STM2457 Inhibits METTL3-Mediated m6A Modification of miR-30c to Alleviate Spinal Cord Injury by Inducing the ATG5-Mediated Autophagy.

OBJECTIVE: The study aimed to investigate the role of N6-methyladenosine (m6A) modification in spinal cord injury (SCI) and its underlying mechanism, focusing on the interplay between m6A methyltransferase-like 3 (METTL3), miR-30c, and autophagy-related proteins. METHODS: An SCI model was established in rats, and changes in autophagy-related proteins, m6A methylation levels, and miR-30c levels were analyzed. Hydrogen peroxide (H2O2)-stimulated spinal cord neuron cells (SCNCs) were used to assess the impact of METTL3 overexpression. The effects of STM2457, an antagonist of METTL3, were evaluated on cell viability, apoptosis, and autophagy markers in H2O2-stimulated SCNCs. RESULTS: In the SCI model, decreased levels of autophagy markers and increased m6A methylation, miR-30c levels, and METTL3 were observed. Overexpression of METTL3 in SCNCs led to reduced cell viability, increased apoptosis, and suppressed autophagy. Conversely, co-overexpression of autophagy-related protein 5 (ATG5) or miR-30c inhibition reversed these effects. Knocking out METTL3 yielded opposite results. STM2457 treatment improved cell viability, reduced apoptosis, and upregulated autophagy markers in SCNCs, which also enhanced functional recovery in rats as measured by the Basso-Beattie-Bresnahan score and inclined plate test. CONCLUSION: STM2457 alleviated SCI by suppressing METTL3-mediated m6A modification of miR-30c, which in turn induces ATG5-mediated autophagy. This study provides insights into the role of m6A modification in SCI and suggests a potential therapeutic approach through targeting METTL3.

Functionalized 3D-printed GelMA/Laponite hydrogel scaffold promotes BMSCs recruitment through osteoimmunomodulatory enhance osteogenic via AMPK/mTOR signaling pathway.

The migration and differentiation of bone marrow mesenchymal stem cells (BMSCs) play crucial roles in bone repair processes. However, conventional scaffolds often lack of effectively inducing and recruiting BMSCs. In our study, we present a novel approach by introducing a 3D-bioprinted scaffold composed of hydrogels, with the addition of laponite to the GelMA solution, aimed at enhancing scaffold performance. Both in vivo and in vitro experiments have confirmed the outstanding biocompatibility of the scaffold. Furthermore, for the first time, Apt19s has been chemically modified onto the surface of the hydrogel scaffold, resulting in a remarkable enhancement in the migration and adhesion of BMSCs. Moreover, the scaffold has demonstrated robust osteogenic differentiation capability in both in vivo and in vitro environments. Additionally, the hydrogel scaffold has shown the ability to induce the polarization of macrophages from M1 to M2, thereby facilitating the osteogenic differentiation of BMSCs via the bone immune pathway. Through RNA-seq analysis, it has been revealed that macrophages regulate the osteogenic differentiation of BMSCs through the AMPK/mTOR signaling pathway. In summary, the functionalized GelMA/Laponite scaffold offers a cost-effective approach for tailored in situ bone regeneration.

Whether the potential degree of cervical instability and cervical muscle degeneration in patients with cervical spondylosis radicular affect the efficacy of cervical traction.

To explore whether the potential instability of the cervical spine and cervical muscle degeneration in patients with cervical spondylotic radiculopathy (CSR) affect the efficacy of cervical traction, and whether cervical traction can aggravate the potential instability of the cervical spine. We divided the 113 recruited CRS patients into three groups based on the differences in horizontal displacement and abnormal angle, and measured the degree of cervical muscle degeneration in the patients through MRI. Considering functional scores, VAS, NDI and PCS scores of the three groups post-treatment were significantly improved. Through the intergroup analysis, we found that the improvement in functional scores in the mild and moderate instability trend groups was better than that in the severe group. Through MRI measurements, we found that the degree of cervical muscle degeneration was significantly increased in the severe instability trend group. Regarding the changes in X-Ray imaging parameters pre- and post-treatment, no significant differences were observed pre- and post-treatment. For patients with CSR, the more serious their predisposition for cervical instability was, the more severe the degree of cervical muscle degeneration was, which means the worse the curative effect was, but cervical traction did not aggravate the potential degree of cervical instability.

