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.

Data has emerged as a premier,novel factor of production and the central engine driving the growth of the digital economy.The empowerment of Traditional Chinese Medicine(TCM)with data elements to foster new quality productive forces is an intrinsic prerequisite for the high-quality development of both the TCM discipline and its associated industries.This integration is poised to play a pivotal role in catalyzing systemic transformations in TCM's scientific research paradigms and clinical models,upgrading the traditional TCM industry,and nurturing a host of emerging and future-oriented industrial sectors.As a novel form of data infrastructure,the Trusted Data Space(TDS)serves as a critical vehicle for facilitating the unimpeded circulation of data resources.In this context,constructing a Trusted Data Space for Traditional Chinese Medicine(TCM-TDS)to empower the inheritance and innovation of TCM through data elements holds profound contemporary significance. In the digital era,data is a core asset,and its effective utilization defines advanced productive forces.For TCM,a field rich with empirical knowledge,this digital transformation presents an unprecedented opportunity to shift from experience-based practices to evidence-based,data-driven methodologies.This transition allows for the validation of traditional theories with modern scientific rigor,bridging historical wisdom with contemporary data analytics,thereby enhancing the precision,personalization,and efficacy of diagnostics and treatments.A TDS provides the foundational governance,legal,and technical framework for this shift,enabling secure and sovereign data sharing among research institutions,hospitals,and enterprises.It addresses the critical need to dismantle data silos and foster a collaborative ecosystem for innovation,which is especially crucial given the sensitive nature of medical data and the need for patient privacy. This paper elaborates on the construction pathway for a TCM-TDS,detailing its foundational infrastructure,functional architecture,and the associated technical and business workflows.The objective is to formulate a replicable and scalable construction model for the TCM sector that can support the demands of a nationally integrated data market and promote the value of TCM data as a key economic asset.The discussion outlines a detailed pathway,including the physical and virtualized resources for data handling,and the essential modules for data governance,identity management,and access control,ensuring a robust and secure operational environment for all participants. Furthermore,this paper proposes several developmental countermeasures and recommendations for the application of the TCM-TDS.These include fostering institutional and mechanistic innovations,developing high-quality datasets and enhancing the underlying data infrastructure,advancing theoretical and technological innovations in digital and smart TCM,and leveraging diverse application scenarios—from drug discovery to personalized health management—to drive the formation of a comprehensive TCM data ecosystem and promote industrial development.The successful implementation of the TCM-TDS will ultimately depend on this multi-faceted approach,cultivating a vibrant ecosystem that spurs new avenues for industrial growth and contributes significantly to societal well-being and public health.

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.

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.

Purpose:Cervical radiculopathy (CR) poses a significant challenge due to its debilitating impact. Cervical rotation-traction manipulation (CRTM) is a representative manual therapy of traditional Chinese medicine (TCM) in China, which is beneficial to improve the pain, numbness, and dysfunction of CR patients. However, the optimal treatment frequency for CRTM remains systematically underexplored in randomized controlled trials (RCTs). This clinical study aims to assess the effectiveness and safety on three sessions per week of CRTM (TSWM) compared to one session per week of CRTM (OSWM) and cervical traction (CT) in patients with CR. Patients and Methods:This multicenter, three-arm, prospective RCT is conducted at four hospitals in China. Participants will be randomly allocated in a 1:1:1 ratio to one of the TSWM group, OSWM group, or CT group through the central randomization system. All participants will receive 4-week treatment and 16-week follow-up (total 20 weeks). The primary outcome is pain intensity of neck and arm measured by the Visual Analog Scale (VAS) at week 4. The secondary outcomes include VAS for pain intensity, VAS for numbness intensity, Neck Disability Index (NDI), Short Form 12 (SF-12), the total cost, the recurrence rate, and Expectation of Treatment and Credibility Scale (ETCS). Adverse events (AEs) will be monitored and reported throughout the trial. Conclusion:We expect this clinical study to evaluate the optimal frequency of CRTM for CR. It will also serve as a reference and exploration for investigating the dose-response relationship of manual therapy. Trial Registration:This clinical trial was registered at ClinicalTrials.gov (registration number: NCT06320249) on March 15, 2024.

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.

Cardiovascular calcification is a pathological process commonly observed in the elderly. Based on the location of the calcification, cardiovascular calcification can be classified into two main types: vascular calcification and valvular calcification. Collagen plays a critical role in the development of cardiovascular calcification lesions. The content and type of collagen are the result of a dynamic balance between synthesis and degradation. Unregulated processes can lead to adverse outcomes. During cardiovascular calcification, collagen not only serves as a scaffold for ectopic mineral deposition but also acts as a signal transduction pathway that mediates calcification by guiding the aggregation and nucleation of matrix vesicles and promoting the proliferation, migration and phenotypic changes of cells involved in the lesion. This review provides an overview of collagen subtypes in the cardiovascular system under physiological conditions and discusses their distribution. Additionally, we introduce pathological changes and mechanisms of collagen in blood vessels and heart valves. Then, the formation process and characteristic stages of cardiovascular calcification are described. Finally, we highlight the role of collagen in cardiovascular calcification, explore strategied for mediating calcification, and suggest potential directions for future 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.

