In-depth look into urban and rural disparities in prehospital delay in patients with acute ST-elevation myocardial infarction and its impact on prognosis: a prospective observational study.

OBJECTIVES: In line with the cardiac fast track, the 'green pathway for patients with heart attack' policy in China is implemented to reduce door-to-balloon time in patients with ST-segment elevation myocardial infarction (STEMI). However, the difference in prehospital delay between urban and rural areas of China and its impact on prognosis is unclear. DESIGN: Prospective observational study. SETTING: This study was conducted in a tertiary hospital, the only nationally accredited chest pain centre with percutaneous coronary intervention (PCI) capacity in Pizhou, China. PARTICIPANTS: 394 patients with STEMI without patients with in-hospital STEMI or patients lost to follow-up were included. PRIMARY OUTCOME MEASURES: Primary outcome was major adverse cardiovascular events (MACEs), including cardiac death, non-fatal myocardial infarction and heart failure. RESULTS: Among 394 patients enrolled, 261 (66.2%) were men, the median age was 69 years (interquartile range: 61-77 years), and 269 (68.3%) were from rural areas. Symptom-to-door (S2D) time was significantly longer for rural patients than for urban patients (p<0.001). Cox regression analyses revealed living in rural areas was independently associated with prolonged S2D time (adjusted HR 0.59; 95% CI 0.43 to 0.81; p=0.001). HR of <1 indicates that the S2D time is longer for patients in the rural group (group of interest). During 1-year follow-up, the incidence of MACEs was higher in rural patients (p=0.008). The unadjusted OR for MACEs between rural and urban patients was 2.22 (95% CI 1.22 to 4.01). Adjusting for sex did not attenuate the association (OR 2.06; 95% CI 1.13 to 3.76), but after further adjusting for age, cardiac function classification, S2D time and performance of primary PCI, we found that odds were similar for rural and urban patients (OR 1.19; 95% CI 0.59 to 2.38). CONCLUSIONS: Rural patients with STEMI had a longer S2D time, which led to a higher incidence of MACEs. This study provides rationales for taking all the measures to avoid prehospital delay.

Antithrombotic Therapy With Ticagrelor in Atrial Fibrillation Subjects After Percutaneous Coronary Intervention.

Background: Warfarin, along with aspirin and clopidogrel, has long been recommended for patients with atrial fibrillation (AF) who are undergoing percutaneous coronary intervention with a drug-eluting stent (PCI-DES). However, this triple therapy has been known to increase the risk of bleeding complications. Meanwhile, there is no evidence from prospective trials on the use of ticagrelor in a dual therapy. We here aimed to compare the antiplatelet drug ticagrelor as a dual antithrombotic agent to aspirin and clopidogrel in bleeding events. Methods: In this multicenter, active-controlled, open-label, randomized trial, patients with AF taking warfarin who had undergone PCI-DES were randomly assigned to the ticagrelor therapy group (Dual group) or the clopidogrel plus aspirin therapy group (Triple group). The primary and secondary endpoints were overall bleeding events and major bleeding events, respectively, according to the Thrombolysis in Myocardial Infarction (TIMI) criteria at 6 months. Cardiovascular events [re-PCI, surgical bypass, myocardial infarction (MI), heart failure, rehospitalization due to angina pectoris, stent thrombosis and death due to cardiovascular causes] at 6 months were also recorded. Results: A total of 296 patients from 12 medical centers in China were randomized after PCI-DES to either the Dual therapy group (n = 148) or the Triple group (n = 146) for 6 months. The overall incidence of bleeding events at 6 months was 36.49% in the Dual therapy group and 35.62% in the Triple group [hazard ratio, 0.930; 95% confidence interval (CI), 0.635 to 1.361; P = 0.7088]. The incidence of the secondary endpoint over 6 months was 4.73% in the Dual therapy group and 1.37% in the Triple group (hazard ratio, 0.273; 95% CI, 0.057 to 1.315; P = 0.1056). Cardiovascular event occurrence was also comparable in both groups at 6 months (18.24 vs. 16.44%; hazard ratio, 0.845; 95% CI, 0.488 to 1.465; P = 0.5484). Conclusions: The incidence of total bleeding events in AF patients treated with ticagrelor was comparable to that in patients treated with clopidogrel plus aspirin at 6 month; Meanwhile, the incidence of cardiovascular events were also comparable between the groups. Clinical Trial Registration: MANJUSRI, ClinicalTrials.gov# NCT02206815, 2014, August 1st.

Mannosylated PEGylated-Polyethyleneimine as Efficient CpG Oligodeoxynucleotide Carriers for Efficient Dendritic Cell Targeting Delivery and Activation.

CpG ODN acts as a 'pathogen-associated' molecular pattern that is recognized by intracellular Toll-like receptor 9 and can induce a robust dendritic cells (DCs) activation to against various diseases. However, the CpG ODN is restricted with critical defects of easily enzymolysis and negligible phagocytosis. To overcome these issues, a simpler and competent nanocarrier of mannose modified PEGylated branched PEI25k (PEI-PEG-Man) was designed to achieve excellent DCsspecific delivery of CpG. Nanoparticles of PEI-PEG-Man encapsulating CpG (PEI-PEG-Man@CpG) possessed elevated gene loading capacity, biological stability and admirable anti-enzymolysis ability. PEI-PEG-Man@CpG could be selectively uptake by DCs through a receptor-mediated endocytosis, which generates a potent immunostimulatory activity on bone marrow derived dendritic cells (BMDCs) evidenced by significantly upregulation of the pro and anti-inflammatory cytokines (TNF-α, IL-6) and the co-stimulatory molecules (CD40, CD80, CD86, and MHC class II) on BMDCs in vitro. More importantly, the results of in vivo targeting assay showed that PEI-PEG-Man@CpG nanoparticles could remarkably boost CpG accumulation in lymph lodes upon subcutaneous administration in C57BL/6 mice, which facilitated maturation of DCs and productions of anti-inflammatory cytokines. Our results suggested that PEI-PEG-Man@CpG nanoparticles, in the future, might function as a powerful vector for ex vivo engineering to promote DC targeting and maturation, which enhance vaccine efficiency against cancer or infectious disease.

Gene expression profile of THP-1 cells treated with heat-killed Candida albicans.

BACKGROUND: Mechanisms under immune response against Candida albicans (C. albicans) remain largely unknown. To better understand the mechanisms of innate immune response against C. albicans, we analyzed the gene expression profile of THP-1 cells stimulated with heat-killed C. albicans. METHODS: THP-1 cells were stimulated with heat-killed C. albicans for 9 hours at a ratio of 1:1, and gene expression profile of the cells was analyzed using Whole Human Genome Oligo Microarray. Differentially expressed genes were defined as change folds more than 2 and with statistical significance. Gene ontology (GO) and pathway analysis were used to systematically identify biological connections of differentially expressed genes, as well as the pathways associated with the immune response against C. albicans. RESULTS: A total of 355 genes were up-regulated and 715 genes were down-regulated significantly. The up-regulated genes were particularly involved in biological process of RNA processing and pathway of the spliceosome. In case of down-regulated genes, the particularly involved immune-related pathways were G-protein coupled receptor signaling pathway, calcium signaling pathway, MAPK signaling pathway and Ras pathway. CONCLUSIONS: We depict the gene expression profile of heat-killed C. albicans stimulated THP-1 cells, and identify the major pathways involved in immune response against C. albicans. These pathways are potential candidate targets for developing anti-C. albicans agent.