Mechanobiology in Medicine最新文献_第3页

Early diabetes screening via red blood cell mechanics using microfluidic chip integration 利用微流控芯片集成红细胞力学进行早期糖尿病筛查

Mechanobiology in Medicine

Pub Date : 2025-05-29 DOI: 10.1016/j.mbm.2025.100136

Yibo Feng , Bingchen Che , Yonggang Liu , Cangmin Zhang , Jiameng Niu , Jiangcun Yang , Guangyin Jing , Dan Sun , Xiaobo Gong , Ce Zhang

Early diagnosis of diabetes is crucial, as diabetes, particularly type 2, can eventually lead to irreversible changes and complications. Conventional techniques, such as the Fasting Plasma Glucose (FPG) Test and Hemoglobin A1c (HbA1c) Test, measure blood glucose levels, which fluctuate over time and are insensitive to early stages. In this study, we focus on measuring the mechanical properties of red blood cells, as their irreversible changes can indicate early pathological impacts of diabetes. We developed a microfluidic chip with a symmetrical hyperbolic structure. By periodically altering the state of the valve membrane, we generate a reciprocating shear flow field that repeatedly acts on groups of RBCs. We then quantify the morphological parameters of the RBCs, establishing a correlation between the reciprocating shear flow field and the morphological changes of the cells. Using the developed microfluidic chip, we investigated the resistance of blood cells from 20 healthy volunteers to mechanical stimuli. The results indicated a significant correlation between the deformability of red blood cells and age, while no such correlation was found among individuals of the same gender. This study highlights the potential of utilizing the mechanical properties of red blood cells as an early diagnostic tool for diabetes. Furthermore, given the ease of integration of microfluidic chips, they present a promising high-throughput diagnostic solution for large-scale clinical screening.

糖尿病的早期诊断至关重要，因为糖尿病，特别是2型糖尿病，最终可能导致不可逆转的变化和并发症。传统的技术，如空腹血糖（FPG）测试和血红蛋白A1c （HbA1c）测试，测量血糖水平，随着时间的推移而波动，对早期阶段不敏感。在这项研究中，我们着重于测量红细胞的力学特性，因为它们的不可逆变化可以指示糖尿病的早期病理影响。我们研制了一种对称双曲结构的微流控芯片。通过周期性地改变阀膜的状态，我们产生了一个往复剪切流场，反复作用于红细胞群。然后，我们量化了红细胞的形态参数，建立了往复剪切流场与细胞形态变化之间的相关性。利用所研制的微流控芯片，研究了20名健康志愿者的血细胞对机械刺激的抵抗力。结果表明，红细胞的变形能力与年龄之间存在显著相关性，而在同性个体中没有发现这种相关性。这项研究强调了利用红细胞的机械特性作为糖尿病早期诊断工具的潜力。此外，考虑到微流控芯片易于集成，它们为大规模临床筛查提供了一个有前途的高通量诊断解决方案。

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引用次数: 0

Mechanosensitive nuclear checkpoint: nuclear envelope as a sensor of chromosomal instability and driver of cell fate 机械敏感核检查点：核包膜作为染色体不稳定性的传感器和细胞命运的驱动因素

Mechanobiology in Medicine

Pub Date : 2025-05-21 DOI: 10.1016/j.mbm.2025.100135

Chenyang Ji, Junwei Chen, Fuxiang Wei

The nuclear envelope (NE) is a dynamic, mechanosensitive structure that functions as a protective barrier for the genome and serves as a checkpoint responding to external stimuli. It plays a critical role in maintaining genomic stability and regulating cell fate. This review synthesizes recent research highlighting the role of NE as a mechanical checkpoint in ensuring accurate chromosome segregation, regulating cell cycle progression, and contributing to cancer development. Chromosome mis-segregation during cell division is a major driver of aneuploidy, a condition closely associated with genomic instability and cellular transformation. The role of NE in chromatin organization and gene expression regulation is also discussed, underscoring its importance in cell differentiation and identity.

