Repeat Surgery after Percutaneous Endoscopic Lumbar Discectomy for Adolescent Lumbar Disc Herniation: A Multicenter Observational Study.

OBJECTIVE: The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. METHODS: A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed-rank test. RESULTS: A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re-herniation (homo-lateral re-herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro-endoscopic discectomy (MED), open discectomy and instrumented lumbar inter-body fusion. The NRS scores decreased significantly in follow-up evaluations and these scores demonstrated significant improvement at the last follow-up (p < 0.002). For the modified MacNab criteria, at the last follow-up, 18 patients (78.26%) had an excellent outcome, and the overall success rate was 86.95%. CONCLUSION: This study's data suggest that young patients who underwent repeat surgery improved significantly compared to baseline. The chief cause was re-herniation. Revision PELD was the main surgical procedure, which provides satisfactory clinical results in young patients who underwent repeat surgeries.

Prediction Model and Risk Factor Analysis of Adjacent Segment Disease After L4-5 Transforaminal Lumbar Interbody Fusion Through Preoperative Radiographic Features.

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the risk of adjacent segment disease (ASD) after L4-5 transforaminal lumbar interbody fusion (TLIF) in patients diagnosed with lumbar spinal stenosis (LSS), a prediction model for ASD is established and validated. METHODS: A retrospective study was carried out on a sample of 290 patients who underwent L4-5 TLIF at Zhongda Hospital, Southeast University, from January 2015 to January 2021. The study collected baseline data and preoperative radiographic features of L3-4 and L5-S1. The determination of the outcome variable was based on X-ray results spanning over 24 months and JOA scores. Multivariate logistic regression was used to identify the risk factors in constructing a nomogram. RESULTS: Independent risk factors for L3-4 degeneration after TLIF included osteoarthritis of L3-4 facet joints, L3-4 foraminal stenosis, L4 upper endplate osteochondritis, L3-4 local lordosis angle, and L3-4 spinal stenosis. Independent risk factors for L5-S1 degeneration after TLIF included osteoarthritis of L5-S1 facet joints, L5-S1 intervertebral disc degeneration, L5-S1 spinal stenosis, L5-S1 coronal imbalance, and S1 upper endplate osteochondritis. A predictive model was developed. The AUC for the prediction models at L3-4 and L5-S1 were .945 and .956. The calibration curve demonstrated good consistency between the predicted and actual probabilities. The DCA curve indicated the clinical benefit and practical value of this predictive model. CONCLUSION: This study established nomograms for postoperative degeneration at L3-4 and L5-S1 based on selected preoperative radiographic features. These models provide a valuable auxiliary decision-making system for clinicians and aid in early surgical decisions.

Endoplasmic reticulum stress-mediated autophagy alleviates lipopolysaccharide-induced nucleus pulposus cell pyroptosis by inhibiting CHOP signaling in vitro.

Pyroptosis, a newly discovered pro-inflammatory programmed necrosis of cells, serves as an initiating and promoting event that leads to intervertebral disc (IVD) degeneration (IDD). Endoplasmic reticulum stress (ERS) and autophagy are vital regulatory mechanisms of cellular homeostasis, which is also closely related to IDD. However, the role and relationship of ERS and autophagy in the pyroptosis of nucleus pulposus cell (NPC) are not well understood. In this research, we aimed to elucidate the role and mechanism of ERS-C/EBP homologous protein (CHOP) in lipopolysaccharide (LPS)-induced cell pyroptosis and determine its interaction with autophagy. ERS and autophagy inducers or inhibitors were used or not in the preconditioning of rat NPCs. Cell viability, pyroptosis-related protein expression, caspase-1 activity assay, and enzyme-linked immunosorbent assay were performed to observe rat NPC pyroptosis after the treatment of LPS. Activation of the ERS pathway and autophagy were assessed by quantitative real-time PCR, western blot analyses, and immunofluorescence staining assay to classify the molecular mechanisms. Our results showed that LPS stimulation induced NPC pyroptosis with concomitant activation of the ERS-CHOP pathway and initiated autophagy. Activation of the ERS-CHOP pathway exacerbated rat NPC pyroptosis, whereas autophagy inhibited cell pyroptosis. LPS-induced cell pyroptosis and CHOP upregulation were negatively regulated by autophagy. LPS-induced autophagy was depressed by the ERS inhibitor but aggravated by the ERS inducer. Taken together, our findings suggested that LPS induced NPC pyroptosis by activating ERS-CHOP signaling and ERS mediated LPS-induced autophagy, which in turn alleviated NPC pyroptosis by inhibiting CHOP signaling.

