Exosomes Derived from Astragaloside IV-pretreated Endothelial Progenitor Cells (AS-IV-Exos) Alleviated Endothelial Oxidative Stress and Dysfunction Via the miR-210/ Nox2/ROS Pathway.

BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.

[Shenqi Dihuang Decoction inhibits high-glucose induced ferroptosis of renal tubular epithelial cells via Nrf2/HO-1/GPX4 pathway].

This study aims to explore the effects of Shenqi Dihuang Decoction on high-glucose induced ferroptosis and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) axis in human renal tubular epithelial cells(HK-2) and to clarify the underlying mechanism. The cell injury model was established by exposing HK-2 to high glucose, and the Shenqi Dihuang Decoction-medicated serum was prepared. The optimal concentration and intervention time of Shenqi Dihuang Decoction were determined. HK-2 were divided into normal, high glucose, and low-, medium-, and high-dose Shenqi Dihuang Decoction groups. After interventions, the cell proliferation rate in each group was determined and the cell morphology and mitochondrial ultrastructure were observed. Then, the levels of intracellular reactive oxygen species(ROS), ferrous ion(Fe~(2+)), glutathione(GSH), and malondialdehyde(MDA) and the protein levels of Nrf2, HO-1, GPX4, and xCT were measured. The optimal concentration and intervention time of Shenqi Dihuang Decoction-medicated serum were determined to be 10% and 24 h, respectively. Compared with the high glucose group, high-dose Shenqi Dihuang Decoction promoted the proliferation of HK-2. The cells in the low-, medium-, and high-dose Shenqi Dihuang Decoction groups presented tight arrangement, an increased cell count, improved morphology from a spindle-fiber shape to a cobblestone shape, and improved morphology and structure of mitochondrial membrane and cristae, compared with those in the high glucose group. Meanwhile, all the doses of Shenqi Dihuang Decoction inhibited ROS elevation to mitigate the peroxidation damage, lowered the Fe~(2+) and MDA levels and elevated the GSH level to inhibit lipid peroxidation, and activated the antioxidant pathway to upregulate the protein levels of Nrf2, HO-1, xCT, and GPX4. In conclusion, Shenqi Dihuang Decoction-medicated serum can inhibit high-glucose induced ferroptosis of HK-2 in vitro, which involves the antioxidant effect and the activation of the Nrf2/HO-1/GPX4 pathway.

IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ.

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.

Down-expression of Foxj1 on airway epithelium with impaired cilia architecture in non-cystic fibrosis bronchiectasis implies disease severity.

INTRODUCTION: The pathogenesis of non-cystic fibrosis bronchiectasis has not been clearly clarified. This study aimed to investigate the expression of ciliary regulating protein forkhead box protein j1 (Foxj1) on airway epithelium in non-cystic fibrosis bronchiectasis and its association with airway cilia structure disorder and disease severity. METHODS: Lung tissue sections excised from 47 patients with non-cystic fibrosis bronchiectasis were included between January 2018 and June 2021. Specimens from 26 subjects who underwent a lobectomy due to lung nodule were chosen as controls. Clinical information was collected, and pathologic analysis was performed to assess the epithelial structure and expression of ciliary regulating Foxj1. RESULTS: Of the 47 patients with non-cystic fibrosis bronchiectasis, 25 were considered as mild, 12 were moderate whereas the remaining 10 cases were severe according to the bronchiectasis severity index score evaluation. Epithelial hyperplasia, hyperplasia of goblet cells and inflammatory cell infiltration were observed in non-cystic fibrosis bronchiectasis, compared with control subjects. Cilia length in non-cystic fibrosis bronchiectasis patients were shorter than that in the control group, (5.34 ± 0.89) µm versus (7.34 ± 0.71) µm, respectively (P = 0.002). The expression of Foxj1 was (2.69 ± 1.09) × 106 in non-cystic fibrosis bronchiectasis, compared with (6.67 ± 1.15) × 106 in the control group (P = 0.001). Moreover, patients with lower expression of Foxj1 showed shorter airway cilia and worse in disease severity. CONCLUSION: Foxj1 declined in the airway epithelium of patients with non-cystic fibrosis bronchiectasis, positively correlated to cilia length and might imply worse disease severity.

