Identifying and exploring the favorable factors that help to slow the progression of disease in patients with mild cervical spondylotic myelopathy.

To explore the favorable factors that help slow the progression of disease in patients with mild Cervical Spondylotic Myelopathy (CSM). A retrospective analysis was conducted, involving the enrollment of 115 CSM patients. The categorization of patients into two groups was based on the duration of symptoms, assessments using the mJOA scale and Health Transition (HT) scores: mild-slow group and severe-rapid group. We found that the patients in both groups had similar degrees of spinal cord compression, but mild-slow group were older and had smaller C2-C7 cobb angle (Flexion) (CL(F)), C2-C7 cobb angle (Range of motion) (CL(ROM)), Transverse area (TA), Normal-TA, Compressive spinal canal area (CSCA), Normal-Spinal canal area (Normal-SCA) and lower Spinal cord increased signal intensity (ISI) Grade than the severe-rapid group. A binary logistic regression analysis showed that CL(ROM) and Normal-TA are favorable factors to help slow the progression of disease patients with mild CSM. Through ROC curves, we found that when CL(ROM) < 39.1° and Normal-TA < 80.5mm2, the progression of disease in CSM patients may be slower. Meanwhile, we obtained a prediction formula by introducing joint prediction factor: L = CL(ROM) + 2.175 * Normal-TA. And found that when L < 213.0, the disease progression of patients may be slower which was superior to calculate CL(ROM) and Normal-TA separately.

An injectable and photocurable methacrylate-silk fibroin/nano-hydroxyapatite hydrogel for bone regeneration through osteoimmunomodulation.

Tissue engineering has emerged as a promising approach for addressing bone defects. Most of the traditional 3D printing materials predominantly relying on polymers and ceramics. Although these materials exhibit superior osteogenic effects, their gradual degradation poses a limitation. Digital light processing (DLP) 3D bioprinting that uses natural biomaterials as bioinks has become one of the promising strategies for bone regeneration. In this study, we introduce a hydrogel biomaterial derived from silk fibroin (SF). Notably, we present the novel integration of nano-hydroxyapatite (nHA) into the hydrogel, forming a composite hydrogel that rapidly cross-links upon initiation. Moreover, we demonstrate the loading of nHA through non-covalent bonds in SilMA. In vitro experiments reveal that composite hydrogel scaffolds with 10 % nHA exhibit enhanced osteogenic effects. Transcriptomic analysis indicates that the composite hydrogel promotes bone regeneration by inducing M2 macrophage polarization. Furthermore, rat femoral defect experiments validate the efficacy of SilMA/nHA10 in bone regeneration. This study synthesis of a simple and effective composite hydrogel bioink for bone regeneration, presenting a novel strategy for the future implementation of digital 3D printing technology in bone tissue engineering.

FUNDC1-induced mitophagy protects spinal cord neurons against ischemic injury.

Local ischemia and hypoxia are the most important pathological processes in the early phase of secondary spinal cord injury (SCI), in which mitochondria are the main target of ischemic injury. Mitochondrial autophagy, also known as mitophagy, acts as a selective autophagy that specifically identifies and degrades damaged mitochondria, thereby reducing mitochondria-dependent apoptosis. Accumulating evidence shows that the mitophagy receptor, FUN14 domain-containing 1 (FUNDC1), plays an important role in ischemic injury, but the role of FUNDC1 in SCI has not been reported. In this study, we aimed to investigate whether FUNDC1 can enhance mitophagy and inhibit neuronal apoptosis in the early stage of SCI. In a rat SCI model, we found that FUNDC1 overexpression enhanced neuronal autophagy and decreased neuronal apoptosis in the early stage of injury, thereby reducing spinal cord damage. In vitro studies showed that the neuroprotective effects of FUNDC1 were achieved by inhibiting mitochondria-dependent apoptosis and improving mitochondrial function. In addition, FUNDC1 enhanced mitophagy. The protective effects of FUNDC1 against apoptosis and mitochondrial dysfunction were reversed by 3-methyladenine (3-MA), an autophagy inhibitor. Taken together, our results confirm that FUNDC1 can protect against neuronal loss after SCI by inducing mitophagy, inhibiting mitochondria-dependent apoptosis, and improving mitochondrial function.

Apelin-13 Protects Neurons by Attenuating Early-Stage Postspinal Cord Injury Apoptosis In Vitro.

