帕罗西汀血药浓度检测方法研究进展

帕罗西汀为5-羟色胺（5-HT）阻断药,具有起效快、疗效好、不良反应低等优点,为目前临床上常用抗抑郁症药物。帕罗西汀疗效和不良反应与该药血药浓度密切相关,并且个体差异性较大。因此,研究开发专一性强、灵敏度高的血药浓度检测方法十分必要,具有重要的临床和实践意义。本文综述帕罗西汀血药浓度检测时血样的前处理方法,同时对高效液相色谱法和气相色谱法检测帕罗西汀血药浓度进展进行论述,为该领域的临床合理用药和相关领域的研究提供借鉴。     

我国现行医疗卫生政策的相关问题分析

医疗卫生是构建和谐社会的重要因素之一,也是关乎百姓切身利益的重大问题之一,近年来,医疗体制的不断改革,医疗卫生的相关政策的不断出台,已经大大地改善了我国广大人民群众的“看病难,看病贵”等问题,增加了医保的覆盖人群,减轻了城市低收入人群及农村的医疗负担,但是,我们仍面临着巨大的挑战,新的问题也不断涌现,医疗卫生政策不适应现在的医疗需求发展、经济发展不均衡、不同层次群众的医疗需求有差异等,都是医疗卫生改革中面临的问题,医疗改革的不断推进势在必行。我国的医疗保障制度覆盖率已经达到95％,但是,现行的医疗保障制度的还不能从根本上解决人民群众的“就医难,治病贵”的问题,其他医疗保险不能与现行的医疗保障制度相适应,从而,影响了我国整体的医疗水平的提高。     

A Simple and Computationally Efficient Approach to Multifactor Dimensionality Reduction Analysis of Gene-Gene Interactions for Quantitative Traits

We present an extension of the two-class multifactor dimensionality reduction (MDR) algorithm that enables detection and characterization of epistatic SNP-SNP interactions in the context of a quantitative trait. The proposed Quantitative MDR (QMDR) method handles continuous data by modifying MDR’s constructive induction algorithm to use a T-test. QMDR replaces the balanced accuracy metric with a T-test statistic as the score to determine the best interaction model. We used a simulation to identify the empirical distribution of QMDR’s testing score. We then applied QMDR to genetic data from the ongoing prospective Prevention of Renal and Vascular End-Stage Disease (PREVEND) study.     

Stress-Derived Corticotropin Releasing Factor Breaches Epithelial Endotoxin Tolerance

Background and aims

Loss of the endotoxin tolerance of intestinal epithelium contributes to a number of intestinal diseases. The etiology is not clear. Psychological stress is proposed to compromise the intestinal barrier function. The present study aims to elucidate the role of the stress-derived corticotropin releasing factor (CRF) in breaching the established intestinal epithelial endotoxin tolerance.

Methods

Epithelial cells of HT-29, T84 and MDCK were exposed to lipopolysaccharide to induce the endotoxin tolerance; the cells were then stimulated with CRF. The epithelial barrier function was determined using as indicators of the endotoxin tolerant status. A water-avoid stress mouse model was employed to test the role of CRF in breaching the established endotoxin tolerance in the intestine.

Results

The established endotoxin tolerance in the epithelial cell monolayers was broken down by a sequent exposure to CRF and LPS manifesting a marked drop of the transepithelial resistance (TER) and an increase in the permeability to a macromolecular tracer, horseradish peroxidase (HRP). The exposure to CRF also increased the expression of Cldn2 in the epithelial cells, which could be mimicked by over expression of TLR4 in epithelial cells. Over expression of Cldn2 resulted in low TER in epithelial monolayers and high permeability to HRP. After treating mice with the 10-day chronic stress, the intestinal epithelial barrier function was markedly compromised, which could be prevented by blocking either CRF, or TLR4, or Cldn2.

Conclusions

Psychological stress-derived CRF can breach the established endotoxin tolerance in the intestinal mucosa.     

