CircCOX6A1 suppresses osteogenic differentiation and aggravates osteoporosis via miR-512-3p/DYRK2 axis.

BACKGROUND: Osteoporosis (OP), characterized by compromised bone integrity and increased fracture risk, poses a significant health challenge. Circular RNAs (circRNAs) have emerged as crucial regulators in various pathophysiological processes, prompting investigation into their role in osteoporosis. This study aimed to elucidate the involvement of circCOX6A1 in OP progression and understand its underlying molecular mechanisms. The primary objective was to explore the impact of circCOX6A1 on bone marrow-derived mesenchymal stem cells (BMSCs) and its potential interactions with miR-512-3p and DYRK2. METHODS: GSE161361 microarray analysis was employed to assess circCOX6A1 expression in OP patients. We utilized in vitro and in vivo models, including BMSC cultures, osteogenic differentiation assays, and an OVX-induced mouse model of OP. Molecular techniques such as quantitative RT-PCR, western blotting, and functional assays like alizarin red staining (ARS) were employed to evaluate circCOX6A1 effects on BMSC proliferation, apoptosis, and osteogenic differentiation. The interaction between circCOX6A1, miR-512-3p, and DYRK2 was investigated through dual luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down assays. RESULTS: CircCOX6A1 was found to be upregulated in osteoporosis patients, and its expression inversely correlated with osteogenic differentiation of BMSCs. CircCOX6A1 knockdown enhanced osteogenic differentiation, as evidenced by increased mineralized nodule formation and upregulation of osteogenic markers. In vivo, circCOX6A1 knockdown ameliorated osteoporosis progression in OVX mice. Mechanistically, circCOX6A1 acted as a sponge for miR-512-3p, subsequently regulating DYRK2 expression. CONCLUSION: This study provides compelling evidence for the role of circCOX6A1 in osteoporosis pathogenesis. CircCOX6A1 negatively regulates BMSC osteogenic differentiation through the miR-512-3p/DYRK2 axis, suggesting its potential as a therapeutic target for mitigating OP progression.

Bioinformatics analysis and validation of mesenchymal stem cells related gene MT1G in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a primary malignant bone tumor arising from mesenchymal cells. The standard clinical treatment for OS involves extensive tumor resection combined with neoadjuvant chemotherapy or radiotherapy. OS's invasiveness, lung metastasis, and drug resistance contribute to a low cure rate and poor prognosis with this treatment. Metallothionein 1G (MT1G), observed in various cancers, may serve as a potential therapeutic target for OS. METHODS: OS samples in GSE33382 and TARGET datasets were selected as the test cohorts. As the external validation cohort, 13 OS tissues and 13 adjacent cancerous tissues from The Second Affiliated Hospital of Nanchang University were collected. Patients with OS were divided into high and low MT1G mRNA-expression groups; differentially expressed genes (DEGs) were identified as MT1G-related genes. The biological function of MT1G was annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) and gene set enrichment analysis (GSEA). Gene expression correlation analysis and competing endogenous RNA (ceRNA) regulatory network construction were used to determine potential biological regulatory relationships of DEGs. Survival analysis assessed the prognostic value of MT1G. RESULTS: MT1G expression increased in OS samples and presented higher in metastatic OS compared with non-metastatic OS. Functional analyses indicated that MT1G was mainly associated with spliceosome. A ceRNA network with DEGs was constructed. MT1G is an effective biomarker predicting survival and correlated with increased recurrence rates and poorer survival. CONCLUSIONS: This research identified MT1G as a potential biomarker for OS prognosis, highlighting its potential as a therapy target.

Investigating Novel Therapeutic Approaches for Idiopathic Short Stature: Targeting siRNA and Growth Hormone Delivery to the Growth Plate Using Exosome Nanoparticles.

Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.

Modified Percutaneous Endoscopic Interlaminar Discectomy through the Near-spinous Process Approach for L4/5 Disc Herniation: A Retrospective Clinical Study.

