Background: Osteoarthritis (OA) is a common aging-related degenerative joint disease with chronic inflammation as its possible pathogenesis. Oroxin B (OB), a flavonoid isolated from traditional Chinese herbal medicine, possesses anti-inflammation properties which may be involved in regulating the pathogenesis of OA, but its mechanism has not been elucidated. Our study was the first to explore the potential chondroprotective effect and elucidate the underlying mechanism of OB in OA.Methods: In vitro, primary mice chondrocytes were stimulated with IL-1β along with or without the administration of OB or autophagy inhibitor 3-methyladenine (3-MA). Cell viability assay was measured with a cell counting kit-8 (CCK-8). The phenotypes of anabolic-related (Aggrecan and Collagen II), catabolic-related (MMP3, MMP13, and ADAMTS5), inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1β), and markers of related signaling pathways in chondrocytes with different treatment were detected through western blot, RT-qPCR, and immunofluorescent staining. In vivo, the destabilized medial meniscus (DMM) operation was performed to establish the OA mice model. After knee intra-articular injection with OB for 8 weeks, the mice’s knee joints were obtained for subsequent histological staining and analysis.Results: OB reversed the expression level of anabolic-related proteins (Aggrecan and Collagen II) and catabolic-related (MMP3, MMP13, and ADAMTS5) in IL-1β-induced chondrocytes. Mechanistically, OB suppressed the inflammatory response stimulated by IL-1β, as the inflammation-related (iNOS, COX-2, TNF-α, IL-6, and IL-1β) markers were downregulated after the administration of OB in IL-1β-induced chondrocytes. Besides, the activation of PI3K/AKT/mTOR signaling pathway induced by IL-1β could be inhibited by OB. Additionally, the autophagy process impaired by IL-1β could be rescued by OB. What’s more, the introduction of 3-MA to specifically inhibit the autophagic process impairs the protective effect of OB on cartilage. In vivo, histological staining revealed that intra-articular injection of OB attenuated the cartilage degradation, as well as reversed the expression level of anabolic and catabolic-related proteins such as Aggrecan, Collagen II, and MMP13 induced in DMM-induced OA models.Conclusions: The study verified that OB exhibited the chondroprotective effect by anti-inflammatory, inhibiting the PI3K/AKT/mTOR signaling pathway, and enhancing the autophagy process, indicating that OB might be a promising agent for the treatment of OA.

Ferroptosis, as an iron‐dependent form of necrotic cell death, has been reported to affect activities of nucleus pulposus cells (NPCs). However, its role in the pathogenesis of intervertebral disc degeneration (IDD) is largely unknown. Notably, our bioinformatics analysis predicted that circ_0072464 was downregulated in nucleus pulposus of IDD mice. Therefore, this study is aimed at clarifying the mechanisms of extracellular vesicle‐ (EV‐) encapsulated circ_0072464 derived from bone marrow mesenchymal stem cells (BMSCs) in NPC ferroptosis in IDD. EVs were extracted from mouse BMSCs (BMSC‐EVs) and then cocultured with IL‐1β‐induced NPCs, followed by detection of matrix synthesis, proliferation, and ferroptosis of NPCs based on gain‐ or loss‐of‐function experiments. It was found that the uptake of BMSC‐EVs by NPCs alleviated IDD. circ_0072464 and NRF2 were downregulated, and miR‐431 was upregulated in IDD. Mechanistically, circ_0072464 competitively bound to miR‐431, which targeted and inhibited NRF2 expression. BMSC‐derived EVs carrying circ_0072464 inhibited NPC ferroptosis to promote matrix synthesis and proliferation of NPCs by inhibiting miR‐431 and upregulating NRF2. Besides, in vivo experiments also confirmed that BMSC‐EVs alleviated intervertebral disc lesions in mice with IDD through the circ_0072464/miR‐431/NRF2 axis. Collectively, BMSC‐EV‐loaded circ_0072464 inhibited NPC ferroptosis to relieve IDD via upregulation of miR‐431‐mediated NRF2, therefore providing a potential therapeutic target against IDD.

Objective: This meta-analysis with statistical power analysis aimed to evaluate the difference between full-endoscopic and microscopic spinal decompression in treating spinal stenosis.Methods: We searched PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CNKI (China National Knowledge Infrastructure) for relevant randomized controlled trials (RCTs) regarding the comparison of full-endoscopic versus microscopic spinal decompression in treating lumbar spinal stenosis through February 28, 2022. Two independent investigators selected studies, extracted information, and appraised methodological quality. Meta-analysis was conducted using RevMan 5.4 and STATA 14.0, and statistical power analysis was performed using G*Power 3.1.Results: Six RCTs involving 646 patients met selection criteria. Meta-analysis suggested that, compared with microscopic decompression, full-endoscopic spinal decompression achieved more leg pain improvement (mean difference [MD], -0.20; 95% confidence interval [CI], -0.30 to -0.10; p = 0.001), shortened operative time (MD, -12.71; 95% CI, -18.27 to -7.15; p < 0.001), and decreased the incidence of complications (risk ratio, 0.43; 95% CI, 0.22–0.82; p = 0.01), which was supported by a statistical power of 98.57%, 99.97%, and 81.88%, respectively.Conclusion: Full-endoscopic spinal decompression is a better treatment for lumbar spinal stenosis, showing more effective leg pain improvement, shorter operative time, and fewer complications than microscopic decompression.

Background: The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear. Methods: We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs). Results: The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites. Conclusion: These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.

Whether there are increased rates of chronic diseases associated with the combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlap syndrome (OVS) has not been determined. The purpose of this study was to assess the prevalence of five comorbidities in COPD and OVS patients. A total of 968 patients with confirmed COPD were included in this study. Participants were requested to fill out a questionnaire involving their basic information and medical history. All subjects underwent one overnight polysomnography and were then divided into an OVS group or a COPD only group according to their apnea–hypopnea index. The prevalence of hypertension, diabetes, cardiovascular disease, arrhythmia and cerebrovascular disease were compared and risk factors for comorbidities in COPD patients were identified. Compared with the COPD only group, the prevalence of hypertension was significantly higher in the OVS group, however, the prevalence rates of the other four kinds of diseases were not statistically different between the two groups. In COPD patients, the prevalence of hypertension increased with the severity of OSA and the prevalence of arrhythmia increased with airflow limitation severity. Risk factors for OSA in patients with COPD included BMI, FEV₁%, Epworth Sleepiness Scale score and the Sleep Apnea Clinical Score. OSA was an independent risk factor for hypertension. The other risk factors for hypertension in COPD patients included age, BMI, CAT score and alcohol consumption. Age, lower FEV₁% may be risk factors for arrhythmia. OVS patients were associated with a high prevalence rate of hypertension, while OSA was an independent risk factor for hypertension.