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Background Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes. This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids. Methods Forty-two asthma patients (27 women and 15 men) admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled. Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry. Sex hormones(estradiol, progesterone, testosterone, and androstenedione) and multiple inflammatory factors (periostin, leptin, IgE, IL-4, IL-5, IL-10, IL-13, IL-17A, and IFN-γ) were also assessed. The eosinophil percentage in induced sputum was also detected. All these data were applied to comparative analysis between sexes. Results Testosterone was negatively related to periostin (ρ = −0.420, P = 0.009) and IL-5 (ρ = −0.540, P = 0.012), while estradiol was positively related to the blood eosinophil percentage (ρ = 0.384, P = 0.025). Among the eighteen species of sphingolipids detected in the 42 patients, five ceramide (Cer) species (Cer16:0, Cer:20:0, Cer22:0, Cer24:0, and Cer26:0) and one sphingomyelin (SM) species (SM38:0) were significantly higher in male than in female patients. Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males (ρ = 0.943, P = 0.005) but negative in females (ρ = −0.561, P = 0.030). Conclusions Testosterone was negatively correlated with eosinophil inflammatory factors, but estradiol was positively correlated. Male asthma patients had higher ceramide and sphingomyelin levels than female patients. Different sexes had opposite correlations with ceramide and IL-5, respectively, suggesting that therapeutic strategies targeting ceramide should be different between sexes.

Background The outbreak of the novel 2019 coronavirus disease (COVID-19) was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020. The diagnosis of COVID-19 is frequently based on a positive serological test. We noted the occurrence of false-positive results for COVID-19 in the colloidal gold-based immunochromatographic strip (ICS) assay in sera from patients with autoimmune diseases (ADs). This study aimed to evaluate the possible reasons for the false-positive results in two ICS assays (Wondfo ICS and Innovita ICS) and to investigate the effect of urea dissociation in reducing false-positive results. Methods The sera of 135 patients with ADs, 13 confirmed COVID-19 patients, 95 disease controls, and 120 healthy controls were tested for immunoglobin M (IgM) and IgG against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Wondfo and Innovita ICS kits. The distributions of auto-antibodies in antibody-positive and antibody-negative groups were also compared, and bivariable logistic regression was used to assess auto-antibodies associated with false-positive results. A urea dissociation test of ICS was performed for the SARS-CoV-2 antibody-positive samples. Results Specificity of Wondfo ICS for the 95 disease controls was 94.74% compared to 98.95% and 96.84% for Innovita SARS-CoV-2 IgM and IgG, respectively. Specificity of Wondfo ICS for the 120 healthy controls was 97.5% compared to 100% and 99.17% for Innovita SARS-CoV-2 IgM and IgG, respectively. Specificity of Wondfo ICS for AD patients was 73.33% compared to 97.78% and 96.30% for Innovita SARS-CoV-2 IgM and IgG, respectively. Sensitivity was 74.07% for Wondfo compared to 70.37% for Innovita IgM and 66.67% for Innovita IgG. Using the Wondfo ICS, the percentage of elevated rheumatoid factor (RF) level (>20 IU/mL) was higher in the SARS-CoV-2 antibody-positive group compared with the antibody-negative group [27/36 (75.0%) vs. 34/99 (34.34%), P=0.001]. The elevated RF was associated with antibody positivity, with an odds ratio of 4.671 [95% confidence interval (CI), 1.88-11.69]. The specificity of the Wondfo ICS assay for the AD patients was increased from 73.33% to 94.07% after the urea dissociation assay. Conclusions An elevated serum RF level could lead to false-positive results when detecting SARS-CoV-2 antibodies using the Wondfo ICS kit, and the urea dissociation assay would be helpful in reducing the incidence of false-positive results.

Studies have shown that glycerophospholipids are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study adopted targeted metabolomic analysis to investigate the changes in serum glycerophospholipids in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their differential expression in patients with different inflammatory subtypes. Patients with AECOPD admitted between January 2015 and December 2017 were enrolled, and their clinical data were collected. The patients’ gender, age, body mass index, and lung function were recorded. Routine blood and induced sputum tests were performed. Liquid chromatography-mass spectrometry was used to detect the serum glycerophospholipid metabolic profiles and to analyze the metabolic profile changes between the acute exacerbation and recovery stages as well as the differences between different inflammatory subtypes. A total of 58 patients were hospitalized for AECOPD, including 49 male patients with a mean age of 74.8 ± 10.0 years. In the metabolic profiles, the expression of lysophosphatidylcholine (LPC) 18:3, lysophosphatidylethanolamine (LPE) 16:1, and phosphatidylinositol (PI) 32:1 was significantly reduced in the acute exacerbation stage compared to the recovery stage (P < 0.05). The three glycerophospholipids were used to plot the receiver operating characteristic curves to predict the acute exacerbation/recovery stage, and the areas under the curves were all above 70%. There were no differential metabolites between the two groups of patients with blood eosinophil percentage (EOS%) ≥2% and P < 0.05). Abnormalities in the metabolism of glycerophospholipids may be involved in the onset of AECOPD, especially in the non-eosinophilic subtype.