OBJECTIVE: Compared with traditional open surgery, percutaneous endoscopic lumbar discectomy (PELD) has the advantages of less trauma, faster recovery, and less postoperative pain, so it has been widely used in the field of spinal surgery. However, it still has the defect of intraoperative fluoroscopy occurrences, complications, and even the risk of damage to the spinal cord and nerve. This study aims to compare the clinical efficacy of modified percutaneous endoscopic interlaminar discectomy (MPEID) with percutaneous endoscopic transforaminal discectomy (PETD) in treating L4/5 lumbar disc herniation (LDH) and to evaluate the effectiveness and safety of MPEID. METHODS: Thirty-four L4/5 LDH patients treated at the Second Affiliated Hospital of Nanchang University from June 2020 to June 2021 were studied retrospectively. Seventeen underwent MPEID and seventeen PETD. Variables analyzed included demographics, operative duration, intraoperative fluoroscopy occurrences, and surgical outcomes. Effectiveness was evaluated using the visual analogue scale (VAS), Oswestry disability index (ODI), and modified MacNab criteria. Lumbar Magnetic Resonance Imaging (MRI) was used to assess radiological outcomes. A paired t-test was performed to compare intragroup pre- and postoperative clinical data, VAS, and ODI scores. RESULTS: The average operative time in PETD group was 91.65 ± 14.04 min, and the average operative time in MPEID group was 65.41 ± 12.61 min (p < 0.001). In PETD group, the fluoroscopy occurrences averaged 9.71 ± 1.05 times, with fluoroscopy occurrences averaging 6.47 ± 1.00 times (p < 0.001) in MPEID group. At 12 months follow-up, the clinical effect showed significant improvement in both two groups. The MPEID group showed a decrease in average VAS-back score from 5.41 ± 2.18 to 1.76 ± 1.09 (p < 0.001) and VAS-leg score from 6.53 ± 1.66 to 0.82 ± 0.64 (p < 0.001). The ODI scores decreased from 51.35 ± 10.65 to 11.71 ± 2.91 (p < 0.001). In the PETD group, the VAS-back score decreased from 4.94 ± 1.98 to 2.06 ± 1.25 (p < 0.001), VAS-leg score from 7.12 ± 1.73 to 1.12 ± 0.60 (p < 0.001), and ODI scores from 48.00 ± 11.62 to 12.24 ± 2.56 (p < 0.001). According to the modified MacNab criteria, MPEID had 15 excellent and two good results; PETD had 12 excellent and 5 good (p = 0.23). No nerve root injuries, dural tears, or significant complications were reported. CONCLUSION: MPEID and PETD effectively treat L4/5 LDH, with MPEID showing shorter operative times and fewer fluoroscopies. Furthermore, the MPEID group can provide excellent clinical efficacy as the PETD group in the short term.

Molecular characterization of Golgi apparatus-related genes indicates prognosis and immune infiltration in osteosarcoma.

BACKGROUND: The Golgi apparatus (GA) is crucial for protein synthesis and modification, and regulates various cellular processes. Dysregulation of GA can lead to pathological conditions like neoplastic growth. GA-related genes (GARGs) mutations are commonly found in cancer, contributing to tumor metastasis. However, the expression and prognostic significance of GARGs in osteosarcoma are yet to be understood. METHODS: Gene expression and clinical data of osteosarcoma patients were obtained from the TARGET and GEO databases. A consensus clustering analysis identified distinct molecular subtypes based on GARGs. Discrepancies in biological processes and immunological features among the subtypes were explored using GSVA, ssGSEA, and Metascape analysis. A GARGs signature was constructed using Cox regression. The prognostic value of the GARGs signature in osteosarcoma was evaluated using Kaplan-Meier curves and a nomogram. RESULTS: Two GARG subtypes were identified, with Cluster A showing better prognosis, immunogenicity, and immune cell infiltration than Cluster B. A novel risk model of 3 GARGs was established using the TARGET dataset and validated with independent datasets. High-risk patients had poorer overall survival, and the GARGs signature independently predicted osteosarcoma prognosis. Combining risk scores and clinical characteristics in a nomogram improved prediction performance. Additionally, we discovered Stanniocalcin-2 (STC2) as a significant prognostic gene highly expressed in osteosarcoma and potential disease biomarker. CONCLUSIONS: Our study revealed that patients with osteosarcoma can be divided into two GARGs subgroups. Furthermore, we have developed a GARGs prognostic signature that can accurately forecast the prognosis of osteosarcoma patients.

