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To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP).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).A total of 343 patients were randomized (sitafloxacin 100 mg qd,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.

Coronavirus disease 2019 (COVID-19) was declared a serious global public health emergency. Hospitalization and mortality rates of lung cancer patients diagnosed with COVID-19 are higher than those of patients presenting with other cancers. However, the reasons for the outcomes being disproportionately severe in lung adenocarcinoma (LUAD) patients with COVID-19 remain elusive. The present study aimed to identify the possible causes for disproportionately severe COVID-19 outcomes in LUAD patients and determine a therapeutic target for COVID-19 patients with LUAD. We used publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and various bioinformatics tools to identify and analyze the genes implicated in SARS-CoV-2 infection in LUAD patients. Upregulation of the SARS-CoV-2 infection-related molecules dipeptidyl peptidase 4, basigin, cathepsin B (CTSB), methylenetetrahydrofolate dehydrogenase, and peptidylprolyl isomerase B rather than angiotensin-converting enzyme 2 may explain the relatively high susceptibility of LUAD patients to SARS-CoV-2 infection. CTSB was highly expressed in the LUAD tissues after SARS-CoV-2 infection, and its expression was positively correlated with immune cell infiltration and proinflammatory cytokine expression. These findings suggest that CTSB plays a vital role in the hyperinflammatory response in COVID-19 patients with LUAD and is a promising target for the development of a novel drug therapy for COVID-19 patients.

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 7â10 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 7â10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7â10 days is recommended for future Phase III clinical trials.ClinicalTrials.gov identifier: NCT01537250. Keywords: clinical trial, community-acquired pneumonia, efficacy, nenomoxacin, safety

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.

The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards. This year's update, HMDB 4.0, represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB’s chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC–MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.

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

Background/Purpose: Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP. Methods: A phase 3, multicenter, randomized (2:1) controlled trial was conducted in adult CAP patients receiving nemonoxacin 500 mg or levofloxacin 500 mg orally once daily for 7–10 days. Clinical, microbiological response and adverse events were assessed. Non-inferiority was determined in terms of clinical cure rate of nemonoxacin compared with that of levofloxacin in a modified intention-to-treat (mITT) population. NCT registration number: NCT01529476. Results: A total of 527 patients were randomized and treated with nemonoxacin (n = 356) or levofloxacin (n = 171). The clinical cure rate at test-of-cure visit was 94.3% (300/318) for nemonoxacin and 93.5% (143/153) for levofloxacin in the mITT population [difference (95% CI), 0.9% (−3.8%, 5.5%)]. The microbiological success rate was 92.1% (105/114) for nemonoxacin and 91.7% (55/60) for levofloxacin in the bacteriological mITT population [difference (95% CI), 0.4% (−8.1%, 9.0%)]. The incidence of adverse events (AEs) was comparable between nemonoxacin (33.1%, 118/356) and levofloxacin (33.3%, 57/171) (P > 0.05). Conclusion: Nemonoxacin 500 mg once daily for 7–10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile.ClinicalTrials.gov identifier: NCT01529476. Keywords: Clinical outcome, Community-acquired pneumonia, Levofloxacin, Nemonoxacin, Randomized controlled trial, Safety

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.

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, recoloring 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. © 2013 The Author(s). Published by Oxford University Press.

To investigate the relationship between acute graft rejection early after renal transplantation and the variations of platelet parameters.We retrospectively analyzed the clinical data of 167 renal transplant recipients before and within 2 months after the surgery. Before and at 1-10 days, 15 days, 30 days, 45 days and 60 days after the transplantation, 5 platelet parameters, including platelet count (PLT), platelet hematocrit (PCT), mean platelet volume (MPV), platelet volume distribution width (PDW), and large platelet ratio (P-LCR), were detected in the 35 patients with acute graft rejection within two months (AR group) and in the other 132 recipients with good graft recovery (control group).The AR group and control group showed no significant difference in PLT, PCT, MPV, or P-LCR before the surgery, but the PDW was significantly higher in the AR group (t=2.18, P=0.035). These parameters were similar within 5 postoperative days between the two groups (P0.05), but in postoperative days 6-15, the AR group showed significantly increased MPV, PDW and P-LCR compared with the control group (P0.05). In postoperative days 6-9, MPV, PDW and P-LCR became stable in AR group but tended to decrease in the control group, showing obviously different patterns of variation between the two groups (P0.05).Preoperative PDW may have a positive correlation with acute graft rejection after renal transplantation. Monitoring the variations of MPV, PDW and P-LCR may help in the diagnosis of acute graft rejection early after renal transplantation.

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.

Adoptive cell transfer immunotherapy using tumor infiltrating lymphocytes (TILs) was an important therapeutic strategy against tumors. But the efficacy remains limited and development of new strategies is urgent. Recent evidence suggested that CpG-ODNs might be a potent candidate for tumor immunotherapy. Here we firstly reported that CpG-ODNs could significantly enhance the antitumor efficacy of adoptively transferred TILs in vivo accompanied by enhanced activity capacity and proliferation ofCD8+T cells andCD8+T cells, as well as a Th1 polarization immune response. Most importantly, we found that CpG-ODNs could significantly elevate the infiltration of Th17 cells in tumor mass, which contributed to anti-tumor efficacy of TILs in vivo. Our findings suggested that CpG ODNs could enhance the anti-tumor efficacy of adoptively transferred TILs through modifying Th1 polarization and local infiltration of Th17 cells, which might provide a clue for developing a new strategy for ACT based on TILs.

The Small Molecule Pathway Database (SMPDB) is an interactive, visual database containing more than 350 small-molecule pathways found in humans. More than 2/3 of these pathways (>280) are not found in any other pathway database. SMPDB is designed specifically to support pathway elucidation and pathway discovery in clinical metabolomics, transcriptomics, proteomics and systems biology. SMPDB provides exquisitely detailed, hyperlinked diagrams of human metabolic pathways, metabolic disease pathways, metabolite signaling pathways and drug-action pathways. All SMPDB pathways include information on the relevant organs, organelles, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to detailed descriptions contained in the Human Metabolome Database (HMDB) or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All SMPDB pathways are accompanied with detailed descriptions, providing an overview of the pathway, condition or processes depicted in each diagram. The database is easily browsed and supports full text searching. Users may query SMPDB with lists of metabolite names, drug names, genes/protein names, SwissProt IDs, GenBank IDs, Affymetrix IDs or Agilent microarray IDs. These queries will produce lists of matching pathways and highlight the matching molecules on each of the pathway diagrams. Gene, metabolite and protein concentration data can also be visualized through SMPDB’s mapping interface. All of SMPDB’s images, image maps, descriptions and tables are downloadable. SMPDB is available at: http://www.smpdb.ca.