WHAT IS KNOWN AND OBJECTIVE Vancomycin efficacy is dependent on appropriate dosing, which should aim to achieve a target serum trough level. The purpose of this study was to determine the variables that predicted vancomycin serum trough concentrations in elderly patients with sepsis. METHODS This retrospective cohort study, which was conducted in the medical ICU of a university-affiliated teaching hospital in China, included 87 medical patients with sepsis who were enrolled from January 2014 to December 2017. RESULTS AND DISCUSSION All the patients were at least 60 years old (mean age = 74.8 ± 8.2 years), and 51.7% (n = 45) of them were male. The most common primary site of infection was the lungs (67.8%), followed by the abdomen (12.6%). Patients with septic shock accounted for 21.8% (n = 19) of the cases. The proportion of patients with vancomycin serum trough concentrations reaching target concentrations (≥15 mg/L) was 47.1% (41 cases). Multivariate linear regression showed that the creatinine clearance rate (CCR) and the daily dosage of vancomycin were independent predictors of vancomycin serum trough concentrations (both p's

BackgroundWith the spread of COVID-19 from Wuhan, Hubei Province to other areas of the country, medical staff in Fever Clinics faced the challenge of identifying suspected cases among febrile patients with acute respiratory infections. We aimed to describe the prevalence and clinical features of COVID-19 as compared to pneumonias of other etiologies in a Fever Clinic in Beijing.MethodsIn this single-center, retrospective study, 342 cases of pneumonia were diagnosed in Fever Clinic in Peking University Third Hospital between January 21 to February 15, 2020. From these patients, 88 were reviewed by panel discussion as possible or probable cases of COVID-19, and received 2019-nCoV detection by RT-PCR. COVID-19 was confirmed by positive 2019-nCoV in 19 cases, and by epidemiological, clinical and CT features in 2 cases (the COVID-19 Group, n=21), while the remaining 67 cases served as the non-COVID-19 group. Demographic and epidemiological data, symptoms, laboratory and lung CT findings were collected, and compared between the two groups.FindingsThe prevalence of COVID-19 in all pneumonia patients during the study period was 6.14% (21/342). Compared with the non-COVID-19 group, more patients with COVID-19 had an identified epidemiological history (90.5% versus 32.8%, P9/L (±1.47) versus 7.21×109/L (±2.94), P9/L (±1.48) versus 5.38×109/L (±2.85), PP=0.008).InterpretationIn the period of COVID-19 epidemic outside Hubei Province, the prevalence of COVID-19 in patients with pneumonia visiting our Fever Clinic in Beijing was 6.14%. Epidemiological evidence was important for prompt case finding, and lower blood WBC and neutrophil counts may be useful for differentiation from pneumonia of other etiologies.FundingNone.

Reduced forced expiratory volume in 1 second percentage (FEV1%) predicted is closely related to cardiovascular mortality. However, evidence regarding the correlation between FEV1% predicted and the severity of coronary atherosclerosis observed on coronary angiography is still limited. We aimed to explore whether a decline in FEV1% predicted was associated with diffuse coronary atherosclerosis in hospitalized patients.A cross-sectional study enrolling hospitalized patients with cardiovascular symptoms undergoing both coronary angiography and lung function testing was conducted. The correlation between FEV1% predicted and angiographic characteristics, including the number of diseased vessels, total number of coronary lesions and Gensini score was analyzed.Eighty-five patients were included. Patients with ≥2-vessel disease had significantly lower FEV1% predicted than patients with2-vessel disease (60.9% ± 19.7% versus 77.2% ± 19.7%, P0.001). FEV1% predicted was inversely related to the total number of coronary lesions (β = -0.029, P = 0.002) and Gensini score (β = -0.525, P = 0.006). FEV1% predicted was independently associated with ≥2-vessel disease (odds ratio = 0.961, P = 0.007), total number of coronary lesions (adjusted β = -0.039, P0.001) and Gensini score (adjusted β = -0.602, P = 0.005) after adjustment for other traditional cardiovascular risk factors. In the coronary artery disease subgroup, FEV1% predicted maintained an independent and negative relationship with ≥2-vessel disease, total number of coronary lesions and Gensini score.Reduced FEV1% predicted was closely associated with multivessel coronary disease and diffuse coronary atherosclerosis in hospitalized patients undergoing coronary angiography.

Introduction: Reports of hypermucoviscous Klebsiella pneumoniae (hvKP) isolated from fluids other than blood or abscess are rare. The aim of the study was to compare clinical and microbiological characteristics of hvKP found in blood or abscess fluid with those isolated from other loci. Methodology: A total of 24 non-repetitive hvKP isolates were collected from January 2013 to June 2014 from patients with hvKP infections. There were 15 in Group 1 (fluid other than blood or abscess) and 9 in Group 2 (blood or abscess fluid). Medical records of all patients were reviewed. Capsular polysaccharide (CPS) typing, virulence factor determination, and multilocus sequence typing (MLST) of hvKP isolates were performed. Results: Seventeen sequence types (STs) and 6 capsular serotypes were identified. Type K2CC65 was most commonly identified in Group 1 and type K2CC86 in Group 2. Deletion of pLVPK-derived loci were found in K2 and non-K1/K2 hvKP strains. Two virulent genes, fimH and ycfM, were identified more frequently in Group 2 than in Group 1. There was no difference in the frequency of other virulent genes or serotypes in the two groups. Two imipenem resistant hvKP isolates (cr-hvKP) were found in non-blood or abscess samples. Conclusions: hvKP isolated from different body fluids had similar clinical and microbiological characteristics. cr-hvKP identified in non-blood or abscess samples should raise our attention to the challenging situation and management of hvKP infection.

