Diabetic retinopathy (DR) is the leading cause of new-onset blindness. The roles of microRNAs in diabetic retinopathy are largely unknown. The aim of this study is to investigate the role of miR20b in DR. Transfection of miR-20b mimic in high glucose (HG)-treated human retinal endothelial cells (HRECs) increased miR-20b expression and decreased the expression level of VEGF mRNA, while transfection of miR-20b inhibitor in control HRECs reduced the miR-20b expression with a corresponding increase of VEGF mRNA. In vitro functional assay showed that transfection of miR-20b mimic prevented HG-induced increase in transendothelial permeability and tube formation in HRECs. Transfection of miR-20b inhibitor or treatment of VEGF increased transendothelial permeability and tube formation in control HRECs. Luciferase reported assay showed that AKT3 is a target of miR-20b. Transfection of miR-20b mimic prevented the up-regulation of AKT3 induced by HG without changing the protein levels of other isoforms of AKT, and silencing of AKT3 caused decrease of VEGF mRNA and protein levels as well as prevented HG-induced increase in transendothelial permeability and tube formation. Finally, we showed that miR-20b was down-regulated in the retina and retinal endothelial cells in diabetic rats, with a correlated up-regulation of VEGF and AKT3. Intravitreal injection of miR-20b mimic in the diabetic rat significantly increased the miR-20b expression and decreased the expression levels of AKT3 and VEGF in the retina tissues, and intravitreal delivery of AKT3 siRNA in the diabetic rat significantly decreased the expressions of AKT3 and VEGF. Collectively, miR-20b is important for the regulation of VEGF-mediated changes in HRECs and rat retinal tissues under hyperglycemic conditions possibly via targeting AKT3.

BackgroundThe optimal procedure for maximizing the diagnostic yield and minimizing the procedural complexity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is controversial. We conducted a prospective randomized controlled trial to determine the optimal procedure of EBUS-TBNA for mediastinal and hilar lymphadenopathy, with a particular focus on the roles of the inner-stylet and suction.MethodsConsecutive patients with enlarged mediastinal and hilar lymph nodes (LNs), detected by computed tomography (CT) or positron emission tomography-CT (PET-CT), who underwent EBUS-TBNA were included. Each LN was sampled with three needle passes using suction–stylet, suction–no stylet, and stylet–no suction procedures. The samples were smeared onto glass slides for cytological evaluation. A single, blinded cytopathologist evaluated each set of slides. The primary outcomes were cytological specimen adequacy rate and diagnostic yield of malignant LNs. The secondary outcomes were tissue-core acquisition rate, procedural time, and the amount of bleeding.ResultsThis study evaluated 97 patients with a total of 255 LNs. The final LN diagnosis was benign in 144, malignant in 104, and inadequate in 7 cases. There were no significant differences among the suction–stylet, suction–no stylet, and stylet–no suction groups in specimen adequacy rate (87.1, 88.2, 85.9%, respectively) or diagnostic yield of malignancy (32.2, 31.8, 31.0%, respectively). However, the use of suction was associated with an increase in tissue-core acquisition rate (P <  0.001). The no-stylet procedure decreased the average procedural time by 14 s (P <  0.001). There was no significant difference in the amount of bleeding among the procedures.ConclusionsThe use of suction or non-use of an inner-stylet does not make a significant difference in cytological specimen adequacy or diagnostic yield when performing EBUS-TBNA. While omitting the stylet can simplify the procedure, applying suction can increase the tissue-core acquisition rate. These findings may assist endoscopic physicians in determining the optimal EBUS-TBNA procedure and warrant clinical verification in a future multicentre study.Trial registrationTrial registration: (ChiCTR-IOR-17010616). Retrospective registered date: 12th February, 2017.

BackgroundInappropriate treatment of non-malaria fevers with artemisinin-based combination therapies (ACTs) is a growing concern, particularly in light of emerging artemisinin resistance, but it is a behavior that has proven difficult to change. Pay for performance (P4P) programs have generated interest as a mechanism to improve health service delivery and accountability in resource-constrained health systems. However, there has been little experimental evidence to establish the effectiveness of P4P in developing countries. We tested a P4P strategy that emphasized parasitological diagnosis and appropriate treatment of suspected malaria, in particular reduction of unnecessary consumption of ACTs.MethodsA random sample of 18 health centers was selected and received a refresher workshop on malaria case management. Pre-intervention baseline data was collected from August to September 2012. Facilities were subsequently randomized to either the comparison (n = 9) or intervention arm (n = 9). Between October 2012 and November 2013, facilities in the intervention arm received quarterly incentive payments based on seven performance indicators. Incentives were for use by facilities rather than as payments to individual providers. All non-pregnant patients older than 1 year of age who presented to a participating facility and received either a malaria test or artemether-lumefantrine (AL) were eligible to be included in the analysis. Our primary outcome was prescription of AL to patients with a negative malaria diagnostic test (n = 11,953). Our secondary outcomes were prescription of AL to patients with laboratory-confirmed malaria (n = 2,993) and prescription of AL to patients without a malaria diagnostic test (analyzed at the cluster level, n = 178 facility-months).ResultsIn the final quarter of the intervention period, the proportion of malaria-negative patients in the intervention arm who received AL was lower than in the comparison arm (7.3 % versus 10.9 %). The improvement from baseline to quarter 4 in the intervention arm was nearly three times that of the comparison arm (ratio of adjusted odds ratios for baseline to quarter 4 = 0.36, 95 % CI: 0.24–0.57). The rate of prescription of AL to patients without a test was five times lower in the intervention arm (adjusted incidence rate ratio = 0.18, 95 % CI: 0.07–0.48). Prescription of AL to patients with confirmed infection was not significantly different between the groups over the study period.ConclusionsFacility-based incentives coupled with training may be more effective than training alone and could complement other quality improvement approaches.Trial registrationThis study was registered with ClinicalTrials.gov (NCT01809873) on 11 March 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0497-y) contains supplementary material, which is available to authorized users.