The repair of bone defects under diabetes mellitus remains challenging due to the hyperglycaemic environment that tends to initiate oxidative stress, leading to poor bone healing. Therefore, the biodegradable, antioxidant and pro-osseointegration properties of bone implants are essential for the healing of diabetic bone defects. Addressing this issue requires bone implants with specialized properties, including biodegradability, antioxidant activity, and the ability to enhance pro-osseointegration. Herein, we developed a novel degradable Zn-Li-Sr ternary alloy aimed at alleviating oxidative stress and promoting the regeneration of diabetic bone defects. Results have shown that the coupling of Zn, Li and Sr not only resists oxidative damage, but also promotes the proliferation and differentiation of osteoblasts. The Zn-Li-Sr alloy implants have been shown to possess multifunctional properties, such as promoting osteogenesis and exhibiting antioxidant activity in vitro, while also facilitating bone ingrowth and osseointegration in vivo. Beyond biological advantages, the alloying of Li and Sr endowed the Zn alloy with significantly improved tensile strength for mechanical support with up to 6 times the UTS and 8 times the YS of pure Zn, and a uniform degradation mode to prevent localized rupture. Overall, Zn-Li-Sr alloy implants demonstrate promising applications for bone regeneration under diabetic conditions, their multifunctional properties not only address the physiological challenges posed by diabetes but also provide robust mechanical support and controlled degradation. This study provides valuable insights into the design and potential clinical applications of implants for bone regeneration under diabetic conditions.

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.

IntroductionA combination of Corydalis Rhizoma (the dried tuber of Corydalis yanhusuo W.T. Wang) and Paeoniae Radix Alba (the root of Paeonia lactiflora Pall.) has been traditionally employed for analgesia. However, the underlying pharmacological mechanisms have not been clarified. The aim of the present study was to investigate the anti-inflammatory and analgesic effects of YB60, the 60% ethanol elution fraction derived from the combination of Corydalis Rhizoma and Paeoniae Radix Alba, and the explore the underlying mechanism.MethodsLipopolysaccharide-induced cellular inflammation model and chronic compression injury (CCI) rat model were used to study the anti-inflammatory and analgesic effects of YB60. Proteomics and molecular biology experiments were applied to explore the potential analgesic mechanism of YB60.ResultsThe results demonstrated that YB60 significantly decreased inflammatory cytokine levels both in cellular models and rat serum, while concurrently elevating pain thresholds in CCI rats. Proteomic analysis indicated that YB60 could upregulate the expression of Membrane Bound O-Acyltransferase Domain Containing 2 (Mboat2), a newly confirmed marker of ferroptosis. Furthermore, YB60 prevented ferroptosis in the spinal cords of CCI rats. Western blotting and immunofluorescent dual staining further revealed that YB60 increased the expression of Mboat2 and its upstream signaling molecule Androgen receptor (AR). Results in PC12 cells in vitro showed that YB60 reversed the downregulation of AR and Mboat2, and ameliorated ferroptosis induced by Erastin, while knockdown of AR eliminated the above effects of YB60.ConclusionThese findings indicated that YB60 exerted its analgesic effect by inhibiting ferroptosis in spinal cord neurons via modulation of the AR/Mboat2 pathway.

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.

