Explore the vast range of titles available.

The main pathological mechanism of intervertebral disc degeneration (IVDD) is the programmed apoptosis of nucleus pulposus (NP) cells. Oxidative stress is a significant cause of IVDD. Whether mitophagy is induced by strong oxidative stress in IVDD remains to be determined. This study aimed to investigate the relationship between oxidative stress and mitophagy and to better understand the mechanism of IVDD in vivo and in vitro. To this end, we obtained primary NP cells from the human NP and subsequently exposed them to TBHP. We observed that oxidative stress induced mitophagy to cause apoptosis in NP cells, and we suppressed mitophagy and found that NP cells were protected against apoptosis. Interestingly, TBHP resulted in mitophagy through the inhibition of the HIF-1α/NDUFA4L2 pathway. Therefore, the upregulation of mitochondrial NDUFA4L2 restricted mitophagy induced by oxidative stress. Furthermore, the expression levels of HIF-1α and NDUFA4L2 were decreased in human IVDD. In conclusion, these results demonstrated that the upregulation of NDUFA4L2 ameliorated the apoptosis of NP cells by repressing excessive mitophagy, which ultimately alleviated IVDD. These findings show for the first time that NDUFA4L2 and mitophagy may be potential therapeutic targets for IVDD. Disc degeneration: Mitochondria at the root of the problem A study in rats highlights the role of mitochondria in intervertebral disc degeneration (IVDD), one of the most important and prevalent predisposing factors for lower back pain. Previous studies have shown that in IVDD, oxidative stress results in the gradual loss of cells in the inner part of vertebral discs which cushion the space between vertebrae. Sheng-Dan Jiang and Lei-Sheng Jiang at Shanghai Jiaotong University School of Medicine found that oxidative stress in these cells causes the selective degradation of mitochondria by preventing the expression of a protein that is essential for mitochondrial function. Overexpressing this protein in the intervertebral discs of rats with IVDD alleviated degeneration, suggesting that restoring mitochondrial function could be an effective therapeutic strategy for easing the pain associated with the condition.

Intervertebral disc degeneration (IVDD) is the most common contributor to low back pain (LBP). Recent studies have found that oxidative stress and reactive oxygen species (ROS) play an important role in IVDD. As a by‐product of aerobic respiration, ROS is mainly produced in the mitochondria by the electron transport chain and other mitochondrial located proteins. With the excessive accumulation of ROS, mitochondria are also the primary target of ROS attack in disc cells. A disrupted balance between intracellular ROS production and antioxidant capacity will lead to oxidative stress, which is the key contributor to cell apoptosis, cell senescence, excessive autophagy, and mitochondrial dysfunction. As the pivotal ingredient of oxidative stress, mitochondrial dysfunction manifests as imbalanced mitochondrial dynamics and dysregulated mitophagy. Mitochondria can alter their own dynamics through the process of fusion and fission, so that disabled mitochondria can be separated from the mitochondrial pool. Moreover, mitophagy participates by clearing these dysfunctional mitochondria. Abnormality in any of these processes either increases the production or decreases the clearance of ROS, leading to a vicious cycle that results in the death of intervertebral disc cells in large quantities, combined with degradation of the extracellular matrix and overproduction of matrix metalloproteinase. In this review, we explain the changes in mitochondrial morphology and function during oxidative stress‐mediated IVDD and highlight the important role of mitochondria in this process. Eventually, we summarize the IVDD therapeutic strategies targeting mitochondrial dysfunction based on current understanding of the role of oxidative stress in IVDD. Graphic overview of the role of mitochondrial dysfunction in the pathogenesis of IVDD. An imbalance between ROS intercellular production and antioxidant defense capacity will directly give rise to the occurrence of oxidative stress, which is mainly represented by cell apoptosis, abnormal autophagy, cell senescence, and mitochondrial dysfunction. Among the oxidative stress‐related pathophysiological processes, mitochondrial dysfunction plays an essential role in the disc pathology of IVDD, which manifests as imbalanced dynamics and dysregulated mitophagy. ROS promotes the fusion of mitochondria, which decreases their fission process, so that disabled mitochondria can be separated from the mitochondrial pool. Further, mitophagy serves as the quality control mechanism, which can be dysregulated under the condition of oxidative stress by overwhelmingly clearing both dysfunctional and normal mitochondria. Overall, the effects of mitochondria dysfunction result in the massive disc cell death with overproduction of MMP and the degradation of ECM, eventually the pathogenesis of IVDD.

