Integrin αVß3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVß3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVß3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVß3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL. METHODS: OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVß3. Integrin αVß3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVß3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo. RESULTS: The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVß3 and regulating the FAK/ERK pathway. CONCLUSIONS: Therefore, the integrin αVß3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

The C2 isthmus screw provided sufficient biomechanical stability in the setting of atlantoaxial dislocation-a finite element study.

BACKGROUND: The emerging of the C2 isthmus screw fixation technique is gaining popularity in the setting of atlantoaxial dislocation or other conditions requiring fixation of C2. However, the biomechanical stability of this fixation is poorly understood. PURPOSE: To compare and elucidate the biomechanical stability of C2 pedicle screw (C2PS), C2 isthmus screw (C2IS) and C2 short isthmus screw (C2SIS) fixation techniques in atlantoaxial dislocation (AAD). METHOD: A three-dimensional finite element model (FEM) from occiput to C3 was established and validated from a healthy male volunteer. Three FEMs, C1 pedicle screw (PS)-C2PS, C1PS-C2IS, C1PS-C2SIS were also constructed. The range of motion (ROM) and the maximum von Mises stress under flexion, extension, lateral bending and axial rotation loading were analyzed and compared. The pullout strength of the three fixations for C2 was also evaluated. RESULT: C1PS-C2IS model showed the greatest decrease in ROM with flexion, extension, lateral bending and axial rotation. C1PS-C2PS model showed the least ROM reduction under all loading conditions than both C2IS and C2SIS. The C1PS-C2PS model had the largest von Mises stress on the screw under all directions followed by C1PS-C2SIS, and lastly the C1PS-C2IS. Under axial rotation and lateral bending loading, the three models showed the maximum and minimum von Mises stress on the screw respectively. The stress of the three models was mainly located in the connection of the screw and rod. Overall, the maximum screw pullout strength for C2PS, C2IS and C2SIS were 729.41N, 816.62N, 640.54N respectively. CONCLUSION: In patients with atlantoaxial dislocations, the C2IS fixation provided comparable stability, with no significant stress concentration. Furthermore, the C2IS had sufficient pullout strength when compared with C2PS and C2SIS. C2 isthmus screw fixation may be a biomechanically favourable option in cases with AAD. However, future clinical trials are necessary for the evaluation of the clinical outcomes of this technique.

MRI-based vertebral bone quality score in cervical ossification of the posterior longitudinal ligament: a comparison with cervical spondylotic myelopathy using propensity score matching.

BACKGROUND: Bone mineral density plays a key role in the assessment of operative instrumentation complications and clinical outcomes. The MRI-based vertebral bone quality (VBQ) score has been introduced as a novel marker of bone quality. However, few studies have investigated the relationship between VBQ score and patients associated with cervical ossification of the posterior longitudinal ligament (OPLL). PURPOSE: The aims of the study were (1) to reveal bone mineral density between cervical OPLL and cervical spondylotic myelopathy (CSM) group by VBQ score, (2) to compare the VBQ score of cervical OPLL between male and female group, (3) to explore the relationship between segmental VBQ scores associated with OPLL. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Consecutive series of 425 patients at a single academic institution. OUTCOME MEASURES: MRI based measurements of C2-C7 VBQ scores. METHODS: Preoperative non-contrast T1-weighted MRIs of the cervical spine was used to measure the VBQ score. The VBQ score was defined as the mean value of the signal intensity of the vertebrae divided by that of the cerebrospinal fluid (CSF) space at the cisterna magna. Patients with cervical OPLL and CSM were matched based on age, sex, body mass index (BMI), comorbidity, medication history, diet habit, smoking, alcohol consumption via propensity score matching (PSM). Normality of each VBQ score was tested by the Shapiro-Wilk test. Wilcoxon's rank-sum test was used to compare matched cohorts. Kruskal-Wallis test was performed to compare the VBQ scores between segments. Multivariate logistic regression analysis was used to evaluate factors associated with the development of cervical OPLL. RESULTS: A total of 425 patients were assessed. For final analysis, 135 paired patients were compared between the cervical OPLL and CSM groups, and 22 paired patients were compared between male and female group associated with cervical OPLL. There were no statistically significant differences in age, sex, BMI, comorbidity, medication history, diet habit, smoking, alcohol between the matched cohorts. OPLL group was associated with lower VBQ score compared with CSM group at C3, while there were no differences in VBQ score for the other levels between the two groups. There were no differences between male and female group associated with OPLL in C2-C7 VBQ scores. VBQ scores of cervical OPLL are variable between segments, with significantly lower scores at C6, C7 compared with C1-C5. Multivariate logistic regression analysis showed that BMI was correlated with the development of OPLL (regression coefficient, 0.162; 95% confidence interval, 0.010-0.037). Additional risk factors included hypertension, calcium supple history and smoking. CONCLUSIONS: This study demonstrates that cervical OPLL is associated with lower VBQ score at C3, with no differences for the other levels when compared with CSM derived from measurements on MRI. No differences were found between male and female group associated with OPLL in C2-C7 VBQ scores. Cervical OPLL were found to have smaller VBQ score at C6, C7 compared with C1-C5. Our findings provide new insight for bone density assessment in cervical OPLL patient.

