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Non pharmacoligical approaches for neurodegenerative diseases: A narrative review 治疗神经退行性疾病的非药物方法:叙述性综述。
IF 3.9 Pub Date : 2024-11-07 DOI: 10.1016/j.exger.2024.112620
Muhammad Liaquat Raza , Areej Bhojani , Syeda Kashaf Batool , Dua Zehra
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引用次数: 0
Functionality loss due to COVID-19 hospitalisation in older adults recovers with inpatient rehabilitation: A systematic review and meta-analysis 老年人因 COVID-19 住院而丧失的功能可通过住院康复恢复:系统回顾和荟萃分析。
IF 3.9 Pub Date : 2024-11-05 DOI: 10.1016/j.exger.2024.112617
Henrique Monteiro Lapo , Amanda Veiga Sardeli , Lilian Oliveira Mariano , Fiona Jayne Howroyd , Paulo Roberto Sokoll , Elizabeth Sapey , Mara Patrícia Traina Chacon-Mikahil

Introduction

Older adults are more likely to acquire the severe manifestation of COVID-19 and the hospitalised survivors experience significant functionality loss. Thus, we aimed to identify the level of functionality in older adults hospitalised due to COVID-19, and the effect of inpatient rehabilitation upon functional recovery.

Methods

A search was performed on July 2024, across five databases to retrieve studies assessing functionality in patients during COVID-19 hospitalisation, with or without rehabilitation.

Results

At admission, higher functionality was significantly higher for survivors than non survivors (standardized mean difference (SMD): 0.83 [0.56; 1.09]). The effect of inpatient rehabilitation on functionality was tested among 38 arms across studies. Inpatient rehabilitation improved functionality SMD across all indexes (1.47 [1.18; 1.77], P ≤ 0.001), with greatest effect in the patients >70 years (2.84 [1.74, 3.93], P = 0.006), compared to their counterparts.

Conclusion

Hospitalisation due to COVID-19 reduced functionality to a higher extent in older adults above 70 years. Inpatient rehabilitation was effective to improve functionality in both age groups.

Protocol registration

PROSPERO CRD42021278619.
简介老年人更容易患上表现严重的 COVID-19,而住院幸存者的功能会明显减退。因此,我们旨在确定因 COVID-19 而住院的老年人的功能水平,以及住院康复对功能恢复的影响:方法:我们于 2024 年 7 月在五个数据库中进行了检索,以检索评估 COVID-19 住院期间患者功能的研究,无论是否进行了康复治疗:入院时,幸存者的功能显著高于非幸存者(标准化平均差异(SMD):0.83 [0.56; 1.09])。住院康复治疗对功能的影响在38项研究中进行了测试。与同类患者相比,住院康复治疗改善了所有指标的功能性SMD(1.47 [1.18; 1.77],P ≤ 0.001),对70岁以上患者的影响最大(2.84 [1.74, 3.93],P = 0.006):结论:COVID-19导致的住院治疗对70岁以上老年人的功能影响更大。住院康复治疗可有效改善这两个年龄组的功能:PREMCORD42021278619。
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引用次数: 0
Predictive value of epicardial adipose tissue volume measured in diagnosis and prognosis of patients with HFPEF 测量心外膜脂肪组织体积对 HFPEF 患者诊断和预后的预测价值。
IF 3.9 Pub Date : 2024-11-01 DOI: 10.1016/j.exger.2024.112618
Yunlu Jiang , Li Su
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引用次数: 0
Activation of spleen tyrosine kinase (SYK) contributes to neuronal pyroptosis and cognitive impairment in diabetic mice via the NLRP3/Caspase-1/GSDMD signaling pathway 脾脏酪氨酸激酶(SYK)的活化通过NLRP3/Caspase-1/GSDMD信号通路导致糖尿病小鼠神经元脓毒症和认知障碍。
IF 3.9 Pub Date : 2024-11-01 DOI: 10.1016/j.exger.2024.112626
Chenglong Zhou , Jun Li , Xiaochu Wu , Fei Liu

Background/aim

Diabetes mellitus (DM) patients are at increased risk of cognitive impairment. The precise mechanisms underlying the association between DM and cognitive impairment remain unclear. Spleen tyrosine kinase (SYK), a crucial regulator of signal transduction, has been implicated in microglial pyroptosis in experimental ischemic stroke models. The present study investigated the potential role of SYK in DM-associated cognitive impairment.

