Patients with Acinetobacter baumannii bacteremia treated with antipseudomonal cephalosporins showed higher 14-day mortality than patients treated with antipseudomonal carbapenems. We hypothesized that the bacterial membrane vesicles (BMVs) induced by antipseudomonal cephalosporins are more virulent than BMVs induced by antipseudomonal carbapenems.To simulate the clinical condition with inadequate antimicrobial treatment, carbapenem-resistant A. baumannii was treated with ceftazidime (an antipseudomonal cephalosporin) or imipenem (an antipseudomonal carbapenem) at 1/2 the minimum inhibitory concentration. BMVs and BMV-carried lipopolysaccharide were measured by nanoparticle tracking analysis and western blotting, respectively. Cytokine expression in RAW264.7 macrophages or mice serum induced by the BMVs was determined by ELISA, fluorescent bead-based immunoassay or western blotting. The virulence of the BMVs was assessed in mice. Liquid chromatography tandem-mass spectrometry was used to determine the protein contents of the BMVs.We found that ceftazidime induced a higher number of BMVs (CAZ-BMV), which carried more LPS, and induced higher expression levels of iNOS, IL-1β, and IL-6 in macrophages, higher expression of many cytokines in mice, more neutrophil infiltration in lung interstitium, and higher mortality in mice than imipenem-induced BMVs (IMP-BMV). When adjusted to same amount of LPS, CAZ-BMV still led to higher mortality than IMP-BMV. Proteomic analysis revealed different protein contents in CAZ-BMV and IMP-BMV. In conclusion, A. baumannii BMVs induced by ceftazidime are more virulent than BMVs induced by imipenem.Purpose To compare the effectiveness and safety outcomes of drug-coated balloon angioplasty (DCBA) vs conventional balloon angioplasty (BA) for arteriovenous fistula (AVF) stenosis. Materials and Methods A systematic review was conducted of PubMed and Embase databases from 1966 to May 2019 to identify English-language articles evaluating DCBA vs BA for the treatment of AVF stenosis. Data extracted from each study were synthesized to evaluate target lesion revascularization (TLR), technical success, and mortality for the 2 approaches. Meta-analyses were performed on these outcomes using random effects models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results Twelve studies [6 randomized controlled trials (RCTs) and 6 cohort studies] comprising 979 patients were included in this meta-analysis. The pooled results showed that AVFs treated with DCBA had significantly fewer TLRs at 6 months (OR 0.31, 95% CI 0.14 to 0.69, p=0.004) and 12 months (OR 0.45, 95% CI 0.21 to 0.97, p=0.04) than BA. The 2 approaches had similar technical success rates (OR 0.22, 95% CI 0.03 to 1.43, p=0.11). Additionally, the pooled OR of 12-month mortality was 0.71 (95% CI 0.20 to 2.51, p=0.60), indicating no significant difference between DCBA and BA. Subgroup analysis based on study design showed the superiority of DCBA to BA in cohort studies but not RCTs, which had high heterogeneity. Significant publication bias was found in the cohort studies. Conclusion In de novo or recurrent AVF stenosis, DCBA appears to be an effective procedure associated with lower 6- and 12-month TLR compared with BA. However, larger and randomized controlled studies are warranted to draw definitive conclusions.This paper is based on the Anne Simmonds Memorial Lecture, given by Monika Löffler at the International Symposium on Purine and Pyrimidine Metabolism in Man, Lyon 2019. It is dedicated to H. Anne Simmonds (died 2010) - a founding member of the ESSPPMM, since 2003 Purine and Pyrimidine Society - and her outstanding contributions to the identification and study of inborn errors of purine and pyrimidine metabolism. The distinctive intracellular arrangement of pyrimidine de novo synthesis in higher eukaryotes is important to cells with a high demand for nucleic acid synthesis. The proximity of the enzyme active sites and the resulting channeling in CAD and UMP synthase is of kinetic benefit. The intervening enzyme dihydroorotate dehydrogenase (DHODH) is located in the mitochondrion with access to the ubiquinone pool, thus ensuring efficient removal of redox equivalents through the constitutive activity of the respiratory chain, also a mechanism through which the input of 2 ATP for carbamylphosphate synthesis is balanced by Oxphos. The obligatory contribution of O2 to de novo UMP synthesis means that DHODH has a pivotal role in adapting the proliferative capacity of cells to different conditions of oxygenation, such as hypoxia in growing tumors. DHODH also is a validated drug target in inflammatory diseases. This survey of selected topics of personal interest and reflection spans some 40 years of our studies from tumor cell cultures under hypoxia to in vitro assays including purification from mitochondria, localization, cloning, expression, biochemical characterization, crystallisation, kinetics and inhibition patterns of eukaryotic DHODH enzymes.Aim Development of a new drug-delivery system using a compound derived from Pronephrium penangianum (J5) for the treatment of cervical cancer. Materials & methods The delivery system was developed using Prussian blue nanoparticles, camouflaged by red blood cell membrane and with folic acid surface modifications. Results Our results showed the successful development of a nanodrug-delivery system, which increases the half-life and immune evasion ability of the drug. The mechanism of this system was through suppressing B-cell lymphoma 2 and increasing B-cell lymphoma 2-associated X protein and the cleaved caspase level. An in vivo study also confirmed good antitumor activity without any side effects to normal tissue. Conclusion This drug-delivery system provides a good alternative for the treatment of cervical cancer using J5.BACKGROUND Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous studies showed the relationship between Ang-2 level and the risk of mortality in patients with acute respiratory distress syndrome (ARDS). However, the link between circulating Ang-2 and the risk of mortality in patients with ARDS varied in different investigations. RESULTS We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating Ang-2 and mortality in patients with ARDS. Among the 10 eligible studies, pooled odds ratio (OR) showed that high Ang-2 level contributed to ARDS mortality [OR = 1.56, 95% confidence interval (CI) 1.30-1.89, I2 = 76.2%]. Stratified analysis revealed that higher circulating Ang-2 was related to a 30% higher risk in the high-quality scores group (OR = 1.68, 95% CI 1.33-2.68, I2 = 62.4%).  https://www.selleckchem.com/products/Rapamycin.html  The I2 of the bad compliance group decreased from 76.