Engineered Macrophage Membrane-Coated Nanoparticles with Enhanced CCR2 Expression Promote Spinal Cord Injury Repair by Suppressing Neuroinflammation and Neuronal death.

Spinal cord injury (SCI) is a severe neurological disorder characterized by significant disability and limited treatment options. Mitigating the secondary inflammatory response following the initial injury is the primary focus of current research in the treatment of SCI. CCL2 (C─C motif chemokine ligand 2) serves as the primary regulator responsible for inflammatory chemotaxis of the majority of peripheral immune cells, blocking the CCL2-CCR2 (C─C chemokine receptor type 2) axis has shown considerable therapeutic potential for inflammatory diseases, including SCI. In this study, it presents a multifunctional biomimetic nanoplatform (CCR2-MM@PLGA/Cur) specifically designed to target the CCL2-CCR2 axis, which consisted of an engineered macrophage membrane (MM) coating with enhanced CCR2 expression and a PLGA (poly (lactic-co-glycolic acid)) nanoparticle that encapsulated therapeutic drugs. CCR2 overexpression on MM not only enhanced drug-targeted delivery to the injury site, but also attenuated macrophage infiltration, microglia pro-inflammatory polarization, and neuronal apoptosis by trapping CCL2. Consequently, it facilitated neural regeneration and motor function recovery in SCI mice, enabling a comprehensive treatment approach for SCI. The feasibility and efficacy of this platform are confirmed through a series of in vitro and in vivo assays, offering new insights and potential avenues for further exploration in the treatment of SCI.

Engineering Copper-Containing Nanoparticles-Loaded Silicene Nanosheets with Triple Enzyme Mimicry Activities and Photothermal Effect for Promoting Bacteria-Infected Wound Healing.

Skin wounds accompanied by bacterial infections threaten human health, and conventional antibiotic treatments are ineffective for drug-resistant bacterial infections and chronically infected wounds. The development of non-antibiotic-dependent therapeutics is highly desired but remains a challenging issue. Recently, 2D silicene nanosheets with considerable biocompatibility, biodegradability, and photothermal-conversion performance have received increasing attention in biomedical fields. Herein, copper-containing nanoparticles-loaded silicene (Cu2.8O@silicene-BSA) nanosheets with triple enzyme mimicry catalytic (peroxidase, catalase, and oxidase-like) activities and photothermal function are rationally designed and fabricated for efficient bacterial elimination, angiogenesis promotion, and accelerated wound healing. Cu2.8O@silicene-BSA nanosheets display excellent antibacterial activity through synergistic effects of reactive oxygen species generated from multiple catalytic reactions, intrinsic bactericidal activity of released Cu2+ ions, and photothermal effects, achieving high antibacterial efficiencies on methicillin-resistant Staphylococcus aureus (MRSA) of 99.1 ± 0.7% in vitro and 97.2 ± 1.6% in vivo. In addition, Cu2.8O@silicene-BSA nanosheets exhibit high biocompatibility for promoting human umbilical vein endothelial cell (HUVEC) proliferation and angiogenic differentiation. In vivo experiments reveal that Cu2.8O@silicene-BSA nanosheets with synergistic photothermal/chemodynamic therapeutics effectively accelerate MRSA-infected wound healing by eliminating bacteria, alleviating inflammation, boosting collagen deposition, and promoting angiogenesis. This research presents a promising strategy to engineer photothermal-assisted nanozyme catalysis for bacteria-invaded wound healing.

C1 Transposterior Arch Lateral Mass Screws Combined With C2 Pedicle Screw and Rod Fixation for Pediatric Atlantoaxial Subluxation: A Minimal 10-Year Follow-up Outcome Analysis.