BackgroundNeck pain with high incidence and recurrence rates significantly impairs patients’ quality of life and imposes a considerable economic burden. Traditional Chinese medicine therapies such as Yijinjing exercise and Tuina have shown promising efficacy in alleviating the local symptoms of neck pain. However, there is currently insufficient high-level evidence to robustly support these findings. ObjectiveThis study aims to evaluate the efficacy and safety of combining Yijinjing exercise with Tuina for the treatment of neck pain. MethodsPubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Database, VIP Chinese Science and Technology Periodicals Full-Text database, and Wanfang database will be systematically searched for all relevant randomized controlled trials (RCTs) from their inception to September 2025, without language or publication status restrictions. The Cochrane Risk of Bias 2 assessment tool will be used to evaluate the risk of bias in the included studies, and the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system will be employed to grade the quality of evidence. Heterogeneity will be evaluated through I2 statistics and Cochran’s Q test: a fixed-effect model will be used when I2<50% and P≥.01. If I2≥50% or P<.01, subgroup analysis will be conducted. When heterogeneity still exists, sensitivity analysis or exploratory subgroup analysis will be performed. If it cannot be explained ultimately, the random-effects model will be adopted and the GRADE evidence level will be reduced. ResultsAs of June 2025, we have completed the preliminary screening of titles and abstracts for 573 studies. The full-text screening is expected to be completed by September 2025, and data analysis is planned to be completed by December 2025. About two-thirds of the studies were published after 2015. Geographically, the samples in the studies were highly concentrated in Asia. The results were comprehensively developed around the core outcomes. The primary outcome was presented by changes in the visual analog scale. The secondary outcomes were evaluated by the neck disability index, self-rating anxiety scale score, mean vertebral artery blood flow velocity, and Cobb angle. ConclusionsIf the results of this study confirm the effectiveness of massage combined with Yijinjing, it can provide a direction for the nonpharmaceutical treatment of neck pain. However, some studies have risks of bias such as insufficient standardization of massage operations and difficulty in implementing blinding methods. The expected heterogeneity is significant due to differences in intervention plans and patients’ cultural backgrounds, and the original RCTs are few and regionally concentrated, with limited extrapolation of conclusions. In the future, it is necessary to optimize the plan and supplement data through high-quality multicenter research to enhance reliability. Trial RegistrationPROSPERO CRD420251026508; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251026508 International Registered Report Identifier (IRRID)DERR1-10.2196/77864

Chronic musculoskeletal disorders(CMSDs)are a class of chronic and progressive osteoarticular diseases resulting from the combined effects of biological and biomechanical factors,which severely impair patients'quality of life and impose a sub-stantial socioeconomic burden.Based on classical traditional Chinese medicine(TCM)theory,Professor MU Xiaohong from Dong-zhimen Hospital,Beijing University of Chinese Medicine,proposed the theory of"Harmony of Tendons and Bones"and applied it in the clinical management of CMSDs.This study elucidates the origins and connotations of the"Harmony of Tendons and Bones"theory,and explores the pathogenesis,treatment,and innovative development pathways of CMSDs under this theoretical framework,aiming to provide a theoretical basis and practical support for TCM interventions in CMSDs.The"Harmony of Tendons and Bones"theory,roots in the Huangdi Neijing(Yellow Emperor's Inner Canon),emphasizes the mutual coordination of tendons and bones,achieves biomechanical balance and functional integration through the nourishment of meridians and qi-blood.The theory posits that tendon-bone imbalance is the core mechanism underlying the dynamic and static instability of CMSDs;disharmony of meridians and qi-blood is the pathological nexus of tendon-bone imbalance;and deficiencies of the liver,kidney,and spleen are the fundamental causes of qi-blood disharmony.At different stages of disease progression,CMSDs manifest as pathological states of tendon-bone im-balance,malnourishment,and flaccidity or weakness.Therapeutic strategies should follow the principles of regulating tendons and correcting bones,attaching equal importance to tendons and bones,tonifying the liver and kidney,harmonizing qi and blood,and im-plementing stage-specific and dynamic interventions.A combination of internal therapy,external therapy,surgery,exercise therapy,and modern rehabilitation methods is recommended,with emphasis on the integration of medical treatment and health maintenance,to achieve the therapeutic goals of"utilizing smoothness"and"pursuing balance",restore the harmonious state of tendons and bones,improve disease progression,and enhance quality of life.Furthermore,the study proposes multidimensional innovations through equipment upgrading,technological development,and system reconstruction,to promote the deep integration of the"Harmony of Tendons and Bones"theory with industrial and scientific advancements,providing a continuous source of innovation and momentum for the modernization of TCM in CMSDs management.

Effective disease management based on real-time physiological changes presents a significant clinical challenge. A flexible electrode system integrating diagnosis and treatment can overcome the uncertainties associated with treatment progress during localized interventions. In this study, we develop a system featuring a biomimetic feedback regulation mechanism for drug delivery and real-time monitoring. To prevent drug leakage, the system incorporates a magnesium (Mg) valve in the outer layer, ensuring zero leakage when drug release is not required. The middle layer contains a drug-laden poly(3,4-ethylenedioxythiophene) (PEDOT) sponge (P-sponge), which supplies the water to partially or fully activate the Mg valve under electrical stimulation and initiate drug release. Once the valve is fully opened, the exposed and expanded P-sponge electrode establishes excellent contact with various tissues, facilitating the collection of electrophysiological signals. Encapsulation with polylactic acid film ensures the system’s flexibility and bioresorbability, thereby minimizing potential side effects on surrounding tissues. Animal experiments demonstrate the system’s capability to mimic feedback modulation mechanisms, enabling real-time monitoring and timely drug administration. This integrated diagnosis and treatment system offers an effective solution for the emergency management of acute diseases in clinical settings.