Association between serum cotinine and muscle mass: results from NHANES 2011-2018.

PURPOSE: Recently, the detrimental effect of cigarette smoking on muscle metabolism has attracted much attention, but the relationship between cigarette smoking and muscle mass is poorly understood. Thus, this study investigated the association between exposure to cigarette smoke, defined based on serum cotinine, and muscle mass in the US population. METHODS: We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2018 for analysis. Data on serum cotinine, muscle mass (quantified by appendicular skeletal muscle mass index, ASMI), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum cotinine and ASMI. Subgroup analyses were stratified by gender, race and smoking status. When nonlinearity was detected, the threshold effects were analyzed using a two-piecewise linear regression model. RESULTS: In total, 8004 participants were included for analysis. The serum level of cotinine was negatively associated with ASMI in the fully adjusted model. Furthermore, comparing participants in the highest vs. the lowest tertile of serum cotinine, we found that ASMI decreased by 0.135 Kg/m2. In subgroup analysis stratified by gender and race, the association between serum cotinine and ASMI remained significant in all genders and races. In addition, the association remained significant among current and former smokers, but not among those who never smoked. Smooth curve fittings showed nonlinear relationships between serum cotinine and ASMI, with the inflection points identified at 356 ng/mL. CONCLUSIONS: Our study revealed that serum cotinine was negatively related to muscle mass. This finding improves our understanding of the deleterious effects of cigarette smoking on muscle mass and highlights the importance of smoking cessation for muscle health.

Zoledronic acid relieves steroid-induced avascular necrosis of femoral head via inhibiting FOXD3 mediated ANXA2 transcriptional activation.

BACKGROUND: Zoledronic acid (ZOL) is a type of bisphosphonate with good therapeutic effects on orthopaedic diseases. However, the pharmacological functions of ZOL on steroid-induced avascular necrosis of femoral head (SANFH) and the underlying mechanism remain unclear, which deserve further research. METHODS: SANFH models both in vivo and in vitro were established by dexamethasone (Dex) stimulation. Osteoclastogenesis was examined by TRAP staining. Immunofluorescence was employed to examine autophagy marker (LC3) level. Cell apoptosis was analyzed by TUNEL staining. The interaction between Foxhead box D3 protein (FOXD3) and Annexin A2 (ANXA2) promoter was analyzed using ChIP and dual luciferase reporter gene assays. RESULTS: Dex aggravated osteoclastogenesis and induced osteoclast differentiation and autophagy in vitro, which was abrogated by ZOL treatment. PI3K inhibitor LY294002 abolished the inhibitory effect of ZOL on Dex-induced osteoclast differentiation and autophagy. FOXD3 overexpression neutralized the downregulation effects of ZOL on Dex-induced osteoclasts by transcriptionally activating ANXA2. ANXA2 knockdown reversed the effect of FOXD3 overexpression on ZOL-mediated biological effects in Dex-treated osteoclasts. In addition, ZOL improved SANFH symptoms in rats. CONCLUSION: ZOL alleviated SANFH through regulating FOXD3 mediated ANXA2 transcriptional activity and then promoting PI3K/AKT/mTOR pathway, revealing that FOXD3 might be a target for ZOL in SANFH treatment.

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.

Carboxymethyl cellulose/quaternized chitosan hydrogel loaded with polydopamine nanoparticles promotes spinal cord injury recovery by anti-ferroptosis and M1/M2 polarization modulation.

