Cellular senescence and the senescence-associated secretory phenotype (SASP) are increasingly recognized as contributors to intervertebral disc degeneration (IVDD). However, clinically relevant SASP-related gene signatures and therapeutic implications remain incompletely defined. Two peripheral whole-blood transcriptomic datasets from GEO (GSE124272 and GSE150408) were integrated. SASP-associated differentially expressed genes (DEGs) were identified by intersecting DEGs between IVDD and control samples with the SenMayo gene set, a literature-derived senescence panel composed predominantly of SASP factors. Functional enrichment analysis and immune infiltration profiling were performed. Hub genes were prioritized using protein-protein interaction networks, consensus clustering, and weighted gene co-expression network analysis. Candidate compounds were predicted using the Connectivity Map and further supported by molecular docking. The candidate drug was further evaluated in vitro using IL-1β-stimulated mouse nucleus pulposus cells by RT-qPCR and Western blotting, and in vivo in a mouse needle-puncture IVDD model assessed by micro-CT and histology. A four-gene SASP-related signature (MMP9, CXCL1, TNFRSF1A, and CXCR2) was significantly associated with IVDD and linked to NF-κB signaling and cellular senescence pathways by gene set enrichment analysis. The signature correlated with pro-inflammatory innate immune infiltration, particularly neutrophils and M0 macrophages. Pinocembrin (PC) exhibited favorable predicted binding affinity to the proteins encoded by the four signature genes. PC suppressed IL-1β-induced upregulation of these signature genes at both mRNA and protein levels in vitro and preserved disc height and structural integrity in vivo. This study identifies a four-gene SASP-related signature associated with IVDD and provides preclinical evidence supporting pinocembrin as a potential therapeutic candidate.

Dentin matrix is a natural scaffold derived from complete or partial demineralization of human or animal dentin, capable of releasing growth factors and proteins essential for tissue regeneration and repair. Recent studies have identified the dentin matrix as an exceptional scaffold for the regeneration of dental and osseous tissues, attributed to its excellent biocompatibility, advantageous mechanical properties, and capacity for chemotactic induction. A substantial body of evidence supports its efficacy in promoting the formation of dentin bridges, facilitating the regeneration of the pulp-dentin complex, enhancing de novo bone formation, and mitigating alveolar bone resorption, thereby presenting innovative therapeutic approaches for the reconstruction of oral tissues. This review categorizes dentin matrices based on the degree of demineralization into partially demineralized dentin matrix and completely demineralized dentin matrix. Furthermore, the review consolidates current advancements and outlines future directions for the application of dentin matrix in pulp-dentin complex and alveolar bone regeneration. Despite the ongoing challenges related to the establishment of standardized preparation protocols, the continuous advancements in tissue engineering and regenerative medicine exhibit an advantageous potential for clinical application.

This study aimed to evaluate an innovative anterolateral approach using portable ultrasound, comparing the accuracy and safety of portable ultrasound-guided, conventional ultrasound-guided, and landmark-based blind injection techniques. In this single-centre, prospective, randomised controlled trial, 117 patients with hip pain were randomly assigned to three groups: landmark-based blind injection (n = 39), conventional ultrasound-guided injection (n = 39), and portable ultrasound-guided injection (n = 39). Each patient received a unilateral injection of 2.5 ml hyaluronic acid and 1 ml betamethasone via the anterolateral approach, using parameters optimized from previous research. Primary endpoints included success and accuracy rates, while secondary endpoints comprised post-injection visual analogue scale (VAS) pain scores, procedure time, puncture depth, and complications. The portable ultrasound group achieved 100