Comprehensive analysis of gene expression profiles of annulus fibrosus subtypes and hub genes in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) has been considered a major cause of low back pain. Therefore, further molecular subtypes of IVDD and identification of potential critical genes are urgently needed. First, consensus clustering was used to classify patients with IVDD into two subtypes and key module genes for subtyping were identified using weighted gene co-expression network analysis (WGCNA). Then, key module genes for the disease were identified by WGCNA. Subsequently, SVM and GLM were used to identify hub genes. Based on the above genes, a nomogram was constructed to predict the subtypes of IVDD. Finally, we find that ROM1 is lowered in IVDD and is linked to various cancer prognoses. The present work offers innovative diagnostic and therapeutic biomarkers for molecular subtypes of IVDD.

Fenton-like Reaction Inspired "·OH Catalyzed" Osteogenic Process for the Treatment of Osteoporosis.

Inspired by the Fenton-like reaction, this work combines copper peroxide (CP) nanoparticles with black phosphorus (BP) nanosheets to form a hydroxyl radical (·OH)-centered "catalytic" osteogenic system. CP-produced ·OH interacts with BP to rapidly produce a large amount of phosphate ions, thus accelerating self-mineralization and promoting bone formation. In turn, BP not only exerts anti-inflammatory effects, thereby providing a favorable microenvironment for bone formation, but also offsets the potential toxicity of CP induced by reactive oxygen species (ROS). Together with copper ions (Cu2+ ), phosphate ions are also released as a byproduct of this process, which can contribute to the comprehensive promotion of osteogenesis.

PMAIP1, a novel diagnostic and potential therapeutic biomarker in osteoporosis.

BACKGROUND: Osteoporosis is a common endocrine metabolic bone disease, which may lead to severe consequences. However, the unknown molecular mechanism of osteoporosis, the observable side effects of present treatments and the inability to fundamentally improve bone metabolism seriously restrict the impact of prevention and treatment. The study aims to identify potential biomarkers from osteoclast progenitors, specifically peripheral blood monocytes on predicting the osteoporotic phenotype. METHODS: Datasets were obtained from Gene Expression Omnibus (GEO). Based on the differentially expressed genes (DEGs) and GSEA results, GO and KEGG analyses were performed using the DAVID database and Metascape database. PPI network, TF network, drug-gene interaction network, and ceRNA network were established to determine the hub genes. Its osteogenesis, migration, and proliferation abilities in bone marrow mesenchymal stem cells (BMSCs) were validated through RT-qPCR, WB, ALP staining, VK staining, wound healing assay, transwell assay, and CCK-8 assay. RESULTS: A total of 63 significant DEGs were screened. Functional and pathway enrichment analysis discovered that the functions of the significant DEGs (SDEGs) are mainly related to immunity and metal ions. A comprehensive evaluation of all the network analyses, PMAIP1 was defined as osteoporosis's core gene. This conclusion was further confirmed in clinical cohort data. A series of experiments demonstrated that the PMAIP1 gene can promote the osteogenesis, migration and proliferation of BMSC cells. CONCLUSIONS: All of these outcomes showed a new theoretical basis for further research in the treatment of osteoporosis, and PMAIP1 was identified as a potential biomarker for osteoporosis diagnosis and treatment.

Ganoderic acid A slows osteoarthritis progression by attenuating endoplasmic reticulum stress and blocking NF-Κb pathway.

Osteoarthritis (OA) is a prevalent degenerative pathology, however, there exists a lack of cost-effective pharmacological interventions that efficaciously inhibit its progression. ganoderic acid A (GAA), a triterpenoid derived from Ganoderma lucidum, possesses antiapoptotic and -inflammatory effects. Our objective was to better understand the therapeutic effects of GAA on OA as well as to elucidate the underlying mechanisms of its action. To establish an OA cell model in vitro, chondrocytes (CHONs) were treated with interleukin (IL)-1ß. Subsequently, the investigation was conducted afterward according to the following indicators: cell viability, apoptosis, inflammation, and extracellular matrix (ECM) degradation. Western blotting analysis (WB) was employed to assess both endoplasmic reticulum (ER) stress and proteins associated with the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, based on molecular docking studies, GAA exhibits a significant binding competence to p65. OA mouse models were constructed by performing a destabilization medial meniscus (DMM) operation. Moreover, histopathology and immunohistochemistry were used to determine the GAA therapeutic effect in reducing OA in vivo. Our findings revealed that GAA has antiapoptotic, anti-inflammatory, and anti-ECM degradation effects by inhibiting the ER stress and NF-κB axis in CHONs in vitro. Furthermore, our findings suggest that GAA may attenuate the progression of osteoarthritis in vivo. GAA can protect CHONs by regulating apoptosis, ECM changes, and inflammation thereby preventing OA progression. These promising results indicate that GAA may be a therapeutic agent for OA treatment.

