Small molecule drug intervention for chondrocytes is a valuable method for the treatment of osteoarthritis (OA). The 4‐octyl itaconate (OI) is a cellular derivative of itaconate with sound cell permeability and transformation rate. We attempted to confirm the protective role of OI in chondrocytes and its regulatory mechanism. We used lipopolysaccharide (LPS) to induce chondrocyte inflammation injury. After the OI treatment, the secretion and mRNA expression of Il‐6, Il‐10, Mcp‐1 and Tnf‐α were detected by ELISA and qPCR. The protective effect of OI on articular cartilage was further verified in surgical destabilization of the medial meniscus model of OA. Cell death and apoptosis were evaluated based on CCK8, LDH, Typan blue staining, Annexin V and TUNEL analyses. The small interfering RNAs were used to knockout the Nrf2 gene of chondrocytes to verify the OI‐mediated Nrf2 signalling pathway. The results revealed that OI protects cells from LPS‐induced inflammatory injury and attenuates cell death and apoptosis induced by LPS. Similar protective effects were also observed on articular cartilage in mice. The OI activated Nrf2 signalling pathway and promoted the stable expression and translocation of Nrf2 into the nucleus. When the Nrf2 signalling pathway was blocked, the protective effect of OI was significantly counteracted in chondrocytes and a mouse arthritis model. Both itaconate and its derivative (i.e., OI) showed important medical effects in the treatment of OA.

Background: Multiple published studies quantitatively analysing the diagnostic value of MRI, MR arthrography (MRA) and CT arthrography (CTA) for labral lesions of the shoulder have had inconsistent results. The aim of this meta-analysis was to systematically compare the diagnostic performance of MRI, MRA, CTA and CT. Methods: Two databases, PubMed and EMBASE, were used to retrieve studies targeting the accuracy of MRI, MRA, CTA and CT in detecting labral lesions of the shoulder. After carefully screening and excluding studies, the studies that met the inclusion criteria were used for a pooled analysis, including calculation of sensitivity and specificity with 95% confidence intervals (CIs) and the area under the hierarchical summary receiver operating characteristic (HSROC) curves. Results: The retrieval process identified 2633 studies, out of which two reviewers screened out all but 14 studies, involving a total of 1216 patients who were deemed eligible for inclusion in the meta-analysis. The results assessing the diagnostic performance of MRI vs. MRA for detecting labral lesions showed a pooled sensitivity of 0.77 (95% CI 0.70–0.84) vs. 0.92 (95% CI 0.84–0.96), a specificity of 0.95 (95% CI 0.85–0.98) vs. 0.98 (95% CI 0.91–0.99), and an area under the HSROC curve of 3.78 (95% CI 2.73–4.83) vs. 6.01 (95% CI 4.30–7.73), respectively. Conclusion: MRA was suggested for use in patients with chronic shoulder symptoms or a pathologic abnormality. MRI is by far the first choice recommendation for the detection of acute labral lesions. CT should be a necessary supplemental imaging technique when there is highly suspected glenoid bone damage.

Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress. LC3B and SQSTM1/p62 were determined by Western blotting, qPCR, and immunofluorescence, indicating that nobiletin significantly activated autophagy. Nobiletin promoted the nuclear translocation of NRF2 and the transcription of its target genes, including Hmox1, Nqo1, and ferroptosis markers (Gpx4, Slc7a11, Fth, and Ftl), thereby inhibiting ferroptosis. Furthermore, RNA sequencing analysis verified that autophagy, ferroptosis, and the NRF2 signaling pathway served as crucial points for the protection of nobiletin against ototoxicity caused by cisplatin. Collectively, these results indicated, for the first time, that nobiletin alleviated cisplatin-elicited ototoxicity through suppressing apoptosis and oxidative stress, which were attributed to the activation of autophagy and the inhibition of NRF2/GPX4-mediated ferroptosis. Our study suggested that nobiletin could be a prospective agent for preventing cisplatin-induced hearing loss.

