Degree Of Lung Injury Research Articles

Effect of MiR-16 on Acute Lung Injury in Neonatal Rats Through Regulating NF-κB Pathway

Acute lung injury represents a widespread, variable type of lung injury characterized by a low oxygen level in the blood, non cardiogenic pulmonary edema, low lung compliance and extensive capillary leakage. In our study, the Wistar rat mode of ALI was established using lipopolysaccharide (LPS). The rats were randomly divided into normal control (NC) group (n = 12) and miR-16 overex-pression group (n = 12), and they were transfected with empty vector and miR-16 overexpression virus, respectively. The lung tissues were extracted in both groups, and then the expression levels of miR-16 and NF-κB were detected via fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the association between their expressions was analyzed via Pearson correlation analysis. Moreover, the morphological changes in lung tissues were detected via hematoxylin-eosin (HE) staining, and the differences in the wet/dry weight (W/D) ratio and the pathomorphological score of lung tissues were compared between the two groups. The expression level of NF-κB was detected via immunohistochemistry (IHC) and Western blotting. Our results showed that, there were different degrees of lung injury in lung tissues in both groups. In miR-16 overexpression group, the W/D ratio was significantly higher than that in NC group (P < 0.05), and the pathomorphological score was also significantly higher than that in NC group (P < 0.05). The results of RT-PCR revealed that the mRNA levels of miR-16 and NF-κB in miR-16 overexpression group were 2.5 and 3.7 times higher than those in NC group. The results of Western blotting and IHC also showed that the activity of NF-κB in lung tissues was evidently enhanced in miR-16 overexpression group compared with that in NC group. According to the Pearson correlation analysis, there was a significant positive correlation between the mRNA levels of miR-16 and NF-κB in lung tissues (r = 0.705, P = 0.012). In conclusion, miR-16 activates the NF-κB pathway to initiate a series of inflammatory responses, thereby contributing to the occurrence of ALI in rats.

Three Ingredients of Safflower Alleviate Acute Lung Injury and Inhibit NET Release Induced by Lipopolysaccharide.

Xuebijing injection is a Chinese herb compound to treat sepsis in China, but it contains many different kinds of components, and each component may have different effects in treating sepsis. The present study was performed to investigate the effect of three ingredients of Xuebijing, safflor yellow A (SYA), hydroxysafflor yellow A (HSYA), and anhydrosafflor yellow B (AHSYB), in lipopolysaccharide- (LPS-) induced acute lung injury (ALI). LPS (10 mg/kg) was injected intratracheally to induce acute lung injury in mice, which were then treated with SYA, HSYA, and AHSYB. The blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected to detect degree of lung injury, level of inflammation, and neutrophil extracellular traps (NETs). In vitro experiments were performed using HL-60 cells stimulated with phorbol myristate acetate (PMA). Lung injury induced by LPS was alleviated by SYA, HSYA, and AHSYB as demonstrated by the histopathologic test. The three components inhibit LPS-induced elevation of the levels of inflammatory factors and wet-to-dry weight ratio as well as the amount of protein and cells in the BALF. They also induced a remarkably less overlay of myeloperoxidase (MPO) and histone in the immunofluorescence assay and reduced level of MPO-DNA complex in plasma. The in vitro assay showed a similar trend that the three components inhibited PMA-induced NET release in neutrophil-like HL-60 cells. Western blot demonstrated that phosphorylation of c-rapidly accelerated fibrosarcoma (c-Raf), mitogen-activated protein kinase ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) in the lungs of LPS-challenged mice, and PMA-treated HL-60 cells were all significantly reduced by SYA, HSYA, and AHSYB. Therefore, our data demonstrated that three components of XBJ, including SYA, HSYA, and AHSYB, showed a protective effect against LPS-induced lung injury and NET release.

Salvia miltiorrhiza Injection Alleviates LPS-Induced Acute Lung Injury by Adjusting the Balance of MMPs/TIMPs Ratio.

