Establishment of a risk prediction model for residual low back pain in thoracolumbar osteoporotic vertebral compression fractures after percutaneous kyphoplasty.

OBJECTIVE: This study aims to identify potential independent risk factors for residual low back pain (LBP) in patients with thoracolumbar osteoporotic vertebral compression fractures (OVCFs) following percutaneous kyphoplasty (PKP) treatment. Additionally, we aim to develop a nomogram that can accurately predict the occurrence of residual LBP. METHODS: We conducted a retrospective review of the medical records of thoracolumbar OVCFs patients who underwent PKP treatment at our hospital between July 2021 and December 2022. Residual LBP was defined as the presence of moderate or greater pain (VAS score ≥ 4) in the low back one day after surgery, and patients were divided into two groups: the LBP group and the non-LBP group. These patients were then randomly allocated to either a training or a validation set in the ratio of 7:3. To identify potential risk factors for residual LBP, we employed lasso regression for multivariate analysis, and from this, we constructed a nomogram. Subsequently, the predictive accuracy and practical clinical application of the nomogram were evaluated through a receiver operating characteristic (ROC) curve, a calibration curve, and a decision curve analysis (DCA). RESULTS: Our predictive model revealed that five variables-posterior fascial oedema, intravertebral vacuum cleft, time from fracture to surgery, sarcopenia, and interspinous ligament degeneration-were correlated with the presence of residual LBP. In the training set, the area under the ROC was 0.844 (95% CI 0.772-0.917), and in the validation set, it was 0.842 (95% CI 0.744-0.940), indicating that the model demonstrated strong discriminative performance. Furthermore, the predictions closely matched actual observations in both the training and validation sets. The decision curve analysis (DCA) curve suggested that the model provides a substantial net clinical benefit. CONCLUSIONS: We have created a novel numerical model capable of accurately predicting the potential risk factors associated with the occurrence of residual LBP following PKP in thoracolumbar OVCFs patients. This model serves as a valuable tool for guiding specific clinical decisions for patients with OVCFs.

Matrix Stiffness Activating YAP/TEAD1-Cyclin B1 in Nucleus Pulposus Cells Promotes Intervertebral Disc Degeneration.

Intervertebral disc degeneration is a leading cause of disability in the elderly population. Rigid extracellular matrix is a critical pathological feature of disc degeneration, leading to aberrant nucleus pulposus cells (NPCs) proliferation. However, the underlying mechanism is unclear. Here, we hypothesize that increased matrix stiffness induces proliferation and thus degenerative phenotypes of NPCs through YAP/TEAD1 signaling pathway. We established hydrogel substrates to mimic stiffness of degenerated human nucleus pulposus tissues. RNA-sequencing identified differentially expressed genes between primary rat NPCs cultured on rigid and soft hydrogels. Dual luciferase assay and gain- and loss-function experiments evaluated the correlation between YAP/TEAD1 and Cyclin B1. Furthermore, single-cell RNA-sequencing of human NPCs was performed to identify specific cell clusters with high YAP expression. Matrix stiffness increased in severely degenerated human nucleus pulposus tissues (p < 0.05). Rigid substrate enhanced rat NPCs proliferation mainly through Cyclin B1, which was directly targeted and positively regulated by YAP/TEAD1. Depletion of YAP or Cyclin B1 arrested G2/M phase progression of rat NPCs and reduced fibrotic phenotypes including MMP13 and CTGF (p < 0.05). Fibro NPCs with high YAP expression were identified in human tissues and responsible for fibrogenesis during degeneration. Furthermore, inhibition of YAP/TEAD interaction by verteporfin suppressed cell proliferation and alleviated degeneration in the disc needle puncture model (p < 0.05). Our results demonstrate that elevated matrix stiffness stimulates fibro NPCs proliferation through YAP/TEAD1-Cyclin B1 axis, indicating a therapeutic target for disc degeneration.

Correlation and reliability of cervical sagittal alignment parameters between plain radiographs and multipositional MRI images.