IL-37 protects against airway remodeling by reversing bronchial epithelial-mesenchymal transition via IL-24 signaling pathway in chronic asthma.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma. METHODS: BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37. RESULTS: We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression. CONCLUSIONS: Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.

IL-24 Contributes to Neutrophilic Asthma in an IL-17A-Dependent Manner and Is Suppressed by IL-37.

PURPOSE: Neutrophilic asthma is associated with asthma exacerbation, steroid insensitivity, and severe asthma. Interleukin (IL)-24 is overexpressed in asthma and is involved in the pathogenesis of several allergic inflammatory diseases. However, the role and specific mechanism of IL-24 in neutrophilic asthma are unclear. We aimed to elucidate the roles of IL-24 and IL-37 in neutrophilic asthma, the relationships with IL-17A and the mechanisms regulating neutrophilic asthma progression. METHODS: Purified human neutrophils were isolated from healthy volunteers, and a cell coculture system was used to evaluate the function of IL-24 in epithelium-derived IL-17A-dependent neutrophil migration. IL-37 or a small interfering RNA (siRNA) targeting IL-24 was delivered intranasally to verify the effect in a murine model of house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic asthma. RESULTS: IL-24 enhanced IL-17A production in bronchial epithelial cells via the STAT3 and ERK1/2 signaling pathways; this effect was reversed by exogenous IL-37. Anti-IL-17A monoclonal antibodies reduced neutrophil chemotaxis induced by IL-24-treated epithelial cells in vitro. Increased IL-24 and IL-17A expression in the airway epithelium was observed in HDM/LPS-induced neutrophilic asthma. IL-37 administration or IL-24 silencing attenuated neutrophilic asthma, reducing IL-17A levels and decreasing neutrophil airway infiltration, airway hyperresponsiveness, and goblet cell metaplasia. Silencing IL-24 inhibited T-helper 17 (Th17) immune responses, but not Th1 or Th2 immune responses, in the lungs of a neutrophilic asthma model. CONCLUSIONS: IL-24 aggravated neutrophilic airway inflammation by increasing epithelium-derived IL-17A production, which could be suppressed by IL-37. Targeting the IL-24/IL-17A signaling axis is a potential strategy, and IL-37 is a potential candidate agent for alleviating neutrophilic airway inflammation in asthma.

Main pulmonary artery enlargement predicts 90-day readmissions in Chinese COPD patients.

BACKGROUND: Numerous studies have shown pulmonary artery enlargement when measured by chest computed tomography (CT) could predict a worse outcome in chronic obstructive pulmonary disease (COPD) patients. Herein, we studied the prognostic implication of main pulmonary artery diameter (MPAD) in Chinese COPD patients. METHODS: This is an observational case-control study. Patients with 90-day readmissions are case group and those without 90-day readmission are control group. The study comprised of 417 COPD patients who underwent chest CT in their initial admission due to acute exacerbation of COPD (AECOPD). We analyzed their clinical characteristics such as MPAD, arterial blood gas (ABG) results, other chest CT findings and comorbidities to identify the cause of readmission within 90 days. RESULTS: Median age of our study population is 75 years old, and 79.6% of them are male. The median MPAD is 2.8 cm and 80.6% were also diagnosed with community acquired pneumonia (CAP) in their first admission. The median MPAD in patients with 90-day readmission was 3.1 cm while patients without 90-day readmission had median MPAD of 2.8 cm. Through multivariate logistic regression analysis CAP (P=0.019, OR: 3.105, 95% CI: 1.203-8.019) and MPAD (P<0.001, OR: 2.898, 95% CI: 1.824-4.605) were statistically significant. In the second stage of analysis, subgroup of patients diagnosed with CAP and AECOPD (pAECOPD) were analyzed, MPAD remained statistically significant (P<0.001, OR: 3.490, 95% CI: 1.929-6.316) and receiver operative characteristic (ROC) curve for pAECOPD patients; area under the curve (AUC) was 0.704 (95% CI: 0.631-0.778) with a MPAD cut off value of 2.9 cm (sensitivity 72%, specificity 53%). CONCLUSIONS: Enlarged MPAD and pAECOPD in initial admission are independent risk factors for 90-day readmission. In our pAECOPD patient population, MPAD >2.9 cm are at increased risk of 90-day readmission.

