Intervertebral disc degeneration (IVDD) is a major cause of low back pain and disability. Excessive reactive oxygen species (ROS) disrupt disc homeostasis. Bushen Huoxue (BSHX) decoction, a traditional Chinese medicine, shows clinical efficacy in IVDD, but its antioxidant mechanisms are not well understood. Public IVDD transcriptomic datasets were analyzed to identify ROS-related gene signatures, followed by immune infiltration assessment. LC-MS/MS was used to characterize the chemical profile of BSHX decoction. Network pharmacology, machine learning, and bioinformatics analyses were integrated to identify potential compound-target interactions. Molecular docking and molecular dynamics simulations were applied to validate binding stability between active components and key targets. Six ROS-related hub genes (NCF1C, SLC11A1, MPO, GSTA4, SLC7A11, AKR1C3) were identified, with immune profiling revealing increased neutrophils, NK cells, and pro-inflammatory macrophages in IVDD. LC-MS/MS identified 77 active compounds in BSHX decoction, including flavonoids and phenolic acids. Network analysis and docking suggested strong interactions with oxidative stress targets, notably MPO. Molecular dynamics simulations confirmed the stability of key compound-target complexes. BSHX decoction shows promise as a multitarget antioxidant therapy for IVDD, offering mechanistic insight into its traditional efficacy. These findings support its further development and experimental validation.
随着我国进入老龄化社会,骨伤科疾病发病率在逐年上升,已成为重大公共卫生问题[1].中医骨伤科作为中医药学的重要组成部分,在防病治病过程中具有独特优势,但同时也面临着知识传承、诊疗标准化与现代化水平有待提升等现实挑战[2].近年来,以ChatGPT为代表的大语言模型(large language models,LLMs)问世,展现出强大的自然语言理解与生成能力,正在深刻改变知识的组织、传播与应用方式.在医学领域,LLMs已在辅助诊断、疾病管理、医学教育等方面展现出巨大潜力[3-4].如何充分利用LLMs技术,助力中医骨伤科数智化传承与发展,既是学科现代化的迫切需求,也是服务健康中国战略、推动中医药传承创新发展的重要命题.本文立足于中医骨伤科学行业现状与国家社会战略需求,系统梳理并讨论LLMs在中医骨伤科领域的应用与发展方向,以期为推动中医骨伤科数智化发展、构建骨健康防控体系提供理论参考与实践指导.
Background Axial neck pain is a common manifestation of cervical degenerative disc disease (CDD). Rotation-traction manipulation (RTM) is widely used in China, but its comparative effectiveness and safety versus cervical traction remain uncertain.Methods In this prospective multicenter randomized controlled trial, 154 adults with CDD-related axial neck pain were randomized 1:1 to receive RTM (7 sessions over 2 weeks) or cervical traction (daily for 2 weeks). Outcomes were assessed at baseline, during treatment, and at 1 and 3 months after treatment. The primary outcome was pain intensity measured by the visual analogue scale (VAS); secondary outcomes were neck tenderness score (NTS) and cervical range of motion (ROM). Intention-to-treat analyses with multiple imputation were performed.Results All 154 randomized participants were included in the analyses, and 151 completed follow-up. Both groups showed significant improvement over time in VAS and ROM (both P < 0.001). Confirmatory mixed-effects analyses did not demonstrate significant between-group differences in VAS or ROM after adjustment for multiple comparisons. Exploratory analyses suggested that RTM provided faster improvement during the treatment phase and a small cumulative advantage in pain reduction, whereas cumulative ROM improvement did not differ significantly between groups. RTM was also associated with a faster reduction in neck tenderness severity. Adverse events were mild and infrequent, and no treatment-related radiographic deterioration was observed.Conclusions Both RTM and cervical traction were associated with clinical improvement in patients with CDD-related axial neck pain. Confirmatory analyses did not demonstrate robust superiority of RTM for pain or cervical ROM, whereas exploratory analyses suggested faster early improvement and a small cumulative pain benefit with RTM. NTS findings should be interpreted cautiously because the tenderness score has not been formally validated. No serious adverse events were observed.Trial registration Chinese Clinical Trial Registry, ChiCTR2400082667. Registered retrospectively on 4 April 2024.
