Spinal cord injury (SCI) triggers a persistent inflammatory microenvironment that contributes to secondary tissue damage and neurological dysfunction. However, the metabolic mechanisms sustaining activation of lesion-associated phagocytes remain incompletely understood. Here, we identify lipid-laden microglia/macrophages as a metabolically stressed inflammatory state that emerges after SCI and investigate the role of lipid efflux in regulating this process. Single-nucleus and immune-enriched transcriptomic analyses revealed coordinated upregulation of cholesterol transport and inflammatory pathways in lesion-associated phagocytes. Among lipid transporters, the ATP-binding cassette transporter ABCA1 was consistently induced across post-injury stages. Conditional deletion of ABCA1 in Cx3cr1-lineage cells led to excessive lipid droplet accumulation, enhanced reactive oxygen species production, sustained pro-inflammatory cytokine expression, and impaired locomotor recovery following SCI. To therapeutically target this pathway, we performed structure-guided virtual screening and identified the small molecule Z231 as an ABCA1-binding compound. Pharmacological activation of ABCA1 reduced lipid accumulation, suppressed oxidative stress and inflammatory gene expression, and partially restored mitochondrial metabolic balance in microglia exposed to myelin debris. In vivo, systemic Z231 administration attenuated inflammatory signaling and improved functional recovery after SCI. Together, these findings identify ABCA1-mediated lipid efflux as a key regulator of microglial metabolic stress and neuroinflammation after spinal cord injury, and suggest that targeting lipid handling pathways may represent a potential therapeutic strategy for SCI.

Study DesignRetrospective cohort study.ObjectivesThis study introduced the screw trajectory-to-vertebral body Hounsfield unit (HU) ratio as a novel parameter, evaluated its predictive value with the pedicle bone quality (PBQ) score for postoperative pedicle screw loosening, and develop a nomogram for risk prediction.MethodsRetrospective analysis included 313 patients undergoing pedicle screw fixation (2022-2024). Screw loosening was defined as a ≥1.0-mm radiolucent zone or double-halo sign on postoperative computed tomography (CT) or radiographs. Preoperative CT and magnetic resonance imaging (MRI) were used to calculate the HU ratio and PBQ score. Candidate predictors were selected based on univariable screening and clinical relevance; multivariable logistic regression was used to develop the prediction model and nomogram. Model performance was evaluated by area under the curve (AUC), Hosmer-Lemeshow test, and bootstrap validation. A sensitivity analysis was performed by additionally including 43 scoliosis patients (n = 356).ResultsAt 12 months follow-up, the loosening rate was 14.3% (45/313) in the patients. Independent risk factors included higher PBQ score, lower HU ratio, older age, and higher Goutallier grade. The nomogram showed excellent discrimination (apparent AUC = 0.904, 95% confidence interval [CI]: 0.856-0.953; optimism-corrected AUC = 0.883) and acceptable calibration (Hosmer-Lemeshow P = .393). At the optimal cutoff (predicted probability ≥0.212), sensitivity was 80.0% and specificity 88.1%. In sensitivity analysis, construct-related factors (fusion length and terminal fusion segment) became statistically significant, while overall model performance remained comparable.ConclusionsThe HU ratio is an independent predictor of postoperative pedicle screw loosening and complements the PBQ score.

Intervertebral disc degeneration (IVDD) is a major cause of low back pain, characterized by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration. Sal attenuates IVDD by activating SIRT1/FOXO3-mediated mitophagy, restoring mitochondrial homeostasis, and reducing NPMSCs apoptosis. These results suggest that the activation of the SIRT1/FOXO3-mitophagy axis may represent a potential therapeutic strategy for mitigating IVDD.

Abstract The immune milieu formed after bone injury critically affects subsequent repair, yet biomaterial-based regulation of regulatory T cells (Tregs) remains less explored than macrophage-centered immunomodulation. Here, cotton-like cerium-doped bioactive glass nanofibers (Ce-BGFs) were fabricated by sol-gel electrospinning to investigate Treg-related osteoimmune regulation during bone regeneration. Ce incorporation improved the compatibility of BGFs with naïve CD4⁺ T cells, preserved efficient Treg induction, and reduced ROS accumulation under calcium-rich conditions. Ce-BGFs also showed moderate direct pro-osteogenic and pro-M2 effects on BMSCs and RAW264.7 macrophages. More importantly, Tregs conditioned by Ce-BGFs exhibited anti-inflammatory and osteogenesis-associated transcriptomic features, and their conditioned medium enhanced BMSC osteogenic differentiation and CD206⁺ macrophage polarization. Transcriptome analysis of BMSCs further indicated enrichment of MAPK and Wnt signaling pathways. In a mouse tibial monocortical defect model, Ce-BGFs increased local Treg accumulation and supported early bone formation. These findings suggest that Ce-BGFs act as ion-releasing fibrous materials that promote bone repair through Treg-associated osteoimmune regulation.