Apelin is a 77-amino-acid peptide that is an endogenous ligand for the G protein-coupled receptor APJ (Apelin receptor, APJ). Apelin-13, as the most bioactive affinity fragment of apelin, plays a role in energy metabolism, myocardial ischemia-reperfusion injury, and the regulation of the inflammatory response during oxidative stress, but its role in spinal cord injury is still unclear. This research identified and verified the differential expression of apelin in rat spinal cord injured tissues and normal spinal cord tissues by transcriptome sequencing in vivo and proved that apelin-13 protects neurons by strengthening autophagy and attenuating early-stage postspinal cord injury apoptosis in vitro. After constructing the model concerning a rat spinal cord hemisection damage, transcriptome sequencing was performed on the injured and normal spinal cord tissues of rats, which identified the differentially expressed gene apelin, with qRT-PCR detecting the representative level of apelin. The oxygen-glucose deprivation (OGD) model of PC12 cells was constructed in vitro to simulate spinal cord injury. The OGD injury times were 2 h, 4 h, 6 h, 8 h, and 12 h, and the non-OGD injury group was used as the control. The expression of apelin at each time point was observed by Western blotting. The expression of apelin was the lowest in the 6 h OGD injury group (p < 0.05). Therefore, the OGD injury time of 6 h was used in subsequent experiments. The noncytotoxic drug concentration of apelin-13 was determined with a Cell Counting Kit-8 (CCK-8) assay. An appropriate dose of apelin-13 (1 µM) significantly improved cell survival (p < 0.05). Thus, subsequent experiments selected a concentration of 1 µM apelin-13 as it significantly increased cell viability. Finally, we divided the experimental groups into four groups according to whether they received drugs (1 µM apelin-13, 24 h) or OGD (6 h): (1) control group: without apelin-13 or OGD injury; (2) apelin-13 group: with apelin-13 but no OGD injury; (3) OGD group: with OGD injury but without apelin-13; and (4) OGD + apelin-13 group: with apelin-13 and OGD injury. The TUNEL assay and flow cytometry results showed that compared with the OGD group, apoptosis in the OGD+Apelin-13 group was significantly reduced (p < 0.001). Determination of cell viability under different conditions by CCK-8 assay results displays that Apelin-13 can significantly improve the cell viability percentage under OGD conditions (p < 0.001). Western blotting results showed that apelin-13 decreased the expression ratios of apoptosis-related proteins Bax/Bcl-2 and cleaved-caspase3/caspase3 (p < 0.05), increasing the key to Beclin1-dependent autophagy pathway expression of the protein Beclin1. This finding indicates that apelin-13 protects neurons by strengthening autophagy and attenuating early-stage postspinal cord injury apoptosis in vitro.

The Pre-Operative Duration of Symptoms: The Most Important Predictor of Post-Operative Efficacy in Patients with Degenerative Cervical Myelopathy.

Objective. To explore the most important predictors of post-operative efficacy in patients with degenerative cervical myelopathy (DCM). Methods. From January 2013 to January 2019, 284 patients with DCM were enrolled. They were categorized based on the different surgical methods used: single anterior cervical decompression and fusion (ACDF) (n = 80), double ACDF (n = 56), three ACDF (n = 13), anterior cervical corpectomy and fusion (ACCF) (n = 63), anterior cervical hybrid decompression and fusion (ACHDF) (n = 25), laminoplasty (n = 38) and laminectomy and fusion (n = 9). The follow-up time was 2 years. The patients were divided into two groups based on the mJOA recovery rate at the last follow-up: Group A (the excellent improvement group, mJOA recovery rate >50%, n = 213) and Group B (the poor improvement group, mJOA recovery rate ≤50%, n = 71). The evaluated data included age, gender, BMI, duration of symptoms (months), smoking, drinking, number of lesion segments, surgical methods, surgical time, blood loss, the Charlson Comorbidity Index (CCI), CCI classification, imaging parameters (CL, T1S, C2-7SVA, CL (F), T1S (F), C2-7SVA (F), CL (E), T1S (E), C2-7SVA (E), CL (ROM), T1S (ROM) and C2-7SVA (ROM)), maximum spinal cord compression (MSCC), maximum canal compromise (MCC), Transverse area (TA), Transverse area ratio (TAR), compression ratio (CR) and the Coefficient compression ratio (CCR). The visual analog score (VAS), neck disability index (NDI), modified Japanese Orthopedic Association (mJOA) and mJOA recovery rate were used to assess cervical spinal function and quality of life. Results. We found that there was no significant difference in the baseline data among the different surgical groups and that there were only significant differences in the number of lesion segments, C2−7SVA, T1S (F), T1S (ROM), TA, CR, surgical time and blood loss. Therefore, there was comparability of the post-operative recovery among the different surgical groups, and we found that there were significant differences in age, the duration of symptoms, CL and pre-mJOA between Group A and Group B. A binary logistic regression analysis showed that the duration of the symptoms was an independent risk factor for post-operative efficacy in patients with DCM. Meanwhile, when the duration of symptoms was ≥6.5 months, the prognosis of patients was more likely to be poor, and the probability of a poor prognosis increased by 0.196 times for each additional month of symptom duration (p < 0.001, OR = 1.196). Conclusion. For patients with DCM (regardless of the number of lesion segments and the proposed surgical methods), the duration of symptoms was an independent risk factor for the post-operative efficacy. When the duration of symptoms was ≥6.5 months, the prognosis of patients was more likely to be poor, and the probability of a poor prognosis increased by 0.196 times for each additional month of symptom duration (p < 0.001, OR = 1.196).