The molecular mechanism of neutrophil extracellular traps and its role in bone and joint disease.

As the body's first line of defense, neutrophils play an important role in the early stages of infection. Neutrophil extracellular traps (NETs), a novel way to kill pathogens, are released from activated neutrophils to trap and kill microorganisms and protect the body from invasion. However, studies have shown that NETs not only play a role in self-defense in vivo but also participate in some pathological processes. Current studies have found that excessive or abnormally activated NETs play a pathogenic role in a variety of diseases. NETs, in addition to killing pathogens during the pathology of sepsis, affect on coagulation function, and blood endothelium. Additionally, NETs have a wide range of effects in other inflammatory, immune, and other related diseases. NETs are involved in the pathology of atherosclerosis. NETs also play a role in systemic lupus erythematosus, diabetes mellitus, Alzheimer's disease, and tumors, but there are relatively few NETs studies on bone and joint diseases. This article discusses NETs, their formation, and their association with bone and joint disorders. New targets for the effective treatment of joint diseases may be identified by studying the relationship between NETs and bone and joint diseases.

Causal relationship between osteoarthritis with atrial fibrillation and coronary atherosclerosis: a bidirectional Mendelian randomization study of European ancestry.

Background: Osteoarthritis (OA) is a degenerative disease with high prevalence. Some observational studies have shown that patients with osteoarthritis often have co-existing cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary atherosclerosis (CA). However, there is still a lack of stronger evidence confirming the association between osteoarthritis and cardiovascular disease. In this study, we used a bidirectional two-sample Mendelian randomization study to investigate the relationship between OA with AF and CA. Methods: OA data from the UK Biobank and arcOGEN (Arthritis Research UK Osteoarthritis Genetics, a study that aimed to find genetic determinants of osteoarthritis and elucidate the genetic architecture of the disease) integration were selected for the study (n = 417,596), AF data were obtained from six studies (n = 1,030,836), and coronary atherosclerosis data were derived from the FinnGen (n = 218,792). MR analysis was performed primarily using the Inverse variance weighted (IVW) method, with MR Egger, weighted median, simple mode, weighted mode as supplements, sensitivity analysis was performed using Cochran Q statistic, and leave-one-out analysis. Results: We found that OA and AF were positively associated [IVW: OR (95% CI): 1.11 (1.04, 1.19), P = 0.002], while OA and CA were negatively associated [IVW: OR (95% CI): 0.88 (0.79, 0.98), P = 0.02]. In the reverse MR analysis, no effect of AF on OA was found [IVW: OR (95% CI): 1.00 (0.97, 1.03), P = 0.84], meanwhile, CA and OA were found to be associated negatively [IVW: OR (95% CI): 0.95 (0.92, 0.99), P = 0.01]. No violations of MR assumptions were found in the sensitivity analysis. Conclusion: This research confirms that OA is a risk factor for AF, and there is a mutual protective factor between OA and CA. However, further studies are still necessary to elucidate the underlying mechanisms.

Efficacy and Safety of Ultrasound-Guided High-Intensity Focused Ultrasound Ablation in Women With Multiple Uterine Fibroids: An Exploratory Study.

OBJECTIVE: The aim of the work described here was to explore the clinical efficacy and safety of ultrasound-guided high-intensity focused ultrasound (USg-HIFU) treatment in women with multiple fibroids and identify the characteristic parameters predicting USg-HIFU efficacy in multiple fibroids. METHODS: From February 2021 to August 2022, 138 patients with multiple fibroids (group A comprising 125 patients with two to four fibroids and 13 patients with five or more fibroids) and 149 patients with solitary fibroids (group B) were included. HIFU treatment information, efficacy comparisons and adverse events were recorded. A nomogram model of the characteristic parameters used to predict the efficacy of USg-HIFU in multiple fibroids was established. RESULTS: After USg-HIFU treatment, the statistical comparison of pre-operative versus post-operative symptom scores and fibroid volume in the two groups indicated obvious symptom relief and substantial shrinkage of fibroid volume (all p values <0.001). Nevertheless, group A required more energy and longer treatment and sonication times to achieve a 70% non-perfused volume (NPV) ratio, and had a lower energy efficiency factor than group B (all p values <0.05). No severe complications were observed in either group. The nomogram model included fibroid volume, fibroid location and signal intensity on T2-weighted imaging (T2WI). The area under the receiver operating characteristic curve and the accuracy of the model were 0.698 and 0.686, respectively. CONCLUSION: USg-HIFU appears to be an effective and safe treatment option for multiple fibroids. Knowledge of the fibroid volume, location and signal intensity on T2WI may help determine the efficacy of USg-HIFU in multiple fibroids.

The Molecular Mechanisms of Ferroptosis and Its Role in Blood-Brain Barrier Dysfunction.

The blood-brain barrier (BBB) is a selective, semi-permeable layer of endothelial cells that protects the central nervous system from harmful substances circulating in blood. It is one of the important barriers of the nervous system. BBB dysfunction is an early pathophysiological change observed in nervous system diseases. There are few treatments for BBB dysfunction, so this motivates the review. Ferroptosis is a novel cell death mode caused by iron-mediated lipid peroxidation accumulation, which has recently attracted more attention due to its possible role in nervous system disorders. Studies have shown that lipid peroxidation and iron accumulation are related to the barrier dysfunction, especially the expression of tight junction proteins. Therefore, examination of the relationship between ferroptosis and BBB dysfunction may reveal new targets for the treatment of brain diseases.