Methods

Diabetes was induced by streptozotocin (STZ) in C57BL/6 mice, and cognitive function and cerebral injury were assessed 12 weeks later using the Morris water maze (MWM), TUNEL assay and Western blotting. In vitro, the inhibition of SYK was investigated in a mouse hippocampal neuronal cell line cultured with high glucose.

Results

Compared with control mice, DM mice presented impaired spatial learning and memory. Additionally, SYK activation was linked to neuronal pyroptosis, as evidenced by increases in the number of TUNEL-positive cells and protein levels of NLRP3, ASC, procaspase-1, caspase-1, GSDMD, the GSDMD N-terminal fragment, pro-IL-1β, and IL-1β in the hippocampus of DM mice. Compared with no treatment, SYK knockdown markedly attenuated cognitive impairment and histologic and ultrastructural pathological changes in the hippocampus of DM mice. The increased expression of pyroptosis-associated proteins and the increased number of TUNEL-positive cells were also significantly reduced. In vitro, high glucose significantly activated SYK to trigger the canonical pyroptotic pathway in cultured HT22 cells. The inhibition of SYK with a small interfering RNA or specific inhibitor significantly ameliorated the neuronal pyroptosis mediated by high glucose.

Conclusion

Our findings demonstrate that SYK activation plays a pivotal role in promoting the cognitive impairment associated with DM. This effect is mediated by triggering neuronal pyroptosis through the canonical NLRP3/Caspase-1/GSDMD pathway. These results suggest that SYK may serve as a potential target for preventing or mitigating cognitive impairment in patients with DM.
背景/目的:糖尿病(DM)患者出现认知障碍的风险增加。糖尿病与认知障碍之间关联的确切机制仍不清楚。脾酪氨酸激酶(SYK)是信号转导的重要调节因子,它与实验性缺血性中风模型中的小胶质细胞脓毒症有关。本研究探讨了SYK在DM相关认知障碍中的潜在作用:方法:用链脲菌素(STZ)诱导 C57BL/6 小鼠患糖尿病,12 周后用莫里斯水迷宫(MWM)、TUNEL 检测和 Western 印迹法评估认知功能和脑损伤。在体外,研究了高糖培养的小鼠海马神经元细胞系对 SYK 的抑制作用:结果:与对照组小鼠相比,DM 小鼠的空间学习和记忆能力受损。此外,SYK的激活与神经元的凋亡有关,这表现在DM小鼠海马中TUNEL阳性细胞数量的增加以及NLRP3、ASC、procaspase-1、caspase-1、GSDMD、GSDMD N-末端片段、pro-IL-1β和IL-1β蛋白水平的升高。与不治疗相比,SYK敲除明显减轻了DM小鼠的认知障碍以及海马的组织学和超微结构病理变化。此外,还显著减少了热核酸相关蛋白表达的增加和TUNEL阳性细胞数量的增加。在体外,高血糖能显著激活 SYK,从而触发培养的 HT22 细胞的典型嗜热通路。用小干扰 RNA 或特异性抑制剂抑制 SYK 能明显改善高糖介导的神经元凋亡:我们的研究结果表明,SYK 的活化在促进与 DM 相关的认知功能障碍中起着关键作用。结论:我们的研究结果表明,SYK 的激活在促进与 DM 相关的认知功能损害中起着关键作用,这种作用是通过 NLRP3/Caspase-1/GSDMD 通路触发神经元凋亡而介导的。这些结果表明,SYK 可能是预防或减轻 DM 患者认知障碍的潜在靶点。
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引用次数: 0
The influence of different tree densities on alpha waves, physical activity enjoyment, and satisfaction of late middle-aged and older adults using virtual cycling. 不同树木密度对中老年人使用虚拟自行车的阿尔法波、体育活动乐趣和满意度的影响。
IF 3.9 Pub Date : 2024-11-01 Epub Date: 2024-10-13 DOI: 10.1016/j.exger.2024.112608
Ta-Wei Tang, Tsai-Chiao Wang, Chia-Liang Tsai

