Screening and staging of chronic obstructive pulmonary disease with deep learning based on chest X-ray images and clinical parameters.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is underdiagnosed with the current gold standard measure pulmonary function test (PFT). A more sensitive and simple option for early detection and severity evaluation of COPD could benefit practitioners and patients. METHODS: In this multicenter retrospective study, frontal chest X-ray (CXR) images and related clinical information of 1055 participants were collected and processed. Different deep learning algorithms and transfer learning models were trained to classify COPD based on clinical data and CXR images from 666 subjects, and validated in internal test set based on 284 participants. External test including 105 participants was also performed to verify the generalization ability of the learning algorithms in diagnosing COPD. Meanwhile, the model was further used to evaluate disease severity of COPD by predicting different grads. RESULTS: The Ensemble model showed an AUC of 0.969 in distinguishing COPD by simultaneously extracting fusion features of clinical parameters and CXR images in internal test, better than models that used clinical parameters (AUC = 0.963) or images (AUC = 0.946) only. For the external test set, the AUC slightly declined to 0.934 in predicting COPD based on clinical parameters and CXR images. When applying the Ensemble model to determine disease severity of COPD, the AUC reached 0.894 for three-classification and 0.852 for five-classification respectively. CONCLUSION: The present study used DL algorithms to screen COPD and predict disease severity based on CXR imaging and clinical parameters. The models showed good performance and the approach might be an effective case-finding tool with low radiation dose for COPD diagnosis and staging.

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.

Interplay of IL-33 and IL-35 Modulates Th2/Th17 Responses in Cigarette Smoke Exposure HDM-Induced Asthma.

Cigarette smoke (CS) facilitates adverse effects on the airway inflammation and treatment of asthma. Here, we investigated the mechanisms by which CS exacerbates asthma. The roles of IL-33 and IL-35 in asthma development were examined by treatment with IL-33 knockout (IL-33 KO) or transfection of adenovirus encoding IL-35 (Ad-IL-35) in a murine model of cigarette smoke-exposure asthma. Furthermore, the involvement of IL-33 and IL-35 in regulating DCs and Th2/Th17 cells was examined in a coculture system of DCs with CD4+ T cells. Additionally, we observed the effect of CpG-ODNs on the balance of IL-33 and IL-35. We show that CS and house dust mite (HDM) exposure induced IL-33 and suppressed IL-35 levels in cigarette smoke-exposure asthma in vivo and in vitro. Treatment with IL-33 KO or Ad-IL-35 significantly attenuated airway hyperreactivity, goblet hyperplasia, airway remodelling, and eosinophil and neutrophil infiltration in the lung tissues from asthmatic mice. Furthermore, we demonstrated reciprocal regulation between CS and HDM-modulated IL-33 and IL-35. Mechanistically, IL-33 KO (or anti-ST2) and Ad-IL-35 attenuated Th2- and Th17-associated inflammation by downregulating TSLP-DC signalling. Finally, administration of CpG-ODNs suppressed the expression of IL-33/ST2 and elevated the levels of IL-35, which is mainly derived from CD4+Foxp+ Tregs, to alleviate Th2- and Th17-associated inflammation by inhibiting the activation of BMDCs. Taken together, the IL-33/ST2 pathway drives the DC-Th2 and Th17 responses of cigarette smoke-exposure asthma, while IL-35 has the opposite effect. CpG-ODNs represent a potential therapeutic strategy for modulating the balance of IL-33 and IL-35 to suppress allergic airway inflammation.

Endothelial Progenitor-Cell-Derived Exosomes Induced by Astragaloside IV Accelerate Type I Diabetic-wound Healing via the PI3K/AKT/mTOR Pathway in Rats.

OBJECTIVE: We explore the effects of endothelial progenitor cell (EPC)-derived exosomes (EPCexos) and of astragaloside IV (ASIV)-stimulated EPCexos (ASIV-EPCexos) on type I diabetic-wound healing, and determine the basic molecular mechanisms of action. METHODS: EPCs were exposed to different concentrations of ASIV to generate ASIV-EPCexos. A chronic-wound healing model involving streptozotocin-stimulated diabetic rats was established. These rats were treated with EPCexos, ASIV-EPCexos, rapamycin, and wortmannin. Wound healing was evaluated by direct photographic observation, hematoxylin and eosin staining, and Masson's trichrome staining. RESULTS: ASIV treatment increased the abilities of EPCs (e.g., proliferation), as well as exosome secretion. EPCexo showed a "cup holder" like structure. Treatment with ASIV-EPCexos increased the wound-healing rate, collagen-deposition area, bromodeoxyuridine uptake, VEGF expression, and the number of CD31- and αSMA- positive cells, whereas decreased epidermal thickness and CD45 expression. The expression of the PI3K/AKT/mTOR pathway increased, whereas the expression of inflammatory factor decreased. However, rapamycin and wortmannin reversed these changes. CONCLUSIONS: ASIV-EPCexos may accelerate type I diabetic-wound healing via the PI3K/AKT/mTOR pathway. This study may lay the foundation for new clinical treatment options for patients with type I diabetic wounds.

