Background Intervertebral disc degeneration (IVDD) is a leading cause of chronic low back pain. Programmed cell death, particularly necroptosis, contributes to nucleus pulposus (NP) cell loss. Mixed lineage kinase domain-like protein (MLKL) phosphorylation plays a critical role in necroptotic execution, but its upstream regulation in IVDD remains poorly defined. Methods We analyzed human and mouse degenerative disc tissues, as well as TNF-α/Smac mimetic/Z-VAD-FMK (TSZ)-treated NP cells, to assess MLKL phosphorylation. MLKL knockdown in human NP cells and conditional knockout (CKO) in mice were performed to determine its functional role. Immunoprecipitation coupled with mass spectrometry identified potential MLKL-binding proteins. Functional assays with USP39 knockdown/overexpression, together with in vitro and in vivo IVDD models, were conducted to explore regulatory mechanisms. Results MLKL phosphorylation was markedly elevated in human IVDD tissues, LSI-induced mouse discs, and TSZ-stimulated NP cells. Genetic knockdown or conditional deletion of Mlkl significantly preserved extracellular matrix integrity and delayed degeneration. USP39 was identified as a novel MLKL-interacting deubiquitinase. USP39 expression was reduced in IVDD, and its overexpression inhibited MLKL ubiquitination and phosphorylation, alleviating NP cell degeneration. In vivo, AAV-mediated Usp39 delivery attenuated disc degeneration and suppressed MLKL activation. Conclusion Our study reveals that MLKL phosphorylation drives necroptosis in IVDD and identifies USP39 as a critical upstream regulator that deubiquitinates MLKL. Targeting the USP39-MLKL axis provides a promising therapeutic strategy for delaying IVDD progression. The Translational Potential of this Article This study reveals that USP39 inhibits MLKL phosphorylation through deubiquitination, thereby suppressing necroptosis of nucleus pulposus cells and alleviating IVDD. Targeting the USP39–MLKL axis provides a potential therapeutic strategy to preserve NP cell viability and slow the progression of IVDD, offering new insight for translational interventions in chronic low back pain.

Intervertebral disc degeneration (IDD) is the main cause of low back pain and is related to the aging of nucleus pulposus (NP) cells (NPCs). However, the underlying mechanism for senescence of NPCs has not been well understood. NPCs (control-NPCs and IDD-NPCs) were separated from the NP tissues of patients, diagnosed with graded I and IV IDD. The proliferation and senescence levels were detected by MTT assay and senescence-associated β-galactosidase staining, respectively. The expression of cyclin B1 and caveolin-1 was evaluated by Western blot analysis. RNA-sequencing technology was used to screen differentially expressed genes (DEGs) in IDD-NPCs. Finally, through the interference and overexpression of MYB proto-oncogene-like 2 (MYBL2), the effect of MYBL2 on cell senescence was explored. Compared with control-NPCs, the proliferation ability of IDD-NPCs was significantly reduced and the senescence level was obviously increased. 1,061 DEGs were screened in IDD-NPCs. By analyzing DEGs related to aging and aging-related pathways and terms, cell cycle arrest was identified. Knockdown of MYBL2 promoted the senescence of control-NPCs, and overexpression of MYBL2 inhibited the senescence of IDD-NPCs. The study found that upregulation of MYBL2 ameliorated the senescence of IDD-NPCs, providing a potential way to inhibit the senescence of NPCs.

Understanding the dynamic behavior of the human trunk during locomotion is critical for addressing prevalent disorders like low back pain and scoliosis, yet current biomechanical models often oversimplify the trunk as rigid segments. To bridge this gap, we introduce a novel approach combining body surface topography changes with network analysis to characterize trunk motion as a dynamic continuum. By employing the skin surface as a non-invasive observer, we utilized community detection algorithms to identify synchronous deformation regions (SDRs) during gait. Our results suggest that the human back operates as a modular system of synchronized kinematic regions rather than a single homogeneous tissue. These SDRs exhibit robust spatial boundaries and long-range synergies across varying walking speeds, reflecting underlying musculoskeletal dynamics, including spinal kinematics and myofascial coordination. We identified stable clustering in thoracic and lumbar regions, alongside speed-dependent pelvic-scapular synchronization, validating the synergy between upper and lower limb girdles. This framework establishes a methodological foundation for precision rehabilitation by observing the motion of the outer skin. In the future, after validation in larger cohorts and clinical populations, this approach may support candidate surface-derived indicators for evaluating pathological deviations, such as asymmetry in scoliosis or rigid movement patterns in low back pain.