Peritoneal effusion is a rare but potentially life-threatening complication. This article aims to report two cases of massive peritoneal effusion following hip arthroscopy, both of whom had favorable outcomes. Two patients of Han Chinese ethnicity underwent hip arthroscopy under epidural anesthesia. Case 1 was a 49-year-old female who had a right acetabular labral tear and cyst, while Case 2 was a 69-year-old female who had left hip femoroacetabular impingement. Both surgeries used standard anterolateral and anterior approaches with 18 L and 24 L of irrigation fluid at 100 mmHg pressure, respectively. During surgery, both patients developed severe abdominal distension; Case 2 also experienced transient hemodynamic instability. Imaging results confirmed extensive fluid accumulation in the abdominal and pelvic cavities. Both patients were treated with diuretics (furosemide), gastrointestinal motility regulators (trimebutine maleate), and intermittent enemas. Case 1 urinated approximately 3000 mL, and Case 2 urinated 1500 mL. Follow-up imaging results showed significant reduction in fluid accumulation, and both were discharged without further complications. Large peritoneal effusion after hip arthroscopy is a rare but serious complication that can lead to intra-abdominal hypertension. Surgeons should be careful, especially in patients with prior abdominal surgeries or prolonged procedures near the iliopsoas tendon sheath, and take preventive measures such as minimizing perfusion pressure and monitoring vital signs.

AimsMagnesium ions (Mg2+) play an important role in promoting cartilage repair in cartilage lesions. However, no research has focused on the role of Mg2+ combined with microfracture (MFX) in hyaline-like cartilage repair mediated by cartilage injury. This study aimed to investigate the beneficial effects of the combination of MFX and Mg2+ in cartilage repair.MethodsA total of 60 rabbits were classified into five groups (n = 12 each): sham, MFX, and three different doses of Mg2+ treatment groups (0.05, 0.5, and 5 mol/L). Bone cartilage defects were created in the trochlear groove cartilage of rabbits. MFX surgery was performed after osteochondral defects. Mg2+ was injected into knee joints immediately and two and four weeks after surgery. At six and 12 weeks after surgery, the rabbits were killed. Cartilage damage was detected by gross observation, micro-CT, and histological analysis. The expression levels of related genes were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR).ResultsThe histological results showed that the 0.5 mol/L Mg2+ group had deeper positive staining in haematoxylin-eosin (H&E), safranin O, Alcian blue, and type II collagen staining. The new cartilage coverage in the injury area was more complete, and the regeneration of hyaline cartilage was higher. The RT-qPCR results showed that sirtuin 1/bone morphogenetic protein-2/sex-determining region Y box 9 (SIRT1/BMP-2/SOX-9) and hypoxia-inducible factor 1-alpha (HIF-1α) messenger RNA levels were up-regulated after Mg2+ injection.ConclusionMFX combined with Mg2+ treatment has a positive effect on cartilage repair. The Mg2+ injection dose of 0.5 mol/L is most effective in enhancing microfracture-mediated cartilage repair.Cite this article: Bone Joint Res 2025;14(1):20–32.

Study DesignA case-controlled retrospective study.ObjectiveWe aimed to explore the effectiveness of MRI-based VBQ scores derived by different MRI sequences in assessing risk of an osteoporotic vertebral compression fracture (OVCF) in age- and sex-controlled patients.MethodsThis retrospective study included patients hospitalized for OVCF (fracture group) and degenerative lumbar disease (non-fracture group) from July 2022 to July 2024. Patients in both groups were matched for sex and age in a 1:1 ratio. VBQ scores were acquired from non-contrast lumbosacral MRI T1-weighted, T2-weighted, and short tau inversion recovery (STIR)-weighted sequences. A receiver operating characteristic (ROC) curve and area under the ROC (AUC) were plotted to evaluate the diagnostic accuracy.ResultsA total of 168 patients (n = 84 in each group) were included. VBQ-T1 scores were higher in the fracture group (4.4 vs 4.1, P = 0.001), with an AUC of 0.641 to predict OVCF. VBQ-T2 scores were higher in the fracture group (0.60 vs 0.55, P < 0.001), with an AUC of 0.697. Additionally, VBQ-T2-STIR scores were higher in the fracture group (0.99 vs 0.83, P = 0.004), with an AUC of 0.644. Multivariate logistic regression analysis identified VBQ-T2, rather than VBQ-T1 or VBQ-T2-STIR, as an independent risk factor for OVFC.ConclusionThis study evaluated the MRI-based VBQ scores in assessing risk of OVCF based on age- and sex-matched cases. The VBQ-T2 score appears most promising for evaluating the risk of OVCF in clinical practice.

