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A mixed-methods approach exploring acceptability and feasibility of trials designed to test drugs targeting prevention of post-traumatic osteoarthritis after knee injury. 采用混合方法探讨旨在测试预防膝关节损伤后创伤性骨关节炎药物的试验的可接受性和可行性。
IF 4.6 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-19 DOI: 10.1302/2046-3758.139.bjr-2024-0109
Raneem Kalsoum,Catherine J Minns Lowe,Sophie Gilbert,Andrew W McCaskie,Martyn Snow,Karina Wright,Geoff Bruce,Deborah J Mason,Fiona E Watt
AimsTo explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design.MethodsHealthcare professionals, clinicians, and/or researchers (HCP/Rs) were surveyed, and the data were presented at a congress workshop. A second and related survey was then developed for people with joint damage caused by knee injury and/or osteoarthritis (PJDs), who were approached by a UK Charity newsletter or Oxford involvement registry. Anonymized data were collected and analyzed in Qualtrics.ResultsSurvey responses (n = 19 HCP/Rs, 39 PJDs) supported studies testing pharmacological agents preventing PTOA. All HCP/Rs and 30/31 (97%) PJDs supported the development of new treatments that improved or delayed knee symptoms and damage to knee structure. PJDs thought that improving structural knee damage was more important than knee symptoms. Both groups found studies more acceptable as expected future benefit and risk of PTOA increased. All drug delivery routes were acceptable. Workshop participants (around n = 60) reflected survey views. Discussions suggested that stratifying using molecular testing for likely drug response appeared to be more acceptable than using characteristics such as sex, age, and BMI.ConclusionOur findings supported PTOA drug intervention studies, including situations where there is low risk of disease, no expected benefit of treatment, and frequent treatment administration. PJDs appeared less risk-averse than HCP/Rs. This work reinforces the benefits of consensus and involvement work in the co-creation of PTOA drug trial design. Involvement of key stakeholders, such as PJDs with different risks of OA and regulatory representatives, are critical for trial design success.
方法对医护人员、临床医生和/或研究人员(HCP/Rs)进行了调查,并在大会研讨会上展示了调查数据。然后,针对膝关节损伤和/或骨关节炎(PJDs)引起的关节损伤患者进行了第二次相关调查,这些患者是通过英国慈善通讯或牛津大学参与登记处联系到的。Qualtrics对匿名数据进行了收集和分析。结果调查回复(n = 19 HCP/Rs,39 PJDs)支持对预防PTOA的药物进行测试研究。所有 HCP/Rs 和 30/31 (97%) PJDs 都支持开发能够改善或延缓膝关节症状和膝关节结构损伤的新疗法。PJDs 认为改善膝关节结构损伤比膝关节症状更重要。随着未来预期获益和 PTOA 风险的增加,这两类人都认为研究更容易被接受。所有给药途径均可接受。研讨会与会者(约 n = 60)反映了调查意见。讨论表明,与使用性别、年龄和体重指数等特征相比,使用分子检测对可能的药物反应进行分层似乎更容易接受。与 HCP/Rs 相比,PJDs 的风险规避程度较低。这项工作加强了在共同创建 PTOA 药物试验设计过程中达成共识和参与工作的益处。关键利益相关者(如具有不同 OA 风险的 PJD 和监管代表)的参与对于试验设计的成功至关重要。
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引用次数: 0
The Clinical Practice Integration of Artificial Intelligence (CPI-AI) framework. 人工智能临床实践整合(CPI-AI)框架。
IF 4.6 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-18 DOI: 10.1302/2046-3758.139.bjr-2024-0135.r1
Luke Farrow,Dominic Meek,Georgios Leontidis,Marion Campbell,Ewen Harrison,Lesley Anderson
Despite the vast quantities of published artificial intelligence (AI) algorithms that target trauma and orthopaedic applications, very few progress to inform clinical practice. One key reason for this is the lack of a clear pathway from development to deployment. In order to assist with this process, we have developed the Clinical Practice Integration of Artificial Intelligence (CPI-AI) framework - a five-stage approach to the clinical practice adoption of AI in the setting of trauma and orthopaedics, based on the IDEAL principles (https://www.ideal-collaboration.net/). Adherence to the framework would provide a robust evidence-based mechanism for developing trust in AI applications, where the underlying algorithms are unlikely to be fully understood by clinical teams.
尽管针对创伤和骨科应用发布了大量人工智能(AI)算法,但能为临床实践提供参考的算法却寥寥无几。其中一个关键原因是缺乏从开发到部署的清晰路径。为了协助完成这一过程,我们开发了人工智能临床实践整合(CPI-AI)框架--基于 IDEAL 原则(https://www.ideal-collaboration.net/),在创伤和骨科临床实践中采用人工智能的五阶段方法。遵守该框架将为建立对人工智能应用的信任提供一个强有力的循证机制,因为临床团队不太可能完全理解其底层算法。
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引用次数: 0
Clinical, oncological, and prognostic differences of patients with subsequent skeletal-related events in bone metastases. 骨转移患者后续骨骼相关事件的临床、肿瘤学和预后差异。
IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-16 DOI: 10.1302/2046-3758.139.BJR-2023-0372.R1
Hsiang-Chieh Hsieh, Hung-Kuan Yen, Wen-Tung Hsieh, Ching-Wei Lin, Yu-Ting Pan, Fu-Shan Jaw, Stein J Janssen, Wei-Hsin Lin, Ming-Hsiao Hu, Olivier Groot

