Epigallocatechin-3-Gallate Protects H2O2-Induced Nucleus Pulposus Cell Apoptosis and Inflammation by Inhibiting cGAS/Sting/NLRP3 Activation.

BACKGROUND: Intervertebral disc degeneration (IDD) is the most common diagnosis of patients with lower back pain. IDD is the underlying lesion of many spinal degenerative diseases; however, the role of cGAS/Sting/NLRP3 pathway and epigallocatechin gallate (EGCG) in the development of IDD remained unclear. METHODS: The expressions of cGAS, Sting and NLRP3 mRNA of intervertebral disc (IVD) samples from IDD patients and controls were detected by RT-PCR. The nucleus pulposus cells (NPCs) were induced by hydrogen peroxide (H2O2) and used as an in-vitro model. Both 5 µM and 25 µM EGCG treatment were used to detect the effect of EGCG on the in-vitro model. Cell viability was detected by the MTT method, and cell apoptosis and cell cycle would be detected by flow cytometry. Western blot was used in the detection of the expression of cGAS/Sting/NLRP3 as well as apoptosis-related protein level. ELISA was used in the detection of pro-inflammatory factors, including IL-1ß, TNF-α, IL-6 and IL-10. RESULTS: The expressions of cGAS, Sting and NLRP3 mRNA were significantly increased in the IVD samples from IDD patients and NLRP3 was associated with cGAS and Sting. Advanced in-vitro study showed that H2O2 significantly increased the expression of cGAS, Sting and NLRP3 protein levels. Advanced experiments showed that EGCG treatment demonstrated significant protective effects in cell viability, apoptosis, cell cycle arrest and inflammatory status through down-regulation of cGAS/Sting/NLRP3 pathway. CONCLUSION: It was shown that the cGAS, Sting and NLRP3 up-regulation was associated with the incidence of IDD. Our findings also suggest that EGCG treatment would provide anti-apoptosis, anti-inflammation and promote cell viability in H2O2 treatment-incubated NPCs through inhibiting cGAS/Sting/NLRP3 pathway.

Feedback modulation of endothelial cells promotes epithelial-mesenchymal transition and metastasis of osteosarcoma cells by Von Willebrand Factor release.

Endothelial cells (ECs), as a tumor niche cell, generate and secrete Von Willebrand factor (VWF) that is linked to osteosarcoma (OS) progression. However, the role and regulatory mechanisms of VWF that underpin OS progression remain unclear. Here, using a coculture system ex vivo, we showed that ECs promoted the epithelial-mesenchymal transition (EMT) process in OS cells via enhanced VWF secretion. VWF secreted by ECs directly contributed to OS EMT and metastasis by activating NF-κB signaling. In addition, OS cells exerted a feedback effect on ECs to promote VWF release via activation of phospholipase D 1 signaling, through which enhanced VWF secretion results in further tumor deterioration. To conclude, ECs served as a modulator and an effector of OS, accelerating OS exacerbation by VWF release.

von Willebrand factor rescued by miR-24 inhibition facilitates the proliferation and migration of osteosarcoma cells in vitro.

von Willebrand factor (vWF) is a major procoagulant molecule that was shown to differentiate between metastatic and primary osteosarcoma (OS) tissues and associated with increased metastasis. However, its functional role in OS progression has been unclear yet. The expression profile of vWF and miR-24 in human OS tissues was characterized using immunofluorescence labeling and quantitative real-time PCR analysis. The interaction between miR-24 and vWF was identified by dual luciferase reporter assay. The effects of vWF and miR-24 on OS cells were assessed by cell proliferation, colony formation, and migration. The clinical significance of miR-24 in OS patients was analyzed using Kaplan-Meier analyses and Pearson's Chi-squared test. Here, we reported that the expression of vWF was significantly increased, but miR-24 was significantly decreased in OS tissues (n=84). vWF was further validated as the target of miR-24 in MG-63 and U2OS cells. miR-24 obviously suppressed the proliferation and migration of MG-63 and U2OS cells. However, the migration-inhibiting activity of miR-24 was predominantly attenuated by vWF overexpression. Clinically, low miR-24 expression in human OS tissues was significantly associated with tumor metastasis and predicted a poor survival in OS patients. This work demonstrated that vWF, as a downstream effector of miR-24, played an important role in controlling OS cell progression. Target miR-24 or vWF, therefore, promises to be an effective biological target for OS treatment.

Comparison of Adjacent Segment Degeneration After Nonrigid Fixation System and Posterior Lumbar Interbody Fusion for Single-Level Lumbar Disc Herniation: A New Method of MRI Analysis of Lumbar Nucleus Pulposus Volume.

