This study aimed to test the hypothesis that a dose-response relationship exists between adherence to Enhanced Recovery After Surgery (ERAS) protocols and postoperative outcomes in geriatric patients undergoing separation surgery for spinal metastases. In a single-center retrospective cohort study, 128 patients aged ≥ 70 years undergoing elective separation surgery for symptomatic spinal metastases (2020–2023) were included. Adherence to eight core ERAS components was assessed, and an overall adherence score was calculated. The primary outcome was composite complications (Clavien-Dindo Grade ≥ II) within 30 days. Multivariable logistic regression, adjusted for frailty and preoperative albumin, analyzed the association between adherence and outcomes. Median ERAS adherence was 75

Cancer neuroscience has revealed the pivotal role of neural pathways in tumor progression and cancer-associated pain, particularly in bone metastases. To address both tumor growth and pain, we developed a novel nanomedicine strategy that targets mitochondrial dysfunction in cancer cells. The engineered H-MnCa/3MA-ALD nanoparticle system combines hollow mesoporous manganese-calcium (H-MnCa) nanoparticles functionalized with alendronate (ALD) for bone targeting, and loaded with 3-Methyladenine (3MA) to inhibit autophagy. This system disrupts mitochondrial ATP production, exploiting the inherent vulnerability of mitochondria to oxidative stress, and enhances reactive oxygen species (ROS) generation. The elevated ROS selectively induces cancer cell death while also reducing the secretion of nerve growth factor (NGF). This dual-action mechanism not only inhibits tumor growth and metastasis but also alleviates cancer-induced bone pain by downregulating neuro-pain mediators such as p-STAT-3 and NGF. This approach overcomes traditional chemodynamic therapy (CDT) limitations, ensuring targeted mitochondrial damage and apoptosis while preventing protective mitophagy. In vivo studies further confirm that H-MnCa/3MA-ALD provides effective tumor eradication and pain relief, offering a comprehensive solution for both cancer progression and pain management.

Nanoparticles (NPs)1have been explored as drugs carriers for treating tumors and central nervous system (CNS)2diseases and for oral administration. However, they lack satisfactory clinical efficacy due to poor extravasation and infiltration through biological barriers to target tissues. Most clinical antitumor NPs have been designed based on enhanced permeability and retention effects which are insufficient and heterogeneous in human tumors. The tight junctions33TJs: tight junctionsof the blood-brain barrier44BBB: blood-brain barrierand the small intestinal epithelium severely impede NPs from being transported into the CNS and blood circulation, respectively. By contrast, transcytosis enables NPs to bypass these physiological barriers and enhances their infiltration into target tissues by active transport. Here, we systematically review the mechanisms and putative application of NP transcytosis for targeting tumor and CNS tissues, explore oral NP administration, and propose future research directions in the field of NP transcytosis.

ObjectiveTo verify the safety and effectiveness of a new percutaneous controllable curved plasma radiofrequency instrument for nucleus pulposus ablation. MethodsA new percutaneous controllable curved plasma radiofrequency instrument were designed (controllable curved group), and its ablation effect was compared with the currently used straight head non-bendable plasma ablation instrument (non-bendable group) on gross specimens. The ablation instrument was placed through the right intervertebral foramen, and continuous ablation on the same intervertebral disc was conducted for three times. The ablation range and trajectory were recorded, and the temperature changes in the front, back, left, and right of the ablation center during and 15 seconds after ablation were monitored by the inserted temperature probe. ResultsThere were no difference in temperature changes in the front, back, right regions of the ablation center during and 15 seconds after ablation between the two groups. The temperature changes in the left region of the ablation center both during and 15 seconds after 3rd ablation were larger than those in the non-bendable group (P＜0.01). Compared with the non-bendable group, the controllable curved group achieved angle control and larger single ablation area (2.282 5 mm² vs 1.135 8 mm², P＜0.000 1). ConclusionsThis new percutaneous controllable curved plasma ablation instrument can achieve angle control and ablation on the side opposite to the puncture site, increase ablation volume, and is safe.