STUDY DESIGN: A retrospective study. OBJECTIVES: To assess the validity and reliability of cervical sagittal alignment parameters from multipositional magnetic resonance imaging (MRI) and dynamic cervical radiography. SETTING: Hospital in Suzhou, China. METHODS: Patients who underwent both multipositional MRI and dynamic plain radiography of the cervical spine within a 2-week interval between January 2013 and October 2021 were retrospectively enrolled in this study. The C2-7 angle, C2-7 cervical sagittal vertical axis (C2-7 SVA), T1 slope (T1S), cervical tilt, cranial tilt, and K-line tilt were measured in three different positions (neutral, flexion, and extension) with multipositional MRI and dynamic radiography. Inter- and intraobserver reliabilities were assessed by intraclass correlation coefficients (ICCs). Pearson correlation coefficients were used for statistical analyses. RESULTS: A total of 65 (30 males and 35 females) patients with a mean age of 53.4 years (range 23-69 years) were retrospectively enrolled in this study. Significant positive correlations were noted regarding all parameters between the plain radiographs and multipositional MRI images. Inter- and intraobserver reliabilities were excellent for all cervical sagittal alignment parameters measured in the two imaging modalities. All cervical sagittal parameters had significant positive correlations with those from multipositional MRI in all three positions (p < 0.05). Pearson correlation coefficients demonstrated moderate and strong correlations between the two examinations. CONCLUSIONS: Cervical sagittal alignment parameters measured on multipositional MRI could reliably substitute for those measured on plain radiographs. Multipositional MRI is a valuable, radiation-free alternative for diagnostic evaluation in degenerative cervical diseases.

Percutaneous Kyphoplasty to Relieve the Rib Region Pain in Osteoporotic Thoracic Vertebral Fracture Patients Without Local Pain of Fractured Vertebra.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) are common. A few patients with thoracic vertebral fracture show pain in the bilateral rib region but not at the fracture site. The point of specific tenderness in the rib region cannot be located. It is not clear whether percutaneous kyphoplasty (PKP) can relieve the pain in the bilateral rib region in these patients. OBJECTIVE: To check whether PKP can alleviate the rib region pain in thoracic vertebral fracture patients without local pain at the fractured vertebra. STUDY DESIGN: Retrospective study. SETTING: The study was carried out at a university hospital. METHODS: We performed a retrospective analysis of thoracic vertebral fracture patients admitted to our hospital for PKP surgery between January 2018 and June 2022. The main clinical manifestations of these patients were pain in the bilateral rib region but no local tenderness and percussion pain at the fractured vertebra. CT and MRI examinations of the thoracic vertebrae were performed after admission. PKP was performed under general anesthesia after no surgical contraindication. Visual analog scale (VAS) scores and heights of the anterior, middle, and posterior edges of the fractured vertebra before the surgery, one day after surgery, and one month after surgery were compared. Also, the Cobb angles formed by the upper and lower endplate of the fractured vertebra before the surgery, one day after surgery, and one month after surgery were compared. RESULTS: A total of 50 patients were included in this study (3 men and 47 women, with an average age of 72.46 ± 8.15 years), of which 7 patients had 2 segmental fractures, so a total of 57 vertebrae were included. The VAS scores on day one and one month after the surgery were significantly lower than that before the surgery. The heights of the anterior, middle, and posterior edges of the fractured vertebra on day one after the surgery were significantly higher than those before the surgery. The Cobb angle of the fractured vertebra on day one after the surgery was lower than that before the surgery. The vertebrae of 23 patients were examined using x-ray one month after the surgery. The heights of the anterior, middle, and posterior edges of the fractured vertebra one month after the surgery were also significantly higher than those before the surgery but significantly lower than those one day after the surgery. Also, the Cobb angle of the fractured vertebra one month after the surgery was significantly lower than that before the surgery. LIMITATIONS: This was a retrospective study, which may be prone to selection and recall bias. Single-center non-controlled studies may also introduce bias. CONCLUSION: The exact location of the pain in the rib region caused by thoracic fracture cannot be identified usually. PKP can alleviate the rib region pain caused by the thoracic fracture.

Utility of Flexion-Extension Radiographs with Brackets and Magnetic Resonance Facet Fluid for the Assessment of Lumbar Instability in Degenerative Lumbar Spondylolisthesis.

