Baoshan Xu

Background:Intervertebral disc degeneration (IDD) is a major pathological contributor to low back pain, and its progression is closely associated with oxidative stress and cell death. Ferroptosis is a form of programmed cell death characterized by iron-dependent lipid peroxidation, which has recently been confirmed to participate in IDD progression. Microsomal glutathione S-transferase 1 (MGST1) plays an important role in glutathione metabolism and cellular antioxidant defense, but its function in IDD remains unclear. This study aimed to investigate the expression profile of MGST1 in IDD and to elucidate its molecular mechanism in delaying degeneration by regulating ferroptosis.Methods:Differentially expressed ferroptosis-related genes associated with intervertebral disc degeneration were screened through bioinformatics analysis. MGST1 expression changes were validated using a needle puncture-induced rat IDD model and a degenerated nucleus pulposus (NP) cell model. MGST1 knockdown and overexpression strategies were employed to evaluate its effects on the extracellular matrix metabolism, apoptosis, and senescence of nucleus pulposus cells. Further examinations of ferroptosis-related indicators were conducted, including levels of lipid peroxidation, reactive oxygen species generation, intracellular Fe2+ content, and changes in mitochondrial membrane potential. For in vivo experiments, the therapeutic effect of MGST1 overexpression was assessed by intradiscal injection of an MGST1-overexpressing lentivirus into the rat intervertebral disc degeneration model.Results:Bioinformatics analysis indicated that MGST1 is a key candidate gene in IDD. MGST1 expression was consistently upregulated with increasing degeneration severity in rat disc tissues and degenerated NP cells. Knockdown of MGST1 significantly promoted extracellular matrix degradation and increased apoptosis and senescence levels in NP cells, while MGST1 overexpression markedly improved these changes. Mechanistic studies revealed that MGST1 deficiency significantly enhanced ferroptosis characteristics in NP cells, including accumulation of lipid peroxides and ROS, increased Fe2+ content, and decreased mitochondrial membrane potential. In vivo experiments demonstrated that MGST1 overexpression significantly alleviated the degree of IDD in rats.Conclusion:MGST1 exhibits compensatory upregulation during the progression of intervertebral disc degeneration and delays its progression by inhibiting ferroptosis in nucleus pulposus cells. This study reveals a novel mechanism by which MGST1 regulates ferroptosis in IDD and provides a potential molecular target for the prevention and treatment of IDD.

To investigate the causes, manifestations, risk factors and management of anesthetic complications of extensive spinal nerve block (ESNB) and total spinal anesthesia (TSA) during percutaneous spinal endoscopic surgery under local anesthesia. We retrospectively reviewed 16,798 patients who underwent percutaneous spinal endoscopic surgery under local anesthesia across three institutions between February 2012 to February 2023. Patient demographics, including gender, age and Body Mass Index (BMI) were collected, along with surgical characteristics such as surgical sites, involved segments, surgical approaches and procedures. Local anesthetic dosage, as well as the onset time, manifestations, management, recovery and prognosis of intraoperative ESNB and TSA were recorded. Statistical analysis including regression analysis was used to identify potential risk factors. 9 patients (0.05%) experienced anesthetic complications of ESNB and TSA, including 4 males and 5 females, with a mean age of 48.44 ± 18.15 years (range: 28-84 years). The median onset time was 7 min (IQR:5-30 min). The mean follow-up duration was 4.84 ± 2.77 years (range: 1-9 years). 6 cases of ESNB presented with sensory and motor disfunction below the block level, accompanied by mild circulatory and respiratory depression. Among them, 5 patients recovered fully, while 1 patient had residual foot drop. 3 cases of TSA manifested as loss of consciousness, complete sensory and motor loss, and significant circulatory and respiratory depression. Among them, 2 patients underwent tracheal intubation, while 1 patient developed multiple complications but recovered following a 31-day ICU treatment. The thoracic and cervical spine, thoracic transforaminal endoscopic surgery were associated with higher incidences of anesthetic complications (P < 0.05). The interlaminar approach demonstrated a higher incidence of anesthetic complications than the transforaminal approach(P = 0.026). No significant differences were observed in anesthetic dosage and addition of ropivacaine between the complication group and the non-complication group (P > 0.05). BMI was identified as an independent risk factor, significantly higher in the complication group (27.00 ± 5.61 kg/m²) than in the non-complication group (P = 0.038). ESNB and TSA are rare but serious anesthetic complications in percutaneous spinal endoscopic surgery under local anesthesia. In addition to limb sensory and motor dysfunction, the respiratory and circulatory systems can also be affected. Heightened vigilance and proactive prevention are warranted especially for patients with high BMI, cervical or thoracic intervention, or an interlaminar approach. Prompt identification and scientific treatment are crucial for favorable outcomes.

