Development and external validation of a nomogram for the early prediction of acute kidney injury in septic patients: a multicenter retrospective clinical study.

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

Safety, tolerability, and pharmacokinetics of a single ascending subcutaneous dose of GSK3772847 in healthy participants.

The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK3772847, compared with placebo administered subcutaneously (SC) in healthy participants, including cohorts of Japanese and Chinese participants. This was a single-center, randomized, placebo-controlled, double-blind, single ascending dose study. Following a screening period of up to 28 days, eligible participants were assigned to one of four cohorts receiving a single dose of GSK3772847 70 mg (cohort 1) or 140 mg (cohorts 2, 3, and 4) or placebo SC. In cohorts 1 and 2, participants were randomly assigned to one of three injection sites (upper arm, abdomen, or thigh), while cohorts 3 and 4 included Japanese and Chinese participants, respectively, assigned to receive GSK3772847 or placebo SC (upper arm). Participants attended follow-up visits on Days 9, 15, 29, 43, 57, 71, and 85 before final analysis. GSK3772847 was generally well tolerated. Most adverse events (AEs) were mild, resolved without treatment and were considered not related to study treatment by the investigator. There were no serious AEs or deaths during the study. The PK and PD were dose dependent, with negligible differences across injection sites or ethnicities. Target engagement was demonstrated by reduced free soluble interleukin 33 (sIL-33) concentrations and substantially increased total sIL-33 concentrations compared with baseline. Subcutaneously administered GSK3772847 was well tolerated in healthy participants, including cohorts of Japanese and Chinese participants, and shows consistent PK and PD across injection sites and ethnicities.

Two-dimensional monitoring of a laser-solid x-ray source spot via penumbral coded aperture imaging technique.

The uncertainties of spot size and position need to be clarified for x-ray sources as they can affect the detecting precision of the x-ray probe beam in applications such as radiography. In particular, for laser-driven x-ray sources, they would be more significant as they influence the inevitable fluctuation of the driving laser pulses. Here, we have employed the penumberal coded aperture imaging technique to diagnose the two-dimensional spatial distribution of an x-ray emission source spot generated from a Cu solid target irradiated by an intense laser pulse. Taking advantage of the high detection efficiency and high spatial resolution of this technique, the x-ray source spot is characterized with a relative error of ∼5% in the full width at half maximum of the intensity profile in a single-shot mode for general laser parameters, which makes it possible to reveal the information of the unfixed spot size and position precisely. Our results show the necessity and feasibility of monitoring the spot of these novel laser-driven x-ray sources via the penumbral coded aperture imaging technique.

Transcription factors AcERF74/75 respond to waterlogging stress and trigger alcoholic fermentation-related genes in kiwifruit.

Kiwifruit plants have a fleshy, shallow root system which is sensitive to waterlogging stress, which results in a decrease in crop yield or even plants death. Although the waterlogging stress responses in kiwifruit have attracted much attention, the underlying molecular mechanism remains unclear. In this study, waterlogging led to drastic inhibition of root growth of 'Donghong' kiwifruit (Actinidia chinensis) plants grown in vitro, which was accompanied by significant elevation of endogenous acetaldehyde and ethanol contents. RNA-seq of roots of plants waterlogged for 0, 1 and 2 days revealed that a total of 149 genes were up- or down-regulated, including seven biosynthetic genes related to the glycolysis/gluconeogenesis pathway and 10 transcription factors. Analyses with real-time PCR, dual-luciferase assays and EMSA demonstrated that AcERF74 and AcERF75, two members of the ERF-VII subfamily, directly upregulated AcADH1 (alcohol dehydrogenase). Moreover, the overexpression of AcERF74/75 in transgenic calli resulted in dramatic increase of endogenous ethanol contents through the triggering of AcADH1 and AcADH2 expression. Although the AcPDC2 (pyruvate decarboxylase) expression was also enhanced in transgenic lines, the endogenous acetaldehyde contents showed no significant changes. These results illustrated that AcERF74/75 are two transcriptional activators on alcoholic fermentation related genes and are responsive to waterlogging stress in kiwifruit.

The effect of NH4+ on phosphoenolpyruvate carboxykinase gene expression, metabolic flux and citrate content of citrus juice sacs.