Aims: Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments.

Methods: This retrospective study included 3,814 adult patients who received local treatment - surgery and/or radiotherapy - for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher's exact test, and Kaplan-Meier curve.

Results: Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians' experiences when treating the initial SRE are not similar when treating a subsequent SRE.

Conclusion: This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs.

目的:治疗方法的进步延长了转移性骨病(MBD)患者的预期寿命。由于这种进步,患者可能会经历更多骨骼相关事件(SRE)。那些已经经历过一次 SRE 的患者可能会因后续的 SRE 而遭遇另一次局部治疗,而这并不是最初 SRE 治疗的一部分。然而,关于需要进一步局部治疗的后续 SRE 的发生率和特征的研究却存在明显的空白,这使得临床医生在面对后续 SRE 时不得不根据初次 SRE 的经验进行推断。本研究旨在调查 MBD 患者发生需要局部治疗的继发性 SRE 的比例,研究初次治疗与继发性 SRE 患者的预后是否存在差异,并确定初次治疗与继发性 SRE 治疗的临床、肿瘤学和预后特征是否存在差异:这项回顾性研究纳入了2010年1月1日至2019年12月31日期间因骨转移而接受局部治疗(手术和/或放疗)的3814名成年患者。所有纳入的患者至少有一次需要接受局部治疗的骨转移灶。随后的 SRE 被定义为需要进行局部治疗的第二次 SRE。使用 Mann-Whitney U 检验、费雪精确检验和 Kaplan-Meier 曲线比较了单次 SRE 和后续 SRE 的临床、肿瘤学和预后特征:在 3,814 例 SRE 患者中,3,159 例(83%)患者发生过单次 SRE,655 例(17%)患者随后发生了 SRE。继发SRE的患者通常具有有利于延长生存期的特征,如较高的体重指数、较高的白蛋白水平、较少的合并症或较低的中性粒细胞计数。一旦患者出现后续SRE,其临床和肿瘤学特征以及一年生存率(28%)都不如仅有一次SRE的患者(35%;P < 0.001),这表明临床医生在治疗初次SRE时的经验与治疗后续SRE时的经验并不相同:本研究发现,17% 的患者需要对第二次、后续的 SRE 进行治疗,而目前的临床指南并未针对这一临床状况提供具体的方法。我们观察到,参照初次治疗,后继 SRE 组患者的 6 周、90 天和 1 年中位生存期均长于单次 SRE 组患者。一旦患者出现继发性 SRE,他们的一年生存率比接受单一 SRE 治疗的患者更差。未来的研究应确定预后因素并评估现有生存预测模型的适用性,以便更好地管理后续的 SRE。
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引用次数: 0
The role of limb alignment on natural tibiofemoral kinematics and kinetics. 肢体排列对自然胫骨股骨运动学和动力学的作用。
IF 4.6 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-13 DOI: 10.1302/2046-3758.139.bjr-2023-0162.r3
Barbara Postolka,William R Taylor,Sandro F Fucentese,Renate List,Pascal Schütz
AimsThis study aimed to analyze kinematics and kinetics of the tibiofemoral joint in healthy subjects with valgus, neutral, and varus limb alignment throughout multiple gait activities using dynamic videofluoroscopy.MethodsFive subjects with valgus, 12 with neutral, and ten with varus limb alignment were assessed during multiple complete cycles of level walking, downhill walking, and stair descent using a combination of dynamic videofluoroscopy, ground reaction force plates, and optical motion capture. Following 2D/3D registration, tibiofemoral kinematics and kinetics were compared between the three limb alignment groups.ResultsNo significant differences for the rotational or translational patterns between the different limb alignment groups were found for level walking, downhill walking, or stair descent. Neutral and varus aligned subjects showed a mean centre of rotation located on the medial condyle for the loaded stance phase of all three gait activities. Valgus alignment, however, resulted in a centrally located centre of rotation for level and downhill walking, but a more medial centre of rotation during stair