Objective To evaluate the effect of exogenous pulmonary surfactant(PS) replacement therapy for infants who suffered pulmonary injury after cardiopulmonary bypass. Methods Seven infants (age 0.49±0 82 year, weight 4.87±2.18kg) who depended on respiratory mechanical support with clinical and radiological evidence of pulmonary surfactant sufficiency were enrolled in the study. Oxygen index(OI), artery oxygen saturation(SaO 2) and artery bicarbonate pressure(PaCO 2) were measured at 4, 6, 12, 24, 48, and 72 h after the first application of PS(100mg/kg). At the meantime, maximum spontaneous respiratory tidal volume, chest X ray changes and ventilator time were recorded. Results Compared to the baseline values, OI and SaO 2 increased significantly 4 h after PS therapy, with a maximal increase slope (34.7%, 6.6%) after 24 h. While PaCO 2 decreased significantly 4 h after PS therapy, with a lowest decrease slope (22.8%) after 6 h ( P lt;0.05, 0.01). Spontaneous tidal volume and chest X ray si...更多gn were improved in all infants. The success rate of extubation was 85 7%. Conclusion Exogenous PS replacement therapy could improve pulmonary function for postoperative infants, and highly decrease the ventilator time.
ObjectiveTo explore the clinical value of three early predictive scale of lung injury (ALI) in patients with high risk of acute lung injury (ALI) after lung cancer surgery.MethodsA convenient sampling method was used in this study. A retrospective analysis was performed on patients with lung cancer underwent lung surgery. The patients were divided into an ALI group and a non-ALI group according to ALI diagnostic criteria. Three kinds of lung injury predictive scoring methods were used, including lung injury prediction score (LIPS), surgical lung injury prediction (SLIP) and SLIP-2. The differences in the scores of the two groups were compared. The correlation between the three scoring methods was also analyzed. The diagnostic value was analyzed by drawing receiver operating characteristic (ROC) curves.ResultsA total of 400 patients underwent lung cancer surgery, and 38 patients (9.5%) developed ALI after operation. Among them, 2 cases progressed to acute respiratory distress syndrome and were treated in intensive care unit. There were no deaths. The predictive scores of the patients in the ALI group were higher than those in the non-ALI group, and the difference was statistically significant (all P<0.001). There was a good correlation between the three scoring methods (allP<0.001). The three scoring methods had better diagnostic value for early prediction of high risk ALI patients after lung cancer surgery and their area under ROC curve (AUC) were larger than 0.8. LIPS score performed better than others, with an AUC of 0.833, 95%CI (0.79, 0.87).ConclusionThree predictive scoring methods may be applied to early prediction of high risk ALI patients after lung cancer surgery, in which LIPS performs better than others.
ObjectiveTo explore the effects of inhibition of paxillin phosphorylation on ventilation associated lung injury. MethodsSixty healthy male SD rats were randomly divided into four groups, namely a control group, a protective ventilation group, a high tidal volume ventilation group, and an inhibitor group. The rats in the control group received only tracheotomy and breathe naturally. The rats in the protective ventilation group received protective ventilation for 2 hours. The rats in the high tidal volume ventilation group and the inhibitor group received high tidal volume ventilation for 2 hours. The rats in the inhibitor group additionally received intraperitoneal injection of tyrosine protein kinase inhibitor PP2 before ventilation. All rats were sacrificed and the specimens of lung tissue were collected. The pathological changes of lungs were observed under light microscope and estimated by the diffuse alveolar damage (DAD) score system. The activity of myeloperoxidase (MPO) and the lungs wet/dry (W/D) weight ratio were measured. The expression of tumor necrosis factor-α(TNF-α) in BALF was detected by ELISA. Evans blue (EB) method was used to detect the pulmonary vascular permeability. The expression levels of phosphorylated paxillin (p-paxillin) and paxillin in lung tissue were measured by Western blot. Apoptosis in situ was detected by TUNEL. ResultsThere were significant differences in the W/D ratio, the EB extravasation, DAD score, the MPO activity and the TNF-αexpression in BALF between the high tidal volume ventilation group and the inhibitor group (P < 0.05). The apoptosis rate of each group was sorted from high to low as the high tidal volume ventilation group, the inhibitor group, the protective ventilation group, and the control group. The expression level of p-paxillin was the highest in the high tidal volume ventilation group which was significantly different from other groups (all P < 0.05). There was no significant difference in the expression of paxillin in the protective ventilation group, the high tidal volume ventilation group and the inhibitor group (P > 0.05). ConclusionInhibition of paxillin phosphorylation can significantly alleviate mechanical ventilation associated lung injury.
