Lesion size as a prognostic factor in the antifungal treatment of pulmonary cryptococcosis: a retrospective study with chest CT pictorial review of 2-year follow up.

BACKGROUND: Pulmonary cryptococcosis (PC) is a fungal infection that can have a variable prognosis depending on several factors. The objective of this study was to analyse the characteristics of pulmonary lesions and identify prognostic factors in patients with PC who were human immunodeficiency virus (HIV) -negative and underwent antifungal treatment. METHODS: The study enrolled patients diagnosed with PC who were negative for HIV. Symptoms, CT characteristics of pulmonary lesions, serum cryptococcal capsular antigen (CrAg) titre, underlying diseases, and duration of antifungal treatment were evaluated over a 2-year follow-up. RESULTS: A total of 63 patients (40 men and 23 women) with a mean age of 50.4 years were included. Half of the patients (50.8%) were asymptomatic, and the most common symptoms were cough (44.4%), expectoration (27.0%), and fever (17.5%). Pulmonary lesions were mainly present in the peripheral and lower lobes of the lung, with 35 cases classified as nodular-type lesions and 28 cases classified as mass-type lesions. At the first, third, sixth, 12th, and 24th-month follow-ups, the median proportion of residual pulmonary lesions were 59.6%, 29.9%, 12.2%, 9.6%, and 0.0%, respectively. During antifungal treatment, the lesions of 33 patients achieved complete response, while the remaining 30 patients did not. Compared with the non-CR group, the CR group had a lower baseline serum CrAg titre (median, 1:20 vs 1:80, P < 0.01), smaller pulmonary lesion size (median area, 1.6 cm2 vs 6.3 cm2, P < 0.01), lower Hounsfield-units (HU) radiodensity (median, - 60.0 HU vs - 28.5 HU, P < 0.05), more nodular-type lesions (72.7% vs 36.7%, P < 0.01), and fewer air-bronchogram signs (18.2% vs 43.3%, P < 0.05). Multivariate logistic regression analysis showed that a larger lesion size on chest CT scans was associated with a lower likelihood of achieving complete response [OR: 0.89; 95% CI (0.81-0.97); P < 0.05]. CONCLUSIONS: PC was more commonly observed in HIV-negative men, and chest CT scans mostly revealed nodular-type lesions. After antifungal treatment, patients with smaller lesions had a better prognosis.

Exposure to particulate matter 2.5 and cigarette smoke induces the synthesis of lipid droplets by glycerol kinase 5.

Particulate matter (PM2.5) and cigarette smoke exposure are leading factors contributing to various diseases, especially respiratory diseases. The purpose of this research was to study the effects of PM2.5 and cigarette smoke on glycerol kinase 5 (GK5) expression and the possible mechanisms by which GK5 participates in lipid droplet (LD) synthesis in alveolar epithelial A549 cells. Real-time polymerase chain reaction (RT-PCR) and western blotting have been used for the detection of messenger RNA (mRNA) and protein expression respectively. GK5 overexpressing cells were established by lentivirus transfection, whereby lentiviral vectors deliver the gene into chromosomes, allowing stable expression. Affymetrix microarray analysis, a widely used tool for measuring genome-wide gene expression, has been used to explore differential gene expression profiles. A549 cells stimulated with PM2.5 and cigarette smoke extract (CSE) showed elevated GK5 expression in a dose-dependent manner. Transmission electron microscopy and oil red O staining were used to observe LDs in cells. Further, GK5 overexpressing cells showed increased LDs and upregulation of genes and proteins related to lipogenesis and lipid transportation. Affymetrix microarray analysis revealed that GK5 overexpression resulted in the differential expression of more than 109 genes, which were mainly involved in the regulation of cell death, cell survival, cellular movement and migration, and those involved in cellular growth and proliferation pathways. Overall, this study demonstrates that GK5 is upregulated during PM2.5 and cigarette smoke exposure and induces LD synthesis.

Zn Promoted Mg-Al Mixed Oxides-Supported Gold Nanoclusters for Direct Oxidative Esterification of Aldehyde to Ester.