descent. Knee adduction/abduction moments were significantly influenced by limb alignment, with an increasing knee adduction moment from valgus through neutral to varus.ConclusionLimb alignment was not reflected in the condylar kinematics, but did significantly affect the knee adduction moment. Variations in frontal plane limb alignment seem not to be a main modulator of condylar kinematics. The presented data provide insights into the influence of anatomical parameters on tibiofemoral kinematics and kinetics towards enhancing clinical decision-making and surgical restoration of natural knee joint motion and loading.
方法采用动态视频荧光镜、地面反作用力板和光学运动捕捉相结合的方法,在平地行走、下坡行走和下楼梯的多个完整周期中对 5 名肢体外翻、12 名肢体中性和 10 名肢体内翻的受试者进行评估。结果在平地行走、下坡行走和下楼梯时,不同肢体排列组之间的旋转或平移模式没有发现明显差异。中立对齐和外翻对齐的受试者在所有三种步态活动的负重站立阶段的平均旋转中心都位于内侧髁上。而外翻对齐的受试者在平地和下坡行走时旋转中心位于中央,但在下楼梯时旋转中心更偏向内侧。膝关节内收/外展力矩受到肢体排列的显著影响,从外翻到中性再到内翻,膝关节内收力矩不断增加。额平面肢体排列的变化似乎不是髁运动学的主要调节因素。所提供的数据有助于深入了解解剖参数对胫骨股骨运动学和动力学的影响,从而提高临床决策和手术恢复膝关节自然运动和负荷的能力。
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引用次数: 0
Identification of age-related genes in rotator cuff tendon. 鉴定肩袖肌腱中与年龄相关的基因
IF 4.6 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-10 DOI: 10.1302/2046-3758.139.bjr-2023-0398.r1
Yibin Liu,Xing Li,Lei Jiang,Jinjin Ma
AimsRotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.MethodsLinear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs.ResultsWe identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)).ConclusionThis study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT.
目的肩袖撕裂(RCT)是肩部疼痛的主要原因,主要与年龄相关的肌腱退化有关。本研究旨在阐明不同年龄组肌腱中潜在的差异基因表达,并研究它们在肌腱退化中的作用。方法对撕裂的冈上肌腱的两个转录组数据集进行线性回归和差异表达分析,以确定与年龄相关的基因。随后对这些候选基因进行了功能分析,以探索它们在肌腱老化中的潜在作用。此外,通过比较病变肌腱和正常肌腱的表达情况,对候选基因进行了二次 DE 分析,以探讨它们与 RCTs 的相关性。其中,与正常肌腱相比,5 个与年龄相关的基因在病变肌腱中表现为 DE。功能分析和先前的研究强调了这些基因在肌肉发育(如肌球蛋白重链 3 (MYH3))、转录调控(如 CCAAT 增强子结合蛋白 delta (CEBPD))和金属离子稳态(如金属硫蛋白 1X (MT1X))等生物功能中的特异性富集。这些发现加深了我们对肌腱变性机制的了解,从而为降低 RCT 的发病率制定了潜在的策略。
{"title":"Identification of age-related genes in rotator cuff tendon.","authors":"Yibin Liu,Xing Li,Lei Jiang,Jinjin Ma","doi":"10.1302/2046-3758.139.bjr-2023-0398.r1","DOIUrl":"https://doi.org/10.1302/2046-3758.139.bjr-2023-0398.r1","url":null,"abstract":"AimsRotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.MethodsLinear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs.ResultsWe identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)).ConclusionThis study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142190271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The interactions of macrophages, lymphocytes, and mesenchymal stem cells during bone regeneration. 骨再生过程中巨噬细胞、淋巴细胞和间充质干细胞的相互作用。
IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-06 DOI: 10.1302/2046-3758.139.BJR-2024-0122.R1
Masatoshi Murayama, Simon K Chow, Max L Lee, Bill Young, Yasemin S Ergul, Issei Shinohara, Yosuke Susuki, Masakazu Toya, Qi Gao, Stuart B Goodman