BACKGROUND AND OBJECTIVES: Although the short-term outcomes of the 1-step reduction and fixation technique using C1 transposterior arch lateral mass screws combined with C2 pedicle screw and rod fixation system for the treatment of pediatric atlantoaxial subluxation (AAS) have been satisfactory, its long-term outcomes and impact on spinal development are not well studied. This study was intended to assess the long-term reliability of this technique for pediatric AAS. METHODS: A retrospective case series study was conducted to analyze the minimum 10-year follow-up outcomes from 7 pediatric patients with AAS who underwent atlantoaxial fusion using the aforementioned technique. Quality of life and cervical range of motion were both measured thoroughly. In addition, vertical growth within the fusion construct (C1-2), overall cervical alignment, and subaxial cervical spine degeneration were evaluated radiographically. RESULTS: The mean age of the 7 patients was 8.14 ± 2.41 (6-12) years at the time of surgery. The mean follow-up period was 11.00 ± 1.15 (10-13) years. No patients presented identifiable intervertebral disk degeneration or segmental instability in the subaxial cervical spine except for 1 patient who showed mild intervertebral disk degeneration. Vertical growth did continue within the atlantoaxial complex after surgery (11.90% ± 2.37%); however, there was a decrease in the percentage of vertical growth compared with the corresponding normal populations of the same age and sex. Moreover, there was a significant decrease in the range of cervical extension and rotation motion, and the overall cervical alignment straightened at the latest follow-up. CONCLUSION: The 1-step reduction and fixation technique is a relatively reliable surgical technique for pediatric AAS, which does not adversely affect the postoperative quality of life or the subaxial cervical degeneration. Nevertheless, certain limitations, such as decreased cervical range of motion and changes in cervical alignment, should be concerned.

In Situ Synthesis of Ru/TiO2- x @TiCN Ternary Heterojunctions for Enhanced Sonodynamic and Nanocatalytic Cancer Therapy.

Albeit nanozymes-based tumor catalytic therapy (NCT) relies on endogenous chemical reactions that could achieve tumor microenvironment (TME)-specialized reactive oxygen species (ROS) production, the unsatisfactory catalytic activity of nanozymes accompanied by complex TME poses a barrier to the therapeutic effect of NCT. Herein, a one-step in situ synthesis strategy is reported to construct ternary Ru/TiO2- x @TiCN heterojunctions through oxidative conversion of TiCN nanosheets (NSs) to TiO2- x NSs and reductive deposition of Ru3+ to Ru nanoparticles. The narrow bandgap and existence of heterojunctions enhance the ultrasound-activated ROS generation of Ru/TiO2- x @TiCN because of the accelerated electron transfer and inhibits electron-hole pair recombination. The augmented ROS production efficiency is achieved by Ru/TiO2- x @TiCN with triple enzyme-like activities, which amplifies the ROS levels in a cascade manner through the catalytic decomposition of endogenous H2 O2 to relieve hypoxia and heterojunction-mediated NCT, as well as depletion of overexpressed glutathione. The satisfactory therapeutic effects of Ru/TiO2- x @TiCN heterojunctions are achieved through synergetic sonodynamic therapy and NCT, which achieve the complete elimination of tumors without recurrence. This strategy highlights the potential of in situ synthesis of semiconductor heterojunctions as enhanced sonosensitizers and nanozymes for efficient tumor therapy.

Diagnostic model based on key autophagy-related genes in intervertebral disc degeneration.

BACKGROUND: Current research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study constructed a diagnostic model to identify autophagy-related markers of intervertebral disc degeneration (IVDD). METHODS: GSE150408 and GSE124272 datasets were acquired from the Gene Expression Omnibus database, and differential expression analysis was performed. The IVDD-autophagy genes were obtained using Weighted Gene Coexpression Network Analysis, and a diagnostic model was constructed and validated, followed by Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Meanwhile, miRNA-gene and transcription factor-gene interaction networks were constructed. In addition, drug-gene interactions and target genes of methylprednisolone and glucosamine were analyzed. RESULTS: A total of 1,776 differentially expressed genes were identified between IVDD and control samples, and the composition of the four immune cell types was significantly different between the IVDD and control samples. The Meturquoise and Mebrown modules were significantly related to immune cells, with significant differences between the control and IVDD samples. A diagnostic model was constructed using five key IVDD-autophagy genes. The area under the curve values of the model in the training and validation datasets were 0.907 and 0.984, respectively. The enrichment scores of the two pathways were significantly different between the IVDD and healthy groups. Eight pathways in the IVDD and healthy groups had significant differences. A total of 16 miRNAs and 3 transcription factors were predicted to be of great value. In total, 84 significantly related drugs were screened for five key IVDD-autophagy genes in the diagnostic model, and three common autophagy-related target genes of methylprednisolone and glucosamine were predicted. CONCLUSION: This study constructs a reliable autophagy-related diagnostic model that is strongly related to the immune microenvironment of IVD. Autophagy-related genes, including PHF23, RAB24, STAT3, TOMM5, and DNAJB9, may participate in IVDD pathogenesis. In addition, methylprednisolone and glucosamine may exert therapeutic effects on IVDD by targeting CTSD, VEGFA, and BAX genes through apoptosis, as well as the sphingolipid and AGE-RAGE signaling pathways in diabetic complications.