PURPOSE: To evaluate the influence of a nonrigid fixation system and posterior lumbar interbody fusion on adjacent intervertebral disc degeneration by using MRI analysis of lumbar nucleus pulposus volume for single-level lumbar disc herniation. MATERIALS AND METHODS: We selected 112 patients who underwent nonrigid fixation (17 men and 44 women) or posterior lumbar interbody fusion (13 men and 38 women) for this retrospective study. Based on the T2-weighted magnetic resonance imaging (MRI) scans taken preoperatively, and 6, 12, and 24 months after surgery, the nucleus pulposus in the upper segments of the operated level was considered an ellipsoid, and their volumes were measured respectively and then compared between the two groups. RESULTS: The posterior lumbar interbody fusion group had significantly lower lumbar nucleus pulposus volume than the nonrigid fixation group at 12 (4.04 ± 1.42 vs. 5.25 ± 1.47 mm3) and 24 months (4.16 ± 0.89 vs. 5.06 ± 1.23 mm3), and had the highest nucleus pulposus. Meanwhile, the h value in the posterior lumbar interbody fusion group was notably smaller than the preoperative level at 12 (0.46 ± 0.03 vs. 0.55 ± 0.05 mm) and 24 months (0.44 ± 0.03 vs. 0.55 ± 0.05 mm). CONCLUSIONS: MRI analysis of lumbar nucleus pulposus volume is a new and quantitative method of analysis, which is a considerable method and contributes to the detection of severe intervertebral disc degeneration. Based on this new method, nonrigid fixation demonstrates excellent outcomes on the adjacent segment in comparison with posterior lumbar interbody fusion.

Short-Term Therapeutic Efficacy of the Isobar TTL Dynamic Internal Fixation System for the Treatment of Lumbar Degenerative Disc Diseases.

BACKGROUND: At present, posterior interbody fusion surgery with pedicle internal fixation is the gold standard for the treatment of lumbar degenerative disc diseases. However, an increasing number of studies have shown that because fused lumbar vertebrae lose their physiological activity, the compensatory range of motion (ROM) of the adjacent levels increases. To address this issue, dynamic internal fixation systems have been developed. OBJECTIVE: Our goal was to investigate the short-term therapeutic efficacy of the Isobar TTL dynamic internal fixation system for the treatment of lumbar degenerative disc diseases and its effect on the ROM of the surgical segments. STUDY DESIGN: Retrospective Evaluation. SETTING: Tertiary hospital setting in China. METHODS: Twenty-four lumbar degenerative disc disease patients who underwent posterior lumbar decompression and single-segment Isobar TTL dynamic internal fixation at our hospital between January 2013 and July 2014 were retrospectively analyzed. The preoperative and one month, 3 month, and 12 month postoperative visual analog scale (VAS) pain scores, Japanese Orthopedic Association (JOA) scores, and Oswestry Disability Index (ODI) scores were observed and recorded to assess the clinical therapeutic effect; the lumbar ROM was measured preoperatively and at the last follow-up to evaluate the preservation of functional movement in the dynamically stabilized segment. RESULTS: All patients underwent the operation successfully without complications during hospitalization and were followed for 12 to 27 months, with an average of 18 months. The patients' preoperative and one month, 3 month, and 12 month postoperative VAS scores were 6.42 ± 0.72, 1.71 ± 0.86, 1.38 ± 0.65, and 1.37 ± 0.58, respectively, and their JOA scores were 9.54 ± 1.89, 21.21 ± 1.98, 22.50 ± 1.47, and 23.46 ± 1.32, respectively. The preoperative ODI score was 42.04 ± 2.63; the one month, 3 month, and 12 month postoperative ODI scores were 22.79 ± 1.61, 18.63 ± 1.61, and 15.08 ± 1.21, respectively. These results suggest that the VAS score at each postoperative time point was significantly lower than the preoperative score and that function was significantly improved postoperatively compared with preoperative function; all of the differences had statistical significance (P < 0.05). The patients' preoperative lumbar ROM and the ROM at 12 months post operation were 3.46 ± 1.02 and 2.25 ± 0.79, respectively; the difference was not statistically significant (P = 0.11). LIMITATIONS: The follow-up time is not long enough. CONCLUSIONS: The treatment of lumbar degenerative disc diseases with the Isobar TTL dynamic internal fixation system can effectively relieve pain, improve quality of life, and preserve the lumbar ROM of the stabilized segment with a satisfactory clinical therapeutic effect.

Effect of pedicle fixation combined with (125)I seed implantation for metastatic thoracolumbar tumors.

