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Acinetobacter baumannii is a strictly aerobic, nonmotile, nonfermenting, gram-negative bacillus. It is a highly infectious and invasive pathogen with high mortality and morbidity rates among immunodeficient patients. Due to increasing levels of drug resistance and the inefficiency of existing antimicrobial treatments, it is crucial to develop novel agents to control this pathogen. Several recent studies have investigated virulence factors that are associated with the pathogenesis of A. baumannii, and could thus serve as novel therapeutic targets. The present review comprehensively summarizes the current understanding of these virulence factors and their mechanisms in A. baumannii. We also highlight factors that could be potential therapeutic targets, as well as list candidate virulence factors for future researchers and clinical practitioners.

Potential of zero charge (PZC) is an important reference for understanding the interface charge and structure at a given potential, and its difference from the work function of metal surface (ΦM) is defined as the Volta potential difference (ΔΦ). In this work, we model 11 metal/water interfaces with ab initio molecular dynamics. Interestingly, we find ΔΦ is linearly correlated with the adsorption energy of water (Eads) on the metal surface. It is revealed that the size of Eads directly determines the coverage of chemisorbed water on the metal surface and accordingly affects the interface potential change caused by electron redistribution (ΔΦel). Moreover, ΔΦ is dominated by the electronic component ΔΦel with little orientational dipole contributing, which explains the linear correlation between ΔΦ and Eads. Finally, it is expected that this correlation can be helpful for effectively estimating the ΔΦel and PZC of other metal surfaces in the future work.

Herein, we have designed and developed a heteromultivalent chitosan base α-Fe2O3/Gadofullerene (GdF) hybrid composite through a simple chemical precipitation method. Unlike other methods, the addition of external stabilizing agents to generate GdF nanoparticles (NPs) was not necessary herein. The prepared chitosan-α-Fe2O3/GdF hybrid nanocomposites were characterized using UV, FT-IR, XRD and morphological microscopic analyses. The results showed that α-Fe2O3 and GdF hybrid nanocomposites were successfully grown on the surface of chitosan. The FT-IR vibration peaks showed the formation of Fe2O3 NPs, and the vibration peak for Fe–O was 568 cm−1. The broad absorption peak observed in the range of 250–350 nm and a sharp absorption peak at 219 nm represents the UV absorption of the synthesized hybrid composites. XRD pattern showed sharp peaks of crystallinity and purity of α-Fe2O3 nanoparticles. Finally, the synthesized chitosan-α-Fe2O3/GdF hybrid composites were screened for their antibacterial resistance against the Escherichia coli, Pseudomonas aeruginosa, Bacilus subtilis, and Staphylococcus aereus. In addition, in vitro biocompatibility results exhibited that developed hybrid samples have provided high cell compatibility with fibroblast (L929) cell line. The in vivo bio inspired nanotherapeutics have the potential action to effective inhibition ability on antibiotic-resistant P. aeruginosa, which has been main factor of inducing pneumonia. In conclusion, we expect biomimicking systems combined with the effective antibacterial agent could be the suitable next generation therapeutic potential factors for prevention and treatment of antibiotic-resistant pneumonia.

Structural system identification aims at identifying the parameters of a theoretical (e.g., finite element) model using measured data of a constructed structure. As a means of extracting relevant information from noisy vibration data, one common strategy is to adopt a ‘two-stage’ approach, where natural frequencies and mode shapes are first estimated from Stage I (modal identification), and then used for further estimating the structural model parameters (e.g., stiffness, mass) in Stage II. In a Bayesian statistical context with sufficient data so that model parameters can be identified uniquely, the identification result is characterized by the ‘most probable value’ (MPV) that gives the best estimate, and a covariance matrix that quantifies the remaining uncertainty. Computationally, determining the MPV involves solving an optimization problem with a measure-of-fit function; the covariance matrix involves taking the Hessian of the function. Exploiting the mathematical structure of the measure-of-fit function in the two-stage problem, this work proposes a Fisher scoring method for determining the MPV, where the Hessian matrix in a Newton’s iteration is replaced by the Fisher information matrix to eliminate repeated computations of second order derivatives and to improve con-vergence robustness. Advanced techniques of eigenvalue sensitivity are applied so that the gradient and Hessian involved in MPV and covariance matrix computations can be obtained accurately and efficiently by solving full-rank matrix equations for the subject modes only. The proposed methodology is investigated with synthetic and laboratory experimental data. Performance in terms of convergence robustness and efficiency is compared with existing methods, including simplex search and Newton’s method. Ministry of Education (MOE) Nanyang Technological University Submitted/Accepted version The research presented in this work is supported by grant SUG/4 (04INS000618C120) from the Nanyang Technological University (NTU) and Academic Research Fund Tier 1 (RG68/22) from the Ministry of Education, Singapore.