Interpretable Machine Learning Model to Predict Bone Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fracture Based on SHapley Additive exPlanations.

STUDY DESIGN: Retrospective study. OBJECTIVES: Our objective is to create comprehensible machine learning (ML) models that can forecast bone cement leakage in percutaneous vertebral augmentation (PVA) for individuals with osteoporotic vertebral compression fracture (OVCF) while also identifying the associated risk factors. METHODS: We incorporated data from patients (n = 425) which underwent PVA. To predict cement leakage, we devised six models based on a variety of parameters. Evaluate and juxtapose the predictive performances relied on measures of discrimination, calibration, and clinical utility. SHapley Additive exPlanations (SHAP) methodology was used to interpret model and evaluate the risk factors associated with cement leakage. RESULTS: The occurrence rate of cement leakage was established at 50.4%. A binary logistic regression analysis identified cortical disruption (OR 6.880, 95% CI 4.209-11.246), the basivertebral foramen sign (OR 2.142, 95% CI 1.303-3.521), the fracture type (OR 1.683, 95% CI 1.083-2.617), and the volume of bone cement (OR 1.198, 95% CI 1.070-1.341) as independent predictors of cement leakage. The XGBoost model outperformed all others in predicting cement leakage in the testing set, with AUC of .8819, accuracy of .8025, recall score of .7872, F1 score of .8315, and a precision score of .881. Several important factors related to cement leakage were drawn based on the analysis of SHAP values and their clinical significance. CONCLUSION: The ML based predictive model demonstrated significant accuracy in forecasting bone cement leakage for patients with OVCF undergoing PVA. When combined with SHAP, ML facilitated a personalized prediction and offered a visual interpretation of feature importance.

Scientific Bibliometric and Visual Analysis of Studies on Autophagy in Intervertebral Disc Degeneration Based on Web of Science.

OBJECTIVE: To analyze the current research trends and potential mechanisms related to the role of autophagy in intervertebral disc degeneration (IVDD) and to provide new ideas for future research in this field. METHODS: All articles on IVDD and autophagy were retrieved and extracted from the Web of Science (WoS) core collection database. The results were evaluated and visualized using the bibliometric Web site, CiteSpace, and VOSviewer software, including annual articles published, countries, institutions, authors, journals, research areas, funding agencies, citations, and keywords. RESULTS: From January 1, 2011, to December 31, 2022, 323 reviews and original articles were included, and the overall trend in the number of articles was increasing rapidly. China and the United States were the countries with the most scientific research achievements. The 323 articles received a total number of citations of 6949, with an H index of 43 and an average citation of 21.51. The top publication country, institution, author, journal, research area, and funding agency were China, Huazhong University of Science and Technology, Cao Yang of Tongji Medical College, Oxidative Medicine and Cellular Longevity, cell biology, and National Natural Science Foundation of China, respectively. Most of the keywords were associated with the mechanisms and regulatory networks of autophagy. In addition, with increasing evidence showing the key role of autophagy in IVDD, therapy, signaling pathway, and mitophagy are emerging as new research hot spots that should be paid more attention. CONCLUSIONS: This study provided a scientific perspective on autophagy in IVDD and elucidated the current research status and hot spots in this field. The mechanism of autophagy and the application of regulating autophagy in the treatment of IVDD deserve further research.

Comparison of thoracolumbar versus non-thoracolumbar osteoporotic vertebral compression fractures in risk factors, vertebral compression degree and pre-hospital back pain.