[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.

The complete chloroplast genome sequence of Zingiber teres S. Q. Tong & Y. M. Xia (Zingiberaceae).

Here, the complete chloroplast genome sequence of Zingiber teres is described using MGI paired-end sequencing. The genome is 163,428 bp in length and contains a small single-copy region (SSC) of 15,782 bp, a large single-copy region (LSC) of 88,142 bp, and two inverted repeat (IR) regions of 29,752 bp. The overall GC content is 36.1%, and the GC content of the IR regions is 41.1%, which is higher than that of both the LSC region (33.8%) and SSC region (29.5%). The genome of Z. teres contains 133 complete genes, including 88 protein-coding genes (79 protein-coding gene species), 38 tRNA genes (28 tRNA species), and 8 rRNA genes (four rRNA species). Maximum likelihood phylogenetic analysis yielded a well-resolved tree of the genus Zingiber, and Z. teres and Zingiber mioga were sister species in this tree. The development of DNA barcodes could aid the identification of Zingiber species.

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.

A CpG-Oligodeoxynucleotide Suppresses Th2/Th17 Inflammation by Inhibiting IL-33/ST2 Signaling in Mice from a Model of Adoptive Dendritic Cell Transfer of Smoke-Induced Asthma.

Tobacco smoke exposure is a major environmental risk factor that facilitates the development and progression of asthma. Our previous study showed that CpG oligodeoxynucleotide (CpG-ODN) inhibits thymic stromal lymphopoietin (TSLP)-dendritic cells (DCs) to reduce Th2/Th17-related inflammatory response in smoke-related asthma. However, the mechanism underlying CpG-ODN -downregulated TSLP remains unclear. A combined house dust mite (HDM)/cigarette smoke extract (CSE) model was used to assess the effects of CpG-ODN on airway inflammation, Th2/Th17 immune response, and amount of IL-33/ST2 and TSLP in mice with smoke-related asthma induced by adoptive transfer of bone-marrow-derived dendritic cells (BMDCs) and in the cultured human bronchial epithelium (HBE) cells administered anti-ST2, HDM, and/or CSE. In vivo, compared to the HDM alone model, the combined HDM/CSE model had aggravated inflammatory responses, while CpG-ODN attenuated airway inflammation, airway collagen deposition, and goblet cell hyperplasia and reduced the levels of IL-33/ST2, TSLP, and Th2/Th17-cytokines in the combined model. In vitro, IL-33/ST2 pathway activation promoted TSLP production in HBE cells, which could be inhibited by CpG-ODN. CpG-ODN administration alleviated Th2/Th17 inflammatory response, decreased the infiltration of inflammatory cells into the airway, and improved the remodeling of smoke-related asthma. The underlying mechanism may be that CpG-ODN inhibits the TSLP-DCs pathway by downregulating the IL-33/ST2 axis.

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.

Astragaloside IV drug-loaded exosomes (AS-IV EXOs) derived from endothelial progenitor cells improve the viability and tube formation in high-glucose impaired human endothelial cells by promoting miR-214 expression.

INTRODUCTION: The high glucose changes caused by diabetes mellitus (DM) can damage the vascular system. Astragaloside IV (AS-IV) can improve diabetes and promote angiogenesis. Exosomes (EXOs) help to carry specific drugs into cells efficiently. However, whether AS-IV loaded EXOs (AS-IV EXOs) can improve damaged endothelial cells through miR-214 remains to be determined. MATERIAL AND METHODS: We prepared and identified AS-IV EXOs derived from endothelial progenitor cells (EPCs) and high glucose stimulated endothelial cell models to investigate whether AS-IV EXOs can improve damaged endothelial cells through miR-214. We used a transmission electron microscope (TEM) and DAPI staining to identify the morphology and characteristic expression of EPCs and EXOs, and then prepared AS-IV EXOs. Cell function tests were performed to detect the cloning, proliferation, and migration capabilities of cells. Western blot (WB) and real-time quantitative polymerase chain reaction (qRT-PCR) were used to assess the expression level of Tie-2, Ang-1, and PI3K/Akt-related protein. RESULTS: The DAPI staining results showed that inducing human umbilical vein endothelial cells (HUVECs) could effectively absorb AS-IV EXOs. The results of plate clone formation assay, CCK-8, cell adhesion, and transwell assay of HUVECs stimulated by high glucose showed that AS-IV EXOs had a damage relief effect. By the detection of WB and qRT-PCR, it was found that AS-IV EXOs promoted the expression of miR-214 and proteins related to blood vessel growth. After transfection of miR-214 to pre-treat HUVECs under high glucose stimulation, AS-IV EXOs promoted the tube formation of HUVECs by regulating the level of miR-214. CONCLUSIONS: By promoting the expression of miR-214, AS-IV EXOs significantly improved the activity and tubularization of HUVECs under high glucose stimulation.

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.

Bioinspired Heteromultivalent Chitosan-α-Fe2O3/Gadofullerene Hybrid Composite for Enhanced Antibiotic-Resistant Bacterial Pneumonia.

