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.

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.

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.

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.

Effects of pulmonary surfactant combined with noninvasive positive pressure ventilation in neonates with respiratory distress syndrome

BACKGROUND Neonatal respiratory distress syndrome(NRDS)is one of the most common diseases in neonatal intensive care units,with an incidence rate of about 7%among infants.Additionally,it is a leading cause of neonatal death in hospitals in China.The main mechanism of the disease is hypoxemia and hypercapnia caused by lack of surfactant AIM To explore the effect of pulmonary surfactant(PS)combined with noninvasive positive pressure ventilation on keratin-14(KRT-14)and endothelin-1(ET-1)levels in peripheral blood and the effectiveness in treating NRDS.METHODS Altogether 137 neonates with respiratory distress syndrome treated in our hospital from April 2019 to July 2021 were included.Of these,64 control cases were treated with noninvasive positive pressure ventilation and 73 observation cases were treated with PS combined with noninvasive positive pressure ventilation.The expression of KRT-14 and ET-1 in the two groups was compared.The deaths,complications,and PaO_(2),PaCO_(2),and PaO_(2)/FiO_(2)blood gas indexes in the two groups were compared.Receiver operating characteristic curve(ROC)analysis was used to determine the diagnostic value of KRT-14 and ET-1 in the treatment of NRDS.RESULTS The observation group had a significantly higher effectiveness rate than the control group.There was no significant difference between the two groups in terms of neonatal mortality and adverse reactions,such as bronchial dysplasia,cyanosis,and shortness of breath.After treatment,the levels of PaO_(2)and PaO_(2)/FiO_(2)in both groups were significantly higher than before treatment,while the level of PaCO_(2)was significantly lower.After treatment,the observation group had significantly higher levels of PaO_(2)and PaO_(2)/FiO_(2)than the control group,while PaCO_(2)was notably lower in the observation group.After treatment,the KRT-14 and ET-1 levels in both groups were significantly decreased compared with the pre-treatment levels.The observation group had a reduction of KRT-14 and ET-1 levels than the control group.ROC curve analysis showed that the area under the curve(AUC)of KRT-14 was 0.791,and the AUC of ET-1 was 0.816.CONCLUSION Combining PS with noninvasive positive pressure ventilation significantly improved the effectiveness of NRDS therapy.KRT-14 and ET-1 levels may have potential as therapeutic and diagnostic indicators.

Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor

BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)patients.Mesenchymal stromal cell-derived microvesicles(MSC-MVs)have been shown to exert antifibrotic effects in lung diseases.AIM To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.METHODS MSC-MVs with low hepatocyte growth factor(HGF)expression(siHGF-MSC-MVs)were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model.Following intubation,respiratory mechanics-related indicators were measured via an experimental small animal lung function tester.Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging.Immunohistochemical,western blotting,ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.RESULTS The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice.Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores.However,low expression of HGF(siHGF-MSC-MVs)significantly inhibited the effects of MSC-MVs(P<0.05).Compared with the ARDS pulmonary fibrosis group,the MSC-MVs group exhibited suppressed expression of type I collagen antigen,type III collagen antigen,and the proteins transforming growth factor-βandα-smooth muscle actin,whereas the siHGF-MVs group exhibited significantly increased expression of these proteins.In addition,pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group,and the effects of the MSC-MVs were significantly inhibited by low HGF expression(all P<0.05).CONCLUSION MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

Outpatient insulin use in type 2 diabetes mellitus and acute respiratory distress syndrome outcomes:A retrospective cohort study

