Holomycin, a novel NLRP3 inhibitor, attenuates cartilage degeneration and inflammation in osteoarthritis.

The contribution of the NLRP3 inflammasome in osteoarthritis (OA) pathogenesis has been uncovered in recent years. Holomycin (HL) has recently been identified as a novel NLRP3 inflammasome inhibitor. Herein, we aimed to explore the benefits of HL for OA. A chondrocyte-macrophage co-culture system and the destabilization of the medial meniscus (DMM) mouse model were established to study the effect of HL on OA in vitro and in vivo. ECM degradation-related proteins (MMP-13, aggrecan, and Collagen II) were detected by Western blot (WB) and immunohistochemistry (IHC). The chondrocyte senescence was determined by cell cycle, p16 and p21 expressions, and SA-ß-Gal staining. The cartilage degeneration was evaluated by OARSI score and Safranin O and H&E staining. Inflammation and NLRP3 inflammasome activation were investigated via RT-PCR, ELISA, WB, and IHC. In vitro studies showed that IL-1ß stimulation caused a significant increase of MMP13, p16, p21, and ß-galactosidase expressions, a G1-phase arrest, and a down-regulation of aggrecan and Collagen II in chondrocytes, and the increased expressions of IL-6, CXCL-1, IL-1ß, NLRP3, and Caspase 1 p20 in both chondrocyte and macrophage. Meanwhile, HL administration could partly reverse these effects induced by IL-1ß. In DMM mouse models, intra-articular administration of HL alleviated cartilage degeneration and inflammation, as evidenced by the decrease of OARSI score and MMP13, p16, p21, Collagen II, IL-6, and CXCL-1 expressions and the restoration of chondrocyte number, proteoglycan, and MMP13 expression in cartilage tissues. This study identified HL as a promising agent for OA.

Effect of tibial component overhang on survivorship in medial mobile-bearing unicompartmental knee arthroplasty.

BACKGROUND: Some studies have shown that the position of the tibial component in Oxford unicompartmental knee arthroplasty with a mobile bearing will affect the clinical outcome of patients. Hence, our study aimed to investigate the relationship between the overhang distance of the tibial component and the survival of the implant. METHODS: A retrospective analysis of patients who underwent unicompartmental knee arthroplasty at the same institution from 2014 to 2018 was presented. The study was divided into three groups: minor underhang group (underhang between -3 and 0 mm); minor overhang group (overhang 0-3 mm); and major overhang group (overhang ≥ 3 mm). Demographic and clinical profile characteristics of each group were compared, and survival curves of each group were also compared using Kaplan-Meier and modeled using multivariate Cox regression. RESULTS: A total of 351 knees were included in this study with a minimum follow up of three years and a mean follow up of 4.8 ± 1.5 years. The revision rates in each group were 3.6% (minor underhang group), 2.7% (minor overhang group), and 20.9% (major overhang group) (P < 0.001). From the three groups' cumulative survival rates, the major overhang group was significantly lower than the other two groups (log rank P < 0.001). Multivariate Cox regression showed an association between the major overhang group and implant survival rate (hazard ratio = 7.515, 95% confidence interval = 2.500-22.593, P < 0.001) CONCLUSION: The risk of revision will increase if the tibial component overhangs more than 3 mm medially. Moreover, the reasons for revision are generally bearing dislocation and aseptic loosening.

Higher radiation doses after partial laryngectomy may raise the incidence of pneumonia: A retrospective cohort study.

Background: Currently, studies have shown that a high dose of radiotherapy to the throat have various harmful and adverse effects on the patients' laryngeal function, resulting in the development of pneumonia. This study aimed to explore how radiotherapy dose affected the probability of pneumonia following laryngeal cancer surgery. Materials and methods: A retrospective analysis was done on patients diagnosed with laryngeal cancer between 2010 and 2020 and were treated surgically and with postoperative radiotherapy in the same institution. This study included 108 patients in total, 51 of who were in the low-dose group and 57 of whom were in the high-dose group. Age, gender, the location of laryngeal cancer, the presence or absence of lymph node metastasis, and other demographic and clinical characteristics were collected, and the prevalence of postoperative pneumonia was compared between the two groups. Results: The total prevalence of postoperative pneumonia was 59.3%, but there was a significant difference between the two groups(high-dose group 71.9% VS low-dose group 45.1%; p=0.005). A total of 9.3% (10/108) of the patients had readmission due to severe pneumonia, and the rate of readmission due to pneumonia was significantly different between the two groups (high-dose group 15.8% VS low-dose group 2.0%, p=0.032). Additionally, the high-dose group's prevalence of Dysphagia was significantly higher than the low-dose group's. According to multivariate logistic modeling, high-dose radiation was a risk factor for pneumonia (OR=4.224, 95%CI =1.603-11.131, p=0.004). Conclusion: Pneumonia risk could increase with radiotherapy doses > 50 Gy in the treatment of laryngeal cancer. Therefore, we recommend that when the radiation dose surpasses 50Gy, doctors should pay particular attention to the lung health of patients with laryngeal cancer.