Herein, we have designed and developed a heteromultivalent chitosan base α-Fe2O3/Gadofullerene (GdF) hybrid composite through a simple chemical precipitation method. Unlike other methods, the addition of external stabilizing agents to generate GdF nanoparticles (NPs) was not necessary herein. The prepared chitosan-α-Fe2O3/GdF hybrid nanocomposites were characterized using UV, FT-IR, XRD and morphological microscopic analyses. The results showed that α-Fe2O3 and GdF hybrid nanocomposites were successfully grown on the surface of chitosan. The FT-IR vibration peaks showed the formation of Fe2O3 NPs, and the vibration peak for Fe-O was 568 cm-1. The broad absorption peak observed in the range of 250-350 nm and a sharp absorption peak at 219 nm represents the UV absorption of the synthesized hybrid composites. XRD pattern showed sharp peaks of crystallinity and purity of α-Fe2O3 nanoparticles. Finally, the synthesized chitosan-α-Fe2O3/GdF hybrid composites were screened for their antibacterial resistance against the Escherichia coli, Pseudomonas aeruginosa, Bacilus subtilis, and Staphylococcus aereus. In addition, in vitro biocompatibility results exhibited that developed hybrid samples have provided high cell compatibility with fibroblast (L929) cell line. The in vivo bio inspired nanotherapeutics have the potential action to effective inhibition ability on antibiotic-resistant P. aeruginosa, which has been main factor of inducing pneumonia. In conclusion, we expect biomimicking systems combined with the effective antibacterial agent could be the suitable next generation therapeutic potential factors for prevention and treatment of antibiotic-resistant pneumonia.

CpG oligodeoxynucleotides attenuate RORγt-mediated Th17 response by restoring histone deacetylase-2 in cigarette smoke-exposure asthma.

BACKGROUND: Cigarette smoke (CS) exposure increases corticosteroid insensitive asthma related to increased Th17 phenotype, and new treatment strategies are needed for CS-associated asthma. Histone deacetylase 2 (HDAC2), found in the airway epithelium, is critical for ameliorating glucocorticoids insensitivity. We recently demonstrated the anti-inflammatory effects of CpG oligodeoxynucleotides (CpG-ODNs) on CS-exposure asthma. However, the effects of CpG-ODNs on HDAC2 expression and enzymatic activity remain unclear. This study aimed to assess whether CpG-ODNs protect against excessive Th17 immune responses in CS-induced asthma through HDAC2-dependent mechanisms and compared their effects with those of corticosteroids. METHODS: The effects of CpG-ODNs alone and in combination with budesonide (BUD) on airway inflammation and Th2/Th17-related airway immune responses were determined using an in vivo model of CS-induced asthma and in cultured bronchial epithelial (HBE) cells administered ovalbumin (OVA) and/or cigarette smoke extract (CSE). HDAC2 and retinoid-related orphan nuclear receptor γt (RORγt) expression were also assessed in mouse lung specimens and HBE cells. RESULTS: CpG-ODNs and BUD synergistically attenuated CS exposure asthmatic responses in vivo by modulating the influx of eosinophils and neutrophils, airway remodeling, Th2/Th17 associated cytokine and chemokine production, and airway hyperresponsiveness and blocking RORγt-mediated Th17 inflammation through induced HDAC2 expression/activity. In vitro, CpG-ODNs synergized with BUD to inhibit Th17 cytokine production in OVA- and CSE-challenged HBE cells while suppressing RORγt and increasing epithelial HDAC2 expression/activity. CONCLUSIONS: CpG-ODNs reversed CS-induced HDAC2 downregulation and enhanced the sensitivity of CS-exposed asthmatic mice and CSE-induced HBE cells to glucocorticoid treatment. This effect may be associated with HDAC2 restoration via RORγt/IL-17 pathway regulation, suggesting that CpG-ODNs are potential corticosteroid-sparing agents for use in CS-induced asthma with Th17-biased immune conditions.

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.

Feasibility study on recycled vegetable oil waste and recycled polyethylene for the modification of aged asphalt.

The application of reclaimed asphalt pavement has been widely encouraged due to its significant economic and environmental benefits. However, it is necessary to add rejuvenators to ensure its performance. Currently, bio-oil-based regenerants have attracted attention owing to their advantages of renewability and cost savings. The purpose of this paper is to study the use of recycled vegetable oil waste (R-oil) and recycled polyethylene particles for the regeneration and modification of aged asphalt. Physical, rheological, and chemical tests were used to figure out their influence on the pavement performance of aged asphalt. According to the physical test indices (penetration, softening point, and ductility), the performance of the rejuvenated asphalt was better than that of virgin asphalt. The workability and low-temperature performance of the rejuvenated asphalt were basically the same as those of virgin asphalt, and its fatigue and high-temperature performance were better. Infrared spectroscopy showed that R-oil diluted the high-polarity sulfoxide base of aged asphalt. Gel permeation chromatography showed that its molecular weight dispersion was better than that of aged asphalt. Therefore, R-oil and polyethylene can improve the pavement performance and chemical properties of aged asphalt.