CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.     

反相高效液相色谱法测定磷酸川芎嗪片的含量

目的建立测定磷酸川芎嗪片含量的反相高效液相色谱法。方法采用XDB-C18分析柱(150.0 mm×4.6 mm,6μm),流动相为甲醇-1%醋酸溶液(35∶65),流速1.0mL/min,检测波长295nm;并用紫外分光光度法做对比试验。结果磷酸川芎嗪的保留时间为6.82min,其质量浓度在5～40μg/mL范围内与峰面积线性关系良好(r=0.9998,n=6),平均回收率为99.02%,RSD为0.46%(n=6)。结论所用方法简单、准确,重复性好,可作为磷酸川芎嗪片的含量测定方法。     

主动脉内气囊反搏辅助急性心肌梗死介入治疗

目的:探讨主动脉内气囊反搏(IABP)对急性心肌梗死(AMI),尤其是ST段抬高的AMI(STEMI)患者经皮冠状动脉介入治疗(PCI)的临床意义。方法:接受PCI治疗并需要IABP支持的AMI患者52例顺利行冠脉造影检查,其中32例(61.5%)冠脉造影前导管室插入IABP,15例(28.8%)造影后、介入治疗前插入,2例术前(3.8%)床旁插入IABP,3例(5.8%)PCI术后插入,无介入操作相关并发症,无术中死亡。IABP维持24~240h。结果:50例(96.1%)行直接PCI治疗成功,术后梗死相关动脉血流均达TIMIⅡ级,2例(3.8%)未行PCI治疗。52例中4例(7.7%)需要呼吸机支持,1例(1.9%)PCI后停用IABP而死亡。IABP相关并发症为肾功能异常伴血尿1例(1.9%),下肢缺血2例(3.8%),局部血肿4例(7.7%)。结论:IABP对血流动力学不稳定的AMI的直接PCI治疗具有较好辅助作用。     

Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China

To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.     

HPLC法测定复方五味子安神胶囊中五味子甲素的含量

目的：建立高效液相色谱法测定复方五味子安神胶囊中五味子甲素含量的方法.方法：采用 Kromasil C18（250mm×4.6 mm,5 μm）色谱柱 以甲醇-0.1%冰醋酸水溶液（80：20）为流动相 流速：1 ml·min-1 检测波长：254 nm 柱温为30℃.结果：五味子甲素在0.1014～0.4056 mg·ml-1范围内与峰面积分别呈良好的线性关系（r=0.999 7,n=6）,平均回收率是100.7%（RSD=0.5%）.结论：本方法简便、准确、专属性强,可用于该制剂的质量控制.     

Characterization of DNA–protein complexes by nanoparticle tracking analysis and their association with systemic lupus erythematosus

Nanotechnology enables investigations of single biomacromolecules, but technical challenges have limited the application in liquid biopsies, for example, blood plasma. Nonetheless, tools to characterize single molecular species in such samples represent a significant unmet need with the increasing appreciation of the physiological importance of protein structural changes at nanometer scale. Mannose-binding lectin (MBL) is an oligomeric plasma protein and part of the innate immune system through its ability to activate complement. MBL also serves a role as a scavenger for cellular debris, especially DNA. This may link functions of MBL with several inflammatory diseases in which cell-free DNA now appears to play a role, but mechanistic insight has been lacking. By making nanoparticle tracking analysis possible in human plasma, we now show that superoligomeric structures of MBL form nanoparticles with DNA. These oligomers correlate with disease activity in systemic lupus erythematosus patients. With the direct quantification of the hydrodynamic radius, calculations following the principles of Taylor dispersion in the blood stream connect the size of these complexes to endothelial inflammation, which is among the most important morbidities in lupus. Mechanistic insight from an animal model of lupus supported that DNA-stabilized superoligomers stimulate the formation of germinal center B cells and drive loss of immunological tolerance. The formation involves an inverse relationship between the concentration of MBL superoligomers and antibodies to double-stranded DNA. Our approach implicates the structure of DNA–protein nanoparticulates in the pathobiology of autoimmune diseases.