As a chronic metabolic disease caused by disorders of purine metabolism, gout has shown increasing incidence rate worldwide. Considering that gout is not easily treated and cured, further studies are explored to prevent gout development through diet modification. Both β-carotin and green tea powder are rich in dietary fiber, which helps maintain the balance of gut microbiota in humans. The aim of this study was to investigate the effects of β-carotin and green tea powder diet on the prevention of gouty arthritis in relation to the bacterial structure of gut microbiota in mice. We successfully induced gouty arthritis in C57BL/6 mice by injecting monosodium urate (MSU) crystals and feeding high-fat diet (HFD), and further investigated the effects of additional β-carotin and green tea powder in the diets of mice on the prevention of gouty arthritis in mice. Our results showed that diet of β-carotin and green tea powder reduced the joint swelling and pain in mice with gout, reduced the levels of serum uric acid (UA) and three types of pro-inflammatory cytokines, i.e., interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), improved the gut microbiota profile, and reduced the metabolic levels of purines and pyrimidines. In conclusion, our study provided evidence to support the application of β-carotin and green tea powder diet as a dietary adjustment method to prevent and treat gouty arthritis.

Ferroptosis, characterized by iron‐dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin‐induced ototoxicity. Existing research has suggested that in cisplatin‐mediated damage to auditory cells and hearing loss, ferroptosis is partially implicated. 4‐Octyl itaconate (4‐OI), derived from itaconic acid, effectively permeates cell membranes, showcasing potent anti‐inflammatory as well as antioxidant effects in several disease models. Our study aimed to investigate the effect of 4‐OI on cisplatin‐induced ferroptosis and the underlying molecular mechanisms. The survival rates of HEI‐OC1 cells and mice cochlea hair cells were measured by CCK8 and immunofluorescence, respectively. The auditory brainstem response (ABR) audiometry was used to detect changes in hearing thresholds in mice before and after treatment. Levels of ROS were evaluated by DCFH‐DA. Real‐time PCR quantified inflammatory cytokines TNF‐α, IL‐6 and IL‐1β. Network Pharmacology and RNA sequencing (RNA‐seq) analysis of the potential mechanism of 4‐OI resistance to cisplatin‐induced ferroptosis. The expressions of ferroptosis‐related factors (GPX4, SLC7A11 and PTGS2) and important antioxidant factors (NRF2, HO‐1, GCLC and NQO1) were tested by real‐time PCR, Western blot and immunofluorescence. Results demonstrated cisplatin‐induced significant ROS and inflammatory factor release, reduced NRF2 expression, hindered nuclear translocation and activated ferroptosis. Pretreatment with 4‐OI exhibited anti‐inflammatory and antioxidant effects, along with resistance to ferroptosis, ultimately mitigating cisplatin‐induced cell loss. In the present study, we show that 4‐OI inhibits cisplatin‐induced ferroptosis possibly through activation of the NRF2/HO‐1 signalling pathway, thereby exerting a protective effect against cisplatin‐induced damage to auditory cells, and providing a new therapeutic strategy for cisplatin‐induced hearing loss.

Objective: To present our experience in managing calcified lumbar disc herniation (cLDH) using a surgical decompression procedure. Methods: Patients who had low back pain radiating to the leg, were preoperatively diagnosed with cLDH by computed tomography and/or magnetic resonance imaging, and were treated with a surgical decompression procedure were studied. Those without cLDH or who were treated with a method other than decompression were excluded. The treatment outcome was analyzed using the visual analog scale (VAS) score, Oswestry Disability Index, and modified Macnab criteria. Results: Thirty-seven patients aged 60.5 ± 9.6 years were evaluated. The VAS scores were significantly decreased 1 day after surgery and remained low at the 3-month and 1-year follow-ups. The Oswestry Disability Index was also significantly lower at the 3-month and 1-year follow-ups. Ninety-four percent of patients rated the results as “excellent” or “good” according to the modified Macnab criteria at the 3-month follow-up. The patients developed few postoperative complications and no recurrence during 1 year of follow-up. Conclusion: Our data suggest that the decompression approach is effective for management of cLDH at least in the short term (1 year) with respect to reducing pain and improving patient satisfaction with few complications.