Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

Relationship between neonatal respiratory distress syndrome pulmonary ultrasonography and respiratory distress score,oxygenation index,and chest radiography grading

BACKGROUND Accurate condition assessment is critical for improving the prognosis of neonatal respiratory distress syndrome(RDS),but current assessment methods for RDS pose a cumulative risk of harm to neonates.Thus,a less harmful method for assessing the health of neonates with RDS is needed.AIM To analyze the relationships between pulmonary ultrasonography and respiratory distress scores,oxygenation index,and chest X-ray grade of neonatal RDS to identify predictors of neonatal RDS severity.METHODS This retrospective study analyzed the medical information of 73 neonates with RDS admitted to the neonatal intensive care unit of Liupanshui Maternal and Child Care Service Center between April and December 2022.The pulmonary ultrasonography score,respiratory distress score,oxygenation index,and chest Xray grade of each newborn before and after treatment were collected.Spearman correlation analysis was performed to determine the relationships among these values and neonatal RDS severity.RESULTS The pulmonary ultrasonography score,respiratory distress score,oxygenation index,and chest X-ray RDS grade of the neonates were significantly lower after treatment than before treatment(P<0.05).Spearman correlation analysis showed that before and after treatment,the pulmonary ultrasonography score of neonates with RDS was positively correlated with the respiratory distress score,oxygenation index,and chest X-ray grade(ρ=0.429–0.859,P<0.05).Receiver operating characteristic curve analysis indicated that pulmonary ultrasonography screening effectively predicted the severity of neonatal RDS(area under the curve=0.805–1.000,P<0.05).CONCLUSION The pulmonary ultrasonography score was significantly associated with the neonatal RDS score,oxygenation index,and chest X-ray grade.The pulmonary ultrasonography score was an effective predictor of neonatal RDS severity.

RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration

The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.

Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

Prevalence and Tasks Associated with Respiratory Symptoms among Waste Electrical and Electronic Equipment Handlers in Ouagadougou, Burkina Faso in 2019

Introduction: The uncontrolled management of waste electrical and electronic equipment (W3E) causes respiratory problems in the handlers of this waste. The objective was to study the stains associated with respiratory symptoms in W3E handlers. Methods: The study was cross-sectional with an analytical focus on W3E handlers in the informal sector in Ouagadougou. A peer-validated questionnaire collected data on a sample of 161 manipulators. Results: the most common W3E processing tasks were the purchase or sale of W3E (67.70%), its repair (39.75%) and its collection (31.06%). The prevalence of cough was 21.74%, that of wheezing 14.91%, phlegm 12.50% and dyspnea at rest 10.56%. In bivariate analysis, there were significant associations at the 5% level between W3E repair and phlegm (p-value = 0.044), between W3E burning and wheezing (p-value = 0.011) and between W3E and cough (p-value = 0.01). The final logistic regression models suggested that the burning of W3E and the melting of lead batteries represented risk factors for the occurrence of cough with respective prevalence ratios of 4.57 and 4.63. Conclusion: raising awareness on the wearing of personal protective equipment, in particular masks adapted by W3E handlers, favoring those who are dedicated to the burning of electronic waste and the melting of lead could make it possible to reduce the risk of occurrence of respiratory symptoms.

Advanced nanomedicines and immunotherapeutics to treat respiratory diseases especially COVID-19 induced thrombosis

Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory diseases.Engineering specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019(COVID-19)infection.COVID-19 causes pulmonary embolisms,thus new therapeutic options are required to target thrombosis,as conventional treatment options are either not effective due to the complexity of the immunethrombosis pathophysiology.In this review,we discuss regulation of immune response in respiratory diseases especially COVID-19.We further discuss thrombosis and provide an overview of some antithrombotic nanoparticles,which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious diseases.We also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways,and thus can be recommended to treat respiratory infectious diseases.