Spinal cord injury (SCI) represents a catastrophic neurological condition resulting in long-term loss of motor, autonomic, and sensory functions. Recently, ferroptosis, an iron-regulated form of cell death distinct from apoptosis, has emerged as a potential therapeutic target for SCI. In this study, we developed an injectable hydrogel composed of carboxymethyl cellulose (CMC), and quaternized chitosan (QCS), loaded with modified polydopamine nanoparticles (PDA NPs), referred to as CQP hydrogel. This hydrogel effectively scavenged reactive oxygen species (ROS), prevented the accumulation of Fe2+ and lipid peroxidation associated with ferroptosis, and restored mitochondrial functions in primary neuronal cells. When administered to animal models (rats) with SCI, the CQP hydrogels improved motor function by regulating iron homeostasis, inhibiting ferroptosis, and mitigating oxidative stress injury. Both in vitro and in vivo studies corroborated the capacity of CQP hydrogels to promote the shift from M1 to M2 polarization of microglia/macrophages. These findings suggest that CQP hydrogels, functioning as a localized iron-chelating system, have potential as biomaterials to enhance recovery from SCI by targeting ferroptosis and modulating anti-inflammatory macrophages activity.

Are the facet joint parameters risk factors for cage subsidence after TLIF in patients with lumbar degenerative spondylolisthesis?

PURPOSE: To assess whether preoperative facet joint parameters in patients with degenerative lumbar spondylolisthesis (DS) are risk factors for cage subsidence (CS) following transforaminal lumbar interbody fusion (TLIF). METHODS: We enrolled 112 patients with L4-5 DS who underwent TLIF and were followed up for > 1 year. Preoperative demographic characteristics, functional areas of paraspinal muscles and psoas major muscles (PS), total functional area relative to vertebral body area, functional cross-sectional area (FCSA) of PS and lumbar spine extensor muscles, normalized FCSA of PS to the vertebral body area (FCSA/VBA), lumbar indentation value, facet joint orientation, facet joint tropism (FT), cross-sectional area of the superior articular process (SAPA), intervertebral height index, vertebral Hounsfield unit (HU) value, lordosis distribution index, t-scores, sagittal plane parameters, visual analog scale (VAS) for low back pain, VAS for leg pain, Oswestry disability index, global alignment and proportion score and European quality of life-5 dimensions (EQ-5D) were assessed. RESULTS: Postoperative CS showed significant correlations with preoperative FO(L3-4), FT (L3 and L5), SAPA(L3-5), L5-HU, FCSA/VBA(L3-4), Pre- T-score, post-6-month VAS for back pain and EQ-5D scores among other factors. According to ROC curve analysis, the optimal decision points for FO(L3-4), L3-SAPA, FCSA/VBA(L3-4), L5-HU, and Pre- T-score were 35.88°, 43.76°,114.93, 1.73, 1.55, 136, and - 2.49. CONCLUSIONS: This study identified preoperative FO, SAPA, preoperative CT, Pre- T-score and the FCSA/VBA as independent risk factors for CS after TLIF for DS. These risk factors should enable spinal surgeons to closely monitor and prevent the occurrence of CS.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering.

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.

Identification of allelic relationship and translocation region among chromosomal translocation lines that leads to less-seed watermelon.

Less-seed and seedless traits are desirable characteristics in watermelon (Citrullus lanatus). Hybridization between watermelon chromosomal translocated lines and wild lines significantly reduced seed counts in the hybrid fruits, approaching even seedless. However, the allelic relationships and the chromosomal translocation breakpoints from different sources are unclear, which limits their utility in breeding practices. This study focused on three groups of chromosomal translocation materials from different sources and conducted inheritance and allelic relationship analysis of translocation points. The results from third-generation genome sequencing and fluorescence in situ hybridization (FISH) revealed that the specific translocations in the naturally mutated material MT-a involved reciprocal translocations between Chr6 and Chr10. The Co60γ radiation-induced mutant material MT-b involved reciprocal translocations between Chr1 and Chr5, Chr4 and Chr8. The Co60γ radiation-induced mutant material MT-c involved complex translocations among Chr1, Chr5, and Chr11. Cytological observation showed that heterozygous translocation hybrids showed chromosomal synapsis abnormalities during meiotic diakinesis. Further, dominant and codominant molecular markers were developed on both sides of the translocation breakpoints, which could facilitate rapid and efficient identification of chromosome translocation lines. This study provides technical guidance for utilizing chromosomal translocation materials in the development of less-seed watermelon varieties.

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.