Salvia miltiorrhiza injection (SMI) is a classical traditional Chinese medicine, which plays an active role in the treatment of many diseases such as promoting blood circulation, removing blood stasis, reducing inflammatory reaction, and improving acute lung injury (ALI). Previous studies have shown that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the pathophysiological process of ALI. However, the relationship between SMI and MMPs/TIMPs remains unclear. In this study, Wistar rats were randomly divided into control group (NC), Salvia miltiorrhiza group (SM), lipopolysaccharide group (LPS), and Salvia miltiorrhiza treatment group (Tsm). The four groups were subdivided into four time points (2, 6, 12, and 24 hours), and specimens were collected after animal sacrifice at each time point. Serum TNF-α and IL-6 levels were detected by ELISA. The degree of lung injury was determined by lung tissue hematoxylin-eosin staining, lung wet/dry weight (W/D) ratio, and lung permeability index. The changes in lung MMPs/TIMPs protein and mRNA were detected by Western blot and real-time quantitative PCR. The results showed that rats injected with LPS experience acute lung injury, and the ratio of MMPs/TIMPs in lung tissues increased gradually with time. In the Tsm group, the ratio of MMPs/TIMPs decreased gradually, and likewise, the balance was gradually restored, while indicators related to lung injury were gradually declined. These data suggest that SMI alleviates LPS-induced acute lung injury; this protective effect may be related to regulation of the balance of MMPs/TIMPs ratio.

Keratinocyte Growth Factor-2 Reduces Inflammatory Response to Acute Lung Injury Induced by Oleic Acid in Rats by Regulating Key Proteins of the Wnt/β-Catenin Signaling Pathway.

Reducing inflammation can effectively relieve acute lung injury (ALI). Objective. To test whether keratinocyte growth factor-2 (KGF-2) can reduce oleic acid-induced inflammation in ALI of rats and explore its possible mechanism. Methods. 45 Sprague-Dawley rats were randomly divided into control group, ALI group, and ALI + KGF-2 group. The animal model of acute lung injury was established by injecting 0.1 mL/kg oleic acid into the tail vein of rats. Rats in the control group were injected with equal volume of normal saline (NS). Each group needs pretreatment 72 hours before the preparation of the acute lung injury model. The control group and ALI group were instilled with 5 ml/kg NS through the airway, and the same amount of KGF-2 was instilled in the ALI + KGF-2 group. It takes 8 hours to successfully prepare the ALI model. Observe the pathological changes of lung tissue through light microscopy, ultrastructural changes through electron microscopy, and the lung wettability/dry weight (w/d) ratio and lung permeability index (LPI). By detecting changes in inflammatory factors in lung tissue and changes in the number of BALF cells, the changes in inflammation in each group were observed. The expressions of Wnt5a, β-catenin, and APC in lung tissue were detected by immunohistochemistry and Western blot. The changes of key proteins in Wnt/β-catenin signaling pathway in the lung tissue of each group were observed. Result. Compared with the ALI group, after KGF-2 pretreatment, the degree of lung injury was reduced, the expression of inflammatory factors was reduced, and the number of red blood cells and white blood cells in BALF was reduced. It can also be observed that the expression of Wnt5a, β-catenin, and APC, a key protein in the Wnt/β-catenin signaling pathway, is reduced. The analysis showed that the number of inflammatory factors, red blood cells, and white blood cells in BALF was positively correlated with the expression of Wnt5a, β-catenin, and APC. Conclusion. KGF-2 may reduce the inflammatory response in ALI induced by oleic acid by regulating key proteins in the Wnt/β-catenin signaling pathway.

Pre-Treatment with Ten-Minute Carbon Dioxide Inhalation Prevents Lipopolysaccharide-Induced Lung Injury in Mice via Down-Regulation of Toll-Like Receptor 4 Expression.

Various animal studies have shown beneficial effects of hypercapnia in lung injury. However, in patients with acute respiratory distress syndrome (ARDS), there is controversial information regarding the effect of hypercapnia on outcomes. The duration of carbon dioxide inhalation may be the key to the protective effect of hypercapnia. We investigated the effect of pre-treatment with inhaled carbon dioxide on lipopolysaccharide (LPS)-induced lung injury in mice. C57BL/6 mice were randomly divided into a control group or an LPS group. Each LPS group received intratracheal LPS (2 mg/kg); the LPS groups were exposed to hypercapnia (5% carbon dioxide) for 10 min or 60 min before LPS. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. LPS significantly increased the ratio of lung weight to body weight; concentrations of BALF protein, tumor necrosis factor-α, and CXCL2; protein carbonyls; neutrophil infiltration; and lung injury score. LPS induced the degradation of the inhibitor of nuclear factor-κB-α (IκB-α) and nuclear translocation of NF-κB. LPS increased the surface protein expression of toll-like receptor 4 (TLR4). Pre-treatment with inhaled carbon dioxide for 10 min, but not for 60 min, inhibited LPS-induced pulmonary edema, inflammation, oxidative stress, lung injury, and TLR4 surface expression, and, accordingly, reduced NF-κB signaling. In summary, our data demonstrated that pre-treatment with 10-min carbon dioxide inhalation can ameliorate LPS-induced lung injury. The protective effect may be associated with down-regulation of the surface expression of TLR4 in the lungs.