BACKGROUND:Bushen Huoxue (BSHX) decoction is effective against intervertebral disc degeneration (IVDD) and osteoarthritis, but its mechanism remains unclear. This study investigates its potential role in regulating efferocytosis in IVDD. METHODS:BSHX decoction, prepared from Eucommia ulmoides, Psoralea corylifolia, Achyranthes bidentata, Salvia miltiorrhiza, Clematis chinensis, and Chaenomeles speciosa, was extracted, concentrated, and analyzed by LC-MS/MS to identify active ingredients. Swiss TargetPrediction analysis predicted all targets. The PPI network was constructed using STRING 12.0 and CytoNCA in Cytoscape, followed by GO and KEGG enrichment analyses. Three publicly available datasets (GSE70362, GSE124272, GSE150408) were analyzed for differential gene expression in IVDD, with efferocytosis-related genes retrieved from GeneCards and KEGG, and candidate targets identified by intersecting PPI network core targets with efferocytosis-related differentially expressed genes (EFRDEGs). A network pharmacology model was then constructed, followed by molecular docking, molecular dynamics simulations, and pharmacokinetic properties. RESULTS:A total of 77 active ingredients and 298 targets were identified, with ELANE, MPO, and RXRA selected as candidate targets through bioinformatics analysis. GO and KEGG analyses highlighted their roles in immune regulation, inflammation, apoptosis, and tissue repair. Network analysis suggests that these compounds regulate multiple pathways, providing a mechanism for BSHX decoction to alleviate IVDD by modulating efferocytosis. Molecular docking showed strong binding affinity (binding energy < -8.0 kcal/mol) of tanshinone II A, pinoresinol diglucoside, and psoralidin with ELANE, MPO, and RXRA. Molecular dynamics simulation of the MPO-pinoresinol diglucoside complex confirmed its stability, and we revealed that pinoresinol diglucoside possesses favorable pharmacokinetic properties and safety characteristics. CONCLUSION:BSHX decoction may exert therapeutic effects on IVDD by targeting ELANE, MPO, and RXRA to regulate multiple pathways involved in efferocytosis. These findings offer valuable insights into the underlying mechanisms of BSHX decoction in the treatment of IVDD, providing a solid theoretical basis for the clinical application of traditional Chinese medicine.
RATIONALE:Jingtong Granules is a clinically approved seven-herb formula for CSR, a condition in which radicular pain is sustained partly by inflammatory and immune processes, yet the immune-cellular state of CSR and the immune-level mechanism of the formula remain poorly defined. METHODS:Using peripheral-blood transcriptomes from GSE223227 (7 controls, 9 CSR, and 30 degenerative cervical myelopathy), we profiled nine immune lineages by signature scoring, prioritized CSR-associated features with six machine-learning methods under permutation-based specificity testing, localized signature genes on the Human Protein Atlas sorted immune-cell reference, and linked the immune program to mass-spectrometry-confirmed constituents of Jingtong Granules by network pharmacology, molecular docking, molecular dynamics, and MM-GBSA. Two-level Mendelian randomization against cervical-specific FinnGen endpoints tested genetic causal directionality. RESULTS:CSR blood showed a bidirectional immune-rebalancing pattern: reduced NK-cell activity (p = 0.0164), increased M1-macrophage activity (p = 0.0311), and directionally higher neutrophil and lower CD8-cytotoxic scores. The neutrophil/myeloid effector program discriminated CSR from controls (AUROC 0.79), exceeding a size-matched random-panel null, whereas a generic NF-κB/TNF panel performed near chance; a composite rebalancing score reached a preliminary AUROC of 0.90 (95% CI 0.71-1.00). Network pharmacology nominated MPO as a formula-associated immune target, whereas patient-upregulated, neutrophil-localized ELANE and CTSG were prioritized as structurally tractable granule enzymes. The validated quality markers nodakenin and paeoniflorin docked favorably to ELANE and CTSG and remained in their catalytic pockets during molecular dynamics, with MM-GBSA binding free energies of -16.0 to -33.5 kcal/mol. Both markers also showed favorable drug-like physicochemical profiles. Mendelian randomization gave no support for an upstream genetic-causal role of the myeloid-skewed immune state in cervical disk disorders or radiculopathy. CONCLUSIONS:These exploratory, single-cohort findings characterize CSR peripheral blood as myeloid-skewed and cytotoxic-attenuated and nominate a traceable constituent-to-enzyme hypothesis in which mass-spectrometry-confirmed Jingtong Granules markers may engage patient-upregulated neutrophil granule enzymes, warranting replication and experimental validation.