核膜（NE）是一种动态的机械敏感结构，作为基因组的保护屏障，并作为响应外部刺激的检查点。它在维持基因组稳定性和调节细胞命运方面起着关键作用。这篇综述综合了最近的研究，强调了NE作为一个机械检查点在确保准确的染色体分离、调节细胞周期进程和促进癌症发展方面的作用。细胞分裂过程中的染色体错分离是非整倍体的主要驱动因素，非整倍体与基因组不稳定性和细胞转化密切相关。NE在染色质组织和基因表达调控中的作用也被讨论，强调其在细胞分化和鉴定中的重要性。

引用次数: 0

Neuromorphic chips for biomedical engineering 生物医学工程用神经形态芯片

Mechanobiology in Medicine

Pub Date : 2025-05-15 DOI: 10.1016/j.mbm.2025.100133

Kaiyang Wang , Shuhui Ren , Yunfang Jia , Xiaobing Yan , Lizhen Wang , Yubo Fan

The modern medical field faces two critical challenges: the dramatic increase in data complexity and the explosive growth in data size. Especially in current research, medical diagnostic, and data processing devices relying on traditional computer architecture are increasingly showing limitations when faced with dynamic temporal and spatial processing requirements, as well as high-dimensional data processing tasks. Neuromorphic devices provide a new way for biomedical data processing due to their low energy consumption and high dynamic information processing capabilities. This paper aims to reveal the advantages of neuromorphic devices in biomedical applications. First, this review emphasizes the urgent need of biomedical engineering for diversify clinical diagnostic techniques. Secondly, the feasibility of the application in biomedical engineering is demonstrated by reviewing the historical development of neuromorphic devices from basic modeling to multimodal signal processing. In addition, this paper demonstrates the great potential of neuromorphic chips for application in the fields of biosensing technology, medical image processing and generation, rehabilitation medical engineering, and brain-computer interfaces. Finally, this review provides the pathways for constructing standardized experimental protocols using biocompatible technologies, personalized treatment strategies, and systematic clinical validation. In summary, neuromorphic devices will drive technological innovation in the biomedical field and make significant contributions to life health.

现代医疗领域面临着两大关键挑战：数据复杂性的急剧增加和数据规模的爆炸性增长。特别是在当前的研究中，依靠传统计算机体系结构的医疗诊断和数据处理设备在面对动态的时空处理要求和高维数据处理任务时，越来越显示出局限性。神经形态设备以其低能耗和高动态信息处理能力为生物医学数据处理提供了新的途径。本文旨在揭示神经形态装置在生物医学应用中的优势。首先，本文强调生物医学工程迫切需要多样化的临床诊断技术。其次，通过回顾神经形态器件从基本建模到多模态信号处理的历史发展，论证了神经形态器件在生物医学工程中应用的可行性。此外，本文还论证了神经形态芯片在生物传感技术、医学图像处理与生成、康复医学工程、脑机接口等领域的巨大应用潜力。最后，本文综述了利用生物相容性技术构建标准化实验方案、个性化治疗策略和系统临床验证的途径。综上所述，神经形态设备将推动生物医学领域的技术创新，并为生命健康做出重大贡献。

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引用次数: 0

The sex-specific effects of RAGE signaling and type 2 diabetes on mouse cortical bone mechanics, structure, and material properties RAGE信号和2型糖尿病对小鼠皮质骨力学、结构和材料特性的性别特异性影响

Mechanobiology in Medicine

Pub Date : 2025-05-13 DOI: 10.1016/j.mbm.2025.100132

Timothy Hung , Kaitlyn S. Broz , Remy E. Walk , Simon Y. Tang

Individuals with type 2 diabetes (T2D) are prone to fracture at numerous skeletal sites despite presenting with a higher bone mineral density (BMD). The accumulation of Advanced Glycation End-products (AGEs) in the bone tissues of patients with T2D could be contributing to this paradox of increased skeletal fragility with higher BMD. AGEs can also impair bone cell homeostasis via the receptor for AGEs (RAGE). To investigate the effects of diabetes, AGE accumulation, and RAGE signaling on mouse cortical bone, we utilized male and female leptin receptor-deficient (db/db) diabetic mice from three age groups ranging from 3 to 12 months of age, which were crossed with mice carrying constitutively active alleles for a RAGE nullifying point mutation (RAGE^−/−). The morphological, mechanical and material outcomes of bone were measured using microCT, three-point bending, and AGE assays. We observed significant impairments dependent on age and sex to the bone matrix and whole-bone mechanical behavior due to diabetes, with some impairments alleviated by the deletion of RAGE. In older female diabetic mice, the removal of RAGE signaling prevented the deficits in bone mechanics, morphology, and tissue mineral density (TMD). Male diabetic mice without RAGE signaling exhibited improved material properties compared to wild type controls. The study demonstrated that bone impairments associated with T2D can be prevented with RAGE deletion, and T2D complications may be partially reversible with the therapeutic inhibition of RAGE signaling.