BACKGROUND: Thoracolumbar spine is at high risk of osteoporotic vertebral compression fractures (OVCF). This study aimed to identify the differences in risk factors, vertebral compression degree and back pain characteristics of thoracolumbar OVCF (TL-OVCF) and non-thoracolumbar OVCF (nTL-OVCF). METHODS: OVCF patients hospitalized in a spine center between June 2016 and October 2020 were retrospectively studied. Demographics, comorbidity, spine trauma, bone mineral density, duration of pre-hospital back pain, extent of vertebral marrow edema, and degree of vertebral compression of patients with nTL-OVCF were summarized and compared to those with TL-OVCF. RESULTS: A total of 944 patients with acute single-segment OVCF were included. There were 708 (75.0%) TL-OVCF located in T11-L2 and 236 (25.0%) nTL-OVCF in lower lumbar (L3-L5) and middle thoracic (T5-T10) spine. The female-male ratio was 4.1 in nTL-OVCF and differed not significantly from TL-OVCF. The middle thoracic OVCF were older and had higher comorbidity of coronary heart disease (21.3%) and cerebral infarction (36.3%) than TL-OVCF (12.1% and 20.6%). In nTL-OVCF the ratio of apparent spine trauma (44.9%) and pre-hospital back pain ≤ 1 week (47.5%) was lower than in TL-OVCF (66.9% and 62.6%). The T-score value of lumbar spine was - 2.99 ± 1.11, - 3.24 ± 1.14, - 3.05 ± 1.40 in < 70, 70-80, > 80 years old TL-OVCF and differed not significantly from nTL-OVCF. The lower lumbar OVCF had more cranial type of vertebral marrow edema (21.8%) and fewer concurrent lumbodorsal fasciitis (30.8%) than TL-OVCF (16.8% and 43.4%). In TL-OVCF the anterior-posterior vertebral height ratio was lower with back pain for > 4 weeks than for ≤ 1, 1-2, and 2-4 weeks. In nTL-OVCF the degree of vertebral compression differed not significantly with pre-hospital back pain for ≤ 1, 1-2, 2-4, and > 4 weeks. CONCLUSIONS: Thoracolumbar spine has 2-folds higher risk of OVCF than non-thoracolumbar spine. Non-thoracolumbar OVCF are not associated with female gender, apparent spine trauma or poor bone mineral density, but tend to maintain the degree of vertebral compression and cause longer duration of pre-hospital back pain.

Nucleus Pulposus Cells Induce M2 Polarization of RAW264.7 via CX3CL1/CX3CR1 Pathway and M2 Macrophages Promote Proliferation and Anabolism of Nucleus Pulposus Cells.

Background: The mechanisms underlying M2 macrophage polarization induced by nucleus pulposus (NP) cells are unclear. The effects that M2-polarized macrophages have on NP cells are also controversial. Methods: Transcriptome sequencing was performed to detect the gene change profiles between NP cells from ruptured intervertebral disc (IVD) and normal IVD. The main difference on biological activities between the two cell groups were analyzed by GO analysis and KEGG analysis. Virus transduction, flow cytometry, immunofluorescence, RT-PCR, western blot, CCK-8, TUNEL staining, and AO/EB staining were performed to explore the interactions between NP cells and RAW264.7 macrophages. Statistics were performed using SPSS26. Results: 801 upregulated and 276 downregulated genes were identified in NP cells from ruptured IVD in mouse models. According to GO and KEGG analysis, we found that the differentially expressed genes (DEG) were dominantly enriched in inflammatory response, extracellular matrix degradation, blood vessel morphogenesis, immune effector process, ossification, chemokine signaling pathway, macrophage activation, etc. CX3CL1 was one of the top 20% DEG, and we confirmed that both NP tissue and cells expressed remarkably higher level of CX3CL1 in mouse models (p < 0.001∗). Besides, we further revealed that both the recombinant CX3CL1 and NP cells remarkably induced M2 polarization of RAW264.7 (p < 0.001∗), respectively, while this effect was significantly reversed by si-CX3CL1 or JMS-17-2 (p < 0.001∗). Furthermore, we found that M2 macrophages significantly decreased the apoptosis rate (p < 0.001∗) and the catabolic gene levels (p < 0.001∗) of NP cells, while increased the viability, proliferation as well as the anabolic gene levels of NP cells (p < 0.01∗). Conclusions: Via regulating CX3CL1/CX3CR1 pathway, NP cells can induce the M2 macrophage polarization. M2 polarized macrophages can further promote NP cell viability, proliferation, and anabolism, while inhibit NP cell apoptosis and catabolism.