OBJECTIVE:To preliminarily construct and validate a diagnostic model for Cervical Spine Instability (CSI) based on multimodal deep learning, and to develop an open-access, web-based prototype platform tailored for clinical scenarios. METHODS:Clinical data from 122 subjects were included, integrating three-position X-ray images and nine structured clinical variables. The model architecture featured an imaging branch built on ResNeXt50 and a clinical branch based on a Fully Connected Neural Network(FCNN), with cross-modal fusion performed at the feature level(ResNeXt50-FCNN). Modality ablation studies were conducted using two control groups:"Imaging-only"(ResNeXt50) and "Clinical-only"(FCNN). Evaluation metrics included Area Under the Receiver Operating Characteristic Curve(AUC), Average Precision(AP), Accuracy, Precision, Recall, F1-score, and Specificity. Grad-CAM was employed for attention visualization of the imaging branch, while SHAP(SHapley Additive exPlanations) was used to interpretglobal and individual feature contributions of the clinical branch. Finally, the optimal model was deployed via the Streamlit framework to create an interactive, clinically usable platform. RESULTS:The multimodal model achieved superior comprehensive performance on the validation set compared to the control groups, yielding an AUC of 0.964, AP of 0.973, Accuracy of 0.919, Precision of 0.875, F1-score of 0.933, and Specificity of 0.813. Ablation studies demonstrated that the fusion strategy significantly compensated for the insufficient sensitivity of the "Imaging-only" model and the low specificity of the "Clinical-only" model. Grad-CAM visualizations revealed that the model consistently focused on suspected abnormal structures across all three positions, effectively suppressing background interference. SHAP analysis identified age, limitation of flexion-extension, tenderness, gender, and headache as the primary contributing variables. The developed AI platform(https://cervical-instability-classifier.streamlit.app/) provides real-time outputs of diagnostic probabilities and visualizations of feature contributions. CONCLUSION:This study successfully constructed and preliminarily validated a CSI discrimination model based on multimodal deep learning, demonstrating promising diagnostic performance, interpretability, and potential for clinical application. However, given the limited sample size of this study, further external validation is required to confirm the model's generalizability and ultimate clinical utility.
The structural and functional integrity of the intervertebral disc (IVD) relies on nucleus pulposus cells (NPCs), whose senescence drives intervertebral disc degeneration (IVDD) through impaired self-repair and a senescence-associated secretory phenotype (SASP). SASP fuels macrophage recruitment and M1 polarization, establishing an inflammation-senescence vicious cycle. Although partial reprogramming with pluripotency-associated factors offers rejuvenation potential, clinical translation is impeded by genetic manipulation risks and protein stability challenges. Here, we developed OCNL@MVs, a biomimetic delivery system comprising carboxymethyl chitosan nanoparticles loaded with OSK reprogramming proteins, functionalized with an endosomolytic peptide and nuclear localization signal (NLS), and cloaked in M1 macrophage membranes. OCNL@MVs demonstrated dual functionality: 1) Membrane-derived receptors neutralized inflammatory cytokines and chemokines, reducing macrophage recruitment and M1 polarization; 2) The OSK@CMC-NLS core achieved lysosomal escape and nuclear delivery of OSK proteins, resulting in attenuation of senescence-associated phenotypes and improved proliferative capacity in senescent NPCs. In vivo, OCNL@MVs mitigated disc degeneration by disrupting the inflammatory niche and attenuating senescence-associated dysfunction. This membrane-coated nanoplatform provides a non-genetic protein-delivery strategy with a favorable preliminary biosafety profile, offering therapeutic potential for IVDD and aging-related disorders.
