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Objective To investigate the role of histone H4 in the polarization of alveolar macrophages (AM) in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in mice. Methods i) The specific pathogen free male C57BL/6 mice were randomly divided into control group and 2, 4, 6 and 8 mg/kg LPS groups, with six mice in each group. The mice in the LPS groups were intratracheally administered LPS according to their respective doses, while the mice in the control group received an equivalent volume of 0.9% saline. After 12 hours, the arterial blood gas was analyzed, and the pulmonary edema and histopathological changes in lung tissues of mice in each group were observed. The level of histone H4 in bronchoalveolar lavage fluid (BALF) of mice was detected using enzyme-linked immunosorbent assay , and mice AMs of the five group were isolated using adherent method. ii) AMs from normal mice were isolated using adherent method and randomly divided into control group, histone H4 injury group, BALF injury group and anti-histone H4 antibody (anti-H4) intervention group. In the histone H4 injury group, AMs were treated with histone H4 at a final concentration of 20 mg/L. In the BALF injury group and anti-H4 intervention group, AMs were treated with 200 μL BALF supernatant from mice intratracheally administered 6 mg/kg body weight LPS, with the latter group treated with 25 mg/L anti-H4 antibody. The control group AMs were treated with phosphate-buffered saline. iii) After 12 hours of stimulation, the cells were collected, and the relative expression of tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), differentiation antigen 206 (Cd206) and arginase 1 (Arg1) in AMs was detected using real-time quantitative polymerase chain reaction. Results i) Compared with the control group, mice in all four LPS groups exhibited rapid breathing, inflammatory reaction and lung edema in lung tissues, which were aggravated in a dose-dependent manner. The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen in mice decreased with the increase of LPS dose (P<0.05). The wet/dry weight ratio of lung, the level of histone H4 in BALF and the relative expression of Tnfa and Il1b mRNA in AMs increased with the increase of LPS dose (all P<0.05). The mice in the 6 and 8 mg/kg LPS groups developed ARDS. The level of histone H4 in BALF and the relative expression of Tnfa and Il1b mRNA in AMs of mice in 6 and 8 mg/kg LPS groups were higher than those in the other three groups (all P<0.05). ii) The relative expression of Tnfa and Il1b mRNA increased (both P<0.05), and the relative expression of Cd206 and Arg1 mRNA decreased (both P<0.05) in AMs of histone H4 injury group and BALF injury group compared with the control group. Compared with BALF injury group, the relative mRNA expression of Tnfa and Il1b in AMs of anti-H4 intervention group decreased (both P<0.05), while the relative expression of Arg1 mRNA increased (P<0.05). Conclusion LPS can induce a dose-dependent increase in histone H4 levels in BALF in mice. Histone H4 drives the development of ARDS by activating AMs to M1 polarization. Antagonizing histone H4 to interfere with AM polarization to M1 could be a target for the treatment of ARDS.
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OBJECTIVE: To study the literature characteristics and research status of occupational hand-arm vibration disease in China. METHODS: Literature information on occupational hand-arm vibration disease published before 2018 in China were searched and collected through the China National Knowledge Infrastructure(CNKI) and Wanfang Database. The bibliometrics was used to analyze the publication time, type, journal sources, authors and their institutions, citation situation, funds and high-frequency key words. RESULTS: From 1975 to 2018, a total of 349 papers on occupational hand-arm vibration disease were published. The main article type was monograph, with a total of 179 articles(accounting for 51.3%). The articles were distributed in 79 kinds of journals, among them, 10 journals including China Occupational Medicine and Industrial Health and Occupational Diseases were the main carriers to publish related articles(237 papers, accounting for 67.9%). The main research institutions of the literature were Jining Medical College and Guangdong Province Hospital for Occupational Disease Prevention and Treatment, with 134 papers(accounting for 38.4%) published. Among the 5 core authors of the literature, 4 were from the above 2 research institutions. A total of 121 articles(accounting for 34.7%) were cited, and 77 articles(accounting for 22.1%) were supported by research fund. The top 3 high-frequency key words used were arm vibration disease, hand-transmitted vibration/local vibration and occupational disease. CONCLUSION: Occupational hand-arm vibration disease has attracted the attention of Chinese researchers, however, follow-up research, literature quality and funding support still need to be improved.