A Pilot Human Cadaveric Study on Accuracy of the Augmented Reality Surgical Navigation System for Thoracolumbar Pedicle Screw Insertion Using a New Intraoperative Rapid Registration Method.

To evaluate the feasibility and accuracy of AR-assisted pedicle screw placement using a new intraoperative rapid registration method of combining preoperative CT scanning and intraoperative C-arm 2D fluoroscopy in cadavers. Five cadavers with intact thoracolumbar spines were employed in this study. Intraoperative registration was performed using anteroposterior and lateral views of preoperative CT scanning and intraoperative 2D fluoroscopic images. Patient-specific targeting guides were used for pedicle screw placement from Th1-L5, totaling 166 screws. Instrumentation for each side was randomized (augmented reality surgical navigation (ARSN) vs. C-arm) with an equal distribution of 83 screws in each group. CT was performed to evaluate the accuracy of both techniques by assessing the screw positions and the deviations between the inserted screws and planned trajectories. Postoperative CT showed that 98.80% (82/83) screws in ARSN group and 72.29% (60/83) screws in C-arm group were within the 2-mm safe zone (p < 0.001). The mean time for instrumentation per level in ARSN group was significantly shorter than that in C-arm group (56.17 ± 3.33 s vs. 99.22 ± 9.03 s, p < 0.001). The overall intraoperative registration time was 17.2 ± 3.5 s per segment. AR-based navigation technology can provide surgeons with accurate guidance of pedicle screw insertion and save the operation time by using the intraoperative rapid registration method of combining preoperative CT scanning and intraoperative C-arm 2D fluoroscopy.

M2 macrophage-derived exosome-encapsulated microneedles with mild photothermal therapy for accelerated diabetic wound healing.

Due to local overactive inflammatory response and impaired angiogenesis, current treatments for diabetic wounds remain unsatisfactory. M2 macrophage-derived exosomes (MEs) have shown considerable potential in biomedical applications, especially since they have anti-inflammatory properties that modulate macrophage phenotypes. However, exosome-based strategies still have limitations, such as short half-lives and instability. Herein, we develop a double-layer microneedle-based wound dressing system (MEs@PMN) by encapsulating MEs in the needle tips and polydopamine (PDA) nanoparticles in backing layer to simultaneously suppress inflammation and improve angiogenesis at the wound site. In vitro, released MEs increased macrophage polarization towards the M2 phenotype. In addition, mild heat (40 â€‹°C) generated by the photosensitive PMN backing layer contributed to improved angiogenesis. More importantly, MEs@PMN also showed promising effects in diabetic rats. The uncontrolled inflammatory response at the wound site was inhibited by MEs@PMN during a 14-day period; in addition, MEs and the photothermal effects produced by PMN provided a combined proangiogenic effect by improving the expression of CD31 and vWF. Collectively, this study provides a simple and efficient cell-free strategy for suppressing inflammation and promoting vascular regeneration to treat diabetic wounds.

Combined photothermal and sonodynamic therapy using a 2D black phosphorus nanosheets loaded coating for efficient bacterial inhibition and bone-implant integration.

