Cellular and molecular mechanisms of Notch signal in pulmonary microvascular endothelial cells after acute lung injury

Abstract This study focused on the effect and mechanism of Notch signal on pulmonary microvascular endothelial cells (PMVECs) following acute lung injury. PMVECs were cultured in vitro and randomly divided into eight groups. Grouping was based on whether cells were co-cultured with T cells (splenic CD4+T cells were isolated using MACS microbeads) and the level of Notch expression: Normal group and Normal+T cells group, Model group and Model+T cells group, Notch low-expression group and Notch low-expression+T cells group, and Notch overexpression group and Notch overexpression+T cells group. Except for the Normal group and Normal+T cells group, all other groups were treated with 500 μL lipopolysaccharide (1 μg/mL). The expression of VE-cadherin and Zo-1 protein in the Model group (with or without T cells) was lower than that in the normal group (with or without T cells), their expression in the Notch low-expression group (with or without T cells) was significantly increased, and their expression in the Notch overexpression group (with or without T cells) was significantly decreased. Compared with the normal+T cells group, the number of Treg cells in the Notch low-expression+T cells group decreased significantly (P<0.01). The number of Th17 cells in the Notch overexpression+T cells group was higher than that in the Model+T cells group (P<0.01), while the number of Treg cells decreased (P<0.01). Our results demonstrated that activated Notch signal can down-regulate the expression of the tight junction proteins VE-Cadherin and Zo-1 in PMVECs and affect Th17/Treg immune imbalance. Autophagy was discovered to be involved in this process.

Clearance effect of regulation of serine/threonine protein kinase-1 signaling pathway by insulin on pulmonary edema in mice with acute lung injury / 中国生物制品学杂志

@#Objective To investigate the mechanism of insulin alleviating pulmonary edema in mice with acute lung injury(ALI) by serine/threonine protein kinase-1(SGK1).Methods 32 male adult C3H/HeN mice were randomly divided into control group(only pumped with the same amount of normal saline as the treatment group),ALI group(continuously pumped with the same amount of normal saline as the treatment group after modeling),treatment group [continuously pumped with 0.1 U/(kg·h) of insulin through jugular vein after establishing ALI model] and SGK1 siRNA group[continuously pumped with 0.1 U/(kg·h) of insulin and given SGK1 siRNA(75 μg SGK1 siRNA diluted in 100 μL saline) simultaneously after establishing ALI model] with 8 mice in each group.After 8 h,the mice were killed for arterial blood gas analysis(1 h after establishment of the model) and the changes of plasma glucose levels were detected(0,1,4and 8 h);The bronchoalveolar lavage fluid(BALF) was collected to detect the content of total protein,and the alveolar epithelial permeability and lung water content were measured;The pathological changes of lung tissue and apoptosis of lung epithelial cells were observed;The protein expressions of alveolar epithelial sodium channel(ENaC) and α_1-Na~+,K~+-ATPase and the phosphorylation level of SGK1 were determined by Western blot.Results There was no significant difference in plasma glucose level of ALI and treatment group at 0,1,4 and 8 h after insulin infusion(t=1.330 0,0.986 0,0.565 7 and 0.724 3,P=0.204 7,0.340 7,0.580 6 and 0.480 8,respectively).Compared with ALI group,the partial pressure of oxygen in arterial blood in treatment group increased significantly(t=6.026,P <0.000 1),while the BALF protein content,alveolar epithelial permeability,lung water content and lung epithelial cells apoptosis decreased significantly(t=7.39,5.286,5.651 and 3.312,P <0.000 1,=0.000 4,=0.000 2 and=0.007 8,respectively),and the expression of α-ENaC and α_1-Na~+,K~+-ATPase and the phosphorylation level of SGK1 in lung tissue significantly increased(t=26,18.67 and 8.547,P <0.000 1,<0.000 1 and=0.000 1,respectively);Compared with the treatment group,the BALF protein content,alveolar epithelial permeability,lung water content and lung epithelial cells apoptosis increased significantly in SGK1 siRNA group(t=5.964,3.449,3.148 and 3.520,P=0.000 2,0.006 2,0.010 4 and0.016 9,respectively),while α-ENaC and α_1-Na~+,K~+-ATPase protein expression and SGK1 phosphorylation level decreased significantly(t=13,9.874 and 7.741,P <0.000 1,<0.000 1 and=0.001 5,respectively).Conclusion Exogenous insulin can alleviate the pulmonary edema in ALI mice,which might be mediated via up-regulation of the expressions of α-ENaC and α_1-Na~+,K~+-ATPase by SGK1.

Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [18F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [18F]FBTA has a strong STING binding affinity (Kd = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [18F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [18F]fluorodeoxyglucose ([18F]FDG).

Potential of modulating fibrinolytic activity in intervention of transfusion-related acute lung injury / 中国输血杂志

Transfusion-related acute lung injury (TRALI), with clinical manifestation, diagnosis and pathological mechanism consistent with acute lung injury(ALI), belongs to a sub-category of ALI. Excessive deposition of fibrin in lung is one of the characteristic of ALI, and reversing fibrin formation is of great significance to intervene ALI. The decrease of fibrinolytic activity is one of the important causes of excessive deposition of fibrin in lung, and also the important pathological feature of TRALI. This article discusses the potential of modulating fibrinolytic activity to intervene TRALI from the perspective of regulating the effectiveness of fibrinolytic activity to intervene ALI.

Mechanism of Tanreqing Injection in treatment of acute lung injury based on network pharmacology and molecular docking / 中国中药杂志

This study aimed to explore the mechanism of Tanreqing Injection in the treatment of acute lung injury(ALI) based on network pharmacology and molecular docking. The active components and action targets of Tanreqing Injection were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), PubChem, and SwissTargetPrediction databases, as well as available literature reports. The ALI-related targets were obtained from the GeneCards database and then mapped with Tanreqing Injection targets. Following the construction of "drug-component-potential target" network with Cytoscape 3.6.1, the potential targets were input into STRING to yield the protein-protein interaction(PPI) network, which was plotted using Cytoscape 3.6.1. Then the screened key targets were subjected to gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis based on DAVID database. The top three key targets RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB) and interleukin-6(IL6) were docked to the top three key compounds by PyMOL and AutoDock vina. A total of 58 active components of Tanreqing Injection, 597 corresponding targets and 503 common targets shared by Tanreqing Injection and ALI were fi-gured out, with the key targets AKT1, ALB and IL6 involved. GO and KEGG enrichment analysis yielded 1 445 biological processes and 148 signaling pathways, respectively. Molecular docking verified a good binding ability of the top three key targets to the top three key compounds. The analysis based on network pharmacology and molecular docking uncovered that Tanreqing Injection directly or indirectly regulated the pulmonary capillary endothelial cells and alveolar epithelial cells via anti-inflammation, thus alleviating ALI.

Multiple components of Mahuang Shengma Decoction on prevention and treatment of acute lung injury based on RAGE/NF-κB signaling pathway / 中国中药杂志

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.

Study of pulmonary functions with DLco in acute respiratory distress syndrome/ acute lung injury syndrome

Background: The objective of this is to study the lung functions with DLco in ARDS/ALI survivors; to study and analyse the lung functions in different diseases causing ARDS/ ALI survivors and to analyse the effect of treatment strategies on lung functions with DLco in survivors.Methods: All patients who survived ARDS/ALI illness from January 2008 to July 2009 are selected and follow up for pulmonary function at discharge, 3 months and 6 months were performed post illness were recorded and compared.Results: In the study period, 37 cases were enrolled in the prospective cohort study, out of which 9(24.3%) were suffering from ALI according to American European Consensus definition. There was varied infections etiology causing ARDS/ ALI. Pulmonary function test at discharge were showing normal flow rates and volumes (94.6%), mild restriction in some cases (8.4%) as the patients included in the study does not have any past respiratory illness out of 37(100%) patients of ARDS/ALI discharged from Hospital 21(56.8%) had low DLco and 16 (43.2%) had normal DLco.Conclusions: Diffusion defect is found to be more common in the patients who had mixed infections than the patients who had single infection. There was no effect of steroids on the outcome of the patients in terms of diffusion defect.