RADIOLOGIC DIAGNOSTIC'S CAPABILITIES OF LUNG INJURY IN ADULT PATIENTS WITH CYSTIC FIBROSIS

Relevance. The viability of patients is determined by the degree of lung injury despite the fact that cystic fibrosis (CF) is a multiple organ disease. Early diagnosis and adequate treatment complex of cystic fibrosis prolong the lives of patients and improves its quality. Therefore, timely and detailed diagnosis of cystic fibrosis lung is particularly important problem. The central role for its solution belongs to radiological studies. Objective. To refine the radiology’s capabilities in detecting lung changes in case of cystic fibrosis in adult patients and to determine the role of the computed tomography (CT) in the diagnostic process. Materials and methods. The results of radiography and CT scans of 15 patients, for whom the diagnosis of CF was established in adulthood, were analyzed. Results. The most typical radiographic and CT signs of lung damage were determined in adult CF patients. It has been shown that the radiographic changes in the lungs are non-specific for CF patients and are determined by the secondary inflammatory process. The diagnostic capabilities of CT scans in detecting subtle structural changes in the lung tissue and bronchial tree are underlined, which allows to diagnose light and atypical forms of CF in adults, determinate the stage and activity of the pathological process and the effectiveness of the treatment. Findings. The radiation studies were able to define the CF’s specific symptoms of lung lesions. Radiography of the thoracic cavity’s organs is a necessary step in the preliminary diagnosis for adult patients with CF or in the medical emergency's cases. The CT has the greatest diagnostic value in detecting subtle structural and functional specific changes of CF. The regular monitoring using CT scans is necessary for improving the control of the respiratory organs’ state and determine the further tactics for the particular patient.

Impact of Early Life Antibiotic Exposure and Neonatal Hyperoxia on the Murine Microbiome and Lung Injury

Cross talk between the intestinal microbiome and the lung and its role in lung health remains unknown. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have an impact on the preterm lung. We hypothesized that perinatal antibiotic exposure leads to long-term intestinal dysbiosis and increased alveolar simplification in a murine hyperoxia model. Pregnant C57BL/6 wild type dams and neonatal mice were treated with antibiotics before and/or immediately after delivery. Control mice received phosphate-buffered saline (PBS). Neonatal mice were exposed to 95% oxygen for 4 days or room air. Microbiome analysis was performed using 16S rRNA gene sequencing. Pulmonary alveolarization and vascularization were analyzed at postnatal day (PND) 21. Perinatal antibiotic exposure modified intestinal beta diversity but not alpha diversity in neonatal mice. Neonatal hyperoxia exposure altered intestinal beta diversity and relative abundance of commensal bacteria in antibiotic treated mice. Hyperoxia disrupted pulmonary alveolarization and vascularization at PND 21; however, there were no differences in the degree of lung injury in antibiotic treated mice compared to vehicle treated controls. Our study suggests that exposure to both hyperoxia and antibiotics early in life may cause long-term alterations in the intestinal microbiome, but intestinal dysbiosis may not significantly influence neonatal hyperoxic lung injury.

Immediate Prone Positioning After Massive Gastric Aspiration Reduces Lung Injury Possibly by Attenuating Interleukin-6-Mediated Lung-Tissue Inflammation in Pigs.

Gastric aspiration, which can cause acute, diffuse, inflammatory lung injury, is of particular concern in critically ill patients. This study aimed to determine the effects of immediate prone positioning on the degree of lung injury and inflammatory response induced by gastric aspiration. Following induction of gastric aspiration by injection of gastric fluid, 16 healthy pigs were randomized to one of two groups: supine position (SP) or prone position (PP). After ventilation and monitoring for 6 hr, all pigs were euthanized. The ratio of the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FIO2) and the partial pressure of arterial carbon dioxide (PaCO2) were recorded during the 6-hr study period. Serum levels of interleukin (IL)-6 were measured every 2 hr, and the mean optical density (MOD) of IL-6 in lung tissues and lung-injury scores were measured at the end of the experiment. The PP group showed a significantly higher PaO2/FIO2 ratio, lower serum IL-6 concentration (p = .015), lower lung-injury scores (p = .012), and lower IL-6 concentration and MOD of IL-6 in lung tissue, especially in dorsal (p = .001, p = .021, respectively) and nondependent regions (p = .005, p = .035, respectively) than the SP group. There were no statistically significant differences in PaCO2 between the groups. Lung-injury severity was positively correlated with the IL-6 concentration and MOD of IL-6 in lung tissues (p < .05). These results suggest that immediate prone positioning alleviated the degree of aspiration-induced lung injury, possibly through mitigating IL-6-mediated lung inflammation.