Meropenem is used for the treatment of severe lower respiratory tract infections (LRTIs) caused by multidrug-resistant Gram-negative bacilli. We evaluated the clinical benefits of a strategy of meropenem dosing based on a population pharmacokinetics/pharmacodynamics (PK/PD) model in elderly patients with an LRTI. In this prospective single-center open-label randomized controlled trial, 79 elderly patients with an LRTI caused by Gram-negative bacilli were randomized to a study group (SG) or a control group (CG). The latter received meropenem according to a regimen decided by the attending physician. The SG received individualized meropenem therapy with a dosing strategy based on software developed from a meropenem population PK/PD model. The primary endpoint was clinical response to meropenem therapy. Secondary endpoints were the amount of antibiotics used and bacteriologic response. Klebsiella pneumoniae was the most common pathogen (32.9%), followed by Pseudomonas aeruginosa (30.4%) and Escherichia coli (17.7%). A total of 63 (79.7%) patients achieved clinical success. Prevalence of clinical success was significantly higher in the SG than in the CG (89.7 vs. 70.0%; p = 0.029). The daily dose of meropenem was significantly lower in the SG than in the CG (1.5 vs. 2.0 g; p = 0.017). A total of 52 (65.8%) patients experienced bacteriologic success, the median duration of meropenem therapy was 9 days, and the median total dose of meropenem was 18.0 g. There were no significant differences between the groups in these parameters. A strategy for meropenem dosing based on a population PK/PD model can improve clinical response and avoid overtreatment in elderly patients with an LRTI. ClinicalTrials.gov registration number NCT01944319.

ObjectiveTo evaluate the impact of body mass index (BMI) on survival of a Chinese cohort of medical patients with sepsis.DesignA single-centre prospective cohort study conducted from May 2015 to April 2017.SettingA tertiary care university hospital in China.ParticipantsA total of 178 patients with sepsis admitted to the medical intensive care unit (ICU) were included.Main outcome measuresThe primary outcome was 90-day mortality while the secondary outcomes were in-hospital mortality, length of ICU stay and length of hospital stay.ResultsThe median age (IQR) was 78 (66–84) years old, and 77.0% patients were older than 65 years. The 90-day mortality was 47.2%. The in-hospital mortality was 41.6%, and the length of ICU stay and hospital stay were 12 (5–22) and 15 (9–28) days, respectively. Cox proportional hazard regression analysis identified that Sequential Organ Failure Assessment score (HR=1.229, pConclusionsBMI was an independent factor associated with 90-day survival in a Chinese cohort of medical patients with sepsis, with patients having a lower BMI at a higher risk of death.

Net ecosystem exchange (NEE) is an essential climate indicator of the direction and magnitude of carbon dioxide (CO2) transfer between land surfaces and the atmosphere. Improved estimates of NEE can serve to better constrain spatiotemporal characteristics of terrestrial carbon fluxes, improve verification of land models, and advance monitoring of Earth’s terrestrial ecosystems. Spatiotemporal NEE information developed by combining ground-based flux tower observations and spatiotemporal remote sensing datasets are of potential value in benchmarking land models. We apply a machine learning approach (Random Forest (RF)) to develop spatiotemporally varying NEE estimates using observations from a flux tower and several variables that can potentially be retrieved from satellite data and are related to ecosystem dynamics. Specific variables in model development include a mixture of remotely sensed (fraction of photosynthetically active radiation (fPAR), Leaf Area Index (LAI)) and ground-based data (soil moisture, downward solar radiation, precipitation and mean air temperature) in a complex landscape of the Reynolds Creek Experimental Watershed (RCEW) in southwest Idaho, USA. Predicted results show good agreement with the observed data for the NEE (r2 = 0.87). We then validate the temporal pattern of the NEE generated by the RF model for two independent years at the two sites not used in the development of the model. The model development process revealed that the most important predictors include LAI, downward solar radiation, and soil moisture. This work provides a demonstration of the potential power of machine learning methods for combining a variety of observational datasets to create spatiotemporally extensive datasets for land model verification and benchmarking.