Citrate is one of the most important metabolites determining the flavour of citrus fruit. It has been reported that nitrogen supply may have an impact on acid level of fruit. Here, the relationship between nitrogen metabolism and citrate catabolism was studied in pumelo juice sacs. Differences in metabolites, gene expression and flux distributions were analyzed in juice sacs incubated in medium with and without NH4+. Compared with those incubated with NH4+, juice sacs under nitrogen deficiency exhibited enhanced flux through phosphoenolpyruvate carboxykinase (PEPCK) and accelerated consumption of citrate, while the other two TCA cycle efflux points, through malic enzyme (ME) and glutamate dehydrogenase (GDH), were both repressed. Consistent with the estimated fluxes, the expression of PEPCK1 was upregulated under nitrogen deficiency, while that of GDH1, GDH2, NAD-ME1 and NADP-ME2 were all repressed. Thus, we propose that PEPCK1 contributes to citrate degradation under nitrogen limitation.

Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD.

Chronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George's Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62-128]; P < 0.001), and significantly improved SGRQ and CAT versus TIO. Treatment safety profiles were similar. Once-daily single-inhaler FF/UMEC/VI significantly improved lung function and health status versus once-daily TIO in symptomatic moderate-to-very-severe COPD patients, with a similar safety profile.

InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations.

BACKGROUND: Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD. METHODS: 8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs). RESULTS: Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile. CONCLUSIONS: Rate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes. TRIAL REGISTRATION: NCT02164513.

Peak Inspiratory Flow Rate in COPD: An Analysis of Clinical Trial and Real-World Data.

BACKGROUND: The influence of peak inspiratory flow (PIF) on dose delivery from dry powder inhalers (DPIs) and association with treatment efficacy in patients with chronic obstructive pulmonary disease (COPD) has not been fully determined. In vitro studies have demonstrated adequate dose delivery through ELLIPTA DPI at PIF ≥30 L/min. This analysis of two clinical trials and a real-world population of COPD patients determined spirometric PIF distribution, and explored the relationship between PIF and outcomes in the trials. METHODS: The replicate Phase IV, 12-week, randomized, double-blind 207608/207609 (NCT03478683/NCT03478696) trials evaluated fluticasone furoate/umeclidinium/vilanterol via ELLIPTA DPI versus budesonide/formoterol+tiotropium in COPD patients. This post hoc analysis assessed spirometric PIF distribution at screening and relationship between PIF and lung function outcomes in the pooled 207608/207609 population. Spirometric PIF distributions in a real-world population of COPD patients were evaluated by retrospective analysis of the Kaiser Permanente Northwest (KPNW) database to assess similarities between clinical trial and real-world populations. RESULTS: A total of 1460 (207608/207609) and 3282 (KPNW) patients were included. There was considerable overlap between spirometric PIF distributions for both populations. Overall, 99.7% and 99.8% of the 207608/207609 and KPNW populations, respectively, reported spirometric PIF ≥50 L/min, estimated as equivalent to ELLIPTA PIFR ≥30 L/min. In the 207608/207609 combined analysis, there was no significant interaction between spirometric PIF and treatment for lung function endpoints, indicating treatment effect is independent of PIF. CONCLUSION: Nearly all COPD patients in the 207608/207609 and KPNW populations achieved spirometric PIF values estimated as equivalent to PIFR of ≥30 L/min through the ELLIPTA DPI. Lack of correlation between spirometric PIF at screening and treatment efficacy aligns with consistent dose performance from the ELLIPTA DPI across a wide range of PIFs, achieved by patients with COPD of all severities.

Transcriptome Analysis Revealed the Roles of Carbohydrate Metabolism on Differential Acetaldehyde Production Capacity in Persimmon Fruit in Response to High-CO2 Treatment.

