Background: Inflammatory response mediated by oxidative stress is considered as an important pathogenesis of spinal cord injury (SCI). Advanced oxidation protein products (AOPPs) are novel markers of oxidative stress and their role in inflammatory response after SCI remained unclear. This study aimed to investigate the role of AOPPs in SCI pathogenesis and explore the possible underlying mechanisms. Methods: A C5 hemi-contusion injury was induced in Sprague-Dawley rats to confirm the involvement of AOPPs after SCI. For in vivo study, apocynin, the NADPH oxidase inhibitor was used to study the neuroprotective effects after SCI. For in vitro study, the BV2 microglia cell lines were pretreated with or without the inhibitor or transfected with or without small interference RNA (siRNA) and then stimulated with AOPPs. A combination of molecular and histological methods was used to clarify the mechanism and explore the signaling pathway both in vivo and in vitro. One-way analysis of variance (ANOVA) was conducted with Bonferroni post hoc tests to examine the differences between groups. Results: The levels of AOPPs in plasma and cerebrospinal fluid as well as the contents in the spinal cord showed significant increase after SCI. Meanwhile, apocynin ameliorated tissue damage in the spinal cord after SCI, improving the functional recovery. Immunofluorescence staining and western blot analysis showed activation of microglia after SCI, which was in turn inhibited by apocynin. Pretreated BV2 cells with AOPPs triggered excessive generation of reactive oxygen species (ROS) by activating NADPH oxidase. Increased ROS induced p38 MAPK and JNK phosphorylation, subsequently triggering nuclear translocation of NF-κB p65 to express pro-inflammatory cytokines. Also, treatment of BV2 cells with AOPPs induced NLRP3 inflammasome activation and cleavage of Gasdermin-d (GSDMD), causing pyroptosis. This was confirmed by cleavage of caspase-1, production of downstream mature interleukin (IL)-1β and IL-18 as well as rupture of rapid cell membrane.

There are few articles in the literature concerning anterior instrumentation in the surgical management of spinal tuberculosis in the exudative stage. So we report here 23 cases of active thoracolumbar spinal tuberculosis treated by one-stage anterior interbody autografting and instrumentation to verify the importance of early reconstruction of spinal stability and to evaluate the results of one-stage interbody autografting and anterior instrumentation in the surgical management of the exudative stage of throracolumbar spinal tuberculosis. Twenty-three patients, including two children (9 and 15 years old, respectively) and 21 adults with thoracolumbar spinal tuberculosis were treated surgically. T9 to L4 spinal segments were affected, and MRI/CT showed evident collapse of the vertebrae because of tuberculous destruction and paravertebral abscess. Neurological deficits were found in 15 patients. Before surgery, patients received standard anti-tuberculosis chemotherapy for 2 to 3 weeks. Under general endotracheal anaesthesia, the patients were placed in right recumbent positions, and a transthoracic, lateral extracavitary or extrapleural approach was chosen according to the tuberculosis lesion segment. After exposure, the tuberculous lesion region, including the collapsed vertebrae and in-between intervertebral disc, was almost completely resected in order to release the segmental spinal cord. Then, autologous iliac, rib or fibular graft was harvested to complete interbody fusion, and an anterior titanium-alloy plate-screw system was used to reconstruct the stability of the affected segments. Anti-tuberculosis chemotherapy was continued for at least 9 months, and the patients were supported with thoracolumbosacral orthosis for 6 months after surgery. All patients were followed up for an average of 2 years. All 23 cases were healed without chronic sinus formation or any recurrence of tuberculosis during the follow-up period. Spinal fusion occurred at a mean of 3.8 months after surgery. Of all patients with neurological deficits, 14 patients showed obvious improvement; only one patient with Frankel C lesion remained unchanged, but none of the patients got worse. During the follow-up period, a mean of 18 degrees of kyphosis correction was achieved after surgery in the adult group. Moderate progressive kyphosis because of this procedure fusion occurred postoperatively in a 9-year-old child after 2 1/2 years; another 15-year-old child did not demonstrate this phenomenon. Except for the early loosening of one screw in two cases (which did not affect the reconstruction of spinal stability), no other complications associated with this procedure were found during follow-up. Early reconstruction of spinal stability plays an important role in the surgical management of spinal tuberculosis. One-stage anterior interbody autografting and instrumentation in the surgical management of the exudative stage of spinal tuberculosis show more advantages in selected patients, but supplementary posterior fusion should be considered to pre...