Deep Learning-Based Available and Common Clinical-Related Feature Variables Robustly Predict Survival in Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Although there are many predictors of death for CAP, there are still some limitations. This study aimed to build a simple and accurate model based on available and common clinical-related feature variables for predicting CAP mortality by adopting machine learning techniques. METHODS: This was a single-center retrospective study. The data used in this study were collected from all patients (≥18 years) with CAP admitted to research hospitals between January 2012 and April 2020. Each patient had 62 clinical-related features, including clinical diagnostic and treatment features. Patients were divided into two endpoints, and by using Tensorflow2.4.1 as the modeling framework, a three-layer fully connected neural network (FCNN) was built as a base model for classification. For a comprehensive comparison, seven classical machine learning methods and their integrated stacking patterns were introduced to model and compare the same training and test data. RESULTS: A total of 3997 patients with CAP were included; 205 (5.12%) died in the hospital. After performing deep learning methods, this study established an ensemble FCNN model based on 12 FCNNs. By comparing with seven classical machine learning methods, the area under the curve of the ensemble FCNN was 0.975 when using deep learning algorithms to classify poor from good prognosis based on available and common clinical-related feature variables. The predicted outcome was poor prognosis if the ControlNet's poor prognosis score was greater than the cutoff value of 0.50. To confirm the scientificity of the ensemble FCNN model, this study analyzed the weight of random forest features and found that mainstream prognostic features still held weight, although the model is perfect after integrating other factors considered less important by previous studies. CONCLUSION: This study used deep learning algorithms to classify prognosis based on available and common clinical-related feature variables in patients with CAP with high accuracy and good generalizability. Every clinical-related feature is important to the model.

Blood urea nitrogen to serum albumin ratio independently predicts 30-day mortality and severity in patients with Escherichia coli bacteraemia

Background: Elevated blood urea nitrogen to serum albumin (BUN/ALB) ratio had been identified as an independent risk factor related to mortality in community-acquired and hospital-acquired pneumonia. This study aimed to investigate whether this clinical index can predict the clinical outcomes of E. coli bacteraemia.Material and methodsClinical data were collected from patients with E. coli bacteraemia attended at our hospital between January 2012 and December 2018. The endpoints were mortality within 30 days after the diagnosis of E. coli bacteraemia and intensive care (IC) requirement. Cox regression analysis was performed to evaluate the risk factors.ResultsA total of 398 patients with E. coli bacteraemia were enrolled in this study and 56 patients died within 30 days after bacteraemia onset. Multivariate Cox regression analysis showed that age greater than 65 years, lymphocyte count<.8×10e9/L, elevated BUN/ALB ratio, increased SOFA score, carbapenem resistance, central venous catheterization before onset of bacteraemia, and infection originating from abdominal cavity were independent risk factors for 30-day mortality (P<.05). The risk factors associated with IC requirement were similar to those for 30-day mortality except central venous catheterization before onset of bacteraemia. The area under the receiver-operating characteristic curve for BUN/ALB ratio predicting 30-day mortality and IC requirement was similar to that for SOFA score, but higher than that for lymphocyte count. The cut-off points of BUN/ALB ratio to predict 30-day mortality and IC requirement were both .3.ConclusionsBUN/ALB ratio is a simple but independent predictor of 30-day mortality and severity in E. coli bacteraemia. A higher BUN/ALB ratio at the onset of bacteraemia predicts a higher mortality rate and IC requirement. (AU)

