Background: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. Methods: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. Results: Overall, 525 patients were randomised and treated with nemonoxacin ( n = 349) or levofloxacin ( n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population ( P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) ( P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacinrelated AEs were mostly mild and resolved after discontinuation of nemonoxacin. Conclusions: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients. (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Objectives To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). Patients and methods This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). Results A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. Conclusion Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

Background Dulanermin is a recombinant soluble human Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that activates apoptotic pathways by binding to proapoptotic death receptor (DR) 4 and DR5. The purpose of this study was to evaluate the efficacy and safety of dulanermin combined with vinorelbine and cisplatin (NP) as the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). Experimental design Patients were randomly assigned to receive NP chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 30 mg/m2 on days 2 to 4) for up to six cycles plus dulanermin (75 μg/kg on days 1 to 14) or placebo every three weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary end point was progression-free survival (PFS), and the secondary end points included objective response rate (ORR), overall survival (OS), and safety evaluation. Results Between October 2009 and June 2012, 452 untreated patients with stage IIIB to IV NSCLC were randomly assigned to receive dulanermin plus NP (n = 342) and placebo plus NP (n = 110). Median PFS was 6.4 months in the dulanermin arm versus 3.5 months in the placebo arm (hazard ratio (HR), 0.4034; 95% CI, 0.3181 to 0.5117, p < 0.0001). ORR was 46.78% in the dulanermin arm versus 30.00% in the placebo arm (p = 0.0019). Median OS was 14.6 months in the dulanermin arm versus 13.9 months in the placebo arm (HR, 0.94; 95% CI, 0.74 to 1.21, p = 0.64). The most common grade ≥ 3 adverse events (AEs) were oligochromemia, leukopenia, neutropenia, and oligocythemia. Overall incidence of AEs, grade ≥ 3 AEs, and serious AEs were similar across the two arms. Conclusion Addition of dulanermin to the NP regimen significantly improved PFS and ORR. However, our results showed that the combination of dulanermin with chemotherapy had a synergic activity and favorable toxic profile in the treatment of patients with advanced NSCLC.

Heatmapper is a freely available web server that allows users to interactively visualize their data in the form of heat maps through an easy-to-use graphical interface. Unlike existing non-commercial heat map packages, which either lack graphical interfaces or are specialized for only one or two kinds of heat maps, Heatmapper is a versatile tool that allows users to easily create a wide variety of heat maps for many different data types and applications. More specifically, Heatmapper allows users to generate, cluster and visualize: (i) expression-based heat maps from transcriptomic, proteomic and metabolomic experiments; (ii) pairwise distance maps; (iii) correlation maps; (iv) image overlay heat maps; (v) latitude and longitude heat maps and (vi) geopolitical (choropleth) heat maps. Heatmapper offers a number of simple and intuitive customization options for facile adjustments to each heat map's appearance and plotting parameters. Heatmapper also allows users to interactively explore their numeric data values by hovering their cursor over each heat map cell, or by using a searchable/sortable data table view. Heat map data can be easily uploaded to Heatmapper in text, Excel or tab delimited formatted tables and the resulting heat map images can be easily downloaded in common formats including PNG, JPG and PDF. Heatmapper is designed to appeal to a wide range of users, including molecular biologists, structural biologists, microbiologists, epidemiologists, environmental scientists, agriculture/forestry scientists, fish and wildlife biologists, climatologists, geologists, educators and students. Heatmapper is available at http://www.heatmapper.ca.

PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized 'Given X, find all associated Ys' query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: 'Find all diseases associated with Bisphenol A'. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation.

PathWhiz (http://smpdb.ca/pathwhiz) is a web server designed to create colourful, visually pleasing and biologically accurate pathway diagrams that are both machine-readable and interactive. As a web server, PathWhiz is accessible from almost any place and compatible with essentially any operating system. It also houses a public library of pathways and pathway components that can be easily viewed and expanded upon by its users. PathWhiz allows users to readily generate biologically complex pathways by using a specially designed drawing palette to quickly render metabolites (including automated structure generation), proteins (including quaternary structures, covalent modifications and cofactors), nucleic acids, membranes, subcellular structures, cells, tissues and organs. Both small-molecule and protein/gene pathways can be constructed by combining multiple pathway processes such as reactions, interactions, binding events and transport activities. PathWhiz's pathway replication and propagation functions allow for existing pathways to be used to create new pathways or for existing pathways to be automatically propagated across species. PathWhiz pathways can be saved in BioPAX, SBGN-ML and SBML data exchange formats, as well as PNG, PWML, HTML image map or SVG images that can be viewed offline or explored using PathWhiz's interactive viewer. PathWhiz has been used to generate over 700 pathway diagrams for a number of popular databases including HMDB, DrugBank and SMPDB.