Objective:Although percutaneous endoscopic lumbar discectomy (PELD) has shown favorable outcomes in the treatment of LDH patients, the issue of recurrence caused by potential disc degeneration remains unresolved. Regenerative therapy with platelet-rich plasma (PRP) injection offers the potential to reduce recurrence rates and improve clinical outcomes. This systematic review and meta-analysis evaluated the clinical efficacy of combining PELD with PRP injection as a novel therapeutic approach for LDH. Methods:A comprehensive literature search was conducted in the PubMed, Embase, Web of Science, and Cochrane databases, with the search period ending on October 30, 2024. Data were extracted and analyzed to evaluate recurrence rates, pain relief, functional outcomes, and intervertebral disc health status. Results:A total of 4 eligible studies were identified in this research, comprising 421 patients, of whom 212 received the combined treatment of PRP and PELD, while 209 underwent PELD alone. The results demonstrated that the combined PELD and PRP therapy significantly reduced recurrence rates (OR: 0.21, 95% CI: 0.07 to 0.64, p = 0.006) and improved VAS pain scores for both back and leg pain at specific follow-up time. Additionally, intervertebral disc height at the final follow-up was significantly greater in the combined PELD and PRP group (MD: 0.88, 95% CI: 0.57 to 1.20, p < 0.00001), indicating the potential of the combined therapy to restore degenerative discs. Conclusions:The study indicates that PELD combined with PRP therapy provides better clinical outcomes compared to PELD alone, particularly in reducing recurrence rates, alleviating pain, and improving functional recovery. However, future studies with larger sample sizes and extended follow-up durations are warranted to validate the long-term efficacy and safety of this innovative therapeutic approach. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/view/CRD42024621150, PROSPERO CRD42024621150.

OBJECTIVE:Studies have described the nonuniform settlement of C2 lateral mass (C2LM-NUS) as an asymmetrical change of the bilateral C2 lateral masses. This study aimed to: (1) identify the objective evidence for the C2LM-NUS and clarify its anatomical basis; (2) explore the association between C2LM-NUS and atlantoaxial osteoarthritis (AAOA), and verify the related biomechanics. METHODS:Seventy-nine dry axis specimens were measured macroscopically. The vertical distance between the superior articular surface and the lower edge of the vertebra was defined as the settlement value of C2 lateral mass (C2LMS). Twelve formalin-embalmed axis specimens were scanned using micro-computed tomography (Micro-CT), and the trabecular microstructure of lateral masses was analyzed. 522 patients who underwent a head and neck or cervical spine CT scan were reviewed. The C2LMS was measured, and the bilateral difference (d-C2LMS) was calculated. The AAOA was recorded. Normal and C2LM-NUS upper cervical spine (C0-C3) finite element models were established. The stress distributions on the alar ligament, transverse ligament, and lateral mass cartilage were analyzed using Abaqus software under varying torque conditions. RESULTS:Macroscopic analysis revealed that the C2LMS measured at the center point was comparable to the overall C2LMS (18.19 ± 1.83 mm vs. 18.18 ± 1.82 mm, p = 0.942). Twenty-seven dry axis specimens (34.2%) were identified as C2LM-NUS because they showed significant differences in bilateral C2LMS (d-C2LMS: 1.21 ± 0.32 mm). Micro-CT analysis revealed that four formalin-embalmed axis specimens with C2LM-NUS exhibited a substantial difference in trabecular microstructural parameters between the settlement and the normal lateral masses. Clinical observations indicated that C2LM-NUS was an independent risk factor for AAOA (adjusted odds ratio = 2.041, p < 0.001). Finite element analysis revealed that in the C2LM-NUS model, the maximum stress on the settlement side of the alar ligament increased by 47.4%-53.3% compared to the opposite side, and the cartilage stress increased by 15.0%-68.5%. Meanwhile, the maximum stress of the transverse ligament in the C2LM-NUS model was 1.3-1.6 times greater than that of the normal model. CONCLUSIONS:The macroscopic measurement of the axis specimens provided objective anatomic evidence for C2LM-NUS. Micro-CT showed that C2LM-NUS was associated with asymmetrical alterations of the trabecular microstructure of the lateral masses, suggesting that it is a pathological change rather than a normal phenomenon. The clinical study indicated that C2LM-NUS is an independent risk factor for AAOA. Stress concentration in unilateral alar ligaments and articular cartilage is a biomechanical contributor to AAOA.