Identification of CXCL16 as a diagnostic biomarker for obesity and intervertebral disc degeneration based on machine learning.

Intervertebral disc degeneration (IDD) is the primary cause of neck and back pain. Obesity has been established as a significant risk factor for IDD. The objective of this study was to explore the molecular mechanisms affecting obesity and IDD by identifying the overlapping crosstalk genes associated with both conditions. The identification of specific diagnostic biomarkers for obesity and IDD would have crucial clinical implications. We obtained gene expression profiles of GSE70362 and GSE152991 from the Gene Expression Omnibus, followed by their analysis using two machine learning algorithms, least absolute shrinkage and selection operator and support vector machine-recursive feature elimination, which enabled the identification of C-X-C motif chemokine ligand 16 (CXCL16) as a shared diagnostic biomarker for obesity and IDD. Additionally, gene set variant analysis was used to explore the potential mechanism of CXCL16 in these diseases, and CXCL16 was found to affect IDD through its effect on fatty acid metabolism. Furthermore, correlation analysis between CXCL16 and immune cells demonstrated that CXCL16 negatively regulated T helper 17 cells to promote IDD. Finally, independent external datasets (GSE124272 and GSE59034) were used to verify the diagnostic efficacy of CXCL16. In conclusion, a common diagnostic biomarker for obesity and IDD, CXCL16, was identified using a machine learning algorithm. This study provides a new perspective for exploring the possible mechanisms by which obesity impacts the development of IDD.

Evaluation of Safety and Efficacy of Preoperative Coronal MRI-Guided Minimally Invasive Surgery for Cervical Spondylotic Radiculopathy.

BACKGROUND Key-hole surgery is a minimally invasive technique that has shown promise in various surgical procedures. This study aimed to assess the clinical effectiveness of preoperative coronal MRI-assisted key-hole surgery for the treatment of patients with cervical spondylotic radiculopathy (CSR). MATERIAL AND METHODS A total of 30 patients diagnosed with CSR and undergoing key-hole surgery with CMRI assistance were included in the study. Various parameters, including surgical segments, incision length, disease duration, operative time, intraoperative fluoroscopy times, intraoperative blood loss, complications, and length of hospitalization, were recorded. Precise measurements of Cobb angles and intervertebral space height were taken before and after the surgical procedure. Surgical outcomes were evaluated using modified Macnab criteria, visual analogue scale (VAS), Japanese Orthopaedic Association Scores (JOA), and neck disability index (NDI). RESULTS The average duration of disease was 6.47±3.29 months, with an average incision length of 1.94±0.15 cm and operative time of 57.83±4.34 minutes. The average intraoperative blood loss was 33.70±9.28 ml, with an average of 3.50±0.73 intraoperative fluoroscopies. The average duration of hospitalization was 4.10±1.27 days. Preoperative and postoperative measurements showed no statistically significant difference in C2-C7 Cobb angles and intervertebral space height. However, there were significant improvements in postoperative VAS, NDI, and JOA scores compared to preoperative scores. The surgical effectiveness rate was 100%, with a high rate of good and excellent outcomes. CONCLUSIONS The findings of this study suggest that preoperative CMRI-assisted key-hole surgery for single-segment CSR is a safe and effective treatment option with low complication rates. The clinical benefits include high security and good outcomes. Further research and larger studies are warranted to validate these findings.

Identification of mitochondrial-related signature and molecular subtype for the prognosis of osteosarcoma.

Mitochondria play a vital role in osteosarcoma. Therefore, the purpose of this study was to investigate the potential role of mitochondrial-related genes (MRGs) in osteosarcoma. Based on 92 differentially expressed MRGs, osteosarcoma samples were divided into two subtypes using the nonnegative matrix factorization (NMF). Ultimately, a univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analysis were performed to construct a prognostic risk model. The single-sample gene set enrichment analysis assessed the immune infiltration characteristics of osteosarcoma patients. Finally, we identified an osteosarcoma biomarker, malonyl-CoA decarboxylase (MLYCD), which showed downregulation. Osteosarcoma cells proliferation, migration, and invasion were effectively inhibited by the overexpression of MLYCD. Our findings will help us to further understand the molecular mechanisms of osteosarcoma and contribute to the discovery of new diagnostic biomarkers and therapeutic targets.