Autoimmune diseases involve a chronic inflammatory response, which often leads to severe organ damage. Innate immunity, especially the complement system, serves a crucial role in instructing the adaptive immune response by facilitating transport of antigen into the lymph nodes and spleen (1–3). Engineered nanoparticles are targets for innate immunity (4, 5). So far it remains unclear whether physiologically formed nanoparticles also can manipulate the immune response or even be a source of autoinflammatory pathologies. Systemic lupus erythematosus (SLE) is a prototypic and potentially fatal multisystem autoimmune disease (6). B cells develop antibodies (Ab) to double-stranded (ds) DNA and spread a loss of host self-tolerance in expanding germinal centers (GCs) (7), which increases the SLE disease activity index (SLEDAI) (6). A missing link remains in our understanding of how dsDNA becomes a strong antigenic stimulus in the GC environment. Furthermore, the physiological significance of such stimulation has recently gained attention from the increasing number of other inflammatory diseases where cell-free DNA appear to play role (8).Mannose (or mannan)-binding lectin (MBL) is part of innate immunity against infections along with other proteins of the complement system. It also contributes to aberrant chronic inflammation with damage to vascularized host tissue, especially the kidney (9). A recent study showed that MBL binds glycosylated proteins in a nanoparticulate vaccine formulation. This augments immunity by strengthening the formation of antigen-reactive GCs (10). MBL binds dsDNA, presumably as a scavenger of cellular debris (11). In animal models of SLE, MBL deficiency is protective (12), while clinical studies did not associate MBL with SLE (13, 14).The 26-kDa MBL protein chain contains a tertiary structure with an N-terminal cysteine-rich segment, followed by a collagen-like region and a C-terminal Ca²⁺-dependent carbohydrate recognition domain (15, 16). Assembly of the collagen triple helix makes a structural trimer unit (MBL₃) (17, 18), which further oligomerizes into polydisperse structures with 3 to 8× MBL₃ units. In purified recombinant protein, atomic force microscopy (AFM) identified forms as large as 16 trimer units (16× MBL₃) (19), and small-angle X-ray scattering spectroscopy (SAXS) characterized anisotropic oligomers with an ∼150-nm long axis (20). Especially the SAXS data suggested a type of oligomerization, which involves juxtaposition of a number of ∼6× MBL₃ units, into resulting molecular ultrastructures that we here term superoligomers. Unfortunately, AFM and SAXS are unsuited for analyzing the MBL structural organization in complex samples such as liquid biopsies, including blood (21). Consequently, it is unclear if superoligomeric (sp)MBL exists in vivo and what its relevance is to human disease.Nanoparticle tracking analysis (NTA) relates the Brownian motion of particles in liquid to their hydrodynamic radius. Motion is tracked by particle scattering of projected laser light (Fig. 1A) or by emission from long-lived fluorescent dyes (Fig. 1D), as recently demonstrated with biotinylated protein aggregates using streptavidin-coupled quantum dots (QDs) (22). Monoclonal Ab-conjugated QDs enable specific targeting of proteins in fluorescence microscopy (23). In principle, a similar application is possible in NTA to characterize changes in the structural organization of proteins, even in complex samples based on the emittance of the QDs (Fig. 1 B–D).Open in a separate windowFig. 1.NTA for detection of MBL oligomers as purified protein and in bioliquids. (A) Principles of detection in NTA based on light scatter. Raw protein, including MBL, scatters laser light, which permits tracking of diffusion in a simple medium without other scattering constituents. (B and C) Design of a QD-based reporter system for detection of MBL. Commercially available 20-nm QDs with a Cd · Se core, Zn · S shell, and a pegylated surface with a chemistry linker enabling covalent coupling to glycan structure in IgG was conjugated to monoclonal Ab to either human MBL or murine MBL-C (or isotypic control Ab) of choice (B). The overall dimensions of the reporter permitted repeated binding to spMBL, here shown with a ligand (dsDNA)-driven lateral oligomerization (C). In both B and C, all items are drawn approximately to scale (scale bars indicated). (D) Detection in NTA based on QD emission. With the MBL Ab-QD reporter, the fluorescent emission at 655 nm permits detection among other constituents of a complex bioliquid such as diluted plasma.Here, we used NTA to characterize the structural variation of MBL oligomers in plasma from SLE patients. The concentration of spMBL is vastly increased in patients, amplified by MBL’s interaction with dsDNA. The spMBL concentration correlates directly with disease activity as may be explained by the large hydrodynamic radii of the oligomers, which pushes spMBL into blood vessel walls, adding to the vascular damage seen in SLE. An even wider link to SLE morbidity derives from the influence of spMBL on the autoimmune pathology, mechanistically supported by an animal model of SLE where spMBL is connected to the formation of autoreactive GC B cells.     

