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.

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.

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.

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.

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.

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)].

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.

Accuracy of Coronal Magnetic Resonance Imaging Diagnosis of Multi-Segmental Lumbar Disc Herniation: A Single-Center Retrospective Analysis.

BACKGROUND Multi-segment herniation of lumbar intervertebral discs is a complex lumbar spine disease, and it is difficult to identify the responsible segment using only magnetic resonance imaging (MRI). The present study screened 47 patients with multi-segment lumbar disc herniation (MSLDH) to evaluate coronal magnetic resonance imaging (CMRI) of three-dimensional fast-field echo with water-selective excitation to identify the responsible segment of multi-segment lumbar disc herniation (MSLDH) and to assess the accuracy and utility of CMRI. MATERIAL AND METHODS This retrospective study included 44 patients with low back pain or lower-extremity symptoms from January 2019 to December 2021. The imaging (including CMRI) and clinical data of the patients were analyzed by 3 independent, blinded experts. The Kappa statistical method was used to characterize the reader-to-reader reliability to qualitatively evaluate the data. RESULTS CMRI showed high diagnostic performance, with 90.2% sensitivity, 94.9% positive predictive value (PPV), 80% negative predictive value (NPV), and 83.4% accuracy, and there were significant differences in hospital length of stay (P=0.013) and surgical bleeding (P=0.006) (P<0.01) between single-segment and multi-segment patients. CONCLUSIONS CMRI is highly accurate in revealing the shape, signal, and position of the intraspinal and extraspinal lumbosacral plexus, and reducing surgical segments can help improve postoperative outcomes for patients.

Does Percutaneous Endoscopic Lumbar Discectomy for Adolescent Posterior Ring Apophysis Fracture Accompanied with Lumbar Disc Herniation Have Better Outcome Than Lumbar Disc Herniation Alone?

Objective: This study aims to compare the efficacy of percutaneous endoscopic lumbar discectomy (PELD) in treating adolescent posterior ring apophysis fracture (APRAF) accompanied by lumbar disc herniation (LDH) and lumbar disc herniation alone. Methods: Herein we present a case series of adolescent patients who underwent PELD surgery from June 2017 to September 2021. All patients were divided into two distinct groups (ie Group A and B), based on their preoperative Computed tomography (CT) scans. Group A included patients with PRAF (type III) accompanied by LDH. Group B patients had LDH alone. The general clinical characteristics, clinical outcomes, and complications in patients from the two groups were assessed and compared. Results: Compared to before surgery, the back and leg visual analog scores (VAS) and Oswestry Disability Index (ODI) were markedly improved in both groups' patients at all follow-ups. Notably, no significant differences were observed in the back and leg VAS scores, and ODI values between the two groups at different time points after surgery. The mean intraoperative blood loss was significantly lower in Group B, relative to Group A. The mean operation time was significantly shorter in Group B, compared to Group A. There was no statistically significant difference in complication and recurrence rates between the two groups. Conclusion: APRAF (type III) accompanied by LDH and LDH alone can obtain roughly equal surgical effects through PELD surgery and turns out to be a safe and effective surgical approach.

Plasma exosome miRNA-26b-3p derived from idiopathic short stature impairs longitudinal bone growth via the AKAP2/ERK1/2 axis.