PURPOSE: The aim of this study was to investigate the clinical efficacy of pedicle fixation combined with (125)I brachytherapy in treating metastatic thoracolumbar tumors. PATIENTS AND METHODS: A retrospective analysis of the clinical data of seven metastatic thoracolumbar tumor patients who received pedicle fixation combined with radioactive (125)I seed implantation brachytherapy in our department between January 2009 and December 2013 was performed. The visual analog scale (VAS) for pain and the Karnofsky performance status (KPS) score before the operation and 1, 6, and 12 months after the operation were observed and recorded. The changes in the scores at each time point were compared. RESULTS: All the patients underwent a successful operation, without any complications during their hospitalization. All the patients received postoperative follow-up, and the duration of follow-up was 15-50 months, with an average of 32.2 months. One pancreatic cancer patient died of liver failure and hypoproteinemia 28 months post surgery. The VAS scores of patients before the operation and 1, 6, and 12 months after the operation were 7.43±0.98, 2.71±0.49, 3.00±0.82, and 4.29±0.98, respectively; the KPS scores were 52.9±9.5, 84.3±5.3, 75.7±5.3, and 72.9±4.9, respectively. These results suggest that the VAS score at each time point was significantly decreased compared with that before the operation, while the KPS score was significantly increased compared with that before the operation. Both differences had statistical significance (P<0.05). CONCLUSION: As a therapy for advanced malignant tumors with thoracolumbar metastasis, pedicle fixation combined with (125)I brachytherapy can effectively relieve short-term pain and improve patient's quality of life.

Bone transport combined with locking plate and bone grafting for treatment of nonunion of the ulna: a case report.

STUDY DESIGN: Nonunion complicating ulna fracture surgery in one patient. OBJECTIVE: To treat nonunion of the ulna using bone transport combined with locking plate and bone grafting. METHODS: A 54-year-old male patient developing nonunion of the ulna 3 years after left ulna fracture surgery was included in this study. Bone transport combined with locking plate and bone grafting was applied to treat the patient, with the purpose of achieving the goal of bone healing at the site where nonunion occurred. RESULTS: Postoperative imaging data of the patient suggested bone healing at the site where nonunion and bone transport (by osteotomy) occurred. The patient had no special chief complaints and his forearm rotation functions were normal. CONCLUSION: Bone transport combined with locking plate and bone grafting can provide a new option for treatment of nonunion of the ulna.

Wide local excision and reconstructive surgery of desmoid tumour of the crus (Case report).

Extra-abdominal desmoid tumour is a rare type of tumour which is conventionally treated with wide local excision. However, wide local excision usually causes irreparable damage to the limbs. Nevertheless, few patients have been subjected to wide local excision and reconstructive surgery in a single procedure. A 52-year-old female reported a slow-growing lump in the right crus which had been growing for two years. The patient complained of persistent pain, especially at night, and was first subjected to lump resection in another hospital. The postoperative histopathological examination indicated muscle fibroma. Three months later, the lump recurred in the same position. The persistent pain induced by the tumour hampered her ability to walk. Wide local excision was conducted on the major parts of the gastrocnemius and soleus. After the pathological examination confirmed that the resection margin was negative, we performed reconstructive surgery on the Achilles tendon. The patient recovered plantarflexion function following the surgery and did not report any recurrence in the 6-year follow-up period. The desmoid tumour is a low-grade malignant tumour. Thus, the main focus of the treatment is to restore the function of the limbs to optimal capacity, such that the incidence of tumour recurrence is minimised.

Sandwich vertebral fracture in the study of adjacent-level fracture after vertebral cement augmentation.

The literature is inconclusive on the development of adjacent-level vertebral fracture after initial cement augmentation. A preliminary hypotheses is that cement injection exaggerates force transmission to the adjacent vertebral bodies, thereby predisposing those levels to future fractures. A sandwich vertebra is an intact vertebral body located between 2 previously cemented vertebrae. The purpose of this study was to determine whether the risk of adjacent-level fracture increased due to load shift after a cement injection procedure. The authors retrospectively investigated the rate of adjacent-level fracture after sandwiching compared with conservative treatment and determined the potential causative factors of sandwich vertebral fracture. Age, sex, weight, height, body mass index, follow-up period, and location of sandwich level (T10-L2 or nonT10-L2 junction) were assessed. Surgical variables, including surgical procedure (vertebroplasty or balloon kyphoplasty), surgical approach (through uni- or bilateral pedicle), volume of cement injected into the painful vertebrae, cement leakage into the intervertebral disk, cumulative number of treated levels, and pre- and postoperative kyphotic angulation of the sandwich region, were also analyzed. Nine of 42 sandwiched levels developed fatigue fractures, whereas 11 of 71 patients treated with conservative therapy sustained new vertebral fractures adjacent to the treated levels. Only preoperative kyphotic angulation was the variable positively associated with sandwich vertebral fracture at follow-up (P=.021). Although subjected to double load shifts, the sandwich vertebra was not prone to structural failure. Thus, cement augmentation protocol does not increase the incidence of adjacent vertebral fracture.

Spinal extradural arachnoid cyst following percutaneous vertebroplasty.

