Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) represent a promising cell-free strategy for intervertebral disc degeneration (IDD). Here, we obtained oxidative stress-preconditioned exosomes (O-Exos) from BMSCs exposed to low-concentration hydrogen peroxide. Compared with exosomes from untreated cells (N-Exos), O-Exos more effectively delayed nucleus pulposus (NP) cell senescence and attenuated IDD in vitro and in vivo. The superior effects of O-Exos were associated with restoration of mitophagy and improved mitochondrial homeostasis in TNF/TNF-α-treated NP cells. BMF (Bcl2 modifying factor) was identified as a functionally relevant downstream target suppressed by O-Exos, and Bmf deficiency promoted mitophagy and alleviated IDD. Further analyses showed that O-Exos relieved the inhibitory effect of BMF on BCL2L13-LC3B coupling, thereby restoring mitophagy. In addition, exosomal Mir29a-3p was required for BMF suppression and the superior activity of O-Exos. Together, these findings identify oxidative stress preconditioning as an effective strategy to enhance exosome potency against IDD.Abbreviations: ACAN: aggrecan; BCL2L13: BCL2 like 13; BMF: Bcl2 modifying factor; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; COL2A1: collagen type II alpha 1 chain; DHI: disc height index; FUNDC1: FUN14 domain containing 1; H2O2: hydrogen peroxide; IDD: intervertebral disc degeneration; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MMP3: matrix metallopeptidase 3; MRI: nuclear magnetic resonance imaging; N-Exos: exosomes derived from untreated BMSCs; NP: nucleus pulposus; O-Exos: exosomes derived from H2O2-preconditioned BMSCs; OCR: oxygen consumption rate; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SA-GLB1/β-gal: senescence-associated galactosidase beta 1; TEM: transmission electron microscopy; TNF/TNF-alpha: tumor necrosis factor; TOMM20: translocase of outer mitochondrial membrane 20; TP53: tumor protein p53; WT: wild type.

Background This study evaluated the efficacy of a perioperative multimodal blood management strategy—combining erythropoietin, iron supplementation, and restrictive transfusion protocols—in patients undergoing surgery for hip bone tumors, to optimize their perioperative care. Methods We conducted a retrospective analysis of 38 patients who underwent hip bone tumor surgery between January 2021 and February 2025. Based on inclusion and exclusion criteria, patients were divided into a control group (n = 24) and a multimodal management group (n = 14). We compared baseline characteristics, preoperative laboratory results, surgical and postoperative data, dynamic hemoglobin changes, FACIT-Fatigue scores, and Harris Hip Scores between the groups. Results Preoperative hemoglobin was lower and surgical duration was longer in the multimodal management group compared to the controls (both p < 0.05). At one month postoperatively, the multimodal group demonstrated significantly greater improvement in both FACIT-Fatigue scores (5.79 ± 2.01 vs. 3.00 ± 0.78, p < 0.05) and Harris Hip Scores (30.57 ± 6.03 vs. 25.25 ± 6.46, p < 0.05). By three months postoperatively, scores between the two groups were comparable (p > 0.05). Conclusions Despite lower preoperative hemoglobin and more complex surgeries, the multimodal blood management strategy facilitated superior early functional recovery and accelerated rehabilitation at a critical postoperative time point.

Diabetic bone repair is impaired by a microenvironment characterized by heightened susceptibility to infection and persistent inflammation. This study presents a dissolvable, dual-responsive (to glutathione and gelatinase) microneedle patch (CGF/PP@MN) for spatiotemporally controlled therapy. The system features a GelMA hydrogel matrix encapsulating Concentrated Growth Factors (CGF) within its core, while its surface is functionalized with a glutathione-reactive anti-inflammatory peptide (pro-AIP) and a gelatinase-cleavable antimicrobial peptide (pro-AMP). This spatial design enables a sequential, pathology-triggered release cascade: upon insertion, pro-AMPs are first cleaved in the presence of bacterial gelatinase to eradicate biofilms; subsequently, the elevated glutathione concentration activates pro-AIPs to mitigate inflammation and promote M2 macrophage polarization, thereby remodeling the hostile immune niche. Finally, the sustained release of CGF from the hydrogel core drives vascularization and osteogenesis. This platform demonstrates precise temporal alignment with endogenous healing, excellent biocompatibility, and robust bioactivity in vitro. In a diabetic bone defect model, it significantly enhanced wound healing, attenuated inflammation, promoted robust bone regeneration, and improved overall repair outcomes. This work provides a novel combinatorial strategy for immunomodulation and regenerative repair of diabetic bone defects.