Comparison of acute single versus multiple osteoporotic vertebral compression fractures in radiographic characteristic and bone fragility.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) are common in aged population with bone fragility. This study aimed to identify the radiographic and bone fragility characteristic of acute single and multiple OVCF. METHODS: OVCF patients hospitalized in a spine center between June 2016 and October 2020 were retrospectively studied. Demographics, comorbidity, bone mineral density, spine trauma, duration of pre-hospital back pain, anatomical location and distribution pattern of OVCF, extent of vertebral marrow edema, and degree of vertebral compression of patients with multi-segment vertebral fractures (MSVF) were summarized and compared to those with single segment vertebral fractures (SSVF). RESULTS: A total of 1182 patients with 1530 acute fractured vertebrae were included. There were 944 SSVF (79.9%) and 238 MSVF (20.1%) simultaneously involving two (MSVF-2) or three and more vertebra (MSVF-3/m). The Female-Male ratio was 4.4 and differed not significantly between SSVF and MSVF. Females in SSVF were younger than males while MSVF-2 tended to occur in older females. L1, T12, and L2 were the three most frequently fractured vertebra and MSVF involved more vertebra in thoracic and lumbar spine. 31.1% in MSVF-2 and 83.1% in MSVF-3/m had at least two vertebral fractures in adjacent. The fractured thoracolumbar vertebra in MSVF was less compressed than that in SSVF. Apparent spine trauma was reported by 61.4% of SSVF, 44.1% of MSVF-2, and 36.3% of MSVF-3/m, while early hospitalization with pre-hospital back pain ≤ 1 week was 58.9% in SSVF, 45.3% in MSVF-2, and 25.9% in MSVF-3/m. Only females aged 70-80 years old in MSVF-3/m showed lower baseline bone mineral density than in MSVF-2 and SSVF. MSVF were not associated with increased comorbidity of hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic pulmonary disease. CONCLUSIONS: 20% of acute OVCF can involve multiple vertebra without significant spine trauma or lower baseline bone mineral density. Multiple OVCF tend to occur in adjacent vertebra with less thoracolumbar vertebral compression but longer duration of pre-hospital back pain.

Machine Learning Prediction Model and Risk Factor Analysis of Reoperation in Recurrent Lumbar Disc Herniation Patients After Percutaneous Endoscopic Lumbar Discectomy.

OBJECTIVE: To investigate the risk factors of reoperation after percutaneous endoscopic lumbar discectomy (PELD) due to recurrent lumbar disc herniation (rLDH) and to establish a set of individualized prediction models. METHODS: Patients who underwent PELD successfully from January 2016 to February 2022 in a single institution were enrolled in this study. Six methods of machine learning (ML) were used to establish an individualized prediction model for reoperation in rLDH patients after PELD, and these models were compared with logistics regression model to select optimal model. RESULTS: A total of 2603 patients were enrolled in this study. 57 patients had repeated operation due to rLDH and 114 patients were selected from the remaining 2546 nonrecurrent patients as matched controls. Multivariate logistic regression analysis showed that disc herniation type (P < .001), Modic changes (type II) (P = .003), sagittal range of motion (sROM) (P = .022), facet orientation (FO) (P = .028) and fat infiltration (FI) (P = .001) were independent risk factors for reoperation in rLDH patients after PELD. The XGBoost AUC was of 90.71%, accuracy was approximately 88.87%, sensitivity was 70.81%, specificity was 97.19%. The traditional logistic regression AUC was 77.4%, accuracy was about 77.73%, sensitivity was 47.15%, specificity was 92.12%. CONCLUSION: This study showed that disc herniation type (extrusion, sequestration), Modic changes (type II), a large sROM, a large FO and high FI were independent risk factors for reoperation in LDH patients after PELD. The prediction efficiency of XGBoost model was higher than traditional Logistic regression analysis model.

Which Criterion for Wound Drain Removal is Better Following Posterior 1-Level or 2-Level Lumbar Fusion With Instrumentation: Time Driven or Output Driven?