Study of etiology and scoring system in acute lung injury and acute respiratory distress syndrome patients

Background: The acute respiratory distress syndrome (ARDS) is a clinical disorder characterized by injury to the alveolar epithelium and endothelial barriers of the lung, acute inflammation, and protein rich pulmonary edema leading to respiratory failure. Present study was carried out to investigate the mortality pattern of ALI/ARDS in the patients and to study the etiological factors leading to ALI/ARDS also to study the clinical pattern in patients with ALI/ARDS.Methods: All patients fulfilling the inclusion criteria as per the 1994 American European Consensus Conference on ARDS/ALI definition of ARDS/ALI were included in the study. On clinical examination the vital parameters were recorded. The respiratory system, abdominal, cardiovascular and central nervous systems were examined in detail. The severity of the illness was measured by the acute physiology and Chronic Health Evaluation (APACHE) Score, Multiple Organ Dysfunction score (MODS), lung injury score (LIS) and Sequential Organ Dysfunction Assessment (SOFA score). These scores were calculated on admission to our intensive care unit.Results: Out of the 65 patients 35 survived and 30 died. A multiple organ dysfunction Score of less than or equal to 4 was seen in 29 patients and more than 4 in 36 patient and a score of less than or equal to 4 was seen in 21 survivors and 8 dead patients, while a score of more than four was found in 14 patients who survived versus 22 patients who died. A lung injury score of less than or equal to 2 was seen in patients and more than 2 in 46 patients and a score of less than or equal to 2 was seen in 14 survivors and 5 non-survivors patients, while a score of more than 2 was found in 21 patients who survived versus 25 patients who died.Conclusions: The commonest etiological conditions leading to ALI/ARDS are pneumonia and tropical diseases including malaria, leptospirosis and dengue. The scoring systems, MODS, LIS and APACHE II are good indicators of the outcome of this condition. They are useful in tropical diseases as well.

Effects of Ghrelin on Inflammatory Signaling Akt,NF-κB and iNOS in Alveolar Macrophages from Septic Rats / 中山大学学报(医学科学版)

[Objective]To investigate the effects of ghrelin on inflammatory signaling protein kinase B(Akt),nuclear factor-κB(NF-κB)and inducible nitric oxide synthase(iNOS)in alveolar macrophage(AM).[Methods]24 Male SD rats were randomly divided into Sham,CLP,CLP+ghrelin,and Sham+ghrelin groups. Cecal ligation and puncture(CLP)was used to induce sepsis. Ghrelin(20 nmol/kg)was administered by intraperitoneal injection at 3 h and 15 h post-operation. Histopathological changes of lungs were observed and scored.AM were extracted from bronchoalveolar lavage fluid(BALF). Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in BALF were detected by ELISA. IL-1β,TNF-α,and IL-6 mRNA in AM were detected by qPCR.NF-κB p65,IκBα,p-IκBα,Akt,p-Akt and iNOS in AM were detected by immunofluorescence(IF)and Western blotting.[Results]The histologic score(6.7±0.8),BALF IL-1β[(146±12)pg/mL]and IL-6[(182±10)pg/mL]from CLP+ghrelin group were respectively 35.4%,44.5% and 46.42% lower than those from CLP group[(10.3±0.7),(263±17)pg/mL,and(273±5)pg/mL],P<0.05.No significant difference was found in BALF TNF-α between CLP group and CLP+ghrelin group.The IL-1β,TNF-α and IL-6 mRNA in AM from CLP+ghrelin group were respectively 54.38%,53.6% and 46.42% lower than those from CLP group,P<0.05. The nuclear NF-κB p65 and cytoplasmic p-IκBα,p-Akt and iNOS from CLP+ghrelin group were respectively 32.58%,45.42%,27.6% and 48.33% lower than those from CLP group,P<0.05. There was no significant difference in all data between Sham group and Sham+ghrelin group.[Conclusion]Ghrelin can decrease the activity of inflammatory signaling proteins Akt,NF-κB and iNOS in AM,therefore restricts AM expressing pro-inflammatory cytokines IL-1β,TNF-α,and IL-6,thus alleviates sep-sis-induced acute lung injury(ALI).