In order to provide scientific support to policy makers in the regulation of PM2.5 pollution in China, it is important to accurately assess the current status, spatiotemporal characteristics and regionalization data for this air pollutant. An analysis of the pollution status of PM2.5 was conducted using daily averaged mass concentration data recorded in 74 cities in 2013 and 161 cities in 2014. The rotated empirical orthogonal function (REOF) method was applied to analyze this data. Results showed that the average annual PM2.5 concentration in urban areas of China is 62.2±21.5 µg/m3, and that the distribution is spatially heterogeneous. The North China Plain, middle and lower Yangtze River Plain, Si Chuan Basin and Guanzhong Plain had relatively high annual PM2.5 concentrations compared with the southeast coastal region, the Tibetan Plateau and the Yungui Plateau. PM2.5 mass concentrations tended to be higher in winter than in summer, however, the data for many cities showed a small peak in concentrations from May to July. An analysis of the spatial correlation of PM2.5 indicated a significant influence of topographic conditions. A lower correlation was observed where terrain features varied greatly. Based on the results of the REOF analysis and topographic characteristics, ten regions were identified in mid-eastern China, which could be considered as basic pollution prevention divisions for PM2.5; these include the North China Plain region, Pearl River Delta region, Jianghuai Plain region, middle Yangtze River Plain region, Northeast Plain region, Jiangnan coastal region, Si chuan Basin region, Qiantao Plain region, Guanzhong-Central Plain region and Yungui Plateau region. Seasonal variations in the regionalization data were observed, especially for the North China Plain and Pearl River Delta regions. Among the ten regions identified in this study, the North China Plain, Guanzhong-Central Plain, middle Yangtze River Plain and Jianghuai Plain had relatively high PM2.5 mass concentrations in comparison with the others. Therefore, these regions should be considered as the key regions to target in developing PM2.5 pollution prevention strategies. This study improves the present understanding of the spatial distribution, seasonal changes and regional status of PM2.5 pollution in China and helps establish possible control strategies for the reduction of this air pollutant.

Shortwave solar radiation is an important component of the surface energy balance and provides the principal source of energy for terrestrial ecosystems. This paper presents a machine learning approach in the form of a random forest (RF) model for estimating daily downward solar radiation flux at the land surface over complex terrain using MODIS (MODerate Resolution Imaging Spectroradiometer) remote sensing data. The model-building technique makes use of a unique network of 16 solar flux measurements in the semi-arid Reynolds Creek Experimental Watershed and Critical Zone Observatory, in southwest Idaho, USA. Based on a composite RF model built on daily observations from all 16 sites in the watershed, the model simulation of downward solar radiation matches well with the observation data (r2 = 0.96). To evaluate model performance, RF models were built from 12 of 16 sites selected at random and validated against the observations at the remaining four sites. Overall root mean square errors (RMSE), bias, and mean absolute error (MAE) are small (range: 37.17 W/m2-81.27 W/m2, -48.31 W/m2-15.67 W/m2, and 26.56 W/m2-63.77 W/m2, respectively). When extrapolated to the entire watershed, spatiotemporal patterns of solar flux are largely consistent with expected trends in this watershed. We also explored significant predictors of downward solar flux in order to reveal important properties and processes controlling downward solar radiation. Based on the composite RF model built on all 16 sites, the three most important predictors to estimate downward solar radiation include the black sky albedo (BSA) near infrared band (0.858 μm), BSA visible band (0.3–0.7 μm), and clear day coverage. This study has important implications for improving the ability to derive downward solar radiation through a fusion of multiple remote sensing datasets and can potentially capture spatiotemporally varying trends in solar radiation that is useful for land surface hydrologic and terrestrial ecosystem modeling.

We investigated ventilation inhomogeneity indices (Sacin, Scond) in patients with chronic obstructive pulmonary disease (COPD) using the multiple breath nitrogen washout test (MBNW) and determined the correlation between the 2 indices ( Scond and Sacin, as a measure of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively) and lung function to investigate the significance of assessing the COPD severity with ventilation inhomogeneity indices.Forty-three stable COPD patients and 56 non-smoking healthy subjects were recruited from November 2014 to February 2015. The differences of ventilation inhomogeneity indices (Sacin, Scond) between the 2 groups were compared, and the correlation between ventilation inhomogeneity indices and traditional parameters of lung function were determined using Pearson linear correlation. According to the FEV1%pred=50%, COPD patients were divided into 2 groups and ventilation inhomogeneity indices (Sacin, Scond) were compared between groups.Compared with the healthy control group,Sacin [0.320 (0.238, 0.432) vs 0.097 (0.073, 0.144), u=144.5, P0.001], and Scond [0.082 (0.043, 0.103) vs 0.018 (0.007, 0.028), u=103.5, P0.001] in COPD patients were significantly increased, and the difference was statistically significant. Sacin and Scond were negatively correlated with FVC%pred (r=-0.686, -0.551, both P0.001), FEV1%pred (r=-0.681, -0.475, both P0.01), FEV1/FVC (r=-0.458, -0.210, both P0.01). Sacin was negatively correlated with DLCO (r=0.413, P0.01). With the increase in the severity of the disease, Sacin and Scond increased gradually.Sacin and Scond in COPD patients increased significantly, which was significantly correlated with lung function. COPD has ventilation inhomogeneity in conductive and acinar zones and ventilation inhomogeneity indices can be used to evaluate the severity of COPD.