Surgical site infection (SSI) remains a major threat for implant failure in orthopedics. Herein, we report a dual-functional coating on Ti implants (named Ti/PDA/BP) with the integration of two-dimensional (2D) photo-sono sensitive black phosphorus nanosheets (BPNSs) and polydopamine (PDA) for efficient bacterial inhibition and bone-implant integration. For the first time, we employ BPNSs as generators of reactive radicals (ROS) under ultrasound (US) stimuli for implant associated infection. Additionally, the application of PDA improves the stability of BPNSs, the biocompatibility and photothermal performance of this hybrid coating. The as-prepared Ti/PDA/BP coating exhibits superior biocompatibility, bioactivity, photothermal and sonodynamic conversion abilities. Owing to the synergistic effect of hyperthermia and ·OH, Ti/PDA/BP damages the membrane and antioxidant system of Staphylococcus aureus, reaching a high antibacterial activity of 96.6% in vitro and 97.3% in vivo with rapid 10 min NIR irradiation and 20 min US treatment. In addition, we firstly unveil the significant effect of Ti/PDA/BP-based sonodynamic therapy (SDT) on bacterial membrane and oxidative stress at the transcriptome level. Moreover, the Ti/PDA/BP coating remarkably promotes osteogenesis in vitro and bone-implant osseointegration in vivo. Overall, development of Ti/PDA/BP bioactive coating provides a new strategy for combating the implant associated infection.

Engineering of M2 Macrophages-Derived Exosomes via Click Chemistry for Spinal Cord Injury Repair.

Spinal cord injury (SCI) is one of the most common causes of death and disability. The effective modulation of complicated microenvironment, regeneration of injured spinal cord tissue, and the functional recovery after SCI are still clinical challenges. Recently, macrophages-derived exosomes have shown great potential for various diseases due to their inflammation-targeting property. However, further modifications are needed to endow exosomes with the neural regenerative potential for SCI recovery. In the current study, a novel nanoagent (MEXI) is designed for SCI treatment by conjugating bioactive IKVAV peptides to the surface of M2 macrophages-derived exosomes via an easy and rapid click chemistry method. In vitro, MEXI inhibits the inflammation by reprograming macrophages and promotes neuronal differentiation of neural stem cells. In vivo, engineered exosomes target the injured site of the spinal cord after tail vein injection. Furthermore, histological analysis reveals that MEXI improves motor functional recovery of SCI mice by reducing infiltration of macrophages, downregulating pro-inflammatory factors, and improving the regeneration of injured nervous tissues. Taken together, this study provides strong evidence for the significance of MEXI in SCI recovery.

Comparison of the outcome after anterior cervical ossified posterior longitudinal ligament en bloc resection versus posterior total laminectomy and fusion in patients with ossification of the cervical posterior longitudinal ligament: a prospective randomized controlled trial.

The optimal procedure for the treatment of ossification of the posterior longitudinal ligament (OPLL) remains controversial. The aim of this study was to compare the outcome of anterior cervical ossified posterior longitudinal ligament en bloc resection (ACOE) with posterior laminectomy and fusion with bone graft and internal fixation (PTLF) for the surgical management of patients with this condition. Between July 2017 and July 2019, 40 patients with cervical OPLL were equally randomized to undergo surgery with an ACOE or a PTLF. The clinical and radiological results were compared between the two groups. The Japanese Orthopaedic Association (JOA) score and recovery rate in the ACOE group were significantly higher than those in the PTLF group during two years postoperatively, provided that the canal occupying ratio (COR) was > 50%, or the K-line was negative. There was no significant difference in JOA scores and rate of recovery between the two groups in those in whom the COR was < 50%, or the K-line was positive. There was no significant difference in the Cobb angle between C2 and C7, sagittal vertical axis, cervical range of motion (ROM), and complications between the two groups. Compared with PTLF, ACOE is a preferred surgical approach for the surgical management of patients with cervical OPLL in that it offers a better therapeutic outcome when the COR is > 50%, or the K-line is negative, and it also preserves better cervical curvature and sagittal balance. The prognosis of ACOE is similar to that of PTLE when the COR is < 50%, or the K-line is positive.

Remote ischemic preconditioning protects against spinal cord ischemia-reperfusion injury in mice by activating NMDAR/AMPK/PGC-1α/SIRT3 signaling.

