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Bone mineral density (BMD) measured by DXA remains the clinical standard for diagnosing osteoporosis, but fails to capture the heterogeneity of skeletal fragility, particularly in patients with chronic diseases. We hereby describe the design of the EraSmus medIcal CeNTer skEletal fRagility (SINTER) Study, which integrates polygenic scores for BMD (PGSBMD) with a multidimensional phenotyping approach in diverse outpatient clinics, as a methodological framework for musculoskeletal research. The study aims at assessing the additional value of combining genetic information with comprehensive musculoskeletal phenotyping to better elucidate the mechanisms of skeletal fragility in chronic conditions. SINTER is an observational, cross-sectional Recall-by-Genotype (RbG) study drawn in two stages: (1) genotyping 5,650 patients from nine internal medicine clinics; (2) recalling 1,500 patients from the extremes of the PGSBMD distribution for multidimensional musculoskeletal phenotyping together with 400 patients with a rare condition (mastocytosis). Phenotyping includes imaging (DXA, EOSEdge, pQCT), macro- and tissue-level skeletal properties (ultrasound, reference point indentation), functional assessments (mechanography, handgrip), lifestyle and systemic exposures (diet, physical activity), and patient perceptions obtained via in-depth interview and questionnaires. The study design is unique in combining a RbG framework with multidimensional phenotyping in outpatient clinics, enabling systematic evaluation of genetic and disease-specific contributors to skeletal fragility. SINTER provides a methodological template for RbG designs with particular emphasis on musculoskeletal clinical research.

Skeletal muscle ischemia-reperfusion (I/R) injury is a clinically significant condition characterized by oxidative stress, inflammation, and histological damage. Emodin, a natural anthraquinone derivative, has been shown to exert antioxidative, anti-inflammatory, and antiapoptotic effects in various organ systems, however its efficacy in skeletal muscle I/R injury remains unclear. This study aimed to evaluate the potential protective role of emodin in a rat model of skeletal muscle I/R injury using biochemical and histopathological assessments. Twenty-four male Wistar rats were randomly assigned to four groups: Sham (S), Emodin (E) (20 mg/kg intraperitoneal), Ischemia-Reperfusion (IR), and IR with E treatment (IR+E). Skeletal muscle I/R was induced by infrarenal aortic clamping for 45 minutes, followed by 120 minutes of reperfusion. Muscle tissue was analyzed for malondialdehyde (MDA) and glutathione (GSH) levels, as well as catalase (CAT) and superoxide dismutase (SOD) activities. Histopathological evaluation included semiquantitative scoring of muscle fiber disorganization, neutrophil infiltration, interstitial edema, and hemorrhage. The IR group demonstrated significantly elevated MDA levels and decreased CAT activity compared with controls. E treatment markedly reduced MDA levels and partially restored CAT activity, while no significant changes were observed in SOD or GSH. Histopathological analysis showed severe disorganization, neutrophil infiltration, and edema in the IR group, which were notably attenuated by emodin, though not completely prevented. Emodin confers partial protection against skeletal muscle I/R injury, primarily by inhibiting lipid peroxidation and partially restoring CAT activity. This study provides the first in-vivo evidence of emodin's effects in skeletal muscle I/R, highlighting its potential as a tissue-specific antioxidant intervention and warranting further investigation of its mechanistic pathways.