Persimmon (Diospyros kaki Thunb.) fruit is unique due to the continuous accumulation of soluble tannins during fruit development in most cultivars, which causes undesired astringency. High-CO2 treatment was the most effective widely used method for astringency removal. However, differential effects of high-CO2 treatment between cultivars were observed and the molecular basis remained inclusive. Previously, one cultivar ("Luoyangfangtianshengshi," LYFTSS) showed rapid deastringency, while two cultivars ("Shijiazhuanglianhuashi," SJZLHS; "Laopige," LPG) showed slow deastringency in response to high-CO2 (95% CO2) treatment. In this study, the metabolites (acetaldehyde and ethanol) related to deastringency were further analyzed and both acetaldehyde and ethanol were higher in SJZLHS and LYFTSS than that in LPG, where acetaldehyde was undetectable. Based on the RNA-seq data, the weighted gene coexpression network analysis (WGCNA) revealed that one module, comprised of 1773 unigenes, significantly correlated with the contents of acetaldehyde and ethanol (P < 0.001). Further analysis based on the acetaldehyde metabolism pathway indicated that the differentially expressed structural genes, including previously characterized DkADH and DkPDC and also their upstream members (e.g., PFK, phosphofructokinase), showed positive correlations with acetaldehyde production. Quantitative analysis of the precursor substances indicated that sucrose, glucose, and fructose exhibited limited differences between cultivar except for malic acid. However, the content of malic acid is much less than the total soluble sugar content. To verify the correlations between these genes and acetaldehyde production, the fruit from 14 more cultivars were collected and treated with high CO2. After the treatment, acetaldehyde contents in different cultivars ranked in 30.4-255.5 µg/g FW. Real-time polymerase chain reaction (PCR) and correlation analysis indicated that the EVM0002315 (PFK) gene, belonging to carbohydrate metabolism, was significantly correlated with acetaldehyde content in fruit. Thus, it could be proposed that the differentially expressed carbohydrate metabolism related genes (especially PFK) are the basis for the variance of acetaldehyde production among different persimmon cultivars.

24-Hour Serial Spirometric Assessment of Once-Daily Fluticasone Furoate/Umeclidinium/Vilanterol Versus Twice-Daily Budesonide/Formoterol in Patients with COPD: Analysis of the FULFIL Study.

INTRODUCTION: Few studies have utilized 24-h serial spirometry to compare the effects of inhaled chronic obstructive pulmonary disease (COPD) therapies on lung function. The FULFIL study previously reported significant lung function improvements with once-daily single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus twice-daily single-inhaler budesonide/formoterol (BUD/FOR) in patients with symptomatic COPD at risk of exacerbations. METHODS: This prespecified analysis evaluated 24-h serial spirometry data from a subgroup of 406 patients in FULFIL. BUD/FOR twice-daily dosing was maintained during 24-h spirometry. A post hoc analysis evaluated serial forced expiratory volume in 1 s (FEV1) at day 1 and week 24 by disease severity at screening (FEV1 < 50% predicted and no moderate or severe exacerbation in prior year, FEV1 < 50% predicted and ≥ 1 moderate or severe exacerbation in prior year, and FEV1 ≥ 50% and < 80% predicted and ≥ 2 moderate or ≥ 1 severe exacerbations in prior year). RESULTS: Odds of achieving a ≥ 100-mL increase from baseline in FEV1 within the first 6 h post dose on day 1 were significantly greater with FF/UMEC/VI than BUD/FOR [odds ratio 2.79 (95% confidence interval 1.56-4.98); p < 0.001]. FF/UMEC/VI led to greater improvements in weighted mean FEV1 over 0-6, 0-12, 0-24, and 12-24 h on day 1 and at week 24, with the greatest between-group differences at week 24 (range 196-210 mL; all p < 0.001). Significant between-treatment differences in FEV1 and forced vital capacity (FVC) in favor of FF/UMEC/VI versus BUD/FOR were seen at all time points at week 24 (FEV1 range 156-231 mL, all p < 0.001; FVC range 139-309 mL, all p ≤ 0.002). Serial FEV1 results were consistent irrespective of disease severity at screening. CONCLUSION: These findings further demonstrate sustained lung function benefits with once-daily FF/UMEC/VI single-inhaler triple therapy in patients with symptomatic COPD at risk of exacerbations across a range of disease severities.

Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials.

