Targeted Antagonism of Vascular Endothelial Growth Factor Reduces Mortality of Mice with Acute Respiratory Distress Syndrome

Summary:Acute respiratory distress syndrome(ARDS)is associated with a mortality of 45%.Our previous rescarch indicated that anti-vascular endothelial growth factor(VEGF)could maintain the normal structure and function of the respiratory barrier.However,systemic application of VEGF antagonists would lead to animal death.This study attempts to study the targeted drug delivery for ARDS.In this study,we used soluble fims-like tyrosine kinase-1(sFlt)-targeted ultrasound microbubbles to antagonize the effect of VEGF on lung tissue.Ninety male BALB/C mice were randomly assigned to 6 groups:phosphate buffer saline(PBS)group(PBS+PBS);blank group(PBS+empty microbubbles);lipopolysaccharide(LPS)group(LPS+PBS);ARDS group(LPS tempty microbubbles);control group(PBS+sFlt microbubbles);and treatment group(LPS+sFIt microbubbles).After administration of LPS or PBS in the corresponding groups,the sFlt-targeted microbubbles or empty microbubbles were injected into the blood circulation.Then the lungs were irradiated with ultrasound,which ruptured the drug-loaded microbubbles and helped release drugs to the lung tissues targeted.The lung injury score,lung wet/dry ratio(W/D),liver and kidney functions,and the mortality of the mice in all groups were investigated at the predetermined time point.The difference in mortality between groups was examined by Fisher test.Other data were analyzed by onc-way analysis of variance(ANOVA).A value of P<0.05 indicates that the difference was significant.The results showed that the PaO2 levels were normal in the PBS group,the blank group,and the control group.The LPS group and ARDS group showed significant hypoxia.PaO2 was improved significantly in the treatment group.The lung injury score and W/D were normal in the PBS group,the blank group,and the control group.The lung injury score and W/D increased significantly in the LPS group and ARDS group and decreased in the treatment group(P<0.05).The mortality rate of the ARDS model was 60%(95%confidence interval 47.5%-72.5%),and that with sFlt-targeted microbubbles was significantly lower at only 40%(95%confidence interval 27.5%-52.5%,P<0.05).It was concluded that anti-VEGF with sFIt targeted ultrasound microbubbles attenuated the lung injury and ultimately reduced the 7-day mortality effectively.It might be a suitable therapeutic tool for the treatment of ARDS.

Large cystic-solid pulmonary hamartoma:A case report

BACKGROUND It now seems that all pulmonary hamartomas(PHs)are large cystic-solid lesions that are difficult to diagnose.However,few cases of large cystic-solid PHs have been reported.The present case report presents a large cystic-solid PH and provides a literature review of the imaging features,formation mechanism and histopathological basis of PHs.CASE SUMMARY A 53-year-old woman with no clinical symptoms underwent a chest computed tomography(CT)examination at our hospital.Nonenhanced CT images revealed a large,flat tumor with multiple air-containing cysts in the left thoracic cavity and a cystic part confined to the medial side of the tumor;the solid part of the tumor showed abundant fat and lamellar soft tissue components.Multiple small blood vessels were detected in the solid part of the tumor on contrast-enhanced CT images.Given the large size of the lesion,the patient elected to undergo surgery.Histological examination revealed PH.A detailed review of the patient’s CT imaging showed that the lesion had a small vascular pedicle to the left lower lobe,which was a clue to its lung tissue histological origin.According to immunohistochemical staining,the confined multiple air-containing cysts were caused by the entrapment of respiratory/alveolar epithelium.CONCLUSION This case shows the imaging manifestations of a large PH.Heightened awareness of its formation mechanism and histopathological basis may alert radiologists to consider this diagnosis in their daily workflow.