Routine use of antifibrinolytic agents in spine surgery is still an issue of debate. To gather scientific evidence for the efficacy and safety of antifibrinolytic agents including aprotinin, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA, traditionally known as Amicar) in reducing perioperative blood loss and transfusion requirements in scoliosis surgery. We conducted a systematic review and meta-analysis for randomized controlled trials (RCTs), retrospective case-control studies, and retrospective cohort studies on the use of antifibrinolytic agents in scoliosis surgery by searching in the MEDLINE and EMBASE databases and the Cochrane Database of Systematic Reviews and Controlled Trials of papers published from January 1980 through July 2014. Safety of the antifibrinolytic agents was evaluated in all included studies, while efficacy was evaluated in RCTs. Eighteen papers with a total of 1,158 patients were eligible for inclusion in this study. Among them, 8 RCTs with 450 patients were included for evaluation of pharmacologic efficacy (1 RCT was excluded because of a lack of standard deviation data). Mean blood loss was reduced in patients with perioperative use of antifibrinolytic agents by 409.25 ml intraoperatively (95% confidence interval [CI], 196.57-621.94 ml), 250.30 ml postoperatively (95% CI, 35.31-465.30), and 601.40 ml overall (95% CI, 306.64-896.16 ml). The mean volume of blood transfusion was reduced by 474.98 ml (95% CI, 195.30-754.67 ml). The transfusion rate was 44.6% (108/242) in the patients with antifibrinolytic agents and 68.3% (142/208) in the patients with placebo. (OR 0.38; 95% CI; 0.25-0.58; P<0.00001, I2 = 9%). All studies were included for evaluation of safety, with a total of 8 adverse events reported overall (4 in the experimental group and 4 in the control group). The systematic review and meta-analysis indicated that aprotinin, TXA, and EACA all significantly reduced perioperative blood loss and transfusion requirements in scoliosis surgery. There was no evidence that the use of antifibrinolytic agents was a risk factor for adverse events, especially thromboembolism, in scoliosis surgery.

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by systemic inflammation and immune dysregulation, leading to a higher risk of all-cause mortality. The Pan-Immune Inflammation Value (PIV), a novel biomarker capturing immune-inflammatory activity, has shown prognostic value in various diseases. However, its role in predicting outcomes in RA patients remains largely unexplored. This study aimed to evaluate the association between PIV and all-cause mortality in RA patients, investigate nonlinear relationships, and identify threshold effects. Data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were used, including 1,882 RA patients. PIV was calculated as (neutrophil count×platelet count×monocyte count)/lymphocyte count and categorized into quartiles (Q1-Q4). Multivariable Cox proportional hazards models were applied to assess the relationship between PIV and mortality, with results expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines (RCS) explored nonlinear trends, and segmented Cox regression identified threshold effects. Kaplan-Meier survival curves and subgroup analyses validated the findings and assessed potential modifiers. Elevated PIV levels were strongly associated with increased all-cause mortality. Compared to Q1, adjusted HRs for Q2, Q3, and Q4 were 1.60 (95% CI: 1.01-2.53, P = 0.047), 1.70 (95% CI: 1.10-2.63, P = 0.016), and 2.12 (95% CI: 1.33-3.37, P = 0.002), respectively (P for trend < 0.001). RCS analysis revealed a nonlinear relationship with a threshold at PIV = 302. Below this threshold, increasing PIV was associated with higher mortality risk (HR = 1.67, 95% CI: 1.07-2.61, P = 0.024). Conversely, above the threshold, further increases in PIV were linked to reduced mortality risk (HR = 0.98, 95% CI: 0.97-0.99, P = 0.026). Kaplan-Meier survival curves showed a clear decline in survival probability with increasing PIV quartiles (P < 0.001). Subgroup analyses confirmed consistent findings, with a notable interaction observed in diabetic patients (P for interaction = 0.002). PIV is a significant and independent predictor of all-cause mortality in RA patients, characterized by a nonlinear association and a distinct threshold effect. These findings highlight the potential of PIV as a pragmatic biomarker for stratifying mortality risk and informing personalized treatment strategies in RA.

