Spinal cord injury (SCI) is characterized by irreversible loss of motor and sensory function, imposing a substantial burden on patients and their families. Tetramethylpyrazine (TMP), a bioactive compound derived from traditional Chinese medicine, possesses a wide range of pharmacological activities and has demonstrated potential therapeutic effects in the treatment of SCI. Therefore, this article provides a comprehensive review of the mechanisms by which TMP promotes spinal cord repair. This review compiles a large body of in vitro, in vivo, and clinical studies, including a total of 86 publications documenting the effects of TMP on SCI. The results indicate that the mechanisms by which TMP exerts its effects in SCI treatment include promoting nerve regeneration, improving vascular dysfunction, exerting anti-inflammatory effects, inhibiting neuronal apoptosis, reducing oxidative stress, regulating iron metabolism, maintaining ion homeostasis, alleviating pyroptosis, and modulating autophagy. Through these mechanisms, TMP contributes to the restoration of spinal cord morphology, motor function, and electrophysiological parameters in experimental animal models. Clinical reports on the use of TMP injection for SCI are relatively limited, and its clinical efficacy requires further investigation. The combined application of nanotechnology or hydrogels provides an efficient targeted delivery and sustained-release system for TMP in the spinal cord, thereby significantly enhancing its bioavailability. Overall, TMP shows promising potential in SCI treatment and may serve as a valuable adjunctive therapeutic strategy.

Hypoxic-ischemic brain damage (HIBD) is a primary cause of neonatal neurological dysfunction, such as cerebral palsy, characterized by complex cascades of neuronal death. Despite the urgent need, effective therapeutic strategies are scarce, and the efficacy of standard interventions, such as therapeutic hypothermia, remains limited. Astragaloside IV (AS-IV), a promising neuroprotective agent, is hindered from wide clinical applications by poor permeability across the blood-brain barrier (BBB) and low bioavailability. To overcome this bottleneck, we developed a novel targeted delivery system based on neural stem cell-derived extracellular vesicle, designated AS-EV, which efficiently deliver AS-IV to the HIBD-affected brain region. AS-EV were successfully prepared via ultracentrifugation and sonication-loading, exhibiting typical exosomal characteristics, and favorable drug-loading efficiency. In vivo experiments confirmed that AS-EV effectively crossed the BBB to accumulate in the injured brain region with satisfying biocompatibility. Mechanistic investigation using primary cortical neurons revealed that the core therapeutic mechanism of AS-EV is mediated by mTOR activation, which consequently suppressed HIBD-induced neuronal apoptosis, an effect that was abrogated by mTOR inhibition. Furthermore, functional and histological assessments demonstrated that AS-EV intervention significantly promoted neurological function recovery, alleviated brain tissue pathology, protected white matter integrity, facilitated neural structural remodeling, and inhibited glial scar proliferation in neonatal HIBD rats. In conclusion, NSC-EV-mediated delivery of AS-IV exerts multifaceted neuroprotective and reparative effects by activating the mTOR pathway, offering a promising therapeutic strategy for HIBD.

Spinal cord injury (SCI) is a severe central nervous system disorder characterized by irreversible damage and lifelong disability, with few effective treatment options. Tetramethylpyrazine (TMP), a bioactive compound from Ligusticum wallichii, has shown promise in SCI therapy. However, its clinical use is limited by poor water solubility, a short half-life, and restricted blood-spinal cord barrier penetration. To address these challenges, a novel self-assembling hydrogel (GAT-H) was developed, utilizing the amphiphilic nature of glycyrrhizic acid (GA) to encapsulate TMP through non-covalent interactions. This environmentally friendly, crosslinker-free formulation produces a uniform, injectable hydrogel with a porous microstructure that matches the mechanical stiffness of spinal cord tissue. It exhibits shear-thinning and self-healing properties, enabling minimally invasive, in situ gelation at irregular lesion sites. Mechanistic studies showed that GAT-H ensures sustained TMP release, inhibiting neutrophil extracellular trap (NET) formation and subsequently blocking the NET-activated cGAS/STING pathway in microglia, which attenuates NLRP3 inflammasome-mediated pyroptosis. Functional assessments revealed significant motor recovery improvements, as indicated by gait analysis. These results position GAT-H as a promising therapeutic platform that combines GA-based self-assembly with TMP’s therapeutic efficacy, offering a preclinical basis for the use of natural product-based hydrogels in SCI treatment.