BACKGROUND: Currently, the etiology of idiopathic short stature (ISS) is still unclear. The poor understanding of the molecular mechanisms of ISS has largely restricted this strategy towards safe and effective clinical therapies. METHODS: The plasma exosomes of ISS children were co-cultured with normal human chondrocytes. The differential expression of exosome miRNA between ISS and normal children was identified via high-throughput microRNA sequencing and bioinformatics analysis. Immunohistochemistry, In situ hybridization, RT-qPCR, western blotting, luciferase expression, and gene overexpression and knockdown were performed to reveal the key signaling pathways that exosome miRNA of aberrant expression in ISS children impairs longitudinal bone growth. RESULTS: Chondrocytes proliferation and endochondral ossification were suppressed after coculture of ISS plasma exosomes with human normal chondrocytes. High-throughput microRNA sequencing and RT-qPCR confirmed that plasma exosome miR-26b-3p was upregulated in ISS children. Meanwhile, exosome miRNA-26b-3p showed a high specificity and sensitivity in discriminating ISS from normal children. The rescue experiment showed that downregulation of miR-26b-3p obviously improved the repression of chondrocyte proliferation and endochondral ossification caused by ISS exosomes. Subsequently, miR-26b-3p overexpression inhibited chondrocyte proliferation and endochondral ossification once again. In situ hybridization confirmed the colocalization of miR-26b-3p with AKAP2 in chondrocytes. In vitro and in vivo assay revealed exosome miRNA-26b-3p impairs longitudinal bone growth via the AKAP2 /ERK1/2 axis. CONCLUSIONS: This study is the first to confirm that miR-26b-3p overexpression in ISS plasma exosomes leads to disorders in proliferation and endochondral ossification of growth plate cartilage via inhibition of AKAP2/ERK1/2 axis, thereby inducing ISS. This study provides a new research direction for the etiology and pathology of ISS and a new idea for the biological treatment of ISS.

Expression Profiles of Long Noncoding RNAs and Messenger RNAs in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious disorder of the central nervous system with a high disability rate. Long noncoding RNAs (lncRNAs) are reported to mediate many biological processes. The aim of this study was to explore lncRNA and mRNA expression profiles and functional networks after SCI. Differentially expressed genes between SCI model rats and sham controls were identified by microarray assays and analyzed by functional enrichment. Key lncRNAs were identified using a support vector machine- (SVM-) recursive feature elimination (RFE) algorithm. A trans and cis regulation model was used to analyze the regulatory relationships between lncRNAs and their targets. An lncRNA-related ceRNA network was established. We identified 5465 differentially expressed lncRNAs (DE lncRNAs) and 8366 differentially expressed mRNAs (DE mRNAs) in the SCI group compared with the sham group (fold change > 2.0, p < 0.05). Four genes were confirmed by qRT-PCR which were consistent with the microarray data. GSEA analysis showed that most marked changes occurred in pathways related to immune inflammation and nerve cell function, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and GABAergic synapse. Enrichment analysis identified 30 signaling pathways, including those associated with immune inflammation response. A total of 40 key lncRNAs were identified using the SVM-RFE algorithm. A key lncRNA-mRNAs coexpression network was generated for 230 951 lncRNA-mRNA pairs with half showing positive correlations. Several key DE lncRNAs were predicted to have "cis"- or "trans"-regulated target genes. The transcription factors, Sp1, JUN, and SOX10, may regulate the interaction between XR_001837123.1 and ETS 1. In addition, five pairs of ceRNA regulatory sequences were constructed. Many mRNAs and lncRNAs were found to be dysregulated after SCI. Bioinformatic analysis showed that DE lncRNAs may play crucial roles in SCI. It is anticipated that these findings will provide new insights into the underlying mechanisms and potential therapeutic targets for SCI.

Exploring the immune microenvironment of osteosarcoma through T cell exhaustion-associated gene expression: a study on prognosis prediction.