Laminoplasty (LP) is a standard motion-preserving procedure for multi-segmental ossification of the posterior longitudinal ligament (OPLL), yet it may permit continued ossification progression due to retained segmental mobility. The anterior controllable antedisplacement and fusion (ACAF) technique offers ventral decompression with segmental stabilization, but its effect on OPLL fate remains unclear. To compare radiographic OPLL progression and neurological outcomes between ACAF and LP in patients with multilevel cervical OPLL. This retrospective study included 100 patients (50 ACAF, 50 LP) treated between 2019 and 2021. Radiographic parameters included OPLL thickness, length, width, cervical range of motion (ROM), and a novel morphological classification (Types 1–4). Neurological status was assessed using the Japanese Orthopaedic Association (JOA) score. Mean follow-up was approximately 34 months. ACAF demonstrated significantly smaller increases in OPLL thickness for Types 1, 2, and 3 lesions (all P < 0.05), with no significant difference in Type 4. ROM was markedly reduced in the ACAF group (7.32° ± 4.21° vs. 31.45° ± 6.23°, P < 0.001) and correlated with OPLL thickness progression (r = 0.612, P = 0.002). Neurological improvement was significantly higher in the ACAF group (70.12

Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain, yet its molecular mechanisms remain unclear. We identified CRISPLD2 (cysteine-rich secretory protein LCCL domain-containing 2) as a critical regulator of nucleus pulposus cells (NPCs) homeostasis during IVDD. Single-cell transcriptomic analysis (scRNA-seq) revealed degenerative NPCs subsets enriched in iron metabolism and lipid peroxidation. CRISPLD2 knockdown in NPCs led to disrupted redox balance, elevated lipid peroxides, and excessive iron accumulation, promoting oxidative stress-induced ferroptosis and disc degeneration. Mechanistically, we identified a CRISPLD2-miR-548I-IL17A axis that governs ferroptotic cell death in IVDD, where CRISPLD2 deficiency was associated with reduced miR-548I expression, accompanied by subsequent upregulation of IL17A, thereby amplifying inflammatory and oxidative stress responses. In vivo, CRISPLD2 knockdown induced spontaneous IVDD and increased pain sensitivity, while restoration of CRISPLD2 or inhibition of IL17A alleviated ferroptosis and improved NPCs survival. Adeno-associated virus (AAV)-mediated overexpression of CRISPLD2 successfully alleviated IVDD in lumbar spine instability and needle-puncture models, reducing oxidative stress-induced ferroptosis and restoring disc integrity. These findings highlight the critical role of CRISPLD2 in regulating oxidative stress-induced ferroptosis in IVDD and suggest that targeting the CRISPLD2-miR-548I-IL17A axis may provide a novel therapeutic strategy for preventing disc degeneration and alleviating discogenic pain.

Phenotypic transitions of nucleus pulposus (NP) cells are increasingly recognized as key drivers of intervertebral disc degeneration (IVDD), yet the differentiation fate of NP cells and its regulation by the immune microenvironment remain unclear. Using single-cell transcriptomic profiling with in vivo and in vitro validation, we identify an osteoblast-like NP cell subpopulation that emerges during IVDD and exhibits enhanced osteogenic differentiation capacity. Genetic disruption of NP cell osteogenic potential attenuates disc degeneration, supporting a causal role for this program in disease progression. We further show that GPNMB+ macrophages promote osteogenic differentiation and degeneration of NP cells through PDGF signaling and that inhibition of PDGF signaling reduces NP cell osteogenic reprogramming and alleviates disc degeneration. Together, these findings define immune-driven osteogenic reprogramming of NP cells as a key pathological mechanism in IVDD and highlight NP cell osteogenic differentiation as a potential therapeutic target.

