Identification and experimental validation of key genes in osteoarthritis based on machine learning algorithms and single-cell sequencing analysis.

Purpose: Osteoarthritis (OA) is a prevalent cause of disability in older adults. Identifying diagnostic markers for OA is essential for elucidating its mechanisms and facilitating early diagnosis. Methods: We analyzed 53 synovial tissue samples (n = 30 for OA, n = 23 for the control group) from two datasets in the Gene Express Omnibus (GEO) database. We identified differentially expressed genes (DEGs) between the groups and applied dimensionality reduction using six machine learning algorithms to pinpoint characteristic genes (key genes). We classified the OA samples into subtypes based on these key genes and explored the differences in biological functions and immune characteristics among subtypes, as well as the roles of the key genes. Additionally, we constructed a protein-protein interaction network to predict small molecules that target these genes. Further, we accessed synovial tissue sample data from the single-cell RNA dataset GSE152805, categorized the cells into various types, and examined variations in gene expression and their correlation with OA progression. Validation of key gene expression was conducted in cellular experiments using the qPCR method. Results: Four genes AGMAT, MAP3K8, PER1, and XIST, were identified as characteristic genes of OA. All can independently predict the occurrence of OA. With these genes, the OA samples can be clustered into two subtypes, which showed significant differences in functional pathways and immune infiltration. Eight cell types were obtained by analyzing the single-cell RNA data, with synovial intimal fibroblasts (SIF) accounting for the highest proportion in each sample. The key genes were found over-expressed in SIF and significantly correlated with OA progression and the content of immune cells (ICs). We validated the relative levels of key genes in OA and normal cartilage tissue cells, which showed an expression trend consistency with the bioinformatics result except for XIST. Conclusion: Four genes, AGMAT, MAP3K8, PER1, and XIST are closely related to the progression of OA, and play as diagnostic and predictive markers in early OA.

Identification of immune-related tumor antigens and immune subtypes in osteosarcoma.

Purpose: The development of tumor vaccines has become a hot topic in immunotherapy for osteosarcoma (OS); however, more tumor antigens with stronger immunogenicity need to be identified. Methods: We downloaded six sets of gene expression profile data from online databases. The overexpressed genes were analyzed, intersected, and used to calculate the immune infiltration abundance in the TARGET OS dataset based on their expression matrix. Potential tumor antigen genes were identified based on whether they exhibited a high correlation with the antigen-presenting cells (APCs). A total of 1330 immune-related genes (IRGs) from the ImmPort website were retrieved based on their expression, and the Consensus Cluster method was used to obtain immune subtypes of the OS samples. Prognosis, immune microenvironment, and sensitivity to drugs were compared among the immune subtypes. Results: In total, 680 genes were overexpressed in at least two datasets, of which TREM2, TNFRSF12A, and THY1 were positively correlated with different APCs. Based on the expression matrix of 1330 IRGs in TARGET-OS, two immune subtypes, IS1 and IS2, were identified. The prognosis of the IS1 subtype was better than that of IS2, the expression of immune checkpoint (ICP)-related genes was higher in patients with the IS1 subtype, and immune cell infiltration and sensitivity to 16 drugs were generally higher in IS1 subtype patients. Conclusion: We identified three APC-correlated genes that can be considered to code for potential novel tumor antigens for OS vaccines. Two immune subtypes in patients with OS were identified to implement personalized treatments using mRNA vaccines.

Identification and validation of hub genes and potential drugs involved in osteoarthritis through bioinformatics analysis.

Purpose: Osteoarthritis (OA) is a common degenerative disease, which still lacks specific therapeutic drugs. Synovitis is one of the most important pathological process in OA. Therefore, we aim to identify and analyze the hub genes and their related networks of OA synovium with bioinformatics tools to provide theoretical basis for potential drugs. Materials and methods: Two datasets were obtained from GEO. DEGs and hub genes of OA synovial tissue were screened through Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment as well as protein-protein interaction (PPI) network analysis. Subsequently, the correlation between expression of hub genes and ferroptosis or pyroptosis was analyzed. CeRNA regulatory network was constructed after predicting the upstream miRNAs and lncRNAs. The validation of hub genes was undertook through RT-qPCR and ELISA. Finally, potential drugs targeting pathways and hub genes were identified, followed by the validation of the effect of two potential drugs on OA. Results: A total of 161 commom DEGs were obtained, of which 8 genes were finally identified as hub genes through GO and KEGG enrichment analysis as well as PPI network analysis. Eight genes related to ferroptosis and pyroptosis respectively were significantly correlated to the expression of hub genes. 24 miRNAs and 69 lncRNAs were identified to construct the ceRNA regulatory network. The validation of EGR1, JUN, MYC, FOSL1, and FOSL2 met the trend of bioinformatics analysis. Etanercept and Iguratimod reduced the secretion of MMP-13 and ADAMTS5 of fibroblast-like synoviocyte. Conclusion: EGR1, JUN, MYC, FOSL1, and FOSL2 were identified as hub genes in the development of OA after series of bioinformatics analysis and validation. Etanercept and Iguratimod seemed to have opportunities to be novel drugs for OA.