To characterize symptom domain-defined trajectories in mild-to-moderate degenerative cervical myelopathy (DCM) during scheduled non-operative follow-up, quantify transition probabilities and sojourn durations using a continuous-time multi-state Markov (MSM) model, and explore latent clinical heterogeneity through latent class analysis (LCA). This study is a secondary analysis of an existing multicenter randomized, double-blind trial dataset and does not evaluate comparative treatment effects. We conducted a secondary analysis of longitudinal data from a multicenter randomized, double-blind trial dataset (ChiCTR-INR-16009723) involving adults with mild-to-moderate DCM in the archived analytic dataset and complete Japanese Orthopaedic Association (JOA) domain data. The present analysis was restricted to the scheduled non-operative follow-up period and was designed to describe symptom-domain trajectories rather than treatment efficacy. Neurological status was classified into six mutually exclusive states based on JOA domains: asymptomatic; sensory-only impairment; isolated upper-extremity motor deficit; isolated lower-extremity motor deficit; combined upper- and lower-extremity motor deficits with normal bladder function; and sphincter involvement. Visits used in the present analysis took place at baseline; weeks 1, 2, 4, 6, and 8; and months 3 and 6. Transition intensities, 1-year transition probabilities, and mean sojourn lengths were estimated using a continuous-time MSM. Covariate effects (sex, age group, BMI category, prior conservative treatment, comorbidities) were modeled only for transitions meeting the prespecified ≥ 5-event threshold. LCA was performed using repeated state indicators across the scheduled visits to identify data-driven trajectory classes. This secondary analysis included only participants who remained on non-operative management throughout the analyzed follow-up period; patients who underwent surgery during treatment or follow-up were excluded at the data-screening stage. Ninety patients (mean age 58.6 years; 61.1% male) exhibited 71 observable state shifts, with the majority of assessments indicating stability. Sensory-predominant states exhibited considerable dynamism, characterized by frequent bidirectional transitions between asymptomatic and sensory-only states, with very brief mean sojourn durations (~ 0.25-0.31 years). Conversely, motor-dominant phenotypes exhibited enhanced short-term persistence; isolated lower-extremity motor deficits revealed the longest mean sojourn time (~ 2.76 years) and the highest one-year persistence (~ 71.9%). The advancement to more severe conditions over one year was infrequent (< 11%), but a significant proportion exhibited improvement from combined motor impairment to less severe stages. Covariate effects were largely unclear owing to limited occurrences; however, prior medication history and elevated BMI exhibited the most robust relationships with certain transitions. LCA supported a three-class solution (entropy ~ 0.99) including diverse longitudinal severity patterns, roughly differentiating between milder/fluctuating and more motor-dominant, more persistently severe trajectories. In non-operatively managed mild-to-moderate DCM, the clinical course during scheduled follow-up appeared non-linear and phenotype-dependent: sensory-only impairment tended to fluctuate with brief sojourn times, whereas motor deficits, especially lower-extremity motor deficits, were more persistent and showed limited spontaneous return to asymptomatic status. These exploratory MSM and LCA findings may help identify patients who warrant closer monitoring, but they should not be interpreted as establishing surgical timing thresholds or proving benefit from earlier intervention.
BackgroundLumbar disc herniation with radiculopathy (LDHR) is a leading cause of disability worldwide. For patients with moderate pain, Traditional Chinese Medicine approaches, including Yaobitong (YBT) capsules and lumbar oblique pull manipulation (LOPM), are widely used in clinical practice, often in combination. However, high-quality evidence supporting the superiority of this combination over monotherapy is lacking. This multicenter, randomized, three-arm, parallel-group controlled trial conducted at 13 tertiary hospitals in China aimed to evaluate the efficacy and safety of combining YBT with LOPM in LDHR patients with moderate pain.MethodsA total of 426 LDHR patients with moderate pain (Visual Analogue Scale [VAS] score ≥ 4 to < 7) were randomly assigned to receive either YBT alone (n = 146), LOPM alone (n = 137), or a combination of both (n = 143). The primary outcome was change in the Oswestry Disability Index (ODI) from baseline to week 2. Secondary outcomes included leg pain VAS scores, low back pain VAS scores, 12-Item Short Form Health Survey (SF-12), adverse events, and disc resorption rates. Outcome measurements were assessed at baseline, 3 days, 1 week, 2 weeks, 6 weeks, 14 weeks, and 26 weeks.ResultsAt 2 weeks, the mean reduction in ODI was −19.4 (95% CI, −21.4 to −17.5) in the YBT group, −19.4 (95% CI, −21.4 to −17.5) in the LOPM group, and −21.1 (95% CI, −23.0 to −19.1) in the combination group. The adjusted mean difference was 0.5 (95% CI, −2.3 to 4.9; p = 0.99) for YBT versus combination and 1.3 (95% CI, −2.1 to 5.1; p = 0.68) for LOPM versus combination. No statistically significant differences in ODI reduction were detected between groups at any follow-up time point (all p > 0.05). No statistically significant differences in any of the secondary outcomes were detected between groups at any follow-up time point (all p > 0.05). No apparent safety signal was observed in any of the three groups during the short 2-week intervention period.ConclusionThe combination therapy with YBT and LOPM was not superior to either monotherapy in improving functional disability, pain, or quality of life among LDHR patients with moderate pain.Clinical trial registrationhttps://www.chictr.org.cn, ChiCTR2200066051.