Hypertrophy of the ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS), and results mainly from fibrosis. Connective tissue growth factor (CTGF) is a profibrotic factor involved in the fibrotic process. This study aimed to evaluate CTGF expression in hypertrophied lumbar LF and the involvement of CTGF in LF hypertrophy. Ten patients with LSS were enrolled in this study. The control group included 10 patients with lumbar disc herniation. LF thickness was measured on the preoperative axial T1-weighted MRI. LF samples were collected during surgery. LF fibrosis was scored by Masson's trichrome staining. CTGF expression was determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Correlation between LF thickness and CTGF expression was analyzed. Human LF cells were cultured and treated with recombinant human (rh) CTGF. Expression of types I and III collagen was determined by real-time PCR and ELISA. The thickness and fibrosis scores of LF in the LSS group were higher than that in the control group (all P < 0.001). CTGF was expressed in the extracellular matrix of all ligament samples, and was significantly higher in the LSS group than that in the control group (P < 0.001). The increase of CTGF expression was positive correlation with the LF thickness (r ¼ 0.969, P ¼ 0.000). rhCTGF treatment increased the mRNA expression and protein synthesis of types I and III collagen of the LF cells (all P < 0.001). Our results suggest that the increased expression of CTGF is associated with hypertrophy of the LF in patients with LSS. ß

Cement leakage is very common with PVP. Higher fracture severity grade and larger volume of bone cement were the two strongest independent risk factors for leakage.

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Interleukin (IL)-1β and tumor necrosis factor (TNF)-α, in particular, control the degeneration of articular cartilage, making them prime targets for osteoarthritis (OA) therapeutic strategies. Advanced oxidation protein products (AOPPs) are prevalent in numerous diseases. Our previous work demonstrates that intra-articular injections of AOPPs accelerate regression of cartilage in OA models. Whether AOPPs exist in the course of OA and their effects on TNF-α and IL-1β expression in chondrocytes are still unclear. This study confirmed that AOPPs levels in human synovial fluid were positively associated with severity of OA. We also found AOPPs deposition in articular cartilage in anterior cruciate ligament transection (ACLT) induced rodent OA models. AOPPs increased expression of TNF-α and IL-1β in chondrocytes in vitro, which was inhibited by pre-treatment with SB202190 (p38-MAPK inhibitor) or apocynin (NADPH oxidase inhibitor) or NOX4 knockdown by siRNAs. Subsequently, we further verified in vivo that exogenous injection of AOPPs in OA mice up-regulated expression of TNF-α and IL-1β in cartilage, which was blocked by treatment with apocynin. In parallel, apocynin attenuated articular cartilage degeneration resulting in substantially lower OARSI scores. Specifically, apocynin reduced NOX4, p-P38, TNF-α and IL-1β and increased collagen II and glycosaminoglycan (GAG). This study demonstrated that AOPPs increased expression of TNF-α and IL-1β in chondrocytes via the NADPH oxidase4-dependent and p38-MAPK mediated pathway, and accelerated cartilage degeneration in OA progression. These findings suggest an endogenous pathogenic role of AOPPs in OA progression. Targeting AOPPs-triggered cellular mechanisms might be a promising therapeutic option for patients with OA.

SummaryOsteoblast apoptosis contributes to age‐related bone loss. Advanced oxidation protein products (AOPPs) are recognized as the markers of oxidative stress and potent inducers of apoptosis. We have demonstrated that AOPP accumulation was correlated with age‐related bone loss. However, the effect of AOPPs on the osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC3T3‐E1 cells to AOPPs caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Increased ROS induced phosphorylation of mitogen‐activated protein kinases (MAPKs), which subsequently triggered intrinsic apoptosis pathway by inducing mitochondrial dysfunction, endoplasmic reticulum stress, and Ca2+ overload and eventually leads to apoptosis. Chronic AOPP loading in aged Sprague‐Dawley rats induced osteoblast apoptosis and activated NADPH oxidase signaling cascade, in combination with accelerated bone loss and deteriorated bone microstructure. Our study suggests that AOPPs induce osteoblast apoptosis by the NADPH oxidase‐dependent, MAPK‐mediated intrinsic apoptosis pathway.