Newly Proposed Diagnostic Criteria for Acute Respiratory Distress Syndrome: Does Inclusion of High Flow Nasal Cannula Solve the Problem?

Acute respiratory distress syndrome (ARDS) is a common life-threatening clinical syndrome which accounts for 10% of intensive care unit admissions. Since the Berlin definition was developed, the clinical diagnosis and therapy have changed dramatically by adding a minimum positive end-expiratory pressure (PEEP) to the assessment of hypoxemia compared to the American-European Consensus Conference (AECC) definition in 1994. High-flow nasal cannulas (HFNC) have become widely used as an effective respiratory support for hypoxemia to the extent that their use was proposed in the expansion of the ARDS criteria. However, there would be problems if the diagnosis of a specific disease or clinical syndrome occurred, based on therapeutic strategies

Chitosan-conjugated lipid microbubble combined with ultrasound for efficient gene transfection

Non-viral vectors, as gene carriers, have advantages of biological safety and cost-efficiency over viral vectors. However, low transfection efficiency hampers their further clinical application. In this study, we developed a novel chitosan-conjugated lipid microbubble (CMB), which has good biocompatibility and high gene loading capacity. By ultrasound-targeted microbubble destruction (UTMD) technology, plasmid DNA could be efficiently delivered into HEK293T cells. The parameters for UTMD including acoustic intensity (AI), duty cycle (DC), exposure time (ET) and microbubble concentration were systematically optimised. Under the optimal conditions (AI, 1.0 W/cm2; DC, 10%; ET, 60 s; 10% CMBs), the gene transfection efficiency was significantly enhanced, without obvious impairment of the cell viability (over 80%). This study described a novel gene transfection strategy that combines CMBs with ultrasound to facilitate safe and efficient gene transfection in vitro with the potential for in vivo targeted gene delivery

Synergistic ultrasonic biophysical effect-responsive nanoparticles for enhanced gene delivery to ovarian cancer stem cells

Ovarian cancer stem cells (OCSCs) that are a subpopulation within bulk tumor survive chemotherapy and conduce to chemo-resistance and tumor relapse. However, conventional gene delivery is unsuitable for the on-demand content release, which limits OCSCs therapeutic utility. Here, we reported ultrasound-targeted microbubble destruction (UTMD)-triggerable poly(ethylene glycol)-disulfide bond-polyethylenimine loaded microbubble (PSP@MB). Taking advantage of glutathione (GSH) responsiveness, ultrasound triggering and spatiotemporally controlled release manner, PSP@MB is expected to realize local gene delivery for OCSCs treatment. But the biophysical mechanisms of gene delivery via PSP@MB and ultrasound remain unknown. The aim of this study is to determine the potential of gene delivery to OCSCs via ultrasonic synergistic biophysical effects and GSH-sensitive PSP@MB. The GSH-sensitive disulfide bond cleavable properties of PSP@MB were confirmed by 1H NMR spectra and infrared spectroscopy. The biophysical mechanisms between PSP@MB and cells were confirmed by scanning electron microscopy (SEM) and confocal laser scanning microscope (CLSM) to optimize the ultrasonic gene delivery system. The gene transfection via ultrasound and PSP@MB was closely related to the biophysical mechanisms (sonoporation, enhanced-endocytosis, sonoprinting, and endosomal escape). Ultrasound combined with PSP@MB successfully delivered aldehyde dehydrogenase 1 (ALDH1) short hairpin RNA (shRNA) plasmid to OCSCs and promoted apoptosis of OCSCs. The gene transfection rate and apoptosis rate were (18.41 ± 2.41)% and (32.62 ± 2.36)% analyzed by flow cytometry separately. This study showed that ultrasound triggering and GSH responsive PSP@MB might provide a novel strategy for OCSCs treatment via sonoporation and enhanced-endocytosis