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Zhou L.,Peking University | Zhang J.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases | Chen M.,Guangzhou University | Hou X.,Huazhong University of Science and Technology | And 4 more authors.
American Journal of Gastroenterology | Year: 2014

OBJECTIVES:Studies conducted in large populations of patients and providing full information on Helicobacter pylori (H. pylori) antibiotic resistance are needed to determine the efficacy of sequential therapy (SQT) against this pathogen. This study compared eradication rates with SQT and standard triple therapy (STT), and evaluated the impact of antibiotic resistance on outcomes.METHODS:The study population included adults with positive H. pylori culture presenting at four centers in China between March 2008 and December 2010. Patients were randomly assigned to 10 days of treatment with esomeprazole, amoxicillin, and clarithromycin (STT; n=140) or to 5 days of treatment with esomeprazole and amoxicillin, followed by 5 days of esomeprazole, clarithromycin, and tinidazole (SQT; n=140). Eradication was assessed 8-12 weeks after treatment.RESULTS:There was no significant difference between the eradication rates achieved with STT (66.4% (95% confidence interval (CI) 59.3-74.3)) and SQT (72.1% (65.0-79.3); P=0.300) in either the intention-to-treat analysis or the per-protocol analysis (72.7% (65.6-79.7) and 76.5% (69.7-83.3), respectively; P=0.475). Clarithromycin resistance (CLA-R, odds ratio (OR)=8.34 (3.13-22.26), P<0.001) and metronidazole resistance (MET-R, OR=7.14 (1.52-33.53), P=0.013) both independently predicted treatment failure in the SQT group. Patients in the SQT group with dual CLA-R and MET-R had a lower eradication rate (43.9%) than those with isolated CLA-R (88.9%, P=0.024) or isolated MET-R (87.8%, P<0.001).CONCLUSIONS:H. pylori eradication rates with STT and SQT were compromised by antibiotic resistance. SQT may be suitable in regions with high prevalence of isolated CLA-R, but it is unsatisfactory when both CLA-R and MET-R are present. © 2014 by the American College of Gastroenterology.


Wang J.,Capital Medical University | Wang P.,Civil Aviation General Hospital | Wang X.,Capital Medical University | Zheng Y.,Peking University | And 2 more authors.
JAMA Internal Medicine | Year: 2014

IMPORTANCE: Appropriate antibiotic use is a key strategy to control antibacterial resistance. The first step in achieving this is to identify the major problems in antibiotic prescription in health care facilities, especially in primary health care settings, which is where most patients receive medical care. OBJECTIVE: To identify current patterns of antibiotic use and explore the reasons for inappropriate prescription in primary health care settings in China. DESIGN, SETTING, AND PARTICIPANTS: A total of 48 primary health care facilities in China were randomly selected from 6 provinces at various levels of economic development. Data for the years 2009 through 2011 from 39 qualifying facilities (23 city and 16 rural primary health care centers) were analyzed retrospectively. The study sample consisted of prescription records for 7311 outpatient visits and 2888 inpatient hospitalizations. MAIN OUTCOMES AND MEASURES: General health center information, drug usage, disease diagnoses, and antibiotic use by outpatients and inpatients were surveyed. Cases of inappropriate antibiotic prescription were identified. RESULTS: Most staff in the primary health care facilities had less than a college degree, and the medical staff consisted primarily of physician assistants, assistant pharmacists, nurses, and nursing assistants. The median (range) governmental contribution to each facility was 34.0% (3.6%-92.5%) of total revenue. The facilities prescribed a median (range) of 28 (8-111) types of antibiotics, including 34 (10-115) individual agents. Antibiotics were included in 52.9% of the outpatient visit prescription records: of these, only 39.4%were prescribed properly. Of the inpatients, 77.5%received antibiotic therapy: of these, only 24.6%were prescribed properly. Antibiotics were prescribed for 78.0% of colds and 93.5%of cases of acute bronchitis. Of the antibiotic prescriptions, 28.0%contained cephalosporins and 15.7% fluoroquinolones. A total of 55.0%of the antibiotic prescriptions were for antibiotic combination therapy with 2 or more agents. In nonsurgical inpatients in cities, the mean (SD) duration of antibiotic therapy was 10.1 (7.8) days. Of the surgical patients, 98.0%received antibiotics, with 63.8% of these prescriptions for prophylaxis. CONCLUSIONS AND RELEVANCE: Antibiotics are frequently prescribed in Chinese primary health care facilities, and a large proportion of these prescriptions are inappropriate. Frequent and inappropriate use of antibiotics in primary health care settings in China is a serious problem that likely contributes to antimicrobial resistance worldwide. Copyright 2014 American Medical Association. All rights reserved.