To analyse population pharmacokinetic (PPK) parameter values of ciprofloxacin in Chinese elderly patients with lower respiratory tract infection.Hospitalized in Respiratory Intensive Care Unit (RICU) due to severe lower respiratory tract infection and at high risks of Pseudomonas aeruginosa. 43 consecutive elderly patients received an intravenous infusion of ciprofloxacin at a dose of 200/400 mg every 12/24 h empirically. Plasma samples were drawn from Day 4 and at 1, 2, 3, 4, 6, 8 and 12 h after infusion. The serum concentrations of ciprofloxacin were determined by high-performance liquid chromatography (HPLC). Ciprofloxacin population pharmacokinetic analysis was conducted by the NONMEM 7.3.0 software.Forty patients aged (78 ± 9) years completed the study. A total of 210 serum concentrations were detected. The mean values of clearance and volume of distribution (V1) were 17.8 L/h and 49.8 L respectively. The serum creatinine level influenced ciprofloxacin according to the equation: Clearance - 17.8 × [1 - 0.001 3 × (serum creatinine - 67)] × e(η1i) × 0.659(n) (at a dose of 200 mg, n - 1, at a dose of 400 mg, n - 0; ηi for inter individual random variation). The values of clearance and V1 were multiplied by 0.659 at a dose of 200 mg. At the doses of 200 and 400 mg, the maximum steady-state concentrations (C(max)) were (4.2 ± 1.1) and (5.3 ± 1.21) mg/L, the minimum steady-state concentrations (C(min)) (1.1 ± 1.1) and (0.8 ± 0.4) mg/L and the area under concentration-time curve measured in steady-state up to 24 h after dosing (AUC(0-24 h)) were (45.5 ± 28.1) and (47.2 ± 11.3) mg · h · L⁻¹ respectively.The clearance of ciprofloxacin in elderly patients significantly decreases as compared with adult patients. Ciprofloxacin PPK model shows a significant influence of serum creatinine level on ciprofloxacin clearance. A single dose of 400 mg may increase serum drug concentration, but causes no in vivo drug retention.

Background: Meropenem is a broad-spectrum antibacterial that is usually used in the treatment of serious lower respiratory tract infections (LRTIs). However, there is a lack of published studies exploring the correlation between the population pharmacokinetics of meropenem, the clinical pharmacodynamics of the drug and the response to the drug in Chinese patients with LRTIs, especially in the elderly. Objective: The aim of this study was to develop a pharmacokinetic model of meropenem using patient data and use this to explore the clinical pharmacodynamics of meropenem in the treatment of LRTIs in elderly Chinese patients. Methods: We measured serum meropenem concentrations in patients who had received meropenem 0.5 or 1.0 g infused over 0.5 hours every 8 or 12 hours, respectively. The pharmacokinetic analysis of meropenem was performed using nonlinear mixed-effects modelling (NONMEM®) software. The minimum inhibitory concentration (MIC) of meropenem against Gram-negative bacilli was tested by the E-test method. The pharmacodynamic parameters of percentage of time above MIC (%T>MIC), the ratio of the drug area under the serum concentration-time curve to MIC (AUC/MIC), the ratio of the maximum serum concentration of the drug to MIC (Cmax/MIC) and the ratio of the minimum serum concentration of the drug to MIC (Cmin/MIC) were analysed for their association with clinical and bacteriological outcomes. Results: A total of 284 serum meropenem concentration measurements were obtained from 75 patients (aged 63–95 years). A two-compartment model fitted the concentration data best. The covariates creatinine clearance (CLCR) and Acute Physiology and Chronic Health Evaluation (APACHE) II score had the most significant effects on meropenem pharmacokinetics. Forty-five patients were enrolled in the pharmacodynamic study, including 25 clinical responders and 21 patients with bacteriological eradication. All of the 45 patients had Gram-negative bacilli isolated from tracheal aspirate or sputum. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values for the 25 clinical responders were significantly higher than those for the nonresponders (all p MIC independently influenced clinical outcome (p = 0.001, odds ratio [OR] = 1.065). The cut-off value for predicting clinical success using %T>MIC was 76%; the sensitivity and specificity of %T>MIC for predicting a successful response were 84% and 85%, respectively. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values, and the serum level of albumin, for the 21 patients with bacteriological eradication were significantly higher than those for patients with bacteriological treatment failure (all p MIC (p = 0.008, OR = 1.047) and serum level of albumin (p = 0.033, OR = 1.434) independently influenced bacteriological eradication. Conclusions: To our knowledge, this is the first study to investigate the population pharmacokinetics and clinical pharmacodynamics of meropenem in elderly Chinese. CLCR and APACHE II score have significant influences on meropenem pharmacokinetics. In LRTI patients, the cut-off value of 76% for %T>MIC can be applied to optimize their meropenem dose regimen to achieve clinical success.

The Cu-SiO2 core-shell nanocable arrays on the Cu wafers have been synthesized via a simple thermal evaporation of the SiO powder. The morphology and structure of the as-synthesized Cu-SiO2 core-shell nanocables are characterized by using scanning electron microscopy, high-resolution transmission electron microscopy, and X-ray energy dispersive spectrometer. The growth of amorphous SiO2 shell follows a vapor-liquid-solid mechanism, and then molten metal Cu will be diffused into the SiO2 nanotubes, forming the Cu-SiO2 core-shell nanocable arrays. It is found that the aligned Cu-SiO2 core-shell nanocables prefer to grow along the grooves of the Cu substrate, and the density of the Cu-SiO2 core-shell nanocable arrays can be controlled by adjusting the growth temperature.