The treatment of osteoporosis and related bone defects remains challenging. This study identifies pyroptosis-driven inflammation as a key disruptor of bone homeostasis. To address this, we develop a magnesium-gelatin composite microsphere scaffold (GelMa/Mg/DMF MS) that exploit pyroptosis blockade and hydrogen-mediated inflammation regulation for osteoporosis treatment. This porous microsphere scaffold is implanted into bone defects to achieve the sustained release of hydrogen gas, magnesium ions (Mg2+), and dimethyl fumarate (DMF). DMF act by activating the nuclear factor erythroid-related factor 2 to prevent osteoblast pyroptosis, and combine with the antioxidant effects of hydrogen, effectively remodel the inflammatory microenvironment and create favorable conditions for the restoration of bone homeostasis. Mg2+ further expedite bone tissue repair. These results demonstrate that the GelMa/Mg/DMF MS effectively reverse inflammatory microenvironments both in vivo and in vitro, resulting in significant tissue repair. These results suggest the combination of hydrogen therapy and pyroptosis blockade as a potential therapeutic strategy.

Study Design. A retrospective real-world study. Objective. Using machine learning models to identify risk factors for residual pain after PLIF in patients with degenerative lumbar spine disease. Summary of Background Data. Residual pain after PLIF is a frequent phenomenon, and the specific risk factors for residual pain are not known. Materials and Methods. Between June 2018 and March 2023, 936 patients with lumbar degenerative disease who underwent PLIF surgery were recruited. Group A (n=501) had <7 days of VAS >= 3 pain within 1 month post-PLIF, whereas group B (n=435) had >= 7 days. Imaging outcomes included PMI, MMI, MMD, lumbar lordosis (LL), and LL improvement rate. Functional outcomes were assessed by VAS. Univariate and multivariate logistic regression analyses were used to determine the potential risk of short-term postoperative pain. Risk factors were identified using machine learning models and predicted whether residual pain would occur. Results. A total of 435 (46.5%) patients experienced residual postoperative pain. Independent risk factors included surgical segment, PMI, MMI, and depression level. The Random Forest Model model had an accuracy of 95.7%, a sensitivity of 96.4%, a specificity of 94.1%, and an F1 score of similar to 95.2% for predicting recurrent pain, indicating high reliability and generalizability. Conclusions. Our study reveals risk factors for the development of residual pain after PLIF. Compared to the pain group, the non-pain group had better paravertebral muscles, good psychological level, lower surgical segment and LL improvement rate. These factors may represent targets for preoperative and perioperative optimization as a means to minimize the potential for residual pain after PLIF.

Background Lumbar disc herniation (LDH) is a prevalent condition encountered in the clinical diagnosis and management of spinal surgery. Certain people may experience excruciating radicular pain in the lower extremities. If these symptoms are not promptly alleviated, they may progressively deteriorate, ultimately resulting in radiating pain in the lower extremities, advancing neurological impairments, and potential trouble in standing, significantly impairing the patient's quality of life. Consequently, clinicians require an expedited and efficacious approach to address radicular discomfort resulting from lumbar radiculopathy and promptly reinstate the patient's normal functionality. Objectives This study seeks to assess the effectiveness of a modified transforaminal epidural steroid injection (TFESI) in conjunction with pulsed radiofrequency (PRF) for treating lumbar radiculopathy using a retrospective analysis. Methods Our study examined patients with unilateral lower limb radicular pain persisting for three months or more due to LDH, in whom conservative therapies were ineffective, from January 1, 2023, to October 31, 2023. This trial comprised 106 patients who received modified TFESI alongside PRF. We evaluated clinical efficacy and follow-up at baseline and at 1 week, 1 month, 3 months, 6 months, and 12 months post-surgery primarily using the Visual Analog Scale (VAS), Oswestry disability index (ODI), and modified MacNab score. Results Patients who received modified TFESI in conjunction with PRF exhibited substantial enhancements across all three assessment instruments (VAS, ODI, MacNab) when compared to pre-treatment evaluations (p < 0.0001). The alleviation of radicular discomfort was notably enduring, meeting the patients' expectations. At the 12-month follow-up, we noted that patients often achieved substantial pain alleviation within 6 months, and only a minor proportion of patients encountered pain recurrence by the 12th month, with no notable problems detected. Conclusions The modified TFESI in conjunction with PRF is a safe, cost-efficient, and successful therapy modality. Our findings indicated that this method can efficiently and swiftly relieve patients' radicular discomfort and produce enduring therapeutic effects.