Cigarette smoke exposure reduces leukemia inhibitory factor levels during respiratory syncytial viral infection.

Background: Viral infections are considered a major driving factor of chronic obstructive pulmonary disease (COPD) exacerbations and thus contribute to disease morbidity and mortality. Respiratory syncytial virus (RSV) is a frequently detected pathogen in the respiratory tract of COPD patients during an exacerbation. We previously demonstrated in a murine model that leukemia inhibitory factor (LIF) expression was increased in the lungs during RSV infection. Subduing LIF signaling in this model enhanced lung injury and airway hypersensitivity. In this study, we investigated lung LIF levels in COPD patient samples to determine the impact of disease status and cigarette smoke exposure on LIF expression.Materials and methods: Bronchoalveolar lavage fluid (BALF) was obtained from healthy never smokers, smokers, and COPD patients, by written informed consent. Human bronchial epithelial (HBE) cells were isolated from healthy never smokers and COPD patients, grown at the air–liquid interface and infected with RSV or stimulated with polyinosinic:polycytidylic acid (poly (i:c)). Mice were exposed to cigarette smoke daily for 6 months and were subsequently infected with RSV. LIF expression was profiled in all samples.Results: In human BALF, LIF protein was significantly reduced in both smokers and COPD patients compared to healthy never smokers. HBE cells isolated from COPD patients produced less LIF compared to never smokers during RSV infection or poly (i:c) stimulation. Animals exposed to cigarette smoke had reduced lung levels of LIF and its corresponding receptor, LIFR. Smoke-exposed animals had reduced LIF expression during RSV infection. Two possible factors for reduced LIF levels were increased LIF mRNA instability in COPD epithelia and proteolytic degradation of LIF protein by serine proteases.Conclusions: Cigarette smoke is an important modulator for LIF expression in the lungs. Loss of LIF expression in COPD could contribute to a higher degree of lung injury during virus-associated exacerbations.

Penehyclidine hydrochloride exerts protective effects in rats with acute lung injury via the Fas/FasL signaling pathway.

Acute lung injury (ALI) is a critical syndrome that is associated with high morbidity and mortality rates. The activation of the Fas/Fas ligand (FasL) signaling pathway may be an important pathophysiological mechanism during ALI development. Penehyclidine hydrochloride (PHC) has been revealed to exhibit anti-apoptotic properties and may attenuate the observed systemic inflammatory response. The present study was performed to elucidate the molecular mechanism of PHC in the regulation of the Fas/FasL signaling pathway in rats with ALI. An ALI rat model was constructed by inducing blunt chest trauma and hemorrhagic shock (T/HS), with PHC administration prior to or following T/HS. At 6 h following T/HS, blood samples and lung tissues were collected. Western blotting, arterial blood gas analysis, ELISA, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and biochemical indicator analysis were performed to determine the degree of lung injury and the key signaling pathways associated with lung damage. The results indicated that the administration of PHC following T/HS effectively attenuates lung injury by improving pulmonary oxygenation, decreasing histopathological damage, decreasing polymorphonuclear neutrophil count and decreasing Fas, FasL, caspase-8, caspase-3, tumor necrosis factor-α, interleukin (IL)-6 and IL-1β expression. The results indicated that PHC exhibits anti-apoptotic functions and exerts protective effects in ALI rats induced by T/HS, which may be attributed to the inhibition of the Fas/FasL signaling pathway.

Sirtuin 6 mitigated LPS-induced human umbilical vein endothelial cells inflammatory responses through modulating nuclear factor erythroid 2-related factor 2.