Ossification of the posterior longitudinal ligament (OPLL) is a progressive condition that may lead to late neurological deterioration even after successful posterior decompression. Although posterior approaches such as laminoplasty and laminectomy with fusion are commonly performed, some patients ultimately require revision surgery due to progressive kyphosis or enlargement of the ossified lesion. The anterior controllable antedisplacement and fusion (ACAF) technique offers a novel solution by enabling controlled anterior migration of the ossified mass without direct resection. This study aimed to evaluate the clinical and radiographic outcomes of ACAF as a revision procedure for OPLL following failed posterior decompression. This single-center retrospective study included 40 patients who underwent ACAF revision surgery between 2018 and 2024 after prior posterior decompression (laminoplasty or laminectomy with or without fusion). All patients underwent pre- and postoperative radiographic evaluation (X-ray, CT, and MRI) and were followed up. Operative parameters (operative time, estimated blood loss), complication rates, neurological function (Japanese Orthopaedic Association [JOA], Visual Analog Scale [VAS], Neck Disability Index [NDI] scores), and radiographic parameters (C2–7 angle, segmental lordosis, anterior shift of ossified mass, spinal cord drift, and rotation angle) were analyzed. The interval from initial posterior surgery to revision was comparable between the laminoplasty-ACAF and laminectomy-ACAF groups. Operative time and blood loss also showed no significant differences between groups. Each group had one case of C5 nerve root palsy, both resolving within six months, while cerebrospinal fluid leakage occurred slightly more often in the LMP-ACAF group. At final follow-up, both groups showed significant improvements in JOA, VAS, and NDI scores, with no intergroup differences. Radiographically, cervical alignment and segmental lordosis improved significantly in both groups, without implant-related complications or restenosis. Measures of ossified mass displacement, spinal cord drift, and rotation angle were similar across groups. The overall fusion rate was favorable, with slightly higher rates in the LMP-ACAF group. Subgroup analysis excluding prior instrumented fusion cases confirmed sustained significant improvements in cervical alignment. As a revision strategy, ACAF demonstrates encouraging clinical and radiological outcomes in this selected cohort. These preliminary findings suggest ACAF may be a viable surgical alternative for managing OPLL in patients with failed prior posterior decompression, though confirmatory comparative studies are needed.

BACKGROUND AND OBJECTIVES:To evaluate the reliability and clinical applicability of a novel classification system for thoracic posterior longitudinal ligament ossification (OPLL) and its utility in guiding surgical approach selection for anterior controllable ante-displacement fusion (TACAF). METHODS:Based on anatomical and clinical characteristics, thoracic OPLL was classified according to: Grades 1-4 (severity), Zones A-B (location), and Arc morphology (kyphotic curvature). Twenty surgeons independently assessed 50 cases to evaluate system reliability. Fleiss kappa coefficients determined inter- and intra-observer agreement. Clinical validation utilized demographic and perioperative data from 50 patients, including: Neurological function (11-point JOA scale), operative time, blood loss, and major complications. RESULTS:For grade 3/4 or zone A OPLL, anterior approaches were predominantly preferred. Grade 2 or zone B lesions permitted selective ossification resection. Laminectomy was contraindicated for grade 4 OPLL. Lesions nearer the arc vertex consistently required anterior approaches. All cases managed per recommended protocols demonstrated uniformly excellent JOA score improvement rates across grades/zones, without statistically significant differences. CONCLUSION:This novel classification system provides reliable and reproducible standardization for thoracic OPLL, effectively guiding surgical decision-making. Clinical outcomes and complication analyses in 50 patients support its validity for selecting thoracic OPLL decompression methods.

