Hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles promote the recovery of spinal cord injury by affecting the phenotype of astrocytes through the miR-21/JAK2/STAT3 pathway.

BACKGROUND: Secondary injury after spinal cord injury (SCI) is a major obstacle to their neurological recovery. Among them, changes in astrocyte phenotype regulate secondary injury dominated by neuroinflammation. Hypoxia-preconditioned mesenchymal stem cells (MSCs)-derived extracellular vesicle (H-EV) plays a multifaceted role in secondary injury by interacting with cellular components and signaling pathways. They possess anti-inflammatory properties, regulate oxidative stress, and modulate apoptotic pathways, promoting cell survival and reducing neuronal loss. Given the unique aspects of secondary injury, H-EV shows promise as a therapeutic approach to mitigate its devastating consequences. Our study aimed to determine whether H-EV could promote SCI repair by altering the phenotype of astrocytes. METHODS: Rat bone marrow MSCs (BMSCs) and EVs secreted by them were extracted and characterized. After the SCI model was successfully constructed, EV and H-EV were administered into the tail vein of the rats, respectively, and then their motor function was evaluated by the Basso-Beattie-Bresnahan (BBB) score, Catwalk footprint analysis, and electrophysiological monitoring. The lesion size of the spinal cord was evaluated by hematoxylin-eosin (HE) staining. The key point was to use glial fibrillary acidic protein (GFAP) as a marker of reactive astrocytes to co-localize with A1-type marker complement C3 and A2-type marker S100A10, respectively, to observe phenotypic changes in astrocytes within tissues. The western blot (WB) of the spinal cord was also used to verify the results. We also compared the efficacy differences in apoptosis and inflammatory responses using terminal deoxynucleotidyl transferase dUTP terminal labeling (TUNEL) assay, WB, and enzyme-linked immunosorbent assay (ELISA). Experiments in vitro were also performed to verify the results. Subsequently, we performed microRNA (miRNA) sequencing analysis of EV and H-EV and carried out a series of knockdown and overexpression experiments to further validate the mechanism by which miRNA in H-EV plays a role in promoting astrocyte phenotypic changes, as well as the regulated signaling pathways, using WB both in vivo and in vitro. RESULTS: Our findings suggest that H-EV is more effective than EV in the recovery of motor function, anti-apoptosis, and anti-inflammatory effects after SCI, both in vivo and in vitro. More importantly, H-EV promoted the conversion of A1 astrocytes into A2 astrocytes more than EV. Moreover, miR-21, which was found to be highly expressed in H-EV by miRNA sequencing results, was also demonstrated to influence changes in astrocyte phenotype through a series of knockdown and overexpression experiments. At the same time, we also found that H-EV might affect astrocyte phenotypic alterations by delivering miR-21 targeting the JAK2/STAT3 signaling pathway. CONCLUSION: H-EV exerts neuroprotective effects by delivering miR-21 to promote astrocyte transformation from the A1 phenotype to the A2 phenotype, providing new targets and ideas for the treatment of SCI.

Percutaneous full endoscopic tumourectomy of a lumbar epidural schwannoma via transforaminal approach: a case report and systematic review of the literature.

STUDY DESIGN: Report of three patients undergoing lumbar epidural schwannoma tumourectomy. Percutaneous endoscopy has been routinely used in the treatment of disk herniation but has not been reported in the management of intraspinal tumours. METHODS: Three patients diagnosed with schwannoma by imaging and pathological examination underwent percutaneous full endoscopic tumourectomy. A 5-mm incision was made, the puncture needle passed through the skin, subcutaneous tissue and the deep fascia and vertebral muscles to the intervertebral foramen area. Next, a working cannula was inserted into the lesion area. Foraminotomy was completed by trephine and microscopic power drill if the foramen was stenosed. Tumour tissue was totally removed piecemeal. After probing the nerve foramen and the nerve root satisfactorily, the working cannula was removed and the incision sutured. RESULTS: Three patients were operated successfully. Symptoms recovered in all cases and no complication or recurrence was found on follow-up. CONCLUSIONS: This case report presents a new technique for non-infiltrating extradural lumbar tumour treatment, demonstrating feasibility and safety of percutaneous full endoscopic lumbar tumourectomy.

Causal associations between gut microbiota and regional cortical structure: a Mendelian randomization study.