2型糖尿病（T2D）患者尽管表现出较高的骨密度（BMD），但仍容易在许多骨骼部位发生骨折。t2dm患者骨组织中晚期糖基化终产物（age）的积累可能导致骨密度升高而骨骼脆性增加的矛盾。AGEs还可以通过AGEs受体（RAGE）破坏骨细胞稳态。为了研究糖尿病、AGE积累和RAGE信号传导对小鼠皮质骨的影响，我们利用3 - 12月龄三个年龄组的雄性和雌性瘦素受体缺陷（db/db）糖尿病小鼠，将其与携带RAGE无效点突变（RAGE - / -）组成型活性等位基因的小鼠杂交。使用微ct、三点弯曲和AGE测定骨的形态学、力学和材料结果。我们观察到糖尿病对骨基质和全骨力学行为的显著损害，这与年龄和性别有关，其中一些损害因RAGE的缺失而减轻。在老年雌性糖尿病小鼠中，去除RAGE信号可以防止骨力学、形态学和组织矿物质密度（TMD）的缺陷。与野生型对照相比，没有RAGE信号的雄性糖尿病小鼠表现出更好的物质特性。该研究表明，与T2D相关的骨损伤可以通过RAGE缺失来预防，并且T2D并发症可能通过治疗性抑制RAGE信号传导部分可逆。

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引用次数: 0

Three-dimensional traction technology and its application in mechanomedicine 三维牵引技术及其在机械医学中的应用

Mechanobiology in Medicine

Pub Date : 2025-04-24 DOI: 10.1016/j.mbm.2025.100131

Xinman Chen , Chenyang Ji , Xi Liu , Ning Wang , Fuxiang Wei , Junwei Chen

Endogenous forces generated by living cells are essential for biological processes and physiological functions of cells and tissues. Over the last several decades, numerous methods for detecting traction forces have been developed. Here we review these methods and discuss their respective strengths and limitations. Being able to reliably quantify tractions in living cells and tissues are critical in understanding how forces drive and regulate cell and tissue functions in physiology and diseases.

活细胞产生的内源性力对细胞和组织的生物过程和生理功能至关重要。在过去的几十年里，已经开发了许多检测牵引力的方法。在这里，我们回顾了这些方法，并讨论了它们各自的优势和局限性。能够可靠地量化活细胞和组织中的牵引力对于理解力如何驱动和调节生理和疾病中的细胞和组织功能至关重要。

引用次数: 0

Prognostic assessment of osteolytic lesions and mechanical properties of bones bearing breast cancer using neural network and finite element analysis☆ 基于神经网络和有限元分析的乳腺癌骨溶解病变和力学特性预后评估

Mechanobiology in Medicine

Pub Date : 2025-03-30 DOI: 10.1016/j.mbm.2025.100130

Shubo Wang , Tiankuo Chu , Murtaza Wasi , Rosa M. Guerra , Xu Yuan , Liyun Wang

The management of skeletal-related events (SREs), particularly the prevention of pathological fractures, is crucial for cancer patients. Current clinical assessment of fracture risk is mostly based on medical images, but incorporating sequential images in the assessment remains challenging. This study addressed this issue by leveraging a comprehensive dataset consisting of 260 longitudinal micro-computed tomography (μCT) scans acquired in normal and breast cancer bearing mice. A machine learning (ML) model based on a spatial–temporal neural network was built to forecast bone structures from previous μCT scans, which were found to have an overall similarity coefficient (Dice) of 0.814 with ground truths. Despite the predicted lesion volumes (18.5 % ± 15.3 %) being underestimated by ∼21 % than the ground truths’ (22.1 % ± 14.8 %), the time course of the lesion growth was better represented in the predicted images than the preceding scans (10.8 % ± 6.5 %). Under virtual biomechanical testing using finite element analysis (FEA), the predicted bone structures recapitulated the loading carrying behaviors of the ground truth structures with a positive correlation (y = 0.863x) and a high coefficient of determination (R² = 0.955). Interestingly, the compliances of the predicted and ground truth structures demonstrated nearly identical linear relationships with the lesion volumes. In summary, we have demonstrated that bone deterioration could be proficiently predicted using machine learning in our preclinical dataset, suggesting the importance of large longitudinal clinical imaging datasets in fracture risk assessment for cancer bone metastasis.