In-doped Ga2O3 zigzag-shaped nanowires and undoped Ga2O3 nanowires have been synthesized on Si substrate by thermal evaporation of mixed powders of Ga, In2O3 and graphite at 1000 °C without using any catalyst via a vapor–solid growth mechanism. The morphologies and microstructures of the products were characterized by field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) and photoluminescence spectroscopy (PL). The nanowires range from 100 nm to several hundreds of nanometers in diameter and several tens of micrometers in length. A broad emission band from 400 to 700 nm is obtained in the PL spectrum of these nanowires at room temperature. There are two blue-emission peaks centering at 450 and 500 nm, which originate from the oxygen vacancies, gallium vacancies and gallium–oxygen vacancy pairs.

Single crystalline Sn-doped ZnO nanowires were successfully synthesized on indium tin oxide (ITO)-coated glass substrate by simple thermal evaporation approach without introducing any catalysts. The morphology and microstructure were determined by field emission scanning electron microscopy (FE-SEM), X-ray diffraction, high-resolution transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) and photoluminescence (PL) spectroscopy. The investigation confirmed that the products were of the wurtzite structure of ZnO. These doped nanowires have diameters in the range 30–50 nm and lengths of several tens of micrometers with growth direction along the c-axis of the crystal plane. Photoluminescence of these doped nanowires exhibits a weak ultraviolet (UV) emission peak at around 400 nm and the strong green emission peak at around 495 nm at room temperature, which may be induced by the Sn-doping. The growth mechanism of the doped nanowires was also discussed.

Bulk-quantity polycrystalline ternary alloyed Si-ZnS nanowires have been successfully synthesized by one-step thermal evaporation of a mixed powder of ZnS and SiO, using metallic gallium as a catalyst. The morphology and structure of the as-synthesized ternary alloyed Si-ZnS nanowires are characterized by using X-ray diffraction, scanning electron microscopy, and high-resolution transmission electron microscopy. The observations reveal that the ternary alloyed Si-ZnS nanowires have the same structure with cubic ZnS or Si. X-ray energy dispersive spectrometer analysis indicates that there is remarkable Si/Zn/S variation along the Si-ZnS nanowire. The room-temperature photoluminescence spectrum shows that the as-synthesized Si-ZnS nanowires have two emission peaks at 355 and 685 nm, and feature the superimposed optical properties of ZnS and Si.

GaN micro/nanocone bundles with controllable size and density have been synthesized on Cu or Cu95In5 alloy wafers using a modified thermal-evaporation process. The size and density of GaN cone bundles could be efficiently controlled by adjusting growth temperatures and the components of metal substrates. The structure and morphology of the as-synthesized GaN cones were characterized using X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The as-synthesized micro/nanocones are single crystals with a hexagonal wurtzite structure, growing along the [ 1 0 1 ¯ 1 ] direction. The growth process follows a vapor–liquid–solid mechanism. The dependence of photoluminescence property on the size and density of GaN cone bundles at room temperature was also investigated.

Aligned Zn2GeO4 coated ZnO nanorods and Ge doped ZnO nanocombs were synthesized on a silicon substrate by a simple thermal evaporation method. The structure and morphology of the as-synthesized nanostructure were characterized using scanning electron microscopy and transmission electron microscopy. The growth of aligned Zn2GeO4 coated ZnO nanorods and Ge doped ZnO nanocombs follows a vapor-solid (VS) process. Photoluminescence properties were also investigated at room temperature. The photoluminescence spectrum reveals the nanostructures have a sharp ultraviolet luminescence peak centered at 382 nm and a broad green luminescence peak centered at about 494 nm.

Large-scale GeO2 nanowire arrays were successfully synthesized by a simple thermal evaporation method with the mechanism of Self-catalytic Vapor–Liquid–Solid growth. Its morphology and microstructure were determined by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) and photoluminescence spectroscopy (PL). The one-dimensional GeO2 nanostructures are extremely sensitive to electron irradiation, and the nanowires were transformed from crystal into amorphous when performing high-resolution transmission electron microscopy (HRTEM). The nanowires have diameters of 100 nm, length of 800 nm and the spherical particles terminating at the tip of the nanowires have diameters of about 500 nm. Two blue emission peaks at 448 nm and 471 nm and a violet emission peak at 411 nm were observed in the room-temperature photoluminescence measurements.

Large scale flower-like ZnO nanosheets have been synthesized on Zinc foil by a simple hydrothermal method. Their morphology and microstructures were characterized and analyzed by X-ray spectroscopy (XRD), field emission scanning electron microscopy (FE-SEM) and high-resolution transmission electron microscopy (HRTEM). The as-synthesized flower-like nanosheets are hexagonal phase single crystal with 200–300 nm in width, 50 nm in thickness. The growth process follows the liquid phase epitaxial growth mechanism. In this approach, the ZnO buffer is used as substrate for the growth of flower-like ZnO nanosheets. The growth direction of the nanosheets is the preferential [0 0 0 1] growth direction of ZnO. The photoluminescence spectrum of the sample exhibits only a sharp and strong UV emission centered at 386 nm, which indicates that the flower-like ZnO nanosheets on Zn foil are of good optical property.