BACKGROUND: To study the protective effects of delayed remote ischemic preconditioning (RIPC) against spinal cord ischemia-reperfusion injury (SCIRI) in mice and determine whether SIRT3 is involved in this protection and portrayed its upstream regulatory mechanisms. METHODS: In vivo, WT or SIRT3 global knockout (KO) mice were exposed to right upper and lower limbs RIPC or sham ischemia. After 24 h, the abdominal aorta was clamped for 20 min, then re-perfused for 3 days. The motor function of mice, number of Nissl bodies, apoptotic rate of neurons, and related indexes of oxidative stress in the spinal cord were measured to evaluate for neuroprotective effects. The expression and correlation of SIRT3 and NMDAR were detected by WB and immunofluorescence. In vitro, primary neurons were exacted and OGD/R was performed to simulate SCIRI in vivo. Neuronal damage was assessed by observing neuron morphology, detecting LDH release ratio, and flow cytometry to analyze the apoptosis. MnSOD and CAT enzyme activities, GSH and ROS level were also measured to assess neuronal antioxidant capacity. NMDAR-AMPK-PGC-1α signaling was detected by WB to portray upstream regulatory mechanisms of RIPC regulating SIRT3. RESULTS: Compared to the SCIRI mice without RIPC, mice with RIPC displayed improved motor function recovery, a reduced neuronal loss, and enhanced antioxidant capacity. To the contrary, the KO mice did not exhibit any effect of RIPC-induced neuroprotection. Similar results were observed in vitro. Further analyses with spinal cord tissues or primary neurons detected enhanced MnSOD and CAT activities, as well as increased GSH level but decreased MDA or ROS production in the RIPC + I/R mice or NMDA + OGD/R neurons. However, these changes were completely inhibited by the absence of SIRT3. Additionally, NMDAR-AMPK-PGC-1α signaling was activated to upregulate SIRT3 levels, which is essential for RIPC-mediated neuroprotection. CONCLUSIONS: RIPC enhances spinal cord ischemia tolerance in a SIRT3-dependent manner, and its induced elevated SIRT3 levels are mediated by the NMDAR-AMPK-PGC-1α signaling pathway. Combined therapy targeting SIRT3 is a promising direction for treating SCIRI.

Can a Nomogram Predict Survival After Treatment for an Ankylosing Spondylitis Cervical Fracture in a Patient With Neurologic Impairment? A National, Multicenter Study.

BACKGROUND: Ankylosing spondylitis-related cervical spine fracture with neurologic impairment (ASCF-NI) is a rare but often lethal injury. Factors independently associated with survival after treatment remain poorly defined, and identifying patients who are likely to survive the injury remains challenging. QUESTIONS/PURPOSES: (1) What factors are independently associated with survival after treatment among patients with ASCF-NI? (2) Can a nomogram be developed that is sufficiently simple for clinicians to use that can identify patients who are the most likely to survive after injury? METHODS: This retrospective study was conducted based on a multi-institutional group of patients admitted and treated at one of 29 tertiary hospitals in China between March 1, 2003, and July 31, 2019. A total of 363 patients with a mean age of 53 ± 12 years were eventually included, 343 of whom were male. According to the National Household Registration Management System, 17% (61 of 363) died within 5 years of injury. Patients were treated using nonsurgical treatment or surgery, including procedures using the anterior approach, posterior approach, or combined anterior and posterior approaches. Indications for surgery included three-column injury, unstable fracture displacement, neurologic impairment or continuous progress, and intervertebral disc incarceration. By contrast, patients generally received nonsurgical treatment when they had a relatively stable fracture or medical conditions that did not tolerate surgery. Demographic, clinical, and treatment data were collected. The primary study goal was to identify which factors are independently associated with death within 5 years of injury, and the secondary goal was the development of a clinically applicable nomogram. We developed a multivariable Cox hazards regression model, and independent risk factors were defined by backward stepwise selection with the Akaike information criterion. We used these factors to create a nomogram using a multivariate Cox proportional hazards regression analysis. RESULTS: After controlling for potentially confounding variables, we found the following factors were independently associated with a lower likelihood of survival after injury: lower fracture site, more-severe peri-injury complications, poorer American Spinal Injury Association (ASIA) Impairment Scale, and treatment methods. We found that a C5 to C7 or T1 fracture (ref: C1 to C4 and 5; hazard ratio 1.7 [95% confidence interval 0.9 to 3.5]; p = 0.12), moderate peri-injury complications (ref: absence of or mild complications; HR 6.0 [95% CI 2.3 to 16.0]; p < 0.001), severe peri-injury complications (ref: absence of or mild complications; HR 30.0 [95% CI 11.5 to 78.3]; p < 0.001), ASIA Grade A (ref: ASIA Grade D; HR 2.8 [95% CI 1.1 to 7.0]; p = 0.03), anterior approach (ref: nonsurgical treatment; HR 0.5 [95% CI 0.2 to 1.0]; p = 0.04), posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.8]; p = 0.006), and combined anterior and posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.9]; p = 0.02) were associated with survival. Based on these factors, a nomogram was developed to predict the survival of patients with ASCF-NI after treatment. Tests revealed that the developed nomogram had good performance (C statistic of 0.91). CONCLUSION: The nomogram developed in this study will allow us to classify patients with different mortality risk levels into groups. This, coupled with the factors we identified, was independently associated with survival, and can be used to guide more appropriate treatment and care strategies for patients with ASCF-NI. LEVEL OF EVIDENCE: Level III, therapeutic study.