Traumatic stress often leads to abnormalities in sex hormone levels, among which elevated estrogen levels are associated with improved patient prognosis. However, the mechanism by which estrogen affects the inflammatory response and repair process in acute skeletal myositis remains unclear. This study aimed to investigate the effects of estradiol (E2) signaling on the resolution of acute skeletal myositis and muscle fiber repair in mice induced by cardiotoxin (CTX). An acute skeletal myositis model was established in C57BL/6 mice. Endogenous E2 levels were reduced by ovariectomy (OVX) in female mice, and interventions were performed with β-Estradiol or the estrogen receptor β (ERβ)-specific antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP). Differentiated C2C12 myotubes were treated with interferon γ (IFN-γ) in combination with β-Estradiol or PHTPP. Serum E2 levels were measured by ELISA. Inflammatory cell infiltration in injured muscle was assessed by HE staining. Immunofluorescence staining was used to detect the expression levels of ERβ, embryonic myosin heavy chain (eMHC), CD45, myogenic determining factor (MyoD) and myogenin. Proportion of CD45+ inflammatory cells in injured muscle was detected by flow cytometry. Western blot was used to detect protein expression levels of mouse major histocompatibility complex class I molecules (MHC-I) H-2Kb, major histocompatibility complex class II molecules (MHC-II) H2-Eα, Toll-like receptor 3 (TLR3), and ERβ in differentiated myotubes. RT-qPCR was used to measure mRNA expression levels of ERα, ERβ, G protein-coupled receptor 30 (GPR30), interleukin-1β (IL-1β), IL-6, IL-10, and monocyte chemoattractant protein-1 (MCP-1) in injured muscle and differentiated myotubes. The results showed that, in acute skeletal myositis, injured muscle of female mice exhibited milder inflammation compared to male mice, and serum E2 levels were significantly higher in the female mice. Meanwhile, expression of ERβ was significantly up-regulated in injured muscle and inflammatory myotubes, whereas no significant changes were observed in ERα and GPR30. OVX decreased serum E2 level, exacerbated inflammation, and increased infiltration of CD45+ inflammatory cells in injured muscle, whereas these effects were reversed by β-Estradiol treatment. The effects of PHTPP were the same as those of OVX, except that it didn't affect serum E2 levels. In inflammatory myotubes, β-Estradiol up-regulated the protein expression level of ERβ, down-regulated the expression levels of immune molecules H-2Kb, H2-Eα, TLR3, and pro-inflammatory factors IL-1β, IL-6, MCP-1, up-regulated the expression of anti-inflammatory factor IL-10, and up-regulated the expression of MyoD and myogenin. The effects of PHTPP were opposite to those of β-Estradiol. The expression of eMHC in the injured muscle of OVX mice was down-regulated, while β-Estradiol restored its expression. These results suggest that in acute skeletal myositis, E2 inhibits the accumulation of inflammatory cells in the injured muscle by binding to ERβ in muscle fibers, regulates the intrinsic immune behavior of inflammatory myofibers, thereby promoting inflammation resolution and muscle fiber regeneration and repair, providing new insights for the clinical treatment of acute skeletal myositis.

MicroRNAs (miRNAs) are critical regulators of skeletal muscle development and adaptation, orchestrating the balance between proliferation, differentiation, and tissue repair. Here, we identify miR-339-5p as a previously unrecognized, conserved regulator of skeletal muscle remodeling. Transcriptomic analysis from human, mouse, and rat studies revealed that miR-339-5p is consistently upregulated in skeletal muscle under conditions of stress or injury and declines during myogenic differentiation in vitro. Gain-of-function experiments demonstrated that miR-339-5p overexpression impairs expression of genes associated with myogenic differentiation and promotes expression of proliferative markers in both primary human myotubes and mouse C2C12 cells. Transcriptomic profiling confirmed widespread repression of pathways involved in cytoskeletal organization, myofibrillar assembly, and mitochondrial function. In vivo, electroporation-mediated overexpression of miR-339-5p in mouse tibialis anterior altered regeneration-associated gene expression and increased the number of immature fibers, therefore modulating tissue remodeling during post-injury growth. Integrated analyses combining target prediction algorithms, differentiation-associated correlations, and overexpression datasets identified seven conserved high-confidence miR-339-5p targets, among which the autophagy-associated phosphatase MTMR3 emerged as the most consistently regulated candidate. Collectively, our data demonstrate that miR-339-5p functions as a conserved inhibitor of myogenic progression, linking injury-induced stress responses to delayed differentiation and altered muscle remodeling. These findings establish miR-339-5p as a potential therapeutic target in conditions characterized by impaired muscle regeneration or dysregulated tissue remodeling.

This study evaluated the immediate skeletal and dentoalveolar effects of Minimally Invasive Surgical and Miniscrew Assisted Rapid Palatal Expansion (MISMARPE), comparing outcomes using two different appliance designs: tooth-bone-borne (TBB) and bone-borne (BB) expanders. This retrospective comparative cohort study included 24 consecutively treated adult patients (mean age 35.9&#x2009;&#xb1;&#x2009;9.5&#x2009;years): 13 in the TBB group and 11 in the BB group. Cone-beam computed tomography scans were obtained pre-treatment (T0) and immediately after expansion (T1) to assess skeletal and dentoalveolar changes. Generalized Estimating Equations analysis, followed by Bonferroni correction for multiple comparisons, was used to compare measurements between groups over time. The MISMARPE technique produced significant increases in all linear measurements except posterior maxillary basal width in the TBB group (p&#x2009;=&#x2009;0.142). Both groups exhibited greater skeletal expansion in the anterior maxillary region, demonstrating a triangular expansion pattern in the axial view. The TBB group showed significantly greater increases in dental distances (6-6CR, p&#x2009;=&#x2009;0.002; 6-6RT, p&#x2009;=&#x2009;0.017) and posterior alveolar width (P-AM, p&#x2009;<&#x2009;0.001) compared to the BB group. No significant changes in molar inclination were observed in either group post-expansion. The MISMARPE technique is effective for adult maxillary expansion, producing a triangular palatal expansion pattern in the axial view with parallel suture opening at the anterior nasal spine level in the coronal view. The TBB expander demonstrated greater transverse dentoalveolar expansion and stability of miniscrews compared to BB design, while both anchorage systems achieved similar skeletal effects.