STUDY DESIGN:A real-world, multicenter retrospective study. OBJECTIVE:To identify independent risk factors for cage subsidence after Posterior Lumbar Interbody Fusion (PLIF) and develop an interpretable machine learning model for risk prediction. MATERIALS AND METHODS:Patients with degenerative lumbar disease who underwent single-level PLIF (January 2018-October 2023) were retrospectively included. A training set (n=620) came from the First Affiliated Hospital of Soochow University, and a validation set (n=100) from the Second Affiliated Hospital. Cage subsidence (≥2 mm intervertebral height loss) was assessed radiographically. Parameters included paraspinal muscle indices [psoas muscle index (PMI), multifidus muscle index (MMI), fat infiltration (FI)], bone density markers [Hounsfield Unit (HU) value, Vertebral Bone Quality (VBQ), Endplate Bone Quality (EBQ)], cage position, and postoperative alignment. Multivariate logistic regression identified risk factors; multiple machine learning models were developed and evaluated. A web-based tool was created for clinical deployment. RESULTS:Multivariate analysis identified PMI, FI, HU value, VBQ, cage position, cage height, postoperative Intervertebral Height (IH), corrected IH, and corrected SA as independent risk factors for cage subsidence. Light Gradient Boosting Machine (LightGBM) outperformed other models, achieving the highest AUC (0.9752), accuracy (0.92), and F1-score (0.9216), with the lowest Brier score (0.0660). After excluding indicators related to paravertebral muscle function from the prediction model, the predictive accuracy of the model decreased substantially. (SHapley Additive exPlanations) SHAP analysis confirmed VBQ, FI and PMI as the most influential predictors. The final model was deployed as a web-based tool for real-time clinical risk assessment. CONCLUSIONS:Key risk factors for PLIF cage subsidence were identified, and a validated machine learning model was developed. The high-performance LightGBM model, deployed in a user-friendly web application, enables spine surgeons to optimize surgical planning and reduce subsidence risk.

Chordoma presents a formidable therapeutic challenge due to its distinct anatomical location, thus complicating its complete surgical resection coupled with marked resistance to both radiotherapy and chemotherapy. Currently, effective systemic therapies remain unavailable, contributing to a poor prognosis for patients. To address this critical unmet need, we have developed a targeted drug delivery system tailored to the tumor biology of chordoma. This system encapsulates the CDK7 inhibitor THZ1 within nanoparticles featuring diselenide bonds as dual-responsive release triggers. Upon exposure to low-dose X-ray irradiation (e.g., 2 Gy) and to the elevated reactive oxygen species (ROS) level in the tumor microenvironment, these diselenide bonds are cleaved and transformed into selenic acid (RSeOOH), which subsequently initiates rapid carrier disassembly and drug release. The synergy between RSeOOH and THZ1 enhances radiotherapy efficacy by modulating p53 signaling, inducing apoptosis, and promoting G2/M phase cell cycle arrest in U-CH1 cells, thereby overcoming the radiotherapy resistance commonly seen in chordoma. To further improve tumor-specificity, we functionalize the carrier with the EGFR-targeting GE11 peptide, which drives selective drug accumulation at tumor sites. In murine models, this delivery system has demonstrated substantial efficacy in combination with radiochemotherapy and yet produces minimal toxicity. Molecular dynamics simulations have further elucidated carrier self-assembly mechanisms, guiding the rational design of this nanoplatform.