Intervertebral disc degeneration (IVDD) is a significant contributor to chronic low back pain and disability worldwide, yet effective treatment options remain limited. Through integrative analysis of single-cell RNA-seq data from intervertebral discs (IVDs), we have firstly uncovered that the aberrant accumulation of R-Loops—a type of triple-stranded nucleic acid structure—can result in the cytoplasmic accumulation of double-stranded DNA (dsDNA) and activate cGAS/STING signaling and induce cellular senescence in nucleus pulposus cells (NPCs) during IVDD. Restoring the R-Loop state significantly mitigated both the activation of the cGAS/STING pathway and NPC senescence. Additionally, we identified ERCC5 as a critical regulator of the R-Loop state and cellular senescence. Thus, we developed an NPC-targeting nano-delivery platform (CTP-PEG-PAMAM) to deliver si-Ercc5 to the NP region of the IVDD. This approach aims to modulate the abnormal R-Loop state and inhibit the activation of cGAS/STING signaling in NPCs for IVDD treatment. CTP-PEG-PAMAM demonstrated excellent targeting capability towards NPCs and NP tissue, and achieved effective silencing of the Ercc5 gene without causing systemic organ complications. Both in vitro and in vivo experiments revealed that CTP-PEG-PAMAM-siERCC5 significantly inhibited cGAS/STING signaling activated by aberrant R-Loops, alleviated cellular senescence and promoting cell proliferation, thereby delayed IVDD in a puncture-induced rat model. In conclusion, the ERCC5-R-Loop-cGAS/STING axis in NPCs represents a promising therapeutic target for delaying IVDD, and the designed CTP-PEG-PAMAM/siRNA complex holds great potential for clinical application in the treatment of IVDD. Targeted inhibition of cGAS/STING signaling induced by aberrant R-loops in the nucleus pulposus to alleviate cellular senescence and intervertebral disc degeneration

The abnormal activation of the inflammatory microenvironment is frequently accompanied by metabolic changes that affect the development of various diseases. However, the relationship between metabolic reprogramming and intervertebral disc degeneration (IVDD) remains unclear. This study aims to reveal the metabolic changes in nucleus pulposus (NPCs) during IVDD and investigate the mechanism of glycolysis-derived lactate on NPCs. Single-cell RNA sequencing reveals that during IVDD, NPCs are characterized by excessively elevated glycolysis, and the resultant lactate causes the dysfunction of NPCs via ferroptosis activation. Mechanistically, lactate results in the transcription of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) via promoting Histon H3K18 lactylation. Interestingly, lactate can also increase the lactylation of ACSL4 at K412 site. In addition, lactate-induced decreased expression of Sirtuin-3 (SIRT3), and further cause the elevation of ACSL4 lactylation. Finally, animal experiments demonstrate that inhibiting glycolysis through gene silencing with adenoviral-associated viruses 9 (AAV9)-si-Ldha or chemical treatment using 2-deoxy-D-glucose can suppress lactate production and lactylation, thereby ameliorating ferroptosis and NPC dysfunction. The findings of this study indicate that lactate plays a crucial role in IVDD by activating ferroptosis and that interventions aimed at lactate production can offer a potential therapeutical option for patients with IVDD.

Intervertebral disc degeneration (IVDD), a primary cause of debilitating low back pain, is driven by a vicious cycle involving a harsh microenvironment (“soil”) and dysfunctional nucleus pulposus cells (“seeds”), which together promote pathological neurovascular ingrowth (“weeds”) and pain. A therapeutic strategy that can simultaneously “condition the soil” and “modulate the seed” is therefore paramount. Thus, we engineered a biomimetic intelligent nanoliposome (NM-LPTK/RSV-MnCDs) for this dual purpose. The platform is camouflaged with NPC membranes for precise “seed”-homing and incorporates a reactive oxygen species (ROS)-responsive linker for on-demand drug release within the degenerative “soil.” It co-delivers carbonized Mn-containing nanodots (MnCDs) to “condition the soil” by scavenging ROS, and resveratrol (RSV) to “modulate the seed” by suppressing pro-neurovascular signaling. The nanoplatform demonstrated outstanding efficacy in vitro and in two distinct murine IVDD models. It effectively scavenged ROS, inhibited axonal and vascular growth, and preserved matrix synthesis. In vivo, it significantly attenuated disc degeneration, suppressed pathological neurovascular ingrowth, and alleviated pain-related behaviors. Mechanistically, we found this synergistic “soil-conditioning” and “seed-modulating” effect was mediated through the inactivation of the Hippo-YAP signaling pathway, which restored redox homeostasis and blocked aberrant remodeling. This study establishes a targeted, intelligent nanoplatform that synergistically alleviates IVDD and discogenic pain by restoring the disc ecosystem via Hippo pathway inhibition, presenting a precise therapeutic paradigm for degenerative disc disease and its associated neuropathic pain.