BACKGROUND:Optimal graft selection for anterior cruciate ligament (ACL) reconstruction (ACLR) remains controversial, particularly regarding tendon-to-bone incorporation and biomechanical performance among autografts, allografts, and hybrid grafts. HYPOTHESIS:Autografts demonstrate superior tendon-to-bone healing, biomechanical strength, and functional recovery compared with allografts and hybrid grafts. STUDY DESIGN:Controlled laboratory study. METHODS:A total of 84 rats underwent ACLR using autograft, allograft, or hybrid grafts (a construct combining autograft and allograft tissues) (n = 21 per group), with an intact group serving as the control group. Grafts were harvested from the peroneus longus tendon. Assessments at 1, 2, 4, and 8 weeks included histology (hematoxylin and eosin; the Masson trichrome staining; immunohistochemistry), gait analysis, micro-computed tomography, and biomechanical testing. RESULTS:Histologically, compared with allografts and hybrid grafts, autografts exhibited significantly improved synovial coverage, lower cartilage degeneration (score, autograft vs allograft vs hybrid graft: 10.80 ± 0.84 vs 3.20 ± 0.84 vs 4 ± 0.71; P < .001), improved collagen alignment, reduced inflammation, and enhanced vascularization and tenogenesis, whereas allografts and hybrid grafts exhibited distinct necrosis. Autografts exhibited superior value of bone volume per total volume (femur, autograft vs allograft vs hybrid graft: 5.40 ± 0.55 vs 2.60 ± 0.86 vs 2.69 ± 0.25; P < .001). Gait parameters, including stride length and step height, were restored to near-control levels only in the autograft group (intact control vs autograft: stride length, 3.09 ± 0.40 vs 2.96 ± 0.35; P = .899; step height, 2.67 ± 0.31 vs 2.26 ± 0.35; P = .199). Biomechanically, autografts demonstrated superior stress (autograft vs allograft: 14.86 ± 4.26 vs 2.64 ± 1.35; P < .001), stiffness (autograft vs allograft: 11.21 ± 5.55 vs 3.15 ± 1.55; P = .027), and tensile modulus (autograft vs allograft vs hybrid graft: 31.71 ± 10.35 vs 3.71 ± 1.83 vs 15.07 ± 4.51; P < .001). CONCLUSION:Autografts provided superior tendon-to-bone integration, biomechanical performance, and functional outcomes compared with allograft and hybrid grafts in a rat ACLR model. CLINICAL RELEVANCE:This preclinical study, conducted in a rat model, provides mechanistic evidence that autografts exhibit superior biological incorporation and mechanical integrity, supporting the existing clinical preference for autograft in ACLR and helping inform graft selection.

Senile osteoporosis and its associated fractures significantly contribute to increased morbidity, mortality, and healthcare costs among older adults. Further research is needed to elucidate the molecular mechanisms underlying senile osteoporosis. This study found that FKBP5 expression in bone marrow mesenchymal stem cells (BMSCs) increases with age and is inversely correlated with patients' bone mineral density and CT values. Functional analyses revealed that FKBP5 plays a crucial regulatory role in BMSC osteogenic differentiation, acting through the canonical WNT/β-catenin signalling pathway. FKBP5 binds to β-catenin, promoting its ubiquitination and degradation. Importantly, administration of SAFit2, a selective FKBP5 inhibitor, enhanced bone mineral density in an animal model of senile osteoporosis. These findings suggest that FKBP5 may represent a novel therapeutic target and provide new insights into the treatment of senile osteoporosis.

ObjectiveSpinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory, and autonomic dysfunction. N6-methyladenosine (m6A) is a reversible RNA modification implicated in various biological processes. However, few studies have examined m6A expression in patients with SCI. We explored the prognostic value of m6A-related genes as potential biomarkers in SCI to establish a set of accurate diagnostic and prognostic prediction models.MethodsDifferentially expressed analysis and weighted gene co-expression network analysis (WGCNA) was used to explore m6a related modules and hub genes. KEGG and GO analyses was utilized to explore the potential role of these hub genes. Gene expression was verified in single-cell data. The correlation of m6A related gene with spinal cord injury severity was explored.ResultsWe found 289 SCI-related and five m6A-related candidate genes with high SCI correlation and high differential expression in the publicly available dataset, GSE151371. These genes are also involved in long-chain fatty acid binding. Early SCI was accompanied by significant immune cell infiltration. Simultaneously, infiltrating immune cells and the innate immune system have a strong cellular interaction, which gradually decreases over time. The number of PPARG-positive cells also increases after SCI. The comparatively higher expression of PPARG and lower expression of AK5 in white blood cells (WBCs) correlates with severity of SCI.ConclusionOur integrated analysis illustrates the hub genes involved in SCI, which can be prognostic markers. Further understanding of the functions of the identified SCI hub genes may provide deeper insights into the molecular mechanisms of SCI.

Endothelial dysfunction is one of the earliest processes in diabetes and a major contributor to diabetic vascular complications, which often exhibit limited response to glucose-lowering therapies. We identified up-regulated S-nitrosoglutathione reductase (GSNOR) as a critical factor associated with diabetic vascular complications by unbiased proteomics. Elevated GSNOR expression was observed in the endothelium of patients with type 2 diabetes and in streptozotocin (STZ)-induced type 1 diabetes mice as well as in db/db type 2 diabetes mouse models. Genetic ablation of endothelial Gsnor promoted angiogenesis, maintained vascular permeability, and improved vasodilation in type 1 diabetes mice induced by STZ. GSNOR deficiency protected against high glucose-induced endothelial dysfunction in vitro, as evidenced by rescued tube formation, enhanced spheroid sprouting, maintained barrier integrity, and reduced permeability. Mechanistically, GSNOR orchestrated endothelial dysfunction independently of its enzymatic activity by binding the transcription factor ETS-related gene (ERG) and triggered its nuclear export through chromosome region maintenance 1. We synthesized NYY-001, an oral agent, that selectively blocks the GSNOR-ERG interaction. The direct targeting of NYY-001 to GSNOR was determined by resolving the crystal structure of their complex using cryo-electron microscopy. NYY-001 treatment enhanced postischemic neovascularization and restored vascular permeability in the peripheral vasculature in STZ-induced type 1 diabetes and db/db type 2 diabetes mouse models. These findings reveal a mechanistic role for the GSNOR-ERG complex in diabetic vascular complications and highlight NYY-001 as a promising therapeutic candidate.

OBJECTIVE:To identify the risk factors that influence the prognosis of patients with cervical spondylotic myelopathy (CSM). METHODS:Clinical data were collected from 158 CSM patients treated between January 2023 and January 2024 at a tertiary medical center. The data were retrospectively analyzed, with a 1-year follow-up. Based on the Japanese Orthopaedic Association (JOA) score, patients were categorized into good and poor recovery groups. Clinical characteristics, laboratory indices, and imaging findings were compared between the groups, and risk factors affecting CSM prognosis were identified. RESULTS:In a multivariable analysis, age, symptom duration, preoperative JOA score, spinal cord compression ratio, regulatory T cell (Treg) cell count, the number of surgical levels and diabetes history were identified as significant predictors of postoperative outcomes. Interestingly, Treg cell counts showed a novel positive correlation with improvement rates (p<0.001), suggesting their potential role in spinal cord recovery after surgery. CONCLUSION:These findings underscore the prognostic relevance of clinical and immunological factors for predicting surgical outcomes in CSM. The observed association between peripheral Treg counts and recovery rates reveals new insights into the immunological mechanisms underlying CSM prognosis, suggesting potential targets for personalized treatment strategies.

Study DesignCase-control Study.ObjectiveTo evaluate the alterations in lumbar stabilizing muscles, particularly the erector spinae (ES), lumbar multifidus (LM), and gluteus maximus (Gmax), and their association with dynamic sagittal imbalance (DSI) after ambulation.MethodsThis study included patients with low back pain and anterior trunk tilt (defined as the DSI group), alongside a control group without significant anterior trunk tilt (defined as the dynamic sagittal balance, DSB group). Propensity score matching was used to align participants for comparison. The participants underwent whole-spine radiography before and after a 10-min walk. Alterations in muscle activity and fatigue were evaluated through surface electromyography (sEMG).ResultsFollowing a 10-min walk, the DSI group exhibited marked deterioration in sagittal parameters, particularly in LL and PT, whereas the parameters in the DSB group remained unchanged. Significant intergroup differences were identified in the changes (Δ) of LL and PT. The sEMG results revealed that after the 10-min walk, the DSI group experienced increased muscle activity and notable fatigue in the ES, LM and Gmax. While the DSB group also showed changes in the activity of ES and LM after walking, the activation and fatigue metrics of the LM didn't demonstrate significant alterations. In contrast, the DSI group exhibited substantially greater changes in the activation of ES and LM, as well as the fatigue levels of LM.ConclusionThis study highlighted the pivotal role of lumbar stabilizing muscles, particularly the LM, whose aberrant activation and fatigue were identified as key contributors to the progression of DSI.

