The exploration of pathogenic single nucleotide polymorphisms in the genome plays a pivotal role in the study of human disease-associated genetic mutations. However, there remains a lack of suitable high-throughput screening platforms to investigate the impact of point mutations on genomic structure and function. CRISPR/Cas9-mediated base editors has enabled large-scale annotation of the human genome and phenotypic characterization of monogenic disorders. Base editors, a precise gene-editing technique capable of achieving targeted base substitutions, can be employed to induce mutations at specific functional sites, thereby observing their effects on gene expression, protein function, and cellular phenotypes. Furthermore, integrating base editors with high-throughput screening technologies allows for large-scale evaluation of multiple candidate sites, accelerating the identification of functional loci and providing a powerful tool for disease research and therapeutic target discovery. This article aims to introduce the working principles of various base editors, including cytosine base editors, adenine base editors, and prime editors, and summarize recent advances in high-throughput screening of functional genomic sites using base-editing techniques.
Humans ; Gene Editing/methods* ; CRISPR-Cas Systems/genetics* ; Genome, Human ; Polymorphism, Single Nucleotide

Objective To evaluate the relative safety of different ventilation methods regarding mortality and rates of complication,on neonatal respiratory distress syndrome (NRDS).Methods Network Meta-analysis was used to collect data on randomized controlled trials of pulmonary ventilation strategies in preterm infants with a mean gestational age of less than 32 weeks.Diagnostic criteria on NRDS were published in the PubMed,Cochrane,Web of Science,EBSCO,and Springer Link databases from January 1986 to June 2018.Revman 5.3 software was used to evaluate the quality of studies,based on the Cochrane quality assessment tool.Data were analyzed by Bayesian and frequency methods,using both Win BUGS 1.4.3 and STATA 13.0 software.Safety of different ventilation strategies for NRDS mortality and complications would include intraventficular hemorrhage (IVH),patent ductus arteriosus (PDA) and retinopathy of prematurity (ROP) and were evaluated.Counted data was displayed by OR and 95％CI.Results A total of 31 RCTs were included in this paper,including 5 827 preterm infants and 11 ventilation strategies.There were no statistically significant differences appearing in 11 ventilation strategies on mortality,PDA or ROE IVH results were reported in 28 studies.Compared with nasal intermittent positive pressure ventilation (NIPPV),both high-frequency oscillation ventilation (HFOV) (OR=3.33,95％ CI:1.08-16.67,P＜0.05) and synchronized intermittent mechanical ventilation (SIMV) (OR=8.22,95％CI:1.25-29.44,P＜0.05) schemes seemed to have increased the risk of IVH in preterm infants with NRDS.NIPPV appeared the optimal ventilation strategy in the rankings of cumulative probability.Results on clustering showed that NIPPV was probably the best ventilation strategy for children with NRDS after considering the orders of IVH,PDA and ROP on mortality,respectively.However,HFOV,IMV,and SIMV did not seem to be the ideal ventilated strategies.Conclusions Most of the clinical decision makers might prefer using NIPPV in the treatment of children with NRDS through mechanical ventilation systems to reduce both the incidence and death caused by IVH,PDA and ROP.It was not recommended to use HFOV,SIMV and IMV in treating NRDS with gestational less than 32 weeks.We suggested that larger numbers of multi-center RCTs ba carried out to make the above conclusions more convincing.