STUDY DESIGN: Case-control study. OBJECTIVES: To compare the outcomes of 2 different criteria (time driven and output driven) for wound drain removal and identify which one is better. METHODS: 743 patients who underwent posterior lumbar fusion with instrumentation involving 1 or 2 motion segments were enrolled in this study. Based on the different criteria for drain removal, the patients were divided into 2 groups. The drains were discontinued by time driven (postoperative day 2) in group I and output driven (<50 ml per day) in group II. Demographic characteristics, perioperative parameters and clinical outcomes were compared between the 2 groups. RESULTS: The demographic characteristics in both groups were comparable. The postoperative drain output, total blood loss, postoperative timing of ambulation, and postoperative duration of hospital stay in group I were lower than those in group II (P < 0.001). There was a higher proportion of patients requiring postoperative blood transfusion in group II, but not to a level of statistical significance (P = 0.054). There was no statistical significant difference in the incidence of surgical site infection (SSI) or symptomatic spinal epidural hematoma (SEH) between the 2 groups (P > 0.05). CONCLUSIONS: This study reveals that there are more benefits of wound drain removal by time driven than that by output driven for patients undergoing posterior 1-level or 2-level lumbar fusion with instrumentation, including less postoperative drain output, less total blood loss, earlier postoperative timing of ambulation and less postoperative duration of hospital stay without increasing the incidence of postoperative SSI or symptomatic SEH.

Instrumented fusion versus instrumented non-fusion following expansive open-door laminoplasty for multilevel cervical ossification of the posterior longitudinal ligament.

PURPOSE: To compare the outcomes of expansive open-door laminoplasty with instrumented fusion (ELIF) and expansive open-door laminoplasty with instrumented non-fusion (ELINF) for multilevel cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: Patients who underwent ELIF or ELINF due to multilevel cervical OPLL from June 2013 to June 2019 were identified. Clinical and radiological outcomes were compared between the two groups. RESULTS: A total of 78 patients were enrolled in this study with a minimum follow-up of 24 months, including 42 patients in the ELIF group and 36 patients in the ELINF group. At the final follow-up, sagittal vertical axis (SVA) and C2-C7 Cobb angle in the ELIF group were significantly better than those in the ELINF group, and cervical range of movement (ROM) in the ELIF group decreased significantly than that in the ELINF group. The incidence of OPLL progression at the final follow-up was 4.76% (2/42) in the ELIF group and 27.78% (10/36) in the ELINF group. Postoperative Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), and visual analog scale (VAS) score improved significantly in each group, but JOA score and recovery rate (RR) in the ELIF group were significantly better than those in the ELINF group at the final follow-up. When K-line was positive, the difference in the final JOA score between the two groups was not significant, but the RR in the ELIF group was significantly better than that in the ELINF group. When K-line was negative, the final JOA score and RR in the ELIF group were significant higher than those in the ELINF group. CONCLUSIONS: ELIF and ELINF were two effective surgical procedures for treating multilevel cervical OPLL. However, ELIF was superior to ELINF due to better postoperative JOA score and RR, significant improvement of C2-C7 Cobb angle and maintenance of SVA, and suppressant effect on OPLL progression, especially for patients with K-line ( - ) OPLL.

A20 ameliorates disc degeneration by suppressing mTOR/BNIP3 axis-mediated mitophagy.

BACKGROUND: The pathological mechanism of intervertebral disc degeneration (IDD) is an unanswered question that we are committed to exploring. A20 is an anti-inflammatory protein of nucleus pulposus (NP) cells and plays a protective role in intervertebral disc degeneration. OBJECTIVE: This study aims to investigate the molecular mechanism by which A20 attenuates disc degeneration. METHODS: The proteins of interest were measured by immunoblotting, immunofluorescence, ELISA assay, and immunohistochemical technique to conduct related experiments. Immunofluorescence assays and mitochondrial membrane potential (JC-1) were used to assess mitophagy and mitochondrial fitness, respectively. RESULTS: Here, we demonstrated that A20 promoted mitophagy, attenuated pyroptosis, and inhibited the degradation of the extracellular matrix, consequently significantly ameliorating disc degeneration. Mechanistically, A20 reduces pyroptosis and further suppresses cellular mTOR activity. On the one hand, A20-induced mTOR inhibition triggers BNIP3-mediated mitophagy to ensure mitochondrial fitness under LPS stimulation, as a result of mitigating mitochondrial dysfunction induced by LPS. On the other hand, A20-induced mTOR inhibition reduces the loss of mitochondrial membrane potential and the generation of Mitochondrial ROS. CONCLUSION: The study revealed that A20 promotes BNIP3-mediated mitophagy by suppressing mTOR pathway activation against LPS-induced pyroptosis.