Association between serum copper levels and muscle mass: results from NHANES 2011-2016.

Copper is essential for various biological processes. However, excess copper has several adverse health effects. The effects of serum copper on muscle mass are poorly understood. This study aimed to investigate the association between serum copper levels and muscle mass in the US population. We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2016 for analysis. Data on serum copper, muscle mass (measured using the appendicular skeletal muscle mass index (ASMI)), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum copper levels and ASMI. Subgroup analyses stratified according to age and sex were performed. In the presence of nonlinearity, threshold effect analysis was performed using a two-piecewise linear regression model. A total of 3860 participants were included in the final analysis. Serum copper levels were negatively associated with ASMI in the fully adjusted model. Furthermore, by comparing participants in the highest and lowest tertiles of serum copper levels, we found that the ASMI decreased by 0.292 kg/m2. In the sex-stratified subgroup analysis, we observed an inverse association between serum copper levels and the ASMI in both men and women. When stratified by age, the association remained significant among participants < 40 years of age, but not among those ≥ 40 years old. Smooth curve fitting revealed a nonlinear relationship between serum copper and ASMI, with an inflection point identified at 150.6 µg/dL. Our study revealed an inverse relationship between serum copper levels and muscle mass. This finding improves the current knowledge on the impact of serum copper on muscle loss and highlights the importance of serum copper homeostasis in muscle health.

Prediction of Lumbar Pedicle Screw Loosening Using Hounsfield Units in Computed Tomography

INTRODUCTION: One of the most common issues following pedicle screw fixation is pedicle screw loosening. There are, however, few trustworthy methods for predicting screw loosening. The goal of the current study was to identify an efficient technique for using preoperative CT scanning to predict screw loosening in older patients and to offer recommendations for preoperative surgical planning. METHODS: The current analysis included retrospectively all patients who underwent lumbar pedicle screw fixation for degenerative lumbar diseases in our department between January 2015 and January 2022. Hounsfield units were used to assess each vertebra's attenuation in a CT scan (HU). Postoperative X-ray testing identified screw loosening. Using IBMSPSS 24.00 software, one-way analysis of variance (ANOVA) and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Over a mean follow-up period of 28.4±11.5 (range 12-44 months) months, screw loosening was noted in 53 of 242 patients (136 male and 106 female, average age 58.7±7.3 years). Gender, BMI, smoking habits, and whether or not a patient had diabetes or spondylolisthesis were not shown to be significantly different among the patients (P>0.05). The difference between the average lumbar vertebral HU values in the screw-loosening group and the control group was significant (P<0.01) at 120.3±31.5HU and 138.6±37.6HU, respectively. The average HU value of L1-L4 exhibited an area under the curve (AUC) of 0.691 (95% CI: 0.614-0.784), according to ROC curve analysis. A HU cut-off value of 122 HU is a likely cut-off point to predict screw loosening with a sensitivity of 70% and a specificity of 58%. CONCLUSION: The use of screw augmentation techniques can be decided using a prospective CT scan HU value-based prediction. An independent risk factor for screw loosening in an instrumented lumbar vertebra is a cutoff L1-L5 average HU value of 122 HU.

The Application of Three-Dimensional-Printed Hydrogels in Bone Tissue Engineering.

Bone defects are a prevalent clinical issue that presents a serious medical challenge. Bone tissue engineering (BTE) has emerged as an effective approach for treating large bone defects. Hydrogels, as hydrophilic three-dimensional polymers, are recognized as suitable material for BTE due to their excellent biocompatibility and degradability. However, the submicron and nanoporous structure of hydrogels limits the survival of osteoblasts, hindering bone tissue regeneration. In recent years, 3D printing technology has attracted appreciable attention. The use of hydrogels as 3D-printed ink facilitates the printing of hydrogels in any desired shape, enabling personalized or more complex requirements. This article provides a systematic review of the latest applications of 3D-printed hydrogels in BTE. These hydrogels serve as a multifunctional platform for the next generation technology in treating bone defects. The advantages and limitations of 3D-printed hydrogels in BTE are discussed, and future research directions are explored. This review can form the basis for future hydrogel design.