Effect of Toll-like receptor nano-inhibitor P12 on pulmonary inflammation in acute lung injury mice / 上海交通大学学报（医学版）

Objective: To investigate the effect of the Toll-like receptor (TLR) nano-inhibitor P12 on THP-1 derived macrophages and acute lung injury (ALI) mouse model induced by lipopolysaccharides (LPS). Methods: In in vitro experiments, THP-1 cells were differentiated into macrophage-like cells and then treated with LPS in the absence and presence of P12. After 24 h incubation, medium was collected to quantify the secretion of pro-inflammatory cytokines using enzyme-linked immunosorbent assay (ELISA). Six- to eight-week-old C57BL/6 mice were randomly divided into three groups, i.e. PBS control, LPS challenge and P12 pretreatment plus LPS. The bronchial alveolar lavage fluid (BALF) and lung tissue of each mouse were collected, and the acute inflammatory response within lung was evaluated by total cell counts, differential cell counts and ELISA. Pathological injury scores in ALI mice were assessed with hematoxylin and eosin (H-E) staining of lung tissue sections under microscope. Results: In THP-1 derived macrophages, P12 significantly inhibited LPS-induced inflammatory cytokine production. In the LPS-induced ALI mouse model, P12 significantly attenuated the acute inflammatory response and alveolar damage in lung, including reducing the number of total cells and neutrophils in BALF, decreasing the expression of chemokine production (KC and CCL-2), and lowering lung injury scores. Conclusion: P12 exhibits potent anti-inflammatory activity in THP-1 derived macrophages and in the LPS-induced ALI mouse model, providing new concepts for the early treatment of ALI.

Intervention Effects of Methylprednisolone to Acute Lung Injury Model of Rats Induced by Oleic Acid / 医学研究杂志

Objective To observe the intervention effects of methylprednisolone (MPred) to acute lung injury(ALI) model of rats induced by oleic acid.Methods Thirty of Sprague-Dawley rats were randomly divided into three groups which were normal control group (NC,n =6),oleic acid model group (n =12),and MPred group (n =12).Rats were injected with oleic acid at dose of 0.1mg/ kg via caudal vein and then ALI model was established.The rats of NC group were injected with 0.1 mg/kg of normal saline instead of oleic acid.In NC group rats were sacrificed by blood collection at 6h after NS injection.Blood samples and tissues were collected and stored freezing.Samples of the other groups were collected at 2h and 6h after the last treatment.The observation indexes are histomorphology of lung tissue,the wet and dry weight of lung (W/D),index of quantitative assessment (IQA) score,partial pressure of oxygen in artery (PaO2),and SOD,MDA,MMP-9 and TIMP-1 levels in the blood plasma and lung tissue.Results Lung surface hyperemia relieved obviously and pink secretion from trachea of rats in MPred group decreased compared with oleic acid model group.In light microscope,compared with oleic acid model group,effusion of inflammatory cell in alveolar space of rats in MPred group eased.W/D of rats in oleic acid model group advanced obviously compared with that in NC group,W/D of rats in medrol group lowered obviously compared with that in oleic acid model group.IQA scores of rats in oleic acid model group advanced obviously compared with that in NC group,IQA score of rats in MPred group lowered obviously compared with that in oleic acid model group.PaO2 of rats in oleic acid model group lowered obviously compared with that in NC group,PaO2 of rats in MPred group advanced obviously compared with that in oleic acid model group.The level of SOD in plasma and lung tissue of rats in oleic acid model group lowered obviously compared with that in NC group,SOD level in plasma and lung tissue of rats in MPred group advanced obviously compared with that in oleic acid model group.The level of MDA in plasma and lung tissue of rats in oleic acid model group lowered obviously compared with that in NC group,MDA in plasma and lung tissue of rats in MPred group advanced obviously compared with that in oleic acid model group.Compared with the NC group,the level of MMP-9 in the plasma and lung tissue of oleic acid induced ALI rats increased and TIMP-1 levels decreased significantly.The level of MMP-9 in the plasma of rats decreased and TIMP-1 level increased significantly in MPred group at 2h and 6h.Conclusion MPred can improve lung pathological injury,increase PaO2 level,decrease lung W/D ratio and IQA scores by modulating the level or activity of the SOD and MDA and MMP-9 and TIMP-1 in the plasma and lung tissues.It is speculated that the effects of anti-inflammation and anti-exudation of sodium aescinate may due to affecting on oxidative stress response as well as the decomposition and remodeling of extracellular matrix during inflammatory lung injury of acute lung injury rats.