Update on the roles of macrophages in the degeneration and repair process of intervertebral discs.

Intervertebral disc (IVD) degeneration is the common cause of lumbar degenerative diseases, causing severe social and economic burden. The process of IVD degeneration involves a complex of pathologic changes on both extracellular matrix degradation and resident cell apoptosis. In recent years, there is increasing evidence that macrophages play vital roles during the damage and repair process of IVD degeneration. Nevertheless, the interactions between macrophages and IVD are not well understood, even if the IVD has long been regarded as the immune privileged site. Therefore, this review mainly focuses on the progress and obstacles of studies investigating the blood supply, immune response and especially macrophages during the IVD degeneration process.

CircRNA-Associated ceRNA Network Reveals Focal Adhesion and Metabolism Pathways in Neuropathic Pain.

Background: Increasing evidence has shown that noncoding RNAs perform a remarkable function in neuropathic pain (NP); nonetheless, the mechanisms underlying the modulation of competitive endogenous RNA in NP remain uncertain. The goal of this research was to investigate the molecular processes underlying NP. Methods: We utilized the Gene Expression Omnibus (GEO) to obtain NP-related microarray datasets that included the expression patterns of circular RNAs (circRNAs) and messenger RNAs (mRNAs). Following that, bioinformatics analyses and a molecular biology experiment were carried out. Results: According to the findings, carrying out enrichment studies of the targeted genes had an impact on a variety of NP-related pathways. Notably, we isolated a ceRNA subnetwork incorporating two upregulated circRNAs (Esrrg and Map3k3) which primarily participate in the focal adhesion pathway by regulating Integrin Subunit Beta 4 (ITGB4) and two downregulated circRNAs (Dgkb and Atp2a2), which potentially regulate metabolism-related molecule Lipase A (LIPA). Conclusions: According to our findings, the focal adhesion and metabolic signaling pathways could be critical in the advancement of NP, and some circRNA might regulate this biological process through the ceRNA network, which might offer pertinent insights into the underlying mechanisms.

Intraoperative Endplate Injury Following Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To investigate the incidence, distribution characteristics, risk factors, and clinical outcomes of intraoperative endplate injury (EI) following transforaminal lumbar interbody fusion. METHODS: Patients who underwent single-level transforaminal lumbar interbody fusion from January 2018 to December 2020 were included. The patients were separated into EI and non-EI groups based on computed tomography obtained immediately postoperatively. Demographic, clinical, and radiographic parameters of all patients were analyzed. Clinical outcomes were evaluated by visual analog scale for low back pain and Oswestry Disability Index. RESULTS: This study enrolled 576 patients. Rates of EI were 19.6% (113/576) of patients and 9.9% (114/1152) of endplates. The rate of superior EI was significantly higher than that of inferior EI. The results showed that older age, lower disc height index, and taller cage height were independent risk factors for intraoperative EI. Postoperative drain output, total blood loss, postoperative duration of drainage tube, and postoperative hospital stay in the EI group were significantly greater than in the non-EI group. There were no statistical differences in Oswestry Disability Index and visual analog scale scores at the same time point between the groups. CONCLUSIONS: Rates of EI were 19.6% of patients and 9.9% of endplates. Superior endplates were more susceptible to injury than inferior endplates. Older age, lower disc height index, and taller cage height were independent risk factors for intraoperative EI. Clinical outcomes were not affected by intraoperative EI during early postoperative follow-up.