BACKGROUND: The comparative efficacy of inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) triple therapy administered via single or multiple inhalers in patients with chronic obstructive pulmonary disease (COPD) has not been evaluated comprehensively. We conducted two replicate trials comparing single- with multiple-inhaler ICS/LAMA/LABA combination in COPD. METHODS: 207608 and 207609 were Phase IV, 12-week, randomized, double-blind, triple-dummy non-inferiority trials comparing once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg via Ellipta inhaler, with twice-daily budesonide/formoterol (BUD/FOR) 400/12 µg via metered-dose inhaler plus once-daily tiotropium (TIO) 18 µg via HandiHaler. Patients had symptomatic COPD and forced expiratory volume in 1 s (FEV1) < 50% predicted, or FEV1 < 80% predicted and ≥ 2 moderate or 1 severe exacerbations in the prior year. The primary endpoint in both trials was weighted mean change from baseline (wmCFB) in 0-24-h FEV1 at Week 12. Secondary endpoints included CFB in trough FEV1 at Day 84 and 85. Other endpoints included serial FEV1 and health status outcomes at Week 12. Safety was evaluated descriptively. RESULTS: The modified per-protocol population included 720 and 711 patients in studies 207608 and 207609 (intent-to-treat population: 728 and 732). FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 (Study 207608 treatment difference [95% confidence interval]: 15 mL [- 13, 43]; Study 207609: 11 mL [- 20, 41]). FF/UMEC/VI improved trough FEV1 CFB versus BUD/FOR+TIO at Day 84 and 85 (Day 85 treatment difference: Study 207608: 38 mL [10, 66]; Study 207609: 51 mL [21, 82]) and FEV1 at 12 and 24 h post-morning dose at Week 12 in both studies. No treatment differences were seen in health status outcomes. Safety profiles were similar between treatments; pneumonia occurred in 7 (< 1%) patients with FF/UMEC/VI and 9 (1%) patients with BUD/FOR+TIO, across both studies. CONCLUSIONS: FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 in patients with COPD. Greater improvements in trough and serial FEV1 measurements at Week 12 with FF/UMEC/VI versus BUD/FOR+TIO, together with similar health status improvements and safety outcomes including the incidence of pneumonia, suggest that once-daily single-inhaler FF/UMEC/VI triple therapy is a viable option for patients looking to simplify their treatment regimen. TRIAL REGISTRATION: GSK (207608/207609; NCT03478683/NCT03478696).

Optical steering of electron beam in laser plasma accelerators.

Using a Dazzler system and tilting a compressor grating, we provide an effective way of using the laser group delay dispersion to continuously steer the electron beam accelerated by an asymmetric laser wakefield. The deviation angle of the electron beam was the same as that of the angularly chirped laser pulse from its initial optical axis, which is determined by the laser pulse-front-tilt (PFT). This method can be utilized to continuously control over the pointing direction of electron bunches to the requisite trajectories, especially for practical applications in highly sensitive alignment devices such as electron-positron colliders or undulators. Additionally, we investigate the effect of PFT on the properties of the electron beam.

Prognostic value of albumin-red cell distribution width score in patients with severe community-acquired pneumonia.

BACKGROUND: It has been recently reported that albumin (ALB) and red cell distribution width (RDW) are correlated with the prognosis of community-acquired pneumonia, while their role in severe communityacquired pneumonia (sCAP) is unknown. This study aimed to investigate the correlation between the ALBRDW score and 90-day mortality of sCAP patients. METHODS: A total of 179 sCAP patients admitted to our hospital between January 1, 2014 and June 30, 2019 were enrolled in this study. Data of patient characteristics and laboratory data were obtained and CURB-65 was calculated. The ALB-RDW score was calculated based on serum ALB and RDW. Receiver operating characteristic (ROC) curve and the value of area under the curve (AUC) were used to evaluate the association between ALB-RDW score and 90-day mortality of sCAP patients. RESULTS: Compared with survivors, age, white blood cell counts, neutrophil counts, RDW, D-dimer, serum creatinine, lactic dehydrogenase, CURB-65 score, ALB-RDW high score ratio, invasive ventilation and septic shock were higher in non-survivors, while ALB and hemoglobin (HB) were lower. Multivariate logistic regression analysis identified that high age, serum creatinine, ALB-RDW score and invasive ventilation were the independent risk factors of 90-day mortality (P<0.05). Moreover, the AUC of ALB-RDW score was 0.742 [95% confidence interval (CI): 0.667-0.817], which was superior to CURB-65 score 0.725 (95% CI: 0.651-0.798). The AUC increased to 0.798 (95% CI: 0.733-0.862) when combined with CURB-65 score. CONCLUSIONS: High age, serum creatinine, ALB-RDW score and invasive ventilation were the independent risk factors of 90-day mortality of sCAP patients. In addition, the correlation between ALB-RDW and 90-day mortality was even stronger when combined with CURB-65 score.

Construction of an anchoring SSR marker genetic linkage map and detection of a sex-linked region in two dioecious populations of red bayberry.