Nuclear factor erythroid 2-related factor 2 (Nrf2) protects the lung from sepsis-induced injury through activating Nrf2-regulated multiple phase 2 detoxification genes, including NAD(P)H: quinine oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO1). Based on the positive effect of Sirtuin 6 on Nrf2, we aim to explore the potential role of SIRT6 in the mechanism of sepsis-induced acute lung injury (ALI). Mouse models of sepsis were constructed by instilling intratracheal of lipopolysaccharide (LPS; 4 ml/kg). After 48-hour treatment, lung tissues were collected to measure the degree of lung injury. The SIRT6, siSIRT6, and siNrf2 plasmids were cotransfected into various concentrations of LPS-treated human umbilical vein endothelial cells (HUVECs; 0, 1, 5, 10, and 50 μg/ml) using Lipofectamine 2000. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay. Expression levels of SIRT6, Nrf2, NQO1, and HO1 was measured by quantitative polymerase chain reaction and Western blot analysis. Cell apoptosis was determined by flow cytometry. Lung tissues in the model group already had basic characteristics of ALI. Compared with the control model, TNF-α and IL-6 levels were much higher (P < 0.01), the levels of SIRT6, Nrf2, and Nrf2-modulated detoxification factors were downregulated (P < 0.01). SIRT6 overexpression decreased the apoptosis below to 10% (P < 0.01), significantly increased the Nrf2 expression, effectively inhibited TNF-α and IL-6 releases, and enhanced NQO1 and HO1 levels (P < 0.01). siNrf2 abolished the protective effects of SIRT6 overexpression, including increasing apoptosis and inhibiting anti-inflammatory and antioxidative genes expressions (P < 0.01). Our study suggested SIRT6 positively regulated Nrf2 expression and activated Nrf2-regulated anti-inflammatory and antioxidative enzymes, which could effectively mitigate LPS-induced HUVECs inflammatory responses. This might reflect the mechanism of ALI induced by sepsis.

Effects of hyperbaric oxygen and iloprost on intestinal ischemia-reperfusion induced acute lung injury.

PurposeTo research the effects of iloprost (IL) and hyperbaric oxygen (HBO) combination treatment on lung injury and on tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), and soluble intercellular adhesion molecule-1 (sICAM-1) levels after tissue or organ ischemia-reperfusion, and on ischemia-reperfusion induced lung neutrophil sequestration.MethodsForty white New Zealand rabbits were assigned randomly into 5 groups: HBO, IL, HBO+IL, control, and sham groups. TNF-α values were checked before ischemia, in the 1st hour of ischemia and in the 1st and 4th hours of reperfusion, also at the end of reperfusion period, plasma and tissue MPO values, MDA values, and sICAM-1 levels were detected. After sacrifice, the degree of lung injury was determined by histopathological examination.ResultsCompared to the control group all therapy groups showed a drastically meaningful reduction in TNF-α increase in 1, 2, and 4 hours. Plasma and lung MDA, MPO, and sICAM-1 levels were significantly lower in IL, HBO, HBO+IL, and sham groups compared with the control group. IL and/or HBO suppressed MDA and MPO increase in the lung tissue and in plasma. Additionally, histopathological score was significantly lower in HBO, IL, HBO+IL, and sham groups than that of the control group.ConclusionBoth HBO and IL therapy have a beneficial effect by causing a meaningful reduction in TNF-α production, MPO, MDA, sICAM-1 levels and pulmonary neutrophil sequestration; which play a role, especially, in ischemia reperfusion induced lung damage.

The effect of adipose-derived stem cells on the lung colonization, TNF-α and IL-4 in rats with LPS-induced acute lung injury