Antecedentes: Se ha identificado la elevación de la proporción de nitrógeno ureico en sangre con respecto a albúmina sérica (NUS/ALB) como un factor de riesgo independiente asociado a la mortalidad de la neumonía adquirida en la comunidad y la neumonía intrahospitalaria. El objetivo de este estudio fue investigar si este índice clínico puede predecir los resultados clínicos de bacteremia por E. coli.Material y métodosSe recopilaron los datos clínicos de los pacientes con bacteremia por E. coli atendidos en nuestro hospital entre enero de 2012 y diciembre de 2018. Las variables de evaluación fueron la mortalidad a 30 días tras el diagnóstico de bacteremia por E. coli y la necesidad de cuidados intensivos (CI). Se realizó un análisis de regresión de Cox para evaluar los factores de riesgo.ResultadosSe incluyó en el estudio a un total de 398 pacientes con bacteremia por E. coli, falleciendo 56 pacientes en el plazo de 30 días tras el inicio de la bacteremia. El análisis de regresión de Cox multivariante reflejó que la edad superior a 65 años, el recuento linfocitario <0,8×109/l, la elevación del ratio NUS/ALB, el incremento de la puntuación SOFA, la resistencia al carbapenem, la cateterización venosa central anterior al inicio de la bacteremia y la infección originada por la cavidad abdominal eran factores de riesgo independientes de la mortalidad a 30 días (p<0,05). Los factores de riesgo asociados a la necesidad de CI fueron similares a los de la mortalidad a 30 días, exceptuando la cateterización venosa central anterior al inicio de la bacteremia. El área bajo la curva característica operador-receptor para el ratio NUS/ALB que predice la mortalidad a 30 días, y la necesidad de CI fue similar a la puntuación SOFA, aunque superior a la correspondiente al recuento linfocitario. Los puntos de corte del ratio NUS/ALB para predecir la mortalidad a 30 días y la necesidad de CI se situaron en 0,3. (AU)

Associations Between Gut Microbiota and Asthma Endotypes: A Cross-Sectional Study in South China Based on Patients with Newly Diagnosed Asthma.

OBJECTIVE: This study aimed to investigate the gut microbiome profile in different inflammatory phenotypes of treatment-naive newly diagnosed asthmatic adults, to gain insight on the associations between intestinal microbiota and phenotypic features that characterize asthma heterogeneity to develop new treatments for asthma. METHODS: Fresh stool samples were obtained from 20 healthy subjects and 47 newly diagnosed asthmatic patients prior to any interventions. The asthmatics were divided into allergic and non-allergic cohorts. Intestinal microbiota was analyzed by 16S rRNA next-generation sequencing. Demographic and clinical parameters were collected. Alpha and beta diversity analysis were calculated to detect differences within sample phylotype richness and evenness between controls and asthmatic patients. Statistically significant differences between samples were analyzed for all used metrics, and features of gut bacterial community structure were evaluated in relation to extensive clinical characteristics of asthmatic patients. RESULTS: Gut microbial compositions were significantly different between asthmatic and healthy groups. Alpha-diversity of the gut microbiome was significantly lower in asthmatics than in controls. The microbiome between allergic and non-allergic asthmatic patients were also different, and 28 differential species were identified. PPAR signaling pathway, carotenoid biosynthesis, and flavonoid biosynthesis were significantly positively correlated with allergy-associated clinical index, including FENO value, blood eosinophil counts, and serum IgE and IL-4 levels. A combination of Ruminococcus bromii, Brevundimonas vesicularis, and Clostridium disporicum showed an AUC of 0.743 in the specific allergic/non-allergic cohort. When integrating C. disporicum, flavone, flavonol biosynthesis, and serum IL-4 values, the AUC achieved 0.929 to classify asthmatics. At the same time, C. colinum and its associated functional pathway exhibited an AUC of 0.78 to distinguish allergic asthmatics from those without allergies. CONCLUSION: We demonstrated a distinct taxonomic composition of gut microbiota in different asthmatic phenotypes, highlighting their significant relationships. Our study may support considerations of intestinal microbial signatures in delineating asthma phenotypes.

Combined Neutrophil-to-Lymphocyte Ratio and CURB-65 Score as an Accurate Predictor of Mortality for Community-Acquired Pneumonia in the Elderly.

