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1.  Genotypic Analysis of Klebsiella pneumoniae Isolates in a Beijing Hospital Reveals High Genetic Diversity and Clonal Population Structure of Drug-Resistant Isolates 
PLoS ONE  2013;8(2):e57091.
Background
The genetic diversity and the clinical relevance of the drug-resistant Klebsiella pneumoniae isolates from hospital settings are largely unknown. We thus conducted this prospective study to analyze the molecular epidemiology of K. pneumoniae isolates from patients being treated in the 306 Hospital in Beijing, China for the period of November 1, 2010–October 31, 2011.
Methodology/Principal Findings
Antibiotic susceptibility testing, PCR amplification and sequencing of the drug resistance-associated genes, and multilocus sequence typing (MLST) were conducted. A total of 163 isolates were analyzed. The percentage of MDR, XDR and PDR isolates were 63.8% (104), 20.9 (34), and 1.8% (3), respectively. MLST results showed that 60 sequence types (STs) were identified, which were further separated by eBURST into 13 clonal complexes and 18 singletons. The most dominant ST was ST15 (10.4%). Seven new alleles and 24 new STs were first identified in this study. Multiple logistic regression analysis revealed that certain clinical characteristics were associated with those prevalent STs such as: from ICU, from medical ward, from community acquired infection, from patients without heart disease, from patients with treatment success, susceptible to extended spectrum cephalosporin, susceptible to cephamycins, susceptible to fluoroquinolones, and with MDR.
Conclusions/Significance
Our data indicate that certain drug-resistant K. pneumoniae clones are highly prevalent and are associated with certain clinical characteristics in hospital settings. Our study provides evidence demonstrating that intensive nosocomial infection control measures are urgently needed.
doi:10.1371/journal.pone.0057091
PMCID: PMC3578803  PMID: 23437318
2.  Combined analysis of serum γ-glutamyl transferase isoenzyme II, α-L-fucosidase and α-fetoprotein detected using a commercial kit in the diagnosis of hepatocellular carcinoma 
γ-glutamyl transferase isoenzyme II (GGT-II) is a sensitive biomarker of hepatocellular carcinoma (HCC). However, numerous disadvantages of the traditional manual method affected its application. The commercial kit provided a convenient and fast method for the determination of GGT-II levels. The purposes of the present study were to compare the reproducibility and sensitivity between the manual and commercial kit methods and to evaluate the diagnostic efficiency for HCC with the combined analysis of GGT-II, α-L-fucosidase (AFU) and α-fetoprotein (AFP). In patients with various liver diseases (HCC, liver cirrhosis and chronic hepatitis) and normal subjects, GGT-II was detected by manual and commercial polyacrylamide gel electrophoresis (PAGE). The levels of AFU and AFP were assayed by colorimetry and a chemiluminescence immunoassay, respectively. The commercial PAGE had equal diagnostic efficiency with traditional manual PAGE and no significant differences were observed in intra- and average-gel reproducibility and GGT-II sensitivities between the manual and commercial PAGE (P>0.05). The incidence of GGT-II detected by commercial PAGE in HCC patients was 84.1% and <8% in benign liver disease. The levels of AFU and AFP in the benign liver diseases and normal subjects were lower than those in HCC. According to the cut-off value obtained by receiver operating characteristic curves, a total of 56.6 and 59.3% of HCC patients (64 out of 113 and 67 out of 113) had AFU >636.5 μmol/l h and AFP >44.0 μg/l, respectively. There were no significant correlations between GGT-II and AFU or AFP. Combined detection of GGT-II with AFU or AFP increased the diagnostic sensitivity to 92.9 and 93.8%, respectively. These results suggest that commercial PAGE provides a simple and reproducible method for GGT-II detection. Combined determination of GGT-II with AFU or AFP exhibited superior sensitivity and specificity for the diagnosis of HCC.
doi:10.3892/etm.2012.783
PMCID: PMC3524245  PMID: 23251247
γ-glutamyl transferase isoenzyme II; α-L-fucosidase; α-fetoprotein; hepatocellular carcinoma; diagnosis
3.  Ionic liquid-stabilized non-spherical gold nanofluids synthesized using a one-step method 
Nanoscale Research Letters  2012;7(1):583.