Musculoskeletal abnormalities are a frequent yet often underrecognized manifestation of systemic disease and may precede visceral involvement, clinical symptoms, or specific laboratory abnormalities. Recognizing characteristic musculoskeletal imaging patterns can provide an important diagnostic clue and prompt investigation of an underlying systemic condition. This review outlines key imaging findings of selected systemic disorders that commonly present with skeletal or soft-tissue involvement, grouped by etiology into metabolic and deposition, inflammatory, infectious, hematologic/histiocytic, and hereditary tumor syndromes. Emphasis is placed on imaging features that may suggest systemic disease, important differential diagnoses, and findings that should prompt further clinical and laboratory evaluation. By recognizing these musculoskeletal abnormalities as potential markers of systemic pathology, radiologists may contribute to earlier diagnosis, reduce diagnostic delay, and directly influence multidisciplinary management and treatment decisions.

This study aimed to investigate whether baseline skeletal muscle status and malnutrition in patients with locally advanced head and neck cancer (HNC) are associated with short-term treatment outcomes and acute radiation oral mucositis (OM). We retrospectively analyzed data from 68 patients with stage III-IV HNC treated at a single center with definitive radiotherapy (66-70 Gy) with or without chemotherapy (induction and/or concurrent) between July 2021 and July 2023. Malnutrition was diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria and Patient-Generated Subjective Global Assessment (PG-SGA). Short-term response was assessed at first post-treatment imaging after radiotherapy according to RECIST 1.1, and OM severity was graded using World Health Organization criteria. Univariate and multivariate logistic regression analyses evaluated the correlation between short-term response and grades III-IV OM. Of the 68 patients, 32.4% had a lower skeletal muscle index (SMI), 26.5% had lower hand grip strength (HGS), 20.6% (GLIM) and 58.8% (PG-SGA) had malnutrition. At the end of treatment, 64.7% of the patients achieved partial remission, and 35.3% achieved a stable condition. Low HGS was associated with low short-term efficacy (OR = 0.31, 95% CI = 0.10-0.95, p = 0.040); however, this difference did not reach statistical significance in the multivariate model. A total of 41.2% of patients had Grade III-IV OM; however, OM was not significantly associated with low SMI, HGS, or malnutrition. Baseline skeletal muscle status and malnutrition did not consistently predict short-term treatment outcomes or severe radiation-induced OM in patients with locally advanced HNC. However, these results suggest a potential relationship between low HGS and treatment response. Further research with larger sample sizes and longitudinal evaluations is needed to clarify muscle and nutritional status impact on multidimensional outcomes in this patient population.

Large population-based studies have demonstrated age- and sex-related differences in phase angle (PhA). However, multifrequency bioelectrical impedance analysis (BIA) systems remain highly device-specific due to proprietary algorithms and prediction equations. This limits comparability across platforms, making descriptive distributions from single-device cohorts essential for routine clinical interpretation. To describe sex- and age-specific distributions of PhA and skeletal muscle mass using a single multifrequency BIA platform in an outpatient cohort, and to explore relationships with other device-derived body composition estimates. A retrospective cross-sectional analysis was conducted on adults in an outpatient program using the SECA mBCA 514 platform. PhA and skeletal muscle mass data were available for 1849 and 1870 participants, respectively. Sex- and age-stratified percentiles were generated. Fat-to-muscle ratio (FMR) was calculated, and its associations with PhA and device-estimated visceral adiposity were evaluated using Spearman correlation. Men demonstrated higher PhA and skeletal muscle mass values than women; both measures declined across age strata in both sexes. Women exhibited higher FMR values. Higher FMR was moderately associated with lower PhA (rho&#xa0;=&#xa0;-0.467, p&#xa0;<&#xa0;0.001), while its association with device-estimated visceral adiposity was weak (rho&#xa0;=&#xa0;0.104, p&#xa0;<&#xa0;0.001). Since all measurements originated from the same platform, these associations are descriptive rather than mechanistic. Device-specific, stratified distributions derived from routine multifrequency BIA assessments assist the clinical contextual interpretation of outpatient body composition measurements. The observed relationships between FMR and PhA are hypothesis-generating and require further validation using independent gold-standard reference methods such as MRI, DXA, or CT.