PURPOSE: Community-acquired pneumonia (CAP) is common among the elderly; it typically has a poor prognosis and high mortality. This study evaluated the factors predicting CAP-related in-hospital mortality in the elderly to identify a simpler and more accurate predictor. PATIENTS AND METHODS: This was a single-center, retrospective study. The data used in this study was collected from all older patients (≥65) with CAP admitted to our hospital between January 2012 and April 2020. RESULTS: A total of 2028 older patients with CAP were included; 121 (5.97%) died in hospital. Of the patients in the study, 1267 (62.5%) were men and 261 (12.9%) had a history of malignant tumors. After performing univariate and multivariate Cox regression analyses, sex, history of malignant tumor, CURB-65 score, neutrophil-to-lymphocyte ratio (NLR), hemoglobin level, and NLR*CURB-65 levels were associated with CAP mortality. By comparing the area under the receiver operating characteristic (ROC) curves of the predicted factors, the NLR*CURB-65 level used to predict CAP mortality in the elderly was 0.755, and was superior to other measurements. All included patients were then dichotomized into two groups based on NLR*CURB-65 level (≤9.06 and >9.06) according to the ROC analysis. Patients with a high NLR*CURB-65 level had higher in-hospital mortality than those with a low NLR*CURB-65 level. The two divided groups showed significant differences in age, sex, smoking history, comorbidity, and laboratory findings. This indicates that NLR*CURB-65 is a predictive index that could reflect the comprehensive condition of older patients with CAP. CONCLUSION: NLR*CURB-65 is a simpler and more accurate predictor of CAP-related in-hospital mortality in the elderly.

Blood urea nitrogen to serum albumin ratio independently predicts 30-day mortality and severity in patients with Escherichia coli bacteraemia.

BACKGROUND: Elevated blood urea nitrogen to serum albumin (BUN/ALB) ratio had been identified as an independent risk factor related to mortality in community-acquired and hospital-acquired pneumonia. This study aimed to investigate whether this clinical index can predict the clinical outcomes of E. coli bacteraemia. MATERIAL AND METHODS: Clinical data were collected from patients with E. coli bacteraemia attended at our hospital between January 2012 and December 2018. The endpoints were mortality within 30 days after the diagnosis of E. coli bacteraemia and intensive care (IC) requirement. Cox regression analysis was performed to evaluate the risk factors. RESULTS: A total of 398 patients with E. coli bacteraemia were enrolled in this study and 56 patients died within 30 days after bacteraemia onset. Multivariate Cox regression analysis showed that age greater than 65 years, lymphocyte count<.8×10e9/L, elevated BUN/ALB ratio, increased SOFA score, carbapenem resistance, central venous catheterization before onset of bacteraemia, and infection originating from abdominal cavity were independent risk factors for 30-day mortality (P<.05). The risk factors associated with IC requirement were similar to those for 30-day mortality except central venous catheterization before onset of bacteraemia. The area under the receiver-operating characteristic curve for BUN/ALB ratio predicting 30-day mortality and IC requirement was similar to that for SOFA score, but higher than that for lymphocyte count. The cut-off points of BUN/ALB ratio to predict 30-day mortality and IC requirement were both .3. CONCLUSIONS: BUN/ALB ratio is a simple but independent predictor of 30-day mortality and severity in E. coli bacteraemia. A higher BUN/ALB ratio at the onset of bacteraemia predicts a higher mortality rate and IC requirement.

A promising approach for screening pulmonary hypertension based on frontal chest radiographs using deep learning: A retrospective study.