Respiratory Distress in Neonates at the Teaching Hospitals of Lomé, Togo

Introduction: Respiratory distress in neonates is a neonatal emergency that can lead to serious complications if not treated appropriately. The aim of this study was to describe the epidemiology, the diagnostic, and the outcomes of neonatal respiratory distress. Methods: This was a cross-sectional study carried out in the pediatric wards of Lomé Teaching Hospitals (CHU Sylvanus Olympio and CHU Campus), including neonates treated for respiratory distress (dyspnea associated with the use of accessory muscles of respiration, noisy breathing and with or without cyanosis) from January 1, 2021 to December 31, 2021. Data were entered using Epi Data 3.1 and SPSS software version 12.0. Results: The total number of neonates hospitalized for respiratory distress was 353, with a frequency of 12.5% and a sex ratio of 1.5. The mean age was 0.82 ± 3.20 days;the 0 - 6-day age group accounted for 92.4% of cases. Neonates had been resuscitated at birth in 46.7% of cases. Dyspnea was tachypnea in 94% of cases and bradypnea in 6%. Dyspnea was associated with cyanosis in 21.5% of cases. The severity of the respiratory distress was moderate in 64.9% of cases. Perinatal asphyxia (49.1%), inhalation pneumonitis (17.1%) and neonatal bacterial infection (14.1%) were the main etiologies. The mortality rate was 20.4%. Age greater than or equal to seven days, no neonatal resuscitation were protective factors against death. Prematurity, no antenatal consultations follow up, neonatal resuscitation, severe respiratory distress were risk factors of death. Conclusion: Neonatal respiratory distress was common in the early neonatal period and its mortality was high.

Suppression of miR-17 Alleviates Acute Respiratory Distress-associated Lung Fibrosis by Regulating Mfn2

Objective Acute respiratory distress syndrome(ARDS)patients currently have relatively high mortality,which is associated with early lung fibrosis.This study aimed to investigate whether miR-17 suppression could alleviate ARDS-associated lung fibrosis by regulating Mfn2.Methods A mouse model of ARDS-related lung fibrosis was constructed via intratracheal instillation of bleomycin.The expression level of miR-17 in lung tissues was detected via quantitative real time polymerase chain reaction(qRT-PCR).In the ARDS mouse model of lung fibrosis,the mitigating effects of miR-17 interference were evaluated via tail vein injection of the miR negative control or the miR-17 antagomir.The pathological changes in the lung tissue were examined via HE staining and Masson’s trichrome staining,and the underlying molecular mechanism was investigated via ELISA,qRT-PCR and Western blotting.Results Bleomycin-induced pulmonary fibrosis significantly increased collagen deposition and the levels of hydroxyproline(HYP)and miR-17.Interfering with miR-17 significantly reduced the levels of HYP and miR-17 and upregulated the expression of Mfn2.The intravenous injection of the miR-17 antagomir alleviated lung inflammation and reduced collagen deposition.In addition,interference with miR-17 could upregulate LC3B expression,downregulate p62 expression,and improve mitochondrial structure.Conclusion Interfering with miR-17 can improve pulmonary fibrosis in mice by promoting mitochondrial autophagy via Mfn2.

A Comparison between Late Preterm and Term Infants with Respiratory Distress Syndrome, Early-Onset Sepsis, and Neonatal Jaundice in Ecuadorian Newborns

Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.

Quality indicators in respiratory therapy

Quality indicators in healthcare refer to measurable and quantifiable parameters used to assess and monitor the performance,effectiveness,and safety of healthcare services.These indicators provide a systematic way to evaluate the quality of care offered,and thereby to identify areas for improvement and to ensure that patient care meets established standards and best practices.Respiratory therapists play a vital role in areas of clinical administration such as infection control practices and quality improvement initiatives.Quality indicators serve as essential metrics for respiratory therapy departments to assess and enhance the overall quality of care.By systematically tracking and analyzing indicators related to infection control,treatment effectiveness,and adherence to protocols,respiratory care practitioners can identify areas to improve and implement evidence-based changes.This article reviewed how to identify,implement,and monitor quality indicators specific to the respiratory therapy departments to set benchmarks and enhance patient outcomes.

Effects of respiratory muscle training on post-stroke rehabilitation:A systematic review and meta-analysis