The Mini-Open Wiltse Approach with Pedicle Screw Fixation Versus Percutaneous Pedicle Screw Fixation for Treatment of Neurologically Intact Thoracolumbar Fractures: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of the present study was to compare the clinical outcomes and complications between the mini-open Wiltse approach with pedicle screw fixation (MWPSF) and percutaneous pedicle screw fixation (PPSF) in treating neurologically intact thoracolumbar fractures. METHODS: We comprehensively searched PubMed, Web of Science, Embase, and the Cochrane Library and performed a systematic review and meta-analysis of all randomized controlled trials and retrospective comparative studies assessing these important indexes of the 2 methods using Review Manager, version 5.4. The clinical outcomes are presented as the risk difference for dichotomous outcomes and the mean difference for continuous outcomes with the 95% confidence intervals. Heterogeneity was assessed using the χ2 test and I2 statistics. The study was registered with PROSPERO (CRD 42021290078). RESULTS: Two randomized controlled trials and six retrospective cohort studies were included in the present analysis. The percutaneous approach was associated with less intraoperative blood loss compared with the mini-open Wiltse approach. No significant differences were found in the total length of the incisions, hospitalization time, postoperative visual analog scale scores, postoperative Oswestry disability index, postoperative Cobb angle, postoperative Cobb angle correction, postoperative Cobb angle correction loss, accuracy rate of pedicle screw placement, and postoperative complications between MWPSF and PPSF. However, the incidence of facet joint violation was significantly higher in the PPSF group. In addition, MWPSF was associated with a shorter operative time, shorter intraoperative fluoroscopy time, lower hospitalization costs, better postoperative vertebral body angle and percentage of vertebral body height compared with PPSF. CONCLUSIONS: Both MWPSF and PPSF are safe and effective treatments of neurologically intact thoracolumbar fractures. Nevertheless, our results have indicated that MWPSF might be the better choice, because it has a shorter learning curve and decreased facet joint violation, operative time, hospitalization costs, and radiation exposure. In addition, MWPSF was associated with better improvement of the postoperative vertebral body angle and percentage of vertebral body height.

A20 attenuates pyroptosis and apoptosis in nucleus pulposus cells via promoting mitophagy and stabilizing mitochondrial dynamics.

BACKGROUND: A20 is an anti-inflammatory molecule in nucleus pulposus (NP) cells. The anti-inflammatory properties of A20 are mainly attributed to its ability to suppress the NF-κB pathway. However, A20 can protect cells from death independently of NF-κB regulation. This study aimed to investigate the effects of A20 on pyroptosis and apoptosis of NP cells induced by lipopolysaccharide (LPS). METHODS: NP cells induced by LPS were used as an in vitro model of the inflammatory environment of the intervertebral disc. Pyroptosis, apoptosis, and mitophagy marker proteins were detected. Then, NP cells were transfected with A20 overexpressed lentivirus or A20-siRNA. Annexin V FITC/PI, Western blotting, and immunofluorescence assays were used to detect the apoptosis, pyroptosis, and mitophagy of NP cells. Furthermore, the expressions of A20, related proteins, and related inflammatory cytokines were detected by western blotting, and ELISA. RESULTS: Apoptosis and pyroptosis of NP cells increased gradually treated with LPS for 12 h, 24 h, and 48 h. Differently, the level of mitophagy increased first and then decreased, and was the highest at LPS treatment for 12 h. Overexpression or knockdown of A20 in NP cells revealed that A20 attenuated the pyroptosis, apoptosis, and production of inflammatory cytokines of NP cells induced by LPS, while A20 sponsored mitophagy, reduced ROS production and collapse of mitochondrial membrane potential (ΔΨm). Moreover, A20 also promoted mitochondrial dynamic homeostasis and attenuated LPS-induced excessive mitochondrial fission. Excitingly, inhibition of mitophagy attenuated the effect of A20 on the negative regulation of pyroptosis of NP cells induced by LPS. Pyroptosis was accompanied by a large release of inflammatory cytokines. Inhibition of pyroptosis also significantly reduced apoptosis of NP cells. Finally, The mitochondria-targeted active peptide SS-31 inhibited LPS-induced pyroptosis and ROS production in NP cells. CONCLUSIONS: To sum up, A20 attenuates pyroptosis and apoptosis of NP cells via promoting mitophagy and stabilizing mitochondrial dynamics. Besides, A20 reduces LPS-induced NP cell apoptosis by inhibiting NLRP3 inflammasome-mediated pyroptosis. It provides theoretical support for the reduction of functional NP cell loss in the intervertebral disc through the gene-targeted intervention of A20.