Aconiti kusnezoffii Radix (Caowu), a traditional Chinese medicine and Mongolian medicine, has been commonly used owing to its analgesic and anti-inflammatory effects. Here, we performed a qualitative analysis of aconite alkaloids (AAs) in raw and processed Aconiti kusnezoffii Radix by ultra-high-performance liquid chromatography (HPLC) electrospray ionization-tandem mass spectrometry. Furthermore, we quantified benzoylaconine, benzoylmesaconine, benzoylhypaconine, aconitine, mesaconitine, and hypaconitine in raw and processed Aconiti kusnezoffii Radix using a HPLC system coupled with a diode array detector. The analysis of AA fragmentation patterns in positive electrospray ionization mode revealed 155 AAs, including 6 with unambiguous identities, 109 with putative assignments, and 40 unknown compounds. Additionally, lipopolysaccharide-treated RAW264.7 macrophages were used to evaluate the anti-inflammatory properties of the alkaloid extracts of Aconiti kusnezoffii Radix. Importantly, alkaloid extracts of Aconiti kusnezoffii Radix at three different concentrations exhibited protective effect against lipopolysaccharide-induced inflammation. Thus, the proposed method can be used not only for the qualitative and quantitative analyses of Aconiti kusnezoffii Radix, but also for evaluating other Aconitum spp. Our study lays a foundation for the clinical application of poisonous Aconitum.

The prevalence of multidrug-resistant bacteria has been increasing rapidly worldwide, a trend that poses great risk to human and animal health and creates urgent need for pharmaceutical and nonpharmaceutical approaches to stop the spread of disease due to antimicrobial resistance. Here, we found that alanine, aspartate, and glutamate metabolism was inactivated, and glutamine was repressed in multidrug-resistant uropathogenic

Adsorbates at the electrode change the structure of the electrode/electrolyte interface. Despite the important influence of the interfacial structure on electrochemical processes, computational investigations targeting this influence are still lacking. Even the impact of one of the most common adsorbates, namely, adsorbed OH, is so far largely unknown. In this study, we choose the Pt(100)/water interface as a model system to investigate the interfacial water structure at various OH coverages with ab initio molecular dynamics. We find that the interfacial water structure is highly sensitive to the adsorption site of OH (namely, top or bridge site) and that the preference of adsorption sites of OH is, in turn, strongly influenced by the solvation caused by interfacial water. This indicates that the structure of water is correlated with that of OH. Based on a detailed analysis, we attribute these observations to a strong hydrogen-bonding network between OH and the interfacial water. This hydrogen-bonding network also results in a complicated dependence of the interfacial potential on the OH coverage, which is governed not only by the dipole induced by OH but also by the influence the OH species have on the interfacial water structure.

Serum resistance is a poorly understood but common trait of some difficult-to-treat pathogenic strains of bacteria. Here, we report that glycine, serine and threonine catabolic pathway is down-regulated in serum-resistant Escherichia coli, whereas exogenous glycine reverts the serum resistance and effectively potentiates serum to eliminate clinically-relevant bacterial pathogens in vitro and in vivo. We find that exogenous glycine increases the formation of membrane attack complex on bacterial membrane through two previously unrecognized regulations: 1) glycine negatively and positively regulates metabolic flux to purine biosynthesis and Krebs cycle, respectively. 2) α-Ketoglutarate inhibits adenosine triphosphate synthase, which in together promote the formation of cAMP/CRP regulon to increase the expression of complement-binding proteins HtrE, NfrA, and YhcD. The results could lead to effective strategies for managing the infection with serum-resistant bacteria, an especially valuable approach for treating individuals with weak acquired immunity but a normal complement system., Serum-resistant bacteria can escape complement killing in the bloodstream. Here, using metabolomics and metabolite perturbations, the authors describe an altered metabolic state in serum-resistant Escherichia coli and show that exogenous glycine potentiates elimination of pathogenic bacteria in vivo.