骨骼相关事件（SREs）的管理，特别是病理性骨折的预防，对癌症患者至关重要。目前对骨折风险的临床评估主要基于医学图像，但将序列图像纳入评估仍然具有挑战性。本研究利用260个纵向微计算机断层扫描（μCT）数据集解决了这个问题，这些数据集来自正常小鼠和乳腺癌小鼠。建立了基于时空神经网络的机器学习（ML）模型来预测μCT扫描的骨结构，发现其与ground truth的总体相似系数（Dice）为0.814。尽管预测的病变体积（18.5%±15.3%）比实际情况（22.1%±14.8%）低估了约21%，但预测图像比之前的扫描（10.8%±6.5%）更好地反映了病变生长的时间过程。采用有限元分析（FEA）进行虚拟生物力学测试，预测骨结构再现了地基真实结构的承载行为，且具有正相关（y = 0.863 3x）和高决定系数（R2 = 0.955）。有趣的是，预测和基础真值结构的顺应性与病变体积表现出几乎相同的线性关系。总之，我们已经证明，在我们的临床前数据集中，使用机器学习可以熟练地预测骨退化，这表明大型纵向临床成像数据集在癌症骨转移的骨折风险评估中的重要性。

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引用次数: 0

Overstretch causes lipid accumulation in vascular smooth muscle cells dependent on NADPH oxidase 1 过度拉伸引起血管平滑肌细胞依赖于NADPH氧化酶1的脂质积累

Mechanobiology in Medicine

Pub Date : 2025-03-26 DOI: 10.1016/j.mbm.2025.100129

Jiazhen Zhang , Qinfen Li , Suoqi Ding , Wei Xu , Jilei Su , Jingang Cui , Yongsheng Ding

At the bend and bifurcation of arteries prone to atherosclerosis, pulsatile blood retention may cause overstretch on the tube wall. It has been reported that more than half of the foam cells found in atherosclerotic plaques are derived from vascular smooth muscle cells (VSMCs), but the mechanism is not adequately understood. In this work, we used a microfluidic device to apply a cyclic stretch (15 % and 0.05 Hz) on the VSMC for 24 h. The stretch caused a significant increase in the intracellular lipid accumulation, accompanying with the increased NOX1 and CD36 protein expression. On the other hand, inhibition of NOX1 activity, elimination of reactive oxygen species (ROS), or knockdown of NOX1 expression could significantly inhibit intracellular lipid accumulation. In addition, the NOX1 upregulation caused by 15 % stretch was related to the JAK/STAT signaling pathway. Our results reveal a novel mechanism of VSMC foam cell formation caused by the upregulation of NOX1.

在动脉易发生动脉粥样硬化的弯曲和分叉处，搏动性血液潴留可能导致管壁过度拉伸。据报道，在动脉粥样硬化斑块中发现的泡沫细胞中有一半以上来自血管平滑肌细胞（VSMCs），但其机制尚不清楚。在这项工作中，我们使用微流体装置在VSMC上施加循环拉伸（15%和0.05 Hz） 24小时。拉伸引起细胞内脂质积累显著增加，并伴有NOX1和CD36蛋白表达增加。另一方面，抑制NOX1活性、消除活性氧（ROS）或敲低NOX1表达可显著抑制细胞内脂质积累。此外，15%拉伸引起的NOX1上调与JAK/STAT信号通路有关。我们的研究结果揭示了一种由NOX1上调引起的VSMC泡沫细胞形成的新机制。

引用次数: 0

Multidimensional excavation of the current status and trends of mechanobiology in cardiovascular homeostasis and remodeling within 20 years 近20年来心血管稳态与重构的力学生物学研究现状与趋势的多维挖掘