OBJECTIVE: To propose a new standardized technique for evaluating lumbar stability in degenerative lumbar spondylolisthesis using lumbar lateral flexion-extension radiographs with brackets and magnetic resonance facet fluid. METHODS: A retrospective analysis of 57 patients diagnosed with lumbar (L4-5) spondylolisthesis was performed. We analyzed lateral flexion-extension radiographs obtained with a bracket (LFEB) and without a bracket (LFE). Sagittal translation, segmental angulation, posterior opening, lumbar instability, and changes in lumbar lordosis were compared using functional radiographs. The mean width and maximum width of the facet fluid, mean facet joint length, and facet fluid index (FFI) of the 2 groups were compared using sagittal translation. RESULTS: The average value of sagittal translation was 1.68 ± 0.96 mm in LFE and 3.07 ± 1.29 mm in LFEB, and the difference was significant (P < 0.05). Segmental angulation, posterior opening, and changes in lumbar lordosis were significantly greater in LFEB than in LFE. The instability detection rate was 14.0% in LFE and 35.1% in LFEB. The FFI, maximum width, and mean width were significantly increased in the unstable lumbar spondylolisthesis group compared with the stable group in LFEB. The FFI and maximum width of the facet fluid were significantly increased in the unstable lumbar spondylolisthesis group compared with the stable group in LFE. CONCLUSIONS: Lumbar lateral flexion-extension radiographs with brackets can standardize the operation process and provide sufficient hyperflexion and hyperextension images. The width of the facet fluid and FFI are significant factors in the evaluation of lumbar stability in patients with lumbar spondylolisthesis.

Local Anesthetic and Steroid Injection to Relieve the Distal Lumbosacral Pain in Osteoporotic Vertebral Compression Fractures of Patients Treated with Kyphoplasty.

BACKGROUND: Percutaneous kyphoplasty (PKP) is widely used in osteoporotic vertebral compression fractures (OVCF). But in some patients, distal lumbosacral pain (DLP) persists even after treatment and affects their quality of life. OBJECTIVE: To investigate the effectiveness of local anesthetic and steroid injection in improving DLP after PKP. STUDY DESIGN: A prospective, randomized, and controlled clinical trial. SETTING: The study was carried out in a university hospital. METHODS: A total of 150 patients were included in this study and randomly divided into 2 groups of 75 patients each. Patients in the control group (PKP) underwent PKP, and those in the observation group (PKP + LAI) received an injection of lidocaine + triamcinolone acetonide suspensions during the surgery. The visual analog scale (VAS) of the fracture site, Oswestry disability index (ODI), and the rate of patients with lower back pain were compared between the 2 groups at 1 day, 3 days, 1 week, 1 month, and 3 months after the surgery. RESULTS: One hundred thirty-nine patients completed the entire postoperative follow-up schedule, with 70 patients in the PKP group and 69 cases in the PKP + LAI group. The VAS and ODI in the PKP + LAI group were significantly lower than those in the PKP group 1 day, 3 days, 1 week, and 1 month after the surgery; there was no significant difference  3 months after the operation. The rate of patients with lower back pain in the PKP + LAI group 1 day, 3 days, and 1 week after the operation was significantly lower than that in the control group; there was no significant difference 1 month and 3 months after the operation. LIMITATIONS: The number of cases was small, and the follow-up time was short. CONCLUSION: Local anesthetic and steroid injection improved the short-term clinical outcome of PKP for OVCF, which will enhance the confidence of patients in performing out-of-bed activities and functional exercises early after the operation.

Utility of a fulcrum for positioning support during flexion-extension radiographs for assessment of lumbar instability in patients with degenerative lumbar spondylolisthesis.