Ionic liquid (IL)-stabilized non-spherical gold nanofluids have been synthesized by a one-step method in aqueous solution. The whole reaction proceeded in room temperature. In the presence of amino-functionalized ionic liquids, gold nanofluids with long-wave surface plasmon resonance (SPR) absorption (>600 nm) could be obtained by adopting tannic acid as the reductant. The specific SPR absorption was related to the non-spherical gold nanoparticles including gold triangle, decahedra, and icosahedra nanocrystals. All the nanocrystals were observed by transmission electron microscopy. It was deduced that the formation of non-spherical gold nanofluids was related to the hydroxyls in tannic acid while IL acted as the synthesis template.
doi:10.1186/1556-276X-7-583
PMCID: PMC3484079  PMID: 23092303
Ionic liquid; Gold; Nanofluid; One-step method; Non-spherical
4.  Analysis of Drug Resistance Determinants in Klebsiella pneumoniae Isolates from a Tertiary-Care Hospital in Beijing, China 
PLoS ONE  2012;7(7):e42280.
Background
The rates of multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) isolates among Enterobacteriaceae isolates, particularly Klebsiella pneumoniae, have risen substantially worldwide.
Methodology/Principal Findings
To better understand the molecular mechanisms of drug resistance in K. pneumoniae, we analyzed the drug resistance determinants for K. pneumoniae isolates collected from the 306 Hospital, a tertiary-care hospital in Beijing, China, for the period of September 1, 2010-October 31, 2011. Drug susceptibility testing, PCR amplification and sequencing of the drug resistance determinants were performed. Conjugation experiments were conducted to examine the natural ability of drug resistance to disseminate among Enterobacteriaceae strains using a sodium azide-resistant Escherichia coli J53 strain as a recipient. Among the 223 consecutive non-repetitive K. pneumoniae isolates included in this study, 101 (45.3%) were extended-spectrum beta-lactamases (ESBLs) positive. The rates of MDR, XDR, and PDR isolates were 61.4% (n = 137), 22.0% (n = 49), and 1.8% (n = 4), respectively. Among the tested drug resistance-associated genes, the following ones were detected at relatively high rates blaCTX-M-10 (80, 35.9%), aacC2 (73, 32.7%), dhfr (62, 27.8%), qnrS (58, 26.0%), aacA4 (57, 25.6%), aadA1 (56, 25.1%). Results from conjugation experiments indicate that many of the drug resistance genes were transmissible.
Conclusions/Significance
Our data give a “snapshot” of the complex genetic background responsible for drug resistance in K. pneumoniae in China and demonstrate that a high degree of awareness and monitoring of those drug resistance determinants are urgently needed in order to better control the emergence and transmission of drug-resistant K. pneumoniae isolates in hospital settings.
doi:10.1371/journal.pone.0042280
PMCID: PMC3409176  PMID: 22860106
5.  Association of cardiac and renal function with extreme N-terminal fragment Pro-B-type natriuretic peptide levels in elderly patients 
Background
The data are inconsistent regarding whether extreme N-terminal fragment pro-B-type natriuretic peptide (NT pro-BNP) levels are associated with impaired renal function. Furthermore, the relationship between extreme NT pro-BNP levels and cardiac and renal function in elderly patients has not been reported. The aim of the present study was to examine a hypothesis that extreme NT pro-BNP levels may be associated with impaired cardiac and renal function in elderly patients.
Methods
We retrospectively analyzed the data of demographic, clinical, and echocardiographic features on 152 consecutive elderly patients aged more than 80 years old (average age, 83.65 ± 3.58 years) with NT pro-BNP levels ≥ 3000 pg/ml. The participants were divided into two categories according to their NT pro-BNP levels: (1) 3000–10000 pg/mL and (2) >10000 pg /mL.
Results
The number of patients with impaired renal function (P = 0.019) and the mortality (P < 0.001) in the period of inpatient was higher in the group with NT pro-BNP > 10000 pg /mL. The levels of serum creatinine and creatine kinase MB (CK-MB) in the group of NT pro-BNP > 10000 pg / mL were higher than those in the group of NT pro-BNP = 3000-10000 pg/mL (P = 0.001 and P = 0.023, respectively). Furthermore, no significant difference in the distribution by NYHA class in different NT pro-BNP levels was observed. Multiple linear regression analyses demonstrated that with NT pro-BNP levels as the dependent variable, NT pro-BNP levels were positively correlated with CK-MB (β = 0.182, P = 0.024) and creatinine levels (β = 0.281, P = 0.001). The area under the receiver-operating characteristic (ROC) curve of NT pro-BNP levels and clinical diagnosis of impaired renal function was 0.596 and reached significant difference (95%CI:0.503-0.688, P = 0.044).