Role of arachidonic acid metabolism in intervertebral disc degeneration: identification of potential biomarkers and therapeutic targets via multi-omics analysis and artificial intelligence strategies.

BACKGROUND: Intervertebral disc degeneration (IVDD) is widely recognized as the primary etiological factor underlying low back pain, often necessitating surgical intervention as the sole recourse in severe cases. The metabolic pathway of arachidonic acid (AA), a pivotal regulator of inflammatory responses, influences the development and progression of IVDD. METHODS: Initially, a comparative analysis was conducted to investigate the relationship between AA expression patterns and different stages of IVDD using single-cell sequencing (scRNA-seq) data. Additionally, three machine learning methods (LASSO, random forest, and support vector machine recursive feature elimination) were employed to identify hub genes associated with IVDD. Subsequently, a novel artificial intelligence prediction model was developed for IVDD based on an artificial neural network algorithm and validated using an independent dataset. The identified hub genes were further subjected to functional enrichment, immune infiltration, and Connectivity Map analysis. Moreover, external validation was performed using flow cytometry and real-time reverse transcription polymerase chain reaction analysis. RESULTS: Both scRNA-seq and bulk RNA-seq data revealed a positive correlation between the severity of IVDD and the AA metabolic pathway. They also revealed increased AA metabolic activity in macrophages and neutrophils, as well as enhanced intercellular communication with nucleus pulposus cells. Utilizing advanced machine learning algorithms, five hub genes (AKR1C3, ALOX5, CYP2B6, EPHX2, and PLB1) were identified, and an incipient diagnostic model was developed with an AUC of 0.961 in the training cohort and 0.72 in the validation cohort. An in-depth exploration of the functionality of these hub genes revealed their notable association with inflammatory responses and immune cell infiltration. Lastly, AH6809 was found to delay IVDD by inhibiting AKR1C3. CONCLUSIONS: This study offers comprehensive insights into potential biomarkers and small molecules associated with the early pathogenesis of IVDD. The identified biomarkers and the developed integrated diagnostic model hold great promise in predicting the onset of early IVDD. AH6809 was established as a therapeutic target for AKR1C3 in the treatment of IVDD, as evidenced by computer simulations and biological experiments.

Molecular characterization of cancer-intrinsic immune evasion genes indicates prognosis and tumour microenvironment infiltration in osteosarcoma.

Cancer-intrinsic immune evasion (IE) to cells is a critical factor in tumour growth and progression, yet the molecular characterization of IE genes (IEGs) in osteosarcoma remains underexplored. In this study, 85 osteosarcoma patients were comprehensively analyzed based on 182 IEGs, leading to the identification of two IE clusters linked to distinct biological processes and clinical outcomes. In addition, two IE clusters demonstrated diverse immune cell infiltration patterns, with IEGcluster A displaying increased levels compared to IEGcluster B. Moreover, an IE score was identified as an independent prognostic factor and nomogram may serve as a practical tool for the individual prognostic evaluation of patients with osteosarcoma. Finally, GBP1, a potential biomarker with high expression in osteosarcoma was identified. The findings of this study highlight the presence of two IE clusters, each associated with differing patient outcomes and immune infiltration properties. The IE score may serve to assess individual patient IE characteristics, enhance comprehension of immune features, and guide more efficacious treatment approaches.

Long intergenic non-coding RNA DIO3OS promotes osteosarcoma metastasis via activation of the TGF-ß signaling pathway: a potential diagnostic and immunotherapeutic target for osteosarcoma.