Mechanobiology in Medicine

Pub Date : 2025-03-19 DOI: 10.1016/j.mbm.2025.100127

Wei Liao , Yuxi Huang , Xiangxiu Wang , Ziqiu Hu , Chuanrong Zhao , Guixue Wang

Mechanobiology is essential for cardiovascular structure and function and regulates the normal physiological and pathological processes of the cardiovascular system. Cells in the cardiovascular system are extremely sensitive to their mechanical environment, and once mechanical stimulation is abnormal, the homeostasis mechanism is damaged or lost, leading to the occurrence of pathological remodeling diseases. In the past 20 years, many articles concerning the mechanobiology of cardiovascular homeostasis and remodeling have been published. To better understand the current development status, research hotspots and future development trends in the field, this paper uses CiteSpace software for bibliometric analysis, quantifies and visualizes the articles published in this field in the past 20 years, and reviews the research hotspots and emerging trends. The regulatory effects of mechanical stimulation on the biological behavior of endothelial cells, smooth muscle cells and the extracellular matrix, as well as the mechanical-related remodeling mechanism in heart failure, have always been research hotspots in this field. This paper reviews the research advances of these research hotspots in detail. This paper also introduces the research status of emerging hotspots, such as those related to cardiac fibrosis, homeostasis, mechanosensitive transcription factors and mechanosensitive ion channels. We hope to provide a systematic framework and new ideas for follow-up research on mechanobiology in the field of cardiovascular homeostasis and remodeling and promote the discovery of more therapeutic targets and novel markers of mechanobiology in the cardiovascular system.

机械生物学对心血管的结构和功能起着至关重要的作用，调节着心血管系统正常的生理和病理过程。心血管系统细胞对其所处的机械环境极为敏感，一旦机械刺激异常，体内平衡机制就会受损或丧失，从而导致病理性重塑疾病的发生。在过去的20年里，关于心血管稳态和重构的机械生物学研究已经发表了许多文章。为了更好地了解该领域的发展现状、研究热点和未来发展趋势，本文利用CiteSpace软件进行文献计量分析，对该领域近20年来发表的文章进行量化和可视化，并对研究热点和新兴趋势进行综述。机械刺激对内皮细胞、平滑肌细胞和细胞外基质生物学行为的调控作用以及心力衰竭中与机械相关的重构机制一直是该领域的研究热点。本文详细综述了这些研究热点的研究进展。本文还介绍了新兴热点的研究现状，如与心脏纤维化、体内平衡、机械敏感转录因子和机械敏感离子通道相关的研究现状。我们希望为心血管稳态与重构领域的后续机械生物学研究提供系统框架和新思路，促进心血管系统中更多机械生物学治疗靶点和新标志物的发现。

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引用次数: 0

Biomechanics of horizontal meniscus tear and healing during knee flexion: Finite element analysis 膝关节屈曲时水平半月板撕裂和愈合的生物力学：有限元分析

Mechanobiology in Medicine

Pub Date : 2025-03-13 DOI: 10.1016/j.mbm.2025.100128

Bingtong Yan , Minmin Lin , Yang Liu , Jiawei Li , Linjing Peng , Yifei Yao , Guangheng Li , Chao Liu

Meniscus horizontal tear is a common injury that mostly occurs in middle-aged and elderly people, and the effect of repair surgery directly affects the functional recovery of the knee joint and prevention of degenerative joint diseases. However, the stress concentration in a horizontal tear is not well understood. The primary objective of this study was to examine the reparative mechanisms involved in addressing horizontal tears of the meniscus and to elucidate the alterations in mechanical behavior throughout the subsequent postoperative healing stages. Based on clinical MRI scan data of normal human knee joint, an accurate three-dimensional finite element model of the knee joint was established to simulate the meniscus at different states: including complete, horizontal torn, repaired and at different degrees of healing. An animal model was established to conduct in vitro loading experiments to assist in validating the model. Static standing simulation revealed the phenomenon of stress concentration in the area of horizontal tears. Knee flexion simulations identified the risk of tear propagation at the endpoints of the horizontal tear. Following suture repair and progressive healing, stress concentration was observed at the site of sutures, while the stress levels decreased at the endpoints of the horizontal tear. As healing progressed, the mechanical function of the meniscus gradually recovered. During progressive healing, the changing trends can provide a reference for patients' postoperative recovery activities. This finding has important implications for guiding clinical treatment strategies and rehabilitation plans for meniscal tears.