BACKGROUND Stroke often results in significant respiratory dysfunction in patients.Respiratory muscle training(RMT)has been proposed as a rehabilitative intervention to address these challenges,but its effectiveness compared to routine training remains debated.This systematic review and meta-analysis aim to evaluate the effects of RMT on exercise tolerance,muscle strength,and pulmonary function in post-stroke patients.AIM To systematically assess the efficacy of RMT in improving exercise tolerance,respiratory muscle strength,and pulmonary function in patients recovering from a stroke,and to evaluate whether RMT offers a significant advantage over routine training modalities in enhancing these critical health outcomes in the post-stroke population.METHODS Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines,a comprehensive search across PubMed,Embase,Web of Science,and the Cochrane Library was conducted on October 19,2023,without temporal restrictions.Studies were selected based on the predefined inclusion and exclusion criteria focusing on various forms of RMT,control groups,and outcome measures[including forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),maximal voluntary ventilation(MVV),peak expiratory flow(PEF),maximal inspiratory pressure(MIP),maximal expiratory pressure(MEP),and 6-min walking test(6MWT)].Only randomized controlled trials(RCTs)were included.Data extraction and quality assessment were conducted independently by two reviewers using the Cochrane Collaboration's risk of bias tool.Statistical analyses,including those using the fixed-effect and random-effects models,sensitivity analysis,and publication bias assessment,were performed using Review Manager software.RESULTS A total of 15 RCTs were included.Results indicated significant improvements in MIP(12.51 cmH2O increase),MEP(6.24 cmH2O increase),and various pulmonary function parameters(including FEV1,FVC,MVV,and PEF).A substantial increase in 6MWT distance(22.26 meters)was also noted.However,the heterogeneity among studies was variable,and no significant publication bias was detected.CONCLUSION RMT significantly enhances walking ability,respiratory muscle strength(MIP and MEP),and key pulmonary function parameters(FEV1,FVC,MVV,and PEF)in post-stroke patients.These findings support the incorporation of RMT into post-stroke rehabilitative protocols.

Effect of nursing on postoperative respiratory function and mental health of lung cancer patients

BACKGROUND Both pulmonary rehabilitation training and psychological care have been shown to have a positive effect on the postoperative recovery of patients with lung cancer.However,few studies have combined the two to explore their combined effect.Therefore,this study aimed to investigate the effects of pulmonary rehabil-itation training combined with psychological care on postoperative respiratory function and mental health in lung cancer patients.AIM To investigate effect of nursing on postoperative respiratory function and mental health of lung cancer patients.METHODS 122 cases of lung cancer patients who underwent surgical treatment in our hospital and were treated in our department from January 2022 to April 2023 were selected and randomly divided into the control group and observation group.The control group performed the routine care intervention.The obser-vation group was given pulmonary rehabilitation training and psychological care based on conventional nursing interventions.Forced expiratory volume,forced vital capacity.Maximum ventilatory volume(MVV)in one second was measured,and the patient's 6-min walking distance and dyspnoea index scale were used to assess the patient's respiratory condition.The Connor-Davidson resilience scale(CD-RISC),self-rating anxiety scale(SAS),and self-rating depression scale(SDS)were used to evaluate the mental health of the patients.RESULTS There was no difference between the two groups regarding age,gender,education level,surgical procedure,type of pathology,and treatment(P>0.05).After treatment,MVV,6-min walking distance,toughness,strength,optimism,and total CD-RISC scores were significantly higher in the observation group(P<0.05),dyspnoea scores,SAS,and SDS scores were substantially lower in the control group compared to the observation group(P<0.05).CONCLUSION Pulmonary rehabilitation training combined with psychological care for patients after lung cancer resection could improve lung function,enhance daily activities,effectively relieve negative emotions such as anxiety and depression,and reduce complications.

Factors Associated with Acute Respiratory Infections in Children Aged 0 - 5 Years in the Yénawa District of Cotonou (Benin) in 2023

Introduction: Acute respiratory infections remain one of the main causes of mortality in children aged 0 to 5. This work aimed to study the associated factors with the occurrence of acute respiratory infections in children 0 to 5 years old in Yénawa, Cotonou in 2023. Subjects and Method: It was an analytical cross-sectional study of children aged 0 - 5 years and their mothers in Yénawa, selected by four-degree random sampling. The sampling size, calculated using the Schwartz formula, was 126 children and 126 mothers. The dependent variable was the occurrence of acute respiratory infections. The independent variables were classified into four groups: socio-demographic and economic characteristics, behavioral factors, child-related factors, and environmental factors. Data collected by observation and questionnaire survey were analyzed using STATA version 15 software. Associated factors were investigated by bivariate analysis and multiple logistic regression, at the 5% significance level. Results: A total of 126 children aged 0 - 5 years and 126 mothers were surveyed, aged 23.5 (11 - 36) months and 30 (18 - 48) years respectively. The prevalence of acute respiratory infections was 74.60% (CI95% = 66.89 to 82.30). The associated factors were the mother’s age between 18 and 28 (OR = 10.77;CI95% = 1.89 to 61.27;p = 0.007), the use of charcoal/wood for cooking (OR = 7.36;IC = 1.99 to 27.10;p = 0.003)), children's poor personal hygiene (OR = 8.87;IC = 2.92 to 26.97;p 0.001)), and cohabitation with domestic animals (OR = 7.27;IC = 1.67 to 31.71;p = 0.015). Conclusion: Communicating with mothers about the factors identified will help reduce the prevalence of acute respiratory infections in children aged 0 to 5.