Conclusion
These data suggest that the extreme elevation of NT pro-BNP levels (≥3000 pg/ml) is mainly determined by impaired renal function in elderly patients above 80 years. Extreme NT pro-BNP levels may be useful for assessing the severity of impaired renal function.
doi:10.1186/1471-2261-12-57
PMCID: PMC3422193  PMID: 22834778
NT pro-BNP; Factors; Elderly; Impaired renal function
6.  2-Amino-4,6-dimeth­oxy­pyrimidin-1-ium 2,2-dichloro­acetate 
In the title salt, C6H10N3O2 +·C2HCl2O2 −, two cations and two anions are linked by N—H⋯O hydrogen bonds, forming chains along the c axis.
doi:10.1107/S1600536812021496
PMCID: PMC3379456  PMID: 22719654
7.  Diagnosis Analysis of 4 TCM Patterns in Suboptimal Health Status: A Structural Equation Modelling Approach 
Background. We illustrated an example of structure equation modelling (SEM) in the research on SHS to explore the diagnosis of the Sub optimal health status (SHS) and provide evidence for the standardization of traditional Chinese medicine (TCM) patterns in SHS. And the diagnosis of 4 TCM patterns in SHS was evaluated in this analysis. Methods. This study assessed data on 2807 adults (aged 18 to 49) with SHS from 6 clinical centres. SEM was used to analyze the patterns of SHS in TCM. Parameters in the introduced model were estimated by the maximum likelihood method. Results. The discussed model fits the SHS data well with CFI = 0.851 and RMSEA = 0.075. The direct effect of Qi deficiency pattern on dampness pattern had the highest magnitude (value of estimate is 0.822). With regard to the construct of “Qi deficiency pattern”, “fire pattern”, “stagnation pattern” and “dampness pattern”, the indicators with the highest load were myasthenia of limbs, vexation, deprementia, and dizziness, respectively. It had been shown that estimate factor should indicate the important degree of different symptoms in pattern. Conclusions. The weights of symptoms in the respective pattern can be statistical significant and theoretical meaningful for the 4 TCM patterns identification in SHS research. The study contributed to a theoretical framework, which has implications for the diagnosis points of SHS.
doi:10.1155/2012/970985
PMCID: PMC3329144  PMID: 22550544
8.  Prevalence of cardiovascular disease in subjects hospitalized due to chronic obstructive pulmonary disease in Beijing from 2000 to 2010 
Objectives
To investigate the overall prevalence of cardiovascular disease (CVD) in subjects hospitalized for chronic obstructive pulmonary disease (COPD), and explore the prevalence of the major CVD complications and trends in patients with COPD over a 10-year period.
Methods
Medical records in the PLA General Hospital, Beijing Union Medical College Hospital, and Beijing Hospital from 2000/01/01 to 2010/03/03 were retrospectively reviewed. A total of 4960 patients with COPD were reviewed in the study (3570 males, mean age, 72.2 ± 10.5 years; 1390 females, mean age, 72.0 ± 10.4 years).
Results
The prevalence of CVD in COPD patients was 51.7%. The three most prevalent CVDs were ischemic heart disease (28.9%), heart failure (19.6%), and arrhythmia (12.6%). During the 10-year study period, the prevalence of various CVDs in COPD patients showed a gradual increasing trend with increasing age. There was higher morbidity due to ischemic heart disease (P < 0.01) in male COPD patients than in the female counterparts. However, heart failure (P < 0.01) and hypertension (P < 0.01) occurred less frequently in male COPD patients than in female COPD patients. Furthermore, the prevalence of ischemic heart disease decreased year by year. In addition to heart failure, various types of CVD complications in COPD patients tended to occur in younger subjects. The prevalence of all major types of CVD in women tended to increase year by year.