Objective: To explore the application effect and value of dynamic scenario simulation combined with a micro-video case teaching model in thyroid cancer nursing teaching.Methods: A total of 60 nursing students who practiced breast and nail surgery from January 2022 to October 2023 were selected as the study objects and grouped according to the practice period.30 nursing students from January 2022 to December 2022 were included in the control group, and 30 nursing students from January 2023 to October 2023 were included in the study group.The nursing students in the control group adopted the conventional teaching mode in the teaching of thyroid cancer nursing, while the nursing students in the study group adopted the dynamic scenario simulation combined with micro-video case teaching mode to evaluate and compare the teaching performance, learning initiative and critical thinking ability of the nursing students in the two groups.Result: The teaching performance statistics of nursing students with thyroid cancer in the study group showed that the scores of theoretical knowledge assessment and comprehensive practical training assessment were higher than those in the control group, with statistical significance (P < 0.05).The evaluation of the learning initiative after teaching showed that the scores of nursing students in the study group were higher than those in the control group in all dimensions of the ALS scale, with statistical significance (P < 0.05).The evaluation of critical thinking ability after teaching showed that the CTDI-CV scores and total scores of nursing students in the study group were higher than those in the control group, and the difference was statistically significant (P < 0.05).Conclusion: The dynamic scenario simulation combined with micro-video case teaching mode in nursing teaching of thyroid cancer can improve the academic performance of nursing students, as well as the learning initiative and critical thinking ability, and the application effect is outstanding.

Purpose As a common clinical disease, lumbar spinal stenosis (LSS) is currently the preferred surgical treatment, and there are various opinions. We conducted a study on whether fusion should be performed simultaneously with decompression for LSS caused by low-grade degenerative lumbar spondylolisthesis and compared the efficacy and safety of the 2 surgeries. Methods We conducted literature searches on Cochrane Library, Embase, PubMed, Scopus, and China National Knowledge Infrastructure databases to search for randomized controlled trials and observational studies that compared decompression alone and decompression plus fusion in the treatment of LSS with low-grade lumbar spondylolisthesis. We conducted a meta-analysis on surgical duration, hospital stay, incidence of complications, intraoperative blood loss, lower back and leg pain scores, and Oswestry Disability Index scores. Results We ultimately included 8 articles, including 2 randomized controlled trials and 6 observational studies. Additional fusion did not benefit patients in relieving lower back pain (P = 0.05) and leg pain (P = 0.12), and there was no significant difference in Oswestry Disability Index (P = 0.12) and perioperative complication rate (P = 0.10) between the 2. However, decompression alone was significantly better than the decompression plus fusion group in terms of surgical time (P = 0.0008), hospital stay (P < 0.0001), and intraoperative blood loss (P < 0.00001). Conclusions In this article, decompression alone has shorter surgical and hospitalization time and less intraoperative bleeding compared to decompression plus fusion. And there was no significant difference in pain score and disability index between the 2 surgeries during follow-up. Therefore, we can say that for patients with LSS caused by low-grade lumbar spondylolisthesis, decompression alone is not inferior to decompression plus fusion.

PURPOSE:To analyze the effects of fixed appliance and invisible appliance without bracket on anterior tooth root and alveolar bone in patients with mild to moderate overcrowding of Class Ⅰmalocclusion. METHODS:A total of 120 patients with mild to moderate dental crowding were selected from January 2018 to February 2022,and divided into control group and experimental group by random number table method, with 60 cases in each group. The control group was treated with traditional fixed appliance, while the experimental group was treated with invisible appliance without bracket. Cone-beam CT(CBCT) was taken before and 12 months after treatment to measure the root length and alveolar bone height and thickness of maxillary central incisor teeth, height of alveolar bone of anterior teeth lip and lingual side and cusp teeth in both groups. Statistical analysis was performed with SPSS 22.0 software package. RESULTS:The root length changes of maxillary central incisor, lateral incisor and cusp teeth in the experimental group were significantly lower than those in the control group before and after treatment(P＜0.05). The alveolar bone height changes in the labial side and lingual palatine side of upper anterior teeth, labial side and lingual palatine side of inferior anterior teeth in the experimental group before and after treatment were significantly lower than those in the control group(P＜0.05). The thickness changes of labiolingual alveolar bone at the neck, middle root and apex of upper and inferior anterior teeth in the experimental group were significantly lower than those in the control group before and after treatment(P＜0.05). CONCLUSIONS:Compared with fixed appliance, invisible appliance without bracket can reduce root resorption and the loss of alveolar bone height and thickness in the treatment of Class I patients with mild to moderate dental crowding.