OBJECTIVE:To investigate the correlation between imaging characteristics of the lumbar bony structure (such as scoliosis, instability, ligament ossification, etc.) and lumbocrural pain as well as functional impairment in patients with lumbar disc herniation (LDH). METHODS:A national multi-center cross-sectional study was performed, enrolling 1 046 patients with lumbar disc herniation (LDH). Bony structural parameters were assessed using X-ray and computed tomography (CT), including scoliosis (Cobb angle >10°), lumbar curvature (normal/straightened/kyphotic), angular instability (intervertebral angular displacement≥11°), horizontal instability (intervertebral horizontal displacement ≥3.5 mm), ossification of the ligamentum flavum, intervertebral disc calcification, and ossification of the posterior longitudinal ligament. Clinical symptoms were evaluated using the visual analogue scale (VAS) for low back and leg pain, and functional status was assessed using the Oswestry disability index (ODI). RESULTS:Leg VAS was positively correlated with ossification of the ligamentum flavum (r=0.080, P=0.009) and ossification of the posterior longitudinal ligament (r=0.069, P=0.025), and negatively correlated with horizontal instability (r=-0.074, P=0.017). Back VAS was positively correlated with abnormal lumbar curvature (r=0.076, P=0.014), ossification of the ligamentum flavum (r=0.070, P=0.024), and disc herniation with ossification (r=0.104, P=0.001). ODI was positively correlated with leg VAS (r=0.540, P=0.001), back VAS (r=0.585, P<0.001), and lumbar scoliosis (r=0.090, P=0.004), and negatively correlated with angular instability (r=-0.110, P<0.001). CONCLUSION:In patients with LDH, bony structural abnormalities (especially ligament ossification and altered lumbar curvature) are partially correlated with low back and leg pain as well as functional impairment. However, pathological changes in bony structures are not the sole factor responsible for severe clinical symptoms. Clinical symptoms in LDH patients are modulated by multiple factors. Future prospective studies are warranted to verify causal relationships, and further exploration should be performed by integrating various imaging modalities and artificial intelligence techniques.
Closed modeling methods for lateral ankle sprain (ALAS) avoid surgical drawbacks but lack standardization due to reliance on the operator's subjective force, leading to variable outcomes. This study aimed to refine a closed ALAS rat model by quantifying manipulation parameters and establishing optimal ranges for different injury grades. Ninety rats were randomly assigned to groups receiving manual ankle inversion under different combinations of force (0-8 N or 8-16 N) and plantar flexion angle (100°-130° or 130°-160°), with control groups. A flexible thin-film pressure sensor and a goniometer were used to standardize the applied force and angle. Multimodal assessments were conducted, including ankle thickness and calcaneofibular ligament (CFL) length measurement, micro-CT, MRI, histopathology (HE and Masson's staining), pain threshold testing, and CatWalk gait analysis at multiple time points up to 28 days postmodeling. The severity of the injury was directly correlated with the applied force and angle. Group D (8-16 N, 130°-160°) exhibited the most severe damage, including avulsion fractures, significant CFL elongation and partial tearing, diffuse MRI signal alterations, and prolonged pain and gait instability (>28 days). Groups A and B (0-8 N, both angles) induced mild injuries (slight edema, minor fiber loosening) with rapid functional recovery by day 7. Group C (8-16 N, 100°-130°) resulted in moderate, partial-thickness ligament injuries with recovery by day 10. Behavioral and imaging findings consistently demonstrated a dose-dependent response to the modeling parameters. This study successfully established a modified and quantifiable closed ALAS rat model. The optimal parameters for a grade I ALAS model are 0-8 N of force with plantar flexion of 100°-130° or 130°-160°. For a grade II ALAS model, the parameters are 8-15 N of force with plantar flexion of 100°-130°. This standardized model enhances reproducibility and provides a reliable foundation for future research into ALAS mechanisms and therapies.