Conclusions
The prevalence of CVD in patients hospitalized for COPD in Beijing was high. Age, sex and CVD trends, as well as life style changes, should be considered when prevention and control strategies are formulated.
doi:10.3724/SP.J.1263.2012.00005
PMCID: PMC3390099  PMID: 22783317
Prevalence; Cross-sectional investigation; Chronic obstructive pulmonary disease; Cardiovascular disease
9.  μ-4,4′-Bipyridine-bis­[aqua­(4-hy­droxy­pyridine-2,6-dicarboxyl­ato)copper(II)] 
The title compound, [Cu2(C7H3NO5)2(C10H8N2)(H2O)2], exhibits a centrosymmetric binuclear molecule. Each completely deprotonated 4-hy­droxy­pyridine-2,6-dicarb­oxy­lic acid mol­ecule assumes a tridentate chelating coordination mode. The square-pyramidal coordination geometry around the CuII ion is completed by the bridging bipyridine ligand and an apical water molecule. Adjacent complexes are connected via O—H⋯O and C—H⋯O hydrogen bonds to generate a three-dimensional supra­molecular structure.
doi:10.1107/S1600536812004758
PMCID: PMC3297272  PMID: 22412462
10.  R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes 
Background
Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication.
Methods
Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848.
Results
We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes.
Conclusions
Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.
doi:10.1186/1471-2334-12-5
PMCID: PMC3274444  PMID: 22243920
Toll-like receptor; HIV; Monocytes; R-848
11.  ABO Blood Group and the Risk of Hepatocellular Carcinoma: A Case-Control Study in Patients with Chronic Hepatitis B 
PLoS ONE  2012;7(1):e29928.
Background
Studies have observed an association between the ABO blood group and risk of certain malignancies. However, no studies of the association with hepatocellular carcinoma (HCC) risk are available. We conducted this hospital-based case-control study to examine the association with HCC in patients with chronic hepatitis B (CHB).
Methods
From January 2004 to December 2008, a total of 6275 consecutive eligible patients with chronic hepatitis B virus (HBV) infection were recruited. 1105 of them were patients with HBV-related HCC and 5,170 patients were CHB without HCC. Multivariate logistic regression models were used to investigate the association between the ABO blood group and HCC risk.
Results
Compared with subjects with blood type O, the adjusted odds ratio (AOR) for the association of those with blood type A and HCC risk was 1.39 [95% confidence interval (CI), 1.05–1.83] after adjusting for age, sex, type 2 diabetes, cirrhosis, hepatitis B e antigen, and HBV DNA. The associations were only statistically significant [AOR (95%CI) = 1.56(1.14–2.13)] for men, for being hepatitis B e antigen positive [AOR (95%CI) = 4.92(2.83–8.57)], for those with cirrhosis [AOR (95%CI), 1.57(1.12–2.20)], and for those with HBV DNA≤105copies/mL [AOR (95%CI), 1.58(1.04–2.42)]. Stratified analysis by sex indicated that compared with those with blood type O, those with blood type B also had a significantly high risk of HCC among men, whereas, those with blood type AB or B had a low risk of HCC among women.
Conclusions
The ABO blood type was associated with the risk of HCC in Chinese patients with CHB. The association was gender-related.
doi:10.1371/journal.pone.0029928
PMCID: PMC3250489  PMID: 22235351
12.  Characteristics and Treatment Outcomes of Patients with MDR and XDR Tuberculosis in a TB Referral Hospital in Beijing: A 13-Year Experience 
PLoS ONE  2011;6(4):e19399.
Background
Information on treatment outcomes among hospitalized patients with multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are scarce in China.
Methodology/Principal Findings
We conducted this retrospective study to analyze the characteristics and treatment outcomes in MDR- and XDR-TB patients in the 309 Hospital in Beijing, China during 1996–2009. Socio-demographic and clinical data were retrieved from medical records and analyzed. Logistic regression analysis was performed to identify risk factors associated with poor treatment outcomes and Cox proportional hazards regression model was further used to determine risk factors associated with death in TB patients. Among the 3,551 non-repetitive hospitalized TB patients who had drug susceptibility testing (DST) results, 716 (20.2%) had MDR-TB and 51 (1.4%) had XDR-TB. A total of 3,270 patients who had medical records available were used for further analyses. Treatment success rates (cured and treatment completed) were 90.9%, 53.4% and 29.2% for patients with non-MDR-TB, patients with MDR-TB excluding XDR-TB and patients with XDR-TB, respectively. Independent risk factors associated with poor treatment outcomes in MDR-TB patients included being a migrant (adjusted OR = 1.77), smear-positivity at treatment onset (adjusted OR = 1.94) and not receiving 3 or more potentially effective drugs (adjusted OR = 3.87). Independent risk factors associated with poor treatment outcomes in XDR-TB patients were smear-positivity at treatment onset (adjusted OR = 10.42) and not receiving 3 or more potentially effective drugs (adjusted OR = 14.90). The independent risk factors associated with death in TB patients were having chronic obstructive pulmonary disease (adjusted HR = 5.25) and having hypertension (adjusted HR = 4.31).