The synthesis of ester compounds is one of the most important chemical processes. In this work, Zn-Mg-Al mixed oxides with different Zn2+/Mg2+ molar ratios were prepared via co-precipitation method and supported gold nanoclusters to study the direct oxidative esterification of aldehyde and alcohol in the presence of molecular oxygen. Various characterization techniques such as N2-physical adsorption, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and CO2 temperature programmed desorption (TPD) were utilized to analyze the structural and electronic properties. Based on the results, the presence of small amounts of Zn2+ ions (~5 wt.%) provoked a remarkable modification of the binary Mg-Al system, which enhanced the interaction between gold with the support and reduced the particle size of gold. For oxidative esterification reaction, the Au25/Zn0.05MgAl-400 catalyst showed the best performance, with the highest turnover frequency (TOF) of 1933 h-1. The active center was believed to be located at the interface between metallic gold with the support, where basic sites contribute a lot to transformation of the substrate.

The association between serum albumin/prealbumin level and disease severity in non-CF bronchiectasis.

Non-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disease that can lead to malnutrition. Serum prealbumin and albumin level are related to inflammatory and nutritional status. Thus, we aimed to confirm our hypothesis that low serum albumin and prealbumin level, as well as body mass index (BMI), is correlated to severe non-CF bronchiectasis. We conducted a retrospective cross-sectional study of 128 patients, including 75 patients with prealbumin test and 79 patients with albumin test. Detailed medical history was recorded, including pulmonary function tests and high-resolution computed tomography. bronchiectasis severity index (BSI) and FACED scores were calculated. Leicester Cough Questionnaire, Quality of Life Questionnaire-Bronchiectasis, chronic obstructive pulmonary disease (COPD) assessment test and Patient Health Questionnaire-9 questionnaires were used to assess patients' clinical symptoms. Correlation analysis showed that BSI score was more correlated to patients' clinical symptoms than FACED. Thus, patients were divided into three groups of different severity based on BSI score. Albumin, prealbumin and BMI showed a significant difference between three groups. Correlation and multivariable linear regression analysis showed that serum albumin and prealbumin level were correlated to BSI, FACED and questionnaires. The analysis between three indices and PFT/high-resolution computed tomography (HRCT) showed that prealbumin, albumin and BMI could reflect the PFT and modified Reiff score in non-CF bronchiectasis. In conclusion, BMI, albumin and prealbumin showed a significant correlation with the BSI, FACED, as well as patients' clinical symptoms. Among them, serum albumin was the indicator most strongly associated with the BSI and questionnaires, while prealbumin could better reflect lung function decline and radiological severity.

Microbial Etiology and Prognostic Factors of Ventilator-associated Pneumonia: A Multicenter Retrospective Study in Shanghai.

Background: The microbial etiology and mortality risk factors of ventilator-associated pneumonia (VAP) have not been investigated extensively in Shanghai. Methods: VAP cases were identified from the patients hospitalized during the period from 1 January 2013 to 30 December 2017 in Shanghai. The relevant data were reviewed and analyzed retrospectively. Results: One hundred ninety-four VAP cases were included in this analysis. The overall mortality rate was 32.47%. The respiratory pathogens isolated from these patients included 212 bacterial strains and 54 fungal strains. The leading pathogens were Acinetobacter baumannii (33.96%), Klebsiella pneumoniae (23.58%), Pseudomonas aeruginosa (19.81%), and Staphylococcus aureus (7.08%). Candida colonization was associated with higher mortality of VAP patients compared to those without Candida colonization (45.45% vs 28.67%, P < .05). The VAP patients with Candida colonization also showed higher prevalence of P. aeruginosa, carbapenem-resistant P. aeruginosa (CRPA), K. pneumoniae, carbapenem-resistant K. pneumoniae (CRKP), A. baumannii, and carbapenem-resistant A. baumannii (CRAB) (P < .05). VAP nonsurvivors had higher prevalence of CRPA, K. pneumoniae, CRAB, and Candida than VAP survivors (P < .05). Multivariate analysis showed that prior antibiotic use was a significant risk factor for Candida colonization, while hypertension and length of hospital stay were significant risk factors of VAP mortality (P < .05). Conclusions: The top pathogens of VAP patients in Shanghai tertiary teaching hospitals are A. baumannii, K. pneumoniae, and P. aeruginosa, with high prevalence of carbapenem resistance. Carbapenem-resistant bacterial pathogens and Candida may predict poor outcome.