Modified FGF Hydrogel for Effective Axon Formation by Enhanced Regeneration of Myelin Sheath of Schwann Cells Using Rat Model.

Introduction: An acute spinal cord injury (SCI) is a debilitating event for which there is no targeted or effective treatment. Previous studies have shown that fibroblast growth factor (bFGF) and Schwann cells (SC) exert a protective effect on the injured tissues. Because of their easy injectability and strength, hydrogels are considered to be ideal candidates for creating loadable tissues. However, the application and mechanism of bFGF-hydrogels have not been explored. Methods: We synthesized a new class of bFGF-hydrosol and evaluated its safety and biocompatibility in vitro and in vivo. Next, an SCI rat model was established to evaluate the effect of the hydrosol on an SCI by detecting various pro-inflammatory markers and evaluating the injury. The ability of hydrosol to promote axon formation was evaluated by detecting corresponding indexes, and its ability to promote remyelination was evaluated by detecting the corresponding indexes in Schwann cells. Results: A novel in situ injectable hydrogel containing bFGF (HA-bFGF) was synthesized and found to have better biocompatibility than other gels. HA-bFGF helped to repair tissue damage after an SCI in vivo. Our mechanistic investigation also showed that HA-bFGF improved axon formation after an SCI by facilitating the regeneration of myelin sheath of Schwann cells. Conclusion: In this study, we found that HA-bFGF could promote neural restoration and tissue recovery after an SCI. Our results indicate that hydrogels loaded with bFGF can alleviate a spinal cord injury by promoting the remyelination of Schwann cells, reducing inflammation at the injured site, and ultimately promoting axon generation.

Clinical outcomes of modified versus traditional expansive open-door laminoplasty for cervical spondylotic myelopathy: A single-institution experience.

PURPOSE: To compare the surgical outcomes of modified expansive open-door laminoplasty (EOL) (C4-C6) and traditional EOL (C3-C7) in patients with cervical spondylotic myelopathy (CSM). METHODS: One hundred and two CSM patients were retrospectively recruited from Fujian Medical University Union Hospital between March 2012 and December 2019. Seventy-one patients with CSM underwent modified EOL, and 31 patients underwent traditional EOL. The primary endpoint was axial symptoms. RESULTS: Patients who underwent modified EOL had a significantly lower incidence of axial symptoms (odds ratio: 0.273; 95% confidence interval: 0.184-0.691; p = .002). The length of hospital stay (p = .263), and intraoperative blood loss (p = .402) were not significantly different between the groups. Significantly more postoperative drainage was observed in patients who underwent modified EOL (p < .001), while the cost of hospitalization in patients treated with traditional EOL was higher (p = .011). There were significant differences between modified and traditional EOL for the changes in range of motion (p < .001), modified Japanese Orthopaedic Association score (p = .001), and the Nurick grade (p = .014), while the changes of visual analogue scale (p = .250), and the neck disability index (p = .134) were not significantly different between the groups. CONCLUSION: This study found modified EOL may decrease the incidence of axial symptoms in patients with CSM compared to traditional EOL.

The impact of time from injury to surgery on the risk of neuropathic pain after traumatic spinal cord injury.

Traumatic spinal cord injury (SCI) is a devastating neurological disorder often accompanied by neuropathic pain (NeP), significantly affecting patients' quality of life. This retrospective study aimed to investigate the impact of the time from injury to surgery on the development of NeP following traumatic SCI. Medical records of patients with traumatic SCI who underwent surgical intervention between January 2017 and January 2021 at two specialized centers were reviewed. Variables associated with NeP including demographics, injury profiles, medical history, surgical details, and pain assessments were investigated. Independent risk factors related to NeP were identified using multivariate logistic regression analysis. A total of 320 patients met the inclusion criteria, with 245 (76.6%) being male and a mean age of 56.5 ± 13.2 years. NeP was identified in 48.4% of patients (155 of 320). The multivariate analysis identifies age at injury, Injury Severity Score, and the neurological level of injury as independent risk factors for the development of NeP in both AIS A and AIS B, C, and D subgroups. Additionally, a significant association between the time from injury to surgery and NeP was observed in AIS B, C, and D patients, while no such association was found in AIS A patients. This study highlights the benefits of early and ultra-early surgical intervention in preventing NeP in patients with incomplete traumatic SCI (AIS B, C, and D), underscoring the importance of optimizing surgical timing to improve patient outcomes. Prospective studies are warranted to establish evidence-based surgical guidelines for managing traumatic SCI and preventing NeP effectively.