OBJECTIVE: The authors investigated a new standardized technique for evaluating lumbar stability in lumbar lateral flexion-extension (LFE) radiographs. For patients with lumbar spondylolisthesis, a three-part fulcrum with a support platform that included a semiarc leaning tool with armrests, a lifting platform for height adjustment, and a base for stability were used. Standard functional radiographs were used for comparison to determine whether adequate flexion-extension was acquired through use of the fulcrum method. METHODS: A total of 67 consecutive patients diagnosed with L4-5 degenerative lumbar spondylolisthesis were enrolled in the study. The authors analyzed LFE radiographs taken with the patient supported by a fulcrum (LFEF) and without a fulcrum. Sagittal translation (ST), segmental angulation (SA), posterior opening (PO), change in lumbar lordosis (CLL), and lumbar instability (LI) were measured for comparison using functional radiographs. RESULTS: The average value of SA was 5.76° ± 3.72° in LFE and 9.96° ± 4.00° in LFEF radiographs, with a significant difference between them (p < 0.05). ST and PO were also significantly greater in LFEF than in LFE. The detection rate of instability was 10.4% in LFE and 31.3% in LFEF, and the difference was significant. The CLL was 27.31° ± 11.96° in LFE and 37.07° ± 12.963.16° in LFEF, with a significant difference between these values (p < 0.05). CONCLUSIONS: Compared with traditional LFE radiographs, the LFEF radiographs significantly improved the detection rate of LI. In addition, this method may reduce patient discomfort during the process of obtaining radiographs.

X-ray Irradiation Improves Neurological Function Recovery of Injured Spinal Cord by Inhibiting Inflammation and Glial Scar Formation.

Spinal cord injury (SCI) is a common clinical disease that can cause permanent disruption of nerve function. Inflammation and glial scar formation influence the recovery of injured spinal cord. X-ray irradiation can reduce inflammation, inhibit cell proliferation and increase cell apoptosis. However, the regulatory effects of X-ray irradiation on inflammation and glial scars and the underlying molecular mechanisms are still unclear. This study was aimed to investigate the therapeutic effect and molecular mechanism of X-ray irradiation on spinal cord injury. Behavioural experiments showed that X-ray irradiation can promote the recovery of nerve function after SCI. X-ray irradiation inhibited the inflammatory response by reducing the expression of inflammatory factors (TNF-α and IL-1ß) at the lesion site, thereby reducing neuronal apoptosis. X-ray irradiation inhibited the formation of the glial scar (GFAP and vimentin) in the lesion. P38MAPK and Akt signalling pathways were involved in these processes. Furthermore, the 10 Gy dose had the most significant effects among the 2 Gy, 10 Gy and 20 Gy doses. In summary, X-ray irradiation may exert an active therapeutic effect on SCI by inhibiting inflammation and glial scar formation, which may be related to the inhibition of p38MAPK and Akt signalling pathways.

Diagnostic and prognostic values of blood microRNA-Let7A for osteosarcoma.

OBJECTIVE: In view of the poor prognosis and difficulties in the diagnosis of osteosarcoma, and the functionality of microRNA-Let7A in different types of human cancers, our study aimed to explore the diagnostic and prognostic values of microRNA-Let7A for osteosarcoma. METHODS: A total of 39 patients with osteosarcoma and 19 normal healthy people were included in this study. All patients received surgical resection, and tumor tissues as well as pericarcinomatous tissues were collected during surgical operation. Venous blood (2 ml) was extracted from each participant. Expression of microRNA-Let7A in tumor tissues and pericarcinomatous tissues, and expression of E2F2 and microRNA-Let7A in blood of each participant was detected by qRT-PCR. ROC analysis was performed to evaluate the diagnostic values of blood E2F2 and microRNA-Let7A for osteosarcoma, and prognostic values of microRNA-Let7A for osteosarcoma was evaluated by survival curve comparisons. RESULTS: Expression level of microRNA-Let7A was significantly lower in tumor tissues than that in pericarcinomatous tissues. MicroRNA-Let7A expression in blood was significantly downregulated in osteosarcoma patients compared with normal control. Expression of microRNA-Let7A was negatively correlated with the expression of E2F2 in blood of osteosarcoma patients. Compared with E2F2, blood microRNA-Let7A can more effectively predict osteosarcoma. Overall survival rate of osteosarcoma patient with low blood expression level of miRNA-let-7a was significantly lower than that of patients with high blood expression level of miRNA-let-7a. CONCLUSION: Blood microRNA-Let7A is a promising diagnostic and prognostic biomarker for osteosarcoma.

