Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS).

Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities with refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With the outbreak of coronavirus disease 19 worldwide, the mortality of ARDS has increased correspondingly. Comprehending the pathophysiology and the underlying molecular mechanisms of ARDS may thus be essential to developing effective therapeutic strategies and reducing mortality. To facilitate further understanding of its pathogenesis and exploring novel therapeutics, this review provides comprehensive information of ARDS from pathophysiology to molecular mechanisms and presents targeted therapeutics. We first describe the pathogenesis and pathophysiology of ARDS that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance and oxidative stress. Next, we summarize the molecular mechanisms and signaling pathways related to the above four aspects of ARDS pathophysiology, along with the latest research progress. Finally, we discuss the emerging therapeutic strategies that show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies and mesenchymal stromal cell therapies, highlighting the pathophysiological basis and the influences on signal transduction pathways for their use.

Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics-a narrative review.

Sepsis is characterized by organ dysfunction resulting from a dysregulated inflammatory response triggered by infection, involving multifactorial and intricate molecular mechanisms. Hypoxia-inducible factor-1α (HIF-1α), a notable transcription factor, assumes a pivotal role in the onset and progression of sepsis. This review aims to furnish a comprehensive overview of HIF-1α's mechanism of action in sepsis, scrutinizing its involvement in inflammatory regulation, hypoxia adaptation, immune response, and organ dysfunction. The review encompasses an analysis of the structural features, regulatory activation, and downstream signaling pathways of HIF-1α, alongside its mechanism of action in the pathophysiological processes of sepsis. Furthermore, it will delve into the roles of HIF-1α in modulating the inflammatory response, including its association with inflammatory mediators, immune cell activation, and vasodilation. Additionally, attention will be directed toward the regulatory function of HIF-1α in hypoxic environments and its linkage with intracellular signaling, oxidative stress, and mitochondrial damage. Finally, the potential therapeutic value of HIF-1α as a targeted therapy and its significance in the clinical management of sepsis will be discussed, aiming to serve as a significant reference for an in-depth understanding of sepsis pathogenesis and potential therapeutic targets, as well as to establish a theoretical foundation for clinical applications.

Dyslipidemia versus obesity as predictors of ischemic stroke prognosis: a multi-center study in China.

BACKGROUND: This multicenter observational study aimed to determine whether dyslipidemia or obesity contributes more significantly to unfavorable clinical outcomes in patients experiencing a first-ever ischemic stroke (IS). METHODS: The study employed a machine learning predictive model to investigate associations among body mass index (BMI), body fat percentage (BFP), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) with adverse outcomes in IS patients. Extensive real-world clinical data was utilized, and risk factors significantly linked to adverse outcomes were identified through multivariate analysis, propensity score matching (PSM), and regression discontinuity design (RDD) techniques. Furthermore, these findings were validated via a nationwide multicenter prospective cohort study. RESULTS: In the derived cohort, a total of 45,162 patients diagnosed with IS were assessed, with 522 experiencing adverse outcomes. A multifactorial analysis incorporating PSM and RDD methods identified TG (adjusted odds ratio (OR) = 1.110; 95% confidence interval (CI): 1.041-1.183; P <  0.01) and TC (adjusted OR = 1.139; 95%CI: 1.039-1.248; P <  0.01) as risk factors. However, BMI, BFP, and HDL showed no significant effect. In the validation cohort, 1410 controls and 941 patients were enrolled, confirming that lipid levels are more strongly correlated with the prognosis of IS patients compared to obesity (TC, OR = 1.369; 95%CI: 1.069-1.754; P <  0.05; TG, OR = 1.332; 95%CI: 1.097-1.618; P <  0.01). CONCLUSION: This study suggests that dyslipidemia has a more substantial impact on the prognosis of IS patients compared to obesity. This highlights the importance of prioritizing dyslipidemia management in the treatment and prevention of adverse outcomes in IS patients.

Elevated MMP-8 levels, inversely associated with BMI, predict mortality in mechanically ventilated patients: an observational multicenter study.