Since this book was originally published in 2007 there has been a significant increase in the number of Salmonella bacteriophages, particularly lytic virus, and Salmonella strains which have been fully sequenced. In addition, new insights into phage taxonomy have resulted in new phage genera, some of which have been recognized by the International Committee of Taxonomy of Viruses (ICTV). The properties of each of these genera are discussed, along with the role of phage as agents of genetic exchange, as therapeutic agents, and their involvement in phage typing.

目的 研究紫草素(shikonin,SK)诱导肺腺癌A549细胞凋亡及其作用机制.方法 不同浓度紫草素作用于肺腺癌A549细胞后,CCK-8法检测细胞的增殖情况;DAPI荧光染色法和FCM检测细胞凋亡;Western blotting检测紫草素处理48 h后Bax、Bcl-2、p-Akt、p-ERK1/2的蛋白水平.结果 紫草素显著抑制肺腺癌A549细胞的增殖活性(P＜0.05),诱导细胞凋亡,与空白对照组比较,紫草素处理组Bax表达上调(P＜0.05),Bcl-2、p-Akt、P-ERK1/2表达下调(P＜0.05).结论 紫草素可以显著抑制肺腺癌A549细胞增殖,诱导细胞凋亡,其机制可能与线粒体凋亡途径,PI3K/Akt信号通路和ERK 1/2信号通路有关.

BACKGROUND/PURPOSE:To compare the clinical efficacy and safety of nemonoxacin with levofloxacin in treating community-acquired pneumonia (CAP) in a Phase II clinical trial. METHODS:One hundred ninety-two patients with CAP were randomized to receive oral nemonoxacin (500 mg or 750 mg) or levofloxacin (500 mg) once daily for 7-10 days. Clinical and bacteriological responses were determined at the test of cure (TOC) visit in the full analysis set (FAS). RESULTS:The clinical cure rate of nemonoxacin (500 mg), nemonoxacin (750 mg), and levofloxacin (500 mg) was 93.3%, 87.3%, and 88.5%, respectively, in the FAS (n = 168), and 93.0%, 93.9%, and 88.9%, respectively in the per protocol set (n = 152). At the TOC visit, nemonoxacin at 500 mg and 750 mg was proven to be noninferior to levofloxacin at 500 mg in the FAS in terms of clinical efficacy. The overall bacteriological success rate was 83.3% in both nemonoxacin groups and 80.0% in the levofloxacin 500 mg group in the bacteriological FAS. The comprehensive efficacy rate was comparable among the three groups (87.5% for the nemonoxacin 500 mg group, 93.8% for the nemonoxacin 750 mg group, and 81.3% for the levofloxacin 500 mg group). Most drug-related adverse events were mild and transient, mainly gastrointestinal symptoms such as nausea and vomiting, transient neutropenia, and elevated liver enzymes. No drug-related serious adverse events occurred. CONCLUSION:Either 500 mg or 750 mg of oral nemonoxacin taken once daily for 7-10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7-10 days is recommended for future Phase III clinical trials. ClinicalTrials.gov identifier: NCT01537250.

Objective To investigate the effect of shikonin on proliferation of human lung adenocarcinoma A549 cells and related mechanisms.Methods A549 cells were incubated with shikonin at different concentration(0.5,1,2 and 4 μg/ml) for 0,12,24 and 48 h.Cell proliferation was measured by CCK-8 assay; cell cycle was examined by flow cytometry using propidium iodide staining; and the expressions of pAkt was tested by Western blot assay.Results The viabilities of A549 cells were significantly inhibited after shikonin treatment.Shikonin can induce A549 cells apoptosis,and blocked the cells developing from G1 phase to S phase.The expression of pAkt was markedly decreased after shikonin treatment for 48 h.Conclusion Shikonin inhibits the growth of A549 cells significantly,which may be associated with inhibition of PI3K/Akt signaling pathway.

