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Abstract Introduction Patent ductus arteriosus (PDA) is one of the most common congenital heart diseases. Once the PDA is diagnosed, it needs to be dealt with in time. At present, main methods include pharmacological treatment, surgical closure, and interventional closure for treatment of PDA. However, the effect of different interventions in PDA management is still controversial. Thus, our study aims to assess the effectiveness of different interventions together and estimate the sequence of these therapies for PDA children. Meanwhile, it is necessary to conduct a Bayesian network meta-analysis to compare the safety of different interventions comprehensively. Methods and analysis To the best of our knowledge, this is the first Bayesian network meta-analysis comparing the efficacy and safety of different interventions for the treatment of PDA. PubMed, Embase, Cochrane Library, Web of Science, gray literature, and trial registry databases were searched from inception to December 2022. We will extract and report data according to methodological guidelines for Bayesian network meta-analysis by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Primary PDA closure, overall PDA closure, technical success, surgical success rate, mortality during hospital stay, operation time, intensive care unit stay, intraoperative radiation dose, radiation exposure time, total postoperative complication rate, and postoperative major complication rate will be defined as the outcomes. The quality of all random studies will be assessed using ROB, and quality of evidence for all outcomes will be judged by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Ethics and dissemination The results will be disseminated through peer-reviewed publication. Since no private and confidential patient data will be contained in the reporting, there are no ethical considerations associated with this protocol. Systematic review registration INPLASY2020110067.

Inherited and age-related retinal degenerations are the commonest causes of blindness without effective treatments. Retinal progenitor cells (RPCs), which have the multipotency to differentiate into various retinal cell types, are regarded as a promising source of cell transplantation therapy for retinal degenerative diseases. However, the self-limited expansion of RPCs causes difficulty in cell source supply and restrict its clinical treatment. In this work, we found that inhibition of microRNA-449a (miR-449a) in RPCs can promote proliferation and inhibit apoptosis of RPCs, partially through upregulating Notch signaling. Further optimization of transduction miR-449a inhibitor into RPCs by endothelial cell-derived exosomes can promote the survival of RPCs transplanted in vivo and reduce cell apoptosis in retinal degeneration mouse models. In summary, these studies have shown that exosome-miR-449a inhibitor can effectively promote the expansion of RPCs in vitro and enhance transplanted RPCs survival in vivo, which might provide a novel intervention strategy for retinal degenerations in the future.

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders. Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here, we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting the expression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentration in serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos could be absorbed by LCs through the blood–testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serum testosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promote autophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor, 3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exos promote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novel evidence for the clinical improvement of CPTD using BMSCs-exos.

Abstract Background The effect of gender on patients with mitral valve regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR) remains to be defined. The aim of the present study is a comprehensive meta-analysis of studies that investigate differences between men and women after TMVR. Methods A systematic literature search was carried out on eight databases to collect all relevant studies on gender-related outcomes of TMVR before March 1, 2021. The main outcomes of interest were mortality, cardiac function, MR class and other complications. Results A total of eight literatures were included, all of which were retrospective observational studies. Compared to women patients, men had lower postoperative New York Heart Association (NYHA) class (OR = 1.53, 95%CI [1.23, 1.91], P = 0.0001) and higher incidence of postoperative acute kidney injury (AKI) (OR = 1.25, 95%CI [1.16, 1.34], P

Schools play a major role in delivering behavioral health services to autistic youth. School culture and climate are strong predictors of the extent to which these services incorporate evidence-based practices; however, little is known about how school leaders shape culture and climate. Drawing on the concept of culture and climate embedding mechanisms, we conducted a qualitative study to understand the ways in which school principals embed cultures and climates that support effective implementation of evidence-based practices for youth with autism. Semi-structured interviews with 32 teachers in schools that implemented three closely related evidence-based practices for youth with autism (discrete trial training, pivotal response training, and visual schedules) explored teachers' experiences regarding (a) implementation of the three evidence-based practices, (b) perceptions of school culture and climate, and (c) principals' behaviors, practices, and decisions that supported or detracted from the aspects of culture and climate that supported successful implementation. Thematic analysis detailed seven mechanisms that principals used to embed cultures and climates that shaped evidence-based practice implementation. These mechanisms represent actionable targets for school leaders and inform strategies to improve the implementation of evidence-based practices for youth with autism in schools.

Background: Ventricular septal defects (VSDs) are one of the mechanical complications of acute myocardial infarction (AMI). Because of the high risks of mortality and postoperative complications, a new alternative method is needed. With the development of interventional medicine, transcatheter closure has been increasingly performed for postmyocardial infarction ventricular septal defects (PMIVSDs). The aim of this study is to explore the feasibility and safety of transcatheter closure of PMIVSDs by meta-analysis. Methods: The included studies were mainly single-arm studies of transcatheter closure of PMIVSDs. We compared VSD size, device size, preoperative risk factors and interventions among PMIVSD patients. We analysed the transcatheter closure success rate, the 30-day mortality rate, and the incidence of residual shunts. Results: A total of 12 single‐arm articles (284 patients) were included. The combined incidences of preoperative hypertension, hyperlipidaemia, and diabetes were 66% [95% CI 0.56–0.75], 54% [95% CI 0.40–0.68], and 33% [95% CI] 0.21–0.46], respectively. Multiple studies reported the combined incidences of preoperative PCI, IABP, and CABG, which were 46% [95% CI 0.15–0.80], 60% [95% CI 0.44–0.75], and 8% [95% CI 0.02–0.18]. Eleven studies reported the number of successful closures and the 30-day mortality rate; the success rate was 90% [95% CI 0.86–0.94], and the 30-day mortality rate reached 27% [95% CI 0.86–0.94]. Conclusion: For patients with PMIVSD, transcatheter closure in the acute phase can be used as a rescue measure, while in the chronic phase, it is more effective and has a lower mortality rate, but the effect of selection bias should be considered. Residual shunts are a long-term complication that have a high incidence and long-lasting effects on patients. More large, multicentre, randomized controlled trials are needed in the future to confirm the safety and reliability of transcatheter closure of PMIVSDs.

With an aging population and the numerous health impacts associated with old age, the identification of anti-aging drugs has become an important new research direction. Although mitochondria have been recognized to affect aging, anti-aging drugs specifically targeting the mitochondria are less well characterized. In this study, diphenyleneiodonium (DPI) was identified as a potential senomorphic drug that functions by promoting mitochondrial fission. DPI significantly reduced the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and increased the number of proliferating Ki-67 positive cells in BrdU or irradiation stress-induced senescent NIH3T3 cells or IMR90 cells and mouse embryonic fibroblasts (MEFs) replicative senescent cells. Cell cycle arrest genes and senescence-associated secretory phenotype (SASP) factors were downregulated with DPI treatment. In addition, the oxygen consumption rate (OCR) of mitochondrial respiration showed that DPI significantly reduced senescence-associated hyper OCR. Mechanistically, DPI promoted mitochondrial fission by enhancing AMPK/MFF phosphorylation and DRP1 mitochondrial translocation. Inhibition of DRP1 by Mdivi-1 abolished DPI-induced mitochondrial fission and the anti-senescence phenotype. Importantly, Eighty-eight-week-old mice treated with DPI had significantly reduced numbers of SA-β-gal positive cells and reduced expression of cell cycle arrest genes and SASP factors in their livers and kidneys. Pathological and functional assays showed DPI treatment not only reduced liver fibrosis and immune cell infiltration but also improved aged-related physical impairments in aged mice. Taken together, our study identified a potential anti-aging compound that exerts its effects through modulation of mitochondrial morphology.