Intervertebral disc degeneration involves loss of nucleus pulposus (NP) cells driven by inflammatory and mitochondrial stress-related death pathways. Because mitophagy maintains mitochondrial quality, its disruption may influence cell fate during degeneration. Using human tissues, a mouse lumbar instability model, a rat disc puncture model, and human NP cells stimulated with TNF-α, SM-164, and Z-VAD-FMK (TSZ), we examined how mitochondrial quality control shapes necroptotic signaling. Necroptotic cells displayed mitochondrial damage and reduced mitophagy, while mitophagy activation limited necroptosis and preserved extracellular matrix components. We identified the mitochondrial protein PHB2 as a key regulator linking mitophagy to suppression of necroptosis. PHB2 loss impaired mitophagy, disrupted mitochondrial function, and intensified necroptotic death, whereas PHB2 overexpression restored mitophagy, maintained mitochondrial membrane potential, and reduced degeneration. In vivo PHB2 delivery mitigated necroptosis and protected disc structure. These findings highlight a mitochondria-centered mechanism that shapes cell survival during disc degeneration.

Intervertebral disc degeneration (IVDD) is a major contributor to lumbar diseases, including low back pain, herniation, and stenosis. Despite significant efforts, there have been limited improvements in treatments to alleviate IVDD. The nucleus pulposus (NP) is a crucial component of the intervertebral disc (IVD), responsible for secreting aggrecan, collagen II, and other extracellular matrix components. Programmed cell death (PCD) of NP cells is believed to play a central role in IVDD. RIPK1 is a key mediator of PCD and recently reported PANoptosis, playing essential role in kidney injury, arteriosclerosis, and acute or chronic inflammation-related diseases. We collected varied degenerated human IVD specimens to examine the expression of RIPK1 and downstream cell death-related markers, including GSDMD, Caspase3, and MLKL, which are indicative of pyroptosis, apoptosis, necroptosis, or the recently denominated PANoptosis. In vitro, we performed RIPK1 knockdown and overexpression to study their effects on IVDD. in vivo, we constructed RIPK1 conditional knockout (CKO) mice to confirm the role of RIPK1 in IVDD. We also utilized a small molecule targeted inhibitor to explore its effects on IVDD in vitro and in vivo. Phosphorylated RIPK1 (p-RIPK1) was significantly increased during IVDD in both human and mouse models. Knockout of RIPK1 effectively alleviated IVDD, as evidenced by the RIPK1 cko mice. Further pathological staining and western blot analysis revealed the overexpression of GSDMD, Caspase3, and MLKL, indicating that RIPK1-mediated PANoptosis plays a crucial role in IVDD. in vitro, overexpression of RIPK1 in NP cells exacerbated PANoptosis and degeneration, while RIPK1 knockdown inhibited these processes. We developed a RIPK1-targeted small molecular inhibitor, compound 3-47, which demonstrated superior efficacy in inhibiting p-RIPK1. Both in vitro and in vivo, 3-47 showed remarkable effects in alleviating IVDD by inhibiting RIPK1-mediated PANoptosis. RIPK1-mediated PANoptosis of NP cells plays a critical role in IVDD. The molecular inhibitor 3-47 could effectively delay IVDD progression in mice, highlighting its therapeutic potential.