BACKGROUND: The present study aimed to investigate the correlation between weight status and mortality in mechanically ventilated patients and explore the potential mediators. METHODS: Three medical centers encompassing 3301 critically ill patients receiving mechanical ventilation were assembled for retrospective analysis to compare mortality across various weight categories of patients using machine learning algorithms. Bioinformatics analysis identified genes exhibiting differential expression among distinct weight categories. A prospective study was then conducted on a distinct cohort of 50 healthy individuals and 193 other mechanically ventilated patients. The expression levels of the genes identified through bioinformatics analysis were quantified through enzyme-linked immunosorbent assay (ELISA). RESULTS: The retrospective analysis revealed that overweight individuals had a lower mortality rate than underweight individuals, and body mass index (BMI) was an independent protective factor. Bioinformatics analysis identified matrix metalloproteinase 8 (MMP-8) as a differentially expressed gene between overweight and underweight populations. The results of further prospective studies showed that overweight patients had significantly lower MMP-8 levels than underweight patients ((3.717 (2.628, 4.191) vs. 2.763 (1.923, 3.753), ng/ml, P = 0.002). High MMP-8 levels were associated with increased mortality risk (OR = 4.249, P = 0.005), indicating that elevated level of MMP-8 predicts the mortality risk of underweight patients receiving mechanical ventilation. CONCLUSIONS: This study provides evidence for a protective effect of obesity in mechanically ventilated patients and highlights the potential role of MMP-8 level as a biomarker for predicting mortality risk in this population.

Protein expression profiling identifies a prognostic model for ovarian cancer.

BACKGROUND: Owing to the high morbidity and mortality, ovarian cancer has seriously endangered female health. Development of reliable models can facilitate prognosis monitoring and help relieve the distress. METHODS: Using the data archived in the TCPA and TCGA databases, proteins having significant survival effects on ovarian cancer patients were screened by univariate Cox regression analysis. Patients with complete information concerning protein expression, survival, and clinical variables were included. A risk model was then constructed by performing multiple Cox regression analysis. After validation, the predictive power of the risk model was assessed. The prognostic effect and the biological function of the model were evaluated using co-expression analysis and enrichment analysis. RESULTS: 394 patients were included in model construction and validation. Using univariate Cox regression analysis, we identified a total of 20 proteins associated with overall survival of ovarian cancer patients (p < 0.01). Based on multiple Cox regression analysis, six proteins (GSK3α/ß, HSP70, MEK1, MTOR, BAD, and NDRG1) were used for model construction. Patients in the high-risk group had unfavorable overall survival (p < 0.001) and poor disease-specific survival (p = 0.001). All these six proteins also had survival prognostic effects. Multiple Cox regression analysis demonstrated the risk model as an independent prognostic factor (p < 0.001). In receiver operating characteristic curve analysis, the risk model displayed higher predictive power than age, tumor grade, and tumor stage, with an area under the curve value of 0.789. Analysis of co-expressed proteins and differentially expressed genes based on the risk model further revealed its prognostic implication. CONCLUSIONS: The risk model composed of GSK3α/ß, HSP70, MEK1, MTOR, BAD, and NDRG1 could predict survival prognosis of ovarian cancer patients efficiently and help disease management.

Serum creatine kinase levels are not associated with an increased need for continuous renal replacement therapy in patients with acute kidney injury following rhabdomyolysis.

Severe rhabdomyolysis can lead to acute kidney injury (AKI). Previous studies have reported a benefit from continuous renal replacement therapy (CRRT) for rhabdomyolysis-associated AKI. Here, we investigated the potential for serum creatine kinase (CK) levels to be used as a marker for CRRT termination in patients with AKI following rhabdomyolysis. We compared different CK levels in patients after CRRT termination and observed their clinical outcomes. We retrospectively collected 86 cases with confirmed rhabdomyolysis-associated AKI, who were receiving CRRT in Tongji Hospital. Patients' renal functions were assessed within 24 h of intermission, patients with urine output ≥ 1,000 mL and serum creatinine ≤ 265 umol/L were considered for CRRT termination. After termination, 33 patients with a CK > 5,000 U/L were included in an experimental group, and 53 patients with a CK < 5,000 U/L were included in a control group. Clinical outcomes were compared between the two groups. Higher CK levels, as well as worse renal functions, predicted the necessity of CRRT. After CRRT termination, the in-hospital mortality (p = 0.389) and Multiple Organ Dysfunction Syndrome (MODS) incidence (p = 0.064) were similar between the two groups, while the experimental group showed a significantly shorter in-hospital length of stay (p = 0.026) and Intensive Care Unit (ICU) length of stay (p = 0.038). CRRT termination may be independent of CK levels for patients with rhabdomyolysis-associated AKI, and this is contingent on their renal functions having recovered to an appropriate level.