BACKGROUND:Lumbar disc herniation (LDH) is a prevalent degenerative spinal disorder, often accompanied by impaired sleep quality and depressive symptoms, which considerably affect patients' quality of life and hinder the recovery process. OBJECTIVE:This study aimed to explore the chain mediating effects of illness acceptance and family intimacy on the relationship between sleep quality and depressive symptoms in patients with LDH. The objective was to elucidate the psychosocial mechanisms influencing the psychological well-being of these patients. METHODS:A total of 110 patients diagnosed with LDH between January 2022 and January 2024 were enrolled in this cross-sectional study. Participants completed validated questionnaires assessing sleep quality, illness acceptance, family intimacy and depressive symptoms, including the Pittsburgh Sleep Quality Index (PSQI), Acceptance of Illness Scale (AIS), Family Adaptability and Cohesion Evaluation Scales II (FACES II) and Self-Rating Depression Scale (SDS). Associations among the measured variables were assessed through Pearson correlation analysis. Mediation effects were analysed using the PROCESS v4.2 macro in SPSS, and the significance of the mediating effects was assessed via bootstrapping. RESULTS:A significant positive correlation was observed between the degree of sleep disturbance and depressive symptoms (r = 0.417, p < 0.01). Illness acceptance and family intimacy served as key mediators in the relationship between sleep quality and depressive symptoms. Specifically, poor sleep quality was associated with increased depressive symptoms through its negative effects on family intimacy (β = -0.211, p = 0.027) and illness acceptance (β = -0.266, p = 0.003). Mediation analysis indicated that the total indirect effect accounted for 35.10% of the total effect. The chain-mediated pathway, sleep quality → family intimacy → illness acceptance → depressive symptoms, had an effect size of 0.062 (Boot SE = 0.010, 95% CI: 0.005 to 0.043), indicating that this pathway was also valid. CONCLUSION:Sleep quality is significantly associated with depressive symptoms in patients with LDH. Illness acceptance and family intimacy function as key mediators in this relationship. These findings underscore the importance of psychosocial factors in the mental health of patients with LDH and provide a theoretical foundation for developing targeted psychological interventions.

BACKGROUND:Diffuse idiopathic skeletal hyperostosis (DISH) is a metabolic disease that is prevalent in elderly patients and is characterized by spinal ankylosis. Traditional surgical treatment requires open long-segment internal fixation. Percutaneous kyphoplasty (PKP), as a minimally invasive spinal surgery technology, can accurately relieve pain and improve quality of life. The objective of this study was to evaluate the efficacy and reliability of PKP in treating vertebral fractures with DISH. METHODS:We retrospectively investigated 209 patients with thoracic or lumbar fractures receiving PKP between January 2019 and December 2020. The patients were divided into 2 groups according to the diagnostic criteria. The anterior and posterior vertebral height restoration ratio and the local kyphotic angle (LKA) were used to evaluate the radiographic results. The visual analog scale score and the Oswestry Disability Index questionnaire were used for the assessment of the clinical function. RESULTS:The average age of the DISH group was significantly older than that of the non-DISH group (P < 0.05). The perioperative prognostic nutritional index measured in the DISH group was significantly worse than that in the non-DISH group (P < 0.05). PKP in DISH patients achieved a significant restoration in the anterior and posterior vertebral height restoration ratio between pre- and postoperative measurements (P < 0.05). The postoperative LKA was significantly corrected at 1 day, 1 month, and the last follow-up (P < 0.05). Significant reductions in visual analog scale and Oswestry Disability Index scores were obtained during follow-up (P < 0.05). CONCLUSION:For vertebral fractures in elderly DISH patients, PKP may be effective and feasible, which restores the vertebral height, corrects the LKA, and achieves pain relief and satisfactory functional improvement. LEVEL OF EVIDENCE: 3:

Purpose:Perioperative pain management in children with Gartland Type III supracondylar humerus fractures (SHF) is crucial but often inadequately addressed, leading to significant pain experiences. This study aimed to evaluate the efficacy and safety of coracobrachialis plane musculocutaneous nerve block (Cora-MNB) compared to supraclavicular brachial plexus block (SC-BPB) for analgesia in pediatric Gartland Type III SHF patients. Methods:A prospective pilot study enrolled 105 pediatric patients with Gartland Type III SHF was performed. Primary outcome was the postoperative FLACC scale measured at 12 h postoperatively. Secondary outcomes included FLACC scale measured at 1 h, 6 h and 24 h postoperatively. They also included postoperative thumb and shoulder strength, opioid use, NSAIDs use, length of hospital stays, patient satisfaction, surgeon satisfaction, operation time and puncture channels. One hundred and five patients were randomized allocated between groups. Results:Patients receiving Cora-MNB showed superior analgesia, with median postoperative FLACC pain scores at 12 h reduced by 40% [Cora-MNB: 3.00 (2.00) vs. SC-BPB: 5.00 (2.00), ***p < 0.001]. Thumb extensor weakness incidence decreased significantly (Cora-MNB: 13.5% vs. SC-BPB: 84.9%, ***p < 0.001). Shoulder mobility preservation was achieved in 98.08% of Cora-MNB cases vs. 20.75% with SC-BPB (***p < 0.001). While opioid consumption showed no intergroup difference, Cora-MNB reduced NSAID rescue times [Cora-MNB: 0.00 (1.00) vs. SC-BPB: 1.00 (1.00), **p = 0.0014]. Procedure duration favored Cora-MNB [4.54 ± 1.21 (min) vs. 9.02 ± 1.94 (min), T = 14.32, 95% CI: 3.88-5.12, ***p < 0.001], with higher surgical and parental satisfaction scores. Hospital stays remained comparable [1.60 ± 0.66 (days) vs. 1.56 ± 0.67 (days), p = 0.98]. Conclusion:Cora-MNB proves to be a safe and effective approach for anesthesia in pediatric SHF cases, offering superior analgesic outcomes, reduced NSAIDs usage, improved shoulder functionality, and high satisfaction levels without extending the hospital stay. This study supports the implementation of Cora-MNB as a valuable technique in perioperative pain management for pediatric SHF patients.

Background: Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, yet current therapies fail to reverse the degenerative process or restore disc function. Ferroptosis, a form of iron-dependent cell death characterized by lipid peroxidation, has been implicated in IVDD progression. Methods: We synthesized Deferoxamine mesylate (DFOM)-loaded cerium oxide nanoparticles (DFOM@CeO2) as a novel ferroptosis-targeting therapeutic. Results: DFOM@CeO2 exhibited dual functionality by scavenging reactive oxygen species (ROS) and chelating excess iron, thereby protecting nucleus pulposus (NP) cells from ferroptosis and extracellular matrix (ECM) degradation. DFOM@CeO2 demonstrated strong antioxidant capacity, effectively reducing iron accumulation and lipid peroxidation, and restoring glutathione peroxidase 4 (GPX4) expression in NP cells. Furthermore, DFOM@CeO2 improved mitochondrial respiratory chain function, reduce mitochondrial ROS production and prevent mitochondrial dysfunction. In a rat model of IVDD, DFOM@CeO2 significantly preserved disc height, reduced ECM degradation, and demonstrated superior therapeutic efficacy compared with DFOM or CeO2 alone. Transcriptome analysis revealed that DFOM@CeO2 modulates key ferroptosis-related genes and promotes mitochondrial reprogramming. Conclusions: These findings highlight DFOM@CeO2 as a promising therapeutic strategy for IVDD, targeting both ferroptosis and mitochondrial dysfunction.

To investigate the influence of facet tropism (FT) on spinal parameters and clinical symptoms of degenerative lumbar spondylolisthesis (DLS) after posterior lumbar intervertebral fusion (PLIF). A total of 108 patients with DLS who received PLIF surgery from June 2016 to June 2020 were retrospectively analyzed and divided into non-facet tropism (NFT) group and FT group according to bilateral facet joint angle (FJA) difference of more than 10°. Pre-postoperative clinical data compared between groups. Correlation analysis was performed between imaging parameter changes and symptom score changes. Groups were divided by preoperative FT segments to compare imaging parameters and symptom score changes with the NFT group. Overall, 54 patients were included in NFT group and 54 patients were included in FT group. The FT group had a lower lumbar range of motion (ROM) than the NFT group, with similar preoperative clinical data. Both groups showed improved imaging parameters and symptom scores after PLIF compared to preoperative levels. The ROM in the FT group was lower than those in the NFT group (P < 0.01). Both groups showed similar symptom improvements, but the FT group had significantly higher VAS and ODI scores at follow-up than the NFT group (P < 0.05). Improvements in VAS and ODI were significantly correlated with changes in imaging parameters and ROM in both groups. PLIF improves DLS symptoms and lumbar curvature but restricts postoperative ROM. FT compromises correction efficacy, necessitating preoperative FT evaluation for optimal surgical planning.