Multi&#x2011;organ degenerative diseases are age-associated or chronic disorders marked by progressive tissue deterioration, impaired repair and functional decline, with representative conditions including sarcopenia, osteoporosis, osteoarthritis, neurodegenerative or ischemia&#x2011;associated neurological disorders, heart failure, chronic kidney disease and diabetes&#x2011;associated tissue dysfunction. Their frequent coexistence in aging populations limits the effectiveness of therapeutic strategies directed at a single organ or pathway. Extracellular vesicles (EVs) are lipid bilayer&#x2011;enclosed particles that shuttle proteins, lipids, metabolites and regulatory RNAs between cells and tissue. As a highly metabolic and secretory tissue, skeletal muscle releases skeletal muscle&#x2011;derived EVs (SkM&#x2011;EVs) that may carry muscle&#x2011;enriched microRNAs, together with other regulatory cargo molecules involved in local tissue remodeling and systemic signaling. SkM&#x2011;EVs have therefore been proposed as mediators of muscle&#x2011;centered cross&#x2011;organ communication and potential delivery vehicles for molecular intervention, although therapeutic evidence remains largely preclinical. The present review examines the biological functions of SkM&#x2011;EVs, their regulation by exercise, aging and metabolic stress and their potential involvement in multi&#x2011;organ degenerative diseases. The present study aimed to discuss engineering strategies for SkM&#x2011;EVs, including cargo loading, surface modification and targeted delivery, with particular attention to controversies, methodological limitations, quality control requirements and barriers to clinical translation.

Early post-mortem interval (PMI) estimation relies mainly on temperature-based nomograms together with rigor and livor mortis, all imprecise in the first hours after death - a limitation underscored by a recent independent validation of the compound method reporting an overall agreement of only&#x2009;~&#x2009;37%. Post-mortem supravital skeletal-muscle excitability, evoked electrically or mechanically, is a long-standing but fragmented adjunctive marker. This scoping review maps the available evidence and derives the methodological requirements of a future prospective study, addressing the question: what evidence exists on post-mortem supravital skeletal-muscle excitability, induced by electrical or mechanical stimulation, as an adjunctive tool for early PMI estimation? Following the JBI methodology and PRISMA-ScR reporting, a Population-Concept-Context framework defined eligibility. PubMed/MEDLINE, Scopus and Web of Science were searched without language or date limits, with citation searching of key authors. Records were charted along ten predefined dimensions and appraised with study-type-adapted instruments. Twenty-six included records - corresponding to approximately 21 independent contributions after collapsing companion papers and consecutive series that report overlapping datasets - were organised into five streams: objectified/subjective electrical excitability, mechanical idiomuscular reaction, the compound method, post-stimulation structural artifacts, and animal models. Electrical methods provided the most precise estimates (95% confidence limits&#x2009;~&#x2009;&#xb1;&#x2009;2.7-&#xb1;2.85 h up to ~&#x2009;13 h) but required invasive instrumentation; mechanical reaction testing was field-deployable but operator-dependent and strongly modulated by biological and environmental factors. Within the compound method, adding non-temperature criteria - including muscular excitability - narrowed the temperature-based interval in roughly two-thirds of scene cases. A recurrent probative caveat is that structural alterations classically regarded as vital can be reproduced post-mortem in the supravital phase. Controlled animal (rat) models complemented the human evidence, characterising the decay of the compound muscle action potential and indicating that its onset latency is comparatively independent of the cause of death. Supravital muscle excitability is a promising adjunctive marker to be standardised and prospectively validated within the compound method, not used as a stand-alone determinant of the time of death. The review specifies the resulting research agenda: a prospective, minimally invasive study in deaths with a certified time of death, with standardised stimulation, objectified outcomes, systematic recording of confounders and internal validation against a temperature-based reference model.