Characteristics of Liver Function in Patients With SARS-CoV-2 and Chronic HBV Coinfection.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is a major global health threat. We aimed to describe the characteristics of liver function in patients with SARS-CoV-2 and chronic hepatitis B virus (HBV) coinfection. METHODS: We enrolled all adult patients with SARS-CoV-2 and chronic HBV coinfection admitted to Tongji Hospital from February 1 to February 29, 2020. Data of demographic, clinical characteristics, laboratory tests, treatments, and clinical outcomes were collected. The characteristics of liver function and its association with the severity and prognosis of disease were described. RESULTS: Of the 105 patients with SARS-CoV-2 and chronic HBV coinfection, elevated levels of liver test were observed in several patients at admission, including elevated levels of alanine aminotransferase (22, 20.95%), aspartate aminotransferase (29, 27.62%), total bilirubin (7, 6.67%), gamma-glutamyl transferase (7, 6.67%), and alkaline phosphatase (1, 0.95%). The levels of the indicators mentioned above increased substantially during hospitalization (all P < .05). Fourteen (13.33%) patients developed liver injury. Most of them (10, 71.43%) recovered after 8 (range 6-21) days. Notably the other, 4 (28.57%) patients rapidly progressed to acute-on-chronic liver failure. The proportion of severe COVID-19 was higher in patients with liver injury (P = .042). Complications including acute-on-chronic liver failure, acute cardiac injury and shock happened more frequently in patients with liver injury (all P < .05). The mortality was higher in individuals with liver injury (28.57% vs 3.30%, P = .004). CONCLUSION: Liver injury in patients with SARS-CoV-2 and chronic HBV coinfection was associated with severity and poor prognosis of disease. During the treatment of COVID-19 in chronic HBV-infected patients, liver function should be taken seriously and evaluated frequently.

Clinical value of blood markers to assess the severity of coronavirus disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is threatening the world with the symptoms of seasonal influenza. This study was conducted to investigate the patient characteristics and clinical value of blood markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 187 patients, diagnosed with COVID-19 (non-severe and severe cases) and admitted to hospital between January 27th and March 8th of 2020, were enrolled in the present study. RESULTS: A higher proportion of clinical symptoms, including cough, expectoration, myalgia, and fatigue were observed in the non-severe group. The level of white blood cell count, neutrophils, CRP, IL-6 and IL-8 were significantly increased, while the platelet count was remarkedly decreased in the severe group. The risk model based on lymphocyte, IL-6, IL-8, CRP and platelet counts had the highest area under the receiver operator characteristic curve (AUROC). The baseline of IL-6, IL-8 and CRP was positively correlated with other parameters except in the cases of lymphocyte, hemoglobin and platelet counts. The baseline of the platelet count was negatively correlated with other parameters except in the lymphocyte and hemoglobin counts. Additionally, there was no connection between the severity of COVID-19 and cultures of blood, sputum or catheter secretion. CONCLUSIONS: The present study suggested that high leucocyte and low platelets counts were independent predictive markers of the severity of COVID-19.

Bacterial characteristics of carbapenem-resistant Enterobacteriaceae (CRE) colonized strains and their correlation with subsequent infection.

BACKGROUND: Searching the risk factors for carbapenem-resistant Enterobacteriaceae (CRE) infection is important in clinical practice. In the present study, we aim to investigate bacterial characteristics of colonizing strains and their correlation with subsequent CRE infection. METHODS: Between May 2018 and January 2019, patients hospitalized in the department of haematology and intensive care unit (ICU) were screened for CRE by rectal swabs and monitored for the outcome of infection. We identified the species and carbapenemase-encoding genes of colonizing strains and performed antimicrobial susceptibility tests and multilocus sequence typing (MLST). Risk factors for subsequent CRE infections were ascertained by univariate and multivariable analysis. RESULTS: We collected a total of 219 colonizing strains from 153 patients. Klebsiella pneumoniae was the most abundant species, and MLST analysis showed rich diversity. K. pneumoniae carbapenemase (KPC) was predominant in the infection group (72.4%). In the non-infection group, 35.4% of strains were non-carbapenemase-producing CRE (NCP-CRE), and New Delhi metallo-ß-lactamase (NDM) was predominant (42.2%). The rate of high-level carbapenem resistance (minimum inhibitory concentration [MIC] ≥ 64 mg/L for meropenem and ertapenem, ≥ 32 mg/L for imipenem) was remarkably higher in the infection group than in the non-infection group (P <  0.001). Univariate analysis showed that K. pneumoniae, high-level carbapenem resistance, CP-CRE and KPC-CRE were infection risk factors after CRE colonization. On multivariable analysis with different carbapenemase dichotomizations, KPC-CRE (adjusted odds ratio [aOR], 4.507; 95% confidence interval [CI], 1.339-15.171; P = 0.015) or imipenem MIC ≥ 32 mg/L (aOR, 9.515; 95% CI, 1.617-55.977; P = 0.013) were respectively identified as independent risk factors for subsequent infection. CONCLUSIONS: Patients colonized with KPC-CRE or strains with an imipenem MIC ≥ 32 mg/L were at particularly high risk of subsequent CRE infections during their hospital stay.