Objectives: This study aims to identify the key senescence genes and potential regulatory mechanisms that contribute to the etiology of intervertebral disc degeneration (IDD).Method: We analyzed GSE34095 and GSE70362 datasets, identifying key senescence-related differentially expressed genes (DEGs) in IDD using lasso regression. Risk scores classified patients into high- and low-risk groups. We compared pathways, functions, and immune infiltration between these groups. Diagnostic ability was assessed using ROC curves and a nomogram predicted IDD incidence. In single-cell dataset GSE165722, we evaluated expression of key senescence-related DEGs.Results: We identified 12 key senescence-related DEGs distinguishing high- and low-risk IDD patients. Enrichment analysis revealed cellular stress response, apoptotic signaling pathway, and protein kinase activation differences. Immune cell analysis showed elevated eosinophils in low-risk group and increased effector memory CD8 T, central memory CD4 T, myeloid-derived suppressor, natural killer, monocyte, Type 1 T helper, plasmacytoid dendritic, and natural killer T cells in high-risk group. A nomogram using AUC >0.75 genes (CXCL8, MAP4K4, MINK1, and TNIK) predicted IDD incidence with good diagnostic power. High senescence scores were observed in neutrophils.Conclusion: Our diagnostic model, based on key senescence-related DEGs and immune cell infiltration, offers new insights into IDD pathogenesis and immunotherapy strategies.

Objective:Osteogenesis imperfecta (OI) is a congenital disorder characterized by muscle defect and skeletal fragility, and no cure is yet available. Crosstalk between bone and muscle has become a new coming focus of therapeutic strategy in OI. Irisin, a secreted myokine, was found to be involved in regulating bone metabolism, and may be beneficial for the treatment of OI. However, its effects in OI have yet to be determined. This study sought to determine whether Irisin therapy is capable of reducing fracture risk in OI and to investigate the potential mechanisms of action.Methods:Fibronectin type III domain containing 5 (FNDC5)/Irisin expression was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. In vivo, X-ray was used for fracture counting and micro-CT, dynamic histomorphometry analysis, immunohistochemistry, histomorphometry, and biomechanical test were used to evaluate the effects of Irisin on fracture frequency and bone quality in OI mouse model, oim/oim mouse. In vitro, osteogenesis-related gene expressions were determined by quantitative real-time PCR (qRT-PCR), western blot, and osteoblastogenesis assay were assessed by alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining. Mechanistically, cell immunofluorescence staining, co-immunoprecipitation (co-IP) (Co-IP), molecular docking, western blot, luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay were used for elucidating the mechanisms of how Irisin antagonized transforming growth factor-β (TGF-β)/Smad signaling in oim/oim osteoblasts and further attenuated the inhibitory effect of TGF-β1 on osteogenic differentiation.Results:Musculoskeletal system-related FNDC5/Irisin was decreased in the serum, muscle, and bone in oim/oim mice. Irisin administration reduced bone fracture and attenuated bone abnormalities by improving bone mass and strength and facilitating the expression of osteogenic differentiation markers. In vivo study and in vitro experiments showed that Irisin antagonized TGF-β/Smad signaling by interfering with TGF-β1-TGF-β receptor II (TβRII) binding. In oim/oim osteoblasts, Irisin alleviated TGF-β1-induced suppression of osteogenic differentiation through both integrin-dependent and integrin-independent mechanisms. Independent of integrin receptors, Irisin affected osteogenesis by activating ERK/p38 signaling and counteracting TGF-β/Smad2/3 signaling. In particular, Irisin alleviated TGF-β1-induced inhibition of Runx2 function at the osteocalcin promoter through decreasing Smad2/3 signaling and inducing HADC4/5 degeneration.Conclusions:Collectively, Irisin could effectively reduce bone fracture in oim/oim mice through promoting osteogenesis and counteracting TGF-β/Smad signaling.Translational potential statement:Findings from this study provided evidence for using Irisin as a potential therapeutic reagent to prevent the progression of OI.