A Prospective Multicenter Clinical Observational Study on Vancomycin Efficiency and Safety With Therapeutic Drug Monitoring.

Background: Vancomycin is a first-line antibiotic used for the treatment of severe gram-positive bacterial infections. Clinical guidelines recommend that the vancomycin trough concentration be 10-15 mg/L for regular infections and 15-20 mg/L for severe infections. We investigated whether increasing the vancomycin concentration would result in better clinical outcomes with sustainable adverse effects (AEs) in the Chinese population. Methods: A prospective, open, multicenter clinical observational study was performed in patients with gram-positive bacterial infections from 13 teaching hospitals. Patients received vancomycin therapeutic drug monitoring. Clinical, microbiological, and laboratory data were collected. Results: In total, 510 patients were enrolled, and 470 were evaluable, of whom 370 were adults and 100 were children; 35.53% had methicillin-resistant Staphylococcus aureus infections (vancomycin 50% minimum inhibitory concentration [MIC50] = 1, 90% minimum inhibitory concentration [MIC90] = 1), and 23.19% had Enterococcus species infections (vancomycin MIC50 = 1, MIC90 = 2). The average trough concentration was 10.54 ± 8.08 mg/L in adults and 6.74 ± 8.93 mg/L in children. The infection was eradicated in 86.22% of adults and 96% of children. Thirty-six vancomycin-related nephrotoxicity cases were reported in the enrolled population. No severe AEs or deaths were related to vancomycin therapy. Logistic regression analysis showed that trough concentration had no relationship with clinical outcomes (adults P = .75, children P = .68) but was correlated with adult nephrotoxicity (P < .0001). Vancomycin trough concentration had an applicable cut point at 13 mg/L. Conclusions: Our study shows that vancomycin trough concentration has no statistical correlation with clinical outcomes, and is an indicator of nephrotoxicity in the observed population. We found no evidence that increasing vancomycin trough concentration to 15-20 mg/L can benefit Chinese patients with complicated infections. Clinical Trials Registration: ChiCTR-OPC-16007920.

Model-based Evaluation of the Clinical and Microbiological Efficacy of Vancomycin: A Prospective Study of Chinese Adult In-house Patients.

Background: Our aims in this prospective study were to evaluate the correlations between pharmacokinetic/pharmacodynamic (PK/PD) indices and the clinical/microbiological efficacy of vancomycin and to identify an appropriate PK/PD target in the Chinese population to guide vancomycin treatment in the clinic. Methods: Adult patients from 11 hospitals in China with gram-positive infections who received vancomycin therapy for ≥5 days and who were under therapeutic drug monitoring (TDM) were enrolled in this study. A 1-compartment population PK model was established and validated. The correlations between PK/PD indices (Cmin, Cmax, 0-24 hour area under the curve (AUC0-24), and AUC0-24/minimum inhibitory concentration (MIC) and clinical outcomes (clinical efficacy and bacterial eradication) were evaluated. Results: In total, 402 adult Chinese patients were enrolled. Among them, 380 patients were evaluable for PK analysis, and 334 were evaluable for PK/PD analysis. In the final population PK model, creatinine clearance (CLCR) was the significant covariate on CL (typical value, 3.87 L/hour; between-subject variability (BSV), 12.5%), and age was the significant covariate on volume of distribution (V) (typical value, 45.1 L; BSV, 24.8%). The univariate analysis showed that Cmax, AUC0-24, and AUC0-24/MIC were significantly different or marginally significantly different (P values were 0.009, 0.0385, and 0.0509, respectively) between microbiological outcome groups with coagulase-negative Staphylococcus infections. However, there were no significant differences (P > .05) in the above PK parameters by multivariate logistic regression analysis, indicating there was no independently associated factor. Conclusions: No significant correlations were identified between PK/PD indices and the clinical or microbiological efficacy of vancomycin in Chinese patients. The necessity of vancomycin TDM based on trough concentration and the current treatment target of AUC0-24/MIC ≥400 need to be further evaluated and confirmed in additional prospective studies.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network.

Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible Citrobacter freundii, Escherichia coli, Enterobacter cloacae, or Klebsiella pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by K. pneumoniae (73.9%), followed by E. coli (16.6%) and E. cloacae (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against E. coli than against K. pneumoniae (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among K. pneumoniae and E. coli The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.

Carbapenem susceptibilities of Gram-negative pathogens in intra-abdominal and urinary tract infections: updated report of SMART 2015 in China.

BACKGROUND: To evaluate the susceptibility rates of aerobic and facultative Gram-negative bacterial isolates from Chinese intra-abdominal infections (IAI) and urinary tract infections (UTI) focusing on carbapenems and comparing their effectiveness between 2014 and 2015. METHODS: A total of 2318 strains in 2015 (1483 from IAI and 835 from UTI) and 2374 strains in 2014 (1438 from IAI and 936 from UTI) were included in the analysis. Antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. Hospital acquired (HA) IAI and UTI were defined as isolates sampled > 48 h and community acquired (CA) as isolates sampled < 48 h after admission. RESULTS: The main species derived from IAI and UTI in 2015 were Escherichia coli (50.86%) and Klebsiella pneumoniae (19.20%). Susceptibilities of Escherichia coli IAI and UTI strains to imipenem (IPM) and ertapenem (ETP) were > 90% in 2014 and 2015, while the susceptibilities to IPM and ETP of Klebsiella pneumoniae IAI strains were >  80% in 2014 but dropped to ≤80% in 2015 for UTI strains. Susceptibilities of IAI Enterobacteriaceae strains to IPM and ETP in 2015 were lowest in the colon and abscesses, and Enterobacteriaceae susceptibilities of UTI and IAI isolates to IPM and ETP were lowest in medical, pediatric and surgery intensive care units (ICUs) in 2015. CONCLUSIONS: IPM and ETP were effective in vitro against Enterobacteriaceae isolated from IAIs and UTIs in 2014 and 2015, but susceptibility to carbapenems in UTIs markedly decreased in 2015.

Secreted frizzled related protein 1 protects H9C2 cells from hypoxia/re-oxygenation injury by blocking the Wnt signaling pathway.

BACKGROUND: In animal models, secreted frizzled related protein 1 (Sfrp1) inhibition of the Wnt signaling pathway is beneficial because Sfrp1 reduces myocardial apoptosis and prevents heart failure. The mechanisms mediating the cellular survival effect of Sfrp1 has not been completely elucidated. The present study was designed to investigate the possible protective actions of Sfrp1 on cardiac muscle cells using an in vitro model of ischemia/reperfusion, and to evaluate the possible involvement of the Wnt signaling pathway. METHODS: We used a recombinant AAV9 vector to deliver the Sfrp1 gene into H9C2 rat cardiomyoblasts and adopted an in vitro model of ischemia/reperfusion. Cell vitality was measured by CKK-8 and the trypan blue exclusion assay. Western blot was used to evaluate the expression of Dvl-1, ß-catenin, c-Myc, Bax, and Bcl-2. Flow cytometry analysis of cardiomyocyte apoptosis was performed. RESULTS: We confirmed that Sfrp1 significantly increased cell viability (assayed by trypan blue and CKK-8) and decreased apoptosis (assayed by flow cytometry analysis and the Bax/Bcl-2 ratio). These effects were partly attributable to the ability of Sfrp1 to down-regulate Wnt signaling pathway (assayed by Western blot to evaluate the expression of Dvl-1, ß-catenin, and c-Myc). Indeed, reactivation of the Wnt signaling pathway activity with the specific activator, Licl, reduced Sfrp1-induced cardioprotection during hypoxia and reoxygenation. CONCLUSIONS: The present study demonstrated that Sfrp1 directly protected H9C2 cells from hypoxia and reoxygenation-induced reperfusion injury and apoptosis through inhibition of the Wnt signaling pathway, and added new mechanistic insight regarding the cardioprotective role of Sfrp1 on ischemic damage.