BACKGROUND: The aim of this study was to determine the underlying potential mechanisms and function of DIO3OS, a lincRNA in osteosarcoma and clarify that DIO3OS can be used as a potential diagnostic biomarker and immunotherapeutic target. METHODS: The expression matrix data and clinical information were obtained from XENA platform of UCSC and GEO database as the test cohorts. The external validation cohort was collected from our hospital. Bioinformatics analysis was used to annotate the biological function of DIO3OS. Immune infiltration and immune checkpoint analysis were applied to evaluate whether DIO3OS can be used as an immunotherapeutic target. ROC curves and AUC were established to assess the diagnostic value of DIO3OS for differentiating patients from other subtypes sarcoma. The expression analysis was detected by qRT-PCR, western blot, and immunohistochemical. Wound healing assay and Transwell assay were applied to determine the migration and invasion function of DIO3OS in osteosarcoma cell lines. The tail vein injection osteosarcoma cells metastases model was used in this research. RESULTS: High expression of DIO3OS was identified as a risk lincRNA for predicting overall survival of osteosarcoma in test cohort. The outcomes of experiments in vitro and in vivo showed that low expression of DIO3OS limited osteosarcoma tumor metastasis with inhibiting TGF-ß signaling pathway. Immune checkpoint genes (CD200 and TNFRSF25) expressions were inhibited in the low DIO3OS expression group. The DIO3OS expression can be applied to reliably distinguish osteosarcoma from lipomatous neoplasms, myomatous neoplasms, nerve sheath tumors, and synovial-like neoplasms. This result was further validated in the validation cohort. CONCLUSIONS: In conclusion, our outcomes indicated that DIO3OS is a potential diagnostic and prognostic biomarker of osteosarcoma, emphasizing its potential as a target of immunotherapy to improve the treatment of osteosarcoma through TGF-ß signaling pathway. TRIAL REGISTRATION NUMBER: The present retrospectively study was approved by the Ethics Committee of The Second Affiliated Hospital of Nanchang University [Review (2020) No. (115)].

Risk Factors and Causes of Reoperation in Lumbar Disc Herniation Patients after Percutaneous Endoscopic Lumbar Discectomy: A Retrospective Case Series with a Minimum 2-Year Follow-Up.

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) has gained popularity as a minimally invasive surgery for treating lumbar disc herniation. However, there is limited research focusing on the reoperation rate and its associated factors. This study aims to investigate the rate of reoperation and identify the causes and risk factors for reoperation after PELD. MATERIAL AND METHODS We conducted a retrospective analysis of patients who underwent PELD (interlaminar and transforaminal approaches) at our hospital from November 2016 to May 2020. A matched case-control design was employed to identify relevant risk factors for reoperation, with a matching ratio of 1:3. Clinical characteristics and radiological parameters were compared, and univariate analysis was performed using independent samples t-test and chi-squared test. RESULTS Among the 435 patients included in the study, the reoperation rate for those with a minimum 2-year follow-up was 6.2% (27/435). The causes of reoperation and their respective rates were as follows: recurrence of lumbar disc herniation (3.2%, 14/435), incomplete decompression (1.8%, 8/435), persistent low back pain (0.7%, 3/435), and postoperative infection (0.5%, 2/435). Univariate analysis revealed that age (P=0.015), Pfirrmann grade IV-V (P=0.017), and lack of active straight leg raise exercises (P=0.026) were significantly associated with reoperation. Multiple logistic regression analysis indicated that age (P=0.001), Pfirrmann grade IV-V (P=0.033), and lack of active straight leg raise exercises postoperatively (P=0.003) were independent risk factors for reoperation after PELD. CONCLUSIONS The primary cause of reoperation in lumbar disc herniation patients after PELD was recurrence of the herniation. Additionally, severe disc degeneration, older age, and lack of active straight leg raise exercises were identified as significant risk factors associated with an increased reoperation rate.

Case report: Traumatic lumbosacral spondyloptosis with locked L5 inferior articular process.

Background: Traumatic lumbosacral spondyloptosis is a very rare spinal disease caused by high-energy trauma. We report a case of traumatic lumbosacral spondyloptosis with locked L5 inferior articular process. Case presentation: A 33-year-old man presented with multisite pain for 6 h following waist trauma and was admitted to the hospital. He suffered multiple injuries from severe impact on the waist after driving an out of control forklift truck. Preoperative imaging examinations revealed that the patient was diagnosed with traumatic lumbosacral spondyloptosis and the L5 inferior articular process was locked into the anterior margin of the S1 vertebra. A posterior instrumentation, decompression of the cauda equina, and interbody fusion procedure was performed. The patient received hyperbaric oxygen and rehabilitation treatment 10 days after the surgery. At the 6-month postoperative follow-up, the muscle strength of the lower limbs was improved, the patient had no numbness of both lower limbs, and the urinary retention symptom was significantly improved. The American Spinal Injury Association grade improved from grade C preoperatively to grade D postoperatively. As far as we know, there have been no relevant reports on traumatic lumbosacral spondyloptosis with locked L5 inferior articular process yet. Conclusion: We believe that the hyperflexion and shear forces were the potential causes of this injury. In addition, the preoperative imaging examinations should be evaluated carefully. If the inferior articular process of L5 were locked, we suggest removing the bilateral inferior articular processes first and then perform reduction.