Intervertebral disc degeneration (IVDD) stands as a predominant cause of low back pain (LBP). The excessive accumulation of reactive oxygen species (ROS) represents a crucial pathophysiological mechanism involved in IVDD, which triggers oxidative stress in the microenvironment, resulting in apoptosis, inflammation, and metabolic imbalance of extracellular matrix (ECM). Here, we ingeniously devised an injectable hydrogel (CMC-PBA/ODEX/HMP@Lut) consisting of phenylboronic acid-modified carboxymethyl chitosan (CMC-PBA), oxidized dextran (ODEX), MnO2 nanoparticles loaded with luteolin (HMP@Lut). The introduction of HMP@Lut as a nanofiller into hydrogels enabled the additional cross-linking of polymer networks through hydrogen bonding. The phenylborate ester bonds, hydrogen bonds, and Schiff base bonds conferred the ROS/pH dual-responsiveness to the hydrogel. It was designed to adapt to the acidic environment and effectively scavenged ROS, ameliorated apoptosis, inflammation and modulated ECM metabolic imbalances. In vitro, the hydrogel could inhibit oxidative stress of nucleus pulposus cells by modulating the PI3K/AKT/NF-κB signaling pathway, exerting anti-inflammatory and anti-apoptotic effects and reducing ECM degradation. In animal experiments, the hydrogel improved the microenvironment and promoted disc regeneration through its injectability, excellent biocompatibility and degradability. In brief, this multifunctional hydrogel endowed with dual response properties presents a new strategy for the IVDD treatment, which is promising for future clinical applications.

INTRODUCTION:Intervertebral disc degeneration (IVDD) stands out as one of the prevalent root causes of low back pain (LBP). In degenerated discs, the dysregulation of glucose metabolism and the impairment of nutrient transport result in the accumulation of lactate, which exacerbates oxidative stress in the microenvironment of the intervertebral disk thereby inducing senescence, apoptosis and metabolic imbalance of the extracellular matrix in the nucleus pulposus cells (NPCs). In this context, elucidating the precise pathogenesis of disc degeneration and advancing the development of targeted molecular therapies hold significant therapeutic implications for future medical interventions. OBJECTIVE:The objective is to systematically evaluate small molecule compounds that influence intracellular oxidative stress and to elucidate their pharmacological effects and underlying molecular mechanisms. METHODS:The small molecule compound cryptotanshinone (Cry) was identified through a comprehensive literature, and the biosignature of the drug-disease target was subsequently analyzed utilizing network pharmacology methodologies. Subsequently, the pharmacological effects and molecular mechanisms of cryptotanshinone in the treatment of IVDD were investigated by ex vivo and in vivo experiments such as RNA-seq, Western blotting, immunofluorescence, SA-β-gal, Tunel, flow cytometry, immunohistochemistry, and animal imaging. RESULTS:In vitro findings demonstrated that Cry mitigates lactate-induced oxidative stress through modulation of the STAT3/SIRT3 signaling pathway, thereby reducing senescence, apoptosis, and extracellular matrix (ECM) degradation in NPCs. Meanwhile, the outcomes of molecular docking and Surface plasmon resonance (SPR) analysis revealed that Cry exhibits a remarkable affinity towards STAT3. In a rat model of IVDD induced by needling, treatment with Cry significantly ameliorated the progression of IVDD. CONCLUSIONS:To summarize, oxidative stress induced by lactate accumulation exhibits a strong correlation with the progression of IVDD. On this foundation, we obtained Cry by screening and demonstrated through mechanistic studies that it could attenuate lactate-induced injury to NPCs and thus improve IVDD, thus Cry may be a promising candidate for the treatment of IVDD.