Sources of sporadic Pseudomonas aeruginosa colonizations/infections in surgical ICUs: Association with contaminated sink trap.

BACKGROUND: Many studies have reported the hospital outbreaks of Pseudomonas aeruginosa due to cross-contamination between patients and water fittings, but the importance of water fittings as sources of sporadic P. aeruginosa colonizations/infections remains ambiguous. AIM: To investigate the sources of sporadic P. aeruginosa colonizations/infections in a clinical intensive surveillance, and further analysis the potential of sink trap for P. aeruginosa transmission in intensive care units (ICUs). METHODS: Patients monitoring and targeted environmental screening for P. aeruginosa was performed prospectively over a 27-week period, in absence of recognized outbreak, in two surgical intensive care units (SICUs). All isolates were genotyped by Pulsed field gel electrophoresis analysis. FINDINGS: 18.9% (46/244) of water fitting samples harbored P. aeruginosa, and active screening samples from 9.2% (55/595) of hospitalized patients carried with P. aeruginosa. According to genotype results, approximately 50% of P. areuginosa colonizations/infections of patients were of exogenous origin. 64.7% (11/17) of exogenous sourced cases were associated with contaminated sink traps. There was a significant correlation between the incidence of exogenous colonization/infection and the prevalence of P. areuginosa in water fitting in SICU-2 (rs = 0.972; p = 0.014). Furthermore, P. areuginosa from sink trap possessed a higher level of resistance to multi-antibiotics as opposed to cross-transmission from other patients. CONCLUSION: Water fitting especially sink trap act as an important role in sporadic P. aeruginosa transmission in SICU patients. This report highlights the necessity of identification of potential environmental reservoirs, such as sinks, for control of infections of environmentally hardy multi-resistant P. areuginosa.

Keratinocyte growth factor-2 inhibits bacterial infection with Pseudomonas aeruginosa pneumonia in a mouse model.

To determine protective effects of concurrent administration of Keratinocyte growth factor-2 (KGF-2) with Pseudomonas aeruginosa (P. aeruginosa) inoculation on the induced pneumonia. KGF-2 (5 mg/kg) was concurrently administered into the left lobe of 55 mice with P. aeruginosa PAO1 (5 × 10(6) CFU, half-lethal dose); 55 mice in the control group were concurrently administered PBS with the PAO1. We detected and analyzed: body temperature; amount of P. aeruginosa in homogenates; count of total number of nucleated cells and of mononuclear macrophages; protein concentration in bronchoalveolar lavage fluid (BALF); lung wet-to-dry weight ratio; cytokines in BALF and blood; and lung morphology. To study survival rate, concurrent administration of KGF-2 (experimental group) versus PBS (control) with a lethal dose of PAO1 (1 × 10(7) CFU was performed, and survivorship was documented for 7 days post-inoculation. The bacterial CFU in lung homogenates was significantly decreased in the KGF-2 group compared to the control group. There were significantly more mononuclear macrophages in the BALF from the KGF-2 group than from the control group (p < 0.05). KGF-2 increased the surfactant protein and GM-CSF mRNA in lung at 6 h and 72 h after inoculation. Significant reduction of lung injury scores, protein concentrations, lung wet-to-dry weight ratio, and IL-6 and TNF-α levels was noted in the KGF-2 treated rats at 72 h after inoculation (p < 0.05). The 7-day survival rate of the KGF-2 group was significantly higher than that of the control group (p < 0.05). Concurrent administration of KGF-2 facilitates the clearance of P. aeruginosa from the lungs, attenuates P. aeruginosa-induced lung injury, and extends the 7-day survival rate in mice model with P. aeruginosa pneumonia.

Denatonium inhibits growth and induces apoptosis of airway epithelial cells through mitochondrial signaling pathways.