Conclusions/Significance
While overall satisfactory treatment success for non-MDR-TB patients was achieved, more intensive efforts should be made to better manage MDR- and XDR-TB cases in order to improve their treatment outcomes and to minimize further emergence of so-called totally drug-resistant TB cases.
doi:10.1371/journal.pone.0019399
PMCID: PMC3084844  PMID: 21559362
13.  5-Amino-7-(4-bromo­phen­yl)-3,7-di­hydro-2H-thieno[3,2-b]pyran-6-carbo­nitrile 1,1-dioxide 
In the title compound, C14H11BrN2O3S, the 2,3-dihydro­thio­phene ring is almost planar [maximum deviation = 0.006 (1) Å]. The pyran ring is in an envelope conformation [puckering parameters Q = 0.115 (2) Å, θ = 77.5 (10), ϕ = 172.9 (10)°]. The pyran and phenyl rings are approximately perpendicular, making a dihedral angle of −76.4 (2)°. The crystal packing is stabilized by inter­molecular N—H⋯O hydrogen bonds, with the sulfone O atoms acting as acceptors.
doi:10.1107/S1600536809055214
PMCID: PMC2979727  PMID: 21579705
14.  5-Amino-7-(3-chloro­phen­yl)-3,7-di­hydro-2H-thieno[3,2-b]pyran-6-carbo­nitrile 1,1-dioxide 
The title compound, C14H11ClN2O3S, with fused thiophene and pyran rings, was synthesized via the condensation of dihydro­thio­phen-3(2H)-one 1,1-dioxide and 2-(3-chloro­benz­yl­idene)malononitrile catalysed by triethyl­amine in ethanol. The thio­phene ring adopts an envelope conformation and the pyran ring is planar (r.m.s. deviation = 0.0067 Å). The dihedral angle between the pyran and phenyl rings is 80.8 (1)°. The crystal packing is stabilized by inter­molecular N—H⋯N and N—H⋯O hydrogen bonds in which the cyano N and sulphone O atoms, respectively, acting as acceptors.
doi:10.1107/S1600536809055202
PMCID: PMC2979823  PMID: 21579718
15.  2-Amino-4,6-dimethyl­pyrimidinium chloro­acetate 
There are two cations and two anions in the asymmetric unit of the title compound, C6H10N3 +·C2H2ClO2 −. In the crystal, the components are linked by inter­molecular N—H⋯O and N—H⋯N hydrogen bonds to form a two-dimensional network. Additional stabilization is provided by weak inter­molecular C—H⋯O inter­actions.
doi:10.1107/S1600536809044444
PMCID: PMC2971421  PMID: 21578492
16.  2-Amino-4,6-dimethyl­pyrimidinium dihydrogenphosphate 
In the crystal structure of the title compound, C6H10N3 +·H2PO4 −, the cations and anions are linked by inter­molecular O—H⋯O and N—H⋯O hydrogen bonds, forming a two-dimensional network. Additional stabilization is provided by weak inter­molecular C—H⋯O inter­actions. N—H⋯N inter­actions are also present.
doi:10.1107/S160053680903880X
PMCID: PMC2971252  PMID: 21578254
17.  tert-Butyl­ammonium 2,3,4,5-tetra­chloro-6-methoxy­carbonyl­benzoate 
In the title compound, C4H12N+·C9H3Cl4O4 −, the benzene ring forms dihedral angles of 62.4 (2) and 64.0 (3)°, respectively, with the essentially planar methoxy­carbonyl and carboxyl­ate groups. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds connect anions and cations, forming one-dimensional chains along [010].
doi:10.1107/S1600536808036398
PMCID: PMC2959952  PMID: 21581294

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