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes - the main cellular components in BMAC - interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

骨骼的再生和修复对行动能力和生活质量至关重要。健康状况不佳、严重的并发症、慢性炎症和老化等因素会导致骨折延迟愈合和不愈合,以及持续性骨缺损。愈合骨骼的生物工程策略通常包括将自体骨髓抽吸物浓缩物(BMAC)或间充质干细胞(MSCs)与生物相容性支架进行移植。虽然BMAC显示出良好的前景,但由于间充质干细胞的浓度和稳健性以及免疫细胞的组成存在差异,其疗效也存在变异。了解巨噬细胞和淋巴细胞--BMAC 的主要细胞成分--与间充质干细胞相互作用的机制,可以提出促进骨愈合的新策略。巨噬细胞被极化为促炎(M1)或抗炎(M2)表型,并通过分泌细胞因子和其他因子影响细胞代谢和组织再生。T细胞,尤其是辅助T1(Th1)和Th17,可促进炎症和破骨细胞生成,而Th2和调节T(Treg)细胞则具有抗炎促进重建的作用,从而支持骨生成。巨噬细胞、T 细胞和间充质干细胞之间的相互作用会影响骨微环境并调节局部免疫反应。操纵这些细胞的比例和相互作用为改变骨的局部再生能力提供了机会,从而有可能提高临床疗效。
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引用次数: 0
Mechanical influence of facet tropism in patients with chronic discogenic pain disorder. 慢性椎间盘源性疼痛症患者面肌腱膜的机械影响。
IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-05 DOI: 10.1302/2046-3758.139.BJR-2023-0363.R1
Jun Y Lee, Hae I Lee, Sang-Heon Lee, Nack H Kim

Aims: The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM).

Methods: Retrospective analysis was conducted on clinical data, with a specific focus on the spinal units displaying facet tropism, utilizing FEM analysis for motion simulation. We studied 318 intervertebral levels in 156 patients who had undergone provocation discography. Significant predictors of clinical findings were identified by univariate and multivariate analyses. Loading conditions were applied in FEM simulations to mimic biomechanical effects on intervertebral discs, focusing on maximal displacement and intradiscal pressures, gauged through alterations in disc morphology and physical stress.

Results: A total of 144 discs were categorized as 'positive' and 174 discs as 'negative' by the results of provocation discography. The presence of defined facet tropism (OR 3.451, 95% CI 1.944 to 6.126) and higher Adams classification (OR 2.172, 95% CI 1.523 to 3.097) were important predictive parameters for discography-'positive' discs. FEM simulations showcased uneven stress distribution and significant disc displacement in tropism-affected discs, where loading exacerbated stress on facets with greater angles. During varied positions, notably increased stress and displacement were observed in discs with tropism compared to those with normal facet structure.

Conclusion: Our findings indicate that facet tropism can contribute to disc herniation and changes in intradiscal pressure, potentially exacerbating disc degeneration due to altered force distribution and increased mechanical stress.

目的:面肌滋养与腰椎间盘病变的易感性相关。我们的目的是通过分析临床数据和有限元建模(FEM),评估切面滋养对慢性腰骶椎盘源性疼痛的影响:方法: 我们对临床数据进行了回顾性分析,重点关注显示出椎体切迹的脊柱单元,并利用有限元分析进行运动模拟。我们研究了 156 名接受椎间盘刺激造影术的患者的 318 个椎间水平。通过单变量和多变量分析确定了临床发现的重要预测因素。在有限元模拟中应用加载条件来模拟生物力学对椎间盘的影响,重点是最大位移和椎间盘内压,通过椎间盘形态和物理应力的改变来衡量:根据椎间盘刺激造影的结果,共有 144 个椎间盘被归类为 "阳性",174 个椎间盘被归类为 "阴性"。椎间盘造影 "阳性 "椎间盘的重要预测参数是存在明确的椎面倾向(OR 3.451,95% CI 1.944 至 6.126)和较高的 Adams 分类(OR 2.172,95% CI 1.523 至 3.097)。有限元模拟显示,在受滋养层影响的椎间盘中,应力分布不均,椎间盘移位明显,其中角度较大的面的应力负荷加重。在不同位置时,与具有正常切面结构的椎间盘相比,有滋养纹的椎间盘的应力和位移明显增加:我们的研究结果表明,椎间盘变性可导致椎间盘突出和椎间盘内压的变化,并可能因力分布的改变和机械应力的增加而加剧椎间盘退变。
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引用次数: 0
Sonodynamic effect based on vancomycin-loaded microbubbles or meropenem-loaded microbubbles enhances elimination of different biofilms and bactericidal efficacy. 基于万古霉素微气泡或美罗培南微气泡的声动力效应增强了对不同生物膜的消除和杀菌效果。
IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-03 DOI: 10.1302/2046-3758.139.BJR-2023-0319.R3
Liqin Yao, Chenghan Chu, Yicheng Li, Li Cao, Jianhua Yang, Wenbo Mu

Aims: This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs).