BACKGROUND The impact of type 2 diabetes mellitus(T2DM)on acute respiratory distress syndrome(ARDS)is debatable.T2DM was suspected to reduce the risk and complications of ARDS.However,during coronavirus disease 2019(COVID-19),T2DM predisposed patients to ARDS,especially those who were on insulin at home.AIMTo evaluate the impact of outpatient insulin use in T2DM patients on non-COVID-19 ARDS outcomes.METHODS We conducted a retrospective cohort analysis using the Nationwide Inpatient Sample database.Adult patients diagnosed with ARDS were stratified into insulin-dependent diabetes mellitus(DM)(IDDM)and non-insulindependent DM(NIDDM)groups.After applying exclusion criteria and matching over 20 variables,we compared cohorts for mortality,duration of mechanical ventilation,incidence of acute kidney injury(AKI),length of stay(LOS),hospitalization costs,and other clinical outcomes.RESULTS Following 1:1 propensity score matching,the analysis included 274 patients in each group.Notably,no statistically significant differences emerged between the IDDM and NIDDM groups in terms of mortality rates(32.8%vs 31.0%,P=0.520),median hospital LOS(10 d,P=0.537),requirement for mechanical ventilation,incidence rates of sepsis,pneumonia or AKI,median total hospitalization costs,or patient disposition upon discharge.CONCLUSION Compared to alternative anti-diabetic medications,outpatient insulin treatment does not appear to exert an independent influence on in-hospital morbidity or mortality in diabetic patients with non-COVID-19 ARDS.

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.

Mechanisms and Research Progress of Traditional Chinese Medicine Regulating NF-κB in the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring the relevance of NF-κB and the pathogenesis of this disease,it was found that this disease was mainly associated with inflammation,dysfunction of the endothelial barrier,oxidative stress,impaired clearance of alveolar fluid,and coagulation disorders.Traditional Chinese medicine(TCM)has the characteristics of multitargeting,multipathway effects,and high safety,which can directly or indirectly affect the treatment of ALI/ARDS.This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS.It provides an overview from the perspectives of Chinese herbal monomers,TCM couplet medicines,TCM injections,Chinese herbal compounds,and Chinese herbal preparations,offering insights into the prevention and treatment of ALI/ARDS with TCM.

Steroids in acute respiratory distress syndrome:A panacea or still a puzzle?

Acute respiratory distress syndrome(ARDS)is a unique entity marked by various etiologies and heterogenous pathophysiologies.There remain concerns regarding the efficacy of particular medications for each severity level apart from respiratory support.Among several pharmacotherapies which have been examined in the treatment of ARDS,corticosteroids,in particular,have demonstrated potential for improving the resolution of ARDS.Nevertheless,it is imperative to consider the potential adverse effects of hyperglycemia,susceptibility to hospital-acquired infections,and the development of intensive care unit acquired weakness when administering corticosteroids.Thus far,a multitude of trials spanning several decades have investigated the role of corticosteroids in ARDS.Further stringent trials are necessary to identify particular subgroups before implementing corticosteroids more widely in the treatment of ARDS.This review article provides a concise overview of the most recent evidence regarding the role and impact of corticosteroids in the management of ARDS.

Effect of different ventilation methods combined with pulmonary surfactant on neonatal acute respiratory distress syndrome

BACKGROUND Acute respiratory distress syndrome precipitates is widespread pulmonary injury in impacted individuals,the neonatal respiratory distress syndrome(NRDS),primarily observed in preterm infants,represents a prevalent critical condition in neonatal clinical settings.AIM To investigate the clinical efficacy of various ventilation strategies combined with pulmonary surfactant(PS)therapy in the treatment of NRDS.METHODS A total of 20 neonates diagnosed with respiratory distress syndrome,admitted between May 2021 and June 2022,were randomly assigned to either a research group or a control group.Neonates in the research group received treatment involving high-frequency oscillatory ventilation(HFOV)in conjunction with PS.In contrast,neonates in the control group were administered either controlled mechanical ventilation or synchronous intermittent mandatory ventilation,combined with PS.Arterial blood samples from the neonates in both groups were collected before treatment,as well as 6 h,12 h,24 h,and 48 h post-treatment.These samples underwent blood gas analysis,with measurements taken for pH value,partial pressures of oxygen(O_(2))and carbon dioxide.Concurrently,data was collected on the duration of ventilator use,length of hospitalization time,O_(2) treatment time,treatment outcomes,and complications of the ventilator.RESULTS From 6-48 h post-treatment,both groups demonstrated significant improvements in arterial blood pH and oxygen partial pressure,along with a significant decrease in carbon dioxide partial pressure compared to pre-treatment values(P<0.05).Although these changes progressed over time,there were no significant differences between the two groups(P>0.05).However,the research group had significantly lower X-ray scores,shorter hospitalization time,and less time on O_(2) therapy compared to the control group(P<0.05).Mortality rates were similar between the two groups(P>0.05),but the research group had a significantly lower incidence of complications(P<0.05).CONCLUSION The integration of HFOV combine with PS has proven to effectively expedite the treatment duration,decrease the occurrence of complications,and secure the therapeutic efficacy in managing NRDS.