COVID-19 vaccine uptake and hesitation among men and women preparing for pregnancy: a cross-section survey based on the theory of planned behavior.

BACKGROUND: Given the accelerated speed of COVID-19 vaccine research and administration, the main barriers to herd immunity appear to be concerns about safety and efficacy. Men and women preparing for pregnancy may have the same concerns about COVID-19 vaccination, but few studies have focused on COVID-19 vaccine uptake and hesitation among them. METHODS: A cross-sectional study was conducted among men and women who were preparing for pregnancy in Southwest China. The questionnaire was designed based on the theory of planned behavior (TPB). Multiple logistic regression was used to explore the determinants of the behaviors of COVID-19 vaccination. RESULTS: A total of 2878 participants completed the survey. A total of 53.89% of participants received at least one dose of the COVID-19 vaccine. A total of 45.21% of participants would receive the COVID-19 vaccine in the future. A total of 0.90% of participants never thought about receiving the COVID-19 vaccine. Multiple logistic regression model 1 showed that female participants (OR:5.497, 95%CI: 4.292-7.041), participants who never received influenza vaccine (OR:2.664, 95%CI: 1.908-3.718), participants who had never been tested for COVID-19 (OR:2.244, 95%CI:1.504-3.349), participants who had higher score of negative attitude (OR:1.448, 95%CI: 1.219-1.719), participants who had lower scores of injunctive norms (OR:0.440, 95%CI: 0.360-0.537) and descriptive norms (OR:0.105, 95%CI: 0.088-0.126) were more likely to delay COVID-19 vaccination. Model 2 showed that participants who had lower scores for positive attitude (OR: 0.406, 95% CI: 0.230-0.716), injunctive norms (OR: 0.283, 95% CI: 0.130-0.614) and descriptive norms (OR: 0.060, 95% CI: 0.038-0.094) were more likely to refuse COVID-19 vaccination. CONCLUSIONS: The COVID-19 vaccination rate of men and women preparing for pregnancy was significantly lower than the average vaccination rate of China. Gender, protective health behaviors, vaccination attitudes, and subjective norms had effects on the vaccination behaviors of couples preparing for pregnancy.

Ferroptosis Plays a Role in Human Chondrocyte of Osteoarthritis Induced by IL-1ß In Vitro.

OBJECTIVE: Osteoarthritis (OA) is a common disease with complex and unclear pathogenesis. Ferroptosis is a new cell death mode, which is proved to be involved in different kinds of disease. We hypothesized that ferroptosis contributes to the progress of human OA. DESIGN: Chondrocytes were extracted from waste cartilage of total knee arthroplasty, and stimulated with interleukin-1ß (IL-1ß). Then, we detected the morphology, proliferation, and viability, and levels of Fe3+, glutathione (GSH), reactive oxygen species (ROS), malondialdehyde (MDA), and 5 proteins related to ferroptosis with or without intervention of ferrostatin-1 (Fer-1). In addition, we compared the effect of Fer-1 and liproxstatin-1 (Lip-1) on ferroptosis and the protection of chondrocytes by detecting several markers of both ferroptosis and OA. RESULTS: After stimulation of IL-1ß, there were significant changes on the shape of chondrocyte, with lower viability and proliferation. There was accumulation of intracellular Fe3+, GSH, ROS, and MDA, with the changes of expression of 5 ferroptosis-related proteins. With the contribution of Fer-1, results above were reversed. Moreover, there was no significant difference in GPX4 and ACSL4 between Fer-1 and Lip-1 group. However, the expression of COLX, ADAMTS5, and MMP-13 are lower after the treatment of Fer-1 compared with Lip-1. CONCLUSIONS: Ferroptosis plays an important role in human OA chondrocytes, which can be reversed by Fer-1, illustrating that inhibitor of ferroptosis may be a potential treatment of OA. Moreover, Lip-1 and Fer-1 can both alleviate the level of ferroptosis in OA chondrocytes, but Fer-1 had a more protective effect.