Objective To study the effects of hyperoxia on ventilator-induced lung injury（VILI） in rats.Methods 48 healthy male SD rats were randomly divided into four groups：Group A received conventional mechanical ventilation（VT=8 mL/kg） with room air，Group B received the same tidal volume as group A with 100% O2，Group C received large tidal volume（VT=40 mL/kg） with room air，group D received the same tidal volume as group C with 100% O2.Arterial blood gases were measured every one hour and oxygenation index（PaO2/FiO2） was calculated.The changes of lung histopathology were assessed by HE staining and observed under light microscope.Wet-to-dry weight ratio（W/D） of left lung，neutrophils and white blood cell（WBC） counts in BALF were measured.TNF-α，IL-1β，and MIP-2 levels in BALF，malondialdehyde（MDA），myeloperoxidase（MPO），and superoxide dismutase（SOD） levels in the lung were assayed，respectively.Results Compared with the Group C，the Group D demonstrated more infiltrating neutrophils in the lung and more destructive changes in the alveolar wall.Meanwhile，the oxygenation index decreased，the WBC and neutrophils counts in BALF increased，and the W/D of left lung was higher in the Group D with significant differences compared with the Group C.Moreover，the BALF levels of TNF-α，IL-1β and MIP-2，the lung levels of MDA increased，and the lung levels of SOD decreased significantly in the Group D compared with those in the Group C.There were no statistical significant differences between the Group B and Group A in all parameters except that MDA levels increased and SOD levels decreased significantly in the Group B.Conclusion Hyperoxia can increase lung injury induced in large tidal volume ventilation in rats，but has mininmal effects in conventional mechanical ventilation.
ObjectiveTo discuss the risk factors of acute respiratory distress syndrome (ARDS) in patients with severe pneumonia.MethodsData of 80 patients with severe pneumonia admitted in our ICU were analyzed retrospectively, and they were divided into two groups according to development of ARDS, which was defined according to the Berlin new definition. The age, gender, weight, Acute Physiology and Chronic Health EvaluationⅡscore, lactate, PSI score and LIPS score, etc. were collected. Statistical significance results were evaluated by multivariate logistic regression analysis after univariate analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the parameter for ARDS after severe pneumonia.ResultsForty patients with severe pneumonia progressed to ARDS, there were 4 moderate cases and 36 severe cases according to diagnostic criteria. Univariate analysis showed that procalcitonin (t=4.08, P<0.001), PSI score (t=10.67, P<0.001), LIPS score (t=5.14, P<0.001), shock (χ2=11.11, P<0.001), albumin level (t=3.34, P=0.001) were related to ARDS. Multivariate logistic regression analysis showed that LIPS ［odds ratio (OR) 0.226, 95%CI=4.62-5.53, P=0.013］ and PSI (OR=0.854, 95%CI=132.2-145.5, P=0.014) were independent risk factors for ARDS. The predictive value of LIPS and PSI in ARDS occurrence was significant. The area under ROC curve (AUC) of LIPS was 0.901, the cut-off value was 7.2, when LIPS ≥7.2, the sensitivity and specificity were both 85.0%. AUC of PSI was 0.947, the cut-off value was 150.5, when PSI score ≥150.5, the sensitivity and specificity were 87.5% and 90.0% respectively.ConclusionsPSI and LIPS are independent risk factors of ARDS in patients with severe pneumonia, which may be references for guiding clinicians to make an early diagnosis and treatment plan.