STUDY DESIGN:A clinical classification of cervical ossification of the posterior longitudinal ligament (COPLL) was developed based on imaging findings. OBJECTIVE:This study aimed to establish a clinical classification for COPLL and provide corresponding surgery strategies for each subtype. SUMMARY OF BACKGROUND DATA:A practical and reliable classification is needed to guide the treatment of COPLL. MATERIALS AND METHODS:This study retrospectively reviewed plain radiographs, computed tomography scans, and magnetic resonance images of patients diagnosed with COPLL between 2018 and 2022 at Shanghai Changzheng Hospital. The types of COPLL were classified according to the location, morphology, and canal-occupying ratio (OR) of the ossification mass. Interobserver and intraobserver reliability were evaluated using Cohen's kappa. RESULTS:A total of 1000 cases were included, which were classified into five types: focal type (F type), short-sequential type (S type), long-sequential type (L type), high type (H type), and mixed type (M type). In addition, each type could be classified into subtype 1 or subtype 2 according to the canal-OR. Then each type could be further classified into other subtypes according to location and morphology. The interobserver reliabilities in the first and second rounds were 0.853 and 0.887, respectively. The intraobserver reliability was 0.888. CONCLUSION:The authors classified COPLL into a system comprised of five types and several subtypes according to canal-OR, location, and morphology. Surgical strategies for each subtype are also suggested. This provides a theoretical guide for the description and surgical management of COPLL.

OBJECTIVE: To propose a novel surgical strategythoracic anterior controllable antedisplacement fusion (TACAF) to treat multilevel thoracic ossification of the posterior longitudinal ligament (mT-OPLL), and investigate its safety and efficacy. METHODS: Between January 2019 and December 2021, a total of 49 patients with thoracic myelopathy due to mT-OPLL surgically treated with TACAF were retrospectively reviewed. Patients ' demographic data, radiologic parameters, and surgery -related complications, modified Japanese Orthopedic Association (mJOA) and visual analog scale (VAS) scores, thoracic kyphosis (TK), kyphosis angle in fusion area (FSK), thoracic curvature, spinal cord curvature, and curvature of curved rod in surgical region, diameter, and area of the spinal cord at the most compressed level were included. RESULTS: All patients acquired satisfactory recovery of neurologic function and overall complication rate was low at the final follow up. The mean mJOA of the laminectomy + TACAF and Full Lamina Preservation + TACAF groups, respectively, was 3.74 +/- 2.05, 3.67 +/- 1.95 before surgery, and 9.97 +/- 0.83, 9.80 +/- 0.68 at the final followed up, with the recovery rate of 84.26% +/- 14.20%, 82.79% +/- 10.35%, as to VAS Scores. The mean FSK was 34.50 +/- 4.46,35.33 +/- 3.44 before surgery, and was restored to 20.97 +/- 5.70, 22.93 +/- 6.34 at the final followed up respectively, as to mean TK ( P < 0.05). Spinal cord curvature was improved from 34.12 +/- 3.59, 33.93 +/- 3.45 before surgery to 19.47 +/- 3.53, 18.80 +/- 3.17 at the final follow-up respectively, as to thoracic curvature ( P < 0.05). In addition, the area and diameter of the spinal cord was also significantly improved at the final follow up (all P < 0.05). The curvature of the thoracic pulp and thoracic vertebra is closely related to the curvature of the rod. There was no statistically significant difference in the incidence of the pelvis and the slope value of the sacrum. CONCLUSIONS: This strategy provides a novel solution for the treatment of mT-OPLL with favorable recovery of neurological function, the tension of spinal cord, and fewer complications.