BackgroundThe systemic impact of dementia on musculoskeletal health remains poorly characterized. We investigated associations of algorithmically ascertained dementia status with bone fragility, functional trajectories, and low grip strength-defined probable sarcopenia, and explored candidate circulating proteomic indirect-effect signals for these associations.MethodsIn a prospective UK Biobank cohort of 151,751 participants (median follow-up 15.1 years), dementia status was defined from algorithmically derived diagnosis records spanning linked follow-up. Descriptive fixed group-status models evaluated associations with incident osteoporosis and fracture, longitudinal grip-strength and physical-activity trajectories, and baseline probable sarcopenia and probable osteosarcopenia proxy. A time-updated Cox analysis assigned person-time before and on the recorded diagnosis date to the reference state and person-time strictly after that date to the exposed state. In a proteomic subcohort (n = 16,652; Olink Explore 3,072), two-stage screening of 2,923 proteins identified candidate protein signals; these were then evaluated using exploratory, model-based indirect-effect analyses with bootstrap resampling.ResultsIn time-updated models, all-cause dementia after diagnosis was associated with osteoporosis (HR = 1.78, 95% CI 1.43–2.20) and fracture (HR = 3.68, 95% CI 2.34–5.77), with estimates strongest within 0–2 years after diagnosis and attenuated thereafter. For descriptive context, fixed group-status analyses of recorded dementia ascertainment status showed associations with osteoporosis (HR = 2.31, 95% CI 2.06–2.59) and fracture (HR = 3.13, 95% CI 2.27–4.31), accelerated grip decline (β = −0.317 kg/year, p = 1.3 × 10−5), and higher baseline odds of probable sarcopenia (OR = 1.41, 95% CI 1.23–1.61). Under the prespecified observed-sample criteria, EGFR (proportion mediated [PM] = 8.7%), EBI3/IL27 (PM = 5.9%), and CKB (PM = 3.8%) had modest indirect-effect estimates. Across the age-adjusted first-stage screen and the 500-resample full-pipeline bootstrap, EGFR and EBI3/IL27 were the most consistently supported signals; CKB showed lower joint selection stability and was classified as exploratory.ConclusionIn the UK Biobank, algorithmically ascertained dementia status was associated with bone fragility, functional trajectories, and baseline probable sarcopenia-related phenotypes. Time-updated analyses supported elevated postdiagnosis bone risks, with the strongest estimates near the time of diagnosis. EGFR and EBI3/IL27 were the most consistently supported candidate circulating indirect-effect signals for the recorded dementia status–probable sarcopenia association. CKB met the prespecified observed-sample criteria but showed lower selection stability and was retained as exploratory; individual proportions mediated were modest.

BackgroundCerebral palsy (CP) is a non-progressive brain injury primarily characterized by abnormal posture and movement disorders. Among them, spastic cerebral palsy (SCP) accounts for 70% of cases. Previous small sample hematological data analyses have revealed significant differences in inflammatory marker ratios between SCP patients and healthy controls. This study aims to expand the sample size and perform a multidimensional data analysis using routine hematological indicators to identify hematological features of spastic cerebral palsy, potentially providing new directions for the treatment of SCP.MethodsThis retrospective study included 305 children with spastic cerebral palsy and 149 healthy children, aged 3–12 years. Previous routine blood and biochemical test results were collected from the participants. Statistical analysis was performed on clinically common indicators and related composite indicators, and subgroup analyses were conducted based on age group (preschool vs. school-age).ResultsCompared to the healthy control group, SCP patients had significantly lower levels of NPAR, alkaline phosphatase (ALP), creatinine (Cr), SII, and MPV/PC (p < 0.05). AST/ALT, NLR, total protein, and SIRI levels were significantly higher in the SCP group (p < 0.05). Logistic regression analysis showed that ALP, Cr, SII, and MPV/PC were protective factors for SCP, while AST/ALT and NLR were risk factors for SCP. Combining these indicators for SCP diagnosis, the ROC curve analysis yielded an AUC of 0.781. Subgroup analysis showed that children aged 3–6 years with SCP had significantly lower Cr, AST/ALT, SII, MPV/PC, and NLR levels compared to children aged 7–12 years with SCP. Furthermore, creatinine, AST/ALT, SII, MPV/PC, and NLR levels were positively correlated with the age of SCP children.ConclusionThis study reveals a significant association between alkaline phosphatase, creatinine, AST/ALT, SII, MPV/PC, NLR in routine blood indicators and the risk of SCP, providing important reference for clinicians to monitor the health status of children with cerebral palsy, optimize treatment plans, and implement nutritional interventions.