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen.

BACKGROUND: Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class. METHODS: Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset. RESULTS: A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion. CONCLUSIONS: Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.

Utilizing reclassification to explore characteristics and prognosis of KDIGOSCr AKI subgroups: a retrospective analysis of a multicenter prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is widespread in the intensive care unit (ICU) and affects patient prognosis. According to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, the absolute and relative increases of serum creatinine (Scr) are classified into the same stage. Whether the prognosis of the two types of patients is similar in the ICU remains unclear. METHODS: According to the absolute and relative increase of Scr, AKI stage 1 and stage 3 patients were divided into stage 1a and 1b, stage 3a and 3b groups, respectively. Their demographics, laboratory results, clinical characteristics, and outcomes were analyzed retrospectively. RESULTS: Of the 345 eligible cases, we analyzed stage 1 because stage 3a group had only one patient. Using 53 or 61.88 µmol/L as the reference Scr (Scrref), no significant differences were observed in ICU mortality (P53=0.076, P61.88=0.070) or renal replacement therapy (RRT) ratio, (P53=0.356, P61.88=0.471) between stage 1a and 1b, but stage 1b had longer ICU length of stay (LOS) than stage 1a (P53<0.001, P61.88=0.032). In the Kaplan-Meier survival analysis, no differences were observed in ICU mortality between stage 1a and 1b (P53=0.378, P61.88=0.255). In a multivariate analysis, respiratory failure [HR = 4.462 (95% CI 1.144-17.401), p = 0.031] and vasoactive drug therapy [HR = 4.023 (95% CI 1.584-10.216), p = 0.003] were found to be independently associated with increased risk of death. CONCLUSION: ICU LOS benefit was more prominent in KDIGOSCr AKI stage 1a patients than in stage 1 b. Further prospective studies with a larger sample size are necessary to confirm the effectiveness of reclassification.

Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019.

OBJECTIVES: Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. DESIGN: Retrospective observational cohort. SETTING: Tongji Hospital in Wuhan, China. SUBJECTS: Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 ± 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 ± 4.40 in survivors (p < 0.001). Acute Physiology and Chronic Health Evaluation II score was independently associated with hospital mortality (adjusted hazard ratio, 1.07; 95% CI, 1.01-1.13). In predicting hospital mortality, Acute Physiology and Chronic Health Evaluation II score demonstrated better discriminative ability (area under the curve, 0.966; 95% CI, 0.942-0.990) than Sequential Organ Failure Assessment score (area under the curve, 0.867; 95% CI, 0.808-0.926) and CURB65 score (area under the curve, 0.844; 95% CI, 0.784-0.905). Based on the cut-off value of 17, Acute Physiology and Chronic Health Evaluation II score could predict the death of patients with coronavirus disease 2019 with a sensitivity of 96.15% and a specificity of 86.27%. Kaplan-Meier analysis showed that the survivor probability of patients with coronavirus disease 2019 with Acute Physiology and Chronic Health Evaluation II score less than 17 was notably higher than that of patients with Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 (p < 0.001). CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.

Position Estimation and Compensation Based on a Two-Step Extended Sliding-Mode Observer for a MSFESS.

