Magnolol protects against acute gastrointestinal injury in sepsis by down-regulating regulated on activation,normal T-cell expressed and secreted

BACKGROUND Sepsis is a major medical challenge.Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects,but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear.AIM To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.METHODS Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,and regulated on activation,normal T-cell expressed and secreted(RANTES)levels in serum and ileal tissue in animal studies.The histopathological changes of the ileal mucosa in different groups were observed under a microscope.Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide(LPS)-induced decrease in permeability.Immunofluorescence and Western blot assays were used to detect the levels of RANTES,inhibitor of nuclear factor kappa-B kinaseβ(IKKβ),phosphorylated IKKβ(p-IKKβ),inhibitor of nuclear factor kappa-B kinaseα(IκBα),p65,and p-p65 proteins in different groups in vitro.RESULTS In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol,magnolol inhibited the expression of proinflammatory cytokines,IL-1β,IL-6,and TNF-αin a dose-dependent manner.In addition,magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats.Moreover,in vitro studies suggested that magnolol inhibited the increase of p65 nucleation,thereby markedly downregulating the production of the phosphorylated form of IKKβin LPS-treated Caco2 cells.Specifically,magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B(NF-κB)from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.CONCLUSION Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways,thereby suppressing IL-1β,IL-6,and TNF-αexpression to alleviate the mucosal barrier dysfunction in sepsis.

医院获得性血流感染的流行病学和病原学特征分析:482例感染病例的回顾性调查(英文)

目的：分析某三级中医院医院获得性血流感染（nBSIs）的流行病学和病原学特征，探索影响28天病死率的相关危险因素。创新点：纳入2009-2011年所有确诊的血流感染病例，而非只依靠血培养结果做判定。收集包括患者的基础性疾病、侵入性操作等感染相关危险因素、标本送检及抗菌药物使用情况等全面的临床资料，分析了nBSIs的发生率、病区分布、人群分布、病原体分布、细菌耐药性及病死率，并对影响死亡的危险因素进行了多因素分析。方法：采用回顾性调查的方法，从病历资料中获得预先设置好的相关信息。病原体的分离鉴定和药敏检测由医院微生物实验室专职人员完成。使用WHONET5．6软件对药敏结果进行分析。采用SPSS16．0对所有数据进行统计分析，死亡危险因素判定先用单因素分析，再用多因素Logistic回归分析。结论：某三级中医院nBSIs的发生率为5．7／1000入院人数，大肠埃希菌和凝固酶阴性的葡萄球菌（CONS）是检出最多的两种细菌。约有1／3的肠杆菌对第三代头孢菌素耐药（表4），90．7％的CoNS对甲氧西林耐药（表3）。碳青霉烯类和糖肽类是用于治疗nBSIs使用最广泛的两类抗生素（图1）。感染性休克、血液透析、Pitt菌血症得分〉4和尿路感染是28天死亡的危险因素，而合理的经验性用药可以明显改善预后（表6）。