Background:Cerebral palsy (CP) represents the most prevalent motor disability in childhood, with spastic cerebral palsy (SCP) constituting the predominant subtype. However, systematic characterization of differences in systemic inflammatory status and metabolic profiles between children with SCP and healthy peers remains limited. Here, we applied an interpretable machine-learning framework to evaluate and identify clinically informative inflammation- and metabolism-related biomarkers in children with SCP, thereby providing potential implications for disease monitoring and informing targeted intervention strategies. Methods:In this retrospective study, 330 children with spastic cerebral palsy (SCP) and 150 healthy controls were enrolled. Complete blood count and serum biochemical parameters were collected, from which 10 systemic immune-inflammation indices were derived. Feature preselection was performed using least absolute shrinkage and selection operator (LASSO) regression, followed by univariable and multivariable logistic regression to identify biomarkers independently associated with the outcome. Model interpretability was assessed using SHapley Additive exPlanations (SHAP), and feature importance was ranked according to SHAP values. Restricted cubic splines (RCS) were applied to evaluate potential nonlinear associations between key indicators and outcome risk, while receiver operating characteristic (ROC) curves were used to assess discriminative performance. Additionally, children with SCP were stratified into severe and mild subgroups according to the Gross Motor Function Classification System (GMFCS) levels, and inflammatory and biochemical differences across severity strata were analyzed. Data were split in a 7:3 ratio using outcome-stratified sampling, with the training set used for model development and the test set for independent performance validation. Results:Multivariable logistic regression identified 7 independently associated biomarkers: MPV, CHO, DBIL were protective factors, whereas PDW, BASO%, GLB, MCHC were risk factors. A nomogram constructed based on these biomarkers demonstrated favorable performance in discriminating SCP from controls; in the independent test set, the AUC was 0.972 (95% CI, 0.935-0.998). In the SCP subgroup analysis, 330 children were stratified by GMFCS into a severe group (n = 160, levels 4-5) and a mild group (n = 170, levels 1-3). Multivariable logistic regression indicated that ALT and WBC were positively associated with severe cerebral palsy, whereas ALP showed a weak negative association. The subgroup model yielded an AUC of 0.717 (95% CI, 0.615-0.817) in the independent test set (n = 99), indicating modest discriminative ability and thus should be interpreted as exploratory. Conclusion:This study systematically characterized the inflammation- and metabolism-related profiles that distinguish children with spastic cerebral palsy (SCP) from healthy controls and identified biomarkers associated with disease severity. Indicators such as mean platelet volume (MPV) and platelet distribution width (PDW) may serve as potential biological correlates for monitoring disease status and evaluating intervention responses in SCP.

OBJECTIVE:To evaluate the effectiveness and implementation of digital health interventions (DHIs) for patients with spinal cord injury (SCI) compared with control groups. METHODS:We conducted a systematic review of relevant randomized controlled trials (RCTs). Five electronic databases were searched from inception to January 1, 2026. The analysis examined the effects of DHIs on patients' clinical symptoms, quality of life, psychological status, and other outcomes. Quantitative analyses were performed using Review Manager software (version 5.4), and the results were presented using forest plots. The Cochrane Risk of Bias (RoB 1.0) tool was used to assess risk of bias, and the GRADE approach was applied to evaluate the overall certainty of evidence. RESULTS:A total of 26 RCTs were included. The meta-analysis showed that DHIs significantly reduced pain in patients with spinal cord injury (SMD = -0.19, 95% CI -0.38 to -0.00, P = 0.05) and improved independent living ability as measured by the Functional Independence Measure (FIM) (MD = 10.69, 95% CI 9.33-12.04, P < 0.00001). DHIs also significantly improved depressive symptoms (SMD = -0.25, 95% CI -0.51 to -0.00, P = 0.05) and anxiety symptoms (MD = -1.11, 95% CI -1.99 to -0.23, P = 0.01). In addition, DHIs significantly improved lower limb function, as reflected by improvements in the Timed Up and Go test (TUG) (MD = -0.92, 95% CI -1.60 to -0.23, P = 0.009) and the 10-Meter Walk Test (10MWT) (MD = -1.61, 95% CI -2.93 to -0.28, P = 0.02), and also enhanced balance ability (MD = 30.61, 95% CI 6.97-54.26, P = 0.010). However, no significant improvement was observed in upper limb function. DHIs also improved quality of life in the psychological domain (MD = 2.66, 95% CI -0.03-5.36, P = 0.05), social domain (MD = 1.52, 95% CI 0.75-2.30, P = 0.0001), and environmental domain (MD = 1.10, 95% CI 0.19-2.01, P = 0.02). Among the included studies, the reach of digital health technologies ranged from 14.05% to 100%, feasibility ranged from 58.33% to 100%, and adherence ranged from 51.05% to 100%. Only two studies reported mild adverse events. In this review, seven studies were assessed as having a low risk of bias, while 19 studies were rated overall as having a high risk of bias. The certainty of evidence in this review ranged from very low to moderate. CONCLUSION:Current evidence suggests that digital health technologies, as a supplement to conventional rehabilitation, may help improve certain functional outcomes, psychological health, and quality of life in patients with spinal cord injury, while also alleviating pain to some extent. However, the certainty of these findings is limited by multiple factors. Future high-quality studies are needed to further strengthen the evidence in these areas.