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Objective@#To observe the changes of extracellular histones and pulmonary microvascular endothelial cells, and study the activating role of extracellular histones to pulmonary microvascular endothelial cells in the pathogenesis of acute respiratory distress syndrome (ARDS) .@*Methods@#The correlation of the severity of acute lung injury with extracellular histones and pulmonary endothelial damage was studied through mice model, and acute lung injury was produced by aspiration of different concentrations of hydrochloric acid (0.01、0.1、0.3 and 0.5 mol/L, 2 ml/kg). Tumor necrosis factor-α (TNF-α), soluble thrombomodulin (sTM) and lung pathological change were measured. The pro-inflammatory role of extracellular histones was tested by injecting calf thymus histones (CTH) or specific anti-H4 antibody through tail vein. The direct activating role of extracellular histones to pulmonary microvascular endothelial cells was studied through pulmonary endothelial model.@*Results@#The extracellular histones in plasma were increased obviously 6h after aspiration of different concentrations of hydrochloric acid in mice. A positive correlation was seen between extracellular histones and concentrations of aspirated hydrochloric acid (r=0.9180, P<0.05). The sTM in plasma also showed a positive correlation with concentrations of aspirated hydrochloric acid (r=0.8701, P<0.05). Merely administering CTH could not only increase TNF-α and sTM in plasma but also cause obvious lung injury, while specific anti-H4 antibody could relieve the inflammation and lung damage caused by CTH. Extracellular histones could directly damage pulmonary endothelial cells to release sTM in pulmonary endothelial model in vitro, while anti-H4 antibody could protect the endothelial cells.@*Conclusion@#Extracellular histones are the key endogenic inflammatory mediators during the pathogenesis of ARDS caused by aspiration of hydrochloric acid, which could promote inflammation by directly activating pulmonary endothelial cells.
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Objective@#In order to explore the role of heparan sulfate (HS) during the pathogenesis of acute respiratory distress syndrome (ARDS) , the protective effect of HS and its fragments against extracellular histones was compared.@*Methods@#Calf thymus histones (CTH) were injected via femoral vein to induce ARDS in rats. HS, HS fragments or saline was intraperitoneally injected (10mg/kg, Q6h, 24h) to test the protective effect against CTH. The ratio of wet/dry lung weight, protein content in bronchoalveolar lavage fluid (BALF) , total leukocyte and neutrophil count in BALF were measured.@*Results@#After CTH injection, the ratio of wet/dry lung weight (5.7±0.95) was much higher than the saline control group (3.1±0.15). The protein content (0.47±0.086mg/ml) , total leukocyte[ (97.4±15.6l) ×104/ml] and neutrophil (18±3.4/LPF) in BALF were obviously increased compared with the saline control group. The intervention of HS evidently decreased ratio of wet/dry lung weight (4.2±0.41) , protein content[ (0.26±0.019) mg/ml], leukocyte[ (61.3±5.74) ×104/ml] and neutrophil (12±1.8/LPF) in BALF. HS fragments also decreased ratio of wet/dry lung weight, protein content, leukocyte and neutrophil count in BALF though the strength was much less than HS.@*Conclusion@#HS and its fragments could provide protection against extracellular histones during the pathogenesis of ARDS. For the protective effect full length HS was much better than HS fragments.
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Objective@#To investigate the effect of baicalin on the changes in hemorheology and its mechanism during the development of Acute Respiratory Distress Syndrome(ARDS) induced by oleic acid (OA) in rats.@*Methods@#Rats were randomized into 3 groups: control, ARDS (OA induction, 0.12 mg/kg) and ba-icalin-treated group (300 mg/kg). The blood samples were collected at 30 min, 1, 2, 3, 6, 12 and 6 h after OA injection. The whole blood viscosity, plasma viscosity, Maximum erythrocyte deformability index (DImax) were detected. Meanwhile, blood gas analysis and Routine blood test were also performed.@*Results@#The level of arte-rial oxygen partial pressure and oxygenation index decreased (P<0.01 vs. control) and oxygenation index (178 mm Hg, 1 mm Hg=0.133 kPa) reached the diagnostic standard of ARDS at 2 h in ARDS group. In baicalin-treated group, the level of arterial oxygen partial pressure and oxygenation index increased versus the ARDS group. The platelet count (PLT) decreased in baicalin-treated and ARDS groups. Compared with the ARDS group, the level of PLT increased significantly in baicalin-treated group at 30min, 1, 2, and 3 h. Hematocrit (HCT) increased in baicalin-treated and ARDS groups. Compared with the ARDS group, the level of HCT de-creased significantly in baicalin-treated group at 2, 3, 6 and 12 h. Meanwhile, all the index of hemorheology improved in baicalin-treated group.@*Conclusion@#Baicalin may improve hypoxemia of ARDS induced by OA in rats. It may be due to the Improvement of microcirculation of lung.