Research Progress on Structure-Activity Relationship of 1,8-Naphthalimide DNA Chimeras Against Tumor.

The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.

Analysis of risk factors for early stent thrombosis in the Chinese population: A multicenter restrospective study.

BACKGROUND: The predictive scoring systems for early stent thrombosis (EST) remains blank in China. The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population. METHODS: EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention (PCI). Patients from ten Chinese hospitals diagnosed as stent thrombosis (ST) from January 2010 to December 2016 were retrospectively included as the study group. A control group (1 case:2 controls) was created by including patients without ST, major adverse cardiovascular events, or cerebrovascular events during follow-up. The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients, who were included to identify factors that predicted EST and to develop a prediction scoring system. The other 171 patients without integrated 1:2 pair were used for external validation. RESULTS: EST was independently associated with a low hemoglobin concentration (adjusted odds ratio [OR] 0.946, 95% confidence interval [95% CI] 0.901-0.993, P=0.026), a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score (OR 1.166, 95% CI 1.049-1.297, P=0.004), and a DAPT (DAPT) duration of <30 days (OR 28.033, 95% CI 5.302-272.834, P<0.001). The simple EST prediction score provided an area under the curve (AUC) of 0.854 (95% CI 0.777-0.932, P<0.001) with 70.0% sensitivity and 90.0% specificity, and 0.742 (95% CI 0.649-0.835, P<0.001) with 54.5% sensitivity and 81.0% specificity for external validation dataset. CONCLUSIONS: EST may be independently associated with DAPT discontinuation within 30 days, a low hemoglobin concentration, and a high SYNTAX score. The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.

Residual platelet reactivity is preferred over platelet inhibition rate in monitoring antiplatelet efficacy: insights using thrombelastography.

Although thrombelastography (TEG) has been widely implemented in the clinical setting of endovascular intervention, consensus on the optimal parameter for defining high ischemic risk patients is lacking due to the limited data about the relationship between various TEG parameters and clinical outcomes. In this article, we report a post hoc analysis of a prospective, single-center cohort study, including 447 patients with acute coronary syndrome (ACS). Arachidonic acid (AA)- or adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAAA or MAADP) was indicative of the net residual platelet reactivity after the treatment with aspirin or clopidogrel, respectively. AA% or ADP% was indices of the relative platelet inhibition rate on AA or ADP pathway. We found that each parameter alone was predictive of the risk of 6-month ischemic event, even after adjusting for confounding factors. However, the association between AA% and clinical outcome disappeared when further adjusted for MAAA. Likewise, inclusion of MAADP changed the significant relation between ADP% and clinical outcome. MAADP > 47.0 mm and MAAA > 15.1 mm were identified as the optimal cutoffs by receiver operating characteristic analysis. High MAAA (HR = 3.963; 95% CI: 1.152-13.632; P = 0.029) and high MAADP (HR = 5.185; 95% CI: 2.228-12.062; P < 0.001) were independent predictors when both were included in multivariable Cox regression hazards model. Interestingly, an even higher risk was found for the coexisting high MAAA and high MAADP (HR = 7.870; 95% CI: 3.462-17.899; P < 0.001). We conclude that when performing TEG to predict clinical efficacy, residual platelet reactivity has superiority over platelet inhibition rate as a measure of thrombotic risk in patients treated with aspirin and clopidogrel after ACS.