The rising co-occurrence of cardiometabolic diseases and musculoskeletal degeneration poses a critical challenge to healthy aging, yet the shared biological mechanisms underlying this multimorbidity remain poorly defined. This study aimed to establish an integrative clinical-genetic framework to elucidate the common frailty factor, the ‘F’ factor, that captures the systemic vulnerability linking cardiometabolic multimorbidity (CMM) and musculoskeletal aging. Utilizing the prospective China Health and Retirement Longitudinal Study (CHARLS) cohort, we developed and validated novel Frailty-Integrated Indices for CMM risk prediction, evaluated with machine learning models interpreted via SHapley Additive exPlanations (SHAP). Independently, we applied genomic structural equation modeling (Genomic-SEM) to integrate genome-wide association data from six traits—coronary artery disease, type 2 diabetes, hypertension, bone mineral density, frailty, and telomere length—to model a shared latent genetic factor (‘F’ factor). This was followed by multivariate GWAS, fine-mapping, transcriptome-wide association study (TWAS), gene-based analysis, and functional annotation to prioritize causal genes, pathways, and cell types. Clinically, several Frailty-Integrated Indices significantly improved CMM risk prediction, with the optimal model achieving an AUC of 0.727. Genetically, we modeled a significant shared latent genetic factor (‘F’ factor), pinpointing novel risk loci and implicating key genes such as APOE and SLC22A3. These genes were enriched in pathways including cellular senescence and cholesterol metabolism and showed specific expression patterns in developmental brain stages and across multi-organ endothelial cells. Our findings provide converging evidence for Musculoskeletal‑Heart crosstalk of metabolic aging and inferred the ‘F’ factor as a genetic correlate of a transdiagnostic state, which links genetic predisposition to metabolic dysregulation, and systemic functional decline. This work provides a multi-level biological characterization of multimorbidity liability, informing early-risk detection and preventive strategies for complex aging-related comorbidities. This figure has been designed using resources from Flaticon.com and BioGDP.com.

Objective This study investigated the effects of Fu's subcutaneous needling (FSN) combined with sodium hyaluronate (HA) intra-articular injection on knee function and inflammatory factor levels in patients with knee osteoarthritis (KOA). Materials and Methods A total of 122 patients with KOA were randomly assigned to an observation group (OG) or control group (CG). Outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), serum inflammatory cytokines, Lysholm Knee Scoring Scale (LKSS), visual analogue scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), overall response rate, and adverse events (AEs). Results At 2 months after treatment, WOMAC pain, stiffness, function, and total scores decreased significantly in both groups, with greater reductions in the OG than in the CG (all P < 0.05). Serum interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha levels also decreased significantly, with greater reductions in the OG (all P < 0.05). LKSS and KOOS scores increased significantly in both groups and were higher in the OG, whereas VAS scores decreased significantly and showed a greater reduction in the OG (all P < 0.05). The overall response rate was higher in the OG than in the CG (96.72% vs. 85.25%, P < 0.05). AE incidence was numerically lower in the OG, but the between-group difference was not significant ( P > 0.05). Conclusion FSN combined with intra-articular HA injection produced greater improvements in knee function, pain, and inflammatory responses than floating needling alone and may be a valuable adjunctive treatment for KOA.