The Small Molecule Pathway Database (SMPDB, http://www.smpdb.ca) is a comprehensive, colorful, fully searchable and highly interactive database for visualizing human metabolic, drug action, drug metabolism, physiological activity and metabolic disease pathways. SMPDB contains >600 pathways with nearly 75% of its pathways not found in any other database. All SMPDB pathway diagrams are extensively hyperlinked and include detailed information on the relevant tissues, organs, organelles, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures. Since its last release in 2010, SMPDB has undergone substantial upgrades and significant expansion. In particular, the total number of pathways in SMPDB has grown by >70%. Additionally, every previously entered pathway has been completely redrawn, standardized, corrected, updated and enhanced with additional molecular or cellular information. Many SMPDB pathways now include transporter proteins as well as much more physiological, tissue, target organ and reaction compartment data. Thanks to the development of a standardized pathway drawing tool (called PathWhiz) all SMPDB pathways are now much more easily drawn and far more rapidly updated. PathWhiz has also allowed all SMPDB pathways to be saved in a BioPAX format. Significant improvements to SMPDB's visualization interface now make the browsing, selection, re-coloring and zooming of pathways far easier and far more intuitive. Because of its utility and breadth of coverage, SMPDB is now integrated into several other databases including HMDB and DrugBank.

The exposome is defined as the totality of all human environmental exposures from conception to death. It is often regarded as the complement to the genome, with the interaction between the exposome and the genome ultimately determining one's phenotype. The 'toxic exposome' is the complete collection of chronically or acutely toxic compounds to which humans can be exposed. Considerable interest in defining the toxic exposome has been spurred on by the realization that most human injuries, deaths and diseases are directly or indirectly caused by toxic substances found in the air, water, food, home or workplace. The Toxin-Toxin-Target Database (T3DB--www.t3db.ca) is a resource that was specifically designed to capture information about the toxic exposome. Originally released in 2010, the first version of T3DB contained data on nearly 2900 common toxic substances along with detailed information on their chemical properties, descriptions, targets, toxic effects, toxicity thresholds, sequences (for both targets and toxins), mechanisms and references. To more closely align itself with the needs of epidemiologists, toxicologists and exposome scientists, the latest release of T3DB has been substantially upgraded to include many more compounds (>3600), targets (>2000) and gene expression datasets (>15,000 genes). It now includes extensive data on 'normal' toxic compound concentrations in human biofluids as well as detailed chemical taxonomies, informative chemical ontologies and a large number of referential NMR, MS/MS and GC-MS spectra. This manuscript describes the most recent update to the T3DB, which was previously featured in the 2010 NAR Database Issue.

Objective To investigate the association of interleukin-6( IL-6) gene-572C /G polymorphism with susceptibility to chronic obstructive pulmonary disease( COPD). Methods IL-6 gene-572C /G polymorphism was genotyped with PCR-RFLP method in 192 COPD patients and 195 healthy subjects. The association of genetic polymorphism of IL-6 gene with the degree of airway obstruction was analyzed. Results The-572 CG + GG genotype and G allele were more frequent in COPD patients than those in healthy controls( P 0. 01). The relative risk of genotypes CG and GG for COPD was 2. 09( 95% CI: 1. 03 ~ 4. 23) and 5. 44( 95% CI: 1. 20 ~ 24. 75) to genotype CC, respectively. However,the distribution of IL-6 gene-572C /G polymorphism was not correlated with the degree of severity of COPD patients( P 0. 05). Conclusion IL-6 gene-572G allele may be associated with susceptibility to COPD.

The diaphragm is an important respiratory organ. The aim of this study was to quantitatively evaluate the longitudinal deformation of the right hemidiaphragm in normal subjects using two-dimensional strain ultrasound speckle tracking. Twenty-one healthy subjects were enrolled in this study. GE Healthcare Vivid E9 equipment with M5S probe and Q-analysis software were used. Negative strain values first appeared in the zone of apposition and then in the crura of the right hemidiaphragm in the inspiratory phase; the dome of the diaphragm was observed to be passively stretched. The longitudinal strain of the right hemidiaphragm in the zone of apposition was higher than that in the crura in forced breathing (P=0.024). The strains of the whole diaphragm and the zone of apposition changed significantly in quiet (P=0.000) and forced breathing (P=0.005). Ultrasound strain imaging may quantitatively assess diaphragm deformation and provide another useful modality for evaluating diaphragm kinetics.