Study DesignScoping review.ObjectivesTo map longitudinal evidence on natural history, nonoperative management, progression definitions, clinical decision variables, and multimodal surveillance in mild to moderate degenerative cervical myelopathy (DCM), while distinguishing the treatment implications of mild and moderate disease.MethodsPubMed/MEDLINE, Embase, Web of Science Core Collection, Scopus, and the Cochrane Library were searched from inception to March 22, 2026. The review followed PRISMA-ScR. Eligible studies were adult longitudinal reports of mild or moderate DCM/cervical spondylotic myelopathy, extractable mild/moderate subgroups, or clinically relevant progression-surveillance evidence. Data were charted for design, population, management, follow-up, endpoints, progression definitions, examination findings, imaging variables, CT-relevant pathology, and alignment or motion factors.ResultsOf 6,193 records, 4,137 remained after deduplication and 766 underwent full-text consideration. Thirty-two reports underwent final eligibility assessment; 28 were retained, including 13 main analytic studies, 7 supplementary or conditional studies, and 8 adjunct multimodal narrative studies. Evidence was heterogeneous in severity thresholds, progression definitions, endpoints, and follow-up schedules. Nonoperative and natural-history cohorts showed that mild to moderate disease is not uniformly stable; some patients remained stable, whereas others deteriorated or crossed over to surgery. Objective function, quantitative MRI, electrophysiology, and selected structural measures may detect change more sensitively than symptom scales or conventional MRI alone.ConclusionsMild to moderate DCM represents a surveillance population, but mild and moderate disease should not be treated as having identical indications. Nonoperative cohorts help define progression and escalation risk, and multimodal follow-up appears more informative than single-scale monitoring.
Intervertebral disc degeneration (IDD) is characterized by the abnormal synthesis of extracellular matrix (ECM) proteins, increased inflammatory cytokines, and upregulated degradative enzymes. According to the Traditional Chinese Medicine (TCM) concept, the degenerative disease of the intervertebral disc falls under the heading of “stagnation syndrome.” Bu-Shen-Huo-Xue-Fang (BSHXF) is commonly applied to the treatment of IDD. In the present study, IDD models were established in rats, and degeneration, including morphological and histopathological alterations, the loss of collagen and proteoglycan, and increased MMP-13 and ADAMTS-5 were observed. BSHXF significantly ameliorated these degenerative alterations, decreased pro-inflammatory factors, and inhibited NF-κB signaling activation. Aucubin and Tanshinol were identified as the two main active ingredients of BSHXF. In IDD rats, Aucubin or Tanshinol treatment also remarkably relieved degenerative alterations. Moreover, Aucubin or Tanshinol treatment reduced IL-1β, TNF-α, P16, and P19 mRNA and protein expression, suppressed p65 phosphorylation, and decreased β-catenin protein contents within IDD samples. In conclusion, BSHXF, Aucubin, or Tanshinol improves IDD through affecting nucleus pulposus (NP) cell senescence and ECM metabolism; the Wnt/β-catenin and NF-κB signaling might contribute to the BSHXF, Aucubin, or Tanshinol process, ameliorating IDD.
Large Language Models (LLMs) show significant potential in healthcare, but their application in Traditional Chinese Medicine (TCM) lacks systematic evaluation. This study aims to comprehensively review LLMs tuning techniques, data construction strategies, evaluation methods, and application scenarios in TCM clinical practice. A scoping review following PRISMA-ScR guidelines was conducted. Researchers systematically searched seven databases for relevant studies published between database inception to May 2025. The analysis focused on identifying model characteristics, tuning techniques, data sources, evaluation methods, application domains and performance limitations to assess the current state and future directions of TCM-oriented LLMs. We included 27 studies (21 in English, 6 in Chinese). Application domains comprised TCM knowledge consultation (10 studies) and diagnostic assistance (13 studies), with 4 studies establishing TCM LLMs evaluation benchmarks. LoRA fine-tuning was most widely used (65.2
IntroductionLumbar range of motion is an important biomechanical parameter for understanding spinal function. However, the repeatability, measurement error, and between-method agreement of dynamic fluoroscopy and optical motion capture remain insufficiently characterized in controlled cadaveric spine testing.MethodsPlanar lumbar kinematics were measured using dynamic fluoroscopy within a dynamic X-ray system (DXRS) and optical motion capture with bone-fixed markers (OMCS) in six fresh-frozen ovine lumbar spine specimens, each comprising a continuous L1-L5 segment, during quasi-static flexion-extension and lateral bending. Three repeated trials were performed for each condition. Repeatability was assessed using the intraclass correlation coefficient (ICC(2,1)), the standard error of measurement (SEM), and the minimum detectable change at the 95% confidence level (MDC95). Between-method agreement was evaluated using a repeated-measures Bland-Altman approach with specimen-level clustering, exploratory proportional-bias assessment, and specimen-level bootstrap confidence intervals (CIs) (10,000 replicates) for the bias and limits of agreement (LoA).ResultsICC point estimates were generally high within each method across motion conditions and vertebral levels; however, given the modest specimen sample (n = 6), the corresponding 95% CIs were wide and these estimates are reported as preliminary, condition-specific values. OMCS showed numerically smaller SEM and MDC95 than DXRS in this dataset, but specimen-level bootstrap intervals indicated uncertainty around most between-method differences, so these descriptive differences should not be interpreted as evidence of general method superiority. Between-method analysis showed a small positive OMCS-minus-DXRS bias with condition-dependent LoA, and these agreement estimates should likewise be interpreted as preliminary and condition-specific.ConclusionIn this controlled ovine cadaveric model, both DXRS and bone-fixed OMCS provided repeatable measurements of projected planar lumbar motion. OMCS showed numerically smaller measurement-error indices in this dataset and under the present bone-fixed ex vivo ovine configuration; these descriptive, configuration-specific differences do not imply general method superiority, clinical equivalence, or interchangeability with routine human skin-marker motion capture. Cross-device comparisons should account for systematic bias, LoA, and uncertainty related to repeated-measures clustering. The reported error and agreement estimates may help inform method selection and interpretation of longitudinal change in preclinical spine biomechanics studies.
The cardiometabolic index (CMI) has been associated with multiple metabolic disorders; however, its relationship with osteoarthritis (OA) remains unclear. This study aimed to examine the association between CMI and OA. Utilizing data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES), this cross-sectional study included 2,331 participants after propensity score matching (PSM). Participants in the OA group were matched to those in the non-OA group at a 1:2 ratio, with age and sex used to estimate the propensity scores, resulting in 777 OA participants and 1,554 non-OA participants. Multivariable logistic regression, smoothed curve fitting, and subgroup analyses were used to assess the association between CMI and OA. Receiver operating characteristic (ROC) analyses were performed to compare the predictive performance of CMI, the atherogenic index of plasma (AIP), and the non-HDL-C/HDL-C ratio (NHHR). Following multivariable adjustment, the risk of developing OA increased with higher CMI levels (OR = 1.31, 95
Chronic mechanical compression in lumbar spinal stenosis (LSS) disrupts neuroimmune homeostasis and promotes the development of neuropathic pain. In this study, we identified that mechanical stress activates the mechanosensitive ion channel Piezo1, which plays a pivotal role in both the initiation and maintenance of LSS-associated neuropathic pain. Using a rat model of LSS, we performed behavioral assessments, histological examinations, and molecular analyses. The results revealed that Piezo1 expression was markedly upregulated in compressed spinal cord tissue, activating focal adhesion kinase (FAK) and the downstream RhoA/ROCK signaling cascade, thereby compromising the structural integrity of the blood–spinal cord barrier (BSCB). Moreover, Piezo1-mediated calcium influx triggered the CaMKII/NF-κB axis, inducing M1 macrophage polarization and elevating pro-inflammatory cytokine expression (e.g., TNF-α, IL-1β). These neuroinflammatory processes contributed to neuronal apoptosis and persistent mechanical allodynia. Pharmacological inhibition of Piezo1 with GsMTx4 effectively reversed these pathological changes and alleviated pain behaviors in LSS rats. Collectively, our findings establish Piezo1 as a critical mechanosensor linking chronic mechanical stress to neuroinflammation and pain sensitization. Targeting Piezo1 and its downstream signaling pathways may provide a promising therapeutic strategy for neuropathic pain associated with degenerative spinal disorders.
