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Qiao Y.,Tianjin University | Huang Y.,Fudan University | Huang Y.,State Key Laboratory for Infectious Disease Prevention and Control | Qiu C.,Fudan University | And 9 more authors.
Biomaterials | Year: 2010

To minimize the cytotoxicity of poly (2-(dimethylamino) ethyl methacrylate) (PDMAEMA) as a gene delivery vector, we synthesized PEGylated PDMAEMA by atom transfer radical polymerization (ATRP). Here we report its effects on transfection efficiency in vitro delivered with a GFP expression plasmid and immunogenicity in vivo after complexed with a HIV gag gene DNA vaccine. mPEG113-b-PDMAEMA94 was efficient in condensing DNA and formed polyplexes with an average diameter of about 150 nm. The in vitro transfection experiments demonstrated that PEGylation dramatically decreased the cytotoxicity at the N/P ratios above 30, although the transfection efficiency in vitro was reduced. Interestingly, mice in vivo vaccination study clearly showed that PEGylated PDMAEMA used as DNA delivery vector significantly improved the prime effect of DNA vaccine through intranasal administration. Importantly, PEGylated PDMAEMA was further proved its ability to induce cytokines production by murine macrophages. Overall, mPEG-b-PDMAEMA can be used as an efficient DNA vaccine vector which enhances adaptive immune responses by activating innate immunity. © 2009 Elsevier Ltd. All rights reserved. Source

Zhang H.,CAS Institute of Biophysics | Li D.,BGI Shenzhen | Li D.,Shenzhen Key Laboratory of Unknown Pathogen Identification | Zhao L.,Chinese National Institute for Communicable Disease Control and Prevention | And 30 more authors.
Nature Genetics | Year: 2013

The worldwide emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis threatens to make this disease incurable. Drug resistance mechanisms are only partially understood, and whether the current understanding of the genetic basis of drug resistance in M. Tuberculosis is sufficiently comprehensive remains unclear. Here we sequenced and analyzed 161 isolates with a range of drug resistance profiles, discovering 72 new genes, 28 intergenic regions (IGRs), 11 nonsynonymous SNPs and 10 IGR SNPs with strong, consistent associations with drug resistance. On the basis of our examination of the dN/dS ratios of nonsynonymous to synonymous SNPs among the isolates, we suggest that the drug resistance-Associated genes identified here likely contain essentially all the nonsynonymous SNPs that have arisen as a result of drug pressure in these isolates and should thus represent a near-complete set of drug resistance-Associated genes for these isolates and antibiotics. Our work indicates that the genetic basis of drug resistance is more complex than previously anticipated and provides a strong foundation for elucidating unknown drug resistance mechanisms. © 2013 Nature America, Inc. All rights reserved. Source

Liu G.,Chinese National Institute for Communicable Disease Control and Prevention | Liu G.,State Key Laboratory for Infectious Disease Prevention and Control | Xu X.,Capital Medical University | He L.,Chinese National Institute for Communicable Disease Control and Prevention | And 7 more authors.
Helicobacter | Year: 2011

Background: The antimicrobials resistance of Helicobacter pylori (H. pylori) was able to sharply decline the eradication rate of H. pylori both in adults and children, but there are limited studies about the primary antibiotic resistance and the related gene mutations, specifically in China. Materials and Methods: The primary resistance to 9 antibiotics of 73 H. pylori strains isolated from gastric biopsies of children recruited at Beijing Children's Hospital was assessed, and the mutations in 23S rRNA gene of 65 macrolide-resistant strains and in gyrA and gyrB of 12 quinolone-resistant strains were investigated. Results: The resistance rate to clarithromycin, azithromycin, metronidazole, levofloxacin, moxifloxacin, and rifampicin was 84.9%, 87.7%, 61.6%, 13.7%, 15.1%, and 6.8%, respectively. No resistance to amoxicillin, gentamicin, and tetracycline was observed. Dual, triple, and quadruple antibacterial resistant percentage was 46.6% (34/73), 15.1% (11/73), and 2.7% (2/73), respectively. The gene mutation rate of A2142C, A2142G, and A2143G in 23S rRNA gene was 1.5% (1/65), 6.2% (4/65), and 84.6% (55/65), respectively. The detection rate of mutations of Asn87, Asp91, and Met191 in GyrA was 41.7% (5/12), 25% (3/12), and 25% (3/12), respectively. Conclusion: The high prevalence of primary antibiotic resistance was out of expectation in H. pylori strains isolated from the children in Beijing. Antibiotic susceptibility should be made clear before the antibiotic was used in the anti-H. pylori therapy in this population. The A2143G was the most populated mutation in macrolide-resistant strains, and Asn87 and Asp91 of GyrA were the most common mutation points in quinolone resistance strains. © 2011 Blackwell Publishing Ltd. Source

