Cervical spondylosis and low back pain caused by intervertebral disc degeneration (IVDD) are among the leading causes of clinical disability. Although excessive reactive oxygen species (ROS) are established drivers of IVDD, the mechanisms linking ROS accumulation to disc cell dysfunction, cell death programs, and disruption of intervertebral disc tissue homeostasis remain insufficiently elucidated, limiting the development of effective redox-targeted therapies. Here, we revealed the "ROS-Mitochondrial dysfunction-Ferritinophagy" oxidative stress feedback loop serves as the central mechanism driving ROS-induced nucleus pulposus cell (NPC) ferroptosis to promote IVDD progression. Furthermore, we identified the membrane protein ADGRG1 as a biomarker of ROS-induced ferroptosis in injured NPCs and developed ADGRG1-tethered peptide (A1TP)-modified hypoxia preconditioned extracellular vesicles (HX-EVs) with targeted antioxidant therapeutic potential. The engineered HX-EVs selectively accumulated in injured NPCs and delivered high levels of taurine, which bound to LKB1 (Glu165, Arg301) and MO25 (Arg194, Leu197) residues to facilitate the assembly of the LKB1-STRAD-MO25 kinase complex. This interaction regulated the expression of NCOA4 and TFAM by activating the AMPK/NRF2 signaling pathway, which suppressed ferritinophagy, enhanced mitochondrial repair and regeneration, and protected NPCs from ROS-induced ferroptosis, ultimately facilitating the repair of degenerated intervertebral discs. In summary, the A1TP-HX-EV system developed in this study provides a promising theranostic application for IVDD and offers valuable insights into the mechanisms of targeted HX-EV delivery and intervertebral disc regeneration.

Background:Ganglioneuroma (GN) of the lumbar spine is rare, typically occurring in children and young adults. Its diagnosis in middle-aged patients can be challenging. This paper reports a case of a dumbbell-shaped lumbar GN in a middle-aged woman. Case: A 46-year-old woman presented with low back pain and radiating leg pain. MRI revealed a dumbbell-shaped mass at the L2 level. She underwent posterior microscopic total tumor resection with L2-L3 pedicle screw fixation. Postoperative pathology confirmed GN. Conclusion:At the 1-year follow-up, there was no recurrence. For dumbbell-shaped lumbar GN, a posterior approach combined with internal fixation is an effective strategy. This case suggests that GN should be considered in the differential diagnosis of foraminal masses in middle-aged patients.

Background:Postoperative re-fractures in elderly osteoporotic vertebral compression fracture (OVCF) patients with comorbidities pose a major clinical challenge, with rates up to 52%. Traditional risk models overlook complex underlying diseases interactions in elderly patients. This study pioneers a machine learning (ML) framework for this high-risk group, integrating multidimensional factors to predict re-fractures and identify novel predictors. Methods:We analyzed 560 OVCF patients with comorbidities who underwent percutaneous vertebroplasty (PVP). Fourteen characteristic variables-including scoliosis, chronic kidney disease (CKD), mental disorders, and cardiovascular comorbidities-were selected using feature engineering. Six ML models [Random Forest (RF), XGBoost, support vector machine (SVM), etc.,] were trained and validated. Model performance was rigorously assessed via AUC-ROC, precision-recall curves, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) values provided interpretable risk quantification. Results:The RF model achieved superior predictive performance (test AUC = 0.88, sensitivity = 0.77, specificity = 0.87), outperforming conventional approaches. Notably, we identified scoliosis (SHAP = 0.14), mental disorders (0.12), and CKD (0.10) as the three top risk factors, with biomechanical and comorbidity interactions playing pivotal roles. DCA confirmed high clinical utility, with RF providing the greatest net benefit across risk thresholds. Conclusion:This pioneering study establishes ML as a transformative tool for re-fracture prediction in OVCF patients with underlying diseases, uncovering previously underappreciated risk factors. Our findings highlight the critical need for integrated management of spinal deformity, mental health, and renal function in this vulnerable population. This ML framework offers a paradigm shift in personalized risk stratification and postoperative care.