High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer's Disease.

Alzheimer's disease (AD) is an aging-related neurodegenerative disease. We aimed to investigate the metabolic mechanisms of aging and AD and to identify potential biomarkers for the early screening of AD in a natural aging population. To analyze the plasma metabolites related to aging, we conducted an untargeted metabolomics analysis using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry in a two-stage cross-sectional study. Spearman's correlation analysis and random forest were applied to model the relationship between age and each metabolite. Moreover, a systematic review of metabolomics studies of AD in the PubMed, Cochrane and Embase databases were searched to extract the differential metabolites and altered pathways from original studies. Pathway enrichment analysis was conducted using Mummichog. In total, 669 metabolites were significantly altered with aging, and 12 pathways were enriched and correlated with aging. Three pathways (purine metabolism, arginine and proline metabolism, and the TCA cycle) were shared between aging and AD. Arginine and proline metabolism play a key role in the progression from healthy to mild cognitive impairment and to AD in the natural aging population. Three metabolites, 16-a-hydroxypregnenolone, stearic acid and PC[16:0/22:5(4Z,7Z,10Z,13Z,16Z)] were finally proposed as potential markers of AD in the natural aging population. The underlying mechanism shared between aging and AD and the potential biomarkers for AD diagnosis were proposed based on multistep comparative analysis.

Role of tranexamic acid in blood loss control and blood transfusion management of patients undergoing multilevel spine surgery: A meta-analysis.

BACKGROUND: This study aimed to explore the role of tranexamic acid (TXA) in blood loss control and blood transfusion management of patients undergoing multilevel spine surgery. METHODS: In this meta-analysis, a comprehensive search of literatures was performed from PubMed, Embase, Cochrane Library, and Web of Science from inception to June 23rd, 2020. Weighed mean difference (WMD) was used as the effect size for measurement data, and risk ratio for enumeration data. Publication bias was assessed by Begg test. RESULTS: Totally 23 studies (11 randomized controlled trials and 12 cohort studies) involving 1621 participants were enrolled in this meta-analysis. The results showed that the administration of TXA can significantly decrease the intraoperative [WMD: -215.655, 95%CI: (-307.462, -123.847), P < .001], postoperative [WMD: -69.213, 95%CI: (-104.443, -33.983), P = .001] and total [WMD: -284.388, 95%CI: (-437.66, -131.116), P < .001] volumes of blood loss of patients undergoing multilevel spine surgery. It can also significantly reduce the intraoperative [WMD: -333.775, 95%CI: (-540.45, -127.099), P = .002] and postoperative [WMD: -114.661, 95%CI: (-219.58, -9.742), P = .032] volumes of transfusion. In addition, TXA was found to significantly increase the preoperative [WMD: 0.213, 95%CI: (0.037, 0.389), P = .018] and postoperative [WMD: 0.433, 95%CI: (0.244, 0.622), P < .001] hemoglobin levels as well as the preoperative platelet count [WMD: 14.069, 95%CI: (0.122, 28.015), P = .048]. CONCLUSION: The administration of TXA can effectively reduce blood loss and transfusion, and improve hemoglobin levels and preoperative platelet count in patients undergoing multilevel spine surgery.

Comparisons of different vitamin D supplementation for prevention of osteoporotic fractures: a Bayesian network meta-analysis and meta-regression of randomised controlled trials.

Previous randomised controlled trials have shown the controversial effectiveness of oral vitamin D supplementation in preventing osteoporotic fractures. PubMed, EMBASE and Cochrane Library electronic databases were searched. Pairwise meta-analysis, Bayesian network meta-analysis and meta-regression were applied. A total of 33 studies containing 83,083 participants were included. Oral vitamin D supplementation showed no statistically significant on reducing the risk of total fractures (RR = 0.96, 95%CI = 0.87-1.05 p = 0.389). Vitamin D3 (700-800IU/d) plus calcium showed statistical significance in reducing the incidence of total, hip and non-vertebral fractures in the pairwise meta-analysis. Significant reductions were specifically identified in female in total and hip fractures. However, we did not observe any above significant results using Bayesian network meta-analyses. Strikingly, a meta-regression analysis identified an inverse association between the efficacy of fracture prevention and increased body mass index. Thus, we recommended that the vitamin D dose should be adjusted according to BMI based on further confirmation.