Intervertebral disc degeneration (IVDD) is a primary cause of chronic low back pain. Recent evidence suggests a potential association between low-virulence

Intervertebral disc (IVD) homeostasis and function depend on the immunological privilege status, while immune cell infiltration constitutes a pivotal pathological driver of intervertebral disc degeneration (IDD). Nevertheless, the immune infiltration landscape and associated molecular targets in IDD remain elusive. We therefore integrated bioinformatic analysis of public datasets and single-cell RNA-sequencing analysis (scRNA-seq) data, flow cytometric (FACS) and experimental validation to delineate immune infiltration dynamics and identify therapeutic targets. CIBERSORT deconvolution analysis revealed significant increases in follicular helper T cells (p < 0.05) and M2 macrophages (p < 0.05) in IDD, with M1 macrophages demonstrating an upward trend. WGCNA showed that the blue module was associated with M1 macrophages infiltration (positive correlation 0.87, P < 0.001), among which VAMP8, JUN and others were mainly enriched in macrophage activation and myeloid leukocyte activation. FACS quantification established postoperative day 14 as the peak of leukocyte infiltration in rat IVDs following puncture. scRNA-seq resolved seven cellular subsets within degenerated rat IVDs: annulus fibrosus cells, smooth muscle cells, fibroblasts, macrophages, monocytes, vascular endothelial cells, and nucleus pulposus (NP) cells, with pronounced expression of Jun and Vamp8. Western blotting confirmed upregulated VAMP8 and JUN expression in TNF-α-stimulated (50 ng/ml, 24 h) NP cells. Immunohistochemistry further demonstrated elevated VAMP8 and JUN levels during rat IDD progression. This work identifies post-puncture day 14 as the critical window for peak immune infiltration in rat IVDs, and reveals VAMP8 and JUN are macrophage-associated regulators of IDD pathogenesis, thereby revealing promising targets for immunomodulatory interventions against disc degeneration.

Introduction: Dental pulp disease represents a prevalent oral pathology with limited success in functional regeneration of the pulp-dentin complex. Stem cell-based endodontic regenerative therapy has emerged as a promising approach, leveraging the principles of tissue engineering through the combination of stem cells, scaffolds, and growth factors. However, recreating the native pulp microenvironment remains a critical challenge.Methods: This study developed a novel strategy to mimic the dental pulp regeneration microenvironment using nucleus pulposus microspheres (NPM) loaded with conditioned medium (CM) for dental pulp stem cells (DPSCs). The biocompatibility of NPM and the effects of NPM-loaded CM on DPSCs differentiation and angiogenesis were systematically evaluated. A semi-isotopic in vivo model was employed to assess pulp-like tissue regeneration.Results: NPM exhibits good biocompatibility, and NPM-loaded CM enhances the odontogenic differentiation and angiogenic potential of DPSCs. Furthermore, the DPSCs+ NPM + CM complexes promoted the regeneration of pulp-like tissue in an in vivo semi-isotopic model. Mechanistically, key bioactive cues secreted in the CM mediated the multi-directional differentiation potential of DPSCs, thereby facilitating pulp tissue regeneration.Discussion: The 3D pulp-specific microenvironment, facilitated by NPM and CM bioactive factors, enables the regeneration of the pulp-dentin complex, offering a novel strategy and experimental basis for pulp regeneration.

To investigate the causal correlation and toxicological mechanisms of omeprazole in intervertebral disc degeneration (IVDD), alongside a particular emphasis on Caspase-3 (CASP3) mediated apoptosis of nucleus pulposus cells (NPCs). Mendelian randomization (MR): GWAS data was employed to assess causal associations between proton pump inhibitors (PPIs) and IVDD. Network toxicology: Shared omeprazole-IVDD targets were identified using STRING, SwissTargetPrediction, and GeneCards databases. Functional enrichment analysis: Biological pathways were explored by employing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular docking: Omeprazole-CASP3 binding affinity was assessed by employing AutoDock Vina. Experimental validation: Rat NPCs were subjected to CCK-8 assay viability, flow cytometry apoptosis, Western blot, and immunofluorescence. MR analysis suggested omeprazole substantially augmented IVDD risk (OR = 1.058, 95% CI = 1.004–1.115, P = 0.034), with no association observed for esomeprazole or lansoprazole. Network toxicology identified 11 overlapping targets, with CASP3 as the hub gene. Molecular docking revealed strong omeprazole-CASP3 binding (free energy: − 6.725 kcal/mol) via hydrogen bonds, π—π stacking, and π—S interactions. Enrichment analysis highlighted the response to reactive oxygen species, caveolae, endopeptidase activity, and IL-17 signaling pathway as key pathways. As revealed by in vitro experiments, omeprazole dose-dependently lessened NPCs viability (300 µM) and heightened apoptosis (28.99% apoptosis rate). Western blot showed significant upregulation of Cleaved-CASP3/pro-CASP3 ratios (P < 0.001), and immunofluorescence demonstrated CASP3 nuclear translocation in omeprazole-treated NPCs. This study found that taking omeprazole may exacerbate IVDD, and its potential mechanism is through CASP3 leading to apoptosis of NPCs. These findings advocate cautious long-term omeprazole use in clinical practice and suggest alternative PPIs.