BACKGROUND With the development of science and technology, self-service facilities have been widely used in hospitals. This study aimed to assess the microbial contamination characteristics on touch surfaces in outpatient, self-service facilities from Monday to Friday. METHODS Touch surfaces in outpatient facilities were swabbed and surveyed for total microbial growth before and after work every morning. Selected bacteria were identified to screen for pathogenic organisms. RESULTS There were 360 samples collected, 87 samples (24.2%) were culture-positive. Staphylococcus species were the main microbial contamination. The three most common bacteria were S. hominis, S. epidermidis and S. hemolyticus. After work, more microbial contamination was found on Monday (p = 0.029). There was no difference in sample positive rates between self-service facilities and manual service area. Although, the antibiotic resistance patterns of different staphylococcus species were different, the overall drug resistance rate is low. Only one S. aureus was methicillin-Sensitive S. aureus. CONCLUSIONS The self-service facilities' touch surfaces microbial contamination were similar to manual service area, but the more used, the more microbial contamination was found. Hospitals should enhance cleaning times of self-service facilities to keep them clean, especially on Mondays.

Purpose Methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin, a pore-forming toxin, is a common cause of necrotizing pneumonia. However, the early pulmonary inflammatory response following PVL(+) MRSA infection is unknown. The purpose of this study was to use a murine model to determine the effect of PVL(+) MRSA on lung tissues and the expression of cytokines and JAK and STAT mRNA and protein. Methods Mice were randomly divided into 3 groups and intra-nasally treated with PBS (control group), recombinant PVL (rPVL group), and PVL(+) MRSA (PVL group). At 24 and 48 h after inoculation, bronchoalveolar lavage fluid (BALF) was tested for cytokine levels, and lung tissues were tested for JAK and STAT mRNA and protein expression, and examined after hematoxylin and eosin staining. Results Mice infected with the PVL(+) strain became ill, characterized by impaired mobility, hunched posture, ruffled fur, and labored breathing. Lung tissue exhibited tissue necrosis and hemorrhage. BALF levels of IL-8, TNF-α, IFN-γ, IL-12, sICAM-1, and sVCAM-1 were increased in the rPVL or PVL groups, while levels of IL-10 and IL-4 levels were similar among the groups. JAK1 and STAT1 mRNA expression and protein levels were increased in lung tissue from mice infected with PVL(+) MRSA and rPVL. Conclusions PVL is a significant S. aureus virulence factor, and upregulates the expression of proinflammatory cytokines but does not affect the expression of anti-inflammatory cytokines. The effect of PVL may be due to JAK/STAT pathway activation. Blockade of the JAK/STAT pathway may decrease the severity of PVL(+) MRSA pneumonia.

The emergence and ongoing spread of multidrug-resistant bacteria puts humans and other species at risk for potentially lethal infections. Thus, novel antibiotics or alternative approaches are needed to target drug-resistant bacteria, and metabolic modulation has been documented to improve antibiotic efficacy, but the relevant metabolic mechanisms require more studies. Here, we show that glutamate potentiates aminoglycoside antibiotics, resulting in improved elimination of antibiotic-resistant pathogens. When exploring the metabolic flux of glutamate, it was found that the enzymes that link the phosphoenolpyruvate (PEP)-pyruvate-AcCoA pathway to the TCA cycle were key players in this increased efficacy. Together, the PEP-pyruvate-AcCoA pathway and TCA cycle can be considered the pyruvate cycle (P cycle). Our results show that inhibition or gene depletion of the enzymes in the P cycle shut down the TCA cycle even in the presence of excess carbon sources, and that the P cycle operates routinely as a general mechanism for energy production and regulation in Escherichia coli and Edwardsiella tarda These findings address metabolic mechanisms of metabolite-induced potentiation and fundamental questions about bacterial biochemistry and energy metabolism.

The emergence of multidrug-resistant bacteria presents a severe threat to public health and causes extensive losses in livestock husbandry and aquaculture. Effective strategies to control such infections are in high demand. Enhancing host immunity is an ideal strategy with fewer side effects than antibiotics. To explore metabolite candidates, we applied a metabolomics approach to investigate the metabolic profiles of mice after Klebsiella pneumoniae infection. Compared with the mice that died from K. pneumoniae infection, mice that survived the infection displayed elevated levels of l-valine. Our analysis showed that l-valine increased macrophage phagocytosis, thereby reducing the load of pathogens; this effect was not only limited to K. pneumoniae but also included Escherichia coli clinical isolates in infected tissues. Two mechanisms are involved in this process: l-valine activating the PI3K/Akt1 pathway and promoting NO production through the inhibition of arginase activity. The NO precursor l-arginine is necessary for l-valine-stimulated macrophage phagocytosis. The valine-arginine combination therapy effectively killed K. pneumoniae and exerted similar effects in other Gram-negative (E. coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. Our study extends the role of metabolism in innate immunity and develops the possibility of employing the metabolic modulator-mediated innate immunity as a therapy for bacterial infections.