Objective To investgate the expression of p38 mitogen-activated protein kinase （p38MAPK） in lung tissue of rats with severe acute pancreatitis （SAP）， and to explore the relationship between p38MAPK and pulmonary capillary barrier injury. Methods Forty male and healthy Sprague-Dawley （SD） rats were randomly （random number method） divided into sham operation （SO） group and SAP group， then rats of SAP group were sub-divided into 3， 6， 12， and 24 h group， each group enrolled 8 rats， respectively. SAP model rats were established by injecting 5% sodium taurocholate solution retrograde into the biliopancreatic duct. ELISA method was used to test the serum tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and pathological changes in lung and pancreas tissues were observed by HE staining. Immunohischemistry method was used to detect phosphorylated p38 （p-p38） protein and aquaporin 1 （AQP1） protein of lung tissues. The expression level of AQP1 mRNA was measured by quantitative real-time PCR. Results Hyperemia， edema， and inflammatory cell infiltration were observed in lung tissues， abundance of necrosis， part gland structure fuzzy or even disappear were observed in pancreas tissues of all 4 time point groups. Compared with SO group， levels of serum TNF-α and IL-1β were significantly higher in 4 time point groups （P＜0.05）. Lower expression level of p-p38 protein was detected in lung tissues of SO group， while in the early stage of SAP （SAP 3 h group）， the expression level of p-p38 protein significantly increased， which peaked in 6 h group and was still higher than SO group in 24 h group （P＜0.05）. Compared with SO group， the expression levels of AQP1 mRNA and protein were significantly lower in all 4 time point groups （P＜0.05）， which had negative correlation with the levels of serum TNF-α，IL-1β， and the expression level of p-p38 protein （r=-0.87， P＜0.05；r=-0.88， P＜0.05；r=-0.78， P＜0.05）. Conclusion The decrease of AQP1 protein in lung tissue is one of the vital causes for pulmonary capillary barrier injury in SAP， which probably works by the activation of p38MAPK and the excessive release of inflammatory cytokines.
Objective To study the protective effects and mechanism of intermittent ventilation on lung injury during cardiopulmonary bypass(CPB). Methods Twenty-four patients with rheumatic heart disease (RHD) were divided into two groups with random number table: treatment group (n=13),given intermittent ventilation once every 5 minutes during CPB; control group (n=11),no ventilation during CPB. Blood samples were obtained preoperatively. A bronchoalveolar lavage was performed at 2 hours after CPB. The numbers of granulocytes, total protein (TP) and tumor necrosis factor-alpha(TNF-α) content in the bronchoalveolar lavage fluids(BALF) were measured, and lung oxygenate index (OI) were measured preoperatively and 1 hour, 4 hours after CPB termination,respectively. Results The numbers of granulocytes, TP and TNF-α content of treatment group in the BALF were significantly lower than those of the control group (Plt;0.01, P=0.02,0.02),and the lung OI of treatment group at 1 hour and 4 hours after CPB termination was also significantly lower than that of the control group(Plt;0.05); a significant increase of lung OI occurred in both groups at 1 hour and 4 hours after CPB when compared with the same group at baseline before CPB(Plt;0.05). Conclusion Intermittent ventilation has the protective effects on lung injury during CPB by decreasing granulocytes adhesion and alleviating lung inflammatory reaction and endothelial cells injury.
Objective To determine the risk factors for acute lung injury（ALI） early after orthotopic liver transplantation.Methods The perioperative clinical data of all 275 patients who had undergone orthotopic liver transplantation were analysed retrospectively.Several statistically significant risk factors were screened out with univarite analysis，then independent risk factors were determined with multivariate stepwise logistic regression analysis.Results Of the all 275 patients，the morbidity of ALI was 9.8% with a mortality of 22.2%.Univariate analysis showed that the occurrence of ALI was associated with preoperative infection，severe hepatitis，renal dysfunction，massive blood transfusion in operation，long non-hepatic period and long cold ischemic time.Multivarite stepwise logistic regression analysis revealed that the independent risk factors for ALI were massive blood transfusion in operation（OR=12.12，95%CI 0.958-25.364），longer non-hepatic period（OR=1.23，95%CI 1.034-1.410） and longer cold ischemic time（OR=22.35，95%CI 1.266-43.421）.Conclusion Massive blood transfusion in operation，long non-hepatic period and long cold ischemic time were independent risk factors for ALI early after orthotopic liver transplantation.
