plaque growth and destabilization, potentially leading to plaque rupture and fatal embolism. However, the exact interactions between neovessels and plaque remain unclear. In this review, we provide a comprehensive analysis of the origin of intraplaque neovessels, the contributing factors, underlying molecular mechanisms, and associated signaling pathways. We specifically emphasize the role of mechanical factors contributing to angiogenesis in atherosclerotic plaques. Additionally, we summarize the imaging techniques and therapeutic strategies for intraplaque neovessels to enhance our understanding of this field.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanotransduction and inflammation: An updated comprehensive representation
Pub Date : 2024-12-14 DOI: 10.1016/j.mbm.2024.100112
Vennila Suriyagandhi , Ying Ma , Veronica Paparozzi , Tiziana Guarnieri , Biagio Di Pietro , Giovanna Maria Dimitri , Paolo Tieri , Claudia Sala , Darong Lai , Christine Nardini
Mechanotransduction is the process that enables the conversion of mechanical cues into biochemical signaling. While all our cells are well known to be sensitive to such stimuli, the details of the systemic interaction between mechanical input and inflammation are not well integrated. Often, indeed, they are considered and studied in relatively compartmentalized areas, and we therefore argue here that to understand the relationship of mechanical stimuli with inflammation – with a high translational potential - it is crucial to offer and analyze a unified view of mechanotransduction. We therefore present here pathway representation, recollected with the standard systems biology markup language (SBML) and explored with network biology approaches, offering RAC1 as an exemplar and emerging molecule with potential for medical translation.
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引用次数: 0
Matrix stiffness and viscoelasticity influence human mesenchymal stem cell immunomodulation
Pub Date : 2024-12-08 DOI: 10.1016/j.mbm.2024.100111
Sara J. Olsen , Rose E. Leader , Abigail L. Mortimer , Bethany Almeida
Human mesenchymal stem cells (hMSCs) have immense wound healing potential due to their immunomodulatory behavior. To control this behavior and reduce heterogeneity, researchers look to biomaterials, as matrix stiffness and viscoelasticity have been shown to control hMSC immunomodulation. However, the understanding of the effects of these biophysical cues on hMSC immunomodulation remains limited; a broad study investigating the potentially synergistic effects of matrix stiffness and viscoelasticity on hMSC immunomodulation is needed in order to support future work developing biomaterials for hMSC wound healing applications. We developed polyacrylamide (PAAm) gels with varying matrix stiffnesses with or without a viscoelastic element and explored the effects of these on hMSC-matrix interactions and immunomodulatory cytokine expression in both a normal growth media and an immunomodulatory growth media mimetic of a chronic, non-healing wound. Expression of IL-10, VEGF, and PGE2 were upregulated in immunomodulatory growth media over normal growth media, demonstrating the synergistic effects of biochemical signaling on hMSC immunomodulatory behavior. In addition, the addition of a viscoelastic element had both inhibitory and accentuating effects based on the cytokine and biochemical signaling in the cell culture media. Overall, this study provides a broad perspective on the immunomodulatory behavior of hMSCs due to stiffness and viscoelasticity.
