JCSM rapid communications最新文献

Enobosarm in Muscle Wasting: The Rest of the Story Enobosarm在肌肉萎缩中的作用：剩下的故事

JCSM rapid communications

Pub Date : 2026-01-04 DOI: 10.1002/rco2.70027

Stephan von Haehling

<p>Testosterone is an important anabolic in humans, but its conversion to dihydrotestosterone in skin and prostate and to oestradiol in adipose tissue also yields untoward androgenic and estrogenic effects. It was therefore a breakthrough of considerable interest, when Dalton and colleagues in 1998 reported the synthesis of non-steroidal arylpropionamide ligands for the androgen receptor. Three of these newly discovered ligands bound the receptor with affinity similar to dihydrotestosterone and mimicked its effects on receptor-mediated transcriptional activation, thus demonstrating agonist activity [<span>1</span>]. Since then, a number of different non-steroidal chemical scaffolds have been developed to mimic androgen receptor ligands, including bicyclic hydantoins, bicyclic thiohydantoins, imidazolopyrazoles, benzimidazoles, anilines and quinolinones. The umbrella term for these substances is selective androgen-receptor modulators (SARMs), and they were developed with the aim of preserving anabolic effects in muscle and bone while reducing androgenic side effects (e.g., prostate stimulation, virilization and gynecomastia) and other safety concerns [<span>2</span>].</p><p>One of the SARMs that has seen considerable research efforts over the last 25 years is enobosarm (GTx-024), also known as ostarine (Figure 1) [<span>3</span>]. The drug was initially licensed and advanced by GTx Inc. (Memphis, TN) for age-related muscle loss and cachexia. In 2007, GTx even struck a large SARM collaboration with Merck to pursue the treatment of sarcopenia/cachexia and other musculoskeletal conditions [<span>4</span>]. Early trials were indeed encouraging: A Phase II randomized controlled trial in healthy elderly men and postmenopausal women (<i>n</i> = 120) showed dose-dependent gains in lean body mass (LBM) and better stair-climb power over 12 weeks [<span>5</span>]. A Phase II cancer-cachexia trial (<i>n</i> = 159) improved LBM with signals in stair-climb power, both in the 1 and 3 mg daily arm, but no signal in the placebo group [<span>6</span>]. The authors concluded that ‘enobosarm might lead to improvements in LBM, without the toxic effects associated with androgens and progestational agents’. This was followed by two near-identical Phase III studies in non-small cell lung cancer (differences mainly in chemotherapy backbone)—POWER-1 and POWER-2—designed with the US Food and Drug Administration (FDA) to use co-primary responder endpoints combining LBM and stair-climb power [<span>7, 8</span>]. It was a major setback when it became clear that both programmes increased LBM but failed to deliver consistent, clinically meaningful functional gains, and thus no approval followed. Subsequent pursuit in stress urinary incontinence (ASTRID, Phase II) was negative [<span>9</span>], reinforcing the lack of approvable benefit on functional endpoints [<span>10</span>]. Broader commentary has since emphasized how regulator-preferred functional endpoints—and safety expect

睾酮是人体重要的合成代谢物质，但它在皮肤和前列腺中转化为二氢睾酮，在脂肪组织中转化为雌二醇，也会产生不利的雄激素和雌激素作用。因此，当道尔顿和他的同事在1998年报道了雄激素受体的非甾体芳基丙酰胺配体的合成时，这是一个相当有趣的突破。其中三种新发现的配体以类似于二氢睾酮的亲和力结合受体，并模仿其对受体介导的转录激活的影响，从而显示出激动剂活性[1]。从那时起，许多不同的非甾体化学支架已经被开发出来，以模拟雄激素受体配体，包括双环羟基苯胺酮、双环硫代羟基苯胺酮、咪唑吡唑、苯并咪唑、苯胺类和喹啉类。这些物质的总称是选择性雄激素受体调节剂（SARMs），它们的开发目的是保持肌肉和骨骼的合成代谢作用，同时减少雄激素副作用（例如，前列腺刺激、男性化和男性乳房发育）和其他安全问题。enobosarm (GTx-024)，也被称为ostarine（图1）[3]，是在过去25年里获得大量研究成果的sarm之一。该药最初是由GTx公司（Memphis， TN）批准并推进的，用于治疗与年龄相关的肌肉损失和恶病质。2007年，GTx甚至与默克公司达成了一项大型SARM合作，以寻求治疗肌肉减少症/恶病质和其他肌肉骨骼疾病。早期试验确实令人鼓舞：一项针对健康老年男性和绝经后女性（n = 120）的II期随机对照试验显示，在12周内，瘦体重（LBM）和爬楼梯能力呈剂量依赖性增加。一项II期癌症-恶病质试验（n = 159）改善了LBM，每天1和3mg组的爬楼梯能力都有信号，但安慰剂组[6]没有信号。作者得出结论，“enobosarm可能导致LBM的改善，而没有与雄激素和孕激素相关的毒性作用”。随后，在非小细胞肺癌中进行了两项几乎相同的III期研究（差异主要在于化疗骨干）——power -1和power -2，这两项研究由美国食品和药物管理局（FDA）设计，使用联合LBM和爬楼梯功率的共同主要应答终点[7,8]。这是一个重大挫折，因为两个项目都增加了LBM，但未能提供一致的、有临床意义的功能收益，因此没有获得批准。随后对应激性尿失禁（ASTRID， II期）的研究结果为阴性[9]，强化了在功能终点[10]上缺乏可批准的益处。此后，更广泛的评论强调了监管机构偏好的功能终点和对非肿瘤性“肌肉减少症”人群的安全性期望如何使批准变得困难，而肿瘤学环境应用不同的收益-风险演算[10]。总的来说，现在已经很清楚，enobosarm对骨骼肌增加有效，使其成为业余和精英运动中滥用的相关候选人。由于其潜在的合成代谢作用，enobosarm（就像所有sarm一样）已于2008年被列入世界反兴奋剂机构（WADA）的禁用名单。尽管如此，在2013年的III期试验失败后，GTx从恶病质转向探索肿瘤应用（例如雄激素受体[AR+]阳性乳腺癌），这一转变也在同期的报告中被注意到。2019年6月，GTx完成了与Oncternal Therapeutics的反向合并；合并后的公司以Oncternal（纳斯达克股票代码：ONCT）的名义运营。GTx随后转移了重点，仅在1年多之后的2020年12月，Veru公司获得了enobosarm的全球独家权利，并将开发方向转向AR+ ER+ HER2 -乳腺癌，以及后来基于胰高血糖素样肽-1受体激动剂（GLP-1RA）的减肥[14]期间的体成分保存。尽管如此，在撰写本文时，enobosarm仍未被批准用于任何适应症。GLP-1RAs的出现激发了人们对节省肌肉减肥方法的兴趣。事实上，在STEP-1 bb0等临床研究中，GLP-1RAs如semaglutide已被证明可诱导体重减轻12%-15%。有问题的是，这样的体重减轻与LBM的显著减少有关，例如，在STEP-1试验中，治疗的第一年瘦体重减少了约10%。因此，2b期QUALITY试验测试了将enobosarm（3或6mg）添加到semaglutide中的老年超重/肥胖患者，以使减肥更加“节省肌肉”。顶级公司通讯（尚未有同行评审的出版物）报道，与semaglutide +安慰剂相比，semaglutide和enobosarm联合治疗达到了16周总瘦质量保存的主要终点（瘦质量损失相对减少71%；3mg剂量~99%保存；p≤0.002）[16]。有趣的是，enobosarm减少的脂肪量更大，这种效果似乎与剂量有关。根据一份新闻稿，相对改善达到了~ 12-42%，6毫克显示出最大的效果，尽管总体体重减轻与单用semaglutide相似，即在semaglutide和enobosarm联合治疗时，脂肪更多，肌肉损失更少。在停用semaglutide后的12周盲法维持延长中，与安慰剂相比，enobosarm 3mg使体重恢复减少了约46%，并防止了脂肪恢复，两个剂量组都保留了瘦质量。总体安全性被认为是有利的，在活动期胃肠道不良事件比单独使用西马鲁肽少。总的来说，制造商认为这些数据证明了将3mg enobosarm推进到3期，用于GLP-1RA治疗的肌肉保存，并且已经与FDA讨论了监管途径。这条路径值得注意，因为已经提出了几种肌肉保护方法，但使用enobosarm确实有希望，并且热切期待研究结果的发表。事实上，enobosarm能否最终将其对瘦体重的强大作用转化为glp - 1ra诱导的减肥的肌肉保留辅助疗法，现在取决于即将到来的III期项目的结果。作者没有什么可报道的。曾担任AstraZeneca、Bayer、Besins Healthcare、Boehringer Ingelheim、BRAHMS、CSL Vifor、Edwards Lifesciences、MSD、Novartis、Novo Nordisk和Pharmacosmos的有偿顾问和/或收取酬金。S.v.H.报告了来自安进、阿斯利康、勃林格殷格翰、Pharmacosmos、IMI和德国心血管研究中心（DZHK）的研究支持。数据共享不适用于本文，因为在当前研究期间没有生成或分析数据集。

