Thioredoxin-interacting protein (TXNIP) is a multifunctional regulatory protein of the α-arrestin family that acts as a redox sensor, an energy-responsive molecule, and a transcription-associated regulator. TXNIP has emerged as a key regulator of skeletal muscle homeostasis and has been implicated in the pathogenesis of multiple muscle disorders. Skeletal muscle is a principal site of systemic glucose disposal, accounting for more than 70% of insulin-stimulated glucose uptake in the human body. TXNIP has been implicated in sarcopenia, obesity-related insulin resistance, limb ischemia-induced muscle injury, disuse muscle atrophy, and hereditary muscular dystrophy through multiple mechanisms, including glutathione metabolic regulation, ferroptosis, NLRP3 inflammasome activation, impaired GLUT4 membrane translocation, and altered mitochondrial substrate oxidation. Recent advances in gene editing, single-cell sequencing, metabolomics, and human clinical research have enabled a more detailed characterization of TXNIP-related molecular mechanisms in skeletal muscle. This review provides a systematic synthesis of recent evidence on TXNIP in skeletal muscle, organized around seven themes: its molecular characteristics, expression and regulatory patterns in skeletal muscle, physiological functions, disease-specific pathogenic mechanisms, intervention-related regulatory networks, current limitations, and future perspectives. This review aims to provide a mechanistic rationale for targeting TXNIP as a potential strategy for the prevention and treatment of skeletal muscle-related diseases.

​Emerging clinical data from Chinese randomized controlled trials (RCTs) suggest Gua Sha (scraping therapy) may deliver adjunct antispastic benefits for spasticity after stroke (SAS) when combined with standard rehabilitation. This study aimed to synthesize clinical efficacy evidence and explore treatment parameters for this intervention. We searched eight electronic databases from database inception to January 1, 2026; two independent reviewers completed study screening, risk-of-bias assessment using Cochrane Risk of Bias 2.0 tool, and data extraction. Meta-analytic effect sizes were calculated using mean difference (MD), and the review protocol was preregistered on PROSPERO. Sixteen eligible RCTs enrolling 1227 stroke survivors were included, all conducted in China, which may limit the external transferability of our results. Pooled random-effects estimates indicated that add-on scraping therapy was associated with reduced Modified Ashworth Scale and Visual Analog Scale for Pain (VAS-P) scores, lower serum hs-CRP and Hcy, as well as improved motor function and activities of daily living. Grading of Recommendations Assessment (GRADE) rated the certainty of evidence for all outcomes as very low due to high heterogeneity, methodological limitations, suspected publication bias and limited cross-regional data. Exploratory subgroup analyses identified numerically larger spasticity relief in regimens with 5-day treatment intervals, 1.5-month treatment duration and intensive scraping stimulation. These cross-study comparisons generate preliminary hypotheses awaiting verification through dedicated head-to-head dosing trials. Proposed mechanistic pathways linking scraping therapy to symptom relief rely largely on preclinical evidence, including enhanced local microcirculation and modulation of inflammatory and neural signaling. Current evidence supports scraping therapy as an investigational adjunctive strategy for SAS. Given the low-certainty evidence base and lack of inclusion in international rehabilitation guidelines, this therapy should be evaluated only in clinical settings with certified practitioners and standardized adverse event monitoring. Further well-designed RCTs are required to clarify its long-term therapeutic benefits and complete safety profile.

Robot-assisted radical prostatectomy remains a favorable treatment option for locally advanced prostate cancer in patients with obstructive lower urinary tract symptoms. However, the steep Trendelenburg lithotomy position required for this procedure can result in serious complications, particularly in patients with obesity. Here, the case of a 66-year-old man with obesity (BMI, 35 kg/m2), insulin-dependent diabetes mellitus, and multiple comorbidities is reported, who underwent robot-assisted radical prostatectomy (console time, approximately 4 h) for clinically staged cT3a cN1 prostate cancer. Immediately after surgery, the patient developed severe gluteal pain, sensorimotor deficits, and massive rhabdomyolysis, resulting in anuric acute kidney injury and respiratory insufficiency. The clinical course was further complicated by heparin-induced thrombocytopenia type II and a grade IV gluteal pressure ulcer. A 22-day intensive care stay was required, including continuous hemodiafiltration and transfusion of 12 units of erythrocytes. With multidisciplinary management, renal function partially recovered, and the patient was discharged with minimal residual neuropathic deficits. This case highlights the importance of comprehensive preoperative risk assessment and provides clinically relevant insights into the recognition and multidisciplinary management of severe complications associated with prolonged positioning during robot-assisted radical prostatectomy.

Long-term glucocorticoid therapy is standard of care for individuals with Duchenne muscular dystrophy (DMD) but often results in impaired growth and delayed or incomplete puberty, impacting their physical and psychosocial health. Although DMD endocrine care has evolved, leading to inclusion in the 2018 Care Considerations, these issues remain prevalent and concerning, and gaps in care persist. The Growth and Puberty Working Group of the OPTIMIZE DMD Consortium, an international multidisciplinary group including endocrinology and neuromuscular specialists with DMD expertise, conducted a literature review and surveyed clinicians to inform updated clinical guidance on growth and puberty. This report is based on evidence where available, plus expert consensus, and thereby provides revised guidance on the investigation and management of growth and pubertal delay, as well as hypogonadism beyond the pubertal years, among individuals with DMD. It also addresses new topics subsequent to the 2018 Care Considerations, including: 1) the dissociative glucocorticoid vamorolone and its impact on growth, and 2) gonadal function in older adolescents and young adults. With the current lack of long-term data on growth and puberty outcomes, prevailing themes underscore the importance of person- and family-centered care with informed shared decision-making aligned with individualized goals plus interdisciplinary team communication. This report also highlights specific areas in these domains in need of research. Through ongoing collaborations within the OPTIMIZE DMD Consortium, growth and puberty care continues to evolve and will inform and advance research to improve the health and quality of life of individuals with DMD.