Abstract Background Deep venous thrombosis (DVT) after spinal surgery has recently attracted increasing attention. Patients with spinal metastases who undergo decompression with fixation are at a high risk of developing DVT. D-dimer levels indicate the risk of DVT, and the purpose of our study was to investigate D-dimer levels as a predictor of DVT perioperatively. Methods We prospectively evaluated 100 patients with spinal metastases. D-dimer tests were performed twice: once before surgery and one day postoperatively. DVT was diagnosed by duplex ultrasonographic assessment of both lower extremities. Pulmonary embolisms (PEs) were diagnosed using multidetector computed tomography and pulmonary angiography. Perioperative serum D-dimer levels were compared between the DVT (+) and DVT (-) groups. The cutoff value of the D-dimer level was calculated using receiver operating characteristic analysis. Results Preoperative and postoperative DVT prevalences were 8.0% (8/100) and 6.6% (6/91), respectively, and none of the patients developed PE. Before surgery, there was no significant differences in D-dimer levels between the pre-DVT (+) and pre-DVT (-) groups. After surgery, the D-dimer level one-day postoperatively for the post-DVT (+) group (17.6 ± 11.8 mg/L) was significantly higher than that of the post-DVT (-) group (5.0 ± 4.7 mg/L). The cutoff value of the postoperative D-dimer level was 9.51(mg/L), and the sensitivity and specificity for the optimum threshold were 83.3% and 89.4%, respectively. Conclusions Our findings suggest that preoperative D-dimer level may not be a predictor of DVT. Preoperative ultrasound examinations should be routinely performed in patients with spinal metastases. Postoperative D-dimer levels greater than 9.51(mg/L) are a predictive factor for the early diagnosis of DVT after spine surgery. Trial registration Our study was registered on Chinese Clinical Trial Registry (No.ChiCTR2000029737). Registered 11 February 2020 - Retrospectively registered, https://www.chictr.org.cn/index.aspx.

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4

Study Design. A prospective consecutive case study. Objective. This study aimed to assess the accuracy of computed tomography perfusion (CTP) in evaluating the vascularity of thoracolumbar metastases and to determine the impact of combining CTP with preoperative embolization on reducing intraoperative blood loss during separation surgery. Summary of Background Data. Surgery for thoracolumbar metastases is a complex procedure with the potential for substantial blood loss. Therefore, assessing tumor vascularity before surgery and taking measures to minimize intraoperative blood loss is essential. Methods. A total of 62 patients with thoracolumbar metastases were prospectively enrolled. All patients underwent separation surgery using the posterior approach. Before surgery, the vascularity of the metastases was evaluated using CTP. On the basis of the CTP results, patients were categorized into hypervascular and hypovascular groups. Preoperative angiography and embolization were performed for the hypervascular group. Clinical data were abstracted, including intraoperative blood loss, perioperative complications, visual analog scale score, neurological status, and the accuracy of vascularity evaluation by CTP confirmed by angiography. χ2 testing was used to compare categorical variables, whereas independent sample t tests were used to compare continuous variables, with paired t tests used to assess differences from preoperative to postoperative time points. Results. The mean intraoperative blood loss was 485±167 and 455±127.6 mL in the two groups, respectively. The accuracy of vascularity evaluation by CTP was 100%. In the hypervascular group, 80.6% of the patients experienced at least one level of improvement in neurological status, while the hypovascular group had 81.5% of patients with similar improvement. None of the patients experienced neurological deterioration. There was a significant reduction in visual analog scale scores in both groups after the operation. Conclusions. The vascularity of thoracolumbar metastases could be accurately evaluated using noninvasive CTP. When combined with preoperative embolization, this approach effectively and safely reduced intraoperative blood loss in the setting of separation surgery.

Nucleus pulposus (NP) cells, situated at the core of intervertebral discs, have acclimated to a hypoxic environment, orchestrating the equilibrium of extracellular matrix metabolism (ECM) under the regulatory influence of hypoxia inducible factor-1α (HIF-1α). Neovascularization and increased oxygen content pose a threat, triggering ECM degradation and intervertebral disc degeneration (IVDD). To address this, our study devised an oxygen-controllable strategy, introducing laccase into an injectable and ultrasound-responsive gelatin/agarose hydrogel. Laccase-mediated reactions were employed to deplete oxygen, establishing a hypoxic microenvironment that upregulated HIF-1α expression. The activation of hypoxia-inducible factors significantly enhanced the expression of aggrecan and collagen II, concurrently suppressing Matrix metalloproteinases (MMP13) and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS5) levels, thereby restoring the equilibrium of ECM metabolism. Simultaneously, the hydrogel facilitated the recruitment of stem cells into the NP through the controlled release of ATI2341, activating C-X-C chemokine receptor type 4 (CXCR4). Moreover, ultrasound amplification enhanced ATI2341 release, promoting the migration of NP stem cells. The hydrogel's efficacy in mitigating metabolic imbalances and inhibiting IVDD progression was substantiated in a rat puncture IVDD model through hydrogel injection into the discs. In conclusion, this hypoxia-inducible hydrogel, responsive to thermal stimuli from ultrasound, presents a promising avenue for IVDD treatment.