Changes in autophagy in rats after spinal cord injury and the effect of hyperbaric oxygen on autophagy.

The purpose of this study was to explore the effects of Hyperbaric oxygen (HBO) on the autophagic changes after induction of spinal cord injury (SCI) in rats. A total of 75 rats were randomly divided into the sham-operated group, the spinal cord injury group, and the SCI+HBO group. We found that at 7 d and 14 d after surgery, the BBB scores were higher in the SCI+HBO group in comparison to the SCI group. The expression of Beclin-1 and LC3II was upregulated in the SCI and SCI+HBO groups after SCI. Fluorescently stained Beclin-1 and LC3II proteins were barely detectable in the sham group. In contrast, Beclin-l and LC3II expression was observed in neurons and glial cells from the SCI and SCI+HBO groups. Beclin-1 and LC3II expression appeared at 6h after SCI. At each time point, Beclin-1 and LC3II expression was significantly higher in the SCI+HBO group compared to the SCI group. These results suggest that autophagy is activated in rats after SCI and sustained over a period of time. HBO treatment enhances autophagy expression in rats after SCI and accelerates cell repair rate, which may represent one of the mechanisms of action of HBO in the treatment of SCI.

Resveratrol abrogates the effects of hypoxia on cell proliferation, invasion and EMT in osteosarcoma cells through downregulation of the HIF-1α protein.

Resveratrol has been shown to have antineoplastic effects in vivo and in vitro. However, the effect of resveratrol on the hypoxia-enhanced proliferation and invasion of osteosarcoma cells remains unclear. In this study, we investigated the role of resveratrol on regulating proliferation and invasion of osteosarcoma cells under hypoxic conditions. Saos-2 cells were cultured under controlled hypoxic conditions (3% O2) or normoxic conditions. Resveratrol (50 µM) was added in the medium, and hypoxia inducible factor-1α (HIF-1α) siRNA was used to inhibit HIF-1α transcription. Proliferation of Saos-2 cells was evaluated by the methabenzthiazuron (MTT) assay. The invasive ability of Saos-2 cells was determined by a Transwell assay. HIF-1α, E-cadherin and vimentin protein levels were detected by western blot analysis. HIF-1α, E-cadherin and vimentin mRNA levels were assessed by RT-PCR. Compared to the control group, hypoxia significantly increased the proliferation rate and invasive ability of Saos-2 cells. Moreover, hypoxia markedly increased the E-cadherin level and decreased vimentin expression. However, resveratrol or HIF-1α silencing reverted all the above effects of hypoxia in Saos-2 cells. Moreover, resveratrol inhibited HIF-1α protein accumulation without affecting the HIF-1α mRNA level. These data suggest that resveratrol can inhibit the hypoxia­enhanced proliferation, invasion and epithelial to mesenchymal transition process in osteosarcoma via downregulation of the HIF-1α protein. Thus, HIF-1α may be a promising drug target of resveratrol in the context of development of anticancer therapy for human osteosarcoma.

Inhibition of proliferation and gene expression regulation by (-)-epigallocatechin-3-gallate in human synovial sarcoma cells.

Synovial sarcoma is an aggressive soft-tissue malignancy with poor prognosis and lack of response to conventional cytotoxic chemotherapy. The regulatory mechanisms for the rapid proliferation of synovial sarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. In this study, we investigate the effect of epigallocatechin-3-gallate (EGCG) on growth and apoptosis of chondrosarcoma cells. The MTT assay and DAPI staining indicated that EGCG effectively inhibited cellular proliferation and induces apoptosis of the synovial sarcoma cells and induced apoptosis as confirmed by flow cytometry. Furthermore, Bcl-2 and Mcl-1 levels significantly decreased, Bax levels significantly increased, whereas expression levels of the proteins Bcl-XL were unchanged in response to EGCG treatment in SW982. In conclusion, our findings demonstrate that EGCG is effective for growth inhibition of synovial sarcoma cell lines in vitro and suggest that EGCG may be a new therapeutic option for patients with synovial sarcoma.