{"title":"Enobosarm in Muscle Wasting: The Rest of the Story","authors":"Stephan von Haehling","doi":"10.1002/rco2.70027","DOIUrl":"https://doi.org/10.1002/rco2.70027","url":null,"abstract":"<p>Testosterone is an important anabolic in humans, but its conversion to dihydrotestosterone in skin and prostate and to oestradiol in adipose tissue also yields untoward androgenic and estrogenic effects. It was therefore a breakthrough of considerable interest, when Dalton and colleagues in 1998 reported the synthesis of non-steroidal arylpropionamide ligands for the androgen receptor. Three of these newly discovered ligands bound the receptor with affinity similar to dihydrotestosterone and mimicked its effects on receptor-mediated transcriptional activation, thus demonstrating agonist activity [<span>1</span>]. Since then, a number of different non-steroidal chemical scaffolds have been developed to mimic androgen receptor ligands, including bicyclic hydantoins, bicyclic thiohydantoins, imidazolopyrazoles, benzimidazoles, anilines and quinolinones. The umbrella term for these substances is selective androgen-receptor modulators (SARMs), and they were developed with the aim of preserving anabolic effects in muscle and bone while reducing androgenic side effects (e.g., prostate stimulation, virilization and gynecomastia) and other safety concerns [<span>2</span>].</p><p>One of the SARMs that has seen considerable research efforts over the last 25 years is enobosarm (GTx-024), also known as ostarine (Figure 1) [<span>3</span>]. The drug was initially licensed and advanced by GTx Inc. (Memphis, TN) for age-related muscle loss and cachexia. In 2007, GTx even struck a large SARM collaboration with Merck to pursue the treatment of sarcopenia/cachexia and other musculoskeletal conditions [<span>4</span>]. Early trials were indeed encouraging: A Phase II randomized controlled trial in healthy elderly men and postmenopausal women (<i>n</i> = 120) showed dose-dependent gains in lean body mass (LBM) and better stair-climb power over 12 weeks [<span>5</span>]. A Phase II cancer-cachexia trial (<i>n</i> = 159) improved LBM with signals in stair-climb power, both in the 1 and 3 mg daily arm, but no signal in the placebo group [<span>6</span>]. The authors concluded that ‘enobosarm might lead to improvements in LBM, without the toxic effects associated with androgens and progestational agents’. This was followed by two near-identical Phase III studies in non-small cell lung cancer (differences mainly in chemotherapy backbone)—POWER-1 and POWER-2—designed with the US Food and Drug Administration (FDA) to use co-primary responder endpoints combining LBM and stair-climb power [<span>7, 8</span>]. It was a major setback when it became clear that both programmes increased LBM but failed to deliver consistent, clinically meaningful functional gains, and thus no approval followed. Subsequent pursuit in stress urinary incontinence (ASTRID, Phase II) was negative [<span>9</span>], reinforcing the lack of approvable benefit on functional endpoints [<span>10</span>]. Broader commentary has since emphasized how regulator-preferred functional endpoints—and safety expect","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904841","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 Effects of Acute Hospitalisation on the Characteristics of Acute Sarcopenia in Older Adults: A Systematic Review and Meta-Analysis 急性住院对老年人急性肌肉减少症特征的影响：系统回顾和荟萃分析

JCSM rapid communications

Pub Date : 2025-12-28 DOI: 10.1002/rco2.70024

Thomas J. Cartledge, Qian Yue Tan, Liam Jones, Taeko Becque, Kinda Ibrahim, Stephen Eu Ruen Lim

<div> <section> <h3> Background</h3> <p>Acute sarcopenia in hospitalised older adults is associated with poor outcomes, such as functional decline, increased risk of falls and prolonged hospital stays. Despite this, its development among older inpatients remains poorly understood. We aimed to quantify the effects of acute hospitalisation on sarcopenia outcomes in older adults.</p> </section> <section> <h3> Methods</h3> <p>MEDLINE, EMBASE, CINAHL and Web of Science were searched from inception until January 2025. Studies that included acutely admitted patients aged 65 years or older and reported changes in at least one measure of sarcopenia during hospitalisation were included. Barthel Index was also included. A random-effects meta-analysis was undertaken.</p> </section> <section> <h3> Results</h3> <p>Fifty-five eligible studies were included, with a participant mean age of 82.2 years (<i>n</i> = 14 919 participants). Our meta-analysis showed grip strength and chair-to-stand performance to significantly increase during hospitalisation (standard mean difference [SMD] = 0.06, 95% confidence interval [CI]: 0.00; 0.13, <i>I</i><sup>2</sup> = 3%, <i>p</i> = 0.05 and SMD = 0.23, 95% CI: 0.13; 0.33, <i>I</i><sup>2</sup> = 0%, <i>p</i> < 0.01, respectively). No physical performance measure showed a significant change. Muscle mass showed no change when measured by bioelectrical impedance analysis (SMD = 0.01, 95% CI: −0.09; 0.08, <i>I</i><sup>2</sup> = 0%, <i>p</i> = 0.86). There were insufficient studies using MRI (<i>n</i> = 2) or DEXA (<i>n</i> = 1) to perform a meta-analysis. Individual studies showed a significant decrease in mid-thigh muscle area (cm<sup>2</sup>) by MRI (mean difference [MD] = −3.9, <i>p</i> < 0.01) and a significant decrease in leg lean mass (kg) by DEXA (MD = −0.16, <i>p</i> < 0.05). Barthel Index score significantly increased from admission to discharge (SMD = 0.26, 95% CI: 0.06; 0.46, <i>I</i><sup>2</sup> = 98.0%, <i>p</i> = 0.01) but significantly decreased from preadmission to discharge (SMD = −0.66, 95% CI: −0.92; −0.39, <i>I</i><sup>2</sup> = 97.5%, <i>p</i> < 0.001). Both age and hospital length of stay had no effect on grip strength (<i>p</i> = 0.615 and <i>p</i> = 0.096) or Barthel Index (<i>p</i> = 0.835 and <i>p</i> = 0.279).</p> </section> <section> <h3> Conclusions</h3> <p>This review has shown that grip strength improves during hospitalisation and decreases in muscle mass are observed when measured using MRI or DEXA. Muscle strength and physical performance assessed on admission are poor indicators of baseli

背景住院老年人急性肌肉减少症与不良预后相关，如功能下降、跌倒风险增加和住院时间延长。尽管如此，它在老年住院患者中的发展仍然知之甚少。我们的目的是量化急性住院治疗对老年人肌肉减少症结局的影响。方法检索自建校至2025年1月的MEDLINE、EMBASE、CINAHL和Web of Science。研究纳入了65岁或以上的急性入院患者，并在住院期间报告了至少一项肌肉减少症指标的变化。Barthel指数也包括在内。进行随机效应荟萃分析。结果纳入55项符合条件的研究，参与者平均年龄为82.2岁（n = 14919名参与者）。我们的荟萃分析显示，住院期间握力和从椅子到站立的表现显著提高（标准平均差[SMD] = 0.06, 95%可信区间[CI]: 0.00; 0.13, I2 = 3%, p = 0.05, SMD = 0.23, 95% CI: 0.13; 0.33, I2 = 0%, p < 0.01）。没有任何物理性能测量显示出明显的变化。生物电阻抗分析显示肌肉质量没有变化（SMD = 0.01, 95% CI: - 0.09; 0.08, I2 = 0%, p = 0.86）。没有足够的研究使用MRI （n = 2）或DEXA （n = 1）进行meta分析。个体研究显示，MRI显示大腿中部肌肉面积（cm2）显著减少（平均差值[MD] = - 3.9, p < 0.01）， DEXA显示腿瘦质量（kg）显著减少（MD = - 0.16, p < 0.05）。Barthel指数评分从入院到出院显著升高（SMD = 0.26, 95% CI: 0.06; 0.46, I2 = 98.0%, p = 0.01），但从入院前到出院显著降低（SMD = - 0.66, 95% CI: - 0.92; - 0.39, I2 = 97.5%, p < 0.001）。年龄和住院时间对握力（p = 0.615和p = 0.096）和Barthel指数（p = 0.835和p = 0.279）均无影响。结论：本综述表明，住院期间握力提高，而使用MRI或DEXA测量时观察到肌肉量减少。入院时评估的肌肉力量和身体表现是基线状态的不良指标，因为它们在急性疾病期间经常受到不利影响，使它们不能代表真实的基线能力。缺乏改善的身体表现结果是一个重要的发现，因为它代表未能恢复到院前的基线能力。

{"title":"The Effects of Acute Hospitalisation on the Characteristics of Acute Sarcopenia in Older Adults: A Systematic Review and Meta-Analysis","authors":"Thomas J. Cartledge, Qian Yue Tan, Liam Jones, Taeko Becque, Kinda Ibrahim, Stephen Eu Ruen Lim","doi":"10.1002/rco2.70024","DOIUrl":"https://doi.org/10.1002/rco2.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute sarcopenia in hospitalised older adults is associated with poor outcomes, such as functional decline, increased risk of falls and prolonged hospital stays. Despite this, its development among older inpatients remains poorly understood. We aimed to quantify the effects of acute hospitalisation on sarcopenia outcomes in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MEDLINE, EMBASE, CINAHL and Web of Science were searched from inception until January 2025. Studies that included acutely admitted patients aged 65 years or older and reported changes in at least one measure of sarcopenia during hospitalisation were included. Barthel Index was also included. A random-effects meta-analysis was undertaken.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-five eligible studies were included, with a participant mean age of 82.2 years (<i>n</i> = 14 919 participants). Our meta-analysis showed grip strength and chair-to-stand performance to significantly increase during hospitalisation (standard mean difference [SMD] = 0.06, 95% confidence interval [CI]: 0.00; 0.13, <i>I</i><sup>2</sup> = 3%, <i>p</i> = 0.05 and SMD = 0.23, 95% CI: 0.13; 0.33, <i>I</i><sup>2</sup> = 0%, <i>p</i> < 0.01, respectively). No physical performance measure showed a significant change. Muscle mass showed no change when measured by bioelectrical impedance analysis (SMD = 0.01, 95% CI: −0.09; 0.08, <i>I</i><sup>2</sup> = 0%, <i>p</i> = 0.86). There were insufficient studies using MRI (<i>n</i> = 2) or DEXA (<i>n</i> = 1) to perform a meta-analysis. Individual studies showed a significant decrease in mid-thigh muscle area (cm<sup>2</sup>) by MRI (mean difference [MD] = −3.9, <i>p</i> < 0.01) and a significant decrease in leg lean mass (kg) by DEXA (MD = −0.16, <i>p</i> < 0.05). Barthel Index score significantly increased from admission to discharge (SMD = 0.26, 95% CI: 0.06; 0.46, <i>I</i><sup>2</sup> = 98.0%, <i>p</i> = 0.01) but significantly decreased from preadmission to discharge (SMD = −0.66, 95% CI: −0.92; −0.39, <i>I</i><sup>2</sup> = 97.5%, <i>p</i> < 0.001). Both age and hospital length of stay had no effect on grip strength (<i>p</i> = 0.615 and <i>p</i> = 0.096) or Barthel Index (<i>p</i> = 0.835 and <i>p</i> = 0.279).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review has shown that grip strength improves during hospitalisation and decreases in muscle mass are observed when measured using MRI or DEXA. Muscle strength and physical performance assessed on admission are poor indicators of baseli","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145887788","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

Comparison of Computed Tomography Derived Muscle Cross-Sectional Area With Dual-Energy X-Ray Absorptiometry Derived Whole-Body Muscle Mass in COVID-19 Survivors COVID-19幸存者计算机断层扫描所得肌肉截面积与双能x线吸收仪所得全身肌肉质量的比较

JCSM rapid communications

Pub Date : 2025-12-22 DOI: 10.1002/rco2.70022

Rohini Bhadra, Debbie Gach, Frits H. M. van Osch, Joop P. van den Bergh, Sucharita Sambashivaiah, Annemie M. W. J. Schols, Rosanne J. H. C. G. Beijers

Background

Muscle mass is an important determinant of clinical outcome in chronic diseases as well as in acute infectious diseases such as COVID-19. Both dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) imaging are utilized to quantify muscle. The objective of this study was to assess the agreement between CT segmental analysis of muscle and whole-body muscle mass from DXA.