Background: Osteosarcoma is a highly aggressive type of bone cancer with a poor prognosis. In the tumor immune microenvironment, T-cell exhaustion can occur due to various factors, leading to reduced tumor-killing ability. The purpose of this study was to construct a prognostic model based on T-cell exhaustion-associated genes in osteosarcoma. Methods: Patient data for osteosarcoma were retrieved from the TARGET and GEO databases. Consensus clustering was employed to identify two novel molecular subgroups. The dissimilarities in the tumor immune microenvironment between these subgroups were evaluated using the "xCell" algorithm. GO and KEGG analyses were conducted to elucidate the underlying mechanisms of gene expression. Predictive risk models were constructed using the least absolute shrinkage and selection operator algorithm and Cox regression analysis. To validate the prognostic significance of the risk gene expression model at the protein level, immunohistochemistry assays were performed on osteosarcoma patient samples. Subsequently, functional analysis of the key risk gene was carried out through in vitro experimentation. Results: Four gene expression signatures (PLEKHO2, GBP2, MPP1, and VSIG4) linked to osteosarcoma prognosis were identified within the TARGET-osteosarcoma cohort, categorizing patients into two subgroups. The resulting prognostic model showed strong predictive capability, with area under the receiver operating characteristic curve (AUC) values of 0.728/0.740, 0.781/0.658, and 0.788/0.642 for 1, 3, and 5-year survival in both training and validation datasets. Notably, patients in the low-risk group had significantly higher stromal, immune, and ESTIMATE scores compared to high-risk counterparts. Additionally, a nomogram was developed, exhibiting high accuracy in predicting the survival outcome of osteosarcoma patients. Immunohistochemistry, Kaplan-Meier, and time-dependent AUC analyses consistently supported the prognostic value of the risk model within our osteosarcoma patient cohort. In vitro experiments provided additional validation by demonstrating that the downregulation of GBP2 promoted the proliferation, migration, and invasion of osteosarcoma cells while inhibiting apoptosis. Conclusion: The current study established a prognostic signature associated with TEX-related genes and elucidated the impact of the pivotal gene GBP2 on osteosarcoma cells via in vitro experiments. Consequently, it introduces a fresh outlook for clinical prognosis prediction and sets the groundwork for targeted therapy investigations in osteosarcoma.

Differential Diagnosis of Mimicking Tumor Discs Using Coronal Magnetic Resonance Imaging of Three-Dimensional Fast-Field Echo with Water-Selective Excitation: A Single Center Retrospective Study.

OBJECTIVE: As disc fragment completely loses contact with the parent disc and can migrate in all directions of the epidural space, making it appear similar to schwannoma, it is fairly difficult to make a definitive diagnosis for mimicking tumor discs. The aim of this research is to differentially diagnose mimicking tumor discs and schwannomas using coronal magnetic resonance imaging (MRI) of three-dimensional fast-field echo with water-selective excitation (CMRI). METHODS: Among 76 patients (38 men and 38 women; mean age, 52.88 ± 15.80 [range, 18-78 years]) who were retrospectively examined in this study, 38 were primarily diagnosed with schwannomas and pathologically diagnosed with mimicking tumor discs after surgery, and 38 were primarily diagnosed with neurogenic tumors and pathologically diagnosed with schwannomas after surgery. Open surgery was performed in all the patients between March 2016 and April 2020. The preliminary diagnosis of all patients was considered an intraspinal tumor based on conventional two-dimensional MRI sequences. After open surgery, the final diagnosis was confirmed to mimic a tumor disc or schwannoma based on postoperative pathology reports. The sensitivity, specificity, and reliability of CMRI and conventional MRI for identifying mimicking tumor discs and schwannomas were compared. Chi-square and McNemar tests were used for statistical analyses. RESULTS: Symptoms were considerably relieved in all the patients after surgery. Seven patients had grade 1 extensor digitorum longus, triceps surae, or quadriceps femoris muscle strength prior to surgery. No nerve root injury was observed in any of the patients. CMRI showed significantly higher sensitivity (94.74%) and specificity (94.74%) than conventional MRI (71.05% and 92.11%, respectively; p = 0.012 < 0.05, and p = 1 > 0.05, respectively) for differential identification between mimicking tumor discs and schwannomas. Moreover, CMRI showed a higher reliability (kappa value = 0.787) than conventional MRI (kappa value = 0.374). CONCLUSIONS: CMRI is a better non-invasive technology for the identification of intraspinal lesions, especially for differentiating between mimicking tumor discs and schwannomas.

Identification of pyroptosis-related genes and long non-coding RNAs signatures in osteosarcoma.