Etiology of Spontaneous Extensor Tendon Injury in Northern-China Rice Farmers.

BACKGROUND: Spontaneous extensor tendon injury is caused by repeated finger flexion and wrist movement. This rare disease has a relatively high incidence in northern China, mostly among rice farmers. This study aimed to elucidate the etiology of spontaneous extensor tendon injury in rice farmers. METHODS: Morphologic changes in the extensor tendons and wrist extensor retinaculum in wrist dorsiflexion were studied via ultrasound examination of the hands of 30 healthy adult men, and 34 patients with a non-rupture extensor tendon injury and 11 patients with spontaneous ruptures of the extensor tendons were also enrolled in the study. The daily workload and potential causes of injuries were assessed. RESULTS: Ultrasound images of healthy male hands showed that during wrist dorsiflexion, the extensor retinaculum of the wrist forms differently shaped trochleas as the dorsiflexion angle changes. Histopathologic examination of the wrist extensor retinaculum revealed that the inner face was abraded evenly, the synovial membrane on the surface of the wrist extensor retinaculum disappeared, the internal coarse fibers were exposed and there was fibrous debris, suggesting that dry friction occurred before the rupture. CONCLUSIONS: From clinical observation it could be concluded that the severity and progress of swelling and pain are related to the force applied during rice transplantation as abrasions were found at the front of the wrist extensor retinaculum.

A Study to Compare the Efficacy of a Biodegradable Dynamic Fixation System With Titanium Devices in Posterior Spinal Fusion Between Articular Processes in a Canine Model.

The objective of this study was to apply a biodegradable dynamic fixation system (BDFS) for lumbar fusion between articular processes and compare the fusion results and biomechanical changes with those of conventional rigid fixation. Twenty-four mongrel dogs were randomly assigned to 2 groups and subjected to either posterior lumbar fusion surgery with a BDFS or titanium rods (TRs) at the L5-L6 segments. Six animals in each group were sacrificed at 8 or 16 weeks. Fusion conditions were evaluated by computed tomography (CT), manual palpation, biomechanical tests, and histological analysis. Biomechanical tests were performed at the L4-7 (for range of motion (ROM)) and L5-6 (for fusion stiffness) segments. Histological examination was performed on organs, surrounding tissues, and the fused area. The magnesium alloy components maintained their initial shape 8 weeks after the operation, but the meshing teeth were almost completely degraded at 16 weeks. The biomechanical analysis revealed an increased lateral bending ROM at 8 weeks and axial torsion ROM at 16 weeks. The L4-5 extension-flexion ROMs in the BDFS group were 2.29 ± 0.86 deg and 3.17 ± 1.08 deg at 16 weeks, respectively, compared with 3.22 ± 0.56 deg and 5.55 ± 1.84 deg in TR group. However, both groups showed similar fusion results. The BDFS design is suitable, and its degradation in vivo is safe. The BDFS can be applied for posterior lumbar fusion between articular processes to complete the fusion well. Additionally, the BDFS can reduce the decline in lateral motion and hypermotion of the cranial adjacent segment in flexion-extension motion.

Identification of Cross-Talk and Pyroptosis-Related Genes Linking Periodontitis and Rheumatoid Arthritis Revealed by Transcriptomic Analysis.