Inhibition effect of flavonoids from Radix tetrastigmae on acute lung injury of aged mice through p38MAPK and NF-κB pathway / 中国药理学通报

Aim To investigate the protective effect of flavonoids from Radix tetrastigmae (RTFs)on lipopo-lysaccharide (LPS)induced acute lung injury (ALI) of aged mice and the mechanism.Methods Aged C57BL/6J mice were bronchially instillated LPS to in-duce ALI.RTFs were orally administered to treat ALI. After 3 days,bronchoalveolar lavage fluid (BALF) was collected to enumerate leukocytes with Wright-Gi-emsa staining,and to detect inflammatory cytokines with ELISA.ELISA and Western blot methods were al-so used to detect the expression of MAPKs and NF-κB in lung tissues.The activity of NF-κB in nucleic pro-tein extract was detected with TransAMkit.Results ALI models were successfully induced through LPS in-stillation.RTFs significantly reduced leukocyte,espe-cially neutrophil infiltration in BALF,inhibited IL-1 β, IL-6,IL-1 2p40,TNF-αand sTNF-R1 secretion,and improved pathohistological change of lung tissues.Be-sides,RTFs significantly attenuated the phosphoryla-tion of p38MAPK,NF-κB and the activity of NF-κB. Conclusion RTFs inhibits LPS-induced ALI through p38MAPK and NF-κB pathway and exhibits significant anti-inflammation effect on aged mice.

Characterization of oleic acid-induced acute respiratory distress syndrome model in rat.

Animal studies using oleic acid (OA) model to produce acute respiratory distress syndrome (ARDS) have been inconsistent. Therefore, the present study was undertaken to establish an acute model of ARDS in rats using OA and to characterize its effect on cardio-respiratory parameters and lethality. The trachea, jugular vein and femoral artery of anesthetized adult rats were cannulated. A dose of OA (30-90 µL; iv) was injected in each animal and changes in respiratory frequency (RF), heart rate (HR) and mean arterial pressure (MAP) were recorded. Minute ventilation and PaO2/FiO2 (P/F) ratio were also determined. At the end, lungs were excised for determination of pulmonary water content and histological examination. At all doses of OA, there was immediate decrease followed by increase in RF, however at 75 and 90 µL of OA, RF decreased abruptly and the animals died by 63 ± 8.2 min and 19 ± 6.3 min; respectively. In all the groups, HR and MAP changes followed the respiratory changes. The minute ventilation increased in a dose-dependent manner while the values of P/F ratio decreased correspondingly. Pulmonary edema was induced at all doses. Histological examination of the lung showed alveolar damage, microvascular congestion, microvascular injury, infiltration of inflammatory cells, pulmonary edema and necrosis in a dose-dependent manner. With these results, OA can be used to induce different grades of ARDS in rats and OA doses of 50, 60 and 75 µL resemble mild, moderate and severe forms of ARDS respectively. Hence, OA model serves as a useful tool to study the pathophysiology of ARDS.

