KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43.

BACKGROUND: Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies. METHODS: qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms. RESULTS: KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5's role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts' osteogenesis. CONCLUSION: KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.

Prognostic Nutritional Index and the Risk of Postoperative Complications After Spine Surgery: A Meta-Analysis.

BACKGROUND: A low prognostic nutritional index (PNI) may reflect malnutrition, which has been associated with poor prognosis in patients with various clinical conditions. The aim of the systematic review and meta-analysis was to investigate the association between preoperative PNI and risk of postoperative complications in adult patients after spine surgery. METHODS: An extensive search was conducted on PubMed, Embase, and Web of Science to identify relevant cohort studies. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. RESULTS: Ten cohort studies involving 3,249 patients receiving spine surgeries were included. Pooled results showed that a low preoperative prognostic nutritional index (PNI) was associated with an increased risk of overall postoperative complications in these patients (odds ratio [OR]: 1.82, 95% confidence interval [CI]: 1.42 to 2.34, P < 0.001; I2 = 49%). Specifically, a preoperative malnutrition as evidenced by a low PNI was associated with a higher incidence of postoperative delirium (OR: 2.36, 95% CI: 1.52 to 3.66, P < 0.001; I2 = 38%) and surgical site infection (OR: 1.41, 95% CI: 1.15 to 1.73, P = 0.001; I2 = 0%). Sensitivity analyses by excluding one study at a time did not significantly change the results (P all <0.05). CONCLUSIONS: A preoperative low prognostic nutritional index (PNI) may be a risk factor of increased incidence of overall postoperative complications, postoperative delirium, and surgical site infection in adult patients after spine surgeries.

ETS1 promoted cell growth, metastasis and epithelial-mesenchymal transition process in melanoma by regulating miR-16-mediated SOX4 expression.

Melanoma is a malignant tumor with high metastasis and mortality. Epithelial-mesenchymal transition (EMT) was reported to be involved in the growth and metastasis of melanoma. To investigate these sections further, we showed that E26 transformation specific 1 (ETS1) could regulate growth, metastasis and EMT process of melanoma by regulating microRNA(miR)-16/SRY-related HMG box (SOX) 4 expression. MiR-16, ETS1, SOX4 and nuclear factor κB (NF-κB) expression levels in melanoma cells were examined using qPCR. ETS1, SOX4, EMT-related proteins and NF-κB signaling pathway-related proteins were examined using western blot. Cell counting kit-8 assay, transwell assay were applied to evaluate the cell proliferation, migration and invasion of melanoma cells, respectively. Besides, a dual-luciferase reporter assay was employed to verify the binding relationship between ETS1 and miR-16, miR-16 and SOX4, miR-16 and NF-κB1. We showed that ETS1 and SOX4 were upregulated in melanoma cells, while miR-16 was downregulated. MiR-16 overexpression suppressed growth, metastasis and EMT process of melanoma. We found ETS1 could bind to the promoter region of miR-16 and inhibited its transcription. ETS1 silence could inhibit growth, metastasis and EMT process of melanoma, and inhibition of miR-16 could reverse the effects. Besides, miR-16 is directly bound to SOX4 and downregulated its expression. Rescued experiments confirmed that SOX4 overexpression abolished the inhibition effect of miR-16 mimics on growth, metastasis and EMT process of melanoma. Finally, NF-κB1 as the target of miR-16 mediated downstream biological responses. ETS1 activated NF-κB signaling pathway through miR-16 via targeting SOX4, thus promoting growth, metastasis and EMT of melanoma.

One-stage surgical management for tuberculosis of the upper cervical spine by posterior debridement, short-segment fusion, and posterior instrumentation in children.

PURPOSE: To evaluate the clinical study efficacy and feasibility of 11 children with tuberculosis of the upper cervical spine treated by one-stage posterior debridement, short-segment fusion, and posterior instrumentation. METHODS: Eleven children who suffered from tuberculosis of the upper cervical spine were admitted to our hospital between June 2005 and December 2010. All of them were treated by one-stage posterior debridement, short-segment fusion, and posterior instrumentation. Then, the clinical efficacy was evaluated using statistical analysis based on the materials about the visual analogue scale (VAS) scores of pain, JOA scores of nerve function and erythrocyte sedimentation rate (ESR), which were collected at certain time. RESULTS: The average follow-up period was 28.1 ± 10.5 months (13-42 months). In the 11 cases, no postoperative complications related to instrumentation occurred and neurologic function was improved in various degrees. The average pretreatment ESR was 58.4 ± 4.9 mm/h (53-69 mm/h), which got normal (8.9 ± 6.5 mm/h) within 3 months in all patients. The average preoperative VAS was 7.4 ± 2.2, which decreased to 1.6 ± 1.8 postoperatively. Mean preoperative JOA was 11.2 ± 3.8, and the JOA at the last visit was 16.3 ± 1.0. All patients got bony fusion within 3-8 months after surgery. CONCLUSIONS: One-stage posterior debridement, short-segment fusion, and posterior instrumentation can be an effective treatment method for the treatment of tuberculosis of the upper cervical spine in children.

A clinical study of internal fixation, debridement and interbody thoracic fusion to treat thoracic tuberculosis via posterior approach only.

PURPOSE: We evaluated the clinical efficacy and feasibility of one-stage posterior internal fixation, debridement and interbody thoracic fusion in the treatment of thoracic tuberculosis. METHODS: Sixty adult patients with monosegmental thoracic tuberculosis were studied retrospectively: 34 men and 26 women with an average age of 37.5 years. Operating time, blood loss, time in bed, complications, neurological function, rate of deformity correction and rate of interbody fusion were investigated. RESULTS: All cases were followed up for 27.5 months on average. Average mean operating time was 251 min, evaluated blood loss during operation 780 ml, rate of kyphosis correction 79%, corrected kyphosis angle 25° and loss of corrected angle 1.2°. Patients whose neurological function improved accounted for 90.1%. Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) decreased to normal levels three months after operation. The rate of bone fusion was 100%, with a 100% cure rate. No severe complications or spinal cord injury occurred. CONCLUSIONS: This approach can successfully remove the focus of tuberculosis with complete interbody thoracic fusion after operation, which restores spinal stability.