Objective To explore the effect of 5-ethynyl-2'-deoxyuridine (EdU) -labeled adipose-derived stem cells (ADSCs) on lung colonization, TNF-α and IL-4 in rats induced by lipopolysaccharide (LPS) with acute lung injury. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into the normal control group (n=10), LPS model group (n=10), and LPS+ADSCs intervention group (n=10). The ALI model rats were intraperitoneally injected with 8 mg/kg LPS, rats in the normal control group were intraperitoneally injected with 4 mL/kg physiological saline, and rats in the LPS+ADSCs group were intravenously injected with 300 μL ADSCs by tail vein after 30 minutes for the ALI model establishment, and rats in the normal control group and LPS group were intravenously injected with 300 μL physiological saline by tail vein. The time of death in rats was observed, lung tissue and blood from left ventricular were collected, and the serum tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-4) were detected by Enzyme-linked immunosorbent assay (ELISA). Lung wet/dry weight (W/D) ratio was detected by thoracotomy, the pathological changes of lung tissue were observed under optical microscope, and the colonization of ADSCs in the lungs were observed under immunofluorescence microscopy. LSD-t method was used to compare between every two groups. Results There was no significant difference in mortality between the LPS group and LPS + ADSCs group (50% vs. 70%, P> 0.05); EdU-labeled ADSCs were extensively colonized in the lungs by tail vein injection after 24 h; Compared with the normal control group, the lung injury of the LPS group was heavier, the ratio of lung W/D and TNF-α were significantly increased (all P< 0.01), and IL-4 level was significantly decreased (P< 0.01). Compared with the LPS model group, the degree of lung injury in the LPS + ADSCs group was significantly reduced, lung W/D ratio (5.57±0.27 vs. 5.98±0.28) and TNF-α level of blood [(41.51±4.14)ng/L vs. (45.52±3.74)ng/L] were significantly reduced (all P< 0.05), whereas the IL-4 levels were significantly increased [(7.01±1.11)pg/mL vs. (3.27±0.54)pg/mL, P< 0.05]. Conclusions EdU-labeled ADSCs could be colonized in the lungs of LPS-induced ALI rats, reduce the inflammatory response from TNF-α and improve the anti-inflammatory response from IL-4. Key words: Acute lung injury; Adipose-derived stem cell; Lipopolysaccharide; EdU; Tracer

Sex influences the association between haemostasis and the extent of lung lesions in tuberculosis

BackgroundWorldwide tuberculosis (TB) reports show a male bias in morbidity; however, the differences in pathogenesis between men and women with TB, as well as the mechanisms associated with such differences, are poorly investigated. We hypothesized that comparison of the degree of lung injury and clinical indices of well-matched men and women with newly diagnosed TB, and statistical analysis of the correlation between these indices and the extent of lung lesions, can provide insights into the mechanism of gender bias in TB.MethodsWe evaluated the acid-fast bacilli grading of sputum samples and compiled computed tomography (CT) data of the age-matched, newly diagnosed male and female TB patients without history of smoking or comorbidities. Inflammatory biomarker levels and routine haematological and coagulation-associated parameters were compared. Binary logistic regression analysis was used to define the association between the indices and lung lesions, and the influence of sex adjustment.ResultsWomen with TB have a longer delay in seeking healthcare than men after onset of the TB-associated symptoms. Men with TB have significantly more severe lung lesions (cavities and healing-associated features) and higher bacterial counts compared to women with TB. Scoring of the CT images before and after anti-TB treatment showed a faster response to therapy in women than in men. Coagulation- and platelet-associated indices were in models from multivariate regression analysis with groups of males or females with TB or in combination. In univariate regression analysis, lower lymphocyte counts were associated with both cavity and more bacterial counts, independent of sex, age and BMI. The association of international normalized ratios (INR), prothrombin times (PTs), mean platelet volumes (MPVs) and fibrinogen (FIB) level with lung lesions was mostly influenced by sex adjustment.ConclusionsSex influences the association between haemostasis and extent of TB lung lesions, which may be one mechanism involved in sex bias in TB pathogenesis.

Ventilator-induced lung injury and lung mechanics.

Mechanical ventilation applies physical stresses to the tissues of the lung and thus may give rise to ventilator-induced lung injury (VILI), particular in patients with acute respiratory distress syndrome (ARDS). The most dire consequences of VILI result from injury to the blood-gas barrier. This allows plasma-derived fluid and proteins to leak into the airspaces where they flood some alveolar regions, while interfering with the functioning of pulmonary surfactant in those regions that remain open. These effects are reflected in commensurately increased values of dynamic lung elastance (EL ), a quantity that in principle is readily measured at the bedside. Recent mathematical/computational modeling studies have shown that the way in which EL varies as a function of both time and positive end-expiratory pressure (PEEP) reflects the nature and degree of lung injury, and can even be used to infer the separate contributions of volutrauma and atelectrauma to VILI. Interrogating such models for minimally injurious regimens of mechanical ventilation that apply to a particular lung may thus lead to personalized approaches to the ventilatory management of ARDS.