Influence of dexamethasone on foxml gene expression in pulmonary tissue following acute lung injury / 中华急诊医学杂志

Objective To study the foxml gene and its protective effect on the lung tissue of rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), and to observe the dexamethason' s (DEX) impacts on foxml gene and the prognosis of ALI. Method Seventy-two healthy mice were randomly(random number) divid-ed into three groups: control group (A group, n = 24), model group (B group, n = 24) and DEX treatment group (C group, n = 24). The observing intervals were respectively set in 24 h, 48 h and 72 hours. At each ob-serving interval, the foxml protein in lung tissue of mice was detected by using immunohistochemistry (IHC), and the expression of foxml gene in lung tissue was detected by using RT-PCR, as well as to observe the pathological changes in lung tissue. Results Comparisons were made between paired groups at 24 h,48 h and 72 h intervals in which the expression of foxml mRNA and the level of foxml protein in lung tissue of mice in C group were signifi-cantly higher than those in B group (P < 0.05), and those in B group were significantly higher than those in A group (P < 0.05). The expression of foxml mRNA and the level of foxml protein in lung tissue of mice in B group at 48 h interval were significantly higher than those both at intervals of 72 h and 24 h (P < 0.05), and the those at 72 interval were significantly higher than those at 24 h interval (P < 0.05). Compared with B group, the pathologi-cal changes in lung tissue of mice in C group were lessened. Conclusions In both model group and dexamethasone treatment group, the expression of foxml mRNA and the level of foxml protein in lung tissue of mice are increased significantly. Dexamethasone lessens the injury of both vascular endothelial cells and alveolar epithelial ceils of lung tissue, and it also significantly increases the expression of foxml mRNA and the level of foxml protein.

Nonventilatory medical treatments for acute respiratory distress syndrome and acute lung injury / 대한내과학회지

Over the past decade, the ventilator management for acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) have yielded improved outcomes. However, studies of the pharmacologic management of ARDS and ALI have been less effective. ARDS/ALI is a heterogeneous disease entity. Although most drug trials in ARDS or ALI have been demonstrated to be ineffective in improving outcomes, some studies suggest that targeting treatments at subgroups of patients may be beneficial. Corticosteroids have good short-term effects when given sooner than 2 weeks. Surfactant may be beneficial in direct lung injury patients. Anticoagulants may have improved outcomes in the severe patients with vascular disease. Recently, ARDS Networks reported the 'conservative fluid management strategy'. This promising fluid strategy showed beneficial effect on outcomes without serious complications. This article reviews the recent research on the Nonventilatory pharmacologic managements for patients with ARDS/ALI.

Lipopolysaccharide "Two-hit" Induced Refractory Hypoxemia Acute Respiratory Distress Model in Rats / 华中科技大学学报（医学）（英德文版）

cs the pathological process of ARDS.

Analysis of factors of impacting on the outcomes of patients with ALI/ARDS / 中华急诊医学杂志

Objective To investigate the factors influencing the outcomes of patients with ALI/ARDS.Method Data of 63 patients with ALI/ARDS in ICU,Cancer Hospital,Chinese Academy of Medical Science,from January 2005 to December 2006,were retrospectively analyzed.Patients were divided into survivor group(n=39)and non-survivor group(n=24)according to different outcomes,and equally,patients were classified in the rcspect of different causes as pulmonary origin and extra-pulmonary origin.Results The incidence of ALI/ARDS was 5.2%(63/1201)in ICU.The univariate analysis showed that the differences in the length of mechanical ventilation(P=0.028),blood creatinine level(P=0.031),oxygenation index(P=0.023),between survivor group and non-survivor group.In addition,the differences in acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores and sequential organ failure assessment(SOFA)on the admission day were significant between survival group and non-survival group(P<0.001,respectively).Logistic regression analysis showed that APACHE Ⅱ scores was the only independent predictor of the mortality in patients with ALI/ARDS(P=0.015,OR:3.809,95%CI:1.295～11.203).There was no significant difference in one-year survival between pul-monary origin cause of ALI/ARDS group and exwa-pulmonary origin cause of ALI/ARDS group(63.9% vs.55.4%).There was significant difference in one-year survival between ARDS and ALI group(44.9% vs.88.9%,P<0.05).Conclusions APACHE Ⅱscores on the admission day of patients is the only independent predictor of the mortality in patients with ALI/ARDS,whereas the underlying cause of ALI/ARDS does not matter to the survival of patients.