{"title":"Matrix stiffness and viscoelasticity influence human mesenchymal stem cell immunomodulation","authors":"Sara J. Olsen ,&nbsp;Rose E. Leader ,&nbsp;Abigail L. Mortimer ,&nbsp;Bethany Almeida","doi":"10.1016/j.mbm.2024.100111","DOIUrl":"10.1016/j.mbm.2024.100111","url":null,"abstract":"<div><div>Human mesenchymal stem cells (hMSCs) have immense wound healing potential due to their immunomodulatory behavior. To control this behavior and reduce heterogeneity, researchers look to biomaterials, as matrix stiffness and viscoelasticity have been shown to control hMSC immunomodulation. However, the understanding of the effects of these biophysical cues on hMSC immunomodulation remains limited; a broad study investigating the potentially synergistic effects of matrix stiffness and viscoelasticity on hMSC immunomodulation is needed in order to support future work developing biomaterials for hMSC wound healing applications. We developed polyacrylamide (PAAm) gels with varying matrix stiffnesses with or without a viscoelastic element and explored the effects of these on hMSC-matrix interactions and immunomodulatory cytokine expression in both a normal growth media and an immunomodulatory growth media mimetic of a chronic, non-healing wound. Expression of IL-10, VEGF, and PGE<sub>2</sub> were upregulated in immunomodulatory growth media over normal growth media, demonstrating the synergistic effects of biochemical signaling on hMSC immunomodulatory behavior. In addition, the addition of a viscoelastic element had both inhibitory and accentuating effects based on the cytokine and biochemical signaling in the cell culture media. Overall, this study provides a broad perspective on the immunomodulatory behavior of hMSCs due to stiffness and viscoelasticity.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143165418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The first embryo, the origin of cancer and animal phylogeny. V. Cancer stem cells as the unifying biomechanical principle between embryology and oncology
Pub Date : 2024-12-05 DOI: 10.1016/j.mbm.2024.100110
Jaime Cofre
The role of embryology in metazoan evolution is rooted deeply in the history of science. Viewing Neoplasia as an evolutionary engine provides a scientific basis for reexamining the disease cancer. Once the embryo is understood as a benign tumor with a pivotal role in the evolution of all animal forms, there will be an immediate paradigm shift in the search for cancer cure, potentially revealing insights that may be buried within the great developmental transitions of metazoans. This article discusses one of the unifying principles between embryology and oncology, namely cancer stem cells. Some considerations are also provided on the central role of physics and biomechanics in the assembly of the first embryo, which can be regarded as a differentiated benign tumor. Mechanical impregnation of the nucleus of a stem cell, culminating in a totipotent/multipotent cell, was a major event safeguarding the success of embryogenesis throughout evolution. Germ cells in the earliest ctenophore embryos underwent delayed differentiation, subsequent to the mechanical assembly of the embryo. Finally, a discussion is presented on the concept that cancer and embryogenesis (cancer and healthy stem cells) are two sides of the same coin, that is, of the same process. The only difference is that cancer stem cells reveal themselves in inappropriate contexts. Neoplasia is a free force, whereas cancer is a force contained by animal organization.
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引用次数: 0
Harnessing mechanobiology to enhance cell therapy 利用机械生物学加强细胞疗法
Pub Date : 2024-11-16 DOI: 10.1016/j.mbm.2024.100102
Peixiang Ma , An Qin , Tobias Winkler , Jie Zhao
Recent developments in cell therapy have revolutionized medical treatment. While various methods of stimulation have been explored, the role of mechanical force has often been overlooked. Although mechanical loading is not easily visible, it can actively reshape organisms, and abnormal mechanical loading can lead to injury and disease. By leveraging the mechanobiology of cells, we can equip them with synthetic mechanosensors that can redirect genetic circuits to express protective factors, such as antibodies and cytokines, according to the mechanical force signal. The advancement of artificial intelligence (AI) presents a fascinating opportunity to redesign more complex mechanoreceptors, allowing cells to respond to intricate stimuli. Additionally, genetic engineering tools like CRISPR-Cas9, base editing, and prime editing enable the creation of multiple gene circuits for cells to react to complex mechanical environments. Advanced mechanical loading techniques, such as focused ultrasound, deliver signals in a confined spatial and temporal manner. Therefore, harnessing mechanobiology in cells can develop more flexible, personalized, and precise cell therapies.