BACKGROUND: To date, the missed diagnosis rate of pulmonary hypertension (PH) was high, and there has been limited development of a rapid, simple, and effective way to screen the disease. The purpose of this study is to develop a deep learning approach to achieve rapid detection of possible abnormalities in chest radiographs suggesting PH for screening patients suspected of PH. METHODS: We retrospectively collected frontal chest radiographs and the pulmonary artery systolic pressure (PASP) value measured by Doppler transthoracic echocardiography from 762 patients (357 healthy controls and 405 with PH) from three institutes in China from January 2013 to May 2019. The wohle sample comprised 762 images (641 for training, 80 for internal test, and 41 for external test). We firstly performed a 8-fold cross-validation on the 641 images selected for training (561 for pre-training, 80 for validation), then decided to tune learning rate to 0.0008 according to the best score on validation data. Finally, we used all the pre-training and validation data (561+80 = 641) to train our models (Resnet50, Xception, and Inception V3), evaluated them on internal and external test dataset to classify the images as having manifestations of PH or healthy according to the area under the receiver operating characteristic curve (AUC/ROC). After that, the three deep learning models were further used for prediction of PASP using regression algorithm. Moreover, we invited an experienced chest radiologist to classify the images in the test dataset as having PH or not, and compared the prediction accuracy performed by deep learing models with that of manual classification. RESULTS: The AUC performed by the best model (Inception V3) achieved 0.970 in the internal test, and slightly declined in the external test (0.967) when using deep learning algorithms to classify PH from normal based on chest X-rays. The mean absolute error (MAE) of the best model for prediction of PASP value was smaller in the internal test (7.45) compared to 9.95 in the external test. Manual classification of PH based on chest X-rays showed much lower AUCs compared to that performed by deep learning models both in the internal and external test. CONCLUSIONS: The present study used deep learning algorithms to classify abnormalities suggesting PH in chest radiographs with high accuracy and good generalizability. Once tested prospectively in clinical settings, the technology could provide a non-invasive and easy-to-use method to screen patients suspected of having PH.

Airway inflammation and remodeling of cigarette smoking exposure ovalbumin-induced asthma is alleviated by CpG oligodeoxynucleotides via affecting dendritic cell-mediated Th17 polarization.

Cigarette smoking (CS) is common in asthma, aggravating inflammatory reactions. However, the current treatment strategies for asthma are still not effective enough, and novel therapeutic approaches are required for CS-induced asthmatic disorders. We here investigated the ability of CpG oligodeoxynucleotides (CpG-ODNs) to inhibit airway inflammation and remodeling in ovalbumin (OVA)-associated asthma in mice exposed to chronic CS, revealing potential mechanistic insights. Lung tissue specimens were histologically analyzed. Th1/Th2/Th17 associated cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung specimens were quantitated by ELISA, qRT-PCR and immunoblot. Parameters of bone marrow-derived dendritic cells (BMDCs) functions were evaluated as well. The results showed that BALB/c mice after CS and OVA treatments developed an asthmatic phenotype with airway inflammation involving both eosinophils and neutrophils, goblet cell metaplasia, airway remodeling, and elevated OVA-specific serum IgE, serum IL-17A, and BALF Th17/Th2 associated cytokines. CpG-ODNs and budesonide were found to synergistically inhibit inflammatory cell recruitment in the lung, airway remodeling, IgE synthesis, and Th17/Th2 associated cytokines. Mechanistically, CpG-ODNs and budesonide acted synergistically on BMDCs via downregulation of TSLP receptor (TSLPR) and IL-23 production, and subsequently contributed to dampen Th17/Th2 polarization in CS-associated asthma. In conclusion, combined administration of CpG-ODNs and budesonide, in a synergistic manner, inhibits airway inflammation, and tissue remodeling mediated by BMDCs by regulating IL-23 secretion and blocking TSLP signaling, which subsequently contribute to alleviate Th17/Th2 imbalance in CS-associated asthma.

Oxidovanadium(V) and Dioxidomolybdenum(VI) Complexes of N'-(3,5-Dichloro-2-hydroxybenzylidene)-4-fluorobenzohydrazide: Synthesis, Characterization, Crystal Structures and Catalytic Property.