Estradiol could protect osteoblast against apoptosis, and apoptosis and autophagy were extensively and intimately connected. The aim of the present study was to test the hypothesis that autophagy was present in osteoblasts under serum deprivation and estrogen protected against osteoblast apoptosis via promotion of autophagy. MC3T3-E1 osteoblastic cells were cultured in a serum-free and phenol red-free minimal essential medium (α-MEM). Ultrastructural analysis, lysosomal activity assessment and monodansycadaverine (MDC) staining were employed to determine the presence of autophagy, and real time PCR was used to evaluate the expression of autophagic markers. Meanwhile, the osteoblasts were transferred in a serum-free and phenol red-free α-MEM containing either vehicle or estradiol. Apoptosis and autophagy was assessed by using the techniques of real-time PCR, Western blot, immunofluorescence assay, and flow cytometry. The possible pathway through which estrogen promoted autophagy in the serum-deprived osteoblasts was also investigated. Real-time PCR demonstrated the expression of LC3, beclin1 and ULK1 genes in osteoblasts under serum deprivation, and immunofluorescence assay verified high expression of proteins of these three autophagic bio-markers. Lysosomes and autolysosomes accumulated in the cytoplasm of osteoblasts were also detected under transmission electron microscopy, MDC staining and lysosomal activity assessment. Meanwhile, estradiol significantly decreased the expression of proteins of the bio-markers of apoptosis, and at the same time increased the expression of proteins of the bio-markers of autophagy in the serum-deprived osteoblasts. Furthermore, the estradiol-promoted autophagy in serum-deprived osteoblasts could be blocked by estrogen receptor (ER) antagonist (ICI 182780), and estradiol failed to rescue the cells pretreated with an inhibitor of vacuolar ATPase (bafilomycin A) from apoptosis. Serum deprivation resulted in apoptosis through activation of Caspase-3 and induced autophagy through inhibition of phospho-mammalian target of rapamycin (p-mTOR). Both 3-methyladenine (3MA) and U0126 led to increase of apoptosis in osteoblasts with serum deprivation. Estradiol failed to over-ride the inhibitory effect of 3MA on phosphorylation of AKT but directly led to dephosphorylation of mTOR and upregulation of LC3 protein expression. However, the estradiol-enhanced LC3 protein expression was significantly suppressed by U0126 through inhibition of phosphorylation of extracellular signal-regulated kinase (ERK). Estradiol rescued osteoblast apoptosis via promotion of autophagy through the ER–ERK–mTOR pathway.