Matrix metalloproteinase (MMP) family member matrilysin (matrilysin) has been indicated to induce apoptosis-resistance and chemoresistance. The purpose of current study was to investigate the potential capacity of induction cisplatin-resistance upon the unremitting exposure to exogenic matrilysin. At the same time, the expressions of apoptosis-related genes were examined to clarify the underlying mechanisms. A549 lung adenocarcinoma cells was used to establish our chronic exposure models. The viability of A549 lung adenocarcinoma cells was determinated by MTT and the apoptosis was assessed by Hoechst 33342 staining and Annexin V-FITC/PI apoptosis kit. The expressions of apoptosis-relative genes were evaluated by flow cytometry, immunocytochemistry staining and real-time quantitative RT-PCR, respectively. Overall, chronic exposure to crescenting level of exogenous matrilysin (10, 50, 100, 200 ng/ml) did not significantly alter the growth rates of A549 cells. However, a certain range of matrilysin might protect tumor cells from cisplatin-medicated death. The underlying mechanism may due to the Bcl-2 overexpression and imbalance in the ratio of Bcl-2/Bax. Our results offer a potential mechanism to explain the impact of matrilysin on apoptosis and provide new insights into the profound mechanisms of acquired cisplatin-resistance. Further researches are highly suggestive of this association which has great clinical implications.

Fundamental studies have suggested that matrix metalloproteinases-7 (MMP-7) expression is associated with chemoresistance and constitutes a prognostic factor in several solid tumors. The present study assessed the prognostic and predictive value of MMP-7 in tumors of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. Immunohistochemistry was performed to evaluate the expression of MMP-7, apoptosis-related proteins Bcl-2, Bax, Fas and FasL and the Ki-67 proliferation marker. The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) method was performed to investigate tumor apoptosis. Ninety carcinomas (56.6%) were identified as high expression of MMP-7. Overexpression of MMP-7 was more frequent in adenocarcinomas than in squamous cell carcinomas (P = 0.032). The expression of MMP-7 was positively related with Ki-67 index and Bcl-2, but not apoptosis index. MMP-7 status was correlated inversely with response to chemotherapy in overall patients (response rates, 20.0% and 35.8%, for patients with high-MMP-7 and low-MMP-7 tumors, respectively, P = 0.036), especially in adenocarcinoma (P = 0.021), but not in patients with squamous cell carcinomas (P = 0.373). The overall survival was significantly lower in NSCLC patients with high MMP-7 than in those with low MMP-7 (P < 0.001). A Cox regression analyses also demonstrated MMP-7 status to be a significant prognostic factor (hazard ratio, 5.49 P = 0.001). These findings suggest that the expression level of MMP-7 in tumor cells is predictive of response to chemotherapy and outcome in patients with advanced NSCLC receiving platinum-based chemotherapy.

Aims and background Matrix metalloproteinase (MMP) family member MMP-7 (matrilysin) cleaves various cell-surface proteins to alter their effector functions in addition to a broad substrate specificity against extracellular matrix components. Matrilysin expression is closely associated with the advanced clinicopathological stages and unfavorable prognosis. The current study tried to describe the comprehensive impacts of matrilysin on proliferation, and focused on its influence on the susceptibility to FasL-induced apoptosis in A549 lung adenocarcinoma cell line. We also detected the expressions of apoptosis-relative genes to further clarify the underlying mechanisms. Study design The viability of A549 cells was determined by MTT and the apoptosis was assessed by Hoechst 33342 staining and Annexin V-FITC/PI apoptosis kit. The expressions of apoptosis-relative genes were evaluated by flow cytometry, ELISA, and real-time quantitative RT-PCR, respectively. Results Overall, matrilysin exhibited the inhibition of cell growth in a dose- and time-dependent manner by arresting in G0/G1 phase of the cell cycle and inducing apoptosis on A549 cells. Although it directly promoted apoptosis at high concentrations, a certain range of matrilysin might protect tumor cells from FasL-mediated death. The underlying mechanism may be due to the imbalance in the susceptibility of surface membrane-bound Fas receptor and ligand to proteolysis activity of matrilysin. Conclusion Our data indicated matrilysin may be multiple, multifarious, and multifaceted functions contributing to early tumor growth. A therapeutic key might be to modulate activity and function of matrilysin under diverse pathological conditions, but not completely eliminate the expression or function.