BACKGROUND:Ligusticum sinense 'Chuanxiong', a Chinese medicinal herb, has long been used clinically to treat injuries. Its primary active compound, tetramethylpyrazine (TMP), has been demonstrated to mitigate oxidative damage in spinal cord injury (SCI) and is emerging as a potential therapeutic agent. However, translating the broad efficacy of natural compounds such as TMP into effective SCI therapies remains difficult, largely because clearly defined primary targets are lacking. This study aims to elucidate the mechanisms through which TMP improves SCI, providing a foundation for targeted therapeutic approaches. METHOD:A rat spinal cord contusion model was employed to investigate therapeutic targets of TMP. Motor function was assessed through behavioral tests, while tissue repair was evaluated by histological analysis. Transcriptome sequencing was utilized to identify key microRNAs and downstream mRNAs. In PC12 cells, an H2O2-induced oxidative stress model and a lentiviral Pannexin 1 (Panx1)-overexpressing stable line were established. Mechanisms were further validated using luciferase assays, dihydroethidium (DHE) and 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, live/dead staining, Western blot, PCR, transmission electron microscopy, and immunofluorescence. RESULTS:TMP enhanced motor function and promoted neuronal survival around the lesion site in SCI rats. Transcriptomic analysis identified miR-144-5p as a crucial mediator, which was upregulated post-treatment. miR-144-5p directly downregulates Panx1, thereby enhancing mitophagy. This reduction in oxidative stress, contributed to improved neuronal survival and functional recovery. CONCLUSIONS:TMP enhances mitochondrial autophagy and reduces ROS production following SCI by upregulating miR-144-5p and inhibiting Panx1 expression.

As a key technique in clinical diagnosis, multimodal medical image fusion (MMIF) integrates functional and metabolic information to assist diagnosis and enhance disease analysis reliability. However, existing methods typically rely on a single optimization objective, failing to meet clinical demands for flexible, on-the-fly result adjustments. To address this, we propose FreeMMIF, an interactive framework integrating a vision-language model (VLM)-based pseudo-labeling strategy and an instruction-aware diffusion model for task-guided, preference-adaptive fusion. During training, a VLM with specific prompts selects optimal candidates from existing methods as pseudo-ground truths to provide robust supervision without reference images. Subsequently, the diffusion process is modulated via an adaptive feature re-weighting branch, training the model to dynamically coordinate outputs by balancing weighted inputs from source images and pseudo-ground truths. Finally, we employ prompt engineering to construct a weight-generating VLM, allowing physicians to adjust source modality ratios via text instructions for direct control over fusion results. Experimental results demonstrate that FreeMMIF generates diagnostic-quality fusion results that precisely align with clinical intentions. Our code is available at: https://github.com/hzbbucm/FreeMMIF.

Spinal cord injury (SCI) induces a detrimental secondary inflammatory cascade driven largely by pro-inflammatory M1 macrophages, which impedes neural repair. Tetramethylpyrazine (TMP), a bioactive alkaloid from Ligusticum chuanxiong, has shown promise in modulating neuroinflammation. In this study, Sprague-Dawley rats subjected to thoracic contusion SCI received daily intraperitoneal TMP at 60 mg/kg or 80 mg/kg for 7 days. TMP treatment significantly improved hindlimb motor function, as evidenced by higher Basso-Beattie-Bresnahan (BBB) locomotor scores from day 7 through day 28 post-injury and increased motor evoked potential (MEP) amplitudes at day 28, confirming enhanced motor pathway conduction. Histological analyses (HE and Nissl staining) revealed reductions in lesion cavitation, preservation of neuronal architecture, and attenuated glial scar formation in TMP-treated groups. Immunofluorescence demonstrated increased NeuN, MAP2, and NF200 and decreased GFAP expression, while double staining for iNOS/CCR2 and Arg1/CCR2 indicated a shift from M1 to M2 macrophage polarization. ELISA showed significant reductions in IL-6 and TNF-α and elevation of IL-10, and both WB and RT-qPCR confirmed TMP-mediated suppression of IL-6/JAK2/STAT3 phosphorylation and gene transcription. In vitro, TMP reversed LPS-induced M1/M2 polarization imbalance in RAW 264.7 cells, meanwhile suppressing IL-6/JAK2/STAT3 phosphorylation and gene transcription, reduced pro-inflammatory cytokine release in TMP groups. Furthermore, rescue experiments demonstrated that co-treatment with recombinant IL-6 reversed TMP-mediated suppression of JAK2/STAT3 phosphorylation and M1-to-M2 polarization shift, confirming the IL-6/JAK2/STAT3 pathway as a direct mechanistic target of TMP. These results indicate that TMP fosters histopathological and functional recovery after SCI by reshaping macrophage polarization via inhibition of the IL-6/JAK2/STAT3 pathway, highlighting its potential as an anti-inflammatory neuroprotective therapy.