台湾和日本拟步甲在纬度分布上的比较研究

台湾和日本处在不同的地理纬度上,同属岛屿海洋性气候,前者地域面积远小于后者,拟步甲的物种多样性却大于后者。为弄清楚这些科学问题,作者采用G-F指数对从台湾到日本不同纬度梯度上的拟步甲多样性分布格局进行了比较分析,得到如下初步结论：(1) G-F指数从大到小依次是：台湾(21°N-25°N)(0．826)>日本(24°N-45°N)(0．824)>日本Ⅱ纬度区(30°N-35°N)(0．792)>日本Ⅰ纬度区(24°N-30°N)(0．765)>日本Ⅲ纬度区(35°N-40°N)(0．761)>日本Ⅳ纬度区(40°N-45°N)(0．603);(2)台湾拟步甲属的多样性(DG)、族的多样性(DF)和G-F指数(DG-F)均最高,分别是4．263、24．464和0．826;(3)各纬度上拟步甲的物种分布情况：台湾(21°N-25°N)(541种)>日本(24°N-45°N)(489种)>日本Ⅰ纬度区(24°N-30°N)(257种)>日本Ⅱ纬度区(30° N-35° N)(231种)>日本Ⅲ纬度区(35° N-40° N)(172种)>日本Ⅳ纬度区(40° N-45° N)(60种)。研究数据显示, G-F指数能较好地反映台湾和日本各地拟步甲族、属的多样性。其物种多样性在纬度上的分布表现为从南向北递减的趋势,并对其基本原因进行分析。作者首次基于台湾和日本两个岛屿拟步甲物种多样性的比较分析,对现有岛屿生物多样性的有关理论提出个人看法,认为岛屿生物地理学的“物种-面积关系理论”中的“岛屿面积越大,物种数量就越多”可能存在一定的局限性,不一定能客观地反映种类众多的现生岛屿昆虫物种多样性的实际情况。     

Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4

The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.     

30年泰山繁殖鸟类种类变化

泰山位于山东省中部,是华北中东部地区海拔最高的山脉,地形多样,生境复杂,是鸟类重要的繁殖地和迁徙停歇地。根据1984~1988年和2013~2015年两个时期野外调查及访谈调查结果,比较了近30年泰山繁殖鸟类种类的组成变化。相比20世纪80年代记录的繁殖鸟类13目35科72种,2013~2015年的调查记录到繁殖鸟类11目34科84种,与30年前相比净增长12种繁殖鸟类,其中新增繁殖鸟类记录32种,消失鸟类记录20种。新增种类主要是林地和灌丛鸟类,多为东洋种,消失的种类主要是湿地和农田草地鸟类,多为古北种和广布种。鸟类新增和消失的原因多样,但主要是栖息地面积和质量的改变,同时私自放生也是一个重要原因。本研究结果可丰富泰山地区随时间尺度变化的鸟类本底数据,并为泰山鸟类的保护提供科学依据。     

河北平山发现锈胸蓝姬鹟

正2015年6月22日,在河北省平山县驼梁国家级自然保护区驼峰附近的华北落叶松林内(113°49′33″E,38°44′59″N,海拔2 056 m)观察到1雌1雄2只鹟科鸟类。雌鸟上体橄榄褐色,两翼各具1道棕白色的翼斑;喉部、胸部浅褐色,并略带皮黄;尾上覆羽沾棕色;眼周白色,嘴黑褐色。雄鸟上体暗蓝灰色,喉、上胸、两胁橙红色,腹部颜色逐渐变白,尾近黑色。发现时,雌鸟往返飞行于落叶松枝和地面进行觅食;雄鸟在落叶松上部的树枝上频繁地鸣唱。经查阅文献(约翰·马敬能等2000,曲利明2014,Clement et al.2016),确定该鸟种为锈胸蓝姬鹟(Ficedula hodgsonii)(图1)。     

Temporal rhythm of petal programmed cell death in Ipomoea purpurea

• Flowers are the main sexual reproductive organs in plants. The shapes, colours and scents of corolla of plant flowers are involved in attracting insect pollinators and increasing reproductive success. The process of corolla senescence was investigated in Ipomoea purpurea (Convolvulaceae) in this study.
• In the research methods of plant anatomy, cytology, cell chemistry and molecular biology were used.
• The results showed that at the flowering stage cells already began to show distortion, chromatin condensation, mitochondrial membrane degradation and tonoplast dissolution and rupture. At this stage genomic DNA underwent massive but gradual random degradation. However, judging from the shape and structure, aging characteristics did not appear until the early flower senescence stage. The senescence process was slow, and it was completed at the late stage of flower senescence with a withering corolla.
• We may safely arrive at the conclusion that corolla senescence of I. purpurea was mediated by programmed cell death (PCD) that occurred at the flowering stage. The corolla senescence exhibited an obvious temporal rhythm, which demonstrated a high degree of coordination with pollination and fertilization.