People have paid much attention on the pesticide residues in agricultural products at present. However there are less concern on processed agricultural products or on final consumption of processed foods, even though most processed foods are being finally consumed. In this paper, pesticide residues such as imidacloprid and triabendazole on the cherry tomatoes were cleaned by conducting different household cleaning methods in the way of normal vegetable cleaning. Results showed that it can effectively remove the residual imidacloprid on cherry tomatoes by soaking first them in water and then rinsing them with running tap water, wherein the removal rates were 30.59%-65.24% and processing factor were 0.3476-0.6941. While to remove the residual triabendazole on cherry tomatoes, we first soaked them in 0.1% edible vinegar solution and then rinsed them with running tap water, which can also effectively remove the triabendazole residues on the cherry tomatoes, with removal rates reaching 29.31%-74.01% and processing factor reaching 0.2599-0.7069. Our research provides an inherent relationship between pesticide residues and cleaning approaches as well as important theoretical basis for risk assessments of agricultural food.

To investigate the effect of budesonide (BUD) on thymic stromal lymphopoietin receptor (TSLPR) of dendritic cells (DCs) in OVA-induced mouse asthma models and to explore the mechanisms by studying the effect of BUD on function of DCs from the model.Eighteen BALB/c female mice were randomly divided into a control group, an asthma group and a BUD intervention group, with 6 mice in each group. Mice were sensitized and challenged with ovalbumin (OVA) to establish the asthmatic model. The bronchoalveolar lavage fluid (BALF) and DCs of spleen from the 3 groups were harvested and the supernatants of BALF and DCs were analyzed for levels of TSLP and TSLPR, respectively, by commercially available ELISA kit. The percentage of eosinophils (EOS) in BALF was counted. The expression of CD₄₀, CD₈₀ and CD₈₆ in DCs was detected by FACS. The DCs were then washed, and co-cultured in vitro with autologous T cells purified by a nylon cotton column. The supernatants of DC-T co-culture were collected after 72 h incubation, and analyzed for levels of interleukin-5 (IL-5) and interferon-γ (IFN-γ) by ELISA.The levels of TSLP in BALF and TSLPR in DCs from the asthma group were significantly increased compared with the control group [(44.0 ± 5.1) ng/L vs (14.2 ± 3.6) ng/L, P0.01 and (19.7 ± 2.2) ng/L vs (10.4 ± 1.2) ng/L, P0.05, respectively]. The expression of CD₄₀, CD₈₀ and CD₈₆ of DCs and IL-5 in the culture supernatants of DC-T co-culture was significant up-regulated in the asthma group compared with the control group (P0.05). Furthermore, the addition of BUD reduced the expression of CD₄₀, CD₈₀, CD₈₆, TSLPR in DCs, IL-5 in the culture supernatants of DC-T co-culture, TSLP and EOS in BALF. The level of INF-γ in the DC-T co-culture supernatants of the 3 groups did not achieve statistical significance (F = 0.82, P0.05).These results demonstrate that the therapeutic activity of BUD in asthmatic mice may be related to modulation of Th1 and Th2 cell functions and this effect is probably mediated through the TSLP-DC pathway.

To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect.A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy.In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%).Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.