细胞疗法的最新发展彻底改变了医学治疗。在探索各种刺激方法的同时,人们往往忽视了机械力的作用。虽然机械负荷不易察觉,但它能主动重塑生物体,异常的机械负荷会导致损伤和疾病。通过利用细胞的机械生物学,我们可以为细胞配备合成机械传感器,从而根据机械力信号重新定向基因回路,表达抗体和细胞因子等保护因子。人工智能(AI)的发展为重新设计更复杂的机械感受器提供了令人着迷的机会,使细胞能够对复杂的刺激做出反应。此外,CRISPR-Cas9、碱基编辑和质粒编辑等基因工程工具可以创建多种基因回路,让细胞对复杂的机械环境做出反应。聚焦超声等先进的机械加载技术能以限定的空间和时间方式传递信号。因此,在细胞中利用机械生物学可以开发出更加灵活、个性化和精确的细胞疗法。
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引用次数: 0
miRNA in mechanobiology: The exploration needs to continue miRNA 在机械生物学中的作用:探索仍需继续
Pub Date : 2024-11-14 DOI: 10.1016/j.mbm.2024.100101
Kai Huang, Yingxin Qi
The 2024 Nobel Prize in Physiology or Medicine has once again sparked considerable interest in microRNA (miRNA). Recent advances have unveiled that miRNAs play critical roles in mediating the effects of mechanical stimuli on gene expression, cellular functions, tissue development, and disease progression. This perspective summarized the history of miRNA research and highlighted the promising research directions of miRNAs in the field of mechanobiology.
2024 年诺贝尔生理学或医学奖再次引发了人们对微 RNA(miRNA)的浓厚兴趣。最新进展揭示,miRNA 在介导机械刺激对基因表达、细胞功能、组织发育和疾病进展的影响方面发挥着关键作用。本视角总结了 miRNA 的研究历史,并强调了 miRNA 在机械生物学领域大有可为的研究方向。
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引用次数: 0
Mechanobiological cues to bone cells during early metastasis drive later osteolysis: A computational mechanoregulation framework prediction
Pub Date : 2024-10-30 DOI: 10.1016/j.mbm.2024.100100
Anneke S.K. Verbruggen , Elan C. McCarthy , Roisin M. Dwyer , Laoise M. McNamara
Bone cells contribute to tumour metastasis by producing biochemical factors that stimulate tumour cell homing and proliferation, but also by resorbing bone matrix (osteolysis) that releases further stimulatory factors for tumour growth in a vicious cycle. Changes in the local mechanical environment of bone tissue occur during early metastasis, which might activate mechanobiological responses by resident bone cells (osteocytes) to activate resorption (osteoclasts) and thereby contribute to tumour invasion. The objective of this study is to investigate whether bone osteolysis is driven by early changes in the bone mechanical environment during metastasis by (a) implementing subject-specific FE models of metastatic femora to predict the mechanical environment within bone tissue during early metastasis (3-weeks after tumour inoculation) and then (b) applying mechanoregulation theory to predict bone tissue remodelling as a function of the evolving mechanical environment within bone tissue during breast cancer-bone metastasis. We implemented a global resorption rate derived from an experimental model, but the mechanoregulation algorithm predicted localised bone loss in the greater trochanter region, the same region where osteolysis was prevalent after three weeks of metastasis development in the animal model. Moreover, the mechanical environment evolved in a similar manner to that reported in separate subject-specific finite element models of these same animals by 6 weeks. Thus, we propose that early changes in the physical environment of bone tissue during metastasis may elicit mechanobiological cues for bone cells and activate later osteolytic bone destruction.