Osteosarcoma is a highly malignant tumor, with very high disability and fatality rates. However, the overall prognosis is not optimistic. Pyroptosis is a newly discovered cell death modality accompanied by inflammation, which is closely related to varieties of cancers. In this study, the RNA-seq data were downloaded from public databases, the differences in the expression of the pyroptosis-related genes (PRGs) were identified, and the six PRGs signature was established through the univariate and LASSO Cox analysis. The patients were grouped according to the PRGs signature, and the prognosis between the two groups was further compared. In addition, a ten pyroptosis-related lncRNAs (PRLs) prognostic signature was also constructed. Through functional analysis of the differentially expressed genes (DEGs), the immune-related pathways were found to be enriched. The Pearson correlation analysis showed a strong correlation between the pyroptosis-related biomarkers. Finally, we identified a promising biomarker, CHMP4C, which is highly expressed in osteosarcoma. Overexpression of CHMP4C promoted the proliferation, migration and invasion of the osteosarcoma cell. Our results thus provide new evidence for exploring prognostic biomarkers and therapeutic targets of osteosarcoma.

Hsa_circ_0008870 suppresses bone formation of growth plate through inhibition of miR-185-3p/ MAPK1 axis in idiopathic short stature.

Idiopathic short stature (ISS) is the most common clinical cause of the short stature with an unclear aetiology and a lack of effective treatment. Circular RNAs have been shown to play a significant regulatory role through various signal transduction pathways in a variety of diseases in recent years. However, the role of circular RNAs on ISS is not yet well-understood and requires a special attention. The differentially expressed circular RNAs were screened by microarray chip analysis, and RT-qPCR was used to verify the expression of hsa_circ_0008870 in ISS patients. Subsequently, in vitro and in vivo experiments were conducted to determine the biological functions of hsa_circ_0008870 in ISS. The authors first confirmed that hsa_ circ_0008870 was downregulated in ISS children. Meanwhile, we also observed that the downregulated hsa_circ _0008870 significantly inhibited chondrocyte proliferation and endochondral ossification in vivo and in vitro. Mechanistically, hsa_circ_0008870 regulates MAPK1 expression by sponge miR-185-3p. This mechanism of action was further verified through rescue experiments. Finally, the authors revealed that the silencing of hsa_circ_0008870 induces low expression of MAPK1 by impairing the sponge action of miR-185-3p, thereby inhibiting chondrocyte proliferation, hypertrophy, and endochondral ossification, which results in a short stature phenotype. In addition to these, we also observed an interesting phenomenon that upregulated of miR-185-3p can in turn inhibit the expression of hsa_circ_0008870 in chondrocytes. This suggests that hsa_circ_0008870 could potentially serve as a therapeutic target for the treatment of ISS.

Percutaneous endoscopic drainage for acute long segment epidural abscess following endoscopic lumbar discectomy: A case report.

Introduction: Acute epidural abscess after percutaneous endoscopic lumbar discectomy is a rare but grievous complication. When faced with a long-segment epidural abscess, open surgery has traditionally been performed which can lead to huge surgical trauma and unpredictable complications. For this reason, surgeons around the world are constantly looking for more minimally invasive and effective surgical methods. Patient Concerns: Our patient was a 32-year-old woman who had been receiving percutaneous endoscopic interlaminar discectomy for L5/S1 lumbar disc herniation one week ago. She returned to our institution with a fever and lower back pain. Diagnoses: Magnetic resonance imaging revealed a long segment epidural abscess accompanied by a paravertebral abscess, and staphylococcus aureus was detected in a bacterial culture of pyogenic fluids extracted from the paravertebral abscess. Treatments: We performed percutaneous endoscopic drainage (PED) for the epidural abscess. Long-term sensitive antibiotic treatment after surgery. Outcomes: Immediate pain relief was achieved and the inflammatory reaction subsided after 4 weeks of antibiotic therapy. Re-examination of the lumbar spine MRI after 1 month showed that the epidural abscess disappeared completely. Conclusion: Percutaneous endoscopy allowed us to approach the epidural abscess directly, enabling the immediate drainage of the abscess with minimal trauma to the patient. The good results obtained show that percutaneous endoscopic drainage is a reliable way to treat a long-segment epidural abscess.