Lei X.,Peking Union Medical College | Xiao X.,Peking Union Medical College | Wang J.,Peking Union Medical College | Wang J.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
Viruses | Year: 2016

Enterovirus genus includes multiple important human pathogens, such as poliovirus, coxsackievirus, enterovirus (EV) A71, EV-D68 and rhinovirus. Infection with EVs can cause numerous clinical conditions including poliomyelitis, meningitis and encephalitis, hand-foot-and-mouth disease, acute flaccid paralysis, diarrhea, myocarditis and respiratory illness. EVs, which are positive-sense single-stranded RNA viruses, trigger activation of the host antiviral innate immune responses through pathogen recognition receptors such as retinoic acid-inducible gene (RIG-I)-likeand Toll-like receptors. In turn, EVs have developed sophisticated strategies to evade host antiviral responses. In this review, we discuss the interplay between the host innate immune responses and EV infection, with a primary focus on host immune detection and protection against EV infection and viral strategies to evade these antiviral immune responses. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


Liu Y.,Tsinghua University | Zhang F.,Guangzhou 8th Peoples Hospital | Liu J.,Tsinghua University | Xiao X.,Tsinghua University | And 6 more authors.
PLoS Pathogens | Year: 2014

C-type lectins are a family of proteins with carbohydrate-binding activity. Several C-type lectins in mammals or arthropods are employed as receptors or attachment factors to facilitate flavivirus invasion. We previously identified a C-type lectin in Aedes aegypti, designated as mosquito galactose specific C-type lectin-1 (mosGCTL-1), facilitating the attachment of West Nile virus (WNV) on the cell membrane. Here, we first identified that 9 A. aegypti mosGCTL genes were key susceptibility factors facilitating DENV-2 infection, of which mosGCTL-3 exhibited the most significant effect. We found that mosGCTL-3 was induced in mosquito tissues with DENV-2 infection, and that the protein interacted with DENV-2 surface envelop (E) protein and virions in vitro and in vivo. In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. The vectorial susceptibility factors that facilitate pathogen invasion may potentially be explored as a target to disrupt the acquisition of microbes from the vertebrate host. Indeed, membrane blood feeding of antisera against mosGCTLs dramatically reduced mosquito infective ratio. Hence, the immunization against mosGCTLs is a feasible approach for preventing dengue infection. Our study provides a future avenue for developing a transmission-blocking vaccine that interrupts the life cycle of dengue virus and reduces disease burden. © 2014 Liu et al.


Fan F.,Chinese National Institute for Communicable Disease Control and Prevention | Liu Z.,University of Pennsylvania | Jabeen N.,University of Karachi | Dillon Birdwell L.,University of Pennsylvania | And 2 more authors.
Infection and Immunity | Year: 2014

Vibrio cholerae is the causative agent of the diarrheal disease cholera. The ability of V. cholerae to colonize and cause disease requires the intricately regulated expression of a number of virulence factors during infection. One of the signals sensed by V. cholerae is the presence of oxygen-limiting conditions in the gut. It has been shown that the virulence activator AphB plays a key role in sensing low oxygen concentrations and inducing the transcription of another key virulence activator, TcpP. In this study, we used a bacterial two-hybrid system to further examine the effect of oxygen on different virulence regulators. We found that anoxic conditions enhanced the interaction between TcpP and ToxR, identified as the first positive regulator of V. cholerae virulence genes. We further demonstrated that the TcpP-ToxR interaction was dependent on the primary periplasmic protein disulfide formation enzyme DsbA and cysteine residues in the periplasmic domains of both ToxR and TcpP. Furthermore, we showed that in V. cholerae, an interaction between TcpP and ToxR is important for virulence gene induction. Under anaerobic growth conditions, we detected ToxR-TcpP heterodimers, which were abolished in the presence of the reducing agent dithiothreitol. Our results suggest that V. cholerae may sense intestinal anoxic signals by multiple components to activate virulence. © 2014, American Society for Microbiology.


Xie L.,Tsinghua University | Yan X.,Tsinghua University | Du Y.,Tsinghua University | Du Y.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
Biosensors and Bioelectronics | Year: 2014

Despite recent progress in localized surface plasmon resonance (LSPR) based bio-sensing, it remains challenging to achieve sensitive and high throughput LSPR detection with facilities available in common laboratories. Here we developed a wall-less LSPR array chip for facile, label-free and high throughput detection of biomolecules using a normal microplate reader. The wall-less LSPR array chip was fabricated by immobilizing plasmonic nanoparticles (NPs) on a hydrophilic-hydrophobic patterned glass slide, enabling high throughput detection. The wall-less configuration simplifies chip fabrication and sample processing, and enables miniaturization to significantly reduce sample and reagent consumption. A double-gold NPs enhanced system comprising of 13-nm-gold NPs conjugated to aptamer modified 39-nm-gold NPs on glass substrate was adopted to constitute competitive replacement assay for signal amplification in small molecule (i.e. ATP) detection. Upon enhancement, the detection sensitivity of ATP was augmented by 5 orders of magnitude from 0.01. μM to 100. μM measured by the laboratory microplate reader. The wall-less LSPR sensor chip can be widely applied for miniaturized and high throughput detection of a variety of targets in biomedical applications and environmental monitoring using facilities available in common laboratories. © 2013 Elsevier B.V.