Well-aligned ZnO nanorods and nanopins are synthesized on a silicon substrate using a one-step simple thermal evaporation of a mixture of zinc and zinc acetate powder under controlled conditions. A self-assembled ZnO buffer layer was first obtained on the Si substrate. The structure and morphology of the as-synthesized ZnO nanorod and nanopin arrays are characterized using X-ray diffraction, and scanning and transmission electron microscopies, energy-dispersive X-ray spectroscopy, and photoluminescence spectroscopy. The influence of the background atmosphere on the two ZnO nanostructures has been studied. Two different growth mechanisms are mentioned to interpret the formation of ZnO nanorod and nanopin arrays in our work. The room-temperature PL features the ZnO nanorods exhibit only sharp and strong ultraviolet (UV) emission emissions, which confirms the better crystalline and optical quality than the ZnO nanopins.

Ultrafine hierarchical tree-shaped nanoarchitectures of ZnS were synthesized by a H 2 -assisted thermal evaporation and condensation technique. Morphology and composition of the ZnS deposit were studied by means of field emission scanning electron microscopy, high-resolution transmission electron microscopy and energy dispersive X-ray spectroscopy. The deposit was found to consist of a layer of oriented submicrorods partly covered by microsheets and randomly oriented submicrowires, and three-dimensional treelike nanoarchitectures grew epitaxially on various submicrorods, microsheets, and submicrowires. The growth of the nanostructures is a spontaneous and self-assembled process. Vapor–solid (VS) growth mechanism is proposed for the formation of the treelike nanostructures because catalyst was not introduced during the synthesis process. This novel hierarchical ZnS nanoarchitecture may offer great potential for applications, including three-dimensional nanoelectronics and high efficient spatial resolved photon detector.

This paper describes a thermal evaporation method that generated large-scale novel doorframe-like ITO nanostructures by regularly switching flow rate of the carried gas. Their morphology and microstructures were determined by scanning electron microscopy, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy and photoluminescence spectroscopy. The as-synthesized doorframe-like nanostructures are single crystal with diameters ranging from hundreds of nm to about 1 μm. The growth direction of the doorframe-like nanostructures are and and the growth process follows a self-catalytic vapor–liquid–solid mechanism. The PL spectrum of the doorframe-like nanostructures shows two emission bands around 418 and 505 nm, which is probably resulted from oxygen vacancies, oxygen–indium vacancy pairs and impurity level, respectively.

A large quantity of Zinc oxide (ZnO) comb-like structure and high-density well-aligned ZnO nanorod arrays were prepared on silicon substrate via thermal evaporation process without any catalyst. The morphology, growth mechanism, and optical properties of the both structures were investigated using XRD, SEM, TEM and PL. The resulting comb-teeth, with a diameter about 20 nm, growing along the [0001] direction have a well-defined epitaxial relationship with the comb ribbon. The ZnO nanorod arrays have a diameter about 200 nm and length up to several micrometers growing approximately vertical to the Si substrate. A ZnO film was obtained before the nanorods growth. A growth model is proposed for interpreting the growth mechanism of comb-like zigzag-notch nanostructure. Room temperature photoluminescence measurements under excitation wavelength of 325 nm showed that the ZnO comb-like nanostructure has a weak UV emission at around 384 nm and a strong green emission around 491 nm, which correspond to a near band-edge transition and the singly ionized oxygen vacancy, respectively. In contrast, a strong and sharp UV peak and a weak green peak was obtained from the ZnO nanorod arrays.

We have prepared the gallium oxide (Ga 2 O 3 ) nanomaterials on Si (1 1 1) substrates by thermal evaporation of gallium in the ammonia atmosphere. The self-catalytic vapor–solid mechanism is used in explaining the formation mechanism. Scanning electron microscopy (SEM) revealed that the products contained many special structures, including spiral nanobelts, nanotrees and nanotubes locating in different temperature zones, respectively. The selected area electron diffraction (SAED) and high-resolution transmission electron microscopy (HRTEM) observations suggest that these as-synthesized products have a single-crystalline structure with a width ranging from 100 nm to several micrometers. Possible mechanism leading to the formation of Ga 2 O 3 nanomaterials, especially the relation between temperature and some special structures is to be discussed in this paper. Photoluminescence spectrum under excitation at 396 nm showed a green emission, which is probably attributed to vacancies in Ga 2 O 3 .

Uniform zinc gallate (ZnGa2O4) nanowires are successfully synthesized by a one-step simple thermal evaporation of a mixture of ZnO and Ga2O3 powders under controlled conditions. Its morphology and microstructures were determined by X-ray powder diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy, and photoluminescence spectroscopy. The observations reveal that the as-synthesized ZnGa2O4 nanowires are single-crystalline with a cubic spinel structure, usually several tens of microns in length. The typical diameters of ZnGa2O4 nanowires range from 100 to 200 nm. The room-temperature photoluminescence spectrum of ZnGa2O4 nanowires features four luminescence peaks around 400, 503, and 686 nm, which are attributed to self-activation center of the octahedral Ga−O, electronic transitions of localized Ga3+ ion in the octahedral Ga−O, and single oxygen vacancies (VO*), respectively. A self-assembled Ga catalytic vapor−liquid−solid (VLS) f...

