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Objective: To identify the platelet-related biomarkers in Proliferative diabetic retinopathy (PDR). Methods: Two mRNA expression profiles of PDR (GSE102485 and GSE60436) were downloaded from the Gene Expression Omnibus (GEO) database with the platelet-related genes from gene set enrichment analysis (GSEA) database. A protein-protein interaction (PPI) network was established to screen out hub genes based on the interaction between differentially expressed platelet-related genes (DEPRGs), followed by the prediction of the associated microRNAs (miRNAs), transcription factors (TFs) and drugs, which were taken to establish the regulatory networks of miRNA-hub gene, TF-hub gene and drug-hub gene. To verify the expression of Hub genes, both retinal samples from experimental diabetes mouse models and human retina microvascular endothelial cells (HRMECs) treated with high glucose (HG) were subjected to quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: A total of 168 DEPRGs were determined, with 146 genes for upregulation and 22 for downregulation. 9 hub genes (CDC42, GNAI2, LCK, LCP2, LYN, PLCG2, PTPN6, RAC1 and SYK) were eventually screened. 446 miRNAs, 46 TFs and 138 hub gene targeted by drugs were presented after prediction. RAC1 and GNAI2 respectively targeted by 156 miRNAs and 19 TFs lied the most connected hub genes in the miRNA-hub gene and TF-hub gene regulatory networks. Based on the drug-hub gene regulatory network, LCK was targeted by 52 drugs. qRT-PCR results indicated that the expression of LPC2 and PTPN6 was upregulated in both diabetes mouse models and HRMECs treated with HG. Conclusions: Nine hub genes were screened with the prediction of miRNAs, which were targeted by TFs and drugs, and may play an essential role in the progression of PDR, utilized as potential biomarkers and therapeutic targets.

Purpose Chemoresistance remains the primary obstacle threatening the prognosis of retinoblastoma (RB). microRNAs (miRNAs) are acknowledged as critical regulator of drug resistance. This study explored the molecular mechanism of miR-130a-3p affecting the chemosensitivity of RB to vincristine (VCR). Methods miR-130a-3p expression of VCR-sensitive and VCR-resistant RB tissues was detected using RT-qPCR. VCR-resistant RB cell line Y79/VCR was induced. miR-130a-3p expression of Y79/VCR cell line and its corresponding parental cell line was detected. Y79/VCR cells were subjected to miR-130a-3p overexpression treatment. The cell proliferation was measured using MTT assay, and the IC50 value and drug resistance index were examined using CCK-8 assay. The targeting relationship between miR-130a-3p and PAX6 was predicted through bioinformatics analysis and verified using dual-luciferase assay. Functional rescue experiments were conducted to confirm the role of PAX6 in chemosensitivity of RB cells. The effect of miR-130a-3p on tumorigenesis and VCR sensitivity was observed in vivo. Results miR-130a-3p was downregulated in VCR-resistant RB tissues and cells. Overexpression of miR-130a-3p repressed the proliferation of VCR-resistant RB cells and enhanced chemosensitivity. miR-130a-3p targeted PAX6 expression. Overexpression of PAX6 reversed the effect of miR-130a-3p on chemosensitivity of RB. Overexpression of miR-130a-3p suppressed tumor growth and reduced VCR resistance in vivo. Conclusion miR-130a-3p enhanced the chemosensitivity of RB cells to VCR by targeting PAX6 expression.

Background: Extracorporeal membrane oxygen (ECMO) has used for rescuing severe pediatric acute respiratory distress syndrome (PARDS) for half a century. Prone position ventilation (PPV) has been suggested according to the surviving sepsis campaign (SSC) guideline in children in 2020. We aimed to compare the outcomes and effect of PARDS patients with ECMO+PPV and ECMO only.Design: Retrospective Multicenter pair-matched StudySetting: In the present study, propensity score matching was conducted and the outcomes of severe PARDS patients were analyzed. The effect of PPV was compared as well. The efficiency of PPV included PaO2, Oxygen Index (OI), PaO2/FiO2, compliance of respiratory system and resistance of airway. The primary outcome was hospital mortality. Secondary outcomes included ECMO running time, PICU time, hospital days and mechanical ventilation time of survivors. Patients: 137 PARDS patients with criteria of ECMO from 11 hospitals in 5 years.Interventions: No interventions.Measurements and Main Results: Among 137 patients, 93 patients received ECMO+PPV at the same time and 44 patients didn’t. After matching, we got 34 pairs. For the survivors receiving ECMO+PPV, the PaO2, OI and PaO2/FiO2 increased significantly during the PPV period (PConclusions: By far, there has been no ECMO+PPV efficiency study in PARDS patients. This study found that PPV was associated with improved oxygen state during ECMO. However, PPV was not associated with survival rate with PARDS patients on ECMO. Clinical Trial Registration: This study was registered at http://www.chictr.org.cn/index.aspx (chiCTR.gov; Identifier: ChiCTR1800019555). Registered 18 November 2018. Name of the registry: Extracorporeal membrane oxygenation in critical ill children with severe acute respiratory distress syndrome - A multicenter study.Take Home Message:1. Our study investigated prone position ventilation (PPV) could improve the oxygen state during ECMO for patients with severe PARDS.2. The results indicated PPV had no influence on the mortality of PARDS with ECMO.