Spinal cord injury (SCI) substantially affects functional capacity and the immune system plays a crucial role in recovery. Examining alterations in microglia metabolism can lead to improved repair mechanisms; however, the molecular subtyping of microglia lacks consensus. In this study, the effects of SCI on macrophages and microglia in mice are investigated to identify tailored therapeutic targets and interventions for patients with SCI. Macrophages infiltrate the spinal cord shortly after injury; however, infiltration decreases over time. Microglial phagocytosis of myelin debris is associated with increased lipid accumulation. Macrophage deletion improves outcomes, whereas microglial deletion worsens them. The PLIN2+ microglia subtype in lipid droplet formation shows abnormal activation of the Pparg signaling pathway compared with that with other subtypes. PPARG promotes lipid metabolism and recovery, and atorvastatin (a PPARG agonist) reverses altered metabolic processes. Macrophages and microglia play complex roles in SCI. Targeting PPARG and its agonists is a promising therapeutic approach for SCI.

The study aimed to evaluate the reliability of the intraoperative extended tangential view (ETV) in assessing the reduction and fixation of the dorsoulnar fragment (DUF) during the treatment of comminuted distal radius fractures (DRFs) with volar plates. A retrospective review included 26 patients who underwent open reduction and volar locking plate internal fixation for AO C3-type DRFs with DUF between March 2023 and January 2024. Each patient received intraoperative ETV fluoroscopy and immediate postoperative wrist CT scans. DUF reduction quality was classified simply as excellent (anatomical reduction), good (<2 mm residual displacement), or poor (> 2 mm displacement). Both reduction quality and screw position relative to DUF were independently evaluated through fluoroscopy and CT. The study found consistent results across both methods: 23 reductions were excellent, 2 were good, and 1 was poor. The screw's mean distance to the distal radioulnar joint was 6.19 ± 2.76 mm on ETV compared to 4.21 ± 2.05 mm on CT, with a Pearson correlation of 0.925 (P < .05). The screw tip's distance to the dorsal cortex measured 3.69 ± 1.08 mm on ETV versus and 2.72 ± 1.01 mm on CT, with a correlation of 0.937 (P < .05). When compared to the postoperative CT evaluation, which was deemed the gold standard, the intraoperative ETV measurements displayed excellent accuracy and substantial relevance to the CT findings. The study suggests that the intraoperative ETV is a valuable tool for assessing the reduction and fixation quality of the DUF in comminuted DRFs. Level IV, retrospective case series.

Spinal cord injury (SCI) causes irreversible motor and sensory dysfunction. Initial mechanical injury breaches the blood-spinal cord barrier (BSCB), triggering a rapid influx of neutrophils. However, previous studies on neutrophils after SCI have been relatively limited, the function and heterogeneity of neutrophils need further study. Here, we identified 3 distinct neutrophil subclusters post-SCI using scRNA-seq in SCI mouse models. Additionally, elevated levels of CD177+ neutrophils may aggravate inflammation and neuronal impairment based on our data from SCI patients and mice models. Further in vivo and in vitro assays indicate that CD177+ neutrophils induce pro-inflammatory polarization of macrophages and microglia via neutrophil extracellular traps (NETs) formation in a peptidyl arginine deiminase 4 (PAD4) and reactive oxygen species (ROS)-dependent manner thus inducing neuronal apoptosis. Additionally, bone marrow transplantation from Cd177 knockout (KO) to Cd177 wild-type (WT) mice improved functional recovery post-SCI. These findings elucidate the role of CD177+ neutrophils in SCI-related inflammation and highlight their potential as therapeutic targets.