Introduction: Observational studies have reported associations between gut microbiota composition and central nervous system diseases. However, the potential causal relationships and underlying mechanisms remain unclear. Here, we applied Mendelian randomization (MR) to investigate the causal effects of gut microbiota on cortical surface area (SA) and thickness (TH) in the brain. Methods: We used genome-wide association study summary statistics of gut microbiota abundance in 18,340 individuals from the MiBioGen Consortium to identify genetic instruments for 196 gut microbial taxa. We then analyzed data from 56,761 individuals from the ENIGMA Consortium to examine associations of genetically predicted gut microbiota with alterations in cortical SA and TH globally and across 34 functional brain regions. Inverse-variance weighted analysis was used as the primary MR method, with MR Egger regression, MR-PRESSO, Cochran's Q test, and leave-one-out analysis to assess heterogeneity and pleiotropy. Results: At the functional region level, genetically predicted higher abundance of class Mollicutes was associated with greater SA of the medial orbitofrontal cortex (ß = 8.39 mm2, 95% CI: 3.08-13.70 mm2, p = 0.002), as was higher abundance of phylum Tenericutes (ß = 8.39 mm2, 95% CI: 3.08-13.70 mm2, p = 0.002). Additionally, higher abundance of phylum Tenericutes was associated with greater SA of the lateral orbitofrontal cortex (ß = 10.51 mm2, 95% CI: 3.24-17.79 mm2, p = 0.0046). No evidence of heterogeneity or pleiotropy was detected. Conclusion: Specific gut microbiota may causally influence cortical structure in brain regions involved in neuropsychiatric disorders. The findings provide evidence for a gut-brain axis influencing cortical development, particularly in the orbitofrontal cortex during adolescence.

Preparation of (R)-3-aminopiperidine by resolution with optically active cyclic phosphoric acids.

(R)-3-aminopiperidine ((R)-APD), a key intermediate for alogliptin, trelagliptin, and linagliptin, was successfully resolved from racemic 3-aminopiperidine with an enantiomerically pure resolving agent, namely, (R)-4-(2-chlohydroxy-1.3.2-dioxaphosphorinane 2-oxide ((R)-CPA), via diastereomeric salt formation. By this resolution approach, (R)-3-aminopiperidine was obtained in 99.5% yield with 99.6%e.e.

Comparative Clinical Effectiveness and Safety of Bone Morphogenetic Protein Versus Autologous Iliac Crest Bone Graft in Lumbar Fusion: A Meta-analysis and Systematic Review.

STUDY DESIGN: This is a systematic literature review and meta-analysis. OBJECTIVE: We aimed to evaluate the efficacy and safety of recombinant human bone morphogenetic protein (RhBMP) and autologous iliac crest bone graft (ICBG) in lumbar fusion. SUMMARY OF BACKGROUND DATA: RhBMP has been emphasized in lumbar fusion due to high fusion success rate. However, ICBG remains the criterion standard graft approach for lumbar fusion. The safety and effectiveness of rhBMP are controversial. METHODS: Prospective randomized controlled trials were searched from PubMed, EMBASE, and Cochrane Central Register of Controlled Trails by using Medical Subject Headings terms "bone morphogenetic protein,' "bone transplantation,' and "spinal fusion.' Two independent investigators screened eligible studies, assessed the bias of original articles, extracted data including fusion success, Oswestry disability index improvement, improved short form 36 questionnaire scores, adverse events and re-operation, and a subgroup analysis. The GRADE approach was used to grade quality of evidence. RESULTS: Twenty randomized controlled trials (2185 patients) met the inclusion criteria. There were higher fusion success rate (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.88-7.63, P = 0.0002), better improvement of Oswestry Disability Index (mean difference 1.54, 95% CI 0.18-2.89, P = 0.03), and lower re-operation rate (OR 0.59, 95% CI 0.43-0.80, P = 0.0007) in rhBMP group. Heterogeneity was obvious in fusion success rate (I = 58%); hence, a subgroup analysis, based on protein type (rhBMP-2 or rhBMP-7), was performed, which suggested that only rhBMP-2 was better than ICBG for lumbar fusion. There was no difference in the incidence of adverse events between rhBMP and ICBG (OR 0.91, 95% CI 0.70-1.18, P = 0.47). CONCLUSION: In lumbar fusion, rhBMP-2 exhibited a higher fusion success rate and reduced the risk of re-operation. No difference in complication rate is between rhBMP (rhBMP-2 and rhBMP-7) and ICBG. We suggest rhBMP especially rhBMP-2 as an effective substitute for ICBG for lumbar fusion. LEVEL OF EVIDENCE: 1.

Effectiveness of personalized 3D printed models for patient education in degenerative lumbar disease.

OBJECTIVE: Three-dimensional printing may play an important role in patients' education. The objective of this study was to assess the effectiveness of personalized 3D printed models for increasing patient understanding of their medical condition and surgical plan. METHODS: Forty-five patients with degenerative lumbar diseases were randomized by block design into three groups: educational program presented by CT & MRI imaging (care-as-usual), 3D reconstructions, or personalized 3D printed models. Patients' level of understanding and satisfaction were evaluated by two questionnaires one day after education. RESULTS: Patients educated with personalized 3D printed models demonstrated an expanded level of understanding than patients educated with CT & MRI imaging (care-as-usual) (P ＜ 0.05) and 3D reconstructions (P ＜ 0.05). Personalized 3D printed models also resulted in a higher degree of patient satisfaction (P ＜ 0.05). CONCLUSIONS: Personalized 3D printed models and 3D reconstructions can simplify and enhance understanding of lumbar anatomy, physiology, and patients' disease and surgical plan. Personalized 3D printed models also enhance patients' subjective satisfaction. PRACTICE IMPLICATIONS: Personalized 3D printed models for patient education are feasible and could be generalized for degenerative lumbar diseases.