N'-(3,5-Dichloro-2-hydroxybenzylidene)-4-fluorobenzohydrazide (H2L) was used to prepare oxidovanadium(V) complex [VOL(OEt)(MeOH)] (1) and dioxidomolybdenum(VI) complex [MoO2L(OH2)]·[MoO2L(EtOH)] (2). The complexes were characterized by IR, UV-Vis, NMR spectroscopy, and single crystal X-ray diffraction. X-ray analysis indicates that the complexes are mononuclear species with the metal atoms in octahedral coordination. The complexes were studied for catalytic oxidation property on some olefins with tert-butyl hydroperoxide as oxidant.

Risk Factors for Mortality Due to Ventilator-Associated Pneumonia in a Chinese Hospital: A Retrospective Study.

BACKGROUND As a common nosocomial infection, ventilator-associated pneumonia (VAP) often has high mortality. This study aimed to assess the risk factor for mortality owing to VAP. MATERIAL AND METHODS This retrospective clinical audit study screened medical records between the period of January 2014 and December 2017. All patients under mechanical ventilation MV) for ≥72 hours were screened against previously reported diagnostic criteria for VAP. The medical records were obtained for cases of documented diagnosis of VAP. RESULTS In all, 145 patients (5.0%) diagnosed with VAP were included in the study; the morbidity of VAP was 19.5 episodes per 1000 days of MV. The 30-day mortality rate was 42.8%. Univariate logistic analysis showed that elevated neutrophil-to-lymphocyte ratio (NLR), high blood urea nitrogen/albumin (BUN/ALB) ratio, Multidrug-resistant organism infection, and a higher sequential organ failure assessment (SOFA) score were risk factors for mortality caused by VAP. In the second multivariate analysis, elevated NLR levels (P=0.038), high BUN/ALB ratio (P=0.016), multidrug-resistant organism infections (P=0.036), and a higher SOFA score (P<0.001) were still associated with the 30-day mortality rate. CONCLUSIONS The 30-day mortality rate of VAP was high. Blood NLR and BUN/ALB levels can be used as risk factors to assess the 30-day VAP-related mortality to help clinicians improve the prognosis of VAP.

Elevated Blood Urea Nitrogen-to-Serum Albumin Ratio as a Factor That Negatively Affects the Mortality of Patients with Hospital-Acquired Pneumonia.

This study aimed to evaluate the factors that affect 30-day mortality of patients with HAP. The data used in this study were collected from all HAP occurred in our hospital between January 2014 and December 2017. A total of 1158 cases were included. 150 (13.0%) of whom died within 30 days. This reported mortality identified by the univariate Cox regression analysis is found to have been affected by the following factors: age greater than 70 years, presence of diabetes mellitus and chronic obstructive pulmonary disease, gastric tube intubation, administration of proton-pump inhibitor, blood albumin level less than 30 g/l, elevated neutrophil-to-lymphocyte ratio, antibiotics therapy in the preceding 90 days, intensive care unit (ICU) admission, blood lymphocyte count less than 0.8 × 109/L, elevated blood urea nitrogen/albumin (BUN/ALB) level, and presence of multidrug-resistant (MDR) pathogens. In the second multivariate analysis, administration of proton-pump inhibitor, administration of antibiotics in the preceding 90 days, ICU admission, blood lymphocyte count less than 0.8 × 109/L, elevated BUN/ALB level, and presence of MDR pathogens were still associated with 30-day mortality. The area under the receiver operating characteristic curves in the BUN/ALB predicting 30-day mortality due to HAP was 0.685. A high BUN/ALB was significantly associated with a worse survival than a low BUN/ALB (P < 0.001). Therefore, an elevated BUN/ALB level is a risk factor for mortality on patients with HAP.

Differences in microbial etiology between hospital-acquired pneumonia and ventilator-associated pneumonia: a single-center retrospective study in Guang Zhou.

