In recent years, adeno-associated virus (AAV) has become the most important vector for central nervous system (CNS) gene therapy. AAV has already shown promising results in the clinic, for several CNS diseases that cannot be treated with drugs, including neurodegenerative diseases, neuromuscular diseases, and lysosomal storage disorders. Currently, three of the four commercially available AAV-based drugs focus on neurological disorders, including Upstaza for aromatic l-amino acid decarboxylase deficiency, Luxturna for hereditary retinal dystrophy, and Zolgensma for spinal muscular atrophy. All these studies have provided paradigms for AAV-based therapeutic intervention platforms. AAV gene therapy, with its dual promise of targeting disease etiology and enabling 'long-term correction' of disease processes, has the advantages of immune privilege, high delivery efficiency, tissue specificity, and cell tropism in the CNS. Although AAV-based gene therapy has been shown to be effective in most CNS clinical trials, limitations have been observed in its clinical applications, which are often associated with side effects. In this review, we summarized the therapeutic progress, challenges, limitations, and solutions for AAV-based gene therapy in 14 types of CNS diseases. We focused on viral vector technologies, delivery routes, immunosuppression, and other relevant clinical factors. We also attempted to integrate several hurdles faced in clinical and preclinical studies with their solutions, to seek the best path forward for the application of AAV-based gene therapy in the context of CNS diseases. We hope that these thoughtful recommendations will contribute to the efficient translation of preclinical studies and wide application of clinical trials.

Transient tachypnea of the newborn (TTN) is one of the most common causes of perinatal dyspnea and is traditionally diagnosed by chest x-ray. This study aimed to explore the diagnostic value of lung ultrasonography (LUS) for TTN as well as differentiate it from respiratory distress syndrome (RDS) by using LUS. From January 2013 to February 2014, 60 infants who were diagnosed with TTN based on medical history, clinical manifestations, arterial blood gas analysis, and chest radiography were recruited to the study group. During the same period, 40 hospitalized neonates with nonlung diseases and 20 patients with RDS were recruited to the control group. In a quiet state, infants were placed in the supine, lateral, or prone position for the examination. Each lung of every infant was divided into 3 regions: the anterior, lateral, and posterior regions as bordered by the anterior axillary and posterior axillary lines. The probe was placed perpendicular to the ribs. Each region of both the lungs was carefully scanned.The common ultrasonographic manifestations of TTN were double-lung point (DLP), interstitial syndromes or white lungs, pleural line abnormalities, and A-line disappearance. A small number of infants (20%) with TTN exhibited pleural effusions, whereas the main ultrasonographic manifestation of RDS was lung consolidation with air bronchograms, which does not occur in TTN. The sensitivity and specificity of DLP for the diagnosis of TTN were 76.7% and 100%, respectively. LUS can accurately and reliably diagnose TTN. The DLP and lung consolidation possess great value in the diagnosis and differential diagnosis of TTN with RDS. Thus, we believe that LUS can be widely used in neonatal intensive care units.

Ultrasound is a safe bedside imaging tool that obviates the use of ionizing radiation diagnostic procedures. Due to its convenience, the lung ultrasound has received increasing attention from neonatal physicians. Nevertheless, clear reference standards and guideline limits are needed for accurate application of this diagnostic modality. This document aims to summarize expert opinions and to provide precise guidance to help facilitate the use of the lung ultrasound in the diagnosis of neonatal lung diseases.

Accompanied by the increasing demand for organ transplants and personalized medicine, recent years have witnessed great developments in the regeneration of tissues/organs, which has benefited from various manufacturing technologies, especially 3D bioprinting. In 3D bioprinting, according to the morphogenesis, cellular microenvironment, and biological functions of the native tissues/organs, cells and biomaterials are printed by layer-by-layer assembly to form 3D bio-functional units. However, there are still substantial differences between existing 3D printed constructs and actual tissues and organs, especially in microscale structures such as vascular networks. By manipulating controllable fluids carrying biomolecules, cells, organisms, or chemical agents, microfluidic techniques aim to integrate biological or chemical functional units into a chip. With its features of biocompatibility, flexible manipulation, and scale integration on the micro/nanoscale, microfluidics has been a tool that has enabled the generation of micro-tissues/organs with precise configurations. With the inspiration of these two technologies, there have been efforts to fabricate functional living tissues and artificial organs with complex structures via a combination of 3D bioprinting and microfluidics, which may lead to unexpected effects. In this review, we discuss advances in microfluidics-assisted bioprinting in the engineering of tissues/organs and provide future perspectives for this combination in the generation of highly biomimetic tissues and organs in vitro.