Lung injury severity changes in response to different blast shock waves in rabbits

Objective To observe the effect of different explosion on rabbit lung injury and decide the death curve, so as to provide a reference for the prediction of lung injury. Methods Six healthy male New Zealand white rabbits with weight of 2.0-2.5 kg and age of (6±1)months were selected. The rabbits were put 0.5 m, 0.6 m, 0.7 m, 0.9 m, 1.0 m, and 1.2 m away from 90 g TNT to carry out the blast injury experiment. The characteristic parameters of blast shock wave and general lung injury were recorded. Based on the experimental results combined with theoretical analysis, the changes of rabbit lung injury depending on the explosion distance as well as the rabbit death curve were determined. Results After the 90 g TNT explosion, the peak overpressure of shock wave and the corresponding specific decreased quickly with the increase of explosion distance. The peak overpressure was 0.79 MPa and the specific was 82 Pa·s at the explosion distance of 0.5 m. The peak overpressure was 0.1 MPa and the specific was 34 Pa·s at the explosion distance of 1.2 m. The rabbits at 0.5 m and 0.6 m died, the rabbit at 0.7 m was severely injured, and the rabbits at 0.9 m, 1.0 m, and 1.2 m were slightly injured. The dependence of lung injury degree on the explosion distance under 90 g TNT explosion was established based on dimensional analysis theory. The lung injury degree was exponentially attenuated with the explosion distance: ϕ= (R/0.6)-5.64 (ϕ represented lung injury degree, and R represented the explosion distance). Considering the combined injury effects of peak overpressure of shock wave and its specific on rabbit lung, the death curve of rabbit was determined: (p-0.1)(I-59)=2.6(p represented peak overpressure, and I represented specific impulse). The criterion of overpressure-specific impulse was used to estimate the death of rabbit, and the death curve of rabbit was determined as (p-0.1)(I-59)=2.6(p represented peak overpressure and I represented specific impulse). The critical overpressure was 0.1 MPa and the critical specific was 59 Pa·s. Conclusions Under the explosion condition of 90 g TNT, the relationship between degree of lung injury in rabbits and explosion distance is established. Death curve of rabbits is determined based on the damage effect of shock wave peak overpressure and specific on the lungs of rabbits, which is significant for predicting the blast injury. Key words: Blast injuries; Lung injury; Rabbits; Injury prediction

Shock waves increase pulmonary vascular leakage, inflammation, oxidative stress, and apoptosis in a mouse model.

Severe lung damage is a major cause of death in blast victims, but the mechanisms of pulmonary blast injury are not well understood. Therefore, it is important to study the injury mechanism of pulmonary blast injury. A model of lung injury induced by blast exposure was established by using a simulation blast device. The effectiveness and reproducibility of the device were investigated. Eighty mice were randomly divided into eight groups: control group and 3 h, 6 h, 12 h, 24 h, 48 h, 7 days and 14 days post blast. The explosive device induced an explosion injury model of a single lung injury in mice. The success rate of the model was as high as 90%, and the degree of lung injury was basically the same under the same pressure. Under the same conditions, the thickness of the aluminum film can be from 0.8 mm to 1.6 mm, and the peak pressure could be from 95.85 ± 15.61 PSI to 423.32 ± 11.64 PSI. There is no statistical difference in intragroup comparison. A follow-up lung injury experiment using an aluminum film thickness of 1.4 mm showed a pressure of 337.46 ± 18.30 PSI induced a mortality rate of approximately 23.2%. Compared with the control group (372 ± 23 times/min, 85.9 ± 9.4 mmHg, 4.34 ± 0.09), blast exposed mice had decreased heart rate (283 ± 21 times/min) and blood pressure (73.6 ± 3.6 mmHg), and increased lung wet/dry weight ratio(2.67 ± 0.11), marked edematous lung tissue, ruptured blood vessels, infiltrating inflammatory cells, increased NF-κB (4.13 ± 0.01), TNF-α (4.13 ± 0.01), IL-1β (2.43 ± 0.01) and IL-6 (4.65 ± 0.01) mRNA and protein, decreased IL-10(0.18 ± 0.02) mRNA and protein ( P < 0.05). The formation of ROS and the expression of MDA5 (4.46 ± 0.01) and IREα (3.43 ± 0.00) mRNA and protein were increased and the expression of SOD-1 (0.28 ± 0.02) mRNA and protein was decreased ( P < 0.05). Increased expression of Bax (3.54 ± 0.00) and caspase 3 (4.18 ± 0.01) mRNA and protein inhibited the expression of Bcl-2 (0.39 ± 0.02) mRNA and protein. The changes of pulmonary edema, inflammatory cell infiltration, and cell damage factor expression increased gradually with time, and reached the peak at 12-24 h after the outbreak, and returned to normal at 7-14 days. Detonation injury can lead to edema of lung tissue, pulmonary hemorrhage, rupture of pulmonary vessels, induction of early inflammatory responses accompanied by increased oxidative stress in lung tissue cells and increased apoptosis in mice experiencing blast injury. The above results are consistent with those reported in other literatures. It is showed that the mouse lung blast injury model is successfully modeled, and the device can be used for the study of pulmonary blast injury. Impact statement The number of patients with explosive injury has increased year by year, but there is no better treatment. However, the research on detonation injury is difficult to carry out. One of the factors is the difficulty in making the model of blast injury. The laboratory successfully developed and produced a simulation device of explosive knocking through a large amount of literature data and preliminary experiments, and verified the preparation of the simulation device through various experimental techniques. The results showed that the device could simulate the shock wave-induced acute lung injury generated, which was similar to the actual knocking injury. The experimental process was controlled. Under the same condition, there was no statistical difference between the groups. It is possible to realize miniaturization and precision of an explosive knocking simulation device, which is a good experimental tool for further research on the mechanism of organ damage caused by detonation and the development of protective drugs.