MicroRNAs (miRNAs) are a novel class of ˜22-nt, non-coding, short single-stranded RNAs produced from endogenous genes by the sequential action of the RNase III enzymes Drosha and Dicer. Increasing evidence shows that miRNAs play a critical role in regulating inflammatory and innate immunity.1,2 However, whether miRNAs are involved in the altered function of innate immune cells and ultimately contribute to the development of acute lung injury (ALI) remains largely unknown. It is worth studying the expression profiles of miRNAs in mouse lungs stimulated by lipopolysaccharide (LPS), which may be very important in the regulation of inflammatory mediators during ALI. In the present study, we investigated the expression profiles of miRNAs in LPS-induced ALI in mice. METHODS Experimental protocols for lung injury models Male BALB/c mice (H-2d, 18-26 g, 4-6 weeks old) were obtained from the Center of Experimental Animals of the Second Army Medical University, Shanghai, China. The mice were randomly chosen for intraperitoneal (IP) injection with 10 mg/kg of LPS (n=80) from Escherichia coli (serotype O111:B4; Sigma-Aldrich, America) or the same volume of sterile PBS as a control (n=16). Six mice in the LPS group at each time point (2 hours, 6 hours, 12 hours, 18 hours and 24 hours) and six mice in the PBS group after 24 hours were anesthetized with an intra-peritoneal injection of sodium pentobarbitone (200 mg/kg). A median sternotomy was performed and lungs were harvested after blood collection from the eye for serum. The mice were sacrificed via en bloc removal of vital organs. The left lungs were immediately placed in liquid nitrogen and processed for miRNA extraction, as described below. The other lobes were prepared for histological examination. The remaining mice were observed for survival for up to seven days to confirm the extent of ALI. Enzyme-linked immunosorben assay (ELISA) for mouse tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 The serum TNF-α, IL-6 and IL-10 levels were measured by “sandwich” ELISA, using commercial kits (R&D Systems, America). Lung histology was examined under light microscope by a histopathologist (Wang JC), who was blind to the experiment settings. miRNA analysis The left lung samples were cryopulverizated using the Biopulverizer and homogenizated with the Mini-Bead-Beater-16. Total RNA was extracted using TRIzol (Invitrogen Life Technologies, America) according to the manufacturer's instruction. RNA was eluted in 20 μl of RNase-free water and stored at −70°C. RNA content and purity was measured in samples diluted 1/50 with RNase-free water using a NanoDrop ND-1000 spectrophotometer. RNA integrity and gDNA contamination were determined by denaturing agarose gel electrophoresis. After having determined the RNA content on the Nanodrop instrument, the samples were labeled using the miRCURY™ Hy3™/Hy5™ Power labeling kit and hybridized on the miRCURY™ LNA Array (v.11.0). The samples were hybridized on a hybridization station. Scanning was performed with the Axon GenePix 4000B microarray scanner. GenePix pro V6.0 was used to read the raw intensity of the images. miRNA microarray analyses were determined according to the manufacturer's instructions (Kangcheng Technologies, Shanghai, China). Quantitative real-time- PCR assays for miRNAs were done to verify the observed changes. Statistical analysis Statistical analyses of the data were performed with the SPSS12.0 software. Data were analyzed using a one-way analysis of variance (ANOVA) with PRISM 4.0 (GraphPad Software Inc.). A P <0.05 was considered statistically significant in all comparisons. RESULTS The survival of the BALB/c mice after 72 hours treated with LPS (10 mg/kg) or PBS alone was 70% and 100% respectively. Wet to dry ratio of lung was significantly higher 12 hours after LPS treatment than in the control group (P <0.05). The concentration of the serum pro-inflammatory factors IL-6 and TNF-α in the LPS treated groups after 24 hours was increased significantly compared with the control group (Figure. 1A). In addition, the concentration of serum IL-10 also increased significantly (Figure 1A). Histopathology showed severe inflammation, intra-alveolar and interstitial hemorrhage, and edema, exudation, interstitial and intra-alveolar deposits of neutrophils and fibrin that were time-dependent (Figure 1B). These data suggest that the murine model of LPS-induced ALI was successfully established.Figure 1.: The establishment of a murine model of LPS-induced acute respiratory distress syndrome. A: The levels of serum IL-6, IL-10 and TNF-α were determined by ELISA assay. B: The HE staining of lung tissue from ALI mouse. Balb/c mice were treated with 10 mg/kg LPS. The lung was harvested from 2 hours to 24 hours later, and stained with hematoxylin-eosin (original magnification ×400). C: Quantification of the LPS-induced expression of representative miRNAs in lung tissues by real-time PCR. * P <0.01.A total of 76 miRNAs were significantly up-regulated ≥1.5 fold and 35 miRNAs were down-regulated ≤0.67 fold at different time points after LPS injection. Table 1 shows the microRNA values at different time points (2 hours, 6 hours, 12 hours, 18 hours and 24 hours) after intra-peritoneal injection of LPS. The eight microRNAs that changed the most were selected among those up- or down-regulated at each time point. Twenty-eight among the 76 up-regulated miRNAs were increased more than 2.0 fold, and 10 miRNAs more than 3.0 fold. Four miRNAs, namely mmu-miR-155, mmu-miR-223, mmu-miR-183, and mmu-miR-582-5p, were up-regulated in all the time points after LPS injection. Three miRNAs, namely mmu-miR-706, mmu-miR-207, and mmu-miR- 489, were up-regulated at three time points, and 20 were up-regulated at two different time points. Four miRNAs, mmu-miR-208, mmu-miR-1, mmu-miR-133b and mmu- miR-33, were down-regulated at all time points. Five miRNAs, mmu-miR-205, mmu-miR-133a, mmu-miR32, mmu-miR-190, and mmu-miR-34b-5p, were down-regulated at three time points, and seven miRNAs were down-regulated at two time points. However, expression levels of most miRNAs were changed transiently and fluctuated at different time points after LPS injection, as derived from the heat map diagram of the two-way hierarchical clustering of genes and samples. Quantitative real-time PCR assays confirmed that the expression levels of mmu-miR-155, mmu-miR-714 and mmu-miR-124 were increased about 15 fold at 24 hours after LPS treatment (Figure 1C, P <0.01).Table 1: The microRNA values at different time points after intra-peritoneal injection of LPS*DISCUSSION ALI represents a state of excessive cytokine secretions that involves inflammation of multiple organs.3 In the present study, we used the LPS-induced lung injury as a murine model to identify potential mechanisms of lung injury, and for the first time we reported here that the expression levels of miRNAs were changed transiently and fluctuated at different time points after LPS injection. From the inflammatory model, we might determine a role for miRNAs in the LPS-induced innate immune response by measuring mature miRNA levels in the lung tissue over 24 hours. LPS injection resulted in a total of 76 miRNAs up-regulated by ≥1.5 fold and 35 miRNAs down-regulated ≤0.67 fold at different times and this response was time-dependent. Since a lot of miRNAs have multiple functions but little is known of the functional role of miRNAs, given the limitations of the programs to predict miRNA targets, unlike mRNA expression data, cluster analysis is unlikely to provide reliable information on the potential mechanism of action of miRNA in an LPS-induced inflammatory response. These transient changes in the miRNA levels suggest that there is rapid turnover of miRNAs in vivo. We speculate that these time-dependent changes are caused by vasodilation, increased blood flow and macrophage recruitment. Although our study found that LPS induced rapid and transient changes of miRNA expression in mouse lung tissue, their biological activities are still obscure, and many studies are needed on the kinetics of their expression and the subsequent putative role in innate immunity. We speculate that a proportion might be involved in the response of inflammatory cytokine production since this miRNA expression change is concomitant to the increased levels of the pro-inflammatory mediators TNF-α, IL-6 and IL-10 and the recruitment of macrophages in the lungs. Significantly, this report suggests that a change in miRNA expression might provide an additional post- transcriptional mechanism for the releasing of inflammatory mediators. A number of recent publications have questioned the utility of miRNA target prediction databases and demonstrated that the biological actions of miRNAs are also influenced by additional factors such as the number of multiple cytokines and second messenger-responsive enhancer sequence (MREs),4 the spacing between MREs,5 and mRNA secondary structure.4 We also found widespread, rapid and transient increases in miRNA expression in the LPS-induced ALI in mice, which are very different from previous in vivo studies. This could be a result of multiple factors including the different pathways induced by LPS, different LPS doses and time periods of LPS treatment. Thus, further studies are warranted to address these discrepancies.