OBJECTIVE:The refracture of the previously cemented vertebrae occurs rarely following percutaneous kyphoplasty (PKP). The present study was designed to assess the therapeutic efficacy of repeated PKP for refractures. METHODS:We conducted a retrospective analysis of 36 patients who underwent repeat PKP for refractures in same cemented vertebrae. The study evaluated the cement distribution pattern, restoration of middle vertebral height (MVH), and kyphosis angle (KA). Clinical efficacy was evaluated using visual analog scale (VAS) and the Oswestry Disability Index. A multivariate logistic regression model evaluated age, sex, cement volume, and bone mineral density, with the group's average pain reduction measured at 4.86 points on the VAS. RESULTS:Preoperative VAS scores averaged 7.75 ± 1.23, significantly decreasing to 2.89 ± 0.92 after surgery (P < 0.05). The Oswestry Disability Index significantly improved from 73.83 ± 14.58 preoperatively to 35.97 ± 9.85 postoperatively (P < 0.05). The MVH significantly increased from 12.49 ± 2.95 preoperatively to 16.83 ± 3.49 postoperatively (P < 0.05). The KA significantly increased from 19.22 ± 4.28 preoperatively to 12.01 ± 4.59 postoperatively (P < 0.05). The mean of the correction of KA was 7.17 ± 5.10 and the mean of the restoration rate of MVH was 17.09 ± 9.68. Cement volumes of up to 4.5 ml had about a 40% probability of achieving a minimum 4.86-point VAS reduction, while volumes of at least 4.5 ml showed an 84.6% probability. CONCLUSIONS:Repeated PKP effectively alleviates pain and restores spinal function in patients with refractures. A minimum cement volume of 4.5 ml appears optimal for achieving significant pain relief.

Background Lumbar disc herniation (LDH) is a prevalent degenerative disc disorder frequently resulting in lumbar and leg pain. Obese patients with LDH often encounter the scenario where the disc herniation is not completely resolved in the short term following percutaneous transforaminal endoscopic discectomy (PTED), necessitating subsequent surgical intervention, or where long-term reherniation occurs post-procedure. Currently, the literature provides little information regarding the application of annulus fibrosus suture (AFS) as a supplementary measure to PTED for diminishing the recurrence of disc herniation. Our aim was to evaluate the short-term and long-term therapeutic outcomes of combining PTED with AFS, with a particular focus on the impact of AFS on the recurrence rate of disc herniation following PTED. Methods We recruited 23 obese patients with single-level LDH diagnosed between December 2021 and December 2023. All patients successfully underwent PTED in conjunction with AFS and the postoperative follow-up. We collected and analyzed data related to baseline parameters, disc degeneration grading, clinical effectiveness, surgery-related factors, lumbar spine function, pain severity, quality of life, and adverse prognosis events. Results Compared with preoperative assessments, all patients exhibited significant improvements in Visual Analog Scale for leg pain (VAS-LP), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores (P < 0.05). During the short-term follow-up period, no patient required a secondary conventional microdiscectomy due to severe complications. At the one-year follow-up, no patient experienced significant recurrent radicular leg pain that would raise suspicion of LDH recurrence. However, when PTED was combined with AFS, the improvement in Visual Analog Scale for back pain (VAS-BP) was relatively less pronounced. Conclusions The synergy of PTED and AFS seems to be a comparatively safe and efficacious approach for treating LDH in obese patients. AFS reduces the incidence of long-term recurrent leg pain, which may in turn reduce the probability of LDH recurrence after PTED. Consequently, AFS should be regarded as an efficacious supplementary procedure to PTED, adept at efficiently reducing the recurrence rate in obese individuals with LDH.