Purpose To assess the safety and efficacy of the extra-facet puncture technique applied in unilateral percutaneous vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures. Methods Demographics (age, gender, body mass index and underlying diseases) were recorded for analyzing. Visual analog scale (VAS) and Oswestry Disability Index (ODI) scores as well as their corresponding minimal clinically important difference (MCID) were used to evaluate clinical outcomes. The segmental kyphotic angle, the vertebral compression ratio and bone cement distribution pattern were evaluated by the plain radiographs. The facet joint violation (FJV) was defined by the postoperative computed tomography scan. Binary logistic regression analysis was performed to investigate relationships between multiple risk factors and residual back pain. Results VAS and ODI scores in both traditional puncture group and extra-facet puncture group were significantly decreased after PVP surgery ( p  < 0.05). However, no significant difference was observed between the two groups according to VAS and ODI scores. The proportion of patients achieving MCID of VAS and ODI scores was higher in extra-facet puncture group as compared to traditional puncture group within a month ( p  < 0.05). Finally, multivariate logistic regression analysis showed that FJV (odds ratio 16.38, p  < 0.001) and unilateral bone cement distribution (OR 5.576, p  = 0.020) were significant predictors of residual back pain after PVP surgery. Conclusions Extra-facet puncture percutaneous vertebroplasty can decrease the risk of FJV and it also has the advantage of more satisfied bone cement distribution.

Purpose. There have been many studies in the operative management of pyogenic spondylodiscitis with foreign materials. However, it still remains an issue of debate on whether the allografts may be used in pyogenic spondylodiscitis. This study sought to evaluate the safety and effectiveness of PEEK cages and the cadaveric allograft in transforaminal lumbar interbody fusion (TLIF) for treating lumbar pyogenic spondylodiscitis. Methods. From January 2012 to December 2019, 56 patients underwent surgery for lumbar pyogenic spondylodiscitis. The posterior debridement of all patients and their fusion with allografts, local bone grafts, and bone chip cages were performed before posterior pedicle screw fusion. An assessment of the residual pain, the grade of neurological injury, and the resolution of infection was conducted on 39 patients. The clinical outcome was evaluated using a visual analog scale (VAS) and the Oswestry Disability Index (ODI), and neurological outcomes were appraised based on Frankel grades. The radiological outcomes were evaluated via focal lordosis, lumbar lordosis, and the state of the fusion. Results. Staphylococcus aureus and Staphylococcus epidermidis were the most common causative organisms. The mean preoperative focal lordosis was −1.2° (−11.4° to 5.7°), and the mean postoperative focal lordosis increased to 10.3° (4.3°–17.2°). At the final follow-up, there were five cases with subsidence of the cage, no case of recurrence, and no case with cage and screw loosening or migration. The mean preoperative VAS and ODI scores were 8.9 and 74.6%, respectively, and improvements in VAS and ODI were 6.6±2.2 and 50.4±21.3%, respectively. The Frankel grade D was found in 10 patients and grade C in 7. Following the final follow-up, only one patient improved from Frankel grade C to grade D while the others recovered completely. Conclusion. The PEEK cage and cadaveric allograft combined with local bone grafts is a safe and effective choice for intervertebral fusion and restoring sagittal alignment without increased incidence of relapse for treating lumbar pyogenic spondylodiscitis.

Purpose Evaluate the efficacy of a novel unilateral dual‐plane puncture technique in improving bone cement distribution and reducing vertebral re‐collapse following percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs). By introducing the novel unilateral dual‐plane puncture technique, this study aims to improve cement distribution, reduce the incidence of re‐collapse, and enhance long‐term clinical outcomes for patients suffering from OVCFs. Methods This is a randomized trial conducted from April 2021 to December 2022, enrolling 145 patients diagnosed with OVCFs. Patients were allocated into either traditional or unilateral dual‐plane puncture groups. Bone cement distribution, vertebral height, and segmental kyphotic angle were measured through postoperative x‐ray, while clinical outcomes were evaluated using the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). Statistical analysis was performed using the Mann–Whitney U test and independent samples t test for continuous variables, and chi‐square or Fisher's exact test for categorical variables. Results The unilateral dual‐plane puncture technique notably augmented bone cement contact with both superior and inferior endplates compared to conventional methods, achieving rates of 64.86% versus 40.85% (p < 0.001). This contributed to a significant reduction in the incidence of vertebral re‐collapse within the first year post‐operation: 18.92% in the unilateral dual‐plane group as opposed to 42.25% in the traditional group (p < 0.001). Furthermore, the unilateral dual‐plane group exhibited markedly superior long‐term efficacy, evidenced by mean VAS and ODI scores of 1.26 and 28.58, respectively, in comparison to 2.03 and 32.45 in the traditional group. Conclusions The unilateral dual‐plane puncture technique advances bone cement distribution within the vertebra, thereby reducing the risk of vertebral re‐collapse following PVP surgery and improving long‐term clinical outcomes for patients with OVCFs. Trajectory of the unilateral dual‐plane puncture. The sagittal CT scan after surgery clearly shows the puncture trajectory of the unilateral dual‐plane puncture. The bone cement simultaneously contacted both the upper and lower end plates.