Methods: A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology.

Results: The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and E. coli biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and E. coli bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and E. coli were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups.

Conclusion: Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics.

目的:本研究调查了万古霉素-微泡(Vm-MBs)和美罗培南(Mp)-MBs与超声靶向微泡破坏(UTMD),以破坏生物膜并提高杀菌效率,为治疗设备相关感染(DRIs)提供一种新的、有前景的策略:方法:采用薄膜水合法制备 Vm-MBs 和 Mp-MBs 并研究其特性。用不同组别处理耐甲氧西林金黄色葡萄球菌(MRSA)和大肠杆菌的生物膜。通过染色确定生物膜生物量的差异。用激光共聚焦扫描显微镜(CLSM)观察生物膜厚度和细菌存活率。通过平板计数确定菌落数。扫描电子显微镜(SEM)观察细菌形态:结果:Vm-MB 和 Mp-MB 均符合实验要求。Vm组、Vm-MBs组、UTMD组和Vm-MBs + UTMD组的生物膜生物量明显低于对照组。在 Vm-MBs + UTMD 组和 Mp-MBs + UTMD 组中,MRSA 和大肠杆菌生物膜分别受到了最明显的破坏,生物膜生物量的平均剩余率分别为 21.55%(SD 0.08)和 19.73%(SD 1.25)。Vm-MBs + UTMD 可显著降低生物膜厚度和细菌存活率(p = 0.005 和 p < 0.0001)。Mp-MBs + UTMD 可明显降低生物膜厚度和细菌活力(均 p < 0.001)。平板计数法显示,与对照组相比,Vm-MBs + UTMD 组和 Mp、Mp-MBs、UTMD、Mp-MBs + UTMD 组的 MRSA 和大肠杆菌菌落数明显减少(p = 0.031)。扫描电镜显示,Vm-MBs + UTMD 组和 Mp-MBs + UTMD 组的 MRSA 和大肠杆菌的形态和结构受到了明显的破坏:结论:Vm-MBs 或 Mp-MBs 与 UTMD 结合使用可有效破坏生物膜,并在超声介导下保护性释放抗生素,显著降低细菌活力,提高抗生素的杀菌效果。
{"title":"Sonodynamic effect based on vancomycin-loaded microbubbles or meropenem-loaded microbubbles enhances elimination of different biofilms and bactericidal efficacy.","authors":"Liqin Yao, Chenghan Chu, Yicheng Li, Li Cao, Jianhua Yang, Wenbo Mu","doi":"10.1302/2046-3758.139.BJR-2023-0319.R3","DOIUrl":"10.1302/2046-3758.139.BJR-2023-0319.R3","url":null,"abstract":"<p><strong>Aims: </strong>This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs).</p><p><strong>Methods: </strong>A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and <i>Escherichia coli</i> were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology.</p><p><strong>Results: </strong>The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and <i>E. coli</i> biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and <i>E. coli</i> bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and <i>E. coli</i> were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups.</p><p><strong>Conclusion: </strong>Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Guanylate cyclase promotes osseointegration by inhibiting oxidative stress and inflammation in aged rats with iron overload. 鸟苷酸环化酶通过抑制氧化应激和炎症,促进铁超载老年大鼠的骨结合。
IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-09-01 DOI: 10.1302/2046-3758.139.BJR-2023-0396.R3
Zhou-Shan Tao, Cai-Liang Shen

Aims: This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods: In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.

Results: Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment.

Conclusion: Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing.