Circulating Exosomal circRNA_0063476 Impairs Expression of Markers of Bone Growth Via the miR-518c-3p/DDX6 Axis in ISS.

OBJECTIVES: Idiopathic short stature (ISS), a disorder of unknown cause, accounts for approximately 80% of the clinical diagnoses of children with short stature. Exosomal circular RNA in plasma has been implicated in various disease processes. However, the role of exosome-derived circRNA in ISS has not been elucidated yet. METHODS: Plasma exosomes of ISS and normal children were cocultured with human chondrocytes. Microarray analysis and RT-PCR identified the differential expression of circRNA in exosomes between ISS and normal children. Hsa_circ_0063476 was upregulated or downregulated in human chondrocytes. Subsequently, overexpression rats of hsa_circ_0063476 was constructed via adenoviral vector to further validate the role of hsa_circ_0063476 on longitudinal bone growth via in vivo experiment. RESULTS: The plasma exosome of ISS children suppressed the expression of markers of chondrocyte hypertrophy and endochondral ossification. Subsequently, upregulation of hsa_circ_0063476 in ISS exosome was identified. In vitro experiments demonstrated that chondrocyte proliferation, cell cycle and endochondral ossification were suppressed, and apoptosis was increased following hsa_circ_0063476 overexpression in human chondrocytes. Conversely, silencing hsa_circ_0063476 in human chondrocytes can show opposite outcomes. Our study further revealed hsa_circ_0063476 overexpression in vitro can enhance chondrocyte apoptosis and inhibit the expression of markers of chondrocyte proliferation and endochondral ossification via miR-518c-3p/DDX6 axis. Additionally, the rats with hsa_circ_0063476 overexpression showed a short stature phenotype. CONCLUSIONS: The authors identified a novel pathogenesis in ISS that exosome-derived hsa_circ_0063476 retards the expression of markers of endochondral ossification and impairs longitudinal bone growth via miR-518c-3p/DDX6 axis, which may provide a unique therapeutic avenue for ISS.

Case Report: The Coronal Magnetic Resonance Imaging of Three-Dimensional Fast-Field Echo With Water-Selective Excitation Can Identify the Wrapping of Spinal Nerve Fibers Into Subdural Tumors Prior to Operation.

Purpose: In the present study, the authors intend to identify the spatial relationship between subdural tumors and spinal nerve fibers of cauda equina prior to operation using the coronal MRI of three-dimensional fast-field echo with water-selective excitation (CMRI). Methods: In total, 30 case series with surgically and pathologically verified subdural tumors were enrolled in the present study. The spatial relationship between subdural tumors and spinal nerve fibers of the cauda equina was assessed via conventional MRI and CMRI by three experts prior to operation. The spatial relationship between subdural tumors and spinal nerve fibers of the cauda equina was classified using CMRI. The accuracy of imaging observation was determined via intraoperative observation. Results: Though conventional MRI and gadolinium (Gd)-enhanced MRI (Gd MRI) cannot identify the spatial relationship between subdural tumors and spinal nerve fibers of cauda equina in all cases, CMRI can identify it prior to operation and divide the spatial relationship of spinal nerve fibers of cauda equina with subdural tumors into three types. CMRI shows higher sensitivity (97.44%) and specificity (90.47%) in identifying the spatial relationship of spinal nerve fibers of cauda equina with subdural tumors. Additionally, CMRI also showed a substantial agreement with a kappa value of 0.78. Conclusion: Herein, the authors first describe a potential novel application that CMRI can successfully identify the spatial relationship between subdural tumors and spinal nerve fibers of cauda equina prior to operation, which play an essential role in making a prudent surgical plan and preventing postoperative nerve damage. Summary: Intraoperative observation confirms spinal nerve fibers of cauda equina are often wrapped into subdural tumors of the thoracolumbar and lumbar region, which can result in a high rate of sensory and motor dysfunction after the operation due to the unconscious about the wrapping of nerves into subdural tumors prior to operation. To date, there is not an effective strategy to identify the wrapping before operation.