Underlying Mechanisms and Related Diseases Behind the Complex Regulatory Role of NOD-Like Receptor X1.

Among nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), NOD-like receptor X1 (NLRX1) is the only known NLR family member that is targeted to the mitochondria, which contains a C-terminal leucine-rich repeat domain, a central conserved nucleotide-binding domain, and an unconventional N-terminal effector domain. It is unique due to several atypical features, such as mitochondrial localization, noninflammasome forming, and relatively undefined N-terminal domain. NLRX1 has multiple functions, including negative regulation of type-I interferon signaling, attenuation of proinflammatory nuclear factor kappa B (NF-κB) signaling, autophagy induction, modulation of reactive oxygen species production, cell death regulation, and participating in cellular senescence. In addition, due to its diverse functions, NLRX1 has been associated with various human diseases, including respiratory, circulatory, motor, urinary, nervous, and digestive systems, to name but a few. However, the exact regulatory mechanisms of NLRX1 are still unclear in many related diseases since conflicting and controversial topics on NLRX1 in the previous studies remain. In this review, we review recent research advances on the underlying mechanisms and related disorders behind the complex regulatory role of NLRX1, which may provide a promising target to prevent and/or treat the corresponding diseases.

GATA4 promotes the senescence of nucleus pulposus cells via NF-κB pathway.

PURPOSE: Cell senescence plays a vital role in intervertebral disc degeneration. The regulatory mechanism of the cellular senescence of nucleus pulposus cells has not been fully elucidated. A recent study identified GATA4 as an emerging regulator of IMR90 cellular senescence. However, whether GATA4 controls senescence in nucleus pulposus cells still needs to be explored. METHODS: Nucleus pulposus cells were exposed to acidified medium mimic the acid environment of intervertebral disc degeneration. RESULTS: We found that GATA4 protein expression was significantly upregulated in older rats and nucleus pulposus cells undergoing stress-induced aging. Moreover, the data indicated that inhibition of GATA4 significantly inhibited the senescence of nucleus pulposus cells cultured under acidic conditions and that over expression of GATA4 promoted a senescence phenotype. The NF-κB pathway has been confirmed in this study to play a role in the regulation of nucleus pulposus cell senescence by GATA4. By using the NF-κB pathway inhibitor, PDTC (100 µmol/L), significantly decreased the IL-6, matrix metallopeptidase (MMP)-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5 expression level, and increased Aggrecan and typeⅡcollagen expression level in GATA4 transfected nucleus pulposus cells compared with the group in the absence of PDTC. CONCLUSION: This outcome suggested that GATA4 might play a significant role in nucleus pulposus cell senescence through the NF-κB signaling pathway, and GATA4 is a promising target for intervertebral disc degeneration treatment in the future.

Unfolded protein response alleviates acid-induced premature senescence by promoting autophagy in nucleus pulposus cells.

Acid-induced cellular senescence is a critical underlying mechanism of intervertebral disc (IVD) degeneration (IDD). Acid stimulation activates a variety of biological changes including autophagy, endoplasmic reticulum stress, and related unfolded protein response (UPR), which are important regulators of cellular senescence. However, the precise mechanism of acid-mediated UPR and autophagy in nucleus pulposus cell (NPC) senescence has not been fully elucidated. In this study, we used acid to mimic the acidic microenvironment of IVD, and rat NPCs were cultured with or without autophagy or UPR signaling small-interfering RNAs. The related proteins and genes were assessed by immunofluorescence staining assay, Western blot analyses, and quantitative real-time polymerase chain reaction to monitor the activation of these signals and classify the molecular mechanisms underlying the correlation between autophagy and UPR pathway. Cell cycle analyses, senescence-associated ß-galactosidase staining, gene expression, and immunoblotting analyses were performed to observe NPC senescence. Results showed that acid stimulation not only induced NPC senescence, but also initiated UPR and autophagy. Silencing the binding immunoglobulin protein signaling of UPR or autophagy signaling promoted rat NPC senescence. Knock-down of the UPR also blocked NPC autophagy. Taken together, UPR inhibits NPC senescence under acidic condition by activating autophagy. Hence, UPR-dependent autophagy could be an effective biologic target for the treatment of IDD in the future.