Yin Y.-D.,Capital Medical University | Zhao F.,Chinese National Institute for Communicable Disease Control and Prevention | Zhao F.,State Key Laboratory for Infectious Disease Prevention and Control | Ren L.-L.,Chinese Academy of Sciences | And 5 more authors.
Respirology | Year: 2012

Background and objective: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Mycoplasma pneumoniae is one of the major causative pathogens of CAP. Early diagnosis of M. pneumoniae pneumonia is crucial for initiating appropriate antibiotic therapy. The aim of this study was to determine whether the Japanese Respiratory Society (JRS) guidelines on CAP are effective for diagnosing M. pneumoniae pneumonia. Methods: Between August 2008 and July 2009, adult outpatients with CAP were consecutively enrolled. The aetiology of CAP was determined by culture and real-time polymerase chain reaction (PCR) methods to detect M. pneumoniae, urine antigen tests to detect Streptococcus pneumoniae and Legionella pneumoniae, blood and sputum culture for bacteria and real-time PCR for eight common respiratory viruses. The predictive value of the JRS guidelines for differentiating M. pneumoniae pneumonia from typical bacterial and viral pneumonias was determined. Results: Data from 215 adult CAP outpatients was analyzed. An aetiological diagnosis was made for 105 patients (48.8%), including 62 patients with M. pneumoniae pneumonia, 17 patients with typical bacterial pneumonia and 23 patients with viral pneumonia. According to the JRS criteria for differential diagnosis of atypical pneumonia, 55 of 62 patients were correctly diagnosed with M. pneumoniae pneumonia (sensitivity 88.7%), and 31 of 40 patients with bacterial and viral pneumonia were correctly excluded (specificity 77.5%). Conclusions: The JRS guidelines on CAP provide a useful tool for the identification of M. pneumoniae pneumonia cases and differentiating these from cases of typical bacterial or viral pneumonia. The Japanese Respiratory Society guidelines on community-acquired pneumonia are useful for identifying cases of Mycoplasma pneumoniae pneumonia and differentiating these from cases of typical bacterial or viral pneumonia. © 2012 Asian Pacific Society of Respirology. Source

Zhang M.,Chinese National Institute for Communicable Disease Control and Prevention | Zhang M.,State Key Laboratory for Infectious Disease Prevention and Control | Zhang M.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases | Lin F.,Beijing Institute of Technology | And 4 more authors.
Analytical Chemistry | Year: 2015

The ability of rapid biomarker quantitation in raw biological samples would expand the application of mass spectrometry in clinical diagnosis. Up until now, the conventional chromatography-mass spectrometry method is time-consuming in both sample preparation and chromatography separation processes, while ambient ionization methods normally suffer from sensitivity. The membrane electrospray ionization (MESI) introduced in this study could not only achieve sensitive biomolecule quantitation, but also minimize the sample handling process. As a unique feature of MESI, both vertical and horizontal chemical separations could be achieved in real-time. With the capability of mass-selectively minimizing matrix effects from salts, small molecules, and macromolecules, ultrasensitive detection of cytochrome C (>500-fold sensitivity improvement) in raw urine samples was demonstrated in less than 20 min. (Graph Presented). © 2015 American Chemical Society. Source

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