BACKGROUND: Denatonium, a widely used bitter agonist, activates bitter taste receptors on many cell types and plays important roles in chemical release, ciliary beating and smooth muscle relaxation through intracellular Ca(2+)-dependent pathways. However, the effects of denatonium on the proliferation of airway epithelial cells and on the integrity of cellular components such as mitochondria have not been studied. In this study, we hypothesize that denatonium might induce airway epithelial cell injury by damaging mitochondria. METHODS: Bright-field microscopy, cell counting kit-8 (CCK-8) assay and flow cytometry analysis were used to examine cellular morphology, proliferation and cell cycle, respectively. Transmission electron microscopy (TEM) was used to examine mitochondrial integrity. JC-1 dye and western blotting techniques were used to measure mitochondrial membrane potential and protein expression, respectively. RESULTS: For airway epithelial cells, we observed that denatonium significantly effects cellular morphology, decreases cell proliferation and reduces the number of cells in S phase in a dose-dependent manner. TEM analysis demonstrated that denatonium causes large amplitude swelling of mitochondria, which was confirmed by the loss of mitochondrial membrane potential, the down-regulation of Bcl-2 protein and the subsequent enhancement of the mitochondrial release of cytochrome c and Smac/DIABLO after denatonium treatment. CONCLUSIONS: In this study, we demonstrated for the first time that denatonium damages mitochondria and thus induces apoptosis in airway epithelial cells.

Genome-Wide Identification and Analysis of the VQ Motif-Containing Protein Family in Chinese Cabbage (Brassica rapa L. ssp. Pekinensis).

Previous studies have showed that the VQ motif-containing proteins in Arabidopsis thaliana and Oryza sativa play an important role in plant growth, development, and stress responses. However, little is known about the functions of the VQ genes in Brassica rapa (Chinese cabbage). In this study, we performed genome-wide identification, characterization, and expression analysis of the VQ genes in Chinese cabbage, especially under adverse environment. We identified 57 VQ genes and classified them into seven subgroups (I-VII), which were dispersedly distributed on chromosomes 1 to 10. The expansion of these genes mainly contributed to segmental and tandem duplication. Fifty-four VQ genes contained no introns and 50 VQ proteins were less than 300 amino acids in length. Quantitative real-time PCR showed that the VQ genes were differentially expressed in various tissues and during different abiotic stresses and plant hormone treatments. This study provides a comprehensive overview of Chinese cabbage VQ genes and will benefit the molecular breeding for resistance to stresses and disease, as well as further studies on the biological functions of the VQ proteins.

Genome-wide identification and analysis of the growth-regulating factor family in Chinese cabbage (Brassica rapa L. ssp. pekinensis).

BACKGROUND: Growth regulating factors (GRFs) have been shown to play important roles in plant growth and development. GRF genes represent a large multigene family in plants. Recently, genome-wide structural and evolutionary analyses of the GRF gene families in Arabidopsis, rice, and maize have been reported. Chinese cabbage (Brassica rapa L. ssp. pekinensis) is one of the most important vegetables for agricultural production, and a full genome assembly for this plant has recently been released. However, to our knowledge, the GRF gene family from Chinese cabbage has not been characterized in detail. RESULTS: In this study, genome-wide analysis was carried out to identify all the GRF genes in Chinese cabbage. Based on the complete Chinese cabbage genome sequence, 17 nonredundant GRF genes, named BrGRFs, were identified and classified into six groups. Phylogenetic analysis of the translated GRF protein sequences from Chinese cabbage, Arabidopsis, and rice indicated that the Chinese cabbage GRF proteins were more closely related to the GRF proteins of Arabidopsis than to those of rice. Expression profile analysis showed that the BrGRF genes had uneven transcript levels in different organs or tissues, and the transcription of most BrGRF genes was induced by gibberellic acid (GA3) treatment. Additionally, over-expression of BrGRF8 in transgenic Arabidopsis plants increased the sizes of the leaves and other organs by regulation of cell proliferation. CONCLUSIONS: The data obtained from this investigation will contribute to a better understanding of the characteristics of the GRF gene family in Chinese cabbage, and provide a basis for further studies to investigate GRF protein function during development as well as for Chinese cabbage-breeding programs to improve yield and/or head size.