Acute respiratory distress syndrome and severe pneumonitis after atezolizumab plus bevacizumab for hepatocellular carcinoma treatment:A case report

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and has a high mortality.However,the treatment options for advanced HCC are limited to tyrosine kinase inhibitors,such as sorafenib and lenvatinib.Since previous regimens have an insufficient efficacy,the combination therapy of atezolizumab and bevacizumab(Ate/Bev)has been investigated,which showed an improvement in progression-free and overall survival.However,the adverse events of this combination therapy in advanced HCC have not been established.Herein,we report a novel case of an unresectable HCC and acute respiratory distress syndrome(ARDS)after a combination therapy of Ate/Bev.CASE SUMMARY An 82-year-old male visited our outpatient clinic for an incidentally detected liver mass.Liver magnetic resonance imaging and enhanced chest computed tomography(CT)were performed,which showed arterial hyperenhancement with washout in delayed phase suggesting HCC,and a well-defined metastatic solid nodule,respectively.F-18 fluorodeoxyglucose positron emission tomography(PET)-CT exhibited multiple hypermetabolic lesions in the iliac bone,lumbar vertebrae,and femur.Because of the high burden of the intrahepatic tumor,transarterial radioembolization was initially performed;after 37 d,a combination therapy of Ate/Bev was administered.The patient visited the emergency department three days after Ate/Bev treatment complaining of dyspnea.He was diagnosed with severe pneumonitis based on CT.Despite administering oxygen via a high-flow nasal cannula,the P/F ratio was only 74;therefore,the patient was diagnosed with ARDS based on the overall examination results.Low tidal volume with high positive end-expiratory pressure,sedative agents combined with a neuromuscular blocker,and a systemic steroid were promptly applied to manage the ARDS.However,the patient did not recover from the hypoxia and expired 31 h after being admitted.CONCLUSION Clinicians should be aware of severe pneumonitis due to the immune-related adverse events of this combination therapy,and patients should be closely monitored after therapy.

Effects of the prone position on arterial blood gas analysis and respiratory parameters of acute respiratory distress syndrome patients:An observational retrospective study

Objective:To investigate the effect of the first prone position on arterial blood gas analysis and respiratory parameters of acute respiratory distress syndrome(ARDS)patients with and without COVID.Methods:This study was conducted retrospectively with 22 COVID-ARDS and 22 non-COVID ARDS patients,who were placed in a prone position for at least 16 hours on the first day at the intensive care unit admission,and arterial blood gas analysis was taken in the pre-prone,prone and post-prone periods.Results:PaO2 were significantly increased in the pre-prone vs.prone comparison in both groups,but the increase in the PaO2/FiO2 ratio was not significant.In comparing the pre-prone vs.post-prone PaO2/FiO2 ratios,there was a significant difference only in the non-COVID ARDS group.Conclusions:The improved oxygenation provided by prone positioning is more permanent with the“post-prone effect”in non-COVID ARDS patients.This can be attributed to the differences in the pathogenesis of the two ARDS types.

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

Acute respiratory distress syndrome(ARDS)is a common and clinically devastating disease that causes respiratory failure.Morbidity and mortality of patients in intensive care units are stubbornly high,and various complications severely affect the quality of life of survivors.The pathophysiology of ARDS includes increased alveolar–capillary membrane permeability,an influx of protein-rich pulmonary edema fluid,and surfactant dysfunction leading to severe hypoxemia.At present,the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema,which primarily improves symptoms,but the prognosis of patients with ARDS is still very poor.Mesenchymal stem cells(MSCs)are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation.MSCs can be isolated from a variety of tissues,such as the umbilical cord,endometrial polyps,menstrual blood,bone marrow,and adipose tissues.Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases.Recently,the potential of stem cells in treating ARDS has been explored via basic research and clinical trials.The efficacy of MSCs has been shown in a variety of in vivo models of ARDS,reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury.This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.