Methods

A prospective observational study was carried out among COVID-19 survivors at least 1 year after the infection. The participants underwent a comprehensive multidimensional health assessment, including DXA and an extended chest CT. Lean mass (LM) and appendicular skeletal muscle mass (SMM) were derived from DXA, and pectoralis, L1 and L3 muscle cross-sectional area (CSA) were assessed using Slice-O-Matic software version 5.0 from the CT scans. Agreement between the two methods was assessed using Pearson correlation and Bland–Altman plots.

Results

One hundred thirty COVID-19 survivors (age 60.8 ± 13.1 years, female % 31.5, BMI 29.9 ± 5.2 kg/m²) were included in the analysis. 83.9% of the participants were obese or overweight. Muscle CSA at L1 and L3 had a strong positive correlation with DXA LM and SMM (L1: r = 0.866 and r = 0.853 for LM and SMM, respectively; L3: r = 0.845 and r = 0.845, p < 0.001). Bland–Altman plots showed good agreement between the two methods. CT pectoralis showed a moderate correlation with DXA LM and SMM (r = 0.659 and r = 0.684, respectively, p < 0.001).

Conclusions

Muscle CSA at L1 and L3 from CT scans is strongly correlated, and pectoralis muscle CSA is moderately correlated with whole-body muscle mass measurement from DXA scans among COVID-19 survivors.

肌肉质量是慢性疾病以及COVID-19等急性传染病临床结果的重要决定因素。双能x线吸收仪（DXA）和计算机断层扫描（CT）成像用于量化肌肉。本研究的目的是评估肌肉的CT分段分析和DXA的全身肌肉质量之间的一致性。方法对感染后至少1年的COVID-19幸存者进行前瞻性观察研究。参与者接受了全面的多维健康评估，包括DXA和扩展胸部CT。瘦肉质量（LM）和阑尾骨骼肌质量（SMM）由DXA计算，胸肌、L1和L3肌肉横截面积（CSA）使用Slice-O-Matic软件5.0版本从CT扫描中评估。使用Pearson相关性和Bland-Altman图评估两种方法之间的一致性。结果纳入新冠肺炎幸存者130例（年龄60.8±13.1岁，女性31.5 %,BMI 29.9±5.2 kg/m2）。83.9%的参与者肥胖或超重。L1和L3肌肉CSA与DXA LM和SMM有很强的正相关（L1: LM和SMM分别r = 0.866和r = 0.853; L3: r = 0.845和r = 0.845, p < 0.001）。Bland-Altman图显示了两种方法之间的良好一致性。CT显示胸肌与DXA LM、SMM有中度相关性（r = 0.659、r = 0.684, p < 0.001）。结论在COVID-19幸存者中，CT扫描L1和L3的肌肉CSA与DXA扫描的全身肌肉质量测量值有很强的相关性，胸肌CSA与DXA扫描的全身肌肉质量测量值有中度相关性。

{"title":"Comparison of Computed Tomography Derived Muscle Cross-Sectional Area With Dual-Energy X-Ray Absorptiometry Derived Whole-Body Muscle Mass in COVID-19 Survivors","authors":"Rohini Bhadra, Debbie Gach, Frits H. M. van Osch, Joop P. van den Bergh, Sucharita Sambashivaiah, Annemie M. W. J. Schols, Rosanne J. H. C. G. Beijers","doi":"10.1002/rco2.70022","DOIUrl":"https://doi.org/10.1002/rco2.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle mass is an important determinant of clinical outcome in chronic diseases as well as in acute infectious diseases such as COVID-19. Both dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) imaging are utilized to quantify muscle. The objective of this study was to assess the agreement between CT segmental analysis of muscle and whole-body muscle mass from DXA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective observational study was carried out among COVID-19 survivors at least 1 year after the infection. The participants underwent a comprehensive multidimensional health assessment, including DXA and an extended chest CT. Lean mass (LM) and appendicular skeletal muscle mass (SMM) were derived from DXA, and pectoralis, L1 and L3 muscle cross-sectional area (CSA) were assessed using Slice-O-Matic software version 5.0 from the CT scans. Agreement between the two methods was assessed using Pearson correlation and Bland–Altman plots.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred thirty COVID-19 survivors (age 60.8 ± 13.1 years, female % 31.5, BMI 29.9 ± 5.2 kg/m<sup>2</sup>) were included in the analysis. 83.9% of the participants were obese or overweight. Muscle CSA at L1 and L3 had a strong positive correlation with DXA LM and SMM (L1: <i>r</i> = 0.866 and <i>r</i> = 0.853 for LM and SMM, respectively; L3: <i>r</i> = 0.845 and <i>r</i> = 0.845, <i>p</i> < 0.001). Bland–Altman plots showed good agreement between the two methods. CT pectoralis showed a moderate correlation with DXA LM and SMM (<i>r</i> = 0.659 and <i>r</i> = 0.684, respectively, <i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Muscle CSA at L1 and L3 from CT scans is strongly correlated, and pectoralis muscle CSA is moderately correlated with whole-body muscle mass measurement from DXA scans among COVID-19 survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824813","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

Association of Sarcopenia With Phase Angle and Urinary Titin Fragment in Patients With Gastrointestinal Malignancies 胃肠道恶性肿瘤患者肌少症与相位角和尿Titin片段的关系

JCSM rapid communications

Pub Date : 2025-12-18 DOI: 10.1002/rco2.70025

Mitsugi Shimoda, Masahiro Shiihara, Mitsuru Watanabe, Ryoichi Miyamoto, Jiro Shimazaki, Shuji Suzuki

Background

Preoperative evaluation of sarcopenia and nutritional status is a crucial prognostic factor in patients with gastrointestinal malignancies (GIM). Whole-body phase angle (Ph A), measured via bioelectrical impedance analysis (BIA), reflects cellular health and nutritional condition, and has gained attention as a potential prognostic marker.

Methods

This study included 149 patients who underwent surgery for GIM at our department between April 2024 and May 2025. Sarcopenia was assessed using skeletal muscle index (SMI; men: < 7.0, women: < 5.7 kg m²) derived from BIA, and those meeting the criteria were classified as ‘presumed sarcopenia (P-sarcopenia)’. Ph A values were also obtained using BIA, and skeletal muscle volume was measured using SYNAPSE VINCENT to determine the volume of large psoas muscle (PV).

Results

Among the 149 patients, 58 (38.9%) were diagnosed with P-sarcopenia, the breakdown being 31 males (53.4%) and 27 females (46.6%). The median age was 76 years (range: 53–89). Multivariate analysis revealed that low Ph A (odds ratio: 0.537, p < 0.04) and low PV (odds ratio: 0.992, p < 0.007) were significant risk factors for P-sarcopenia. These findings suggest that patients with P-sarcopenia tend to have lower Ph A and PV values.

Conclusions

Patients with GIM who present with P-sarcopenia are more likely to exhibit reduced Ph A and PV, indicating compromised cellular and nutritional status. Ph A, as a non-invasive and easily obtainable parameter via BIA, may serve as a useful screening tool for identifying P-sarcopenia in preoperative settings.

背景术前评估肌肉减少和营养状况是胃肠道恶性肿瘤（GIM）患者预后的重要因素。通过生物电阻抗分析（BIA）测量的全身相角（Ph A）反映了细胞的健康和营养状况，并作为潜在的预后指标受到关注。方法本研究纳入了2024年4月至2025年5月在我科接受GIM手术的149例患者。根据BIA的骨骼肌指数（SMI，男性：7.0，女性：5.7 kg m2）评估骨骼肌减少症，符合标准的人被归类为“推定骨骼肌减少症（P-sarcopenia）”。BIA测定Ph A值，SYNAPSE VINCENT测定骨骼肌体积，测定大腰肌（PV）体积。结果149例患者中，58例（38.9%）确诊为p -肌减少症，其中男性31例（53.4%），女性27例（46.6%）。中位年龄为76岁（53-89岁）。多因素分析显示，低Ph A（优势比：0.537,p < 0.04）和低PV（优势比：0.992,p < 0.007）是p -肌少症的显著危险因素。这些结果表明，p型肌肉减少症患者往往具有较低的Ph A和PV值。结论：伴有p型肌肉减少症的GIM患者更容易出现Ph A和PV降低，表明细胞和营养状况受损。Ph A作为一种无创且易于通过BIA获得的参数，可作为术前识别p -肌少症的有用筛查工具。

{"title":"Association of Sarcopenia With Phase Angle and Urinary Titin Fragment in Patients With Gastrointestinal Malignancies","authors":"Mitsugi Shimoda, Masahiro Shiihara, Mitsuru Watanabe, Ryoichi Miyamoto, Jiro Shimazaki, Shuji Suzuki","doi":"10.1002/rco2.70025","DOIUrl":"https://doi.org/10.1002/rco2.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preoperative evaluation of sarcopenia and nutritional status is a crucial prognostic factor in patients with gastrointestinal malignancies (GIM). Whole-body phase angle (Ph A), measured via bioelectrical impedance analysis (BIA), reflects cellular health and nutritional condition, and has gained attention as a potential prognostic marker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 149 patients who underwent surgery for GIM at our department between April 2024 and May 2025. Sarcopenia was assessed using skeletal muscle index (SMI; men: < 7.0, women: < 5.7 kg m<sup>2</sup>) derived from BIA, and those meeting the criteria were classified as ‘presumed sarcopenia (P-sarcopenia)’. Ph A values were also obtained using BIA, and skeletal muscle volume was measured using SYNAPSE VINCENT to determine the volume of large psoas muscle (PV).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 149 patients, 58 (38.9%) were diagnosed with P-sarcopenia, the breakdown being 31 males (53.4%) and 27 females (46.6%). The median age was 76 years (range: 53–89). Multivariate analysis revealed that low Ph A (odds ratio: 0.537, <i>p</i> < 0.04) and low PV (odds ratio: 0.992, <i>p</i> < 0.007) were significant risk factors for P-sarcopenia. These findings suggest that patients with P-sarcopenia tend to have lower Ph A and PV values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with GIM who present with P-sarcopenia are more likely to exhibit reduced Ph A and PV, indicating compromised cellular and nutritional status. Ph A, as a non-invasive and easily obtainable parameter via BIA, may serve as a useful screening tool for identifying P-sarcopenia in preoperative settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824853","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