Objective To determine if mesenchymal stem cells ( MSCs) could be reconstructed as a vehicle for angiopoietin-1 ( Ang1) gene therapy in lung injury. Methods MSCs were obtained from adult male inbred mice and cultured to passage four. The cells were identified by fluorescence-activated cell sorting ( FACS) analysis and cell differentiation detection. Lentiviral vectors contained GFP and Ang1 gene were conducted in 293T cells through three plasmids co-transfection method. Then MSCs were transduced with Ang1 gene efficiently through lentiviral vectors. The mRNA expression of Ang1 in MSCs was detected by RT-PCR before and after transfection. Also fluorescence from MSCs was detected by fluorescence microscope every day after transfection. Two hours after LPS inhalation, mice were infused via jugular veinwith normal saline ( NS group) , lentiviral vector carrying Ang1 ( Ang1 group) , lentiviral vector carrying GFP ( MSCs group) , and lentiviral vector carrying Ang1 /GFP ( MSCs-Ang1 group) , respectively. Kaplan-Meier survival analysis was performed to compare the effects of MSCs-Ang1 on survival. And ectogenic MSCs origined lung cells were investigated in receipt mice. Results After passaged and purification,MSCs were confirmed to have the potential of differentiation. The lentiviral vectors carrying Ang1 and GFP were also identified. After transfection, the mRNA expression of Ang1 in MSCs was enhanced. Through the fluorescence microscope,MSCs get the most green fluorescence expression five days after the transfection when MOI was 20. Kaplan-Meier survival analysis showed that MSCs-Ang1 infusion had improved survival rates of lung injury rats compared with the control, but it did not reach statistical significance ( P = 0. 066) . Cells expressing GFP in lung tissues can be observed after MSCs were transplanted in vivo. Conclusions MSCs expressing Ang1 high can be constructed through lentiviral vector transfer, and MSCs-origined cells can be detected in receipt lungs after transplantation. So MSCs may serve as a vehicle for gene therapy in lung injury.
ObjectiveThe role of ferroptosis-related genes in the occurrence and development of lung injury caused by sepsis was investigated by bioinformatics methods, and the closely related genes were predicted. MethodsThe Dataset GSE154653 was downloaded from the gene expression database (GEO), and a total of 8 cases of microarray gene set were included in normal group and lipopolysaccharide (LPS)-induced sepsis lung tissue. The differential expression genes (DEGs) were screened out under conditions of |log2 FC|>1 and P.adj<0.05. Meanwhile, the selected DEGs were combined with the driver and suppressor genes of ferroptosis downloaded from the ferroptosis database (FerrDb) to obtain the differential genes associated with ferroptosis in sepsis (Fe-DEGs). These Fe-DEGs were further analyzed using R language, DAVID, and STRING online tools to identify GO-KEGG functions and pathways, and the construction of PPI network. Results The Bioinformatics approach screened out 3533 DEGs and intersected 53 key genes related to ferroptosis. The further biological process (BP) of GO enrichment analysis mainly involves the positive regulation of transcription, the positive regulation of RNA polymerase II promoter transcription, the cytokine mediated signaling pathway, and the positive regulation of angiogenesis. The molecular function (MF) mainly involves the same protein binding, transcriptional activation activity and REDOX enzyme activity. The pathways are enriched in iron death, HIF-1 signaling pathway and AGE-RAGE signaling pathway. Five key Fe-DEGs genes were screened by constructing PPI network, including CYBB, LCN2, HMOX1, TIMP1 and CDKN1A. Conclusion CYBB、LCN2、HMOX1、TIMP1 and CDKNIA genes may be key genes involved in ferroptosis of lung tissue caused by sepsis.