1.Literature Analysis of Pediatric Drug-induced Liver Injury in China from 2007 to 2016
Xin ZHENG ; Xiongcai LU ; Xiaolian QIN ; Guanlin LI ; Jiyi WANG ; Fu LIU
China Pharmacy 2017;28(32):4507-4510
OBJECTIVE:To investigate the characteristics of pediatric drug-induced liver injury (DILI) in China,and to provide reference for reducing ADR.METHODS:Using"liver injury liver damage hepatotoxicity hepatitis liver disease""drug induced children" as keywords,related domestic literatures were retrieved from CNKI and Wanfang database during 2007-2016,clinical information of DILI children in literatures were recorded in detail and analyzed comprehensively.RESULTS:A total of 363 literatures were retrieved,including 13 effective literatures and 665 children in total.There were 424 boys (63.76%)and 241 girls (36.24%),with ratio of 1.76 ∶ 1.The youngest child was 1 month old,the oldest child was 14 years old;the average age was 7.87 years,337 children aged more then 7 years old,accounting for 50.68%.Top 3 primary diseases were respiratory tract infection (40 cases,31.50%),hematologic diseases (29 cases,22.83%) and tumor (14 cases,11.02%).Top 3 pediatric DILI-inducing drug types were antibiotics (245 cases,34.41%),TCM (143 cases,20.08%) and antipyretic analgesics (113 cases,15.87%).DILI usually happened within 4 weeks (332 cases,82.18%).The most common clinical classification was hepatocellular type (382 cases,65.30%).The severity of liver injury was mainly mild and moderate (505 cases,86.32%),and 80 cases were severe (13.68%),including 31 cases of hepatic failure (5.30%).Clinical symptoms mainly manifested as anorexia,jaundice,nausea,vomiting,hypodynamia and abdominal discomfort.After drug withdreawd and treatment,96.54% of the patients were recovered or cured,and 4 cases died (0.60%).CONCLUSIONS:Under the premise of rational use of drugs,it is necessary to carry out medication education and supervision for antibiotics,TCM and antipyretic analgesics which mainly induce pediatric DILI,pay attention to allergic history and evaluate the progress of extrahepatic symptoms.When ADR occurred,the timely and drug withdrawal intervention are conducted to improve good prognosis.
2.Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.
Yongchun PAN ; Xiaowei LUAN ; Fei ZENG ; Xuyuan WANG ; Shurong QIN ; Qianglan LU ; Guanzhong HE ; Yanfeng GAO ; Xiaolian SUN ; Xin HAN ; Bangshun HE ; Yujun SONG
Acta Pharmaceutica Sinica B 2024;14(2):795-807
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.