Velocity-Based-Training Induces Positive Changes in Muscle Morphology in Parkinson's Disease Patients: A Pilot Study 基于速度的训练诱导帕金森病患者肌肉形态的积极变化：一项初步研究

JCSM rapid communications

Pub Date : 2025-12-15 DOI: 10.1002/rco2.70023

Caleb P. Calaway, Ana Raquel Calzada, Michel Huyghe, Colten Brown, Humzah Ali, Kylie Martinez, Bryan Mann, Ihtsham Haq, Joseph F. Signorile

<div> <section> <h3> Background</h3> <p>High-speed resistance training has been shown to be a viable intervention for reducing neuromuscular symptoms in older persons with Parkinson's disease. Velocity-based training, a recently developed resistance training modality, utilizes velocity rather than load to dictate progressions. No study has examined the effects of this training method on muscle structure in Parkinson's patients.</p> </section> <section> <h3> Methods</h3> <p>Sixteen older adults with Parkinson's disease (Hoehn and Yahr Stages 1–3) were randomly assigned to a 10% (<i>n</i> = 7, 6 males, 1 female) or 30% (<i>n</i> = 9, 6 males, 3 females) velocity loss threshold protocol twice weekly for 12 weeks of velocity-based training. Changes in ultrasound measures including muscle thickness, echo intensity, pennation angle, shear wave elastography, and performance measurements including specific force and power of the left and right rectus femoris and vastus lateralis were analysed before and after the intervention period.</p> </section> <section> <h3> Results</h3> <p>Significant improvements were seen for the sample in muscle thickness for the right (MDiff ± SE = 0.19 ± 0.05 cm; <i>p</i> = 0.003) and left (0.20 ± 0.09 cm; <i>p</i> = 0.033) rectus femoris and the right (0.14 ± 0.06 cm; <i>p</i> = 0.04) and left (0.19 ± 0.07 cm; <i>p</i> = 0.018) vastus lateralis. For echo intensity, there were significant improvements for the right rectus femoris (−3.37 ± 1.29 units; <i>p</i> = 0.002) and the left vastus lateralis (−7.11 ± 2.68 units; <i>p</i> = 0.019); however, improvements in the left (<i>p</i> = 0.033) and right (<i>p</i> < 0.001) vastus lateralis were seen only by the 30% velocity loss threshold group. Significant increases in pennation angle were detected in the right rectus femoris (2.47° ± 0.84°; <i>p</i> = 0.011) and reductions in shear wave elastography for the left rectus femoris (−3.33 ± 1.29 kPa; <i>p</i> = 0.013) of the sample. For specific power, significant improvements were seen for the right (0.02 ± 0.01 W·cm<sup>3</sup>; <i>p</i> = 0.040) and left (0.04 ± 0.02 W·cm<sup>3</sup>; <i>p</i> = 0.047) rectus femoris muscles for both groups.</p> </section> <section> <h3> Conclusions</h3> <p>Results indicate that 12 weeks of velocity-based training can produce positive changes in muscle morphology and neuromuscular performance of the lower limbs for individuals with Parkinson's disease. Furthermore, using a 30% velocity loss threshold is more effective than using a 10% velocity loss threshold.</p> <p><

高速阻力训练已被证明是减轻老年帕金森病患者神经肌肉症状的一种可行的干预措施。以速度为基础的训练，是最近发展起来的一种阻力训练方式，利用速度而不是负荷来决定进步。目前还没有研究检验这种训练方法对帕金森病患者肌肉结构的影响。方法将16例老年帕金森病患者（Hoehn和Yahr阶段1 - 3）随机分为10% （n = 7, 6男性，1女性）或30% （n = 9, 6男性，3女性）速度损失阈值方案，每周2次，为期12周的速度训练。分析干预前后肌肉厚度、回声强度、穿刺角度、横波弹性成像等超声指标的变化，以及左右股直肌和股外侧肌比力和功率等性能指标的变化。结果右股直肌（MDiff±SE = 0.19±0.05 cm, p = 0.003）、左股直肌（0.20±0.09 cm, p = 0.033）、右股外侧肌（0.14±0.06 cm, p = 0.04）、左股外侧肌（0.19±0.07 cm, p = 0.018）的肌肉厚度均有显著改善。回声强度方面，右侧股直肌（- 3.37±1.29个单位，p = 0.002）和左侧股外侧肌（- 7.11±2.68个单位，p = 0.019）有显著改善；然而，只有30%速度损失阈值组的左股外侧肌（p = 0.033）和右股外侧肌（p < 0.001）有所改善。右侧股直肌的穿刺角显著增加（2.47°±0.84°，p = 0.011），左侧股直肌的横波弹性图显著减少（- 3.33±1.29 kPa, p = 0.013）。在比功率方面，两组右股直肌（0.02±0.01 W·cm3, p = 0.040）和左股直肌（0.04±0.02 W·cm3, p = 0.047）均有显著改善。结果表明，12周的速度训练可以对帕金森病患者的下肢肌肉形态和神经肌肉性能产生积极的影响。此外，使用30%的速度损失阈值比使用10%的速度损失阈值更有效。试验注册：20220489

{"title":"Velocity-Based-Training Induces Positive Changes in Muscle Morphology in Parkinson's Disease Patients: A Pilot Study","authors":"Caleb P. Calaway, Ana Raquel Calzada, Michel Huyghe, Colten Brown, Humzah Ali, Kylie Martinez, Bryan Mann, Ihtsham Haq, Joseph F. Signorile","doi":"10.1002/rco2.70023","DOIUrl":"https://doi.org/10.1002/rco2.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High-speed resistance training has been shown to be a viable intervention for reducing neuromuscular symptoms in older persons with Parkinson's disease. Velocity-based training, a recently developed resistance training modality, utilizes velocity rather than load to dictate progressions. No study has examined the effects of this training method on muscle structure in Parkinson's patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixteen older adults with Parkinson's disease (Hoehn and Yahr Stages 1–3) were randomly assigned to a 10% (<i>n</i> = 7, 6 males, 1 female) or 30% (<i>n</i> = 9, 6 males, 3 females) velocity loss threshold protocol twice weekly for 12 weeks of velocity-based training. Changes in ultrasound measures including muscle thickness, echo intensity, pennation angle, shear wave elastography, and performance measurements including specific force and power of the left and right rectus femoris and vastus lateralis were analysed before and after the intervention period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant improvements were seen for the sample in muscle thickness for the right (MDiff ± SE = 0.19 ± 0.05 cm; <i>p</i> = 0.003) and left (0.20 ± 0.09 cm; <i>p</i> = 0.033) rectus femoris and the right (0.14 ± 0.06 cm; <i>p</i> = 0.04) and left (0.19 ± 0.07 cm; <i>p</i> = 0.018) vastus lateralis. For echo intensity, there were significant improvements for the right rectus femoris (−3.37 ± 1.29 units; <i>p</i> = 0.002) and the left vastus lateralis (−7.11 ± 2.68 units; <i>p</i> = 0.019); however, improvements in the left (<i>p</i> = 0.033) and right (<i>p</i> < 0.001) vastus lateralis were seen only by the 30% velocity loss threshold group. Significant increases in pennation angle were detected in the right rectus femoris (2.47° ± 0.84°; <i>p</i> = 0.011) and reductions in shear wave elastography for the left rectus femoris (−3.33 ± 1.29 kPa; <i>p</i> = 0.013) of the sample. For specific power, significant improvements were seen for the right (0.02 ± 0.01 W·cm<sup>3</sup>; <i>p</i> = 0.040) and left (0.04 ± 0.02 W·cm<sup>3</sup>; <i>p</i> = 0.047) rectus femoris muscles for both groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Results indicate that 12 weeks of velocity-based training can produce positive changes in muscle morphology and neuromuscular performance of the lower limbs for individuals with Parkinson's disease. Furthermore, using a 30% velocity loss threshold is more effective than using a 10% velocity loss threshold.</p>\u0000 \u0000 <p><","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824389","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

Effect of Stretching on Skeletal Muscle Fibrosis in Sarcopenia 拉伸对骨骼肌减少症骨骼肌纤维化的影响

JCSM rapid communications

Pub Date : 2025-12-15 DOI: 10.1002/rco2.70021

Daiki Nohara, Momoko Nagai-Tanima, Shion Masuda, Misa Toyota, Ryo Nakahara, Kazuhiro Hayashi, Tomoki Aoyama

