Yang Chen

MicroRNA (miRNA) mediates RNA interference to regulate a variety of innate immune processes, but how miRNAs coordinate the mechanisms underlying acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with pulmonary inflammatory injury is still unknown. In this study, we demonstrated that miR-223 limits the number of Ly6G+ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate ALI induced by mitochondrial damage-associated molecular patterns (DAMPs) (MTDs). miR-223 expression is increased in the lungs of MTD-induced mice or ARDS patients following trauma/transfusion or following the physiological remission of ALI/ARDS. miR-223-/+ mice exhibited more severe ALI and cytokine dysregulation. Other studies have shown that MTD-induced increases in miR-223 expression are mainly contributed by Ly6G+ neutrophils from the haematopoietic system. miR-223 blocks bone marrow-derived Ly6G+ neutrophil differentiation and inhibits peripheral cytokine release. In addition, MTD-induced miR-223 expression activates a negative feedback pathway that targets the inhibition of NLRP3 expression and IL-1β release; therefore, miR-223 deficiency can lead to the sustained activation of NLRP3-IL-1β. Finally, elimination of peripheral Ly6G+ neutrophils and pharmacological blockade of the miR-223-NLRP3-IL-1β signalling axis could alleviate MTD-induced ALI. In summary, miR-223 is essential for regulating the pathogenesis of DAMP-induced ALI.

Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological endocrine conditions affecting reproductive women. It can feature a variety of symptoms, such as obesity, insulin resistance, skin conditions, and infertility. Women with PCOS are susceptible to illnesses including mood disorders, diabetes, hypertension, and dyslipidemia. Among them, depression is the most common in PCOS and has a detrimental effect on quality of life. Depression may occasionally develop due to the pathological traits of PCOS, but its exact pathogenesis in PCOS have eluded researchers to date. Therefore, there is an urgent need to explore the pathogenesis and treatments of depression in PCOS. The present review discusses the epidemiology of depression in PCOS, potential pathogenic mechanisms underlying PCOS and depression, as well as some potential factors causing depression in PCOS, including obesity, insulin resistance, hyperandrogenism, inflammation, and infertility. Meanwhile, some common treatment strategies for depression in PCOS, such as lifestyle intervention, acupuncture, oral contraceptive pills, psychological intervention, and insulin-sensitizer, are also reviewed. To fully understand the pathogenesis and treatment of depression in PCOS, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies.

Importance: Clinical guidelines recommend that children with pleural empyema be treated with chest tube insertion and intrapleural fibrinolytics. The addition of dornase alfa (DNase) has been reported to improve outcomes in adults but remains unproven in children. Objective: To determine if intrapleural tissue plasminogen activator (tPA) and DNase is more effective than tPA and placebo at reducing hospital length of stay in children with pleural empyema. Design, Setting, and Participants: This multicenter, parallel-group, placebo-controlled, superiority randomized clinical trial included children diagnosed as having pleural empyema requiring drainage aged 6 months to 18 years treated at 6 tertiary Canadian children's hospitals. A total of 379 children were assessed for eligibility; 281 were excluded and 98 were randomized. One child was excluded after randomization for not meeting the inclusion criteria. Data were collected from March 4, 2013, to December 13, 2017. Interventions: Participants underwent chest tube insertion and 3 daily administrations of intrapleural tPA, 4 mg, followed by DNase, 5 mg (intervention group), or 5 mL of normal saline (placebo; control group). Participants, families, clinical staff, and members of the study team were blinded to allocation. Main Outcomes and Measures: The primary outcome was hospital length of stay from chest tube insertion to discharge. Secondary outcomes included time to meeting discharge criteria, time to chest tube removal, mean fever duration, additional pleural drainage procedures, hospital readmissions, and total health care cost. Results: Of the 97 analyzed children with pleural empyema, 52 (54%) were male, and the mean (SD) age was 5.1 (3.6) years. A total of 49 children were randomized to tPA and DNase and 48 were randomized to tPA and placebo. Treatment with tPA and DNase was not associated with decreased hospital length of stay compared with tPA and placebo (mean [SD] length of stay, 9.0 [4.9] vs 9.1 [5.3] days; mean difference, -0.1 days; 95% CI, -2.0 to 2.1; P = .96). Similarly, no significant differences were observed for any of the secondary outcomes. Of the 14 adverse events in the tPA and DNase group, 6 (43%) were serious; of the 21 adverse events in the tPA and placebo group, 8 (38%) were serious. There were no deaths. Conclusions and Relevance: The addition of DNase to intrapleural tPA for children with pleural empyema had no effect on hospital length of stay or other outcomes compared with tPA with placebo. Clinical practice guidelines should continue to support the use of chest tube insertion and intrapleural fibrinolytics alone as first-line treatment for pediatric empyema. Trial Registration: ClinicalTrials.gov identifier: NCT01717742.