BACKGROUND:Destruction of the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI) can result in various harmful cytokines, neutrophils, and macrophages infiltrating into the injured site, causing secondary damage. Growing evidence shows that M2 macrophages and their small extracellular vesicles (sEVs) contribute to tissue repair in various diseases. METHODS AND RESULTS:In our previous proteomics-based analysis of protein expression profiles in M2 macrophages and their sEVs (M2-sEVs), the proteoglycan perlecan, encoded by HSPG2, was found to be upregulated in M2-sEVs. Perlecan is a crucial component of basement membranes, playing a vital role in stabilising BSCB homeostasis and functions through its interactions with other matrix components, growth factors, and receptors. Here, we verified the high levels and remarkable therapeutic effect of M2-sEV-derived perlecan on the permeability of spinal cord microvascular endothelial cells exposed to oxygen glucose deprivation and reoxygenation in vitro. We also decorated the surface of M2-sEVs with a fusion protein comprising the N-terminus of Lamp2 and arginine glycine aspartic acid (RGD) peptides, which have an affinity for integrin αvβ3 and are primarily present on neovascular endothelium surfaces. In SCI model mice, these RGD-M2-sEVs accumulated at injured sites, promoting BSCB restoration. Finally, we identified M2-sEV-derived perlecan as a key player in regulating BSCB integrity and functional recovery post-SCI. CONCLUSION:Our results indicate that RGD-M2-sEVs promote BSCB restoration by transporting perlecan to neovascular endothelial cells, representing a potential strategy for SCI treatment. KEY POINTS:Perlecan, a crucial component of basement membranes that plays a vital role in stabilising BSCB homeostasis and functions, was found to be upregulated in M2-sEVs. M2-sEVs decorated with RGD peptide can effectively target the neovascular endothelium surfaces at the injured spinal cord site. RGD-M2-sEVs promote BSCB restoration by transporting perlecan to neovascular endothelial cells, representing a potential strategy for SCI treatment.

Calcaneal fractures usually arise from high-energy trauma and predominantly impact young individuals. In older adults (aged ≥ 50 years), declining bone density and muscle strength increase fracture risk from low-energy trauma, leading to a bimodal epidemiological distribution. The intricacies of calcaneal fractures in older adults, alongside osteoporosis and soft tissue fragility, complicate surgical intervention. This study aims to analyze age-related differences in calcaneal fracture characteristics using three-dimensional(3D) mapping and assess their impact on medial incision design. A total of 95 patients with closed calcaneal fractures were categorized into two groups: Younger (< 50 years, n = 61) and Older (≥ 50 years, n = 34). The process of 3D fracture mapping was executed utilizing Mimics and 3-matic software, alongside the reconstruction of soft tissue, which encompassed the posterior tibial neurovascular bundle. Differences in fracture distribution and incision parameters (length, α angle, D1, and D2) were statistically analyzed, with p < 0.05 considered statistically significant. Fracture lines in both groups were predominantly located around the lateral Gissane’s angle and critical weight-bearing areas of the calcaneus. In the Younger Group, fracture lines were long, continuous, and involved fewer fragments, correlating with high-energy trauma. The Older Group showed more comminuted lines, characteristic of osteoporotic fractures. The α angle and D1 distance were significantly smaller in the Older Group (p < 0.05), indicating closer proximity to the medial malleolus. D2 values were also smaller (p < 0.05), with 48.65

Small extracellular vesicles (sEVs) are increasingly regarded as a unique class of bioactive materials whose intrinsic membrane composition and nanoscale architecture provide a versatile platform for therapeutic engineering. Rather than passive carriers, sEVs can be actively programmed through diverse strategies to achieve efficient loading, precise targeting, and functional integration with synthetic systems. Endogenous modulation of donor cells—via genetic editing, priming with bioactive glass, cytokine stimulation, or hypoxic cues—enables selective packaging of nucleic acids, proteins, and metabolites into secreted vesicles. Exogenous techniques, including electroporation, sonication, and extrusion, allow controlled incorporation of therapeutic drugs or genome-editing complexes such as CRISPR/Cas. In parallel, surface modifications based on Lamp2b-fusion scaffolds, aptamers, antibodies, and click chemistry confer tissue tropism and extend circulation time. Integration with nanomaterials, scaffolds, and microfluidic platforms further enhances stability, scalability, and reproducibility, positioning sEVs at the intersection of biology and materials science. This review highlights recent advances in engineering sEVs as programmable bioactive materials and discusses their potential to transform regenerative medicine, oncology, and precision therapeutics.

