Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Effects of different skin interventions in the result of penicillin skin test:a network Meta-analysis / 中国实用护理杂志

Objective To evaluate the effects of seven different skin interventions in the result of penicillin skin test by network Meta-analysis. Methods A systematic search of PubMed, Cochrane Library, Web of Science, EBSCO, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang Database from construction to July 2017 was carried out. Control trials examining the effects of skin interventions on the false positive rate of penicillin skin test were included. Methodological quality of included studies was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0.All data was screened,extracted and reviewed by 2 researchers independently and analyzed by WinBUGS, R and Stata. Results Totally 18 trials involving 25 077 patients were included.The results of network Meta-analysis showed the statistically significant difference in favor of saline, 0.5% glutaral and iodine-containing disinfector when compared to alcohol (P<0.05). However,there was no difference in effects between other different skin interventions on the false positive rate (P>0.05). Probability ranking showed that there was a great possibility for saline, direct injection, 0.5% glutaral and iodine-containing disinfector in the reduction of false positive rate. Conclusions Saline, 0.5% glutaral and iodine-containing disinfector were superior to other skin interventions in reducing false positive rate of penicillin skin test.