Cave automatic virtual environment (CAVE), as a novel approach to promoting physical activity, shows great potential for improving the mental health and healthy lifestyle of older adults. Based on stress reduction theory, tree density is regarded as a main characteristic of a virtual sportscape that will affect the experience and benefits of exercising. However, the effect of tree density on the experience of exercising remains unclear. The current study was undertaken to investigate the effects of tree cover density on the alpha waves induced and the enjoyment and satisfaction derived by engaging in physical activity in a virtual environment. Eighty-seven late middle-aged and older adults were randomly assigned to one of the following conditions: a high tree density sportscape (HTDS = 36-60 %), a medium tree density sportscape, (MTDS = 20-35 %), and a control condition. Questionnaires and electroencephalogram read-outs of alpha waves were used to evaluate the changes in stress levels experienced by the participants before, during, and after 20 min of cycling. The results showed that participants exposed to an HTDS exhibited to physical activity with significantly more enjoyment and satisfaction than those in the MTDS and control groups. In contrast, the highest degree of relaxation was exhibited in the MTDS condition, suggesting that an MTDS is more effective at reducing perceived stress among late middle-aged and older adults engaging in virtual cycling. These findings demonstrate that exercising in a virtual reality setting with different densities of tree cover comes with physiological and psychological wellbeing for late middle-aged and older adults.

洞穴自动虚拟环境(CAVE)作为一种促进体育锻炼的新方法,在改善老年人的心理健康和健康生活方式方面显示出巨大的潜力。基于减压理论,树的密度被认为是虚拟运动景观的一个主要特征,会影响运动的体验和益处。然而,树木密度对运动体验的影响仍不明确。本研究旨在调查树木覆盖密度对在虚拟环境中进行体育锻炼所产生的阿尔法波以及乐趣和满意度的影响。87 名中老年人被随机分配到以下条件之一:高树木密度运动景观(HTDS = 36-60%)、中等树木密度运动景观(MTDS = 20-35%)和对照条件。通过问卷调查和脑电图读出的阿尔法波来评估参与者在骑车前、骑车过程中和骑车 20 分钟后的压力水平变化。结果显示,与 MTDS 组和对照组相比,接受 HTDS 的参与者在体育活动中表现出更多的乐趣和满足感。相反,在 MTDS 条件下,参与者表现出的放松程度最高,这表明 MTDS 能更有效地减轻中老年人在参与虚拟自行车运动时感受到的压力。这些研究结果表明,在不同树木覆盖密度的虚拟现实环境中进行锻炼,会给中老年人带来生理和心理上的健康。
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引用次数: 0
High glucose-induced senescence contributes to tubular epithelial cell damage in diabetic nephropathy. 高糖诱导的衰老是糖尿病肾病肾小管上皮细胞损伤的原因之一。
IF 3.9 Pub Date : 2024-11-01 Epub Date: 2024-10-13 DOI: 10.1016/j.exger.2024.112609
Deping Xu, Puseletso Moru, Kainan Liao, Wei Song, Ping Yang, Dandan Zang, Chunlin Cai, Haisheng Zhou

Dysfunctional renal tubular epithelial cells, induced by high glucose, are commonly observed in the kidney tissues of diabetic nephropathy (DN) patients. The epithelial-mesenchymal transition (EMT) of these cells often leads to renal interstitial fibrosis and kidney damage in DN. High glucose also triggers mitochondrial damage and apoptosis, contributing further to the dysfunction of renal tubular epithelial cells. Cellular senescence, a recognized characteristic of DN, is primarily caused by high glucose. However, it remains unclear whether high glucose-induced cellular senescence in DN exacerbates the functional impairment of tubular epithelial cells. In this study, we examined the relationship between EMT and cellular senescence in kidney tissues from streptozotocin (STZ)-induced DN and HK-2 cells treated with high glucose (HG). We also investigated the impact of HG concentrations on tubular epithelial cells, specifically mitochondrial dysfunction, cellular senescence and apoptosis. These damages were primarily associated with the secretion of cytokines (such as IL-6, and TNF-α), production of reactive oxygen species (ROS), and an increase of intracellular Ca2+. Notably, resveratrol, an anti-aging agent, could effectively attenuate the occurrence of EMT, mitochondrial dysfunction, and apoptosis induced by HG. Mechanistically, anti-aging treatment leads to a reduction in cytokine secretion, ROS production, and intracellular Ca2+ levels.