Red bayberry (Morella rubra) is an evergreen fruit tree found in southern China whose whole-genome sequence has recently been published. We updated the linkage map of the species by adding 118 SSR markers and the female-specific marker MrFT2_BD-SEX. The integrated map included eight linkage groups and spanned 491 cM. Eleven sex-associated markers were identified, six of which were located in linkage group 8, in agreement with the previously reported location of the sex-determining region. The MrFT2_BD-SEX marker was genotyped in 203 cultivated accessions. Among the females of the accessions, we found two female-specific alleles, designated W-b (151 bp) and W-d (129 bp). We previously found that 'Dongkui', a female cultivar, could produce viable pollen (we refer to such plants 'Dongkui-male') and serve as the paternal parent in crosses. The genotypes of the MrFT2_BD-SEX marker were W-b/Z in 'Biqi' and W-d/Z in 'Dongkui-male'. The progeny of a cross between these parents produced a 3:1 female (W-) to male (ZZ) ratio and the expected 1:1:1:1 ratio of W-b/W-d: W-b/Z: W-d/Z: Z/Z. In addition, the flowering and fruiting phenotypes of all the F1 progeny fit their genotypes. Our results confirm the existence of ZW sex determination and show that the female phenotype is controlled by a single dominant locus (W) in a small genomic region (59 kb and less than 3.3 cM). Furthermore, we have produced a homozygous "super female" (WW) that should produce all-female offspring in the F2 generation, providing a foundation for commercial use and presenting great potential for use in modern breeding programs.

Short-period high-strength helical undulator by laser-driven bifilar capacitor coil.

Laser wakefield accelerators have emerged as a promising candidate for compact synchrotron radiation and even x-ray free electron lasers. Today, to make the electrons emit electromagnetic radiation, the trajectories of laser wakefield accelerated electrons are deflected by transverse wakefield, counter-propagating laser field or external permanent magnet insertion device. Here, we propose a novel type of undulator that has a period of a few hundred microns and a magnetic field of tens of Tesla. The undulator consists of a bifilar capacitor-coil target that sustains a strong discharge current that generates a helical magnetic field around the coil axis when irradiated by a high-energy laser. Coupling this undulator with state-of-the-art laser wakefield accelerators can, simultaneously, produce ultra-bright quasi-monochromatic x-rays with tunable energy ranging 5-250 keV and optimize the free electron laser parameter and gain length compared with a permanent magnet-based undulator. This concept may pave a path toward ultra-compact synchrotron radiation and even x-ray free electron lasers.

One-step hydrothermal synthesis of silver-doped carbon quantum dots for highly selective detection of uric acid.

In this paper, a simple and convenient fluorescence method for detection of uric acid (UA) based on Ag-doped carbon quantum dots (Ag-CQDs) is developed. The Ag-CQDs contain Ag species could bond with UA, which promoted the electron and/or energy transfer and produced high quenching extent. Thus, the fluorescence intensity of Ag-CQDs decreased in the presence of UA. Under the optimal condition, the UA sensor exhibited a linear response in the range of 0.005-100 µM with a detection limit of 0.35 nM (S/N = 3). Ag-CQDs demonstrated high sensitivity and rapid response to UA over a wide range of concentration indicating their great potential as a fluorescent probe for chemical sensing. Moreover, this method has successfully applied to detect UA in human urine samples.

Predictive role of monocyte-to-lymphocyte ratio in patients with Klebsiella pneumonia infection: A single-center experience.

The aim of the study is to explore whether monocyte-to-lymphocyte ratio (MLR) provides predictive value of the severity in patients with Klebsiella pneumonia infection (KPI).Patients in a tertiary medical center with Klebsiella pneumonia infection from 2014 to 2017 were recruited in this study. Patients with Klebsiella pneumonia infection were stratified into two groups based on the National Early Warning Score (NEWS). MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. The area under the curve (AUC) values was determined using the receiver-operating characteristic (ROC) curve. The correlation between the variables was tested with Pearson or Spearman correlation analysis. Ordinal logistic regression analysis was used to assess the relationship between MLR and the severity of Klebsiella pneumonia infection.One hundred fifty-two patients were finally enrolled for analysis. Among those, 43 (28.29%) cases had severe KPI. MLR was found to be an independent risk factor of the serious Klebsiella pneumonia infection (OR: 23.74, 95% CI: 5.41-104.11, P < .001). Besides, MLR was positively correlated with NEWS score (r = 0.57, P < .001). In the receiver-operating characteristic (ROC) curve analysis, MLR, with an optimal cut-off value of 0.665, predicted the severe coronary lesion with a sensitivity of 79.4% and specificity of 84.4%.MLR was an independent predictor of the severe Klebsiella pneumonia infection. Compared with neutrophil-to-lymphocyte ratio (NLR), MLR has a better performance to evaluate the severity of Klebsiella pneumonia infection.