MicroRNAs (miRNAs) have been shown as an important regulator in the pathologies of acute lung injury (ALI). However, the potential effect of miRNA-based therapeutic studies in ALI remains poorly understood. We assessed the effect of antisense oligonucleotides (ASOs) against miR-155 on the development of ALI using a murine ALI model. We found that miR-155 ASO treatment could enhance the recovery of ALI as evidenced by accelerated body weight back, reduced level of bronchoalveolar lavage (BAL) protein and proinflammatory cytokines, and reduced number of BAL cells. Adoptive cell transfer assay in RAG1(-/-) mice showed that CD4(+)CD25(+) regulatory T cells (Tregs) mediated the enhanced recovery of ALI. Mechanistic evidence showed that enhanced expansion of Tregs in vivo, dominantly induced by IL-10-secreting M2-like macrophages, was critical for their elevated proportion in miR-155 ASO-treated ALI mice. Finally, we report that C/EBP beta, a target molecule of miR-155, was upregulated and associated with IL-10 secretion and M2-like phenotype of macrophages. These data provided a previously unknown mechanism for miRNA-based therapy against ALI, which could ultimately aid the understanding of recovery of ALI and the development of new therapeutic strategies against clinical inflammatory lung disease. The Journal of Immunology, 2013, 190: 4337-4348.