在糖尿病肾病(DN)患者的肾组织中,经常可以观察到由高糖诱导的肾小管上皮细胞功能失调。这些细胞的上皮-间质转化(EMT)通常会导致肾间质纤维化和肾脏损伤。高糖还会引发线粒体损伤和细胞凋亡,进一步导致肾小管上皮细胞功能障碍。细胞衰老是 DN 的公认特征,主要由高糖引起。然而,目前仍不清楚高糖诱导的细胞衰老是否会加剧 DN 中肾小管上皮细胞的功能损伤。在这项研究中,我们检测了链脲佐菌素(STZ)诱导的 DN 肾组织和经高糖(HG)处理的 HK-2 细胞中 EMT 与细胞衰老之间的关系。我们还研究了高浓度 HG 对肾小管上皮细胞的影响,特别是线粒体功能障碍、细胞衰老和细胞凋亡。这些损伤主要与细胞因子(如 IL-6 和 TNF-α)的分泌、活性氧(ROS)的产生以及细胞内 Ca2+ 的增加有关。值得注意的是,白藜芦醇作为一种抗衰老剂,能有效减轻 HG 诱导的 EMT、线粒体功能障碍和细胞凋亡。从机理上讲,抗衰老治疗可减少细胞因子分泌、ROS 生成和细胞内 Ca2+ 水平。
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引用次数: 0
The biological roots of the sex-frailty paradox 性-罪悖论的生物学根源
IF 3.9 Pub Date : 2024-10-28 DOI: 10.1016/j.exger.2024.112619
Beatrice Arosio , Anna Picca
Aging is a dynamic process that requires a continuous response and adaptation to internal and external stimuli over the life course. This eventually results in people aging differently and women aging differently than men. The “gender paradox” describes how women experience greater longevity than men, although linked with higher rates of disability and poor health status.
Recently, the concept of frailty has been incorporated into this paradox giving rise to the “sex-frailty paradox” which describes how women are frailer because they manifest worse health status but, at the same time, appear less susceptible to death than men of the same age. However, very little is known about the biological roots of this sex-related difference in frailty.
Inflamm-aging, the chronic low-grade inflammatory state associated with age, plays a key pathophysiological role in several age-related diseases/conditions, including Alzheimer's disease (AD), for which women have a higher lifetime risk than men. Interestingly, inflamm-aging develops at a different rate in women compared to men, with features that could play a critical role in the development of AD in women.
According to this view, a continuum between aging and age-related diseases that probably lacks clear boundaries can be envisioned in which several shared biological mechanisms that progress at different pace may lead to different aging trajectories in women than in men. It, therefore, becomes urgent to consider a holistic approach in the study of aging, and decline it from a gender medicine perspective also considering the biological roots of the sex-frailty paradox.
衰老是一个动态过程,需要在整个生命过程中不断对内外刺激做出反应和适应。这最终导致人的衰老方式不同,女性的衰老方式也与男性不同。性别悖论 "描述了女性如何比男性更长寿,但同时也伴随着更高的残疾率和更差的健康状况。最近,"虚弱"(frailty)的概念也被纳入了这一悖论,并产生了 "性别-虚弱悖论"(sex-frailty paradox),描述了女性如何更虚弱,因为她们表现出更差的健康状况,但同时又比同龄男性更不容易死亡。炎症老化是一种与年龄相关的慢性低水平炎症状态,在几种与年龄相关的疾病/病症中扮演着关键的病理生理角色,其中包括阿尔茨海默病(AD),女性一生中患该病的风险高于男性。有趣的是,女性炎性衰老的发展速度与男性不同,其特征可能在女性阿尔茨海默病的发展中起到关键作用。根据这一观点,可以设想衰老与老年相关疾病之间存在一个可能缺乏明确界限的连续体,其中一些共同的生物机制以不同的速度发展,可能导致女性的衰老轨迹与男性不同。因此,当务之急是在研究衰老问题时考虑采取一种整体方法,并从性别医学的角度来看待衰老问题,同时考虑到性别-脆弱性悖论的生物学根源。
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引用次数: 0
Circadian rhythms and objective measures of physical activity among middle-aged and older adults in Taiwan 台湾中老年人的昼夜节律和体育活动的客观测量。
IF 3.9 Pub Date : 2024-10-28 DOI: 10.1016/j.exger.2024.112616
Jia-Chian Hu , Szu-Yu Hou , Jeanne L. Shea , Hsiao-Han Tang , Sheng-Fu Liang , Yu-Ching Hsu , Ching-Ju Chiu