How perennial, postmitotic multinucleated tissues, such as skeletal myofibers, maintain their identity and transcriptional adaptation to homeostatic perturbations through adult life is an outstanding question. To address this issue, we investigated the consequences of loss of 3D-genome architecture in skeletal muscles by generating myofiber-specific Ctcf- deficient ( Ctcf mKO ) mice. Ctcf mKO mice did not exhibit muscular phenotype at birth but spontaneously developed a severe myopathy. Integrated analysis of snRNAseq, ATACseq and promoter-capture Hi-C revealed both common and fiber-type specific patterns of dysregulated gene expression associated with alterations in chromatin accessibility and promoter-based interactions in Ctcf-deficient myonuclei at distinct stages of myopathy development. Decreased chromatin accessibility at promoters and changes in their connectivity with distal elements were observed across all myonuclei as a direct consequence of Ctcf deficiency at early stages and associated with downregulation of genes implicated in myofiber contraction and anabolism, metabolism, adhesion and neuromuscular transmission. Conversely, at later stages, upregulation of genes leading to persistent activation of ER stress/UPR and catabolism resulted from global reconfiguration of chromatin structure and connectivity, partly as indirect consequence of Ctcf deficiency. Notably, type-IIB myonuclei exhibited specific alterations in gene expression that culminated in loss of fiber-type identity and ectopic expression of inflammatory genes. These results reveal a requirement of Ctcf for maintenance of fiber-type identity and transcriptional adaptation in vivo , through multilayered control of 3D genome integrity. They also indicate an unprecedented association between Ctcf deficiency in myofibers and susceptibility to develop myopathies, whereby Ctcf dispensability for developmental myogenesis confers vulnerability to develop myopathic syndromes.

Inflammatory skeletal muscle atrophy is a growing clinical challenge, driven by chronic inflammatory conditions and life-threatening illnesses that cause progressive muscle loss. This condition leads to premature muscle fatigue and a decline in muscle function, highlighting the necessity for highly sensitive diagnostic methods to detect impairment prior to the occurrence of structural damage. Conventional diagnostic methods, including electromyography, serum biomarker assays, and medical imaging, often fail to detect early and subtle alterations in myotube electrophysiological responsiveness because of limited temporal accuracy and insufficient target specificity. Furthermore, these techniques are limited in resolving dynamic electrophysiological fluctuations as well as characterizing the coupling between electrical signaling and intracellular calcium dynamics. Herein, we have developed an integrated bimodal biosensing platform that combines microelectrode array (MEA)-based electrophysiological recording with high-resolution, fluorescence-based calcium imaging. This platform performs coordinated and real-time tracking of extracellular field potentials and intracellular calcium transients across networks of differentiated C2C12 myotubes. Using an in vitro model of LPS-induced inflammatory skeletal muscle atrophy, LPS exposure progressively disrupted spontaneous electrical firing, field potential amplitude, and intracellular calcium transients in a concentration- and time-dependent manner. Diclofenac, a clinically applied anti-inflammatory agent, effectively maintained both electrophysiological function and calcium homeostasis in myotubes under inflammatory stress. Therefore, our bimodal platform functions as a robust, real-time preclinical tool for the detection of incipient inflammatory myopathy. Its integrated capabilities enable the precise quantification of drug responses and the scalable screening of therapeutic candidates, thereby establishing a versatile, translationally-oriented platform for the investigation of skeletal muscle atrophy mechanisms and interventions.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by slowly progressive and heterogeneous muscle involvement; therefore, clinical measures show limited sensitivity to short-term change. Magnetic resonance imaging (MRI) provides useful biomarkers of muscle degeneration and disease activity. To investigate one-year longitudinal changes in lower leg muscles of patients with FSHD using qualitative (T1-weighted [T1w], STIR) and quantitative MRI (fat fraction [FF], water T2), and to assess their relationship with clinical function. Thirty-one patients with FSHD (21 men; age 44.2±17 years) and 30 matched controls underwent 3T MRI. Twenty-seven patients completed one-year follow-up. Semi-quantitative grading and quantitative measures were analyzed muscle-wise. Longitudinal changes and correlations with clinical scores were assessed. At baseline, T1w imaging showed marked inter- and intra-individual variability, with heterogeneous proximal-distal involvement in 22% of muscles and asymmetric involvement in 77% of patients. STIR hyperintensity was present in 25 patients. Over one-year, clinical decline was small (MRC: Δ=-0.26, p=0.018, SRM=-0.23; mobility: Δ=-0.41, p=0.031, SRM=-0.44). In contrast, quantitative MRI detected progression, with increases in FF (0.17±0.13 to 0.22±0.15, p<0.001, SRM=0.87), FF heterogeneity, and water T2 heterogeneity, while T1w scores and mean water T2 showed limited change. Progression was greatest in muscles with intermediate baseline FF (ΔFF/year: 0.049 vs 0.007, p<0.001). Baseline STIR and water T2 abnormalities predicted increases in FF but not T1w scores. FF correlated more strongly with clinical measures than T1w grading. Quantitative MRI is more sensitive than qualitative grading for detecting short-term disease progression in FSHD. Measures of heterogeneity and disease activity predict structural progression and represent promising biomarkers for clinical trials.