<div> <section> <h3> Background</h3> <p>Muscle weakness with age precedes muscle mass loss, and muscle quality is an issue in sarcopenia. Muscle tissue fibrosis progresses with age, with an increasing proportion of connective tissue containing collagen fibres. Increased fibrosis reduces the efficiency of force transmission during muscle contraction, leading to decreased muscle tension and overall performance. However, few studies have focused specifically on this condition and examined its treatment and effects. Using senescence-accelerated mouse-prone 8 (SAMP8) models, we aimed to clarify the effects of stretch stimulation on fibrosis and examine muscle function, histological changes in fibrosis and changes in fibrosis-related genes.</p> </section> <section> <h3> Methods</h3> <p>The right side of the gastrocnemius muscle of 8-month-old SAMP8 was the stretch group and the left side the control group (<i>n</i> = 8/group). The intervention was performed 15 times/min, 15 min/day and 5 days/week for 2 weeks. Muscle wet weight (MWW), ankle joint range of motion and passive/active tension were measured to evaluate muscle function. For histological analysis, muscle fibre cross-sectional area (CSA) and collagen content were calculated using haematoxylin and eosin and picrosirius-red staining, respectively. For molecular biological analysis, mRNA expression levels of fibrosis-related genes, transforming growth factor-β, α-smooth muscle actin (SMA), and collagen types I and III were measured using quantitative polymerase chain reaction.</p> </section> <section> <h3> Results</h3> <p>There was no significant difference in body weight and ankle joint's range of motion before and after the intervention. MWW after the intervention was higher in the stretch group (control group, 0.13 ± 0.01 g vs. stretch group, 0.14 ± 0.01 g; <i>p</i> < 0.05). No significant difference occurred in passive tension between groups; active tension was higher in the stretch group (control group, 2.98 ± 0.53 N/g vs. stretch group, 3.67 ± 0.52 N/g; <i>p</i> < 0.05). Histological findings showed a significantly higher CSA (control group, 2065.21 ± 93.98 μm<sup>2</sup> vs. stretch group, 2571.15 ± 187.12 μm<sup>2</sup>; <i>p</i> < 0.05) and a significantly lower collagen content in the stretch group (control group, 1.28 ± 0.47% vs. stretch group, 0.53 ± 0.14%; <i>p</i> < 0.05). Thickening of the perimysium and endomysium was lower in the stretch group. Molecular biological findings showed a significant decrease in the expression levels of fibrosis-related genes, including α-SMA (control group, 1 ± 0.49 vs. stretch group, 0.30 ± 0.16; <i>p</i> < 0.05) and collagen type III (c

背景随着年龄的增长肌肉无力先于肌肉质量的减少，肌肉质量是肌肉减少症的一个问题。肌肉组织纤维化随着年龄的增长而发展，含有胶原纤维的结缔组织的比例增加。纤维化的增加降低了肌肉收缩过程中力传递的效率，导致肌肉张力和整体表现下降。然而，很少有研究专门关注这种情况，并检查其治疗和影响。使用衰老加速小鼠8 （SAMP8）模型，我们旨在阐明拉伸刺激对纤维化的影响，并检查肌肉功能、纤维化组织学变化和纤维化相关基因的变化。方法8月龄SAMP8腓肠肌右侧为拉伸组，左侧为对照组（n = 8/组）。干预15次/分钟，15分钟/天，5天/周，共2周。测量肌肉湿重（MWW）、踝关节活动范围和被动/主动张力来评估肌肉功能。进行组织学分析时，分别采用苏木精、伊红和小红染色法计算肌纤维横截面积（CSA）和胶原蛋白含量。在分子生物学分析方面，采用定量聚合酶链反应法测定了纤维化相关基因、转化生长因子-β、α-平滑肌肌动蛋白（SMA）和ⅰ型和ⅲ型胶原蛋白的mRNA表达水平。结果干预前后患者体重、踝关节活动度无显著差异。拉伸组干预后MWW较高（对照组0.13±0.01 g，拉伸组0.14±0.01 g; p < 0.05）。两组间被动张力无显著差异；张力组主动张力明显高于张力组（对照组为2.98±0.53 N/g，张力组为3.67±0.52 N/g; p < 0.05）。组织学结果显示，拉伸组CSA显著增高（对照组，2065.21±93.98 μm2比拉伸组高，2571.15±187.12 μm2; p < 0.05），胶原含量显著降低（对照组，1.28±0.47%比拉伸组高，0.53±0.14%;p < 0.05）。牵张组肌周和肌内膜增厚较低。分子生物学结果显示，纤维化相关基因α-SMA（对照组，与拉伸组相比，1±0.49,0.30±0.16;p < 0.05）和III型胶原（对照组，与拉伸组相比，1±0.39,0.37±0.23;p < 0.05）的表达水平显著降低。结论拉伸干预SAMP8降低了一些纤维化相关基因的表达，可能导致骨骼肌胶原增殖减少和活性张力增加。

{"title":"Effect of Stretching on Skeletal Muscle Fibrosis in Sarcopenia","authors":"Daiki Nohara, Momoko Nagai-Tanima, Shion Masuda, Misa Toyota, Ryo Nakahara, Kazuhiro Hayashi, Tomoki Aoyama","doi":"10.1002/rco2.70021","DOIUrl":"https://doi.org/10.1002/rco2.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle weakness with age precedes muscle mass loss, and muscle quality is an issue in sarcopenia. Muscle tissue fibrosis progresses with age, with an increasing proportion of connective tissue containing collagen fibres. Increased fibrosis reduces the efficiency of force transmission during muscle contraction, leading to decreased muscle tension and overall performance. However, few studies have focused specifically on this condition and examined its treatment and effects. Using senescence-accelerated mouse-prone 8 (SAMP8) models, we aimed to clarify the effects of stretch stimulation on fibrosis and examine muscle function, histological changes in fibrosis and changes in fibrosis-related genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The right side of the gastrocnemius muscle of 8-month-old SAMP8 was the stretch group and the left side the control group (<i>n</i> = 8/group). The intervention was performed 15 times/min, 15 min/day and 5 days/week for 2 weeks. Muscle wet weight (MWW), ankle joint range of motion and passive/active tension were measured to evaluate muscle function. For histological analysis, muscle fibre cross-sectional area (CSA) and collagen content were calculated using haematoxylin and eosin and picrosirius-red staining, respectively. For molecular biological analysis, mRNA expression levels of fibrosis-related genes, transforming growth factor-β, α-smooth muscle actin (SMA), and collagen types I and III were measured using quantitative polymerase chain reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was no significant difference in body weight and ankle joint's range of motion before and after the intervention. MWW after the intervention was higher in the stretch group (control group, 0.13 ± 0.01 g vs. stretch group, 0.14 ± 0.01 g; <i>p</i> < 0.05). No significant difference occurred in passive tension between groups; active tension was higher in the stretch group (control group, 2.98 ± 0.53 N/g vs. stretch group, 3.67 ± 0.52 N/g; <i>p</i> < 0.05). Histological findings showed a significantly higher CSA (control group, 2065.21 ± 93.98 μm<sup>2</sup> vs. stretch group, 2571.15 ± 187.12 μm<sup>2</sup>; <i>p</i> < 0.05) and a significantly lower collagen content in the stretch group (control group, 1.28 ± 0.47% vs. stretch group, 0.53 ± 0.14%; <i>p</i> < 0.05). Thickening of the perimysium and endomysium was lower in the stretch group. Molecular biological findings showed a significant decrease in the expression levels of fibrosis-related genes, including α-SMA (control group, 1 ± 0.49 vs. stretch group, 0.30 ± 0.16; <i>p</i> < 0.05) and collagen type III (c","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824388","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

A Novel Mouse Model Recapitulating the Clinical Progression of Cancer Cachexia Induced by Renal Carcinoma Cells 一种反映肾癌细胞诱导的恶性恶病质临床进展的新小鼠模型

JCSM rapid communications

Pub Date : 2025-12-11 DOI: 10.1002/rco2.70018

Miaki Uzu, Anzu Aoyama, Takumi Kobayashi, Mayuka Morita, Rumi Murayama, Kenji Hashimoto, Hiroyuki Nakamura

<div> <section> <h3> Background</h3> <p>Cancer cachexia is a multifactorial metabolic syndrome characterized by anorexia and the progressive loss of skeletal muscle and adipose tissue, severely impairing quality of life, shortening survival and reducing treatment efficacy in cancer patients. The development of effective therapies has been hampered by the lack of preclinical models that faithfully replicate the clinical features and underlying mechanisms of cachexia. This study aimed to establish a novel murine model of cancer cachexia using subcutaneous implantation of renal carcinoma (RenCa) cells that align with clinical diagnostic criteria.</p> </section> <section> <h3> Methods</h3> <p>On Day 0, 8-week-old male BALB/c mice were anaesthetised and subcutaneously injected with murine RenCa cells or vehicle (control). A subset of mice was subjected to pair-feeding with RenCa-bearing mice, while another subset underwent subdiaphragmatic vagotomy (SDV) 2 weeks before cell implantation. Plasma levels of acyl-ghrelin and insulin-like growth factor-1 (IGF-1) were measured by ELISA. The gastrocnemius muscle was analysed for gene and protein expression related to atrophy and energy metabolism using quantitative RT-PCR and Western blotting, respectively, and for metabolic alterations using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS).</p> </section> <section> <h3> Results</h3> <p>Mice bearing RenCa tumours exhibited progressive cachexia. By Day 30, compared to controls, RenCa-bearing mice had significantly reduced tumour-free body weight (20.3 vs. 26.1 g), daily food intake (1.8 vs. 3.0 g/day), gastrocnemius muscle mass (112.1 vs. 140.7 mg) and epididymal fat mass (18.6 vs. 307.3 mg; all <i>p</i> < 0.01). Grip strength normalized to body mass remained unchanged even on Day 30. The pair-feeding experiment revealed that anorexia largely contributed to the onset of cachexic-like symptoms. SDV further exacerbated gastrocnemius atrophy (<i>p</i> < 0.05), implicating vagal signalling in the pathogenesis of cachexia, other than anorexia. Muscle expression of <i>Trim63</i> and <i>Fbxo32</i> peaked on Day 20, showing 5.5- and 4.4-fold increases compared with controls, respectively. The expression of <i>Ctsl</i> and <i>4ebp1</i> increased on Day 7 and remained elevated until Day 20. Metabolomic analyses revealed impaired glutathione and Akt-mediated glucose metabolism. Plasma acyl-ghrelin levels were elevated in RenCa-bearing mice (38.5–49.1 pg/mL) compared to controls (33.3–37.9 pg/mL) from Day 14 to Day 30, while IGF-1 levels were significantly reduced on Day 14 (94.6 vs. 220.2 ng/mL; <i>p</i> < 0.05).</p> </section