造血干细胞移植术后肺部感染的多层螺旋 CT 表现

目的：探讨造血干细胞移植(HSCT)术后肺部感染的多层螺旋 CT(MSCT)表现。方法临床证实的 HSCT 术后肺部感染192例患者,分析有完整胸部 CT 资料的69例各时期病原体种类及 CT 表现。结果(1)HSCT 术后肺部感染69例在术后早期(30 d 内)、中期(31~100 d)、后期(100 d 以后)3个时间段的构成比分别为55.1%、24.6%、20.3%。细菌、真菌及混合感染多发生于早期,分别占78.6%、52.6%、56.7%;病毒感染多发生在中期,占66.7%;后期细菌、真菌、病毒及混合感染分别占14.3%、10.6%、33.3%、26.7%。(2)CT 特征：细菌感染以实变影(7/14)及磨玻璃影(6/14)最常见;真菌感染以结节或肿块(15/19)最常见;病毒感染以磨玻璃影(3/6)最常见;结核均为混合感染,以结节(3/5)及多发实变影(2/5)常见;混合感染以磨玻璃影(15/30)及结节或肿块影(15/30)最为常见。在各病原体感染中除真菌感染出现征象的差异具有统计学意义(P <0.05)外,其他无统计学意义(P >0.05)。结论HSCT 术后肺部感染高峰为术后早期;细菌、真菌及混合感染多发生于早期;CT 对于 HSCT 术后肺部感染的诊断具有重要价值。     

云南省2017年乙脑媒介蚊虫监测结果分析

目的 了解云南省重点地区2017年蚊虫种群构成、季节消长及不同栖息地蚊虫密度,为流行性乙型脑炎防控提供科学依据。方法 使用诱蚊灯法于流行性乙型脑炎高发季节进行成蚊密度监测,监测结果使用SPSS软件统计分析。结果 2017年共捕获蚊虫2亚科4属5亚属9种16 173只,平均蚊密度为7.02只/（灯·小时）。三带喙库蚊为优势蚊种,占捕获总数的57.03%,其次为中华按蚊,占捕获数的33.50%,各地三带喙库蚊捕获数量的中位数为158只。蚊种香农-威纳指数H=1.40;三带喙库蚊赫尔芬达尔-赫希曼指数HHI=6 022.80;5月为三带喙库蚊活动最高峰,8月为次高峰,不同栖息地中三带喙库蚊分布差异明显（P=0.00）。结论 云南省蚊虫仍具有多样性,三带喙库蚊密度在流行季节均维持在较高水平,存在乙脑暴发流行风险,4月起即应进行乙脑防控应对。     

抗preS1分子高效单克隆抗体的制备及其在血清LHBs检测中的应用

目的 制备可用于血清LHBs检测的针对preS1高效单克隆抗体并进行初步临床应用研究.方法 对乙肝preS1区段基因(B基因型,adr血清亚型)全长序列(1～119 aa)进行密码子偏嗜性改造后,克隆入质粒pET32a构建原核表达重组质粒并转化入大肠杆菌BL21 (DE3),采用离子交换、HIS亲和层析柱以及肠激酶(E...     

呼吸机相关性肺炎与血清降钙素原水平

目的 通过测定血清降钙素原(PCT)水平,探讨PCT在诊断治疗呼吸机相关性肺炎(VAP)中的价值.方法 对30例VAP患者于确诊48 h内行PCT、血沉(ESR)及外周血白细胞(WBC)计数、中性粒细胞(N)比例及体温(T)测定.同时设20例非VAP组及10例健康对照组行相关指标检查.结果 VAP组PCT高于非VAP组...