{"title":"Mechanobiological cues to bone cells during early metastasis drive later osteolysis: A computational mechanoregulation framework prediction","authors":"Anneke S.K. Verbruggen ,&nbsp;Elan C. McCarthy ,&nbsp;Roisin M. Dwyer ,&nbsp;Laoise M. McNamara","doi":"10.1016/j.mbm.2024.100100","DOIUrl":"10.1016/j.mbm.2024.100100","url":null,"abstract":"<div><div>Bone cells contribute to tumour metastasis by producing biochemical factors that stimulate tumour cell homing and proliferation, but also by resorbing bone matrix (osteolysis) that releases further stimulatory factors for tumour growth in a vicious cycle. Changes in the local mechanical environment of bone tissue occur during early metastasis, which might activate mechanobiological responses by resident bone cells (osteocytes) to activate resorption (osteoclasts) and thereby contribute to tumour invasion. The objective of this study is to investigate whether bone osteolysis is driven by early changes in the bone mechanical environment during metastasis by (a) implementing subject-specific FE models of metastatic femora to predict the mechanical environment within bone tissue during early metastasis (3-weeks after tumour inoculation) and then (b) applying mechanoregulation theory to predict bone tissue remodelling as a function of the evolving mechanical environment within bone tissue during breast cancer-bone metastasis. We implemented a global resorption rate derived from an experimental model, but the mechanoregulation algorithm predicted localised bone loss in the greater trochanter region, the same region where osteolysis was prevalent after three weeks of metastasis development in the animal model. Moreover, the mechanical environment evolved in a similar manner to that reported in separate subject-specific finite element models of these same animals by 6 weeks. Thus, we propose that early changes in the physical environment of bone tissue during metastasis may elicit mechanobiological cues for bone cells and activate later osteolytic bone destruction.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143165419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanotransductive N-cadherin binding induces differentiation in human neural stem cells 机械传导性 N-粘连蛋白结合诱导人类神经干细胞分化
Pub Date : 2024-10-16 DOI: 10.1016/j.mbm.2024.100099
McKay Cavanaugh , Rebecca Kuntz Willits
The neural stem cell niche is a complex microenvironment that includes cellular factors, secreted factors, and physical factors that impact stem cell behavior and development. Cellular interactions through cadherins, cell–cell binding proteins, have implications in embryonic development and mesenchymal stem cell differentiation. However, little is known about the influence of cadherins within the neural stem cell microenvironment and their effect on human stem cell maintenance and differentiation. Therefore, the purpose of this study was to develop synthetic substrates to examine the effect of cadherin mechanotransduction on human neural stem cells. Glass substrates were fabricated using silane, protein A, and recombinant N-cadherin; we used these substrates to examine the effect of N-cadherin binding on neural stem cell proliferation, cytoskeletal structure and morphology, Yes-associated protein-1 (YAP) translocation, and differentiation. Bound exogenous N-cadherin induced concentration-dependent increases in adherens junction formation, YAP translocation, and early expression of neurogenic differentiation markers. Strong F-actin ring structures were initiated by homophilic N-cadherin binding, eliciting neuronal differentiation of cells within 96 ​h without added soluble differentiation factors. Our findings show that active N-cadherin binding plays an important role for differentiation of human iPS-derived neural stem cells towards neurons, providing a new tool to differentiate cells in vitro.