Osteoporotic bone defect is an intractable challenge in clinical practice, involving impaired bone repair ability and abnormal immune response. Despite the development of various tissue-engineered scaffolds for osteoporotic bone repair, the pathogenesis of osteoporosis has been lacking consideration, resulting in poor efficacy. Here, we integrated short-chain chitosan (CS) and nanoparticulate hydroxyapatite (nHAp) into a covalent tetra-armed poly (ethylene glycol) (tetra-PEG) network to create a composite hydrogel (PEG/nHAp/CS, PHC). The constructed PHC hydrogel exhibited ability of enhancing osteogenesis with high mechanical strength, excellent surface properties, and good biocompatibility. PHC hydrogel also had immunomodulatory effects of promoting M2 macrophage polarization and suppressing M1 macrophage polarization via antagonizing TLR4/NF-kappa B signaling. PHC hydrogel further increased osteogenic capacity and inhibited osteoclast formation and resorption indirectly. Parathyroid hormone (PTH) could be effective loaded and sustainable released in the PHC hydrogel (PTH@PHC), in which the osteogenic ability was further enhanced via activation of cAMP/PKA/CREB signaling. By using an osteoporotic calvaria bone defect rat model, we demonstrated that the PTH@PHC hydrogel was able to improve bone regeneration and bone defects healing. Findings of this study indicated that the bioactive composite hydrogel has powerful osteogenic-promoting potency and immunomodulation, which provides a promising therapeutic strategy for future clinical repair of osteoporotic bone defect.

Abstract Background The treatment of acute periprosthetic joint infection (PJI) remains a great challenge. This study aimed to explore the efficacy of vacuum sealing drainage (VSD) used as an adjunct to debridement, antibiotics, and implant retention (DAIR) for acute periprosthetic joint infection of the hip. Methods Patients undergoing debridement, irrigation with component retention, and application of vacuum seal drainage in the deep portion surrounding the infected sites from January 2014 to February 2021 were retrospectively reviewed. The definition of failure included the requirement of prosthesis removal; persistent infection-related symptoms; suppressive antibiotics therapy due to failure of controlling the infection; infection-related death. Results 11 patients were included in this study with a mean follow-up of 32.3 ± 18.3 months. There were 9 males and 2 females with a mean age of 58.6 ± 16.3 years. Eight had sinus tract. The overall success rate was 81.82% with 2 failures. The Harris Hip Scores (HHS) improved in the last follow-up compared with preoperative evaluation (83.0 ± 11.6 vs 43.9 ± 11.8, t=-13.58, P༜0.001). Conclusion The addition of VSD in the deep portion does improve the outcome of DAIR, which might be a safe and effective option for acute PJI.

Intervertebral disc degeneration (IDD) is a chronic disease affecting millions of patients; however, its specific etiology is unknown. G protein-coupled receptors (GPRs) are a superfamily of integral membrane receptors in cells, and the receptors respond to a diverse range of stimuli and participate in multiple cellular activities. Here, using RNA-sequencing (RNA-seq) methods and immunohistochemistry, we revealed that G protein-coupled receptor 35 (GPR35) may have a relationship with IDD. Then, we demonstrated that the deletion of GPR35 in nucleus pulposus cells (NPCs) with siRNA or in Gpr35-/- mice significantly alleviated IDD caused by senescence or mechanical stress, further validating the pathological role of GPR35 in IDD. In addition, GPR35 induced the influx of Ca2+ and upregulation of reactive oxygen species (ROS) under mechanical stress in NPCs, which we believe to be the mechanism of GPR35-induced IDD. Finally, GPR35 caused upregulation of ROS in NPCs under mechanical stress, while excessive ROS stimulated the NPCs to express more GPR35 with a significant dose or time response. The u-regulated GPR35 could sense mechanical stress to produce more ROS and perpetuate this harmful cycle. In summary, our study shows that GPR35 plays a critical role in mediating IDD via mediating the influx of calcium ions and upregulating ROS, which implies a strong potential advantage of GPR35 as a prevention and treatment target in IDD.