To explore the potential roles of serum Dickkopf-1 (DKK-1) and tartrate-resistant acid phosphatase 5b (TRAP5b) in gouty arthritis.Blood serum DKK-1 and TRAP5b were assessed by ELISA method. The serum samples were collected from 150 patients with gouty arthritis, 100 with hyperuricemia and 100 healthy controls. Of the 150 gouty arthritis patients, 40 were diagnosed as acute gout (joint rash and pain), and the other 110 as chronic gout. At the time of serum sampling, various clinical and laboratory parameters were assessed. The correlations of DKK-1 or TRAP5b and clinical/laboratory parameters were analyzed.(1) The serum levels of DKK-1 were elevated in the patients with gouty arthritis [(2 574.8± 997.9) ng/L] and with hyperuricemia [(2 009.4±756.9) ng/L] compared with the healthy controls [(981.8±770.7) ng/L],F=49.59, P0.001. (2) The serum levels of TRAP5b in the three groups were (3.2±1.4)U/L, (2.5±1.4)U/L and (0.2±0.2)U/L, respectively. F=103.039, P0.001. (3) A significant difference of DKK-1 was observed between the patients with gouty arthritis and with hyperuricemia (t=3.998, P0.001). Similarly, a significant difference of TRAP5b was observed between the patients with gouty arthritis and with hyperuricemia(t=3.391, P=0.004). (4) In the patients with gouty arthritis, there was a positive correlation between DKK-1 and TRAP5b(r=0.47, P0.001), while the levels of DKK-1 were not related with age, disease duration, body mass index or serum uric acid(r=-0.153, -0.123, 0.158, 0.00,P=0.126, 0.509, 0.381, 0.926). (5) In the patients with gouty arthritis, the serum levels of TRAP5b were elevated in the patients with tophi compared with the patients without tophi[(8.4±6.4)U/L vs. (4.0±1.6)U/L,t=-2.938,P=0.007]. The level of TRAP5b was associated with the disease duration(r=0.455,P=0.01), while there was no correlation between TRAP5b and age, body mass index or serum uric acid (r=0.135, 0.278, 0.144,P=0.595, 0.117,0.132).In the patients with gouty arthritis, the levels of DKK-1 were remarkably elevated, and there was a positive correlation between DKK-1 and TRAP5b. Our results demonstrate that DKK-1 is involved in bone destruction in gouty arthritis.

To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA).Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed.In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD.The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.

To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors.A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application.In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000).About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.

The aim of this study was to compare more conclusively the efficacy and safety of moxifloxacin, a new respiratory fluoroquinolone antibiotic with levofloxacin therapy which has been reported to possess good efficacy for community acquired pneumonia (CAP) in hospitalized elderly patient. The entire patients were mild to moderate by CAP. All the trials administered intravenously moxifloxacin (400 mg daily) and intravenously levofloxacin (200- 500 mg daily) for 7-14 days. Clinical response during therapy was between days 3 and 5 after the start of therapy. A meta-analysis of randomized controlled trials (RCTs, identified in CNKI, PubMeD, Embase, Google) were performed. Eight RCTs involving 1310 patients were included in meta- analysis. Two reviewers independently extracted data from published trials that compared fluoroquinolones. A meta-analysis was performed with the clinical outcomes of moxifloxacin and levofloxacin. Moxifloxacin monotherapy was associated with better therapeutic effect [(OR=1.63, 95%CI 1.01-2.63) and similar adverse effect (OR=1.12, 95%CI 0.81-1.55)] compared with levofloxacin therapy for CAP. Moxifloxacin has better therapeutic effects with comparable adverse events compared tolevofloxacin. Key words: Moxifloxacin, levofloxacin, randomized control trial, community acquired pneumonia.

To describe the clinical features of reported cases of community-acquired pneumonia (CAP) due to methicillin-resistant Staphylococcus aureus (MRSA), and to evaluate the risk factors related to outcome.A systematic search of databases from January 1995 to December 2009 was performed. Baseline characteristics of survivors and non-survivors in the hospital were compared with the chi2 test for categorical variables. Variables with P0.2 were entered in Logistic regression. Survival analysis was estimated by the Kaplan-Meier method according to use of antimicrobials inhibiting toxin production.Fifty-two articles were identified reporting data on 74 patients, with 41.1% of total mortality, short duration of symptom onset to death [(6.1+/-11.0) days], and prolonged hospital admissions [(28.6+/-29.1) days]. Logistic regression analysis showed that influenza like symptoms (P=0.04), hemoptysis (P0.01), leucopenia (P0.01) were the risk factors associated with death, and using clindamycin or linezolid which could inhibit the Panton-Valentine leukocidin (PLV, P0.01) was the factor associated with survival. Kaplan-Meier analysis indicated that the antibiotic therapies inhibiting toxin production were associated with improved outcome in these cases (chi2=21.59, P0.01).CAP due to MRSA is a severe disease with significant lethality. Empiric therapy of severe CAP with flu-like symptoms, hemoptysis and leucopenia should include coverage for MRSA. Targeted treatment with antimicrobials inhibiting toxin production appear to be more appropriate selection.