Potential of green tea EGCG in neutralizing SARS-CoV-2 Omicron variant with greater tropism toward the upper respiratory tract.

Background: COVID-19 due to SARS-CoV-2 infection has had an enormous adverse impact on global public health. As the COVID-19 pandemic evolves, the WHO declared several variants of concern (VOCs), including Alpha, Beta, Gamma, Delta, and Omicron. Compared with earlier variants, Omicron, now a dominant lineage, exhibits characteristics of enhanced transmissibility, tropism shift toward the upper respiratory tract, and attenuated disease severity. The robust transmission of Omicron despite attenuated disease severity still poses a great challenge for pandemic control. Under this circumstance, its tropism shift may be utilized for discovering effective preventive approaches. Scope and approach: This review aims to estimate the potential of green tea epigallocatechin gallate (EGCG), the most potent antiviral catechin, in neutralizing SARS-CoV-2 Omicron variant, based on current knowledge concerning EGCG distribution in tissues and Omicron tropism. Key findings and conclusions: EGCG has a low bioavailability. Plasma EGCG levels are in the range of submicromolar concentrations following green tea drinking, or reach at most low µM concentrations after pharmacological intervention. Nonetheless, its levels in the upper respiratory tract could reach concentrations as high as tens or even hundreds of µM following green tea consumption or pharmacological intervention. An approach for delivering sufficiently high concentrations of EGCG in the pharynx has been developed. Convincing data have demonstrated that EGCG at tens to hundreds of µM can dramatically neutralize SARS-CoV-2 and effectively eliminate SARS-CoV-2-induced cytopathic effects and plaque formation. Thus, EGCG, which exhibits hyperaccumulation in the upper respiratory tract, deserves closer investigation as an antiviral in the current global battle against COVID-19, given Omicron's greater tropism toward the upper respiratory tract.

Anterior Cervical Decompression and Fusion Surgery for Cervical Spondylosis with Concomitant Tinnitus: A Multicenter Prospective Cohort Study.

OBJECTIVE: Cervical spondylosis is often accompanied by tinnitus. Up to now, there is a lack of large samples and prospective studies to investigate the effect of anterior cervical decompression and fusion (ACDF) on tinnitus associate with cervical spondylosis. To this end, we performed a prospective cohort study to assess the effectiveness of ACDF on the relief of tinnitus. METHODS: This was a multicenter, prospective, cohort clinical study. Between August 2017 and August 2018, 174 patients with cervical spondylosis accompanied by tinnitus were enrolled, with a follow-up of 12 months. Among the 174 patients, 142 received anterior cervical surgery (surgery group) and 32 received conservative treatment (conservative group). The primary end point was the mean change in scores on the tinnitus functional index (TFI). The secondary end points included tinnitus loudness, modified Japanese orthopaedic association scores (mJOA) for spinal cord function, and visual analogue scale (VAS) for neck pain. All the above indexes were measured before treatments and at 1, 3, 6, and 12 months after treatments. One-way analysis of variance and paired samples t-test was adopted for statistical analysis. RESULTS: The TFI score was reduced immediately after cervical decompression surgery (from 54.7 ± 15.6 to 32.3 ± 12.5, P < 0.001) and this was sustained at 12 months (P < 0.001). The TFI score of the conservative group also decreased (from 53.9 ± 16.8 to 45.2 ± 13.6, P < 0.001), but the effect was not maintained at 12 months (P = 0.069). There was a significant improvement in tinnitus loudness (from 5.2 ± 1.6 to 2.6 ± 1.9, P < 0.001), mJOA (from 12.0 ± 1.6 to 14.2 ± 1.6, P < 0.001), and VAS for neck pain (from 58.5 ± 9.6 to 22.0 ± 16.4, P < 0.001) in the surgical group. Improvements in the surgical group were statistically significantly greater than that in the conservative group (P < 0.001). CONCLUSION: This study indicates that anterior cervical surgery can relieve tinnitus in patients with cervical spondylosis and that tinnitus is an accompanying manifestation of cervical spondylosis.

Lyophilized bovine acellular tendon linear fiber material for the reconstruction of attachment structure of paraspinous muscles: an animal in vivo study.