BACKGROUND: The current study is aimed at identifying the cross-talk genes between periodontitis (PD) and rheumatoid arthritis (RA), as well as the potential relationship between cross-talk genes and pyroptosis-related genes. METHODS: Datasets for the PD (GSE106090, GSE10334, GSE16134) and RA (GSE55235, GSE55457, GSE77298, and GSE1919) were downloaded from the GEO database. After batch correction and normalization of datasets, differential expression analysis was performed to identify the differentially expressed genes (DEGs). The cross-talk genes linking PD and RA were obtained by overlapping the DEGs dysregulated in PD and DEGs dysregulated in RA. Genes involved in pyroptosis were summarized by reviewing literatures, and the correlation between pyroptosis genes and cross-talk genes was investigated by Pearson correlation coefficient. Furthermore, the weighted gene coexpression network analysis (WGCNA) was carried out to identify the significant modules which contained both cross-talk genes and pyroptosis genes in both PD data and RA data. Thus, the core cross-talk genes were identified from the significant modules. Receiver-operating characteristic (ROC) curve analysis was performed to identify the predictive accuracy of these core cross-talk genes in diagnosing PD and RA. Based on the core cross-talk genes, the experimentally validated protein-protein interaction (PPI) and gene-pathway network were constructed. RESULTS: A total of 40 cross-talk genes were obtained. Most of the pyroptosis genes were not differentially expressed in disease and normal samples. By selecting the modules containing both cross-talk genes or pyroptosis genes, the blue module was identified to be significant module. Three genes, i.e., cross-talk genes (TIMP1, LGALS1) and pyroptosis gene-GPX4, existed in the blue module of PD network, while two genes (i.e., cross-talk gene-VOPP1 and pyroptosis gene-AIM2) existed in the blue module of RA network. ROC curve analysis showed that three genes (TIMP1, VOPP1, and AIM2) had better predictive accuracy in diagnosing disease compared with the other two genes (LGALS1 and GPX4). CONCLUSIONS: This study revealed shared mechanisms between RA and PD based on cross-talk and pyroptosis genes, supporting the relationship between the two diseases. Thereby, five modular genes (TIMP1, LGALS1, GPX4, VOPP1, and AIM2) could be of relevance and might serve as potential biomarkers. These findings are a basis for future research in the field.

A novel dynamic fixation system with biodegradable components on lumbar fusion between articular processes in a canine model.

The objective of this study was to design a novel dynamic fixation system with biodegradable components, apply it for lumbar fusion between articular processes and compare the fusion results and biomechanical changes to those of conventional rigid fixation. The novel dynamic fixation system was designed using a finite element model, stress distributions were compared and 24 mongrel dogs were randomly assigned to two groups and subjected to either posterior lumbar fusion surgery with a novel dynamic fixation system or titanium rods at the L5-L6 segments. Lumbar spines were assessed in both groups to detect radiographic, manual palpation and biomechanical changes. Histological examination was performed on organs and surrounding tissues. In the novel dynamic fixation system, stress was mainly distributed on the meshing teeth of the magnesium alloy spacer. The magnesium alloy components maintained their initial shape 8 weeks after the operation, but the meshing teeth were almost completely degraded at 16 weeks. The novel dynamic fixation system revealed an increased lateral bending range of motion at 8 weeks; however, both groups showed similar radiographic grades, fusion stiffness, manual palpation and histological results. The novel dynamic fixation system design is suitable, and its degradation in vivo is safe. The novel dynamic fixation system can be applied for posterior lumbar fusion between articular processes and complete the fusion like titanium rods.

A study to compare the efficacy of polyether ether ketone rod device with titanium devices in posterior spinal fusion in a canine model.

BACKGROUND: The benefits of posterior lumbar fusion surgery with orthotopic paraspinal muscle-pediculated bone flaps are well established. However, the problem of non-union due to mechanical support is not completely resolved. The aim of the study was to compare the efficacy of polyether ether ketone (PEEK) rod device with conventional titanium devices in the posterior lumbar fusion surgery with orthotopic paraspinal muscle-pediculated bone flaps. METHODS: This was a randomized controlled study with an experimental animal model. Thirty-two mongrel dogs were randomly divided into two groups-control group (n = 16), which received the titanium device and the treatment group (n = 16), which received PEEK rods. The animals were sacrificed 8 or 16 weeks after surgery. Lumbar spines of dogs in both groups were removed, harvested, and assessed for radiographic, biomechanical, and histological changes. RESULTS: Results in the current study indicated that there was no significant difference in the lumbar spine of the control and treatment groups in terms of radiographic, manual palpation, and gross examination. However, certain parameters of biomechanical testing showed significant differences (p < 0.05) in stiffness and displacement, revealing a better fusion (treatment group showed decreased stiffness with decreased displacement) of the bone graft. Similarly, the histological analysis also revealed a significant fusion mass in both treatment and control groups (p < 0.05). CONCLUSIONS: These findings revealed that fixation using PEEK connecting rod could improve the union of the bone graft in the posterior lumbar spine fusion surgery compared with that of the titanium rod fixation.