ObjectiveFor precise and minimally invasive treatment of ossification of the posterior longitudinal ligament of the cervical spine, the lifting segment is minimized, anterior controllable antedisplacement and fusion (ACAF) was refined and improved. In addition, the development of appropriate surgical procedures for the ossification of each segment was rarely reported. Therefore, this study aimed to compare the efficacy and safety of hybrid anterior controlled antedisplacement fusion (Hybrid ACAF) with laminoplasty for multilevel ossification of the posterior longitudinal ligament (OPLL).MethodsBetween May 2018 and May 2021, 70 patients with multilevel OPLL were divided into a hybrid ACAF group and a laminoplasty group according to surgical methods. All patients were followed up for at least 1 year. Japanese Orthopaedic Association (JOA) score and recovery rate (JOARR), (VAS, NDI) score and C2–C7 Cobb angle, the sagittal vertical axis of the neck (SVA), and complications (cerebrospinal fluid leakage, C5 paralysis, etc.) were compared between the two groups by t test or non‐parametric test.ResultsThe operation time of hybrid ACAF was longer. C5 paralysis and axial pain were more common in the laminoplasty group, while dysphagia and hoarseness were more common in the hybrid ACAF group. At the last follow‐up, the hybrid ACAF group had better recovery and maintenance of cervical lordosis and sagittal plane balance and a higher JOA score and recovery rate than the laminoplasty group.ConclusionsHybrid ACAF can reduce the number of vertebral bodies and expand the decompression range, which is safe, effective, and tailored to local conditions. Compared with laminoplasty, hybrid ACAF is a precise alternative for patients with OPLL.

BackgroundAnterior controllable antedisplacement and fusion (ACAF) is an emerging surgical approach for treating cervical ossification of the posterior longitudinal ligament (C-OPLL), yet there is limited data on its long-term efficacy and safety. The present study aimed to analyze the short- and long-term postoperative clinical and radiological outcomes and perioperative complications of ACAF for patients with C-OPLL.MethodsThis was a single-center, retrospective, cohort study, with the mean duration of follow-up of at least 24 months. A total of 111 patients with C-OPLL in our institution from June 2017 to June 2019 were assessed preoperatively and at 3 days, 3, 6, 12, and 24 months postoperatively. The primary outcome was the recovery of neurological function, measured with the Japanese Orthopedic Association (JOA) score. The secondary outcomes included pain, Cobb angle, spinal canal invasion rate, and surgery-related complications.ResultsThe postoperative JOA score at each follow-up was significantly better than the preoperative JOA score, regardless of preoperative spinal canal invasion rate, K-line, and segment length. The visual analog scale (VAS) score also decreased dramatically 3 days after surgery and was maintained at a low level throughout the follow-up period. Improvements in Cobb angle and invasion rate were observed right after the operation and were maintained for 2 years thereafter.ConclusionsACAF could achieve satisfactory recovery of neurological function in C-OPLL patients during a follow-up of 24 months, regardless of preoperative spinal canal invasion rate, preoperative K-line, or surgical segment length.

Study Design: A retrospective study. Objectives: This study aimed to evaluate the safety and effectiveness of the bridge crane technique versus laminectomy for the treatment of thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). Methods: Totally 41 patients who underwent surgical decompression due to thoracic OLF from May 2017 to June 2018 in our institution were enrolled in this study and were divided into group BG (bridge crane technique, n = 19) and group L (laminoectomy, n = 22). Demographic data was collected from medical records and the modified Japanese Orthopaedic Association (JOA) scoring system was used to evaluate the neurological outcomes during the follow-up. Surgery-related complications were analyzed. Results: The mean duration of follow-up was comparable between group BG (19.4 ± 1.5 months) and group L (19.6 ± 1.4 months). No statistical differences were observed between two groups in terms of gender, age, duration of symptoms, preoperative occupying rate, involved levels, operation time, intraoperative blood loss, and complications. The JOA score significantly increased at the final follow-up in both groups. However, patients in group BG had higher JOA score and recovery rate ( P < 0.05). Four patients in group L experienced complications, including 3 cerebrospinal fluid (CSF) leakage and one postoperative hematoma. Only one patient in group BG had CSF leakage. Conclusion: The results of this study suggested that bridge crane technique may be relatively safe and effective for patients with symptomatic thoracic OLF with more satisfactory clinical improvement. However, high-quality studies are still required to validate the results of this study. Keywords surgical decompression , bridge crane technique , laminectomy , thoracic ossification of ligamentum flavum , surgical innovation