PurposeThis bibliometric and scientometric study mapped the development, collaboration structure, thematic organization, and temporal evolution of Chinese- and English-language research on traditional Chinese medicine (TCM)-related interventions for cerebral palsy (CP).MethodsPublications were retrieved from Web of Science Core Collection, Scopus, PubMed, Embase, China National Knowledge Infrastructure, Wanfang Data, and the Chinese Science and Technology Journal Database from inception to July 20, 2026. Eligible peer-reviewed articles and reviews were analyzed separately by language. Excel supported descriptive analysis, VOSviewer keyword co-occurrence and overlay mapping, CiteSpace keyword burst detection, and Python with NetworkX coauthorship analysis. Parameter sensitivity analyses and an author-developed integrative thematic synthesis were also performed.ResultsThe final corpora included 3,225 Chinese-language and 230 English-language publications. Chinese-language output rose markedly after the late 2000s and peaked in 2020, whereas English-language output remained smaller and more variable. The English-language coauthorship network was more connected and had a higher multi-author publication rate. At a minimum occurrence threshold of five, 179 of 2,115 standardized Chinese keywords and 70 of 955 standardized English keywords were retained. Five research domains were identified: clinical rehabilitation and functional outcomes; spasticity and symptom-oriented management; TCM intervention modalities; clinical research design and evidence synthesis; and experimental and mechanistic research. Temporal analyses indicated a broadening from general clinical applications toward function-oriented assessment, evidence synthesis, and mechanistic investigation. Sensitivity analyses supported the broad thematic structure, although several recent burst signals were parameter-sensitive.ConclusionThe corpora showed distinct publication and collaboration patterns but overlapping thematic structures. These findings map the literature’s organization and evolution but do not establish efficacy, safety, or certainty of evidence. Priorities include prospectively registered multicenter studies, standardized intervention reporting, a core outcome set, systematic safety assessment, and clinically anchored mechanistic research.

STUDY DESIGN:A cross-sectional analysis of 10,000 cervical spine X-rays. OBJECTIVE:This study investigates the variations in C6S and C7S across demographic factors (gender, age, cervical curvature, and symptoms) and explores their correlation. In addition, machine learning models are applied to improve the accuracy of C7S prediction. SUMMARY OF BACKGROUND DATA:The C7S is crucial for assessing cervical balance but is often limited by visibility issues. This study uses a large sample to validate the feasibility of the C6S as a substitute for C7S across diverse populations with varying ages, genders, symptoms, and cervical curvatures. MATERIALS AND METHODS:A retrospective study was conducted on 10,000 subjects who underwent cervical sagittal X-ray imaging. Four orthopedic specialists labeled key points, which were cross-validated, and an algorithm was then used to measure C6S and C7S. Pearson correlation coefficients were calculated to assess the relationship between C6S and C7S, and linear regression derived a predictive equation for C7S. Various machine learning models were compared with improve C7S prediction accuracy. RESULTS:The average angles for C6S and C7S were 15.4° (16.8° in males, 14.7° in females) and 19.1° (21.1° in males, 18.2° in females), respectively, with C7S generally larger than C6S, except in Sigmoid 1 curvature. Males exhibited higher values for both C6S and C7S, and both slopes increased after age 20. Both angles increased significantly with age from 20 to 90 years. A strong positive correlation was found between C6S and C7S ( r >0.75, P <0.001), confirmed by linear regression ( R2 ​​​​​​=0.688). Among the machine learning models, both Ridge regression and linear regression performed better than the others, with R2 =0.855 in predicting C7S. CONCLUSION:The strong correlation between C6S and C7S suggests that C6S can substitute for C7S when visibility is limited. Machine learning models further enhance prediction accuracy, demonstrating promising clinical potential.