癌症恶病质是一种多因素代谢综合征，以厌食和骨骼肌和脂肪组织的进行性损失为特征，严重影响癌症患者的生活质量，缩短生存期，降低治疗效果。由于缺乏临床前模型来忠实地复制恶病质的临床特征和潜在机制，有效治疗方法的发展受到阻碍。本研究旨在建立符合临床诊断标准的肾癌（RenCa）细胞皮下植入的新型小鼠癌症恶病质模型。方法在第0天麻醉8周龄雄性BALB/c小鼠，皮下注射小鼠RenCa细胞或对照。一组小鼠与含renca小鼠配对喂养，另一组小鼠在细胞植入前2周进行膈下迷走神经切开术（SDV）。ELISA法检测血浆中酰基生长素和胰岛素样生长因子-1 （IGF-1）水平。使用定量RT-PCR和Western blotting分别分析腓肠肌萎缩和能量代谢相关的基因和蛋白质表达，并使用毛细管电泳飞行时间质谱（CE-TOF-MS）分析代谢变化。结果RenCa肿瘤小鼠表现出进行性恶病质。到第30天，与对照组相比，renca小鼠的无瘤体重（20.3比26.1 g）、每日食物摄入量（1.8比3.0 g/d）、腓肠肌质量（112.1比140.7 mg）和附睾脂肪质量（18.6比307.3 mg，均p <； 0.01）显著减少。握力与体重的比值即使在第30天也保持不变。配对喂养实验显示，厌食症在很大程度上导致了恶病质样症状的出现。SDV进一步加重了肠肌萎缩（p < 0.05），暗示迷走神经信号在恶病质的发病机制中，而不是厌食症。Trim63和Fbxo32的肌肉表达在第20天达到峰值，分别比对照组增加5.5倍和4.4倍。Ctsl和4ebp1的表达在第7天升高，并持续升高至第20天。代谢组学分析显示谷胱甘肽和akt介导的葡萄糖代谢受损。与对照组（33.3-37.9 pg/mL）相比，renca小鼠血浆中酰胃饥饿素水平在第14天至第30天升高（38.5-49.1 pg/mL），而IGF-1水平在第14天显著降低（94.6 vs. 220.2 ng/mL; p < 0.05）。我们建立了renca诱导的癌症恶病质小鼠模型，该模型概括了关键的临床特征，包括进行性厌食症、体重减轻、肌肉萎缩和ghrelin-IGF-1信号改变，为机制研究和治疗开发提供了有价值的工具。

{"title":"A Novel Mouse Model Recapitulating the Clinical Progression of Cancer Cachexia Induced by Renal Carcinoma Cells","authors":"Miaki Uzu, Anzu Aoyama, Takumi Kobayashi, Mayuka Morita, Rumi Murayama, Kenji Hashimoto, Hiroyuki Nakamura","doi":"10.1002/rco2.70018","DOIUrl":"https://doi.org/10.1002/rco2.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia is a multifactorial metabolic syndrome characterized by anorexia and the progressive loss of skeletal muscle and adipose tissue, severely impairing quality of life, shortening survival and reducing treatment efficacy in cancer patients. The development of effective therapies has been hampered by the lack of preclinical models that faithfully replicate the clinical features and underlying mechanisms of cachexia. This study aimed to establish a novel murine model of cancer cachexia using subcutaneous implantation of renal carcinoma (RenCa) cells that align with clinical diagnostic criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>On Day 0, 8-week-old male BALB/c mice were anaesthetised and subcutaneously injected with murine RenCa cells or vehicle (control). A subset of mice was subjected to pair-feeding with RenCa-bearing mice, while another subset underwent subdiaphragmatic vagotomy (SDV) 2 weeks before cell implantation. Plasma levels of acyl-ghrelin and insulin-like growth factor-1 (IGF-1) were measured by ELISA. The gastrocnemius muscle was analysed for gene and protein expression related to atrophy and energy metabolism using quantitative RT-PCR and Western blotting, respectively, and for metabolic alterations using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mice bearing RenCa tumours exhibited progressive cachexia. By Day 30, compared to controls, RenCa-bearing mice had significantly reduced tumour-free body weight (20.3 vs. 26.1 g), daily food intake (1.8 vs. 3.0 g/day), gastrocnemius muscle mass (112.1 vs. 140.7 mg) and epididymal fat mass (18.6 vs. 307.3 mg; all <i>p</i> < 0.01). Grip strength normalized to body mass remained unchanged even on Day 30. The pair-feeding experiment revealed that anorexia largely contributed to the onset of cachexic-like symptoms. SDV further exacerbated gastrocnemius atrophy (<i>p</i> < 0.05), implicating vagal signalling in the pathogenesis of cachexia, other than anorexia. Muscle expression of <i>Trim63</i> and <i>Fbxo32</i> peaked on Day 20, showing 5.5- and 4.4-fold increases compared with controls, respectively. The expression of <i>Ctsl</i> and <i>4ebp1</i> increased on Day 7 and remained elevated until Day 20. Metabolomic analyses revealed impaired glutathione and Akt-mediated glucose metabolism. Plasma acyl-ghrelin levels were elevated in RenCa-bearing mice (38.5–49.1 pg/mL) compared to controls (33.3–37.9 pg/mL) from Day 14 to Day 30, while IGF-1 levels were significantly reduced on Day 14 (94.6 vs. 220.2 ng/mL; <i>p</i> < 0.05).</p>\u0000 </section","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739836","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

Prehabilitation Meets Cancer Cachexia: Current Challenges and Opportunities 预防与癌症恶病质：当前的挑战与机遇

JCSM rapid communications

Pub Date : 2025-12-04 DOI: 10.1002/rco2.70019

Nicolò Pecorelli, Fabio Penna

<p>In the current issue of <i>JCSM Communications</i>, a systematic review and meta-analysis [<span>1</span>] investigated the impact of resistance exercise training (RET) in prehabilitation protocols implemented in the management of colorectal cancer (CRC) patients. The findings suggest that, despite the limited sample size, heterogeneity and risk of bias, exercise improves physical function, supporting the inclusion of RET for prehabilitation in CRC patients scheduled for surgery.</p><p>This work highlights the importance of supportive oncology interventions in the management of cancer patients throughout the whole cancer continuum. The final aim is to be able to significantly impact on patients' quality of life and survival, beyond the outcome of medical and/or surgical cancer treatment.</p><p>According to a recent scoping review [<span>2</span>], prehabilitation is defined as a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition and psychological strategies that aim to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes (e.g., shorter hospital stay, reduced complications) and facilitate recovery. It is remarkable that most of such objectives are shared with anti-cancer cachexia interventions, primarily aiming to counteract body and lean mass wasting and to improve muscle strength, with a potential impact on prehabilitation targets, including postoperative morbidity and recovery.</p><p>Prehabilitation programmes can be very heterogeneous [<span>3</span>] in terms of setting (e.g., home and hospital-based), duration (e.g., 3–4 weeks, months) and components. Most of the interventions typically include (1) a personalized exercise programme combining endurance and resistance training and (2) a nutritional intervention with a balanced macronutrient diet and protein oral nutritional supplements. Both components aim to improve cardiorespiratory fitness, body composition and nutritional status to better tolerate the stress response and disability resulting from surgery and/or other cancer-related treatments.</p><p>It is thus evident that prehabilitation and cachexia research share the focus on sarcopenia, malnutrition, functional capacity and quality of life. Such common interests open an opportunity for merging knowledge and resources, with the potential to cross-fertilize the respective research fields, eventually providing an acceleration in discoveries and new therapy optimization. As an example, with muscle wasting/sarcopenia well characterized during cancer cachexia and current clinical trials ongoing to prevent it, the same drugs may be tested for preventing sarcopenia during cancer patient prehabilitation. Along the same lines, drugs that improve the nutritional status in cachectic individuals, such as ghrelin analogues or GDF-15 blockers, may be efficiently adopted during prehabilitation interventions

在最新一期的《JCSM通讯》上，一项系统综述和荟萃分析[1]调查了阻力运动训练（RET）对结直肠癌（CRC）患者康复治疗方案的影响。研究结果表明，尽管样本量有限，存在异质性和偏倚风险，但运动可以改善身体功能，支持将RET纳入计划手术的CRC患者的康复治疗。这项工作强调了支持性肿瘤干预在整个癌症连续体中对癌症患者管理的重要性。最终目标是能够显著影响患者的生活质量和生存，超越医疗和/或手术癌症治疗的结果。根据最近的一项范围综述bbb，预康复被定义为从诊断到手术的一个过程，包括一项或多项术前干预，包括运动、营养和心理策略，旨在增强功能能力和生理储备，使患者能够承受手术压力，改善术后结果（如缩短住院时间，减少并发症）并促进康复。值得注意的是，这些目标大多与抗癌恶病质干预措施相同，主要旨在抵消身体和瘦质量的消耗，并提高肌肉力量，对康复目标有潜在影响，包括术后发病率和恢复。在环境（例如，家庭和医院）、持续时间（例如，3 - 4周或几个月）和组成部分方面，康复方案可能非常不同。大多数干预措施通常包括：(1)结合耐力和阻力训练的个性化运动计划；(2)营养干预，包括均衡的宏量营养素饮食和蛋白质口服营养补充剂。这两种成分旨在改善心肺功能、身体成分和营养状况，以更好地耐受手术和/或其他癌症相关治疗引起的应激反应和残疾。由此可见，康复和恶病质研究都关注于肌肉减少症、营养不良、功能能力和生活质量。这种共同的兴趣为合并知识和资源提供了机会，具有相互促进各自研究领域的潜力，最终加速发现和新疗法的优化。例如，在癌症恶病质期间，肌肉萎缩/肌肉减少症已经得到了很好的表征，目前正在进行预防这种疾病的临床试验，同样的药物也可以用于预防癌症患者康复期间的肌肉减少症。同样，改善病毒质个体营养状况的药物，如胃促生长素类似物或GDF-15阻滞剂，可以在康复前干预中有效采用，以最大限度地提高术前患者准备的效果。这种早期干预可以预防或至少减少晚期恶病质的发生，从而全面改善患者的健康状况。这些要点表明，我们面临着一个机会，可以采取共同的、可能更有效的行动，但这种行动并非没有挑战。下面是一个不详尽的列表，讨论如何克服当前的限制。首先，干预的持续时间和时机很重要。目前的预康复包括一个由临床医生、营养学家、物理治疗师和心理学家组成的多专家团队，他们会在有限的时间内跟踪患者。同样，恶病质管理需要多学科的方法，目前只建议积极减肥期，而不考虑长期变化。相反，癌症患者经历了一个漫长的过程，从诊断到治疗，再到可能持续数年的生存期。对患者进行如此长时间的随访需要对患者管理方案进行深入修订，至少在新建立的优化指南可用之前，可能需要分配相关的预算。第二个关键层面是获得这种医疗服务的资格。是否只有接受治疗的患者才有资格获得个性化的支持治疗？是所有患者都接受治疗，还是只接受一个选定的亚组？如果是这样，应该如何识别这些患者？我们认为，使用经过验证的筛查工具对功能、营养和精神状态进行系统和定期的多维度患者评估应该成为强制性的。在这方面，在定期随访期间进行深入评估，包括身体成分分析和表现测试，将使我们能够确定需要并可能从多模式干预中受益的患者。这些评估可以指导治疗的个性化，并在整个癌症连续体中为大多数人提供益处。虽然支持手术康复及其个别组成部分的证据正在积累，但需要更多的数据来确定哪些患者群体可以从这些干预措施中获益更多。最后，人们越来越意识到康复的重要性和恶病质对患者轨迹的影响，这为以患者为中心或患者报告的结果（PROs）的潜在应用开辟了领域。在内科和外科肿瘤学实践中，关于康复或抗恶病质干预的益处的证据仍然需要一个坚实的基础，其中可能包括PROs。建议的结果应关注与健康相关的生活质量（包括日常生活活动）、抗癌治疗的相对剂量强度、药物毒性等。总体而言，在癌症预防和恶病质专家之间共享诊断和治疗工具将允许对整个癌症患者的轨迹产生影响，超越有限的术后结果或活跃的恶病质阶段。Nicolò Pecorelli：写作-原稿（相等），写作-评审和编辑（相等）。Fabio Penna：监督（领导），写作-原稿（领导）。作者没有得到这项工作的特别资助。作者声明无利益冲突。