Right ventricle dysfunction does not predict mortality in patients with SARS-CoV-2-related acute respiratory distress syndrome on extracorporeal membrane oxygenation support

BACKGROUND The prognostic role of right ventricle dilatation and dysfunction(RVDD)has not been elucidated in patients with coronavirus disease(COVID)-related respiratory failure refractory to standard treatment needing extracorporeal membrane oxygenation(ECMO)support.AIM To assess whether pre veno-venous(VV)ECMO RVDD were related to inintensive care unit(ICU)mortality.METHODS We enrolled 61 patients with COVID-related acute respiratory distress syndrome refractory to conventional treatment submitted to VV ECMO and consecutively admitted to our ICU(an ECMO referral center)from 31th March 2020 to 31th August 2021.An echocardiographic exam was performed immediately before VV ECMO implantation.RESULTS Males were prevalent(73.8%)and patients with a body mass index>30 kg/m^(2) were the majority(46/61,75%).The overall in-ICU mortality rate was 54.1%(33/61).RVDD was detectable in more than half of the population(34/61,55.7%)and associated with higher simplified organ functional assessment(SOFA)values(P=0.029)and a longer mechanical ventilation duration prior to ECMO support(P=0.046).Renal replacement therapy was more frequently needed in RVDD patients(P=0.002).A higher in-ICU mortality(P=0.024)was observed in RVDD patients.No echo variables were independent predictors of in-ICU death.CONCLUSION In patients with COVID-related respiratory failure on ECMO support,RVDD(dilatation and dysfunction)is a common finding and identifies a subset of patients characterized by a more severe disease(as indicated by higher SOFA values and need of renal replacement therapy)and by a higher in-ICU mortality.RVDD(also when considered separately)did not result independently associated with in-ICU mortality in these patients.

Effects of Early-stage Phased Rehabilitation Training on Acute Respiratory Distress Syndrome:A Systematic Review and Meta-analysis

[Objectives]To systematically evaluate the effects of early-stage phased rehabilitation training on the oxygenation index,ICU length of stay,duration of mechanical ventilation,and occurrence of complications(ventilator-associated pneumonia,pressure ulcers,delirium)in ARDS patients,thus contributing evidence for the clinical application of early-stage phased rehabilitation training.[Methods]The China National Knowledge Infrastructure(CNKI),Wanfang,and other databases were searched.Literature screening,data extraction,and systematic analysis of the included studies were performed using Revman software.[Results]Thirteen randomized controlled trials involving a total of 860 patients were included in this review.The results of the meta-analysis showed that compared to the traditional rehabilitation training group,the early-stage phased rehabilitation training group demonstrated a significant increase in the oxygenation index of ARDS patients[SMD=1.18,95%CI(1.01,1.35),P<0.01],with statistically significant differences.Furthermore,there were significant reductions in ICU length of stay[SMD=-0.70,95%CI(-0.90,-0.50),P<0.01],duration of mechanical ventilation[SMD=-1.15,95%CI(-1.36,-0.94),P<0.01],and occurrence of complications[OR=0.16,95%CI(0.10,0.26),P<0.01],all of which were statistically significant.[Conclusions]Early-stage phased pulmonary rehabilitation training for ARDS patients effectively improves the oxygenation index,shortens ICU length of stay and duration of mechanical ventilation,and reduces complications.These findings support the clinical application and promotion of early-stage phased rehabilitation training.