The abnormal osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is an important cause of senile osteoporosis (SOP). Glutamine synthetase (GLUL) is a key enzyme in glutamine biosynthesis; however, its functional role in SOP remains unclear. Here, we found that GLUL expression was downregulated in the BMSCs of SOP patients. Mice with BMSC-specific Glul-knockout (KO) exhibited dysplasia of the skull and phalanges and osteoporosis due to disordered osteogenic differentiation. Mechanistically, GLUL competitively bound to the Tripartite Motif Containing 25 (TRIM25) SPRY subunit, reduced the ubiquitin-mediated degradation of UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1) and increased the synthesis of uridine 5-diphosphate N-acetylglucosamine (UDP-GlcNAc), thereby regulating the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of serine 296 residues and increasing Forkhead Box O3 (FOXO3) stability to reduce oxidative stress. Moreover, blocking the O-GlcNAcylation of FOXO3 at Ser296 inhibited osteogenic differentiation. Finally, GLUL supplementation specifically in BMSCs slowed bone loss in SOP model mice. Overall, our study suggests that GLUL plays an important role in regulating osteogenic differentiation and bone development, which may have implications for SOP treatment.

Postoperative refracture of osteoporotic compression fractures in the elderly due to underlying illnesses is a complicated matter involving several variables. A multidisciplinary approach involving orthopedics, geriatrics, endocrinology, and rehabilitation medicine is necessary for an investigation of these issues. investigating the impact of older patients’ underlying medical conditions on the refracture of osteoporotic compression fractures following surgery. A retrospective analysis was conducted on 2383 patients between August 2013 and August 2023. 550 patients with comorbid geriatric underlying diseases were screened, 183 patients underwent refractories, and 367 patients were classified as non-refractories. The patients were then divided into two groups: those undergoing refractories and those not, and the underlying diseases of the patients in both groups were examined using ROC curves and unifactorial and multifactorial logistic regression analyses. Among the patients gathered, the frequency of re-fracture was 33.3

Abstract Background Postoperative refracture of osteoporotic compression fractures in the elderly due to underlying illnesses is a complicated matter involving several variables. A multidisciplinary approach involving orthopedics, geriatrics, endocrinology, and rehabilitation medicine is necessary for an investigation of these issues. investigating the impact of older patients' underlying medical conditions on the refracture of osteoporotic compression fractures following surgery. Methods A retrospective analysis was conducted on 2383 patients between August 2013 and August 2023. 550 patients with comorbid geriatric underlying diseases were screened, 183 patients underwent refractories, and 367 patients were classified as non-refractories. The patients were then divided into two groups: those undergoing refractories and those not, and the underlying diseases of the patients in both groups were examined using ROC curves and unifactorial and multifactorial logistic regression analyses. Results Among the patients gathered, the frequency of re-fracture was 33.3%. A statistically significant difference was observed when re-fracture was linked to patients with long-term alcohol consumption, operated vertebrae ≤ 1, hypertension, COPD, diabetes mellitus, stroke sequelae, conservative treatment of coronary heart disease, trauma, mental abnormality, scoliosis, and chronic renal disease. Having hypertension decreased the risk of re-fracture (P = 0.018, OR = 0.548), while alcohol intake ≥ 10years (P = 0.003, OR = 2.165), mental abnormality (P < 0.001, OR = 4.093), scoliosis (P < 0.001, OR = 6.243), chronic kidney disease (P = 0.002, OR = 2.208), and traumatic injuries (P = 0.029, OR = 3.512) were the risk factors examined in a binary logistic regression analysis. The results of multiple linear stepwise regression analysis indicated that re-fracture was more influenced by scoliosis. Conclusions Hypertensive disorders were protective factors against the formation of re-fracture, while alcohol intake usage for more than ten years, psychological abnormalities, scoliosis, chronic kidney disease, and trauma were risk factors. Scoliosis had the highest influence on re-fracture.

Intervertebral disc degeneration (IDD) leads to low back pain (LBP). This study aimed to determine the regulation of IDD by competing endogenous RNAs (ceRNAs). We obtained the GSE63492, GSE124272, and GSE129789 datasets from the Gene Expression Omnibus database. The changes of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in IDD were characterized. The significantly changed mRNAs were subjected to protein-protein interaction analysis using the STRING database, and its functions and involved pathways were analyzed using the DAVID database and gene set enrichment analysis (GSEA). The significant changed lncRNAs, miRNAs and mRNAs were linked in a ceRNA network based on their interactions - predicted by Starbase and miRWalk. Differentially methylated loci of significantly changed mRNAs in early and advanced IDD were compared using the GSE129789 dataset. We identified 245 significantly changed mRNAs, 133 lncRNAs, and 228 miRNAs between patients with IDD and normal individuals. GSEA suggested that 17 pathways related to cell proliferation were activated while 35 cell signaling and immune-related pathways were suppressed in IDD. The following ceRNA network in IDD was built: LINC00665/hsa-miR-7-5p/FZD3, ZNF549; LINC00665/hsa-let-7e-5p/FZD3, ACVR2B; TRG-AS1/hsa-miR-574-5p/ACVR2B, P3H2; TRG-AS1/ hsa-let-7e-5p/FZD3, ACVR2B; and ZNF571-AS1/let-7e-5p/ACVR2B, FZD3. A lncRNA-miRNAmRNA ceRNA network which might regulate the progression of IDD was developed.