Background:Neck pain presents significant clinical heterogeneity, while current assessment methods lack systematic approaches for quantifying muscle function. This study established a multi-dimensional surface electromyography (sEMG) framework to quantify the predictive value of muscle function features for clinical outcomes and identify neuromuscular compensatory states. Methods:Eighty-nine participants were enrolled, including 69 chronic neck pain patients and 20 age-, sex-, and BMI-matched healthy volunteers. Surface EMG signals from six bilateral cervical muscles were recorded during functional postural control tasks in four directions. Following preprocessing and quality control, seven features spanning coordination (co-contraction index [CCI], deep-to-superficial ratio [DSR], asymmetry index [ASI]), control (sample entropy [SampEn], coefficient of variation trend [CoV_trend]), and fatigue (initial fatigue rate [IFR], median frequency slope [MDF_Slope]) dimensions were extracted. Six regression models (multiple linear regression, Ridge, Lasso, ElasticNet, Random Forest, and XGBoost) were compared using Repeated K-Fold cross-validation (5 folds × 10 repeats), with SHapley Additive exPlanations (SHAP) quantifying feature contributions. K-means clustering with multi-index validation identified distinct neuromuscular states. Results:Data quality reached 95.3% (263/276 segments). Six of seven EMG features significantly discriminated between healthy controls and patients (p < 0.05), with five showing large effect sizes (|d| > 0.8). Comparative model evaluation revealed XGBoost as the superior predictor for NDI scores (CV R 2 = 0.449 ± 0.182, MAE = 4.66 ± 0.74), outperforming all linear models by 13%-16%; a permutation test confirmed statistical significance (p = 0.001). SHAP analysis identified CCI (mean |SHAP|: 3.68), CoV_trend (1.74), and MDF_Slope (1.56) as primary NDI predictors. Four features exhibited significant severity gradients: CCI progressively increased from mild (0.57 ± 0.06) to severe groups (0.73 ± 0.10, p < 0.001); DSR was significantly higher in mild versus moderate patients (1.73 vs. 1.37, p = 0.033); CoV_trend decreased with severity (p = 0.013); MDF_Slope showed progressive changes (p < 0.001). Multi-index clustering validation (Silhouette, Calinski-Harabasz Index, Davies-Bouldin Index, Gap Statistic) supported K = 2 as the optimal cluster number. Two candidate neuromuscular states were identified: Asymmetric Compensation (63.8%, high ASI: 26.7%, preserved DSR: 1.744, low CCI: 0.635) and Global Stiffening (36.2%, high CCI: 0.771, low DSR: 1.077, steep MDF_Slope: -0.408), consistent with established models of pain-motor reorganization. Cluster membership was associated with disease severity (χ2 = 6.06, p = 0.048). EMG-NDI associations were independent of demographic confounders (partial correlations virtually identical to zero-order values after controlling for age, sex, and BMI; maximum change <0.1%). Conclusion:This interpretable multi-dimensional sEMG framework quantifies muscle function features' predictive value for functional disability. Severity-related neuromuscular changes may enable disease progression monitoring, while the identification of candidate compensatory states provides preliminary stratification criteria for personalized rehabilitation pending prospective validation.
Intervertebral disc degeneration is a major structural correlate of low back pain and is increasingly viewed as a disorder of mechanobiological dysregulation rather than simple mechanical overload. Over the past decade, disc cells have been shown to engage a diverse mechanosensory repertoire, including Piezo1, transient receptor potential channels, integrin–focal adhesion complexes, acid-sensing ion channels, primary cilia, and cytoskeletal–nuclear signaling axes. These upstream sensors converge on a more limited set of downstream hubs, most notably Yes-associated protein and transcriptional co-activator with PDZ-binding motif and mitogen-activated protein kinase/nuclear factor kappa B, which then shape cell-fate programs such as senescence, autophagy, pyroptosis, and ferroptosis. The extracellular matrix functions both as the substrate and as the output of mechanotransduction, creating a self-reinforcing loop in which degenerative matrix changes amplify pathological mechanosensing. Despite substantial molecular progress, mechanistic understanding remains concentrated in nucleus pulposus models, whereas matched cross-compartment analyses involving the annulus fibrosus, cartilage endplate, and vertebral interface remain limited. As a result, the relative importance of mechanosensors across compartments and loading contexts is still unresolved. Multiscale platforms, including finite element modeling, tunable hydrogels, organ culture, and quantitative magnetic resonance imaging, have strengthened causal interrogation, but translational progress remains largely preclinical. The clearest advance to date has come from biomaterial-based strategies, supported by early human feasibility data for injectable hydrogel implants. In this Review, we synthesize mechanotransduction in intervertebral disc degeneration, summarize the relative maturity of current mechanistic understanding across compartments and signaling branches, and discuss the importance of systematic cross-compartment comparison alongside single-sensor, single-compartment studies.
OBJECTIVE:To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS:A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS:All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION:Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.