{"title":"Prehabilitation Meets Cancer Cachexia: Current Challenges and Opportunities","authors":"Nicolò Pecorelli, Fabio Penna","doi":"10.1002/rco2.70019","DOIUrl":"https://doi.org/10.1002/rco2.70019","url":null,"abstract":"<p>In the current issue of <i>JCSM Communications</i>, a systematic review and meta-analysis [<span>1</span>] investigated the impact of resistance exercise training (RET) in prehabilitation protocols implemented in the management of colorectal cancer (CRC) patients. The findings suggest that, despite the limited sample size, heterogeneity and risk of bias, exercise improves physical function, supporting the inclusion of RET for prehabilitation in CRC patients scheduled for surgery.</p><p>This work highlights the importance of supportive oncology interventions in the management of cancer patients throughout the whole cancer continuum. The final aim is to be able to significantly impact on patients' quality of life and survival, beyond the outcome of medical and/or surgical cancer treatment.</p><p>According to a recent scoping review [<span>2</span>], prehabilitation is defined as a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition and psychological strategies that aim to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes (e.g., shorter hospital stay, reduced complications) and facilitate recovery. It is remarkable that most of such objectives are shared with anti-cancer cachexia interventions, primarily aiming to counteract body and lean mass wasting and to improve muscle strength, with a potential impact on prehabilitation targets, including postoperative morbidity and recovery.</p><p>Prehabilitation programmes can be very heterogeneous [<span>3</span>] in terms of setting (e.g., home and hospital-based), duration (e.g., 3–4 weeks, months) and components. Most of the interventions typically include (1) a personalized exercise programme combining endurance and resistance training and (2) a nutritional intervention with a balanced macronutrient diet and protein oral nutritional supplements. Both components aim to improve cardiorespiratory fitness, body composition and nutritional status to better tolerate the stress response and disability resulting from surgery and/or other cancer-related treatments.</p><p>It is thus evident that prehabilitation and cachexia research share the focus on sarcopenia, malnutrition, functional capacity and quality of life. Such common interests open an opportunity for merging knowledge and resources, with the potential to cross-fertilize the respective research fields, eventually providing an acceleration in discoveries and new therapy optimization. As an example, with muscle wasting/sarcopenia well characterized during cancer cachexia and current clinical trials ongoing to prevent it, the same drugs may be tested for preventing sarcopenia during cancer patient prehabilitation. Along the same lines, drugs that improve the nutritional status in cachectic individuals, such as ghrelin analogues or GDF-15 blockers, may be efficiently adopted during prehabilitation interventions ","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695057","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

Oral Treatment of Water-Soluble Rutin Protects Against Cast Immobilisation–Induced Cognitive Impairment 口服水溶性芦丁对石膏固定所致认知障碍的保护作用

JCSM rapid communications

Pub Date : 2025-11-27 DOI: 10.1002/rco2.70016

Chihiro Tohda, Mizuho Kaneda, Tsukasa Nagase, Kaori Nomoto

<div> <section> <h3> Background</h3> <p>Muscle atrophy is critical to cognitive decline, as evidenced in previous studies which showed that disuse-induced skeletal muscle atrophy in the hind limbs accelerated early cognitive decline in young Alzheimer's model 5XFAD mice and nontransgenic young mice. As physical activity is challenging for individuals with muscle loss due to aging or immobilisation, effective medications are needed to prevent cast immobilisation–induced cognitive decline. Rutin, a candidate medication for preventing muscle loss and cognitive decline, has numerous biological effects but is limited by its low bioavailability owing to water insolubility. EubioQuercetin (ws Rutin), a highly absorbable Rutin formula, offers over 2000-fold improved solubility. This study investigated whether oral water-soluble Rutin (ws Rutin) treatment prevents cast immobilisation–induced memory dysfunction in young mice and explored its underlying mechanism.</p> </section> <section> <h3> Methods</h3> <p>Healthy young male ddY mice (10 weeks old) were used. Tissue distribution of Rutin was determined using LC-MS/MS at 0.5, 3, 6 and 16 h after oral administration of ws Rutin or conventional Rutin. Muscle atrophy was induced via bilateral hindlimb immobilisation by placing them in casts for 17 days. Cognitive function was evaluated using an object recognition test. RNA-seq was used to comprehensively analyse mRNA expression in the hippocampus and triceps surae. Expression levels of candidate molecules, affected by immobilisation and ws Rutin treatment, were confirmed using immunohistochemistry and Western blotting. Cultured hippocampal neurons and myocytes were treated with ws Rutin or Rutin, and parameters such as Klotho expression, axon/dendrite length, neuron numbers, ATP6 expression and myotube length were quantified by immunocytochemistry.</p> </section> <section> <h3> Results</h3> <p>ws Rutin prevented cast immobilisation–induced memory deficits in young mice (<i>n</i> = 9; training vs. test, <i>p</i> = 0.0167) and increased Klotho in mRNA and protein levels in the brain. By orally administering Rutin, Rutin rapidly reached the blood, brain and skeletal muscles. Direct treatment of cultured hippocampal neurons with ws Rutin or conventional Rutin increased Klotho expression (<i>p</i> < 0.0001), axon length (<i>p</i> < 0.0001), dendrite number (<i>p</i> < 0.001) and neuron number (<i>p</i> < 0.0001). Recombinant Klotho treatment also increased hippocampal neuron numbers (<i>p</i> < 0.0001). In skeletal muscles, ws Rutin treatment enhanced mitochondrial protein MTCO1 expression in vivo (<i>n</i> = 5 mice, <i>p</i> = 0.0224). In myocytes,

肌肉萎缩是认知能力下降的关键，先前的研究表明，废用性诱导的后肢骨骼肌萎缩加速了年轻阿尔茨海默病模型5XFAD小鼠和非转基因年轻小鼠的早期认知能力下降。由于身体活动对因衰老或固定而导致肌肉损失的个体具有挑战性，因此需要有效的药物来预防固定引起的认知能力下降。芦丁是预防肌肉损失和认知能力下降的候选药物，具有许多生物效应，但由于不溶于水，其生物利用度低，因此受到限制。EubioQuercetin （ws Rutin）是一种高度可吸收的芦丁配方，提供超过2000倍的溶解度。本研究探讨了口服水溶性芦丁（ws Rutin）是否能预防幼年小鼠固定不动诱导的记忆功能障碍，并探讨其潜在机制。方法选用10周龄健康雄性小鼠。采用LC-MS/MS法分别在给药后0.5、3、6、16 h测定芦丁的组织分布。用石膏固定双侧后肢17天诱导肌肉萎缩。使用物体识别测试评估认知功能。采用RNA-seq综合分析海马和三头肌mRNA的表达。候选分子的表达水平受固定和芦丁处理的影响，使用免疫组织化学和Western blotting证实。分别用ws芦丁或芦丁处理培养的海马神经元和肌细胞，采用免疫细胞化学定量测定Klotho表达、轴突/树突长度、神经元数量、ATP6表达和肌管长度等参数。结果芦丁可预防幼年小鼠固定固定诱导的记忆缺陷（n = 9；训练与测试，p = 0.0167），并增加脑内Klotho mRNA和蛋白水平。通过口服芦丁，芦丁迅速到达血液、大脑和骨骼肌。用ws芦丁或常规芦丁直接处理培养的海马神经元，可增加Klotho表达（p < 0.0001）、轴突长度（p < 0.0001）、树突数量（p < 0.001）和神经元数量（p < 0.0001）。重组Klotho处理也增加了海马神经元数量（p < 0.0001）。在骨骼肌中，芦丁处理提高了线粒体蛋白MTCO1在体内的表达（n = 5只小鼠，p = 0.0224）。在肌细胞中，芦丁直接处理可增强Klotho表达（p < 0.05）和肌管形成（p < 0.05）。结论芦丁对固定固定所致的记忆衰退具有保护作用，并可诱导脑内Klotho表达，从而增强神经功能，延缓衰老，延长寿命。芦丁在解决老龄化人口的虚弱方面显示出了很大的潜力。