LCN2 is a new diagnostic biomarker and potential therapeutic target in idiopathic short stature.

Idiopathic short stature (ISS) is the most common paediatric endocrine disease. However, the underlying pathology of ISS remains unclear. Currently, there are no effective diagnostic markers or therapeutic strategies available for ISS. In this study, we aimed to identify differential plasma protein expression and novel biomarkers in patients with ISS, and elucidate the biological functions of candidate proteins in ISS pathogenesis. Four specimen pairs from four ISS children and age-/sex-matched control individuals were subjected to proteomics analysis, and 340 samples of children with a mean age 9.73 ± 0.24 years were utilized to further verify the differentially expressed proteins by enzyme-linked immunosorbent assay (ELISA). The receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were plotted. A total of 2040 proteins were identified, of which 84 were differentially expressed. In vitro and in vivo experiments confirmed the biological functions of these candidate proteins. LCN2 overexpression in ISS was verified using ELISA. Meanwhile, LCN2 showed high sensitivity and specificity in discriminating children with ISS from those with growth hormone deficiency, precocious puberty and normal control individuals. The upregulated expression of LCN2 not only suppressed food intake but also impaired chondrocyte proliferation and bone growth in chondrocytes and rats. As a result, the rats presented a short-stature phenotype. Subsequently, we found that bone growth inhibition recovered after LCN2 overexpression was stopped in immature rats. To our knowledge, this is the first study to report that LCN2 may be a significant target for ISS diagnosis and treatment.

A Novel Diagnostic Predictive Model for Idiopathic Short Stature in Children.

Objective: Idiopathic short stature (ISS), an endocrine-related disease, is difficult to diagnose. Previous studies have shown that many children with some inflammation-related diseases often have short stature, but whether inflammation is the underlying mechanism of ISS has not been studied. Here, we attempt to explore the role of inflammation in the occurrence and development of ISS and to demonstrate an available clinical diagnostic model of ISS. Methods: Frozen serum samples were collected from ISS patients (n = 4) and control individuals (n = 4). Isobaric tags for relative and absolute quantitation (iTRAQ) combined with LC-MS/MS analysis were applied to quantitative proteomics analysis. To assess clusters of potentially interacting proteins, functional enrichment (GO and KEGG) and protein-protein interaction network analyses were performed, and the crucial proteins were detected by Molecular Complex Detection (MCODE). Furthermore, serum levels of two selected proteins were measured by ELISA between ISS patients (n = 80) and controls (n = 80). In addition, experiments in vitro were used to further explore the effects of crucial proteins on endochondral ossification. Results: A total of 437 proteins were quantified, and 84 DEPs (60 upregulated and 24 downregulated) were identified between patients with ISS and controls. Functional enrichment analysis showed that the DEPs were primarily enriched in blood microparticle, acute inflammatory response, protein activation cascade, collagen-containing extracellular matrix, platelet degranulation, etc. According to the results of top 10 fold change DEPs and MCODE analysis, C1QA and C1QB were selected to further experiment. The expression levels of C1QA and C1QB were validated in serum samples. Based on the logistic regression analysis and ROC curve analysis, we constructed a novel diagnostic model by serum levels of C1QA and C1QB with a specificity of 91.2% and a sensitivity of 75% (AUC = 0.900, p <0.001). Finally, the western blotting analysis confirmed the expression levels of OCN, OPN, RUNX2, and Collagen X were downregulated in chondrocytes, and the outcome of Collagen II was upregulated. Conclusion: Our study is the first to demonstrate the significant role of inflammation in the development of ISS. In addition, we identify C1QA and C1QB as novel serum biomarkers for the diagnosis of ISS.