This paper aims to deal with the problem of rotor position estimation and compensation for a magnetically suspended flywheel energy storage system under the consideration of measurement noise and unknown disturbances. First, the flywheel system working principle and description are analyzed and, based on this, the mathematical model as well as the coordinates transformation are introduced. For the purpose of the state estimation, a two-step extended sliding-mode observer is considered to obtain the estimates of the rotor angular position. In this control strategy, a traditional sliding-mode observer is adopted as a first-step original state estimator. After that, the relationship between the angular position and the estimation error is established and a second-step observer is designed to obtain the estimation of the error. The estimated error is then used to compensate the real values of the rotor angular position generated by the first-step observer. To reject the influences of the measurement noise and unknown disturbances, the H∞ optimization strategy is considered to determine the second-step observer structure. Finally, experimental results are presented to demonstrate the effectiveness of the proposed method. It is demonstrated that the proposed two-step observer method has a better estimation accuracy and control performance.

Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study.

BACKGROUND: Poor inter-rater reliability in chest radiograph interpretation has been reported in the context of acute respiratory distress syndrome (ARDS), although not for the Berlin definition of ARDS. We sought to examine the effect of training material on the accuracy and consistency of intensivists' chest radiograph interpretations for ARDS diagnosis. METHODS: We conducted a rater agreement study in which 286 intensivists (residents 41.3%, junior attending physicians 35.3%, and senior attending physician 23.4%) independently reviewed the same 12 chest radiographs developed by the ARDS Definition Task Force ("the panel") before and after training. Radiographic diagnoses by the panel were classified into the consistent (n = 4), equivocal (n = 4), and inconsistent (n = 4) categories and were used as a reference. The 1.5-hour training course attended by all 286 intensivists included introduction of the diagnostic rationale, and a subsequent in-depth discussion to reach consensus for all 12 radiographs. RESULTS: Overall diagnostic accuracy, which was defined as the percentage of chest radiographs that were interpreted correctly, improved but remained poor after training (42.0 ± 14.8% before training vs. 55.3 ± 23.4% after training, p < 0.001). Diagnostic sensitivity and specificity improved after training for all diagnostic categories (p < 0.001), with the exception of specificity for the equivocal category (p = 0.883). Diagnostic accuracy was higher for the consistent category than for the inconsistent and equivocal categories (p < 0.001). Comparisons of pre-training and post-training results revealed that inter-rater agreement was poor and did not improve after training, as assessed by overall agreement (0.450 ± 0.406 vs. 0.461 ± 0.575, p = 0.792), Fleiss's kappa (0.133 ± 0.575 vs. 0.178 ± 0.710, p = 0.405), and intraclass correlation coefficient (ICC; 0.219 vs. 0.276, p = 0.470). CONCLUSIONS: The radiographic diagnostic accuracy and inter-rater agreement were poor when the Berlin radiographic definition was used, and were not significantly improved by the training set of chest radiographs developed by the ARDS Definition Task Force. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (registration number NCT01704066 ) on 6 October 2012.

Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS. RESULTS: A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes. CONCLUSIONS: Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS.

Preparation of fluorescent polyurethane microspheres and their applications as reusable sensor for 4-nitrophenol detection and as microplastics model for visualizing polyurethane in cells and zebrafish.

Fluorescent microspheres are of significant interests due to their wide applications in biotechnology fields. However, their preparation presents several challenges, such as the need for dye labeling, the complexity of materials and often sophisticated preparation conditions. Here a simple process for hydrophilic and crosslinked polyurethane (CPU) microspheres, with carboxyl groups on the surface via one-step precipitation polymerization in 40 min, is presented. The microsphere size is easily adjusted by varying experimental conditions. CPU microspheres exhibit high thermal and pH stability with good redispersibility in water, and emit fluorescence without any modification or dye labeling. The emission mechanism is discussed. CPU microspheres are used as fluorescent probe to detect 4-nitrophenol (4-NP) based on their emission in UV light region, with excellent selectivity and sensitivity. In addition, they are reusable with detection limit unchanged after 7 cycles of reuses, a significant feature of this work. The mechanism of fluorescence detection is thoroughly explored and ascribed to the internal filtration effect. Based on the emission in visible light region, CPU microspheres are used as a model of PU microplastics (MPs) to visualize their biodistribution in HeLa and macrophage cells, as well as in zebrafish larvae, providing a reliable tracer for the visualization and tracking of PU MPs in organisms.

Characteristics of critically ill patients in ICUs in mainland China.

