Lipopolysaccharide (LPS), or endotoxin, is the major component of the outer surface of gram-negative bacteria. LPS is a potent activator of the cells of the immune and inflammation systems, including macrophages, monocytes and endothelial cells, and contributes to systemic changes seen in septic shock.1,2 It has long been believed that LPS is responsible for several fatal consequences of gram-negative infection. Cell activation by LPS constitutes the first step in the cascade of events believed to lead to the manifestation of gram-negative sepsis, which results in approximately 20 000 annual deaths in the United States3 and 30% mortality rate of known cases in China.Therefore, the action mechanism of LPS is one of the most important problems in the research field of immunity, inflammation and surgery. Researchers have investigated the mechanism of cell activity and injury of LPS for a long time. In 1990, CD14，the glycosyl-phosphatidylinositol (GPI)-linked plasma membrane protein, was identified as a proximal LPS receptor on the cell surface of macrophages, and it was suggested that CD14 and LBP (lipopolysaccharide binding protein) played an important role in the effect mechanism of LPS. CD14 seemed to receive LPS via transfer from the plasma protein LBP. Then, two action patterns were recognized. CD14 positive cells, such as macrophages and leukocytes, were activated after LPS combined with LBP and interacted with CD14. But, CD14 negative cells (for example, endothelial cells), were activated through other receptors that we did not know of in the cell surface after LPS, LBP and soluble CD14 (sCD14) combined with the compounds. However, there are some questions to be answered. Firstly, because CD14 lacks cytoplasmic doman, it is unlikely to act as the transducer. Secondly, the action pattern of LPS through CD14 and LBP may be in dose-dependent mode, but, in conditions of high dosage and long exposure to LPS action, CD14 and LBP do not play an important role in LPS activation effect. Finally, for CD14 negative cells, the receptor combined LPS-LBP-sCD14 compound has not yet been identified. Some details indicated that a “co-receptor” for LPS signal transduction must exist. Although standard biochemical approaches, transfection assay, and immunologic tacties were all employed to search for this co-receptor, it has not yet been found. The find of Toll-like receptor 4 (TLR4) provides a new opportunity to study the mechanism of LPS action.

阿尔茨海默病及轻度认知功能障碍患者后扣带回皮质与全脑有向功能连接研究

目的探讨阿尔茨海默病（alzheimer disease，AD）和轻度认知功能障碍（mild cognitive impairment，MCI）患者及正常老年人之间后扣带回皮质（posterior cingulate cortex，PCC）与全脑间有向功能连接的差异。方法选取2012年7月至2014年6月浙江省人民医院收治的 AD 患者32例（AD 组）及MCI 患者26例（MCI 组），同期另择健康体检正常老年人58例作为正常对照组。在静息态脑功能成像的基础上，利用Granger causality 分析（GCA）和独立成分分析进行有向功能连接的研究。采用单因素方差分析筛选出3组间有向功能强度有差异的连接，然后对其脑区进行感兴趣区分析；再利用DPARSF 及REST 软件进行静息态脑功能原始数据分析，采用t 检验删选出两组间有差异的功能连接。结果（1）差异有统计学意义的有向连接都是单向的，即全脑到PCC 有向连接的异常节点在接受PCC 信息时并未出现异常，反之亦然；（2）与正常对照组比较，AD 组的异常有向连接主要在默认脑网络（default mode network，DMN）脑区外；而与MCI 组比较，AD 组的异常有向连接则大多是在DMN 脑区内，主要集中在左侧大脑半球，并呈现左右不对称的特点。结论 PCC 作为 DMN 脑区中一个重要的枢纽节点，在AD 的进展中起着非常重要的作用。PCC 的有向连接异常进一步证实AD 的信息传递异常是有方向性的，且左右侧连接异常的不对称与优势大脑的使用相关。