目的:本研究旨在探讨维利奎特(VIT)对铁超载老年大鼠钛棒骨结合的影响,同时探讨维利奎特在成骨细胞和破骨细胞分化中的作用:在这项研究中,60 只大鼠被纳入钛棒植入模型,并接受了随后的鸟苷酸环化酶治疗。采用影像学、组织学和生物力学方法评估各组大鼠的骨整合情况。首先,研究了 VIT 对铁超载老年大鼠骨整合的影响。随后,在铁超载条件下,使用 VIT 调节 MC3T3-E1 细胞和 RAW264.7 细胞的分化:结果:利用 OVX 大鼠模型,我们观察到在铁超载的老龄大鼠体内施用 VIT 后,骨量和骨结合发生了显著变化。观察到的影响与骨代谢、氧化应激和炎症的减少同时发生。为了阐明这些效应是否与破骨细胞和成骨细胞的活性有关,我们使用 MC3T3-E1 细胞和 RAW264.7 细胞进行了体外实验。我们的研究结果表明,铁积累抑制了 MC3T3-E1 的活性,同时增强了 RAW264.7 的功能。此外,铁超载明显降低了氧化应激水平;然而,这些不利影响可以通过 VIT 治疗得到缓解:总之,我们的数据提供了令人信服的证据,证明 VIT 有可能逆转铁超载对老化过程中骨结合和骨量的有害影响。
{"title":"Guanylate cyclase promotes osseointegration by inhibiting oxidative stress and inflammation in aged rats with iron overload.","authors":"Zhou-Shan Tao, Cai-Liang Shen","doi":"10.1302/2046-3758.139.BJR-2023-0396.R3","DOIUrl":"10.1302/2046-3758.139.BJR-2023-0396.R3","url":null,"abstract":"<p><strong>Aims: </strong>This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.</p><p><strong>Methods: </strong>In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.</p><p><strong>Results: </strong>Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment.</p><p><strong>Conclusion: </strong>Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of the molecular link: STAT3 is a shared key gene linking postmenopausal osteoporosis and sarcopenia. 确定分子联系:STAT3 是连接绝经后骨质疏松症和肌肉疏松症的共同关键基因。
IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-08-28 DOI: 10.1302/2046-3758.138.BJR-2023-0351.R2
Dian Liu, Ke Wang, Jinpeng Wang, Fangming Cao, Lin Tao

Aims: This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods: We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.

Results: Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation.

Conclusion: STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases.

目的:本研究探讨了绝经后骨质疏松症(POMP)和肌肉疏松症之间的共同遗传特征和分子相互作用。我们假设这两种运动系统疾病在病理生理学和调控机制方面存在重叠:方法:我们使用加权基因共表达网络分析(WGCNA)、机器学习和京都基因与基因组百科全书(KEGG)富集分析法分析了基因表达总库(GEO)数据库中的微阵列数据,以确定 POMP 和肌肉疏松症之间的共同遗传因素。通过新队列中的差异基因表达进行了进一步验证。单细胞分析确定了高表达细胞亚群,其中包括骨质疏松症中的单核巨噬细胞和肌肉疏松症中的肌肉干细胞。竞争性内源性 RNA 网络提示了这些基因的调控元件:结果:信号转导和转录激活因子 3(STAT3)在两种情况下都有显著表达。单细胞分析确定了 STAT3 高表达的特定细胞,microRNA(miRNA)-125a-5p 成为潜在的调控因子。实验证实了 STAT3 在破骨细胞分化和肌肉增殖中的关键作用:结论:STAT3 已成为 POMP 和肌肉疏松症的关键基因。结论:STAT3 已成为 POMP 和肌肉疏松症的关键基因,这一观点将 STAT3 定位为潜在的共同治疗靶点,从而有可能改善这些与年龄相关疾病的治疗策略。
{"title":"Identification of the molecular link: STAT3 is a shared key gene linking postmenopausal osteoporosis and sarcopenia.","authors":"Dian Liu, Ke Wang, Jinpeng Wang, Fangming Cao, Lin Tao","doi":"10.1302/2046-3758.138.BJR-2023-0351.R2","DOIUrl":"10.1302/2046-3758.138.BJR-2023-0351.R2","url":null,"abstract":"<p><strong>Aims: </strong>This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.</p><p><strong>Methods: </strong>We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.</p><p><strong>Results: </strong>Signal transducer and activator of transcription 3 (<i>STAT3</i>) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high <i>STAT3</i> expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of <i>STAT3</i> in osteoclast differentiation and muscle proliferation.</p><p><strong>Conclusion: </strong><i>STAT3</i> has emerged as a key gene in both POMP and sarcopenia. This insight positions <i>STAT3</i> as a potential common therapeutic target, possibly improving management strategies for these age-related diseases.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Bone & Joint Research
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