目的:探讨在胸腰椎转移瘤分离手术中应用骨水泥强化椎弓根螺钉固定的临床疗效.方法:回顾性分析2018年2月～2019年10月于我院行分离手术治疗的伴有硬脊膜外脊髓压迫症(epidural spinal cord compression,ESCC)的胸腰椎转移性肿瘤患者59例,其中男25例,女34例,年龄56.2±7.5岁(45～76岁).所有患者均采用骨水泥强化椎弓根螺钉固定,共置入236枚螺钉.统计手术时间、术中失血量、输血量、术后住院天数,患者术前、术后3个月的Frankel脊髓损伤分级,患者术前、术后7d、3个月及末次随访的疼痛视觉模拟评分(visual analogue scale,VAS)及Karnofsky功能评分,围手术期相关并发症情况.收集患者术前、术后7d及末次随访时手术节段正侧位X线片,随访观察有无内固定失败及手术节段矢状位Cobb角的变化.结果:患者随访时间为18.3±3.9个月(5～34个月);患者手术时间为169.0±23.7min(125～210min),术中出血量为535±120.0ml(200～1300ml),术中输少浆血 1.2±0.6u(0～6u)、血浆 105±32ml(0～400ml);术后住院时间 6.5±2.3d(5～11d).术中发生骨水泥渗漏2例,均为椎前静脉少量渗漏,暂停注射后渗漏未进展,术后无不良反应;脑脊液漏1例,患者俯卧位以及补液等对症处理后痊愈;伤口愈合不良2例,予以清创缝合后伤口愈合.术后VAS评分、Frankel分级、Karnofsky功能评分与术前相比均有显著性改善(P＜0.05).无内固定失败,末次随访时手术节段Cobb角较手术后即刻无显著性差异(22.5°±2.1°vs 21.2°±1.8°,P＞0.05).结论:对伴有ESCC的脊柱转移瘤患者行分离手术时,应用骨水泥强化椎弓根螺钉可以提供更加坚强的脊柱稳定性.

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the β-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.

Critical-sized bone defects, especially for irregular shapes, remain a significant challenge in orthopedics. Although various biomaterials are developed for bone regeneration, their application for repair of irregular bone defects is limited by the complicated preparation procedures involved, and their lack of shape-adaptive capacity, physiological adhesion, and potent osteogenic bioactivity. In the present study, a simple strategy of precipitation by introducing tannic acid (TA) with abundant phenolic hydroxyl groups and Fe3O4 nanoparticles, as metal-phenolic networks (MPN), is developed to easily prepare a fast gelling, shape-adaptive, and highly adhesive regenerated silk fibroin (RSF)/TA/Fe3O4 hydrogel system that can respond to a static magnetic field (SMF). The RSF/TA/Fe3O4 hydrogel exhibits sufficient adhesion in biological microenvironments and good osteogenic effect in vitro and in vivo, under an external SMF, and thus, can be applied to repair critical-sized bone defects. Moreover, bioinformatics analysis reveals that the synergistic mechanism of Fe3O4 NPs and SMF on osteogenic effects can be promotion of osteoblast differentiation via activation of the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/extracellular signal-regulated kinase (ERK) signaling pathway. This study provides a promising biomaterial with potential clinical application for the future treatment of (irregular) critical-sized bone defects.

Oxidative stress can lead to nucleus pulposus cell (NPC) apoptosis, which is considered to be one of the main contributors to intervertebral disc degeneration (IVDD). Procyanidin B2 is a natural antioxidant that protects against oxidative stress. However, whether procyanidin B2 protects NPCs from oxidative stress remains unknown. In this study, we demonstrated that procyanidin B2 could reduce tert-butyl hydroperoxide-induced reactive oxygen species in rat NPCs and attenuate rat NPC apoptosis. Further experiments revealed that procyanidin B2 upregulated the expression of both nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylation of protein kinase B (Akt). We then used silencing of Nrf2 and LY294002 to silence Nrf2 expression and block the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited. Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment.