The spatiotemporal dynamics and specific roles of regulatory T (Treg) cells in spinal cord injury (SCI) remain unclear. Using single-cell RNA sequencing, flow cytometry, and immunofluorescence, we found that thymus-derived Treg cells infiltrate the injured spinal cord via peripheral blood around 3 days post-SCI. Treg cell depletion worsened SCI and impaired long-term recovery. Transcriptomic profiling revealed strong anti-inflammatory functions of Treg cells and the potential to regulate cholesterol metabolism in neighboring microglia. Further single-cell RNA sequencing uncovered the clonality of SCI-associated Treg cells. Major histocompatibility complex class II (MHC II) expression on microglia, not macrophages, was crucial for sustaining Treg cell numbers and neuroprotective function, with myelin-phagocytosing microglia-activated Treg cells showing significant neuroprotective effects. Treg cells mitigated microglial inflammation via CTLA-4 and upregulated the ATP-binding cassette transporter G1 (Abcg1) receptor in microglia, helping to manage myelin load and reduce lipid droplet formation. Our findings offer mechanistic insights into SCI-associated Treg cells and lay the groundwork for future Treg-based therapies in SCI treatment.

Spinal cord injury (SCI) is a severe neurological disorder that significantly impacts patients’ quality of life. Following SCI, the blood-spinal cord barrier (BSCB) is destroyed, leading to ischemia and hypoxia, which further exacerbates the imbalance in the spinal cord microenvironment. A2-type astrocytes, which arise under ischemic and hypoxic conditions, have been reported to promote SCI repair. However, the roles of exosomes derived from A2 astrocytes (A2-Exos) in SCI have not been explored. This study aims to investigate the role of A2-Exos in SCI repair, particularly in BSCB restoration, and to elucidate its potential mechanisms. GEO database analysis, western blotting, and immunofluorescence were used to detect A2 astrocyte polarization after SCI in mice. In vitro, A2 astrocytes were obtained through hypoxia induction, and A2-Exos were extracted via ultracentrifugation. An in vivo SCI model and a series of in vitro experiments demonstrated the reparative effects of A2-Exos on BSCB following SCI. Furthermore, miRNA sequencing analysis and rescue experiments confirmed the role of miRNAs in A2-Exos-mediated BSCB repair. Finally, luciferase assays and western blotting were performed to investigate the underlying mechanisms. The results showed that A2-Exos promote motor function recovery and BSCB repair in mice following SCI. In vitro, A2-Exos facilitated BSCB reconstruction and endothelial cell autophagy. miRNA sequencing identified miR-5121 as the most significantly enriched miRNA in A2-Exos, suggesting its involvement in BSCB repair and autophagy regulation. AKT2 was identified as a potential downstream target of miR-5121. Functional gain- and loss-of-function experiments further validated the miR-5121/AKT2 axis. Finally, we demonstrated that the AKT2/mTOR/p70S6K pathway may mediate the effects of miR-5121 in A2-Exos on BSCB repair.

Background:Clinical management of lumbar infectious spondylodiscitis is challenging due to its variable presentation and complex course, and its treatment remains controversial. This study aims to evaluate the clinical efficacy of unilateral biportal endoscopic (UBE) debridement and drainage for treating lumbar infectious spondylodiscitis. Methods:We retrospectively analysed sixteen patients diagnosed with lumbar infectious spondylodiscitis who underwent UBE debridement and drainage between April 2022 and July 2023. Biopsy specimens were sent to the laboratory to identify pathogens immediately after surgeries. Clinical outcomes were assessed by the visual analog scale (VAS) scores of the back, Oswestry Disability Index (ODI), the modified MacNab criteria (MNC), and regular serological tests at pre- and post-operation. Results:Fourteen patients (87.5%) experienced a significant improvement in their clinical symptoms. Their VAS and ODI scores significantly improved compared to those before the operation throughout the follow-up (p<0.05). The modified MNC at the last follow-up indicated that 87.50% of these participants were rated excellent or good. Causative bacteria were identified in 13 (81.25%) of 16 biopsy specimens. At the final follow-up, all patients' kyphotic angle changes were less than 10° without spinal instability. A 12-month follow-up CT scan revealed bony intervertebral fusion in 10 cases (62.5%). The postoperative regular serological tests were significantly improved than before surgery (p< 0.05). No recurrent infections or significant surgery-related complications were observed during postoperative follow-up. Conclusion:UBE surgery was successful in debridement, back pain relief, and bacteriologic diagnosis of lumbar infectious spondylodiscitis. This procedure could be an effective alternative for patients when conservative treatments fail.