Background: Although community-acquired Staphylococcus aureus pneumonia with highly virulent Panton-Valentine leukocidin (PVL)-positive strains, a severe disease with significant lethality, is rare, especially in adult and adolescent patients, recent reports highlight that these infections are on the rise. Objectives: To describe the demographic and clinical features of reported cases of life-threatening community-acquired S. aureus pneumonia with usually PVL-positive strains in adult and adolescent patients, to evaluate the variables related to death, and to select a more appropriate antimicrobial treatment for this potentially deadly disease. Methods: We summarized all of the 92 reported cases and our case. The effect of 5 variables on mortality was measured using logistic regression. Results:S. aureus community-acquired pneumonia (CAP) with usually PVL-positive strains is a severe disease with significant lethality, i.e. 42.9%; a short duration of the time from the onset of symptoms to death, i.e. 5.5 ± 10.1 days, and prolonged hospital admissions, i.e. 33.2 ± 29.5 days. Seventy-three cases have been tested for the gene for PVL, and 71 strains have been found to carry the PVL gene. Logistic regression analysis showed that leucopenia (p = 0.002), influenza-like symptoms or laboratory-confirmed influenza (p = 0.011), and hemoptysis (p = 0.024) were the factors associated with death. Antibiotic therapies inhibiting toxin production were associated with an improved outcome in these cases (p = 0.007). Conclusions: Physicians should pay special attention to those patients who acquired severe CAP during influenza season and have flu-like symptoms, hemoptysis, and leucopenia, and they should consider S. aureus more frequently among the possible pathogens of severe CAP. Empiric therapy for severe CAP with this distinct clinical picture should include coverage for S. aureus. Targeted treatment with antimicrobials inhibiting toxin production appears to be a more appropriate selection.

To investigate the clinical, imaging and pathogenic features of pulmonary nocardiosis and the drug resistance of Nocardia.The clinical and radiological data of 2 cases of pulmonary nocardiosis in this hospital were presented, and 32 cases reported in the Chinese literature since 1982 were reviewed.Among the 34 cases of Nocardia infections, there were 26 cases of pulmonary nocardiosis, and 4 of whom died. Multiple organ infection occurred in 11 patients, including 7 with pulmonary and skin infections, 3 with pulmonary, skin and intracranial infections, and 1 with pulmonary and intracranial infections. All patients with pulmonary nocardiosis had cough. Of the 34 cases, 27 had fever, including intermittent fever in 5, and sustained fever in 22 cases. Of the 11 cases of pulmonary nocardiosis complicated with skin or intracranial dissemination, 8 patients were immunocompromised and 3 were immunocompetent (chi(2) = 2.08, P0.05). Three cases died in the immunocompromised group and 1 died in the immunocompetent group. Nocardia asteroides was identified in 14 cases, Nocardia brasiliensis in 4 cases, and the other 8 were not classified. In the patients with complicated skin or intracranial infections, 8 were caused by Nocardia asteroids, and 2 were caused by Nocardia brasiliensis. Chest X-ray or CT imaging of the lungs showed pleural effusion in 8, masses in 7, infiltrates in 6, cavities in 6, and nodular lesions in 5 cases. Antimicrobial susceptibility testing showed that Nocardia was sensitive to sulfonamide, amikacin, cefotaxime, ceftriaxone, minocycline, fluoroquinolones, and linezolid.Immunosuppression is the most important predisposing factor for pulmonary nocardiosis. The most common pathogenic bacterium is Nocardia asteroids, which is frequently associated with disseminated lesions. The radiographic abnormalities of the lung show pleural effusion, masses, infiltration or cavity. With the increasing rate of resistance of Nocardia to the sulfonamide, the combination of antibiotic regimen according to susceptibility testing needs to be considered. Poor outcome is mostly found in immunocompromised hosts.

To evaluate the clinical features, etiology, and outcome of patients over 65 years old hospitalized for community-acquired pneumonia (CAP).A retrospective cohort analysis was performed for adult patients hospitalized with CAP in a 1000-bed teaching hospital between Jan 2002 and Jan 2006. Differences betweenor = 65 yrs and65 yrs groups were calculated using chi(2) test.A total of 302 patients (166 males), with a mean age of (68 +/- 21) yrs, were enrolled. Of the 216 elderly patients, 67.1% had comorbid conditions, mostly cardiovascular diseases and chronic obstructive lung disease. For the risk stratification, 175 patients were classified as IV - V according to Fine's index. The mean hospital stay was 12 days and in-hospital mortality was 12.0%. The most frequent pathogen was Streptococcus pneumoniae in elderly patients. As compared to 86 younger patients (or = 65yrs), altered mental status, dyspnea, tachypnea and tachycardia on hospital admission were more frequent in the elderly. The etiological distribution was also different between the two groups.CAP in elderly patients is a prevalent disease with high incidence of complications and mortality. More attention should be paid to the specific clinical manifestations of this patient population.