Single Lung Acute Respiratory Distress Syndrome

Hydatid disease or echinococcosis is a zoonotic parasitic disease. The lungs are the second most commonly affected organ after the liver. Intrathoracic and extrapulmonary hydatid disease can affect the pleura, mediastinum, heart, diaphragm, and chest wall. The unusual location or complications of thoracic hydatid disease can present both a diagnostic problem and a therapeutic and surgical problem. We present results of a case of multilocular thoracic hydatid disease complicated by aortic wall erosion and cystic fistula in a 23-year-old patient who developed acute respiratory distress syndrome (ARDS) on the 4th day after emergency pneumonectomy. The surgery was carried out under the conditions of the auxiliary artificial circulation. This case represented a serious clinical situation with the highest risk to life. The need for immediate respiratory support was due to the development of severe respiratory failure, and the presence of direct and indirect harmful factors of ARDS. The correct choice of modes and techniques of mechanical ventilation resulted in significant and sustained improvement in gas exchange parameters without hemodynamic disorders with a further favorable outcome.

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.

Review:Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism,present strategies and future perspectives of therapies

Acute lung injury/acute respiratory distress syndrome （ALI/ARDS）, which manifests as non-cardiogcnic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.

Early Intratracheal Administration of Corticosteroid and Pulmonary Surfactant for Preventing Bronchopulmonary Dysplasia in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Meta-analysis

There is uncertain result with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. This meta-analysis was designed to evaluate the efficacy and safety of early airway administration (within 2 days after birth) of corticosteroids and pulmonary surfactant (PS) for preventing bronchopulmonary dysplasia (BPD) in premature infants with neonatal respiratory distress syndrome (NRDS). The related studies were retrieved in PubMed, EMBASE, the Cochrane Library, Clinical Trial, CNKI, Wanfang and VIP Database from inception to August 2018. Two reviewers independently screened the studies to ensure that all patients with diagnosis of NRDS were enrolled to studies within 1 day after birth, assessed the quality of included studies by GRADEpro system and extracted the data for review. The meta-analysis was performed by RevMan 5.2 software. A subgroup analysis about inhaled corticosteroid (ICS) delivery method was made between ICS inhalation subgroup [inhalation of ICS by nebulizer or metered dose inhaler (MDI)] and ICS intratracheal instillation subgroup (PS used as a vehicle). Eight randomized controlled trials were enrolled in the meta-analysis, 5 trials of which stated the randomized method, grouping and blinded method, and the follow-up procedures were reported. GRADEpro system showed high quality of 4 trials (5 articles), and the rest 4 trials had moderate quality. Meta-analysis showed that the incidence of BPD was decreased in ICS group, the relative risk (RR) was 0.56 (95% CI: 0.42-0.76), and similar trends were found in ICS inhalation subgroup and ICS intratracheal instillation subgroup, with the corresponding RR being 0.58 (95% CI: 0.41-0.82) and 0.47 (95% CI: 0.24-0.95) respectively. ICS could also significantly reduce the mortality risk as compared with placebo control group (RR: 0.67;95% CI: 0.45-0.99), with RR of ICS inhalation subgroup and ICS intratracheal instillation subgroup being 0.81 (95% CI: 0.34-1.94) and 0.64 (95% CI: 0.41-0.99) respectively. Moreover, the percentage of infants using PS more than one time was lower in ICS group than in the placebo control group, with the RR and 95% CI being 0.55 (95% CI: 0.45-0.67), and that in ICS intratracheal instillation subgroup lower than in ICS inhalation subgroup (RR: 0.56;95% CI: 0.45-0.69, and RR: 0.35;95% CI:0.08-1.52 respectively). There was no significant difference in the incidence of infection or retinopathy of prematurity and neuro-motor system impairment between ICS group and placebo control group, with the corresponding RR being 0.95 (95% CI:0.59-1.52), 0.92 (95% CI: 0.62-1.38) and 1.13 (95% CI: 0.92-1.39), respectively. It was concluded that early administration of ICS and PS is an effective and safe option for preterm infants with NRDS in preventing BPD and reducing mortality, decreasing the additional PS usage, especially for the ICS intratracheal instillation subgroup. Furthermore, the appropriate dose and duration of ICS, combined use of inhalation or instillation of ICS with PS and the long-term safety of airway administration of corticosteroids need to be assessed in large trials.