Sesamin inhibits IL-1ß-stimulated inflammatory response in human osteoarthritis chondrocytes by activating Nrf2 signaling pathway.

Sesamin, a bioactive component extracted from sesame, has been reported to exert anti-inflammatory and anti-oxidant effects. In this study, we evaluated the anti-inflammatory effects of sesamin on IL-1ß-stimulated human osteoarthritis chondrocytes and investigated the possible mechanism. Results demonstrated that sesamin treatment significantly inhibited PGE2 and NO production induced by IL-1ß. Sesamin inhibited MMP1, MMP3, and MMP13 production in IL-1ß-stimulated chondrocytes. Sesamin also inhibited IL-1ß-induced phosphorylation of NF-κB p65 and IκBα. Meanwhile, sesamin was found to up-regulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory effects of sesamin. In conclusion, our results suggested that sesamin showed anti-inflammatory effects in IL-1ß-stimulated chondrocytes by activating Nrf2 signaling pathway.

A comparison of osteocyte bioactivity in fine particulate bone powder grafts vs larger bone grafts in a rat bone repair model.

The osteogenic potential for bone grafts is based on numbers and activities of cells that survive transplantation. In this study, we compared the bioactivity of osteocytes in 300-500 µm fine particulate bone powder grafts to 2 mm larger bone grafts in a rat radial defect model. Expression levels of bone morphogenetic protein-2 (BMP-2), transforming growth factor-beta 1 (TGF-ß1), alkaline phosphatase (ALP), and collagen I were semi-quantified by both immunohistochemistry and RT-PCR at days 1 and 4, as well as weeks 1, 2, 4, 6 and 10 post-transplantation. Within two weeks post-transplantation, more cells stained positively for BMP-2, TGF-ß1, ALP, and collagen I within the bone grafts and in the surrounding tissues in the group transplanted with the fine particulate bone powder grafts than in those with larger bone grafts (P<0.05). The mRNA levels of all four markers in the group transplanted with fine particulate bone powder graft peaked earlier and were expressed more highly than in the larger bone graft group, suggesting that fine particulate bone powder grafts provide more viable and active osteocytes to accelerate bone defect healing than larger bone grafts.

In vitro and in vivo evaluation of a biphasic calcium phosphate scaffold coated with a native allogeneic extracellular matrix.

This study evaluated the osteogenic properties of biphasic calcium phosphate (BCP) scaffolds coated with extracellular matrix (ECM) derived in vitro from allogeneic mesenchymal stem cells (MSCs). BCP/ECM and plain BCP scaffolds were seeded with MSCs from F344 rats and cultured in osteoinductive medium. At 1, 7, 14 and 21 days post-seeding, assessments were made of cellularity, alkaline phosphatase (ALP) activity and RNA expression of osteocalcin, bone sialoprotein and osteopontin. MSCs seeded on BCP/ECM scaffolds exhibited significantly higher cellularity, ALP activity and transcript levels for the three genes examined. For the in vivo study, BCP/ECM and BCP scaffolds with and without MSCs were implanted subcutaneously into F344 rats. After four weeks of implantation, the extent of new bone formation and tissue response were examined by histology and histomorphometry; histological evidence showed that the seeded cell scaffolds induced new bone formation at the ectopic site and a higher average ratio of bone in the cell-seeded BCP/ECM scaffold group. Results suggest that modification of the BCP scaffold with an in vitro generated allogeneic ECM can effectively enhance osteogenic properties in vitro and in vivo.

Curcumin promotes the spinal cord repair via inhibition of glial scar formation and inflammation.

Spinal cord injury (SCI) is a serious clinical situation without any effective therapy to date. Traumatic SCI triggers a complex pathological process including inflammatory response and glial scar formation. In this study, we demonstrated that curcumin, a natural product which functions as an anti-inflammatory agent, inhibited the activation of signal transducer and activator of transcription-3 and NF-kappa B in the injured spinal cord. Curcumin treatment greatly reduced the astrogliosis in SCI mice and significantly decreased the expression of IL-1ß and NO, as well as the number of Iba1(+) inflammatory cells at the lesion site. Notably, more residual axons and neurons were protected and significantly improved functional recovery was observed in the curcumin-treated mice, compared to the mice without curcumin treatment. These findings indicate that curcumin promotes spinal cord repair through inhibiting glial scar formation and inflammation and suggests the therapeutic potential of curcumin for SCI.