Background

To identify the association between daytime activity with objectively monitor and subjective variables at a different time-zone of day as well as the sex differences.

Methods

Participants aged 50 years and older living in the community in Taiwan were recruited. The activity was measured by wearable actigraphy devices, diaries, and self-reported questionnaires. The study used nonparametric analysis to examine the association between mean activity level and demographic and subjective measurement variables.

Results

Among the 55 participants enrolled in the study, data of 34 (62 %) participants who meet the criteria that wore a wearable actigraphy device for at least 7 completed days were analyzed. There is no significant relationship between each demographics and subjective measurement variables. However, actigraphy counts are significantly related to female's nutrition (Z = -2.367, p = 0.017*), and male's retirement status (Z = -2.132, p = 0.033*).

Conclusions

The activity in morning is highest of the day with significant correlation to evening activities. Moreover, actigraphy counts that indicating objective measure of physical activity in female is significantly related to physiological variables (nutritional status), while male are predicted by social variables (retired status).
背景:旨在确定白天活动与不同时区的客观监测和主观变量之间的关联以及性别差异:目的:确定不同时区的日间活动与客观监测和主观变量之间的关联以及性别差异:方法:招募居住在台湾社区的 50 岁及以上的参与者。活动量通过可穿戴式活动记录仪、日记和自我报告问卷进行测量。研究采用非参数分析法检验了平均活动量与人口统计学变量和主观测量变量之间的关联:在参加研究的 55 名参与者中,有 34 人(62%)符合佩戴可穿戴式行动记录仪至少 7 天的标准,对他们的数据进行了分析。各人口统计学变量与主观测量变量之间没有明显关系。然而,活动量与女性的运动量(Z = -2.653,p = 0.007**)和营养状况(Z = -2.367,p = 0.017*)以及男性的退休状况(Z = -2.132,p = 0.033*)有显著关系:早上的活动量是一天中最大的,与晚上的活动量有显著相关性。此外,能客观衡量女性体力活动的活动量计数与生理变量(定期体力活动和营养状况)显著相关,而男性则受社会变量(退休状况)的影响。
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引用次数: 0
Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms 建立地塞米松诱导斑马鱼骨骼肌萎缩模型并探索其机制
IF 3.9 Pub Date : 2024-10-26 DOI: 10.1016/j.exger.2024.112615
Chen-Chen Sun , Ye-Jun Li , Dan-Ting Zhu , Zhang-Lin Chen , Jiang-Ling Xiao , Xiang-Tao Chen , Lan Zheng , Xi-Yang Peng , Chang-Fa Tang

Background

Skeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms.

Methods

Zebrafish soaked in 0.01 % dexamethasone solution for 10 days. Loli Track (Denmark) and Loligo Swimming Respirometer were used to observe the effect of dexamethasone on swimming ability. The effects of dexamethasone on zebrafish skeletal muscle were observed by Transmission electron microscopy, H&E, and wheat germ agglutinin techniques. Enriched genes and signaling pathways were analyzed using Transcriptome sequencing. Further, the levels of mitochondrial and endoplasmic reticulum-related proteins were examined to investigate possible mechanisms.

