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.

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.

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.

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.

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.

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.

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.

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.

Ulinastatin for acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis

AIM: To investigate the efficacy and safety of ulinastatin for patients with acute lung injury(ALI) and those with acute respiratory distress syndrome(ARDS).METHODS: A systematic review of randomized controlled trials(RCTs) of ulinastatin for ALI/ARDS was conducted. Oxygenation index, mortality rate [intensive care unit(ICU) mortality rate, 28-d mortality rate] and length of ICU stay were compared between ulinastatin group and conventional therapy group. Meta-analysis was performed by using Rev Man 5.1.RESULTS: Twenty-nine RCTs with 1726 participants were totally included, the basic conditions of which were similar. No studies discussed adverse effect. Oxygenation index was reported in twenty-six studies(1552 patients). Ulinastatin had a significant effect in improving oxygenation [standard mean difference(SMD) = 1.85, 95%CI: 1.42-2.29, P < 0.00001, I2 = 92%]. ICUmortality and 28-d mortality were respectively reported in eighteen studies(987 patients) and three studies(196 patients). We found that ulinastatin significantly decreased the ICU mortality [I2 = 0%, RR = 0.48, 95%CI: 0.38-0.59, number needed to treat(NNT) = 5.06, P < 0.00001], while the 28-d mortality was not significantly affected(I2 = 0%, RR = 0.78, 95%CI: 0.51-1.19, NNT = 12.66, P = 0.24). The length of ICU stay(six studies, 364 patients) in the ulinastatin group was significantly lower than that in the control group(SMD =-0.97, 95%CI:-1.20--0.75, P < 0.00001, I2 = 86%). CONCLUSION: Ulinastatin seems to be effective for ALI and ARDS though most trials included were of poor quality and no information on safety was provided.

Acute lung injury and acute respiratory distress syndrome： experimental and clinical investigations

Acute lung injury （ALl） or acute respiratory distress syndrome （ARDS） can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALl or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Acute respiratory distress syndrome and lung injury: Pathogenetic mechanism and therapeutic implication

To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide(NO) through the inducible NO synthase(i NOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In con-scious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Effects of dynamic ventilatory factors on ventilatorinduced lung injury in acute respiratory distress syndrome dogs

BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries （VILI） and to explore its potential mechanisms.METHODS： Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.RESULTS： IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-a ray degree of group B was significantly higher than that in the other groups （P〈0.01）, especially in group C （P〉0.05）. The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.CONCLUSION： Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.

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.

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.

Basic and clinical research progress in acute lung injury/acute respiratory distress syndrome

Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS) is an acute progressive respiratory failure caused by severe infection, trauma, shock, poisoning, inhaled harmful gas, acute pancreatitis, and pathological obstetrics. ALI and ARDS demonstrate similar pathophysiological changes. The severe stage of ALI is defined as ARDS. At present, a significant progress has been achieved in the study of the pathogenesis and pathophysiology of ALI/ARDS. Whether or not ALI/ARDS patients can recover depends on the degree of lung injury, extra-pulmonary organ damage, original primary disease of a patient, and adequacy in supportive care. Conservative infusion strategies and protective lung ventilation reduce ARDS disability and mortality. In this study, the pathogenesis of ALI/ARDS, lung injury, molecular mechanisms of lung repair, and conservative infusion strategies and pulmonary protective ventilation are reviewed comprehensively.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

Effects of pulmonary stretch reflex on lung injury in rabbits with acute respiratory distress syndrome

BACKGROUND： Pulmonary stretch reflex plays an important role in regulation of respiratorymovement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury inrabbits with acute respiratory distress syndrome （ARDS）.METHODS： ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilatedwith neurally adjusted ventilatory assistance （NAVA） with a tidal volume （VT） of 6 mL/kg and theelectrical activity of diaphragm （EAdi）-determined positive end expiratory pressure. After isolation ofthe bilateral vagus nerve trunk, the rabbits were randomized into two groups： sham operation （SHAM）group （n=5） and bilateral vagotomy （VAG） group （n=5）. Gas exchange and respiratory mechanicswere detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively.Pulmonary permeability index, pathological changes and infl ammatory response were also measured.RESULTS： Compared with the SHAM group, PaO2/FiO2 in the VAG group decreased signifi cantly2 and 3 hours after ventilation （P〈0.05）. There was no significant difference in PaCO2 betweenthe SHAM and VAG groups （P〉0.05）, and the VAG group had a high VT, peak pressure （Ppeak）,and mean pressure （Pm） compared with the SHAM group 1, 2, 3 hours after ventilation （P〈0.05）.Compared to the SHAM group, dead space fraction （VD/VT） and respiratory system elastance （Ers）in the VAG group increased （P〈0.05） and static pulmonary compliance （Cst） decreased markedly（P〈0.05） after ventilation for 3 hours. Lung wet/dry weight ratio （W/D） （8.4±1.2 vs. 6.6±1.0）, lung injuryscore （6.3±1.8 vs. 3.8±1.3）, tumor necrosis factor-# （TNF-#） （779±372 pg/mL vs. 355±130 pg/mL）and interleukin-8 （IL-8） （169±21 pg/mL vs. 118±17 pg/mL） increased significantly in the VAG groupcompared with the SHAM group （P〈0.05）.CONCLUSION： Lung injury is aggravated after bilateral vagotomy, demonstrating thatpulmonary stretch refl ex may have protective effect on the lung.