[Clinical application of a novel posterior lumbar fusion method and the short-term observation of its effect].

OBJECTIVE: To increase local blood supply of bone graft, a novel posterior lumbar spine fusion method with orthotopic paraspinal muscle-pediculated bone flaps was constructed, and the fusion rate and clinical effect.were observed. METHODS: From June 2007 to December 2010, 117 patients of lumbar spinal stenosis or lumbar destabilization treated with the novel posterior lumbar fusion method were studied, 49 males and 68 females, aged from 40 to 77 years, average 61.5 years. Clinical effect was evaluated by JOA and VAS score preoperatively and postoperatively, and the fusion result was evaluated by three-dimensional CT reconstruction postoperatively. RESULTS: Seventeen cases lost of follow up, the rest were followed up from 7 to 38 months, average 19 months. There was significant difference between pre- and postoperative JOA and VAS score (P < 0.01), the preoperative JOA score was 10.3 ± 1.9, and 25.4 ± 4.2 at the latest follow-up, the improvement rate was 81.0% ; the preoperative VAS score was 8.5 ± 0.8, and 2.3 ± 0.4 at the latest follow-up. The three-dimensional CT reconstruction showed that 126 of the 133 segments formed solid fusion in 100 patients who completed the follow-up, the fusion rate was 94.7%. CONCLUSION: The novel posterior lumbar fusion method make the bone graft position more precise, stable and increases the fusion rate, which can effectively reduce pseudarthrosis and have a promising clinical effect.

Tumor necrosis factor-α-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model.

STUDY DESIGN: A prospective molecular mechanism of macrophages infiltration in experimental disc herniation. OBJECTIVE: To investigate the mechanisms of macrophages infiltration into the dorsal root ganglion (DRG) in a rat model of disc herniation. SUMMARY OF BACKGROUND DATA: Macrophages infiltrate the DRG after application of nucleus pulposus (NP) on the DRG, and may play an important role in radiculopathy. However, the mechanisms of macrophages infiltration after NP application remain poorly understood. METHODS: After experimental disc herniation in this study, we investigated changes in the expression of ED1 (a marker of macrophages) and vascular cell adhesion molecule-1 (VCAM-1) in DRG using immunofluorescence. We also investigated the expression of ED1 and VCAM-1 in DRG by treatment with tumor necrosis factor-α (TNF-α) inhibitor at the time of surgery. RESULTS: We found a massive ED1-positive macrophages infiltrated the DRG, and VCAM-1-like immunoreactivity vessels became evident after NP application. Furthermore, both macrophage infiltration and VCAM-1 expression were prevented by treatment with TNF-α inhibitor at the time of surgery. CONCLUSION: These findings indicated that macrophages infiltration into the DRG was TNF-α-dependent, and might be partly mediated by VCAM-1 in the early stage of experimental lumbar disc herination. Taken together, this study provides important preliminary data suggesting that TNF-α plays an important role in the macrophage infiltration. LEVEL OF EVIDENCE: N/A.

Surgical treatment of cervicothoracic junction spinal tuberculosis via combined anterior and posterior approaches in children.

BACKGROUND: Cervicothoracic junction spinal tuberculosis (CJST) in children is uncommon, especially when accompanied by a huge abscess. However, its consequences can be severe. Because of the special anatomic location of the cervicothoracic junction, surgical treatment is difficult and rarely reported. The aim of this clinical study was to assess the effectiveness of combined anterior and posterior approaches for focal debridement, decompression, allografting and anterior instrumentation in the treatment of CJST in children. METHODS: Ten pediatric CJST patients underwent focal debridement and cord decompression through combined anterior and posterior approaches. Then an appropriate allograft and titanium plate were applied to reconstruct the spine. The patients were asked to wear head-neck-chest braces for six months and received regular anti-tubercular drugs therapy for 12 months. RESULTS: The patients were followed-up for an average of 26 months (range, 15-32 months). There was no recurrent tuberculous infection. The bone grafts incorporated well and the instrumentation was stable. Cervical and thoracic kyphosis was successfully corrected from 40° (range, 30-52°) before the operation to 18° (range, 12-26°) post-operation. Neurological function was improved in all patients. CONCLUSIONS: Combined anterior and posterior approaches for focal debridement, decompression, bone allografting and anterior instrumentation provided an effective means of treatment in children of CJST with a huge abscess in the posterior part of the vertebral body.