Results

0.01 % dexamethasone reduced zebrafish skeletal muscle mass (p < 0.05), myofibre size and cross-sectional area (p < 0.001), and increased protein degradation (ubiquitination and autophagy) (p < 0.05). In addition, 0.01 % dexamethasone reduced the swimming ability of zebrafish, as evidenced by the reluctance to move, fewer movement trajectories, decreased total distance traveled (p < 0.001), average velocity of movement (p < 0.001), oxygen consumption (p < 0.001), critical swimming speed (p < 0.01) and increased exhaustive swimming time (p < 0.001). Further, 0.01 % dexamethasone-induced mitochondrial dysfunction (decreased mitochondrial biogenesis, disturbs kinetic homeostasis, increased autophagy) and endoplasmic reticulum stress.

Conclusions

0.01 % dexamethasone induces skeletal muscle atrophy and impairs the swimming ability of zebrafish through mitochondrial dysfunction and endoplasmic reticulum stress.
背景:骨骼肌萎缩是大剂量或连续使用糖皮质激素(如地塞米松)的主要副作用之一。然而,有关地塞米松诱导斑马鱼骨骼肌萎缩的研究十分有限,对其分子机制的探索更是少之又少。本研究旨在构建地塞米松诱导斑马鱼骨骼肌萎缩的模型,并研究其分子机制:方法:将斑马鱼浸泡在 0.01 % 地塞米松溶液中 10 天。使用 Loli Track(丹麦)和 Loligo Swimming Respirometer 观察地塞米松对斑马鱼游泳能力的影响。通过透射电子显微镜、H&E 和小麦胚芽凝集素技术观察地塞米松对斑马鱼骨骼肌的影响。利用转录组测序分析了丰富的基因和信号通路。此外,还检测了线粒体和内质网相关蛋白的水平,以研究可能的机制:结果:0.01% 的地塞米松会降低斑马鱼骨骼肌的质量(p 结论:0.01% 的地塞米松会降低斑马鱼骨骼肌的质量(p0.01 % 地塞米松通过线粒体功能障碍和内质网应激诱导斑马鱼骨骼肌萎缩并损害其游泳能力。
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引用次数: 0
The interplay between osteoarthritis and osteoporosis: Mechanisms, implications, and treatment considerations – A narrative review 骨关节炎与骨质疏松症之间的相互作用:机制、影响和治疗考虑因素--叙述性综述。
IF 3.9 Pub Date : 2024-10-23 DOI: 10.1016/j.exger.2024.112614
Kai Huang , Haili Cai
This comprehensive review examines the relationship between osteoarthritis (OA) and osteoporosis (OP), two common disorders in the elderly. OA involves joint cartilage degeneration and pain, while OP leads to fractures due to reduced bone mass. Despite different pathologies, both conditions share risk factors such as age and genetics. Studies reveal mixed results: some show higher bone mineral density (BMD) in OA patients, suggesting an inverse relationship, while others find no significant link. Proposed mechanisms include mechanical loading, bone remodeling, and inflammation. Clinical strategies focus on maintaining bone health in OA and monitoring joint health in OP, with treatments like bisphosphonates and exercise. Understanding these interactions is crucial for developing integrated treatments to improve patient outcomes and quality of life. Further research is needed to clarify these complex mechanisms.
这篇综合评论探讨了骨关节炎(OA)和骨质疏松症(OP)这两种老年人常见疾病之间的关系。骨关节炎会导致关节软骨退化和疼痛,而骨质疏松症则会因骨量减少而导致骨折。尽管病因不同,但这两种疾病都有年龄和遗传等风险因素。研究结果喜忧参半:一些研究显示,OA 患者的骨质密度(BMD)较高,表明两者之间存在反向关系,而另一些研究则发现两者之间没有明显联系。研究提出的机制包括机械负荷、骨重塑和炎症。临床策略侧重于维持 OA 患者的骨骼健康和监测 OP 患者的关节健康,并采用双膦酸盐和运动等治疗方法。了解这些相互作用对于开发综合疗法以改善患者预后和生活质量至关重要。要弄清这些复杂的机制,还需要进一步的研究。
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引用次数: 0
期刊
Experimental gerontology
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