Purpose: Nosocomial pneumonia is a common nosocomial infection that includes hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia(VAP). It is an important cause of morbidity and mortality in hospitalized patients. This study aimed to evaluate the differences in microbial etiology and outcomes between HAP and VAP, particularly in related risk factors of multidrug-resistant organism (MDRO) causing HAP and VAP. Patients and methods: This single-center retrospective, observational study included patients with HAP/VAP. Clinical and epidemiological data of nosocomial pneumonia confirmed by microbial etiology that occurred in the Third Affiliated Hospital of Sun Yat-sen University, China, from January 2014 to December 2017 were obtained. Results: A total of 313 HAP cases and 106 VAP cases were included. The leading pathogens of HAP and VAP were similar, including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Antimicrobial susceptibility of the pathogens was low, and P. aeruginosa in VAP was less susceptible. In the multivariate logistic regression analysis, the risk factors associated with MDRO-HAP were chronic obstructive pulmonary disease, antibiotic therapy in the preceding 90 days, and prior endotracheal tracheostomy. The risk factor of MDRO-VAP was ≥5 days of hospitalization. The 30-day mortality rates of HAP and VAP were 18.5% and 42.5%. Conclusion: The leading pathogens were similar in both HAP and VAP, and antimicrobial susceptibility of the pathogens was low. The risk factors associated with MDRO infection in HAP and VAP have significant variability; hence, attention should be paid to improve prognosis. VAP was associated with poorer outcomes compared with HAP.

Factors influencing mortality in hospital-acquired pneumonia caused by Gram-negative bacteria in China.

BACKGROUND: Hospital-acquired pneumonia (HAP) remains an important cause of morbidity and mortality despite advances in antimicrobial therapy. The emergence of Gram-negative bacteria (GNB) is of major concern. The objective of this study was to describe the epidemiology, microbiology, and predictors of infection-related 30-day mortality in HAP with GNB. METHODS: We performed a retrospective, single-center analysis of HAP patients with GNB occurring from January 2014 and December 2017. Univariate and multivariate analyses were performed to identify the risk factors for mortality. RESULTS: During the observational period, there were 1472 cases of HAP; 314 cases were bacterial culture-positive, 269 cases were caused by GNB, with a predominance of Acinetobacter baumannii and Pseudomonas aeruginosa. The mortality related to GNB was 14.5% (39 deaths).In the multivariate logistic regression analysis, the risk factors for mortality were age >70 years, intensive care unit (ICU) admission, blood lymphocyte count < 0.8 × 109/L, multidrug-resistant Gram-negative bacteria(MDR-GNB) infection, and elevation of blood urea nitrogen(BUN) level. We identified these factors as significant predictors of GNB related mortality; the area under the receiver operating characteristic (ROC) curves was 0.836. CONCLUSION: The results provided can help clinicians in identifying individuals who are at risk of infection-related 30-day mortality in HAP with GNB.

IL-37 alleviates house dust mite-induced chronic allergic asthma by targeting TSLP through the NF-κB and ERK1/2 signaling pathways.

Interleukin (IL)-37 has been described as a negative regulator of immune responses and is critical for asthma pathogenesis, but the mechanisms behind the protective role of IL-37 against allergic asthma are less well understood. We show here that IL-37 administered intranasally inhibited house dust mite (HDM)-induced chronic airway eosinophilic inflammation, goblet cell hyperplasia, peribronchial collagen deposition and airway hyperresponsiveness (AHR) to methacholine. In contrast to a weakened Th2 response in the lung that was characterized by the downregulation of Th2-associated cytokines and chemokines in IL-37-treated mice, IL-37 has no effect on relevant markers of systemic Th2 immune including serum immunoglobulins expression and in vitro production of Th2-associated cytokines by splenocytes on HDM recall. We demonstrated that the production of thymic stromal lymphopoietin (TSLP) in the lung tissue was associated with IL-37. Importantly, compared with IL-37 alone, TSLP coadministration with IL-37 restored HDM-induced airway inflammation and structural alterations, increased AHR to methacholine and promoted Th2-associated cytokine production. We further found that IL-37 inhibited the induction of TSLP expression by the main antigen of house dust mite, Der p1, by suppressing NF-κB and extracellular signal regulated kinase 1/2 (ERK1/2) activation in human bronchial epithelial (16-HBE) cells in vitro. These data highlight the importance of TSLP in IL-37-mediated protective role in asthma. IL-37 might represent a useful innovative and alternative therapy to control TSLP production in the airway.