Role of non­coding RNAs in cartilage endplate (Review).

Cartilage endplate (CEP) degeneration is considered one of the major causes of intervertebral disc degeneration (IDD), which causes non-specific neck and lower back pain. In addition, several non-coding RNAs (ncRNAs), including long ncRNAs, microRNAs and circular RNAs have been shown to be involved in the regulation of various diseases. However, the particular role of ncRNAs in CEP remains unclear. Identifying these ncRNAs and their interactions may prove to be is useful for the understanding of CEP health and disease. These RNA molecules regulate signaling pathways and biological processes that are critical for a healthy CEP. When dysregulated, they can contribute to the development disease. Herein, studies related to ncRNAs interactions and regulatory functions in CEP are reviewed. In addition, a summary of the current knowledge regarding the deregulation of ncRNAs in IDD in relation to their actions on CEP cell functions, including cell proliferation, apoptosis and extracellular matrix synthesis/degradation is presented. The present review provides novel insight into the pathogenesis of IDD and may shed light on future therapeutic approaches.

Impact of Hepatitis B virus infection on postoperative complications and length of stay in elderly patients with hip fracture: A retrospective cohort study.

BACKGROUND: Osteoporosis and subsequent fractures are common in the chronic hepatitis B (CHB) population, especially in the elderly. This study investigated the effects of hepatitis B virus (HBV) infection on postoperative outcomes following hip fracture surgery. METHODS: The study identified elderly patients who underwent hip fracture surgery at three academic tertiary care centres between January 2014 and December 2020. Propensity score matching was performed to compare the outcomes of 1,046 patients with HBV infection to 1,046 controls. RESULTS: The seroprevalence of HBV among elderly patients undergoing hip surgery was 4.94%. The HBV cohort had significantly higher rates of medical complications (28.1 vs. 22.7%, p = 0.005), surgical complications (14.0 vs. 9.7%, p = 0.003), and unplanned readmissions (18.9 vs. 14.5%, p = 0.03) within 90 days of surgery. Patients with HBV infection were more likely to have increased length of stay (6.2 vs. 5.9 days, p = 0.009) and in-hospital charges (¥52,231 vs. ¥49,832, p < 0.00001). Multivariate logistic regression suggested that liver fibrosis and thrombocytopenia were independent risk factors for major complications and extended LOS. CONCLUSION: Patients with HBV infection were at greater risk of adverse postoperative outcomes. We should pay more attention to the considerable burden of perioperative management of CHB patients. Due to the high proportion of undiagnosed patients in the Chinese elderly population, universal HBV screening should be considered preoperatively.

Deubiquitinase USP33 promotes the glycolysis and growth of osteosarcoma by modifying PFKFB3 ubiquitination and degradation.

Osteosarcoma (OS) is the most common malignant tumor of the bone tissue with the lowest survival rate among all pediatric cancers. OS cells grow vigorously under malnutrition; however, the mechanism by which they adapt to metabolic stress via metabolic reprogramming remains undefined. Here, we demonstrated that USP33, a member of the DUBs family, was significantly upregulated in the tissues of patients with OS compared to normal tissues. Moreover, high USP33 expression was significantly associated with poor survival. Functional assays suggested that USP33 promoted OS cell growth through the induction of aerobic glycolysis. Additionally, we confirmed that 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) was critical for USP33-induced proliferation and aerobic glycolysis in OS cells, and the protein expression levels of PFKFB3 and USP33 were positively correlated in the OS tissues. Mechanistically, USP33 stabilized the expression of PFKFB3 by suppressing the ubiquitin mediated PFKFB3 degradation. Collectively, these findings reveal a mechanism by which OS cells survive in a dystrophic tumor microenvironment, with the USP33-PFKFB3 axis as a critical driver of aerobic glycolysis and OS proliferation. Furthermore, these findings reveal novel insights into the adaptation of cancer cells to metabolic stress in OS.