Neuromodulation-related intervertebral disc degeneration (IVDD) is a novel IVDD pattern and are proposed recently. However, the mechanistic basis of neuromodulation and intervertebral disc (IVD) homeostasis remains unclear. Here, this study aimed to investigate the expression of postganglionic sympathetic nerve fiber-derived vasoactive intestinal peptide (VIP) system in human IVD tissue, and to assess the role of VIP-related neuromodulation in IVDD. Patient samples and in vitro cell experiments showed that the expression of receptors for VIP is negatively correlated with the severity of IVDD, and the administration of exogenous VIP can ameliorate interleukin 1β-induced nucleus pulposus (NP) cell apoptosis and inflammation. Further mRNA-seq analysis revealed that fibroblast growth factor 18- (FGF18)-mediated activation of V-akt murine thymoma viral oncogene homolog signaling pathway is involved in the protective effects of VIP on inflammation-induced NP cell degeneration. Further analysis identified VIP via its receptor vasoactive intestinal peptide receptor 2 can directly result in decreased expression of miR-15a-5p, which targeted FGF18. Finally, in vivo mice lumbar IVDD model confirmed that focally exogenous administration of VIP can effectively ameliorated the progression of IVDD, as shown by the radiological and histological analysis. In conclusion, these results indicated that sympathetic neurotransmitter, VIP, delayed IVDD via FGF18/FGFR2-mediated activation of V-akt murine thymoma viral oncogene homolog signaling pathway, which will broaden the horizon concerning how the neuromodulation correlates with IVDD and shed new light on novel therapeutical alternatives to IVDD.

Background: Neurological complications after lumbar fusion surgery could be as high as 10%. No noticeable compression was found in or after surgery. Failed quantitative assessment of neurological state during surgery might be the actual cause. Contrast-enhanced ultrasound (CEUS) was conducted to evaluate the blood perfusion of substantive organs but not the lumbar spine. This prospective study was to test whether CEUS could be applied to guide lumbar decompression surgery quantitatively.Methods: Patients who underwent posterior lumbar fusion surgery were included. CEUS was performed before and after the decompression technique. Ultrasonography and parameters were recorded, including appearance time (AT), time to peak (TTP), rising slope (RS), retreat time (RT), and peak intensity (PI) of the contrast agent. Anatomical and kinematic parameters of nerve roots were also recorded.Findings: The study included twenty-one patients. Before decompression, AT, TTP, RS, RT, and PI were 27.70 ± 4.04s, 44.50 ± 7.59s, 0.65 ± 0.32, 66.08 ± 11.07s, and (10.10 ± 3.19) * (10–5), respectively. After full decompression, AT, TTP, RS, RT, and PI were 27.03 ± 5.42s(p=0.47), 37.89 ± 3.93s (p<0.001), 2.03 ± 0.97(p<0.001), 56.67 ± 9.17s (p<0.001), and (20.10 ± 8.10) * (10–5) (p<0.001), respectively. The diameter of nerve root was 1.78 ± 0.15 mm and 1.83 ± 0.17 mm before and after surgery. The pulsation interval and amplitude were [0.87 ± 0.15 s, 0.80 ± 0.17 mm] and [0.91 ± 0.13 s, 0.92 ± 0.21 mm] before and after decompression, as observed by M-mode ultrasound.Interpretation: Ultrasonography and parameters, including TTP, RS, RT, and PI, proved that the nerve root perfusion significantly improved after decompression, which could be used to assess neurological status during lumbar surgery quantitatively. CEUS is an effective tool to guide full lumbar decompression.Funding: This work was supported by the National Natural Science Foundation of China (81702141).Declaration of Interest: None to declare. Ethical Approval: The study was approved by the ethics committee of Changzheng Hospital. All patients were informed and consented to the research.