Effects of active ingredients from Coleus forskohlii on human neutrophil / 中华急诊医学杂志

Objective To study the effect of plant Coleus forskohlii active elements Isoforskolin(ISOF)and CT-E(analogs mixture of Isoforskolin)on human neutrophill(PMN)in vitro in order to uncover the mechanism of their properties of mitigating acute lung injury(ALI).Method The effects of ISOF and CF-E on PMN aggregation induced by N-formyl-methiony-leucyl-phenylalanine(fMLP)was performed by using a 4-channel platelet aggregometer.Cytometry Was applied to analyze the effect of tested samples on adhension between PMN and endothelial cells(ECV-304)activated by using lipopolysaccharides(LPS).Expression of LPS-induced PMN adhension molecules was determined with flow cytometry.Radioimmunoassay Was applied to detect the level of TNT-α liberated bv PMN and intracellular cyclic adenosine monophosphate(cAMP)level of PMN.Results It was found that ISOF(25,50,100 μmnol/L)and CF-E(1.25,2.5,5 mg/ml)inhibitted PMN aggregation induced by fMLP,PMN adhemion to ECV-304 indeed by LPS,expression of PMN adhesion molecules,and TNF-α level released by PMN.ISOF and CF-E also increased intracellular cAMP level of PMN.Condusions ISOF and CF-E inhibit PMN aggregation,adhension and adhension molecules,and TNF-α released by PMN,while they increase intracellular cAniP level of PMN.It suggests that their specific alleviating the ALI by the mechanism of the modulation of PMN function.

Protective effect of Ginaton on lipopolysaccaride-induced acute lung injury in rats / 中华急诊医学杂志

Objective To investigate the effects of Ginaton on acute lung injury (ALI) induced by lipopolysaccaride (LPS).Methods The acute lung injury rat model was induced by receiving 5 mg/kg LPS injection in tail vein.A total of 63 Wistar rats were divide into 3 groups without caring sex.Saline control group,LPS treated group and Ginaton treated group.The samples of different groups were collected 2 h,6 h,and 10 h after tail vein administration.Serum soluble cell ashesion molecule-1 (sICAM-1) was measured by ELISA,immunohistochemical staining and Western blotting of NF-kB were performed on sections of lung specimens.Results The acute lung injury rat model was successfully induced by receiving LPS injection in tail vein.The sICAM-1 levels increased more in Ginaton treated group than those in Saline control group (P＜0.01),and the increase in LPS treated group were the highest.By immunohistochemical staining,the positive NF-kB cells in Ginaton treated group were much less than those in LPS treated group (P＜0.01),and in Saline control group were least (P＜0.01).The results of the Western-blot method were consistent with immunohistochemical method.Conclusion ALI could be induced by LPS,Ginaton showed a protective effect through probably inhibiting activation of NF-kB on LPS-induced-ALI in this animal model.

The changes of phosphodiesterase-4 activity in rat acute lung injury / 中国药理学通报

Aim To investigate the changes of phosphodiesterase4(PDE4,type 4 cAMP-specific PDE) activity,TNF-? and neutrophil recruitment in experimental rat lung injury(ALI).Methods ALI in the rat was induced by lipopolysacdharide(LPS).PDE4 activity was measured with HPLC,and the level of TNF-? was detected with ELISA,neutrophil infiltration in bronchoalveolar lavage fluid(BALF) and lung tissues was detected by cell count and morphological analysis.Result Lung tissue PDE4 activity significantly increased as early as 1 h,peaked 6 h,and then markedly lowered at 24 h after intratracheal administration of LPS,while there was a same time-course change of total white cell and neutrophil in the BALF(r=0.83,P