Short-term effects of low-level PM_(2.5),PM_(10),O_(3),and tropical meteorological conditions on emergency department visits for respiratory diseases in Haikou,China

Objective:To assess the correlation between atmospheric pollutants,meteorological factors,and emergency department visits for respiratory diseases in Haikou City.Methods:Daily data on atmospheric pollutants,meteorological factors,and emergency department visits for respiratory diseases in Haikou City from 2018 to 2021 were collected.The Spearman rank correlation test was used to analyze the correlation,and a distributed lag non-linear model was employed to analyze the health effects and lag impacts of environmental factors.Subgroup analyses were conducted based on sex and age.Results:According to the criteria of International Classification of Diseases(ICD-10:J00-J99),a total of 221913 cases were included,accounting for 21.3%of the total emergency department visits in Haikou City.For every 1℃increase in temperature,the risk of emergency department visits increased by 1.029%(95%CI 1.016%-1.042%).Relative humidity greater than 80%reduced the risk of visits,while higher atmospheric pressure(>1010 hpa)also decreased the likelihood of daily emergency department visits.Higher concentrations of PM_(2.5)(30-50μg/m^(3)),PM10(>60μg/m^(3)),and O_(3)(75-125μg/m^(3))were associated with increased visits.Higher temperatures(>25℃)have a greater impact on females and children aged 0-14 years,while males are more sensitive to low atmospheric pressure.Individuals aged 65 and above exhibited increased sensitivity to O_(3)concentration,and the effects of PM2.5,PM10,and O_(3)are more pronounced in individuals over 14 years old.Conclusions:Short-term exposure to high temperatures,particulate matter pollutants(PM_(2.5)and PM_(10)),and ozone(O_(3))is associated with increased emergency department visits for respiratory diseases.

Positron Emission Tomography Lung Image Respiratory Motion Correcting with Equivariant Transformer

In addressing the challenge of motion artifacts in Positron Emission Tomography (PET) lung scans, our studyintroduces the Triple Equivariant Motion Transformer (TEMT), an innovative, unsupervised, deep-learningbasedframework for efficient respiratory motion correction in PET imaging. Unlike traditional techniques,which segment PET data into bins throughout a respiratory cycle and often face issues such as inefficiency andoveremphasis on certain artifacts, TEMT employs Convolutional Neural Networks (CNNs) for effective featureextraction and motion decomposition.TEMT’s unique approach involves transforming motion sequences into Liegroup domains to highlight fundamental motion patterns, coupled with employing competitive weighting forprecise target deformation field generation. Our empirical evaluations confirm TEMT’s superior performancein handling diverse PET lung datasets compared to existing image registration networks. Experimental resultsdemonstrate that TEMT achieved Dice indices of 91.40%, 85.41%, 79.78%, and 72.16% on simulated geometricphantom data, lung voxel phantom data, cardiopulmonary voxel phantom data, and clinical data, respectively. Tofacilitate further research and practical application, the TEMT framework, along with its implementation detailsand part of the simulation data, is made publicly accessible at https://github.com/yehaowei/temt.

Outcomes of combined mitochondria and mesenchymal stem cellsderived exosome therapy in rat acute respiratory distress syndrome and sepsis