Transcriptome analysis of rosette and folding leaves in Chinese cabbage using high-throughput RNA sequencing.

In this study, we report the first use of RNA-sequencing to gain insight into the wide range of transcriptional events that are associated with leafy head development in Chinese cabbage. We generated 53.5 million sequence reads (90 bp in length) from the rosette and heading leaves. The sequence reads were aligned to the recently sequenced Chiifu genome and were analyzed to measure the gene expression levels, to detect alternative splicing events and novel transcripts, to determine the expression of single nucleotide polymorphisms, and to refine the annotated gene structures. The analysis of the global gene expression pattern suggests two important concepts, which govern leafy head formation. Firstly, some stimuli, such as carbohydrate levels, light intensity and endogenous hormones might play a critical role in regulating the leafy head formation. Secondly, the regulation of transcription factors, protein kinases and calcium may also be involved in this developmental process.

[The incidence and risk factors for heterogeneous vancomycin intermediate Staphylococcus aureus].

OBJECTIVES: To investigate the prevalence of heterogeneous vancomycin intermediate Staphylococcus aureus (hVISA) and the sensitivity of hVISA to novel antibiotics, and to explore the risk factors and infection attributable mortality associated with hVISA infection. METHODS: A total of 456 methicillin resistant Staphylococcus aureus (MRSA) isolates were isolated in Zhongshan Hospital from January, 2008 to November, 2010. All MRSA isolates were investigated for hVISA by two agar screening methods BHIA5T (brain-heart infusion containing teicoplanin 5 mg/L) or BHIA6V (brain-heart infusion containing vancomycin 6 mg/L), as well as macroEtest method (MET). Possible hVISA isolates were tested by modified population analysis profile-area under the curve (PAP-AUC). The minimal inhibitory concentrations (MICs) of vancomycin, teicoplanin and linezolid were determined by microbroth dilution as recommended by Clinical Laboratory Standards Institute (CLSI). The contribution difference between hVISA and vancomycin susceptible Staphylococcus aureus (VSSA) in different MIC range was compared. A retrospective case-control study of the patients with hVISA infection or VSSA infection was carried out and statistical analysis was performed using t test, Mann-Whitney test, χ(2) test and Fisher exact test. RESULTS: A total of 105 isolates of hVISA were screened by BHIA5T and BHIA6V (23.0%) with other 23 isolates by MET (5.0%) and 21 by PAP-AUC (4.6%). All isolates were 100% sensitive to vancomycin, teicoplanin and linezolid. The vancomycin MIC [(1.76 ± 0.16) mg/L] in hVISA group was significantly higher than that in VSSA group [(1.09 ± 0.07) mg/L, P < 0.01], which was a potential risk factor for hVISA infection. The retrospective study showed chronic obstructive pulmonary disease (COPD) was also a risk factor for hVISA infection of the lower respiratory tract. No significant difference in infection attributable mortality was showed between the hVISA group and the VSSA group. CONCLUSIONS: The overall prevalence of hVISA in Zhongshan Hospital is estimated as 4.6%, while the prevalence of hVISA isolated from blood is as high as 12.5%. All isolates are 100% sensitive to vancomycin and linezolid. COPD is a risk factor for hVISA infection of the lower respiratory tract.

Correlation of elevated serum uric acid with coronary artery disease in Xinjiang, China: A retrospective case-control study.