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

Abstract 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.

Inhibitory effect of circulating fibrocytes on injury repair in acute lung injury/acute respiratory distress syndrome mice model.

The study was aimed to explore the functions of circulating fibrocytes (CFs) on injury repair in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) mice model and its clinical value as a biomarker for ALI/ARDS. ALI/ARDS mice model was established by intratracheal instillation of lipopolysaccharide (LPS). Mononuclear cells were isolated from peripheral blood of ALI/ARDS model and flow cytometry was used to measure CFs defined as cells positive for CD45 and collagen-1. Histological changes of lung tissues were evaluated by H&E staining and Masson's trichrome staining. The correlations of CFs counts with damnification of lung tissue and the severity of pulmonary fibrosis were evaluated by Pearson correlation analyses. Western blot was used to detect the protein expression of collagen-1. ELISA was applied to determine cytokine CXCL12 concentration. Clinical relevance between CFs and ALI/ARDS was investigated. The greater number of CFs in the ALI/ARDS group implied higher degree of lung injury and more severe pulmonary fibrosis. The protein expression of collagen-1 and concentration of cytokine CXCL12 in ALI/ARDS group were higher than that in control group. Clinical and prognostic analysis revealed the higher injury degree and death rates in ALI/ARDS group than those in control group, and identified a greater severity and mortality for patients with ARDS than those with ALI. ROC curve analysis indicated the counts of CFs greater than 5.85% can predict death rates with AUC = 0.928. CFs had an inhibitory effect on injury repair in ALI/ARDS mice model. This might be unfavorable as a clinical marker for progression of ALI/ARDS.

A self-organized actomyosin drives multiple intercellular junction disruption and directly promotes neutrophil recruitment in lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI), with the hallmarks of vascular integrity disruption and neutrophil recruitment, is associated with high morbidity and mortality. Enhanced actomyosin assembly contributes to endothelial cell contact dysfunction. However, the roles and mechanisms of actomyosin assembly in ALI are not totally clear. We investigated the dynamic alterations and roles of actomyosin in ALI in vivo and in vitro models induced by LPS. Pulmonary levels of E-cadherin, vascular endothelial-cadherin, occludin, myosin phosphatase target subunit 1, and thymosin β4 were decreased, and the number and activity of neutrophils and the levels of actomyosin, p-ρ-associated protein kinase, p-myosin light-chain kinase, and profilin1 were increased within 3 d after LPS administration, and then, those alterations were recovered within the next 4 d, which was consistent with the alterations of lung histology, vascular permeability, edema, and serum levels of IL-6 and TNF-α. Direct or indirect inhibition of increased F-actin or myosin assembly ameliorated the reduction of intercellular junction molecules, the activation and migration of neutrophils, and the degree of lung injury. Moreover, neutrophil activation further promoted actomyosin assembly and aggravated lung injury. Conclusively, the enhancement of self-organized actomyosin contributes to alveolar-capillary barrier disruption and neutrophil recruitment in inflammatory response, which is a potential therapeutic target for ALI.-Chen, B., Yang, Z., Yang, C., Qin, W., Gu, J., Hu, C., Chen, A., Ning, J., Yi, B., Lu, K. A self-organized actomyosin drives multiple intercellular junction disruption and directly promotes neutrophil recruitment in lipopolysaccharide-induced acute lung injury.