Low back pain is common after lumbar spine surgery and the injury from extensive detachment of paraspinal muscles during the surgery may play a vital role. Previously, we prepared a bovine acellular tendon fiber (ATF) material through lyophilization and proved that it could retain its original fibrillar structure and mechanical properties. The objective of this study is to evaluate the effectiveness of this new fiber material used for attachment structure reconstruction of paraspinal muscle. Defect of spinous process, interspinous and supraspinous ligament was established on lumbar spine in rabbit and rat and ATF linear material was implanted to reconstruct the attachment structure. Ultrasound showed the cross-sectional area of the paraspinal muscle in ATF group was larger than that of control group in rats. MRI showed the irregular shape and high signal changes in control group, but regular shape and uniform signal in the ATF group in rabbit. For Electromyogram, the frequency of evoked potential in control group was lower than ATF group and normal rats. HE and Masson staining showed good tissue healing, and immunohistochemical results showed the immune rejection of ATF is significantly lower than that of suture. Reconstruction of the attachment structure of paraspinous muscles with ATF linear material could maintain the morphology, volume and function of paraspinal muscle. ATF material has the potential to be used to manufacture personalized ligaments and other tissue engineering scaffolds. Graphical abstract.

Factors affecting titanium mesh cage subsidence in single-level anterior cervical corpectomy and fusion for ossification of the posterior longitudinal ligament.

PURPOSE: To analyze risk factors of titanium mesh cage (TMC) subsidence in single-level anterior cervical corpectomy and fusion (ACCF) for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: TMC subsidence is defined as the reduction of the adjacent vertebral bodies by ≥ 2 mm. Patients with cervical OPLL who were treated with single-level ACCF between January 2019 and May 2021 were retrospectively analyzed in two groups: patients with TMC subsidence as Group S and patients with no TMC subsidence as Group N during the one-year follow-up period. The degree of distraction of surgical segment and correction of the cervical curvature was measured to analyze their relationship with TMC subsidence. RESULTS: A total of 128 patients were included in Group S, and 138 patients were included in Group N. There was no significant difference in patient demographics and complications between the two groups. The degree of distraction in Group S was significantly higher than that in Group N (11.4% ± 7.6% vs. 4.7% ± 9.7%, P < 0.01). The change of C2 to C7 Cobb angle (α) in Group S was significantly greater than that in Group N (5.7 ± 2.7 vs. 1.4 ± 4.7, P < 0.01), and the change of interspinous process distance (SPD) in Group S was also significantly greater than that in Group N (7.0 ± 4.2 vs. 4.1 ± 2.7, P < 0.01). The JOA score and JOA recovery rate were not statistically different between the two groups. CONCLUSIONS: Intraoperative selection of overlength TMC in single-level ACCF for OPLL, over-distraction and excessive correction of the cervical curvature may cause TMC subsidence after surgery. No significant impact of TMC subsidence on the surgical outcome was observed during the 1-year follow-up period.

Anterior cervical decompression and fusion surgery for cervicogenic headache: A multicenter prospective cohort study.

Background: Cervicogenic headache (CEH) has long been recognized as a referred pain deriving from pathological changes in the upper cervical nerves. However, previous clinical studies found that anterior lower cervical discectomy for the treatment of cervical myelopathy and/or radiculopathy can also help relieve associated headaches. To date, there is still a lack of large sample and prospective study to investigate the effect of anterior cervical decompression and fusion (ACDF) on CEH associated with cervical spondylosis. Methods: A total of 656 patients with cervical radiculopathy and/or myelopathy were enrolled in three spinal centers. Among them, 221 patients who were diagnosed with CEH were collected in this study, and 204 completed a 1-year follow-up. The primary endpoint was headache intensity during a 12-month follow-up period measured by the numeric pain rating scale (NPRS). The secondary outcome measures included headache frequency, headache duration, and the neck disability index (NDI). Results: Among all 204 patients with CEH who completed a 1-year follow-up, 166 received anterior cervical surgery (surgery group) and 38 received conservative treatment (conservative group). There were statistically significant lower NPRS in the surgical group during follow-up. Between-group differences showed that NPRS in the surgery group was significantly greater improvement at 1 month (2.8, 95% CI: 2.0, 3.6), 3 months (2.6, 95% CI: 1.8, 3.4), 6 months (2.4, 95% CI: 1.6, 3.2), and 12 months (1.5, 95% CI: 0.7, 2.4) (p < 0.05 for all). There were statistically significant lower NDI, less frequent headaches, and lower headache duration in the surgery group during follow-up (p < 0.05 for all). Conclusion: This study indicates that ACDF can effectively relieve CEH associated with cervical myelopathy and/or radiculopathy.