Elevated serum uric acid (SUA) levels are associated with coronary artery disease (CAD). However, whether this association is independent of traditional cardiovascular risk factors remains controversial. Our study aimed to determine the concentration of SUA in the presence and severity of CAD in multi-ethnic patients in Xinjiang, China. For this study, 412 consecutive patients with percutaneous coronary intervention (PCI) and 845 individuals with normal coronary angiograms were included in the study. CAD severity was evaluated using the Gensini score index. The SUA concentrations and the levels of various cardiometabolic risk factors were investigated. We assessed the relationship between SUA levels and other cardiometabolic risk factors. Logistic regression was used to evaluate risk factors for PCI patients. SUA levels were significantly elevated in PCI patients compared to those in control subjects (P < .01). With increased UA levels, we found that the risk factors for CAD increased. SUA concentration had a significant positive relationship with total cholesterol (P < .01), triglycerides (P < .01), low-density lipoprotein cholesterol (P < .01), and creatinine (P < .01) in both sexes. In the PCI group, there was no significant correlation between UA levels. SUA levels are not an independent risk factor for CAD. It can be concluded that in Xinjiang, China, SUA is related to multiple risk factors for CAD, but not related to the severity of CAD.

Integrative analysis of physiology, biochemistry and transcriptome reveals the mechanism of leaf size formation in Chinese cabbage (Brassica rapa L. ssp. pekinensis).

Introduction: The leaf, the main product organ, is an essential factor in determining the Chinese cabbage growth, yield and quality. Methods: To explore the regulatory mechanism of leaf size development of Chinese cabbage, we investigated the leaf size difference between two high-generation inbred lines of Chinese cabbage, Y2 (large leaf) and Y7 (small leaf). Furtherly, the transcriptome and cis-acting elements analyses were conducted. Results and Discussion: According to our results, Y2 exhibited a higher growth rate than Y7 during the whole growth stage. In addition, the significant higher leaf number was observed in Y2 than in Y7. There was no significant difference in the number of epidermal cells and guard cells per square millimeter between Y2 and Y7 leaves. It indicated that cell numbers caused the difference in leaf size. The measurement of phytohormone content confirmed that GA1 and GA3 mainly play essential roles in the early stage of leaf growth, and IPA and ABA were in the whole leaf growth period in regulating the cell proliferation difference between Y2 and Y7. Transcriptome analysis revealed that cyclins BraA09g010980.3C (CYCB) and BraA10g027420.3C (CYCD) were mainly responsible for the leaf size difference between Y2 and Y7 Chinese cabbage. Further, we revealed that the transcription factors BraA09gMYB47 and BraA06gMYB88 played critical roles in the difference of leaf size between Y2 and Y7 through the regulation of cell proliferation. Conclusion: This observation not only offers essential insights into understanding the regulation mechanism of leaf development, also provides a promising breeding strategy to improve Chinese cabbage yield.

Peripheral neutrophils and oxidative stress-associated molecules for predicting the severity of asthma: a cross-sectional study based on multidimensional assessment.

Objectives: This study aims to explore the relationship between the severity of asthma and neutrophils and related oxidative stress-associated molecules in peripheral blood and induced sputum. Methods: A total of 67 subjects were included in this study, namely, 25 patients with severe asthma and 42 patients with non-severe asthma. Clinical data, induced sputum and peripheral blood were collected. Lung function and molecules related to oxidative stress in induced sputum and peripheral blood of asthma patients were detected. The relationship between neutrophils and asthma severity was analyzed. HDAC2 mRNA and protein expression levels and HDAC2 activity were also analyzed. Multivariate logistic regression was performed to select statistically significant variables. Results: The absolute value of neutrophils and percentage of neutrophils were higher in the severe asthma patients. These two values were used to predict the severity of asthma by ROC analysis, with the best cutoff values being 4.55 × 109/L (sensitivity 83.3%, specificity 64.0%) and 55.15% (sensitivity 54.8%, specificity 88.0%). The ROS concentration of neutrophils in the induced sputum samples and the 8-iso-PGF2α concentration in the peripheral blood samples were higher in the severe asthma group (P = 0.012; P = 0.044), whereas there was reduced HDAC2 protein activity in PBMCs (P < 0.001). A logistic equation and a nomogram were created to give a precise prediction of disease severity. Conclusion: Oxidative stress is increased in severe asthma patients. Peripheral blood neutrophils and 8-iso-PGF2α can be used as biomarkers to predict the severity of asthma. A prediction model was created for evaluating asthma severity.