Cancer-associated skeletal muscle atrophy is a major manifestation of cachexia and is closely associated with inflammation, metabolic disturbance, and muscle structural deterioration. Aerobic exercise has been considered a promising non-pharmacological intervention, but its molecular mechanisms in tumor-associated muscle wasting remain incompletely understood. This study aimed to investigate transcriptomic changes associated with the effects of aerobic exercise on skeletal muscle wasting-related alterations in CT26 tumor-bearing mice and to identify candidate hub genes using weighted gene co-expression network analysis. Eight-week-old specific pathogen-free male BALB/c mice were randomly assigned to four groups: control, exercise, tumor-bearing, and tumor-bearing plus exercise. CT26 cells were subcutaneously inoculated to establish the tumor-bearing model. Mice in the exercise groups underwent treadmill-based aerobic training for 4 weeks. Gastrocnemius muscles were collected for hematoxylin-eosin staining and transcriptome sequencing. Differentially expressed genes were identified, followed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses. Weighted gene co-expression network analysis was further performed to identify phenotype-related modules and candidate hub genes. Tumor-bearing mice showed reduced gastrocnemius wet weight and histological abnormalities characterized by disorganized muscle fiber arrangement and structural damage. Compared with the tumor-bearing group, the tumor-bearing plus exercise group exhibited a significant increase in gastrocnemius wet weight alongside a qualitative trend toward histomorphological recovery. Transcriptomic analysis showed that tumor burden upregulated pathways related to inflammation and protein degradation, while downregulating pathways associated with energy metabolism and maintenance of muscle structure. Aerobic exercise was associated with partial reversal of these transcriptional trends. Enrichment analyses indicated that the differentially expressed genes were mainly involved in the PI3K-Akt, NF-kappa B, and IL-17 signaling pathways. Weighted gene co-expression network analysis identified an inflammation-related module closely associated with the tumor-bearing phenotype, in which S100a8 was recognized as a candidate hub gene. Aerobic exercise was associated with a significant improvement in gastrocnemius wet weight and a mitigating trend in histomorphological abnormalities in CT26 tumor-bearing mice, which may be associated with remodeling of inflammation- and metabolism-related transcriptional networks. S100a8 may represent a candidate hub gene associated with this process, although further functional validation is required.

A dual-pathway skeletal editing of isoquinolines was described. A common Tf2O-activated intermediate reacts with secondary amines and can be selectively directed under orthogonal conditions. Blue-light irradiation enables N-to-C transmutation to form naphthalenes, whereas microwave heating promotes cascade skeletal editing/annulation to yield benzo[f]quinazolines. Acetonitrile acts as a bifunctional C1 synthon, enabling stepwise N-to-C and C-to-C transformations, providing a rare route to benzo[f]quinazolines.

Skeletal muscle plasticity is shaped by mechanical loading, metabolic flux, and intercellular signaling. Beyond its canonical role as a tricarboxylic acid (TCA) cycle intermediate, succinate is increasingly viewed as a potential extracellular signaling metabolite that may link mitochondrial metabolism to tissue remodeling. However, whether succinate acts as a causal mediator rather than a correlate of metabolic stress remains incompletely defined. In this hypothesis-driven narrative review, we propose the Succinate Dual-Function Hub framework, in which succinate is considered a context-dependent metabolic signal whose effects may depend on kinetics, concentration, compartmentalization, receptor availability, transport capacity, and co-emergent exercise signals. Current evidence suggests that high-intensity contraction can induce transient succinate accumulation and release, which may contribute to mitochondrial remodeling, vascular or niche-related signaling, immune regulation, and satellite cell responses through SUCNR1-dependent and SUCNR1-independent mechanisms. In contrast, sustained succinate elevation associated with mitochondrial dysfunction or metabolic disease has been linked to inflammatory, epigenetic, and oxidative stress-related programs. This adaptive-maladaptive distinction should be viewed as a testable organizing model rather than an established causal rule. We discuss key evidence gaps and the preliminary translational potential of the succinate-SUCNR1 axis as a candidate biomarker or research target for myopathic conditions.