ABSTRACTBackgroundChronic low back pain (LBP) is a significant global health concern, often linked to vertebral bone marrow lesions (BML), particularly fatty replacement (FR). This study aims to explore the relationship between the gut microbiome, serum metabolome, and FR in chronic LBP patients.MethodsSerum metabolomic profiling and gut microbiome analysis were conducted in chronic LBP patients with and without FR (LBP + FR, n = 40; LBP, n = 40) and Healthy Controls (HC, n = 31). The study investigates alterations in branched‐chain amino acids (BCAAs) levels and identifies key microbial species associated with BCAA metabolism. In vitro experiments elucidate the role of BCAAs in adipogenesis of bone marrow mesenchymal stem cells (BM‐MSCs) via the SIRT4 pathway.ResultsChronic LBP patients with FR exhibit depleted BCAA levels in their serum metabolome, along with alterations in the gut microbiome. Specific microbial species, including Ruminococcus gnavus, Roseburia hominis, and Lachnospiraceae bacterium 8 1 57FAA, are identified as influential in BCAA metabolism and BM‐MSCs metabolism. In vitro experiments demonstrate the ability of BCAAs to induce BM‐MSCs adipogenesis through SIRT4 pathway activation.ConclusionThis study sheds light on the intricate relationship between the disturbed gut ecosystem, serum metabolites, and FR in chronic LBP. Dysbiosis in the gut microbiome may contribute to altered BCAA degradation, subsequently promoting BM‐MSCs adipogenesis and FR. Understanding these interactions provides insights for targeted therapeutic strategies to mitigate chronic LBP associated with FR by restoring gut microbial balance and modulating serum metabolite profiles.

Osteosarcoma (OS), a highly aggressive bone tumor, presents significant challenges in terms of effective treatment. We identified that cellular autophagy was impaired within OS by comparing clinical OS samples through bioinformatic analyses and further validated the inhibition of mitochondrial autophagy in OS at the transcriptomic level. Based on this finding, we investigated the therapeutic potential of a dual functional metal nanoplatform (MnSx) to facilitate a transition from the protective effect of low-level autophagy in OS to the killing effect of high-level autophagy in OS. MnSx facilitated intracellular H2S generation via endocytosis, leading to the S-sulfhydration of ubiquitin-specific peptidase 8 (USP8) and subsequent promotion of mitochondrial autophagy in vitro. Additionally, MnSx activated the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway, further enhancing the cellular autophagic response and accelerating tumor cell death. Moreover, it was demonstrated in vivo that MnSx, on the one hand, mediated the activation of tumor autophagy by USP8 via intracellular H2S, while Mn2+ promoted the maturation of dendritic cells, activated cytotoxic T lymphocytes and contributed to tumor eradication. Such tumor killing could be suppressed by the autophagy inhibitor chloroquine. Importantly, synergistic combination therapy with immune checkpoint inhibitors showed promise for achieving complete remission of OS. This study highlights the potential of MnSx as a dual-functional therapeutic platform for OS treatment and offers novel directions for future research in this field.

Intervertebral disc degeneration (IVDD) is a major contributor to chronic back pain and disability, with limited effective therapeutic options. Current treatment options, including conservative management and surgical interventions, often fail to effectively halt disease progression and come with notable side effects. IVDD is characterized by the breakdown of the extracellular matrix (ECM) and the infiltration of inflammatory cells, which exacerbate disc degeneration. This study presents a novel therapeutic strategy aimed at addressing the dual challenges of inflammation and ECM degradation in IVDD. We developed a gelatin methacryloyl (GelMA) hydrogel system loaded with interleukin-10 (IL-10), an anti-inflammatory cytokine, and kartogenin (KGN), a small-molecule compound known for its regenerative properties. The KGN + IL-10@GelMA hydrogel was designed to deliver these agents in a controlled manner directly to the degenerated disc, targeting both the inflammatory microenvironment and the promotion of nucleus pulposus (NP) tissue regeneration. In a puncture-induced IVDD model, this hydrogel system effectively delayed the degenerative progression and facilitated NP regeneration. Our findings suggest that the KGN + IL-10@GelMA hydrogel holds significant potential as a nonsurgical treatment option for IVDD, offering a promising approach to mitigate the progression of IVDD and enhance disc repair.

ObjectiveTo investigate the use of anti‐osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real‐world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real‐world scenarios to enhance the management of bone health in OVCF patients.MethodsThis retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55–90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on‐treatment and off‐treatment groups according to whether they received a second dose of denosumab, with follow‐up beginning on the index day (225 days after the first denosumab dose). In this study, the off‐treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti‐osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed.ResultsA total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on‐treatment group than in the off‐treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on‐treatment group than in the off‐treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti‐osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%–15% taking oral bisphosphonates.ConclusionPostmenopausal women have a high refracture rate and a low proportion of anti‐osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.

This study aimed to evaluate the clinical effect of different vertebral body heights restoration rate after percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures (OVCF). The patients were divided into two groups according to the height restoration rate of the anterior edge of the vertebral body fracture after PKP operation using X-Ray imaging. The group A was below 80