半月板水平撕裂是一种常见的损伤，多发生于中老年人，修复手术的效果直接影响到膝关节的功能恢复和退行性关节疾病的预防。然而，水平撕裂中的应力集中尚未得到很好的理解。本研究的主要目的是研究解决半月板水平撕裂的修复机制，并阐明在随后的术后愈合阶段力学行为的改变。基于正常人膝关节的临床MRI扫描数据，建立准确的膝关节三维有限元模型，模拟半月板完整、水平撕裂、修复和不同程度愈合的不同状态。建立动物模型进行体外加载实验，以协助验证模型。静态站立模拟揭示了水平撕裂区存在应力集中现象。膝关节屈曲模拟确定了水平撕裂终点撕裂传播的风险。在缝合修复和逐步愈合后，观察到缝合线部位的应力集中，而水平撕裂终点的应力水平下降。随着愈合的进展，半月板的机械功能逐渐恢复。在渐进式愈合过程中，其变化趋势可为患者术后恢复活动提供参考。这一发现对指导半月板撕裂的临床治疗策略和康复计划具有重要意义。

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引用次数: 0

Swimming induces bone loss via regulating mechanical sensing pathways in bone marrow 游泳通过调节骨髓中的机械感应通路诱导骨质流失

Mechanobiology in Medicine

Pub Date : 2025-03-12 DOI: 10.1016/j.mbm.2025.100125

Shaotian Fu , Yahong Lu , Wenkun Sun , Wugui Chen , Chengshou Lin , An Qin

Bone is an organ capable of perceiving external mechanical stress in real time and responding dynamically via mechanosensing proteins such as Piezo1 and YAP/TAZ. Upon sensing the mechano-signals, cells within the bone matrix collaborate to coordinate bone formation and resorption, while bone marrow cells are also stimulated and mobilized. High-load exercise stimulates osteoblast differentiation and bone formation. However, the mechanism through which the low-load exercises affect bone homeostasis is still unclear. In this work, we established a long-term swimming training model to unload the mechanical stress in mice. Throughout the training model, we observed a significant loss in trabecular bone mass, as evidenced by microCT scanning and histological staining. Single-cell sequencing of the tibial bone marrow tissue revealed a significant increase in the percentage of bone marrow neutrophils, along with alterations in Integrins and the ERK1/2 signaling pathway. Notably, the changes in both Integrins and the ERK1/2 signaling pathway in macrophages were more pronounced than in other cell types, which suggests a mechanical adaptive response in these cells. Moreover, the involvement of Integrins is also critical for the crosstalk between monocyte precusors and macrophages during swimming. Together, this study provides a resource of the alterations of bone marrow cell gene expression profile after swimming and highlights the importance of Integrins and the ERK1/2 signaling pathway in the bone marrow microenvironment after swimming.

骨是一种能够实时感知外部机械应力并通过Piezo1和YAP/TAZ等机械传感蛋白动态响应的器官。在感知到机械信号后，骨基质内的细胞协同协调骨的形成和吸收，同时骨髓细胞也受到刺激和动员。高负荷运动刺激成骨细胞分化和骨形成。然而，低负荷运动影响骨稳态的机制尚不清楚。在这项工作中，我们建立了一个长期游泳训练模型来卸载小鼠的机械应力。在整个训练模型中，我们观察到骨小梁骨量的显著减少，这一点可以通过微ct扫描和组织学染色来证明。胫骨骨髓组织的单细胞测序显示骨髓中性粒细胞百分比显著增加，整合素和ERK1/2信号通路也发生改变。值得注意的是，巨噬细胞中整合素和ERK1/2信号通路的变化比其他细胞类型更为明显，这表明巨噬细胞中存在机械适应性反应。此外，整合素的参与也对游泳过程中单核细胞前体和巨噬细胞之间的串扰至关重要。综上所述，本研究为游泳后骨髓细胞基因表达谱的改变提供了资源，并强调了游泳后整合素和ERK1/2信号通路在骨髓微环境中的重要性。

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引用次数: 0