Carbapenem-resistant Enterobacteriaceae (CRE) mainly cause hospital-acquired infections, which have become an major threat in clinical practice and there are few antibacterial drugs available for CRE infection. At present, the main drugs for CRE treatment are polymyxin, tigecycline, ceftazidime-avibactam, fosfomycin and aminoglycoside antibiotics. Polymyxin and tigecycline are highly sensitive to CRE in vitro and are not affected by the type of carbapenemase produced by bacteria. Due to heterogeneous resistance and dose-related nephrotoxicity, polymyxin is often used in combination with other antibiotics. Tigecycline is difficult to reach sufficient concentrations in blood and alveolar lining fluid when using conventional dose. Therefore, it is necessary to increase the dose or to be used in combination with other drugs. Ceftazidime-avibactam lacks effective antibacterial activity against metalloenzyme-producing CRE, which can be used for the treatment of non metalloenzyme-producing CRE infection. The most common site of CRE colonization is the gastrointestinal tract. If the patient have intestinal mucosal destruction and decreased immune function, CRE can cause persistent bacteremia from intestinal blood.

Objective: To explore the effect of heme oxygenase-1 (HO-1) on level of reactive oxygen species (ROS) induced by zinc oxide nanoparticles (ZnO-NPs) in Human umbilical vein endothelial cells line EA.hy926. Methods: The EA.hy926 cells in logarithmic growth phase were incubated with 0.0, 2.5, 5.0, 10.0 and 15.0 mg/L ZnO-NPs respectively. The ROS level, reflected by mean fluorescence intensity (MFI), was examined by flow cytometer after 4 hours exposure, the protein expression of HO-1 which was determined by Western Blot after exposed to ZnO-NPs for 24 hours. Cells incubated with 15.0 mg/L were set as the ZnO-NPs group; a blank control group was set at the same time. Cells were pretreated with HO-1 inhibitor zinc protoporphyrin (ZnPPIx) and HO-1 activator cobalt protoporphyrin (CoPPIx), they were classified as ZnPPIx group and CoPPIx group. 15 mg/L ZnO-NPs was chosen to conduct the experiment of HO-1 activation and inhibition. Cells were classified as ZnPPIX+ ZnO-NPs group and CoPPIx+ ZnO-NPs group after pretreated with 10 μmol/L ZnPPIx or CoPPIx for 1 h, added 15 mg/L ZnO-NPs to cell culture medium. In all groups ROS levels were detected after exposed to ZnO-NPs for 4 hours, the protein expression of HO-1 was detected after exposed to ZnO-NPs for 24 hours. Results: With the increased dose of ZnO-NPs, levels of ROS and HO-1 in EA.hy926 cells were clearly elevated (the MFI of 0.0, 2.5, 5.0, 10.0 and 15.0 mg/L ZnO-NPs incubated groups was 22 627.22±718.27, 24 726.47±568.52, 31 141.75±1 312.24, 39 824.82±4 774.74, 50 569.03±1 497.63 respectively, and HO-1 relative expression were 0.16±0.01, 0.19±0.02, 0.16±0.01, 0.23±0.02, 0.92±0.06 respectively). HO-1 expression in ZnPPIx pretreatment group decreased compared with ZnO-NPs group (1.05±0.05 vs. 1.12±0.01, P<0.05), meanwhile ROS level enhanced (62 683.95±2 589.59 vs. 53 654.53±2 229.01, P<0.05). However, CoPPIx pretreatment had higher HO-1 level and lower level of ROS compared with ZnO-NPs group (HO-1: 1.74±0.11 vs. 0.22±0.03, P<0.05; ROS: 32 845.04±993.48 vs. 53 654.53±2 229.01, P<0.05). Conclusions Exposure to ZnO-NPs significantly induced ROS generation in EA.hy926 cells in a dose-dependent manner. HO-1 regulated ZnO-NPs-induced oxidative stress.

Objective:To evaluate the clinical factors affecting the probability of malignant micro-sized (≤10 mm) solitary pulmonary nodules (≤10 mm, micro-sized SPN), and established a clinical prediction model. Methods:Medical records from 102 patients with a pathological diagnosis of micro-sized SPN (Group A), established between June 2012 and March 2014, were reviewed. Clinical data were collected to evaluate the independent predictors of malignant micro-sized SPN using single factor analysis and Logistic regression analysis. A clinical prediction model was subsequently created. Receiver-operating characteristic (ROC) curves were constructed using the prediction model. Between January 2015 and August 2017, data from an additional 10 patients enrolled from January 2015 to August 2017 from Jinhua Guangfu Hospital (Group B) with a pathological y diagnosed micro-sized SPN were used to validate this clinical prediction model. The model was also compared with the Mayo Clinic Model. Results:Median age of 102 patients (Group A) was 55.31±10.77 years old. There were 75.5％malignant nodules and 24.5％benign ones. Logistic regression analysis identified six clinical characteristics (no symptoms, upper lobe, diameter>5 mm, no clear border, not irregular round, no calcification) as independent predictors of malignancy in patients with micro-sized SPN. The area under the ROC curve for our model was 0.922 (95％CI:0.857-0.986). In our model, the diagnosis sensitivity and specificity were 88.3％and 84.0％, respectively. The test power of the model was better compared with the Mayo Clinic Model. Conclusions:In this study, we had found the independent predictors of malignant micro-sized SPN, and developed a prediction model that could accurately identify malignant micro-sized SPN in patients.