OBJECTIVES: We sought to describe the demographics, case mix, interventions, and clinical outcome of critically ill patients admitted to ICUs in Mainland China. DESIGN: A 2-month (July 1, 2009, to August 31, 2009) prospective, observational cohort study. SETTING: Twenty-two ICUs in Mainland China. PATIENTS: Adult patients admitted to participating ICUs during the study period with an ICU length of stay >24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, including demographics, underlying diseases, severity of illness, admission status, complications, intervention and treatment during ICU stay, and clinical outcome were recorded in case report form. The primary outcome measure was all-cause hospital mortality. Independent predictors for hospital mortality were determined with multivariate logistic regression analysis. One thousand two hundred ninety-seven patients met the inclusion criteria for the study, 821 (63.3%) were male, and mean age was 58.5 ± 19.2 yrs. Mean Acute Physiology and Chronic Health Evaluation II score was 18.0 ± 8.1, and mean Sequential Organ Failure Assessment score was 6.5 ± 3.8. One third of the patients were postoperative ICU admissions. Seven hundred sixty-five patients (59.0%) developed infections, followed by severe sepsis or septic shock (484, 37.3%), acute kidney injury (398, 30.7%), and acute lung injury/acute respiratory distress syndrome (351, 27.1%). Mechanical ventilation was used in almost three fourths of the patients, whereas any type of renal replacement therapy was used in 173 patients (13.3%). Hospital mortality was 20.3%. Multivariate logistic regression analysis found that Acute Physiology and Chronic Health Evaluation II score, solid tumor, severe sepsis/septic shock, acute lung injury/acute respiratory distress syndrome, and acute kidney injury were independent risk factors for hospital mortality. CONCLUSIONS: Critically ill patients in ICUs in Mainland China exhibited a case mix similar to those of Western countries, although there are significant differences in intensive care unit admission rates and disease severity between Western and Chinese ICUs.

Efficient quantum dot light-emitting diodes with solution-processable molybdenum oxide as the anode buffer layer.

Quantum dot light-emitting diodes (QD-LEDs) are characterized by pure and saturated emission colors with narrow bandwidth. Optimization of the device interface is an effective way to achieve stable and high-performance QD-LEDs. Here we utilized solution-processed molybdenum oxide (MoOx) as the anode buffer layer on ITO to build efficient QD-LEDs. Using MoOx as the anode buffer layer provides the QD-LED with good Ohmic contact and a small charge transfer resistance. The device luminance is nearly independent of the thickness of the MoOx anode buffer layer. The QD-LEDs with a MoOx anode buffer layer exhibit a maximum luminance and luminous efficiency of 5230 cd m(-2) and 0.67 cd A(-1) for the yellow emission at 580 nm, and 7842 cd m(-2) and 1.49 cd A(-1) for the red emission at 610 nm, respectively.

Protective effect of ginsenoside Rb1 against lung injury induced by intestinal ischemia-reperfusion in rats.

Intestinal ischemia-reperfusion (I/R) is a critical event in the pathogenesis of multiple organ dysfunction syndromes (MODS). The lungs are some of the most vulnerable organs that are impacted by intestinal I/R. The aim of this study is to investigate whether ginsenoside Rb1 can ameliorate remote lung injury induced by intestinal I/R. Adult male Wistar rats were randomly divided into four groups: (1) a control, sham-operated group (sham group); (2) an intestinal I/R group subjected to 1 h intestinal ischemia and 2 h reperfusion (I/R group); (3) a group treated with 20 mg/kg ginsenoside Rb1 before reperfusion (Rb1-20 group); and (4) a group treated with 40 mg/kg ginsenoside Rb1 before reperfusion (Rb1-40 group). Intestinal and lung histology was observed. The malondialdehyde (MDA) levels in intestinal tissues were measured. Myeloperoxidase (MPO), TNF-α, MDA levels, wet/dry weight ratio and immunohistochemical expression of intracellular adhesion molecule-1 (ICAM-1) in lung tissues were assayed. In addition, a western blot of lung NF-kB was performed. Results indicated that intestinal I/R induced intestinal and lung injury, which was characterized by increase of MDA levels and pathological scores in intestinal tissues and MPO, TNF-α , MDA levels, wet/dry weight ratio and ICAM-1, NF-kB expression in the lung tissues. Ginsenoside Rb1 (20, 40 mg/kg) ameliorated intestinal and lung injury, decreased MPO, TNF-α, MDA levels, wet/dry weight ratio, ICAM-1 and NF-kB expression in lung tissues. In conclusion, ginsenoside Rb1 ameliorated the lung injuries by decreasing the NF-kB activation-induced inflammatory response.