Magnesium–zinc–calcium alloy has emerged as a key focus in the field of medical degradable materials due to its excellent biodegradability and osteoconductive properties. Grain size is crucial for the physicochemical and biological properties of Mg–Zn–Ca alloy, but it has not been clearly elucidated yet. In this research, Mg‐1Zn‐0.2Ca‐1.0MgO with different grain sizes were prepared to investigate the effect of grain size on the physicochemical properties, corrosion resistance, and osteogenesis. The results indicate that grain refinement improves the mechanical properties and enhances the corrosion resistance of the alloy. The bone surface area to bone volume ratio, bone surface area to tissue volume ratio, and bone volume fraction of the 0.6–0.8 μm group show significantly better performance compared to the 2–3 μm group and 5–6 μm group, indicating that grain refinement can promote the osseointegration between alloy and natural bone. This may be achieved by enhancing the metabolic intensity of alanine, aspartate, glutamate, serine, and glycine around the implant. This work illustrates the effect of grain size on the osseointegration of bone implants and provides a reference for optimizing the properties of bone implant alloys.

Through analyzing the data of the NHANES 2007-2020 cycle, this study concluded that high-intensity exercise 1-2 sessions a week can help maintain bone mass, and there is no significant difference from regular exercise more than 3 times a week. This study aims to explore the relationship between the various physical activity(PA) patterns and the risk of low bone mineral density(BMD) in Americans of working age. A total of 6482 participants aged 20-60 were selected from the National Health and Nutrition Survey (NHANES) conducted from 2007 to 2020. The PA data of the participants were obtained through individual interviews, and the participants were divided into four groups (inactive, insufficiently active, less frequent but sufficiently active(1-2 sessions a week and PA ≥ 150 min), and regularly active). Weighted logistic regression was used to analyze the correlation between PA patterns and the risk of low BMD. Subgroup analyses were applied to display the correlation between PA patterns and low BMD in different subgroups. After adjusting for confounding factors, the multiple logistic regression model showed that compared with inactive individuals, sufficiently active and regularly active individuals had a 35% (OR, 0.65; 95% CI, 0.46-0.92) and 24% (OR, 0.76; 95% CI, 0.62-0.93) lower risk of low BMD, respectively. Compared with regularly active adults, inactive adults had a 32% (OR, 1.32; 95% CI, 1.07-1.62) increased risk of low BMD, while sufficiently active individuals (OR, 0.85; 95% CI, 0.59-1.23) showed no significant difference compared with regularly active adults. Compared with inactive adults, less frequent but sufficiently active adults have a lower risk of low BMD and showed benefits similar to those in regularly active groups. The sufficiently active pattern may become a new trend in modern working-age adults' PA patterns.

Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, and patients with severe degeneration usually require lumbar fusion or total disc arthroplasty. Lumbar fusion carries the risk of accelerated degeneration of the adjacent intervertebral disc (IVD), and total disc arthroplasty could reduce the risk. However, the clinical application of artificial IVD whose nondegradable properties make it difficult to restore the biological function of the IVD. Therefore, we intend to fabricate a novel biomimetic microchannel integrated silk fibroin scaffold (BMI-SF scaffold) containing annulus fibrosus with oriented cross-microchannels and nucleus pulposus with interconnected porous structure. The BMI-SF scaffold exhibits controllable microchannels as well as excellent biocompatibility and biodegradability. In vitro and in vivo studies have demonstrated that microchannels can direct cells into the BMI-SF scaffold and enhance neovascularization, supplying adequate nutritional support for tissue regeneration. The IVD replacement model showed that the BMI-SF scaffold has superior regenerative effects, such as restoring IVD height and providing motion segments with dynamic mechanical properties akin to the natural IVD. In this study, the BMI-SF scaffold developed using controlled microchannels provides a new strategy for patients with severe IVDD and has broad clinical application prospects.