Zhu D.,Shandong University | Wang L.,Tsinghua University | Wang L.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases | Shang G.,Shandong University | And 8 more authors.
Molecular Cell | Year: 2014

Cyclic dinucleotides are a newly expanded class of second messengers that contribute to the regulation of multiple different pathways in bacterial, eukaryotic, and archaeal cells. The recently identified Vibrio cholerae dinucleotide cyclase (DncV, the gene product of VC0179) can generate three different cyclic dinucleotides and preferentially synthesize a hybrid cyclic-GMP-AMP. Here, we report the crystal structural and functional studies of DncV. We unexpectedly observed a 5-methyltetrahydrofolate diglutamate (5MTHFGLU2) molecule bound in a surface pocket opposite the nucleotide substrate-binding groove of DncV. Subsequent mutagenesis and functional studies showed that the enzymatic activity ofDncV is regulated by folate-like molecules, suggesting the existence of a signaling pathway that links folate-like metabolism cofactors to the regulation ofcyclic dinucleotide second messenger synthesis. Sequence analysis showed that the residuesinvolved in 5MTHFGLU2 binding are highly conserved in DncV orthologs, implying the presence of this regulation mechanism in a wide variety of bacteria. © 2014 Elsevier Inc.


Xiao X.,Tsinghua University | Liu Y.,Tsinghua University | Zhang X.,Tongji University | Wang J.,Tsinghua University | And 5 more authors.
PLoS Pathogens | Year: 2014

The complement system functions during the early phase of infection and directly mediates pathogen elimination. The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism. Thioester (TE)-containing proteins (TEPs), which show high similarity to mammalian complement C3, are thought to play a key role in innate immunity in arthropods. Herein, we report that a viral recognition cascade composed of two complement-related proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti macroglobulin complement-related factor (AaMCR), belonging to the insect TEP family, is a crucial effector in opposing the flaviviral infection of A. aegypti. However, AaMCR does not directly interact with DENV, and its antiviral effect requires an A. aegypti homologue of scavenger receptor-C (AaSR-C), which interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore, recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of antimicrobial peptides (AMPs), which exerts potent anti-DENV activity. Our results both demonstrate the existence of a viral recognition pathway that controls the flaviviral infection by inducing AMPs and offer insights into a previously unappreciated antiviral function of the complement-like system in arthropods. © 2014 Xiao et al.


Zhao Y.,Huazhong University of Science and Technology | Zhao Y.,CAS Wuhan Center for Magnetic Resonance | Wu J.,CAS Wuhan Center for Magnetic Resonance | Li J.V.,Imperial College London | And 4 more authors.
Journal of Proteome Research | Year: 2013

The gut microbiome is known to be extensively involved in human health and disease. In order to reveal the metabolic relationship between host and microbiome, we monitored recovery of the gut microbiota composition and fecal profiles of mice after gentamicin and/or ceftriaxone treatments. This was performed by employing 1H nuclear magnetic resonance (NMR)-based metabonomics and denaturing gradient gel electrophoresis (DGGE) fingerprint of gut microbiota. The common features of fecal metabolites postantibiotic treatment include decreased levels of short chain fatty acids (SCFAs), amino acids and primary bile acids and increased oligosaccharides, d-pinitol, choline and secondary bile acids (deoxycholic acid). This suggests suppressed bacterial fermentation, protein degradation and enhanced gut microbial modification of bile acids. Barnesiella, Prevotella, and Alistipes levels were shown to decrease as a result of the antibiotic treatment, whereas levels of Bacteroides, Enterococcus and Erysipelotrichaceae incertae sedis, and Mycoplasma increased after gentamicin and ceftriaxone treatment. In addition, there was a strong correlation between fecal profiles and levels of Bacteroides, Barnesiella, Alistipes and Prevotella. The integration of metabonomics and gut microbiota profiling provides important information on the changes of gut microbiota and their impact on fecal profiles during the recovery after antibiotic treatment. The correlation between gut microbiota and fecal metabolites provides important information on the function of bacteria, which in turn could be important in optimizing therapeutic strategies, and developing potential microbiota-based disease preventions and therapeutic interventions. © 2013 American Chemical Society.


Li Z.,Zhejiang University | Yi W.,Zhejiang University | Yi W.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
Glycoconjugate Journal | Year: 2014

Cancer cells exhibit increased uptake of glucose and glutamine, and rewire the metabolic flux toward anabolic pathways important for cell growth and proliferation. Understanding how this altered metabolism is regulated has recently emerged as an intense research focus in cancer biology. O-linked β-N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification of serine and/or threonine residues of nuclear and cytosolic proteins. O-GlcNAcylation has been identified in numerous proteins that are involved in many important cellular functions, including transcription, translation, signal transduction, and stress responses. More recently, increasing evidence indicates that O-GlcNAcylation plays important roles in regulating cancer metabolic reprogramming by modifying key transcription factors, metabolic enzymes and major oncogenic signaling pathways. Thus, O-GlcNAcylation emerges as a novel regulatory mechanism linking altered metabolism to cancer pathogenesis. © 2013 Springer Science+Business Media.

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