{"title":"Oral Treatment of Water-Soluble Rutin Protects Against Cast Immobilisation–Induced Cognitive Impairment","authors":"Chihiro Tohda, Mizuho Kaneda, Tsukasa Nagase, Kaori Nomoto","doi":"10.1002/rco2.70016","DOIUrl":"https://doi.org/10.1002/rco2.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Muscle atrophy is critical to cognitive decline, as evidenced in previous studies which showed that disuse-induced skeletal muscle atrophy in the hind limbs accelerated early cognitive decline in young Alzheimer's model 5XFAD mice and nontransgenic young mice. As physical activity is challenging for individuals with muscle loss due to aging or immobilisation, effective medications are needed to prevent cast immobilisation–induced cognitive decline. Rutin, a candidate medication for preventing muscle loss and cognitive decline, has numerous biological effects but is limited by its low bioavailability owing to water insolubility. EubioQuercetin (ws Rutin), a highly absorbable Rutin formula, offers over 2000-fold improved solubility. This study investigated whether oral water-soluble Rutin (ws Rutin) treatment prevents cast immobilisation–induced memory dysfunction in young mice and explored its underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Healthy young male ddY mice (10 weeks old) were used. Tissue distribution of Rutin was determined using LC-MS/MS at 0.5, 3, 6 and 16 h after oral administration of ws Rutin or conventional Rutin. Muscle atrophy was induced via bilateral hindlimb immobilisation by placing them in casts for 17 days. Cognitive function was evaluated using an object recognition test. RNA-seq was used to comprehensively analyse mRNA expression in the hippocampus and triceps surae. Expression levels of candidate molecules, affected by immobilisation and ws Rutin treatment, were confirmed using immunohistochemistry and Western blotting. Cultured hippocampal neurons and myocytes were treated with ws Rutin or Rutin, and parameters such as Klotho expression, axon/dendrite length, neuron numbers, ATP6 expression and myotube length were quantified by immunocytochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ws Rutin prevented cast immobilisation–induced memory deficits in young mice (<i>n</i> = 9; training vs. test, <i>p</i> = 0.0167) and increased Klotho in mRNA and protein levels in the brain. By orally administering Rutin, Rutin rapidly reached the blood, brain and skeletal muscles. Direct treatment of cultured hippocampal neurons with ws Rutin or conventional Rutin increased Klotho expression (<i>p</i> < 0.0001), axon length (<i>p</i> < 0.0001), dendrite number (<i>p</i> < 0.001) and neuron number (<i>p</i> < 0.0001). Recombinant Klotho treatment also increased hippocampal neuron numbers (<i>p</i> < 0.0001). In skeletal muscles, ws Rutin treatment enhanced mitochondrial protein MTCO1 expression in vivo (<i>n</i> = 5 mice, <i>p</i> = 0.0224). In myocytes, ","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618944","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

Automated Segmentation of Forearm Muscles: Clinical Associations With Hand Function, Muscle Volume and Intramuscular Fat 前臂肌肉的自动分割：与手功能、肌肉体积和肌内脂肪的临床关系

JCSM rapid communications

Pub Date : 2025-10-19 DOI: 10.1002/rco2.70015

Joel Fundaun, Valeria Oliva, Sandrine Bédard, Evert Onno Wesselink, Benjamin P. Lynn, Anoosha Pai S., Dario Pfyffer, Merve Kaptan, Nazrawit Berhe, John Ratliff, Serena S. Hu, Zachary A. Smith, Trevor J. Hastie, Sean Mackey, Marnee J. McKay, James M. Elliott, Scott L. Delp, Akshay S. Chaudhari, Christine S. W. Law, Andrew C. Smith, Kenneth A. Weber II

Background

Hand function is critical for daily activities and declines early in many diseases, conditions or disorders affecting the musculoskeletal and neurologic systems. Muscle health markers derived from clinically available magnetic resonance imaging (MRI) scans are strongly associated with functional capacity, may enhance clinical assessment and inform management options. However, traditional muscle MRI assessments require time-intensive manual segmentations. Here, we aim to develop and test a computer-vision model for automated forearm muscle segmentation and investigate associations between MRI-derived muscle markers and age, sex, BMI, functional grip strength and dexterity measures.

Methods

We recruited 42 healthy, right-handed adults (54.8% female, median age 37.3 years, median BMI: 23.0). Grip strength and dexterity were measured using the NIH Toolbox motor battery. Dixon fat-water MRI of the right forearm was acquired at 3.0 T, and forearm flexor and extensor muscle compartments were manually segmented for model training. A 2D U-Net convolutional neural network model was trained and tested for segmentation of the forearm flexors and extensors for the assessment of muscle volume and intramuscular fat. Testing accuracy and reliability were assessed using Sørensen–Dice indices, intraclass correlation coefficients (ICCs) and Bland–Altman analyses. Associations between the MRI-derived muscle markers, demographic factors, muscle metrics and hand function were evaluated using partial correlations and regression models.

Results

The segmentation model showed high test accuracy, achieving mean Sørensen–Dice indices of 0.89 (flexors) and 0.85 (extensors) and ICCs of 0.75–0.99 for muscle volume and intramuscular fat. Muscle volume was positively correlated with BMI (p < 0.001) but not age (p > 0.249). Males had larger muscle volumes than females (p < 0.001), with no sex differences in intramuscular fat (p > 0.141), and no association between intramuscular fat and grip strength or dexterity (p > 0.350). We observed strong positive correlations between grip strength and both flexor (p = 0.004) and extensor (p = 0.001) muscle volumes, while dexterity showed no significant associations.

Conclusions

Our findings highlight the accuracy and reliability of automated forearm muscle segmentation using computer vision. BMI emerged as a key determinant of m

手功能对日常活动至关重要，在影响肌肉骨骼和神经系统的许多疾病、病症或障碍中，手功能会早期下降。从临床可用的磁共振成像（MRI）扫描中获得的肌肉健康标志物与功能能力密切相关，可以增强临床评估并为管理选择提供信息。然而，传统的肌肉MRI评估需要耗费大量时间的人工分割。在这里，我们的目标是开发和测试用于自动前臂肌肉分割的计算机视觉模型，并研究mri衍生的肌肉标记物与年龄、性别、BMI、功能性握力和灵活性测量之间的关联。方法我们招募了42名健康的右撇子成年人（女性54.8%，中位年龄37.3岁，中位BMI: 23.0）。握力和灵巧度测量使用NIH工具箱电机电池。3.0 T时获得右前臂Dixon脂水MRI，手动分割前臂屈、伸肌隔室进行模型训练。我们训练并测试了2D U-Net卷积神经网络模型，用于分割前臂屈肌和伸肌，以评估肌肉体积和肌内脂肪。采用Sørensen-Dice指数、类内相关系数（ICCs）和Bland-Altman分析评估检测的准确性和可靠性。使用偏相关和回归模型评估mri衍生的肌肉标记物、人口统计学因素、肌肉指标和手功能之间的关联。结果该分割模型具有较高的测试精度，平均Sørensen-Dice指数（屈肌）为0.89，平均Sørensen-Dice指数（伸肌）为0.85，肌肉体积和肌内脂肪的ICCs为0.75 ~ 0.99。肌肉体积与BMI呈正相关（p < 0.001），而与年龄无关（p > 0.249）。男性的肌肉体积比女性大（p > 0.001），肌内脂肪没有性别差异（p > 0.141），肌内脂肪与握力或灵活性之间没有关联（p > 0.350）。我们观察到握力与屈肌（p = 0.004）和伸肌（p = 0.001）肌肉体积呈正相关，而灵巧度无显著相关性。结论本研究结果强调了计算机视觉自动前臂肌肉分割的准确性和可靠性。体重指数是肌肉体积的关键决定因素，与年龄无关。肌肉体积和握力之间的强烈关联证明了这些指标的临床相关性，提示在手部功能受损疾病的治疗计划中的潜在应用。基于性别的肌肉量差异强调了量身定制评估的重要性。计算机视觉模型与Dixon脂肪-水MRI相结合，可以有效、准确地评估前臂肌肉健康状况。未来的研究应该在临床人群中探索这些指标及其在追踪功能结果方面的效用。

{"title":"Automated Segmentation of Forearm Muscles: Clinical Associations With Hand Function, Muscle Volume and Intramuscular Fat","authors":"Joel Fundaun, Valeria Oliva, Sandrine Bédard, Evert Onno Wesselink, Benjamin P. Lynn, Anoosha Pai S., Dario Pfyffer, Merve Kaptan, Nazrawit Berhe, John Ratliff, Serena S. Hu, Zachary A. Smith, Trevor J. Hastie, Sean Mackey, Marnee J. McKay, James M. Elliott, Scott L. Delp, Akshay S. Chaudhari, Christine S. W. Law, Andrew C. Smith, Kenneth A. Weber II","doi":"10.1002/rco2.70015","DOIUrl":"https://doi.org/10.1002/rco2.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hand function is critical for daily activities and declines early in many diseases, conditions or disorders affecting the musculoskeletal and neurologic systems. Muscle health markers derived from clinically available magnetic resonance imaging (MRI) scans are strongly associated with functional capacity, may enhance clinical assessment and inform management options. However, traditional muscle MRI assessments require time-intensive manual segmentations. Here, we aim to develop and test a computer-vision model for automated forearm muscle segmentation and investigate associations between MRI-derived muscle markers and age, sex, BMI, functional grip strength and dexterity measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 42 healthy, right-handed adults (54.8% female, median age 37.3 years, median BMI: 23.0). Grip strength and dexterity were measured using the NIH Toolbox motor battery. Dixon fat-water MRI of the right forearm was acquired at 3.0 T, and forearm flexor and extensor muscle compartments were manually segmented for model training. A 2D U-Net convolutional neural network model was trained and tested for segmentation of the forearm flexors and extensors for the assessment of muscle volume and intramuscular fat. Testing accuracy and reliability were assessed using Sørensen–Dice indices, intraclass correlation coefficients (ICCs) and Bland–Altman analyses. Associations between the MRI-derived muscle markers, demographic factors, muscle metrics and hand function were evaluated using partial correlations and regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The segmentation model showed high test accuracy, achieving mean Sørensen–Dice indices of 0.89 (flexors) and 0.85 (extensors) and ICCs of 0.75–0.99 for muscle volume and intramuscular fat. Muscle volume was positively correlated with BMI (<i>p</i> < 0.001) but not age (<i>p</i> > 0.249). Males had larger muscle volumes than females (<i>p</i> < 0.001), with no sex differences in intramuscular fat (<i>p</i> > 0.141), and no association between intramuscular fat and grip strength or dexterity (<i>p</i> > 0.350). We observed strong positive correlations between grip strength and both flexor (<i>p</i> = 0.004) and extensor (<i>p</i> = 0.001) muscle volumes, while dexterity showed no significant associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlight the accuracy and reliability of automated forearm muscle segmentation using computer vision. BMI emerged as a key determinant of m","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317774","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

1
2
3
4
5
6
7
...
10

下一页尾页