We report a rare complication of extradural arachnoid cyst following percutaneous vertebroplasty in a spinal metastasis patient. Percutaneous vertebroplasty has been established as a safe and effective treatment for osteoporotic vertebral fractures and vertebral metastatic lesions. To our knowledge, extradural arachnoid cyst following vertebroplasty has not been reported in literature. A 48-year-old woman diagnosed with adenocarcinoma underwent percutaneous vertebroplasty at the L3 vertebral level due to painful solitary spinal metastasis. At 5 months after surgery, the patient complained of low back pain radiating to the left lower extremity. MRI showed a large cystic lesion in the spinal canal at the L2-L3 level with compression to adjacent dura sac. On T1- and T2-weighted images, the signal within the cyst had the same intensity as cerebrospinal fluid. The patient underwent laminectomy for excision of the extradural cyst. Intraoperatively, a small communication between the cyst and the subarachnoid space was seen at the level of the L3 pedicle. Pathological examination revealed that the cyst wall was composed of non-specific fibrous connective tissue and the content of the cyst was the same as that of cerebrospinal fluid. Postoperatively, the patient's symptom was relieved immediately. The iatrogenic dural injury produced by puncture of the pedicle during vertebroplasty may be the cause of formation of the extradural arachnoid cyst.

Risk factors for postoperative wound infections of sacral chordoma after surgical excision.

STUDY DESIGN: A retrospective study, analyzing the risk factors for postoperative wound infections of the sacral chordoma after surgical excision. OBJECTIVE: To determine the preoperative, intraoperative, and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing sacral chordoma resection. SUMMARY OF BACKGROUND DATA: Postoperative wound infection after spinal operations is a dreaded complication. The risk factors have been investigated earlier, but the patients with sacral chordoma may be distinct. METHODS: Between January 1992 and December 2007, 45 patients with sacral chordomas were treated with surgical resection. Data regarding preoperative and intraoperative risk factors for postoperative wound infection were evaluated using univariate analysis and multivariable conditional logistic regression. Odds ratios with 95% confidence intervals and P values were calculated. RESULTS: Of the 45 patients with sacral chordoma, 16 (35.6%) acquired postoperative wound infection. Significant risk factors associated with postoperative wound infection in the univariate analysis included the following: albumin <3.0, previous surgery, operating time, instrumentation, and surgical team. Albumin<3.0, operating time >6 hours, and previous surgery were statistically significant in the multivariable model. CONCLUSIONS: Patients undergoing sacral tumor surgery may be at greater risk for developing wound complications. In this study, it seems that albumin<3.0, operating time >6 hours, and previous surgery may predict those patients that were more prone to developing postoperative wound infection. Using a single surgical team and no instrumentation seems to provide protection against postoperative wound infection in this patient population.

Effectiveness of surgical treatment for traumatic central cord syndrome.

OBJECT: The authors undertook a study in patients with traumatic central cord syndrome (TCCS) who underwent surgical intervention. They retrospectively assessed the motor score improvement and functional status and identified prognostic predictors of improvement. METHODS: Between March 1999 and May 2004, 49 patients with TCCS were surgically treated. Motor scores were collected at admission and follow-up using the American Spinal Injury Association (ASIA) Impairment Scale. The 36-Item Short Form Health Survey (SF-36) was administered. Other parameters including walking index, spasticity, bladder management, and neuropathic pain scores were recorded. Patients were asked to assess their level of satisfaction with their final symptoms. RESULTS: The average ASIA score, converted into numeric values, was increased from 54.9 at admission to 81.9 and 89.6 at 6 months and final follow-up, respectively. Significant improvement of ASIA score was achieved within the first 6 months of surgery. No significant difference was found between patients who underwent surgery within 4 days of injury or after 4 days of injury, adopting different approaches (anterior, posterior, or a combination), or with different pathological entities (acute disc herniation, fracture or dislocation, or multilevel degeneration). The ASIA score improvement had a positive correlation with the age at injury (r = 0.505, p = 0.023). The SF-36 data at 6 months and final follow-up were not as satisfactory as the improvement in ASIA scores, and almost one-third of patients expressed dissatisfaction with their final symptoms. For patients who were older than 65 years at injury, the mean follow-up Walking Index for Spinal Cord Injury (WISCI) score was statistically lower than it was in younger patients. The presence of spasticity or neuropathic pain at follow-up was not related to age, sex, ASIA motor score, or WISCI outcome. CONCLUSIONS: Surgical intervention can be safely applied in patients with TCCS. Significant improvement of ASIA score was achieved during the first 6-month period of follow-up. Factors including type of lesion, timing of surgery within or after 4 days of injury, and surgical approach were not significantly associated with final ASIA score. The improvement in the ASIA motor score was positively correlated with age at injury. No significant correlation was found between or among the presence of spasticity, neuropathic pain, and ASIA score at final visit. Almost one-third of patients were not satisfied with their final symptoms.