Osteonecrosis of the femoral head (ONFH) is a debilitating condition often linked to glucocorticoid use. This research aims to explore the influence of mammalian sterile 20-like kinase 1 (Mst1) on glucocorticoid-induced ONFH, particularly its effects on bone microvascular endothelial cells (BMECs). Methylprednisolone (MPS) was applied to induce BMECs injury in vitro, with or without Mst1 inhibition via shRNA. Significantly improved cell viability, reduced apoptosis, and enhanced angiogenic and migratory capabilities were found after inhibiting Mst1. These protective effects correlated with elevated levels of autophagy-related factors such as Beclin1and LC3, as well as reduced P62 expression, indicating that Mst1 inhibition enhances autophagy. Animal studies using a glucocorticoid-induced ONFH rat model also corroborated these findings. The Mst1 inhibitor XMU-MP-1 treatment improved femoral head condition by enhancing bone microstructure and decreasing apoptosis. Furthermore, XMU-MP-1 treatment upregulated autophagy-related proteins in vivo. These results suggest that Mst1 plays a critical role in glucocorticoid-induced ONFH by modulating autophagy and that Mst1 inhibition may offer a promising therapeutic strategy for this condition.

Skeletal aging, a core determinant of systemic aging, poses a global public health challenge due to its association with chronic diseases and functional decline. This study aimed to decode the genetic architecture of skeletal aging by identifying novel loci and multi-system crosstalk using genomic structural equation modeling (Genomic SEM). We integrated genome-wide association study (GWAS) data from five musculoskeletal-related traits (osteoporosis [OP], osteoarthritis [OA], lumbar spinal stenosis [LSS], telomere length [TL], and low back pain [LBP]) across 462,933 to 472,174 European individuals. Genomic SEM, FUMA, FUSION, and fine-mapping tools (SuSIE/FINEMAP) were applied to model latent skeletal aging ("mvSAge") and identify causal variants, enriched pathways, and tissue-specific gene expression. The latent factor model (CFI = 0.993, SRMR = 0.065) revealed shared genetic architecture among OP, OA, LSS, TL, and LBP. We identified 514 lead SNPs (P < 5 × 10⁻12), including 136 novel loci enriched in regulatory regions (e.g., brain putamen, frontal cortex). Fine-mapping prioritized causal variants (posterior probability > 0.95) near MTPAP, GRAMD4, and DPP8, implicating mitochondrial function and immune regulation. Transcriptome-wide analyses highlighted PPP6R3 (bone mineral density) and SLC33A1 (anticancer target) as key genes. Enrichment analyses linked mvSAge to Wnt signaling, ER stress, and Mendelian disorders (e.g., ALS). Chromosomes 1, 2, and 4 showed elevated heritability contributions, driven by conserved regulatory elements (RUNX2, SP7) and chromatin accessibility hotspots. This study establishes mvSAge as a genetically cohesive construct and uncovers novel loci, pathways, and multi-system interactions underlying skeletal aging. These findings advance precision medicine strategies for aging-related musculoskeletal disorders.

Spinal cord injury (SCI) is a severe central nervous system disorder that disrupts neural circuit integrity, leading to significant motor and sensory dysfunction or loss. Despite the urgent need, no effective treatments are currently available in clinical practice. Tetramethylpyrazine (TMP), a compound extracted from the plant Ligusticum wallichii, has shown therapeutic potential for SCI, but its efficacy is constrained by the blood-spinal cord barrier and a short half-life. To address this limitation, we developed a polyvinyl alcohol (PVA) hydrogel with an oriented porous structure (TMP/OPH) designed to achieve sustained, localized TMP delivery at the injury site. The TMP/OPH was synthesized via a combined sol-gel transition and freeze-casting method, which enables physical gelation of PVA without additional crosslinking agents, making it a simple, and safe approach that enables the gel to revert to sol upon heating for complete recyclability. TMP/OPH not only functions as a local drug delivery system but also features an anisotropic porous structure that supports axonal regeneration and synaptic reconstruction at the injury site. Mechanistic studies revealed that TMP/OPH, through the sustained TMP release in the early stages of SCI, regulates the TNF signaling pathway, promotes M2 polarization of microglia, suppresses neuroinflammation, and improves the local microenvironment, thus creating favorable conditions for nerve repair. Long-term therapeutic effects, including axonal regeneration, synaptic reconstruction, reduction of glial scar, and improved motor function further support TMP/OPH as a promising therapeutic strategy for SCI repair.