神经干细胞龛是一种复杂的微环境,包括影响干细胞行为和发育的细胞因子、分泌因子和物理因子。通过粘附蛋白(细胞-细胞结合蛋白)进行的细胞相互作用对胚胎发育和间充质干细胞分化有影响。然而,人们对神经干细胞微环境中的粘附蛋白的影响及其对人类干细胞维持和分化的作用知之甚少。因此,本研究的目的是开发合成基底,以研究固着蛋白机械传导对人类神经干细胞的影响。我们使用硅烷、蛋白A和重组N-粘连蛋白制作了玻璃基底,并利用这些基底研究了N-粘连蛋白结合对神经干细胞增殖、细胞骨架结构和形态、Yes相关蛋白-1(YAP)转位和分化的影响。结合外源N-cadherin可诱导粘连接头形成、YAP转位和神经原分化标记早期表达的浓度依赖性增加。同亲和的N-cadherin结合启动了强大的F-actin环结构,在96小时内激发了细胞的神经元分化,而无需添加可溶性分化因子。我们的研究结果表明,活跃的N-cadherin结合在人类iPS神经干细胞向神经元分化的过程中发挥了重要作用,为体外细胞分化提供了一种新工具。
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引用次数: 0
Relationship between bilateral symmetry of foot posture and lower limb musculoskeletal injuries among workers engaged in physically demanding occupations: A cross-sectional investigation 从事体力要求高的职业的工人脚部姿势的双侧对称性与下肢肌肉骨骼损伤之间的关系:横断面调查
Pub Date : 2024-10-01 DOI: 10.1016/j.mbm.2024.100098
Chunhua Liao , Jing Liu , Shuanglong Hou , Wendong Zhang , Xin Zhao , Zhipan Hou , Honglei Quan , Zhaohui Tian , Rui Liu , Yuting Zhao
Even though the link between foot posture and lower-extremity injuries remains controversial, there has been little research focus on bilateral foot symmetry. This study evaluated the correlation between bilateral symmetry in foot posture and lower extremity musculoskeletal injuries among workers in physically intensive occupations. A total of 248 participants with physically demanding roles were enrolled. Historical data on lower-limb musculoskeletal injuries were obtained through a review of medical records, supplemented by results from on-site consultations. The foot arch index (AI) was quantitatively measured using a 3D laser foot scanner, and foot posture was evaluated using the foot posture index-6 (FPI-6). The participants were categorized into subgroups based on bilateral symmetry assessments of their feet. Logistic regression analyses were performed for statistical comparisons after adjusting for potential confounding factors. The results indicate that abnormalities in foot posture and arch, assessed using the FPI-6 and AI, were identified in 42.3 ​% and 47.2 ​% of participants, respectively, with 20.9 ​% and 16.5 ​% demonstrating bilateral asymmetry in these parameters. When comparing bilateral and unilateral foot protonation with bilaterally normal feet, the risk adjustments revealed differences of 2.274 (95 ​% CI: 1.094–4.729, P ​= ​0.028) and 2.751 (95 ​% CI: 1.222–6.191, P ​= ​0.015), respectively. Furthermore, the risk adjustment for age, BMI, smoking status, physical training years, training time, training frequency, warm-up before training, relaxation after training, MIS prevention, and treatment learning for unilateral flatfoot relative to bilateral normal feet was 3.197 (95 ​% CI:1.235–8.279, P ​= ​0.017). This study demonstrates that workers in physically demanding occupations who exhibit unilateral foot protonation or unilateral flatfoot are at an increased risk of lower-extremity musculoskeletal injuries.
尽管足部姿势与下肢损伤之间的关系仍存在争议,但有关双侧足部对称性的研究却很少。本研究评估了从事体力密集型工作的工人脚部姿势的双侧对称性与下肢肌肉骨骼损伤之间的相关性。研究共招募了 248 名从事体力密集型工作的参与者。下肢肌肉骨骼损伤的历史数据是通过查阅病历和现场咨询结果获得的。使用三维激光足部扫描仪对足弓指数(AI)进行了定量测量,并使用足部姿势指数-6(FPI-6)对足部姿势进行了评估。根据足部的双侧对称性评估结果,将参与者分为不同的亚组。在调整了潜在的混杂因素后,进行了逻辑回归分析以进行统计比较。结果表明,使用 FPI-6 和 AI 评估足部姿势和足弓异常的参与者分别占 42.3% 和 47.2%,其中 20.9% 和 16.5% 的参与者在这些参数上表现为双侧不对称。在比较双侧和单侧足部质子化与双侧正常足部时,风险调整结果显示两者的差异分别为 2.274(95 % CI:1.094-4.729,P = 0.028)和 2.751(95 % CI:1.222-6.191,P = 0.015)。此外,在对年龄、体重指数、吸烟状况、体育训练年限、训练时间、训练频率、训练前热身、训练后放松、MIS 预防和治疗学习进行风险调整后,单侧扁平足相对于双侧正常足的风险调整值为 3.197 (95 % CI:1.235-8.279, P = 0.017)。这项研究表明,从事体力要求高的职业的工人,如果表现出单侧足原位或单侧扁平足,其下肢肌肉骨骼受伤的风险就会增加。
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引用次数: 0
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Mechanobiology in Medicine
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