The oncostatin M‐stromal cell axis in health and disease

The field of stromal immunology has risen to prominence in the last decade, fuelled by accumulating evidence that nonhaematopoietic mesenchymal cells are not simply involved in modulating tissue structure, but actively contribute to immune processes. In addition to regulating tissue integrity during homoeostasis, stromal cells are sensitive sensors of inflammatory stimuli produced downstream of tissue injury or infection, and respond by producing a wide variety of chemokines, cytokines and adhesion factors that contribute to immunity and tissue repair. When not appropriately regulated, these same processes can result in inflammatory pathology and organ dysfunction. In this review, we provide a brief overview of stromal immunology, followed by a comprehensive discussion of how the IL ‐6 family cytokine oncostatin M (OSM ) coordinates stromal cell activity in diverse physiological and pathological contexts. We conclude by providing a perspective on the potential clinical value of the OSM ‐stromal cell axis and how this pathway might be exploited therapeutically.     

PM2.5‐induced lung inflammation in mice: Differences of inflammatory response in macrophages and type II alveolar cells

Particulate matter 2.5 (<PM2.5 μm) leads to chronic obstructive pulmonary disease. In this study, biomarkers related to inflammation and oxidative stress in vitro and in vivo experiments were investigated to clarify the PM2.5‐induced lung inflammation mechanisms. In an in vitro study using RAW264.7 cells, PM2.5 caused phosphorylation of nuclear factor‐κB, p38 mitogen‐activated protein kinase and extracellular response kinases, an increase of proinflammatory gene and protein expressions (e.g. monocyte chemotactic protein‐1, tumor necrosis factor‐α). These biomarkers were substantially attenuated by polymyxin B (PMB). PM2.5 induced heme oxygenase‐1 (HO‐1) gene, which was attenuated by N‐ acetylcysteine (NAC). However, the suppressive effects of NAC on inflammatory biomarkers were very weak. In bone marrow‐derived macrophages (BMDMs) of wild‐type BALB/c mice, the effects of PMB and NAC on PM2.5‐induced inflammatory responses were similar to RAW264.7 cells. In BMDMs of MyD88^−/− mice, PM2.5‐induced proinflammatory mediators were substantially more attenuated. PM2.5 caused an increase of proinflammatory gene expressions (interleukin‐6, cyclooxygenase 2) and HO‐1 gene in MLE‐12 cells (mouse alveolar cell line). These biomarkers were substantially attenuated by NAC, but not by PMB. When BALB/c mice were exposed intratracheally to 0.2 mg PM2.5, PM2.5 caused severe lung inflammation, an increase of neutrophils along with proinflammatory mediators in bronchoalveolar lavage fluid. The inflammation was attenuated by NAC, particularly by NAC + PMB, but not by PMB alone. These results indicate that macrophages may act sensitively to lipopolysaccharide (LPS) present in PM2.5 and release proinflammatory mediators via the LPS/MyD88 pathway. However, type II alveolar cells may react sensitively to oxidative stress induced by PM2.5 and cause inflammatory response. Therefore, overall, PM2.5 may cause predominantly oxidative stress‐dependent inflammation rather than LPS/MyD88‐dependent inflammation in type II alveolar cell‐rich lungs. Copyright © 2017 John Wiley & Sons, Ltd.     

74例慢性乙型肝炎患者急性发作临床特征分析

目的探讨慢性乙型肝炎急性发作临床特点,为诊断、治疗慢性乙型肝炎急性发作提供循证医学证据。方法回顾性分析海口市人民医院2011年1月-2015年10月确诊的74例慢性乙型肝炎急性发作患者的临床资料。将纳入患者分为HBe Ag阳性组(n=51)和阴性组(n=23)。计量资料两组间比较采用t检验,计数资料组间比较采用χ2检验。结果慢性乙型肝炎急性起病,ALT水平为523~2940 U/L,表现为黄疸型肝炎64例(86.49%),4周内临床治愈65例(87.84%)。HBe Ag阳性组与HBe Ag阴性组基线ALT、AST、HBV DNA水平差异均无统计学意义(P值均0.05),但HBe Ag阴性组患者的TBil水平[(141.1±132.9)μmol/L]较阳性组[(80.1±68.8)μmol/L]高,差异有统计学意义(t=2.745,P=0.007)。结论慢性乙型肝炎急性发作发病过程类似于急性乙型肝炎,HBe Ag阴性患者的TBil水平较高,肝细胞损伤较重。     

The role of infection and immunity in atherosclerosis

Cardiovascular diseases account for 20% of deaths worldwide, rising to 50% in developed countries. Current understanding of atherosclerosis derives from a combination of research in animals and cell cultures, analysis of human lesions, clinical investigations of patients with acute coronary syndromes and epidemiological studies of coronary artery disease. By measuring serologic titers in the serum of patients after cardiovascular events, it was observed that the greater the infectious exposure of a patient, the larger the atherosclerotic lesion extension. In addition, gene targeting or pharmacological inhibition of certain cytokines aggravates atherosclerosis in animal experiments. Other animal experiments have succeeded in proving that B cells play a protective role in atherosclerosis through induced immunity against oxidized low-density lipoprotein and other epitopes. Molecular mimicry might respond to the question of how infection may trigger vulnerability in previously stable atherosclerotic lesions. The FLU Vaccination Acute Coronary Syndromes trial enhanced the debate on atherosclerosis prevention by the application of antiflu vaccine. So far, antibiotics have failed to reduce cardiovascular risk, as recent trials could not demonstrate a statistically significant risk reduction. Having assumed atherosclerosis to be an inflammatory disease, the WHO considered the possible role of secondary prevention with antiflu vaccine.     

老年慢性阻塞性肺疾病急性加重期患者IL-8、IL-6、TNF-α水平变化与肺功能的相关性研究

目的探讨老年慢性阻塞性肺疾病急性加重期(AECOPD)患者IL-8、IL-6、TNF-α水平变化和肺功能的相关性。方法选取我院收治的AECOPD患者78例。分别于患者急性加重期和稳定期检测其血清IL-8、IL-6、TNF-α水平以及肺功能。对比不同肺功能综合评估分级的患者IL-8、IL-6、TNF-α的水平,同时对比急性加重期和稳定期患者IL-8、IL-6、TNF-α和FEV1%预计值的检测结果,并分析IL-8、IL-6、TNF-α与FEV1%预计值的相关性。结果肺功能综合评估分级级别越高,其IL-8、IL-6和TNF-α的水平显著增高(p<0.05);COPD急性加重期及稳定期患者的IL-8、IL-6、TNF-α水平和FEV1%预计值水平均呈负相关(p<0.05)。结论老年AECOPD患者IL-8、IL-6和TNF-α水平和FEV1%预计值呈负相关,检测IL-8、IL-6和TNF-α的水平可反应出患者病情的严重程度,有助于临床评估患者的病情,指导临床治疗。     

基于“脑-肠轴”学说论治慢性乙型肝炎合并肠易激综合征

慢性乙型肝炎合并肠易激综合征的发病机制尚未完全清楚,西医疗效亦不容乐观,但"脑-肠轴异常"理论被认为是本病发病的关键,此恰与中医理论不谋而合,且中医理论认识更深、更广。基于"脑-肠轴"学说,以针刺头针胃区和头针肠区作为切入点,运用"调神针法"调节"脑神"进而调节"五脏神",以达到阴平阳秘,百病不生的状态,从而治愈本病。