Genetic biomarkers for the diagnosis of ankylosing spondylitis (AS) remain unreported except for human leukocyte antigen B27 (HLA-B27). Therefore, the aim of the present study was to screen the differentially expressed genes (DEGs), and those that also possess differential single nucleotide polymorphism (SNP) loci in the whole blood of AS patients compared with healthy controls by integrating two mRNA expression profiles (GSE73754 and GSE25101) and SNP microarray data (GSE39428) collected from the Gene Expression Omnibus (GEO). Using the t-test, 1,056 and 1,073 DEGs were identified in the GSE73754 and GSE25101 datasets, respectively. Among them, 234 DEGs were found to be shared in both datasets, which were subsequently overlapped with 122 differential SNPs of genes in the GSE39428 dataset, resulting in identification of two common genes [eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and serpin family A member 1 (SERPINA1)]. Their expression levels were significantly upregulated and the average expression log R ratios of SNP sites in these genes were significantly higher in AS patients than those in controls. Function enrichment analysis revealed that EEF1E1 was involved in AS by influencing the aminoacyl-tRNA biosynthesis, while SERPINA1 may be associated with AS by participating in platelet degranulation. However, only the genotype and allele frequencies of SNPs (rs7763907 and rs7751386) in EEF1E1 between AS and controls were significantly different between AS and the controls, but not SERPINA1. These findings suggest that EEF1E1 may be an underlying genetic biomarker for the diagnosis of AS.

Blood blister–like aneurysms (BBAs) are rare but dangerous and challenging to treat. Recurrence and rebleeding are often reported, and many neurosurgeons and interventional radiologists are discouraged by such poor outcomes. Currently, there is no standard method to treat this type of aneurysm.We describe 5 cases of ruptured BBAs in the supraclinoid segment of the internal carotid artery, which were treated successfully using a suturing technique. No patient experienced recurrence or rebleeding, and all patients had a good prognosis.We conclude that this suturing technique is an optional safe and reliable method to treat BBAs.

The role of AMP-activated protein kinase (AMPK) in the regulation of energy metabolism and the control of skeletal muscle regeneration post injury has been described previously. It remains unknown whether this metabolic sensor plays a role in the mechanism of axonal regeneration post injury. In this study, we used a sciatic nerve crushed mouse model to detect the expression of AMPK in sciatic nerve and spinal motor neurons at 1 week, 2 weeks and 3 weeks after injury by immunofluorescence staining. Electrophysiological and histopathological studies were used to confirm the nerve injury and regeneration. Our results showed that frequency of AMPK-positive spinal motor neurons was significantly higher on day 7 after sciatic nerve crush (SNC) and peaked on day 14. No expression of AMPK was detected in axons of the sciatic nerve before and after the injury. Taken together, our study suggested a possible role of AMPK in the mechanism of motor nerve regeneration after injury.

BACKGROUND:Isolating of primary motor neurons from animal embryos is critical for the study of neurological disease including mechanistic discovery and therapeutic development. Density gradient centrifuge taking advantage of the buoyant of motor neuron permits the enrichment of motor neurons. Despite the metrizamide, an OptiPrep medium has been introduced to separate the motor neurons by gradient centrifuge. NEW METHOD:We hereby used single density gradient of OptiPrep medium to isolate the spinal motor neurons from the fetal mouse. RESULTS:Single density gradient of OptiPrep medium is effective to isolate spinal motor neurons from the fetal mouse. The immunofluorescence staining analysis showed that the purity of cultured motor neurons at 72h was between 90% and 95%. COMPARISON WITH EXISTING METHOD:Four gradients of OptiPrep medium have been previously used to isolate the motor neurons from spinal cord of mouse. In this study, the single gradient of OptiPrep medium was demonstrated to effectively isolate spinal motor neurons from the fetal mouse. CONCLUSIONS:The single gradient of OptiPrep medium is enough to produce high purity of spinal motor neurons from the fetal mouse.