Taurine is a semi-essential amino acid with diverse cytoprotective effects and is associated with anti-aging. This study explores the role and molecular mechanism of taurine in muscle aging. Senescence-accelerated mouse prone 8 (SAMP8) and its resistant (senescence-accelerated mouse resistant 1, SAMR1) mice were given 1% taurine water from 5 to 10 months of age, while control mice were given distilled water (DW). At 10 months of age, a rotarod test was performed to assess muscle endurance. SAMP8 mice had a shorter running time on the rotarod test than SAMR1 mice. Taurine significantly extended running time compared with that of DW-drinking group in SAMP8 mice, a similar trend was observed in SAMR1 mice. The gastrocnemius muscle was used for the RNA-sequencing analysis. Among differentially expressed genes between taurine and DW, Tbx5 and Alb showed some significant differences between the treatment by RT-qPCR. Myoblast C2C12 cells underwent cellular senescence induction with D-galactose (D-gal), which was detected by SA-&#x3b2;-gal staining. Taurine reduced SA-&#x3b2;-gal-positive area induced by D-gal, suggesting its protective effect against cellular senescence. Myotube induction was inhibited by D-gal treatment and restored by taurine, as detected by immunocytochemistry of myosin heavy chain (MHC) and Western blot of myogenin. D-gal-induced decrease trend in protein level of TBX5 was significantly increased in C2C12 myotubes treated with taurine. Taurine may have a protective effect on muscle senescence and myotube regeneration.

Communications between organs contribute to propel physiological functions, as well as pathological processes. Growing evidence indicates that bone is continuously regulated by multiple layers of endocrine, immune, metabolic, and neural networks. The common bone diseases, including osteoporosis, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, are reported with tight associations to other nonbone organs. These organ-bone axes emphasize the interorgan communications that maintain the bone homeostasis and maintain individual health. In this review, we systematically summarize recent advances in the organ-bone communications, highlighting mechanistic innovations, such as the gut-bone-immune axis, neuro-immune-bone integration, hypothalamic-pituitary-adrenal axis, adipo-neuro-bone axis, and their connections with bone pathophysiology. Furthermore, we highlight circulating biomarkers and imaging advances reflecting organ-bone crosstalk. Finally, we discuss the clinical relevance, current research gaps, and unsolved questions of organ-bone communications in the diagnostic stratification, treatment selection, and multidisciplinary management of bone diseases.

To systematically review and exploratorily analyze the effects of blood flow restriction combined with neuromuscular electrical stimulation (BFR-NMES) compared with neuromuscular electrical stimulation (NMES) alone on skeletal muscle strength and morphological adaptations in healthy adults. This systematic review was conducted in accordance with the PRISMA guidelines and registered in PROSPERO (CRD420251141357). Relevant studies published up to September 2025 were retrieved from PubMed, Web of Science, and Embase. Randomized and non-randomized controlled studies comparing BFR-NMES with NMES alone were included. Primary outcomes included muscle strength (isometric and isokinetic strength) and muscle morphology outcomes (muscle thickness, cross-sectional area, muscle mass, and thigh circumference). Risk of bias was assessed using the ROB 2.0 tool, methodological quality was evaluated using the modified Jadad scale, and evidence quality was assessed using the GRADE approach. Due to substantial clinical and methodological heterogeneity among studies, the present study primarily adopted a qualitative synthesis combined with exploratory quantitative visualization analyses. Seven studies involving 124 healthy adults were included. Qualitative findings demonstrated that acute BFR-NMES interventions consistently induced greater immediate strength loss and neuromuscular fatigue, while simultaneously producing more pronounced acute muscle swelling and fluid shift responses. In contrast, long-term BFR-NMES interventions demonstrated more favorable trends in both muscle strength and muscle morphological adaptations compared with NMES alone. Exploratory forest plots further showed that acute studies generally favored NMES alone, whereas long-term studies consistently favored BFR-NMES. Collinearity analysis revealed substantial confounding between intervention duration and pressure prescription strategy: all long-term studies employed fixed-pressure protocols, whereas all acute studies adopted individualized arterial occlusion pressure (%AOP)-based strategies. No statistically significant differences were observed in the overall pooled analyses for muscle strength or rectus femoris thickness; however, substantial heterogeneity was present across studies. GRADE assessment indicated that the quality of evidence for most outcomes ranged from low to very low. Current evidence suggests that BFR-NMES may provide superior benefits over NMES alone in promoting acute muscle swelling and long-term muscle morphological adaptations, with potential advantages for long-term muscle strength development. However, the available evidence remains limited, and substantial confounding exists between intervention duration and pressure prescription strategies. Therefore, these findings should be interpreted cautiously. Future high-quality randomized controlled trials with larger sample sizes and independent manipulation of pressure strategies and intervention duration are warranted to clarify the true effects and optimal prescription strategies of BFR-NMES. PROSPERO, identifier: CRD420251141357.