To study the active efflux gene qacB, qacJ and smr in methicillin resistant Staphylococcus aureus (MRSA) and to investigate their effect on the multi-drug resistance (MDR) of MRSA.The three pairs of ideal primers of active efflux gene qacB, qacJ and smr were designed by computer with Primer Premier 5.0 software. A total of 124 clinical isolates of MRSA were amplified respectively by polymerase chain reaction (PCR) with above mentioned primers. The PCR products were separated by electrophoresis on an 1.5% agarose gel with 0.5 microg/ml ethidium bromide. Reserpine inhibition test was used to observe the changes of the susceptibility to antibiotics of MRSA which had qacB, qacJ and smr genes separately.Of the 124 strains of MRSA, 86 strains had qacB, 45 strains had qacJ and 32 strains had smr gene. Reserpine inhibition test showed that the minimal inhibitory concentration (MIC) decreased 2 to 32 times for MRSA to levofloxacin and rifampin.MRSA have qacB, qacJ and smr active efflux systems, which play a very important role in multiple antibiotic resistance.

To study the therapeutic effect of interleukin-2 (IL-2) and interleukin-12 (IL-12) with and without amphotericin B on pulmonary fungal infection of mice.A mouse model of pulmonary invasive aspergillus fumigatus (IPA) infection was established and the mice were divided into different groups, treated with IL-2 and IL-12 with and without amphotericin B. The survival number of mice in 15 days and the colony count of lung tissue in the different groups were observed.IL-2, IL-12 and amphotericin B showed synergistic effect in prolonging the survival of the infected mice and reducing the colony count in the lung tissue.IL-2 and IL-12 are effective adjuvant therapeutic agents in the immunosuppressed hosts.

To investigate the susceptibility and genotype characteristics of gram-negative bacteria producing plasmid-mediated class I cephalosporinase (AmpC beta lactamase) epidemic in Southern China.A total of 1,187 clinical isolates of nonrepetive gram-negative bacteria were collected from different cities in Southern China. AmpC beta lactamase producing isolates were identified by cefoxitin three-dimensional test, and antimicrobial susceptibility test was identified by Kirby-Bauer agar diffusion test; plasmid conjugation, plasmid extraction, universal PCR for gene amplication of corresponding group was done, and the PCR products were sequenced subsequently.The positive rate of cefoxitin three-dimensional test in gram-negative bacteria was 5.9% (70/1,187), and the prevalence of plasmid-mediated AmpC beta lactamase was: E. coli: 4.2% (19/451), Klebsiella: 4.7% (16/339), Enterobacter: 2.1% (4/190), Alcaligenes: 5.3% (1/19), Acinetobacter: 2.2% (1/45) and the total positive rate was: 3.5% (41/1,187). The susceptibility test showed that compared with the clinical isolates, the transconjugations remained resistance to cephamycins and ampicillin, and susceptible to cefepime and imipenem. PCR amplication and sequencing confirmed them to be bla(DHA-1) gene and bla(ACT-1) gene, and they were mainly distributed in Klebsiella and Escherichia.DHA-1 and ACT-1 were the most common genotypes in plasmid-mediated AmpC beta-lactamase produced by clinical isolates in Southern China. Fourth-generation cephalosporins and carbapenems could be better choices for the treatment of infection caused by AmpC betalactamase producers.

To investigate the molecular mechanism of transferable multiple-antibiotic resistance in extended-spectrum beta-lactamases (ESBLs) producing isolates.Antibiotics susceptibility was tested by E-test method, and multi-resistance plasmids were screened and isolated by extracting transformant plasmids. Inserted gene Cassettes of class 1 integron were amplified and analyzed by polymerase chain reaction (PCR) and DNA sequencing.Eight of the nine ESBL-producing plasmids were found to comprise class 1 integron sequence, of them 7 harbored 1 or 2 antibiotic resistant gene cassettes which encoding resistance to aminoglycosides (aacA4, aadA2 or aadA5), trimethoprim (dhfrA12 or dfrA17), rifampicin (arr-3) and chloramphenicol (cmlA6). The function of these gene cassettes corresponded to the resistance profiles of their electro-transformants.Multi-resistance gene cassettes located on plasmids and mediated by class 1 integron may play an important role in causing the development and dissemination of multiple-antibiotic resistance in ESBL-producing clinical isolates.