BACKGROUND:Spinal cord injury (SCI) leads to permanent paralysis, with no current treatments capable of enhancing neurological recovery. Tetramethylpyrazine (TMP) has recently emerged as a potential therapeutic agent for SCI, although further investigation is required to clarify its mechanisms of action. METHODS:To evaluate the therapeutic effects of TMP on SCI, SCI models were established in rats, followed by assessment of therapeutic efficacy. Motor function recovery was quantified using the Beattie, Bresnahan and Basso (BBB) score, electrophysiological measurements, footprint analysis, and CatWalk gait analysis. Spinal cord tissues were examined through HE, Nissl, dihydroethidium (DHE), transmission electron microscopy, and immunofluorescence. Key molecular targets and functional pathways were analyzed via transcriptomic and proteomic sequencing. Additionally, PC12 cells were cultured to validate the molecular mechanisms of TMP, employing cell counting kit-8 (CCK-8) assays, live/dead staining, 2, 7-dichlorodihydrofluorescein diacetic acid fluorescent probe (DCFH-DA), western blotting (WB), and immunofluorescence staining. RESULTS:TMP treatment significantly enhanced neuronal survival and improved motor function in rats. Sequencing analysis revealed a considerable number of differentially expressed genes following SCI and TMP administration, predominantly associated with stress response, external stimuli, and defense mechanisms. Venn analysis identified PKD1 as a key target, showing reduced expression after SCI and upregulation following TMP treatment. Further validation in spinal cord tissues and cells confirmed these findings. The reduction in PKD1 expression post-SCI was correlated with a marked oxidative stress response, which TMP effectively reversed. CONCLUSIONS:TMP may promote functional recovery by upregulating PKD1 and alleviating oxidative stress-related damage.

Chinese herbal medicine (CHM) is widely used for the treatment of spinal cord injury (SCI). However, its exact mechanisms are not yet fully understood. The aim of this study was to evaluate the clinical efficacy and potential pharmacological mechanisms of CHM in treating SCI. Eight databases were searched for randomized controlled trials (RCTs) published from their inception until January 2025 regarding the use of Chinese medicine for SCI. The quality of the included studies was assessed using the Cochrane risk of bias tool. A meta-analysis was performed to evaluate the efficacy of Chinese medicine in treating SCI, and data mining and network pharmacology were used to identify core drugs and active ingredients. Finally, clustering and enrichment analyses were performed to explore potential targets and signaling pathways. A total of 41 studies involving 2,483 patients were included. The meta-analysis showed that compared with the control group, the Chinese medicine group significantly improved sensory function (ASIS-SIS), motor function (ASIS-MS), activities of daily living (BI), and pain levels (VAS) in patients with SCI: ASIS-SIS: standardized mean difference (SMD) = 11.52, 95

Background Assessing various types of dysfunction in cerebral palsy is a key factor in the treatment and rehabilitation of patients. The objective of this study was to use meta-analysis and systematic review to identify the specific white matter lesions and DTI metrics strongly associated with various types of dysfunction in cerebral palsy. Methods We conducted a literature search of PubMed, Embase, Cochrane Library and Web of Science databases to identify trials published that had evaluated the correlation between DTI metrics in sensorimotor pathways and function scores in cerebral palsy. Correlation coefficient (r) values were extracted for each study, and the extent of r was quantitatively explored. The remaining part of the study was analyzed qualitatively. Results 46 studies involving 1458 children with cerebral palsy, were included. 19 articles for Meta-analysis and 27 articles were descriptively analyzed. DTI metrics such as FA、MD in both sensory and motor pathways significantly correlated with various function ratings. In overall motor dysfunction, compared with the CST and PTR, FA of the PLIC correlated more strongly with GMFCS, and showed no significant heterogeneity (r = -1.28, confidence interval [CI]-1.70 to -0.87,I2 = 38.2%,P = 0.233). In upper limb dysfunction, compared with the AHA and MA2, FA of the CST correlated more strongly with BBT, and showed no significant heterogeneity (r = -0.56, confidence interval [CI]-0.78 to -0.34,I2 = 0.0%,P = 0.511). Lower limb dysfunction and other dysfunctions we used qualitative analysis. The qualitative analysis offered a concise overview of each investigation. Conclusions This study basically identifies the specific white matter lesions corresponding to overall motor dysfunction, upper limb and lower limb motor deficits and other dysfunctions in patients with cerebral palsy, as well as the associated DTI metrics.