Objective Lumbar disc degeneration (LDD) is a common cause of low back pain and disability, and its prevalence increases with age. The aim of this study is to investigate whether endplate Hounsfield unit (HU) values have an effect on lumbar disc degeneration (LDD) after transforaminal lumbar interbody fusion (TLIF) surgery in patients with degenerative lumbar stenosis. Methods This study was a retrospective analysis of patients who underwent TLIF surgery in January 2016 to October 2019. One hundred and fifty‐seven patients who underwent TLIF surgery for degenerative lumbar stenosis were enrolled in this study. Demographic data was recorded. VAS and ODI values were compared to assess the surgical outcomes in patients with or without process of LDD after TLIF surgery. Correlation analysis was performed to investigate associations between LDD and endplate HU value. Binary logistic regression analysis was carried out to study relationships between the DDD and the multiple risk factors. Results There was a statistically significant correlation between LDD, body mass index (BMI), age, paraspinal muscle atrophy, and total endplate scores (TEPS). Also, a strong and independent association between endplate HU value and LDD was found at every lumbar disc level (p < 0.01). After conditioning on matching factors, multivariate logistic regression analysis showed that higher endplate HU (odds ratio [OR]: 1.003, p = 0.003), higher TEPS (OR: 1.264, p = 0.002), higher BMI (odds ratio [OR]: 1.202, p = 0.002), a smaller cross‐sectional area (CSA) of the paraspinal muscle preoperatively (OR: 0.096, p < 0.001) were significant predictors of LDD development after TLIF surgery. Conclusions There is a significant association between LDD and endplate HU value after TLIF surgery in patients with degenerative lumbar stenosis. Beyond that, results from this study provide a mechanism by which high endplate HU value predisposes to LDD after TLIF surgery. Measurement of the Hounsfield units (HU) values of endplate. Locating the endplate in the sagittal plane then trailing edge of hyperintense area and recording the mean HU value in the coronal plane.

There have been an increasing number of patients with degenerative disc diseases due to the aging population. In light of this, studies on the pathogenesis of intervertebral disc degeneration have become a hot topic, and gene knockout mice have become a valuable tool in this field of research. With the development of science and technology, constitutive gene knockout mice can be constructed using homologous recombination, zinc finger nuclease, transcription activator‐like effector nuclease technology and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) system, and conditional gene knockout mice can be constructed using the Cre/LoxP system. The gene‐edited mice using these techniques have been widely used in the studies on disc degeneration. This paper reviews the development process and principles of these technologies, functions of the edited genes in disc degeneration, advantages, and disadvantages of different methods and possible targets of the specific Cre recombinase in intervertebral discs. Recommendations for the choice of suitable gene‐edited model mice are presented. At the same time, possible technological improvements in the future are also discussed. In this review, we described the development process and principles of the gene knockout technologies, functions of the edited genes in disc degeneration, advantages and disadvantages of different methods and possible targets of the specific Cre recombinase in intervertebral discs. Recommendations for the choice of suitable gene‐edited model mice for the study of disc degeneration are presented. At the same time, possible technological improvements in the future are also discussed.