We report on the realization of novel 3-D hierarchical heterostructures with 6-and 4-fold symmetries by a transport and condensation technique. It was found that the major core nanowires or nanobelts are single-crystalline In2O3, and the secondary nanorods are single-crystalline monoclinic beta-Ga2O3 and grow either perpendicular on or slanted to all the facets of the core In2O3 nanobelts. Depending on the diameter of the core In2O3 nanostructures, the secondary Ga2O3 nanorods grow either as a single row or multiple rows. The one-step growth of the unique Ga2O3/In2O3 heteronanostructures is a spontaneous and self-organized process. The simultaneous control of nanocrystal size and shape together with the possibility of growing heterostructures on certain nanocrystal facets opens up novel routes to the synthesis of more sophisticated heterostructures as building blocks for opto- and nanoelectronics.

Mass production of transparent semiconducting ternary oxide Zn 2 SnO 4 nanowires is successfully synthesized by the thermal evaporation method without any catalyst. The as-synthesized products are characterized with field-emission scanning electron microscope (FE-SEM), X-ray powder diffraction (XRD), energy-dispersive spectroscopy (EDS), high-resolution transmission electron microscope (HR-TEM) and selected area electron diffraction (SEAD). A formation of Zn 2 SnO 4 nanowires based on a self-catalytic VLS growth mechanism is discussed. The photoluminescence spectrum (PL) of the nanowires shows a broad blue-green emission around the 300–600 nm wavelengths with a maximum center at 580 nm under room temperature.

Background The beneficial outcome associated with the use of proton pump inhibitors (PPIs) in idiopathic pulmonary fibrosis (IPF) has been reported in retrospective studies. To date, no prospective study has been conducted to confirm these outcomes. In addition, the potential mechanism by which PPIs improve measures of lung function and/or transplant-free survival in IPF has not been elucidated. Methods Here, we used biochemical, cell biological and preclinical studies to evaluate regulation of markers associated with inflammation and fibrosis. In our in vitro studies, we exposed primary lung fibroblasts, epithelial and endothelial cells to ionizing radiation or bleomycin; stimuli typically used to induce inflammation and fibrosis. In addition, we cultured lung fibroblasts from IPF patients and studied the effect of esomeprazole on collagen release. Our preclinical study tested efficacy of esomeprazole in a rat model of bleomycin-induced lung injury. Furthermore, we performed retrospective analysis of interstitial lung disease (ILD) databases to examine the effect of PPIs on transplant-free survival. Results The cell culture studies revealed that esomeprazole controls inflammation by suppressing the expression of pro-inflammatory molecules including vascular cell adhesion molecule-1, inducible nitric oxide synthase, tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6). The antioxidant effect is associated with strong induction of the stress-inducible cytoprotective protein heme oxygenase-1 (HO1) and the antifibrotic effect is associated with potent inhibition of fibroblast proliferation as well as downregulation of profibrotic proteins including receptors for transforming growth factor β (TGFβ), fibronectin and matrix metalloproteinases (MMPs). Furthermore, esomeprazole showed robust effect in mitigating the inflammatory and fibrotic responses in a murine model of acute lung injury. Finally, retrospective analysis of two ILD databases was performed to assess the effect of PPIs on transplant-free survival in IPF patients. Intriguingly, this data demonstrated that IPF patients on PPIs had prolonged survival over controls (median survival of 3.4 vs 2 years). Conclusions Overall, these data indicate the possibility that PPIs may have protective function in IPF by directly modulating the disease process and suggest that they may have other clinical utility in the treatment of extra-intestinal diseases characterized by inflammatory and/or fibrotic phases. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0614-x) contains supplementary material, which is available to authorized users.

Long-term impacts of acidic deposition on the Great Smoky Mountains National Park (GRSM) include elevated inputs of sulfate, nitrate, and ammonium; the depletion of available nutrient cations from soil; and acidification of high-elevation streams. Critical loads and target loads (CLs/TLs) are useful tools to help guide future air quality management. We evaluated past and potential future effects of nitrate and sulfate deposition for 12 watersheds in the GRSM, USA, using the hydrochemical model, photosynthesis evapotranspiration biogeochemical (PnET-BGC). Two of the streams studied were listed by the state of Tennessee as impaired due to low stream pH. We reconstructed historical meteorological, atmospheric deposition, and land disturbance data for study watersheds for the period 1850 to present for model hindcasts. As future emissions are expected to decline, the model was run under a range of future scenarios from 2008 to 2200 of decreases in sulfate, nitrate, and ammonium and combinations of sulfate and nitrate deposition to estimate CLs and TLs of how watersheds might respond to emission control strategies. Model simulations of stream chemistry generally agreed with long-term (>10 years) observations. Model hindcasts indicate that watersheds in the GRSM are inherently sensitive to acidic deposition. Simulated mean projected stream ANC of 71 μeq/L (range 32 to 107 μeq/L) prior to industrial development (~1850) decreases in response to historical acidic deposition to 33 μeq/L (−13 to 88 μeq/L) in 2007. Future model projections show that decreases in sulfate deposition result in smaller increases in stream ANC compared with equivalent decreases in nitrate deposition; simultaneous controls on nitrate and sulfate deposition are more effective in ANC increases than individual control of nitrate or sulfate. Although there are no current programs in the USA to control ammonia emissions, model simulations suggest that decreases in ammonium deposition could also help mitigate acidification to a greater extent than equivalent controls on nitrate deposition.