Preventing clinically important deterioration with single-inhaler triple therapy in COPD.

Clinically important deterioration (CID) is a novel composite end-point (lung function, health status, exacerbations) for assessing disease stability in patients with chronic obstructive pulmonary disease (COPD). We prospectively analysed CID in the FULFIL study. FULFIL (ClinicalTrials.gov NCT02345161; randomised, double-blind, double-dummy, multicentre study) compared 24 weeks of once daily, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg with twice daily budesonide/formoterol (BUD/FOR) 400/12 µg in patients aged ≥40 years with symptomatic advanced COPD (Global Initiative for Chronic Obstructive Lung Disease group D). A subset of patients received study treatment for up to 52 weeks. Time to first CID event was assessed over 24 and 52 weeks using two approaches for the health status component: St George's Respiratory Questionnaire and COPD assessment test. FF/UMEC/VI significantly reduced the risk of a first CID event by 47-52% versus BUD/FOR in the 24- and 52-week populations using both CID definitions (p<0.001). The median time to first CID event was ≥169 days and ≤31 days with FF/UMEC/VI and BUD/FOR, respectively. Only stable patients with no CID at 24 weeks demonstrated sustained clinically important improvements in lung function and health status at 52 weeks versus those who had experienced CID. Once daily, single-inhaler FF/UMEC/VI significantly reduced the risk of CID versus twice daily BUD/FOR with a five-fold longer period without deterioration.

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium/Vilanterol via a Single Inhaler in Patients with COPD.

A population pharmacokinetic analysis was conducted from a subset of samples obtained from the Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy trial to characterize the pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol in patients with symptomatic COPD following treatment with fluticason furoate-umeclidinium-vilanterol combined in a single inhaler. This was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticason furoate-umeclidinium-vilanterol, 100 µg/62.5 µg/25 µg; Ellipta inhaler) with twice-daily dual therapy (budesonide/formoterol 400 µg/12 µg; Turbuhaler). The analyses were conducted in a subset of 74 patients who received fluticason furoate-umeclidinium-vilanterol and provided serial or sparse samples. Monte Carlo simulations and a model-based estimation approach both indicated that systemic drug concentrations of fluticasone furoate, umeclidinium, and vilanterol after administration of fluticason furoate-umeclidinium-vilanterol triple combination therapy from a single inhaler were within the ranges observed following administration of these drugs as monotherapy (fluticasone furoate, umeclidinium, and vilanterol) or as dual-combination therapy (fluticasone furoate/vilanterol or umeclidinium/vilanterol).

Low FT3 is a valuable predictor of severe acute pancreatitis in the emergency department.

OBJECTIVE: To investigate the relationship between serum levels of thyroid hormones and disease severity at the early stage of acute pancreatitis (AP). METHODS: Cohort data from 172 patients with AP attending the Emergency Department of our hospital from 2012 to 2017 were retrospectively reviewed and analyzed. Patients were categorized into mild (MAP), moderately severe (MSAP) and severe AP (SAP) groups based on the disease severity. The MSAP and SAP groups were combined into a non-MAP group for analysis. The predictive values of C-reactive protein (CRP) levels, Ranson score, APACHE II score and serum thyroid hormone levels were analyzed. RESULTS: In total, 76 (44.2%), 85 (49.4%) and 11 (6.4%) patients were included in the MAP, MSAP and SAP groups, respectively. The free triiodothyronine (FT3) levels were significantly lower in the combined non-MAP group than in the MAP group. The tetraiodothyronine (T4) levels were significantly lower in the SAP group than in the MAP and MSAP groups (P = 0.002). Logistic regression analysis revealed that a low FT3 level was an independent risk factor for the incidence of non-MAP (P = 0.004). The area under the receiver operating characteristic curve and sensitivity of FT3 were 0.729 and 88.2%, respectively, which were higher than those of CRP, Ranson and APACHE II scores. CONCLUSION: Monitoring FT3 levels in the early stage of AP is helpful for evaluating disease severity and predicting the incidence of non-MAP, making it a useful tool for guiding AP treatment.