BACKGROUND The treatment of acute respiratory distress syndrome(ARDS)complicated by sepsis syndrome(SS)remains challenging.AIM To investigate whether combined adipose-derived mesenchymal-stem-cells(ADMSCs)-derived exosome(EXAD)and exogenous mitochondria(mitoEx)protect the lung from ARDS complicated by SS.METHODS In vitro study,including L2 cells treated with lipopolysaccharide(LPS)and in vivo study including male-adult-SD rats categorized into groups 1(sham-operated-control),2(ARDS-SS),3(ARDS-SS+EXAD),4(ARDS-SS+mitoEx),and 5(ARDS-SS+EXAD+mitoEx),were included in the present study.RESULTS In vitro study showed an abundance of mitoEx found in recipient-L2 cells,resulting in significantly higher mitochondrial-cytochrome-C,adenosine triphosphate and relative mitochondrial DNA levels(P<0.001).The protein levels of inflammation[interleukin(IL)-1β/tumor necrosis factor(TNF)-α/nuclear factor-κB/toll-like receptor(TLR)-4/matrix-metalloproteinase(MMP)-9/oxidative-stress(NOX-1/NOX-2)/apoptosis(cleaved-caspase3/cleaved-poly(ADP-ribose)polymerase)]were significantly attenuated in lipopolysaccharide(LPS)-treated L2 cells with EXAD treatment than without EXAD treatment,whereas the protein expressions of cellular junctions[occluding/β-catenin/zonula occludens(ZO)-1/E-cadherin]exhibited an opposite pattern of inflam-mation(all P<0.001).Animals were euthanized by 72 h post-48 h-ARDS induction,and lung tissues were harvested.By 72 h,flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflam-matory cells(Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+)and albumin were lowest in group 1,highest in group 2,and significantly higher in groups 3 and 4 than in group 5(all P<0.0001),whereas arterial oxygen-saturation(SaO2%)displayed an opposite pattern of albumin among the groups.Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers(CD68+/γ-H2AX)displayed an identical pattern of SaO2%among the groups(all P<0.0001).The protein expressions of inflammatory(TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress(NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged(cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic(beclin-1/Atg-5/ratio of LC3B-II/LC3B-I)biomarkers exhibited a similar manner,whereas antioxidants[nuclear respiratory factor(Nrf)-1/Nrf-2]/cellular junctions(ZO-1/E-cadherin)/mitochondrial electron transport chain(complex I-V)exhibited an opposite manner of albumin among the groups(all P<0.0001).CONCLUSION Combined EXAD-mitoEx therapy was better than merely one for protecting the lung against ARDS-SS induced injury.

Effect of different cold air intensities and their lagged effects on outpatient visits for respiratory illnesses in Handan in different seasons

本文利用2016年到2019年邯郸市气象要素和呼吸系统疾病门诊数据,分析了不同季节不同强度的冷空气过程及其对呼吸系统疾病的影响,结果显示:尽管呼吸系统疾病在冬季高发,夏季最低,但冷空气对呼吸系统疾病的影响在夏,春季最大,就诊人数分别在冷空气日后两天和五天增加18.4%和13.3%,而冬季就诊人数在冷空气日后三天仅增加3.2%.冷空气对疾病影响的滞后时间在夏,秋和冬季随冷空气强度的增加而减少,而春季的滞后时间总是很长.这些发现可为科学应对气候异常导致的人群健康风险提供针对性依据.

Clinical significance of platelet mononuclear cell aggregates in patients with sepsis and acute respiratory distress syndrome

BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.

Respiratory Mechanics, Respiratory Muscle Strength, Control of Ventilation and Gas Exchange in Patients with Autoimmune Liver Disease

Objectives: To assess respiratory elastance and resistive properties in patients with autoimmune liver disorders using the passive relaxation expiration technique and compare findings to a group of patients with non-autoimmune liver disease and control subjects. These findings were then related to control of ventilation and gas exchange. A secondary objective was to assess respiratory muscle strength and gas exchange and their relation to respiratory mechanics. Methods: Measurements included respiratory elastance and resistance using the passive relaxation method. Pulmonary function, gas exchange and control of ventilation were assessed using standard methods. Results: a) Compared to control subjects, Ers in patients with liver disease was on average 50% greater than in controls;b) mean respiratory resistance, expressed as the respiratory constants, K1 and K2 in the Rohrer relationship, Pao/V’ = K1 + K2V’, was not different from control resistance;c) mean maximal inspiratory and maximal expiratory pressures averaged 36% and 55% of their respective control values;d) inspiratory occlusion pressure in 0.1 sec (P0.1) was increased and negatively associated with FVC;and e) increases in P0.1, mean inspiratory flow (Vt/Ti) and presence of respiratory alkalosis confirmed the increase in ventilatory drive. Despite inspiratory muscle weakness in patients, P0.1/Pimax averaged 5-fold higher than in control subjects. Conclusions: Despite inspiratory muscle weakness and a V’E similar to that in normal subjects, central drive is increased in patients with chronic liver disease. The increase in ventilatory drive is related to smaller lung volumes and weakly associated with increase in respiratory elastance. Findings confirm that P0.1 is a reliable measure of central drive and is an approach that can be used in the evaluation of control of ventilation in patients with chronic liver disease.