Spine surgeons should weigh the risks of anticoagulants against their benefits in preventing deep venous thrombosis (DVT), as they may increase the risk of bleeding. Spinal metastasis patients undergoing decompression with fixation are at a high risk for DVT, which may occur preoperatively. Therefore, anticoagulants should be administered preoperatively. This study aimed to evaluate the safety of the administration of anticoagulants in treating spinal metastasis patients with preoperative DVT. Therefore, we prospectively investigated the prevalence of DVT in these patients. Patients who were diagnosed with preoperative DVT were included in an anticoagulant group. Subcutaneous low-molecular-weight heparin (LMWH) was administered. Patients without DVT were included in a non-anticoagulant group. Data on patient information, clinical parameters, blood test results, and bleeding complications were also collected. Moreover, the safety of anticoagulants was analyzed. The prevalence of preoperative DVT was 8.0%. None of the patients developed pulmonary thromboembolism. Furthermore, no significant differences in blood loss, drainage volume, hemoglobin levels, number of transfusions, or preoperative trans-catheter arterial embolization were observed between the two groups. None of the patients developed major bleeding. However, two patients experienced wound hematoma and one experienced incisional bleeding in the non-anticoagulant group. Therefore, LMWH is safe for spinal metastasis patients. Future randomized controlled trials should be conducted to evaluate the validity of perioperative prophylactic anticoagulation therapy in these patients.

Progress has been made in the application of nanomedicine in rheumatoid arthritis (RA) treatment. However, the whole process of monitoring and treatment of RA remains a formidable challenge due to the complexity of the chronic autoimmune disease. In this study, we develop a Janus nanoplatform (denoted as Janus-CPS) composed of CeO2-Pt nanozyme subunit on one side and periodic mesoporous organosilica (PMO) subunit on another side for simultaneous early diagnosis and synergistic therapy of RA. The Janus nanostructure, which enables more active sites to be exposed, enhances the reactive oxygen species scavenging capability of CeO2-Pt nanozyme subunit as compared to their core-shell counterpart. Furthermore, micheliolide (MCL), an extracted compound from natural plants with anti-osteoclastogenesis effects, is loaded into the mesopores of PMO subunit to synergize with the anti-inflammation effect of nanozymes for efficient RA treatment, which has been demonstrated by in vitro cellular experiments and in vivo collagen-induced arthritis (CIA) model. In addition, by taking advantage of the second near-infrared window (NIR-II) fluorescent imaging, indocyanine green (ICG)-loaded Janus-CPS exhibits desirable effectiveness in detecting RA lesions at a very early stage. It is anticipated that such a Janus nanoplatform may offer an alternative strategy of functional integration for versatile theranostics.

脊柱是恶性肿瘤骨转移最常发生的部位,约30％～70％的恶性肿瘤患者会发生脊柱转移,进而导致局部疼痛以及根性疼痛、行走困难、大小便功能障碍等严重并发症.一般认为,预期寿命大于6个月,具有以下情况之一的患者可考虑手术治疗:(1)对放疗不敏感的转移性肿瘤;(2)病理性骨折导致脊柱不稳;(3)病椎压迫脊髓、马尾、神经根;(4)急性或进展性神经功能障碍;(5)放、化疗或激素治疗失败;(6)诊断不清需要病理组织学确诊.

Estrogen receptor-positive (ER+) breast cancer (BC) is a malignancy that is prone to metastasis to the spine, which is difficult to treat and often results in poor prognosis. However, the mechanism underlying the tumorigenesis and spinal metastasis of ER+ BC remains unclear. Lysosomal protein transmembrane 5 (LAPTM5) has been reported as a tumor suppressor in several types of cancer, but its role in ER+ BC has not been described. Here, by analyzing a gene sequencing dataset and ER+ BC tissues, tumor-adjacent normal tissues and spinal metastatic tissues from patients and mouse models, we found that LAPTM5 expression is negatively related to the progression and spinal metastasis of ER+ BC. Subsequently, in vitro experiments demonstrated that downregulation of LAPTM5 expression promoted the proliferation, migration, and chemoresistance of ER+ BC cells by activating glutamine-dependent mTOR signaling. A high level of CX3CL1 could inhibit LAPTM5 expression, explaining how ER+ BC metastasized to the spine. Thus, we found that LAPTM5 functions as a tumor suppressor in ER+ BC and that the CX3CL/CX3CR1/LAPTM5/glutamine axis mediates the spinal metastasis of ER+ BC. This axis may be a promising therapeutic target for ER+ BC.