Propionibacterium acnes infection in intervertebral discs (IVDs) is a newly identified cause of low back pain (LBP). In the present study, we aimed to determine whether the nerve growth factor (NGF), a critical pro-algesic factor, is involved in P. acnes-induced LBP. After co-culturing with P. acnes, nucleus pulposus cells (NPCs) produced NGF, which was upregulated after inoculation of P. acnes into IVDs of rats. In addition, administration of P. acnes into rat IVDs leads to significant mechanical allodynia and cold hyperreflexia, and significant upregulation of the pain-related factors, including substance P (SP), calcitonin gene-related peptide (CGRP), and Transient Receptor Potential Vanilloid 1 (TRPV1), in rat dorsal root ganglia (DRG), suggesting that P. acnes-inoculated rats had obvious discogenic LBP. However, inhibition of NGF bioactivity significantly ameliorated P. acnes-induced discogenic LBP, suggesting that P. acnes induced LBP via NGF. Finally, an in vitro mechanism study demonstrated that P. acnes stimulated NPCs to secrete NGF via TLR-2 receptor and NF-κB p65/JNK pathway, or ROS-related pathway. Therefore, P. acnes had a strong association with LBP by stimulating NPCs to secrete NGF via the TLR2-NF- κB/JNK or ROS-related pathway. These findings propose a novel potential therapeutic strategy for LBP.

The destruction of the low oxygen microenvironment in nucleus pulposus (NP) cells played a critical role in the pathogenesis of intervertebral disc degeneration (IVDD). The purpose of this study was to determine the potential role of integrin alpha 6 (ITG α6) in NP cells in response to high oxygen tension (HOT) in IVDD. Immunofluorescence staining and western blot analysis showed that the levels of ITG α6 expression were increased in the NP tissue from IVDD patients and the IVDD rat model with mild degeneration, which were reduced as the degree of degeneration increases in severity. In NP cells, the treatment of HOT resulted in upregulation of ITG α6 expression, which could be alleviated by blocking the PI3K/AKT signaling pathway. Further studies found that ITG α6 could protect NP cells against HOT-induced apoptosis and oxidative stress and protect NP cells from HOT-inhibited ECM protein synthesis. Upregulation of ITG α6 expression by HOT contributed to maintaining NP tissue homeostasis through the interaction with hypoxia-inducible factor-1α (HIF-1α). Furthermore, silencing of ITG α6 in vivo could obviously accelerate puncture-induced IVDD. Taken together, these results revealed that the increase of ITG α6 expression by HOT in NP cells might be a protective factor in IVD degeneration as well as restore NP cell function.

We focus on providing the first comprehensive national dataset on the incidence, injury aetiology and mortality of TSCI in China. A multi-stage stratified cluster sampling method was used. We included TSCI cases from all hospitals in three regions, nine provinces and 27 cities in China via search of electronic medical records and retrospectively analysed the characteristics of TSCI in China from 2009 to 2018. We estimated the incidence of TSCI in the total population and subgroups. There were 5954 actual cases in 2009, corresponding to a total estimated TSCI incidence of 45.1 cases per million population (95% CI, 44.0–46.3). There were 10,074 actual cases in 2018, corresponding to a total estimated TSCI incidence of 66.5 cases per million population (95% CI, 65.2–67.8) (P < 0.001; annual average percentage change (AAPC), 4.4%). From 2009 to 2018, the incidence of almost all sex/age groups showed an increasing trend over time (P < 0.001; AAPC, 0.7–8.8%). The elderly population (aged 65–74) displayed the highest incidence of TSCI (with an average annual incidence of 127.1 cases per million [95% CI, 119.8–134.3]). The TSCI incidence increased significantly from 2009 to 2018. The incidence in the elderly populations was consistently high and continues to increase over time. The mortality of TSCI patients in hospitals is relatively low and continues to decrease each year, but elderly individuals remain at a high risk of hospital death.