目的 探讨白细胞介素(IL)-6启动子区域基因-572C/G单核苷酸多态性与慢性阻塞性肺疾病(COPD)易感性及吸烟因素之间的关系.方法 应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法,检测并分析COPD患者和健康对照者IL-6-572C/G位点基因型分布情况,同时分析该多态性位点与吸烟相关COPD之间是否存在相关性.结果 中国上海地区汉族人群存在IL-6基因-572C/G多态性；COPD组CG、GG基因型、G等位基因频率均高于对照组(P＜0.01)；基因型频率的相对风险分析发现,CG、GG基因型各自患COPD的风险分别是CC基因型的2.09倍(95％ CI:1.03 ～4.23)和5.44倍(95％ CI:1.20 ～ 24.75)；-572C/G多态性在轻中度、重度COPD组间的分布比较差异无统计学意义；该突变位点与吸烟所致的COPD之间无相关性存在.结论 IL-6基因-572G等位基因可能是中国汉族人COPD发生的易感因子,可能与携带该等位基因的人群存在IL-6水平高表达有关,其基因分布与吸烟相关的COPD无明显相关.

Objective To compare the selective power of anti-drug-resistant mutant of vancomycin , teicoplanin , linezolid and rifampicin to methicillin-resistant Staphylococcus aureus (MRSA) .Methods The minimum inhibitory concentration (MIC) to MRSA was determined by E-test method. Mutant prevention concentration (MPC) was measured by mix-bacterial method (the inoculated bacterial concentration1×1010CFU/mL) .Selection index (MPC/MIC) and the ratio of MPC to target maximum serum concentration (MPC/Cmax) of the four antibiotics were compared.Results MIC values of vancomycin , teicoplanin , linezolid and rifampin against MRSA were 0.5,1.0,0.5and≤0.5μg/mL; MPC values were 51.2, 25.6 , 9.6and 1024.0 μg/mL ; Selection indices were 102.4 , 25.6 , 19.2and2 048.0; MPC/Cmax were 1.28 , 0.57 , 0.64 and107.80 , respectively.Conclusion Linezolid and teicoplanin have narrower mutant selection window than vancomycin and rifampin , and they have obvious advantages in preventing bacterial antibiotic resistance.

Originally released in 2005, BacMap is an electronic, interactive atlas of fully sequenced bacterial genomes. It contains fully labeled, zoomable and searchable chromosome maps for essentially all sequenced prokaryotic (archaebacterial and eubacterial) species. Each map can be zoomed to the level of individual genes and each gene is hyperlinked to a richly annotated gene card. The latest release of BacMap (http://bacmap.wishartlab.com/) now contains data for more than 1700 bacterial species (∼10× more than the 2005 release), corresponding to more than 2800 chromosome and plasmid maps. All bacterial genome maps are now supplemented with separate prophage genome maps as well as separate tRNA and rRNA maps. Each bacterial chromosome entry in BacMap also contains graphs and tables on a variety of gene and protein statistics. Likewise, every bacterial species entry contains a bacterial ‘biography’ card, with taxonomic details, phenotypic details, textual descriptions and images (when available). Improved data browsing and searching tools have also been added to allow more facile filtering, sorting and display of the chromosome maps and their contents.