Concomitant malnutrition and frailty are significant risk factors for poor outcome following two-stage revision for chronic periprosthetic joint infection.

BACKGROUND: Two-stage revision remains the gold standard for periprosthetic joint infection (PJI) treatment. Although previous studies have examined malnutrition and frailty independently, their cumulative effects are not clear. Therefore, this study aimed to assess the individual and combined influence of malnutrition and frailty on the two-stage revision surgery. METHODS: Patients with chronic PJI undergoing two-stage revision were retrospectively included. The definition of PJI is completely consistent with the evidence-based definition of PJI recorded by the MSIS in 2018. Preoperative serum albumin levels and 11-item modified frailty index scores were collected. Four cohorts were created: (1) Normal (N), (2) Frail (F), (3) Malnourished (M), and (4) Malnourished and frail (MF). Demographic data, comorbidities, and postoperative complications were collected and compared between the four cohorts. RESULTS: A total of 117 consecutive patients were enrolled, 48% of patients were healthy (27.4% F, 16.2% M, and 9.4% MF). MF group showed lower scores on the physical composite scale of the 12-item short-form health survey (SF12-PCS), mental composite summary (SF12-MCS), Harris hip score (HHS), and knee society score (KSS) (P < 0.05). The incidence of reinfection in the MF group was higher than that in all other groups (MF vs. N; odds ratio [OR] 3.7, 95% confidence interval [CI] 1.37 - 8.82, P = 0.032). The incidence of complications in the MF group was higher than that in all other groups (MF vs. N; OR 4.81, 95% CI 1.58-9.26, P = 0.018). Postoperative transfusion events (OR 2.92, 95% CI 1.27-3.09, P = 0.021), readmission at 60 days after the operation (OR 4.91, 95% CI 1.82-13.80, P = 0.012) was higher in the MF patients. In addition, the extended length of stay after the operation was highest in the MF patients, with an OR of 5.78 (95% CI 2.16-12.04, P = 0.003). CONCLUSION: The concurrent presence of concomitant malnutrition and frailty in patients with PJI is related to poor prognosis and may be a predictor of the efficacy of two-stage revision. Future research will be needed to describe the benefits of improving these risk factors for patients with PJI.

METTL3 Affects Spinal Cord Neuronal Apoptosis by Regulating Bcl-2 m6A Modifications After Spinal Cord Injury.

OBJECTIVE: Spinal cord injury (SCI) is a severe type of neurological trauma. N6-methyladenosine (m6A) modification is one of the most common internal modifications of RNA. The role of METTL3, the predominant methylation enzyme of m6A modification, in SCI remains unclear. This study aimed to investigate the role of methyltransferase METTL3 in SCI. METHODS: After establishing the oxygen-glucose deprivation (OGD) model of PC12 cells and rat spinal cord hemisection model, we found that the expression of METTL3 and the overall m6A modification level were significantly increased in neurons. The m6A modification was identified on B-cell lymphoma 2 (Bcl-2) messenger RNA (mRNA) by bioinformatics analysis, and m6A-RNA immunoprecipitation and RNA immunoprecipitation. In addition, METTL3 was blocked by the specific inhibitor STM2457 and gene knockdown, and then apoptosis levels were measured. RESULTS: In different models, we found that the expression of METTL3 and the overall m6A modification level were significantly increased in neurons. After inducing OGD, inhibition of METTL3 activity or expression increased the mRNA and protein levels of Bcl-2, inhibited neuronal apoptosis, and improved neuronal viability in the spinal cord. CONCLUSION: Inhibition of METTL3 activity or expression can inhibit the apoptosis of spinal cord neurons after SCI through the m6A/Bcl-2 signaling pathway.