OBJECTIVETo evaluate the application of echocardiography in diagnosis of pediatric pulmonary artery sling.

METHODSTwenty-five children diagnosed as pulmonary artery sling in the Children's Hospital, Zhejiang University School of Medicine from July 2012 to August 2017, and 50 healthy children(control group) were enrolled in the study. Echocardiography was performed in all subjects. The origins of the left pulmonary artery(LPA) and right pulmonary artery(RPA) were observed; the internal diameters of LPA, RPA and main pulmonary artery(MPA) were measured; and the ratios of LPA/MPA and RPA/MPA were calculated. The value of RPA/MPA and LPA/MPA in diagnosing pulmonary artery sling was evaluated by ROC curve.

RESULTSEchocardiography showed that the internal diameters of RPA were increased in all patients; while the LPA and blood flow signals in common pulmonary arterial bifurcation were not found in 24 cases, in whom the MPA was directly extended to the RPA, and the LPA was from the massive RPA. The ultrasound of one special case showed that there was no distinct bifurcation of MPA; the MPA walked to the right and then to the left with no change in the internal diameter. There were significant differences in RPA/MPA(0.50±0.05 vs. 0.71±0.15, =7.06, <0.01) and LPA/MPA(0.52±0.05 vs. 0.39±0.09, =6.94, <0.01) between controls and the patients. ROC curve analysis showed that the AUC of RPA/MPA and LPA/MPA in diagnosis of pulmonary artery sling were 0.90 and 0.89, respectively. When taking 0.60 as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of RPA/MPA in diagnosis of pulmonary artery sling were 79%, 100%, 100%, 91% and 93%, respectively. When taking 0.43 as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of LPA/MPA in diagnosis of pulmonary artery sling were 71%, 96%, 89%, 87% and 88%, respectively.

CONCLUSIONSs Echocardiography can effectively diagnose pediatric pulmonary artery sling. The RPA/MPA ratio of 0.60 and the LPA/MPA ratio of 0.43 can be used as cutoff values for diagnosis.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Bone Regeneration ; Cell Differentiation ; Circadian Clocks ; Cryptochromes/metabolism* ; Osteoblasts/metabolism* ; Osteogenesis ; Transcription Factors/metabolism*

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.