螺旋CT增强扫描对孤立性肺结节的诊断价值

目的:研究螺旋CT增强扫描时孤立性肺结节的诊断价值。方法:回顾分析经病理证实的恶性结节50例、炎性结节26例、结核瘤12例的螺旋CT增强扫描的表现。结果:恶性结节和炎性结节增强扫描的强化程度明显高于结核瘤(P＜0．05)。炎性结节强化峰值的时间较恶性结节延迟。恶性结节增强扫描出现点、条状及边缘强化。结论:螺旋CT增强扫描对孤立性肺结节的诊断具有重要临床应用价值。     

PBL教学法联合PACS系统在医学影像学教学中的应用

目的:探讨采用PBL和PACS相结合的教学模式在影像学实习教学中的应用效果。方法:对我院2010级临床本科生40人采用传统教学法授课,另40人采用PBL和PACS相结合的教学法授课。课程结束后以考试成绩作为教学效果的评价指标,评价两种教学方法的教学效果;以调查问卷的方法评价学生对两种教学方法的感兴趣程度,并对结果进行统计学分析。结果:我们的研究结果显示,采用PBL和PACS相结合的方法进行教学的学生与传统教学法相比,理论考试成绩有所提高,但缺乏统计学意义(p0.05),病例分析成绩显著提高,差异有统计学意义(P0.05)。问卷调查显示,PBL和PACS结合的教学方法更受同学欢迎,更能培养学生的自学能力和团队合作能力(P0.05)。结论:采用PBL和PACS相结合的教学方法,有助于提高学生的学习兴趣,提高学习成绩,值得在教学中应用。     

肩袖间隙影像解剖及常见病变的研究进展

肩袖间隙在解剖学上是肩关节的一个复合区域,在维持肩关节稳定性和保护肱二头肌长头肌腱功能起重要作用。对肩袖间隙解剖结构及功能的深入认识有助于肩袖间隙损伤性病变、挛缩性病变等的及时诊断和合理治疗。影像学检查尤其是磁共振逐步成为肩袖间隙疾病最主要的检查方法,包括常规扫描、直接及间接性磁共振肩关节造影、增强扫描等。本文将就肩袖间隙的影像解剖及常见病变的相关研究进行综述。     

Inhibition of Paclitaxel-induced Decreases in Calcium Signaling

Peripheral neuropathy is one of the most severe and irreversible side effects caused by treatment from several chemotherapeutic drugs, including paclitaxel (Taxol®) and vincristine. Strategies are needed that inhibit this unwanted side effect without altering the chemotherapeutic action of these drugs. We previously identified two proteins in the cellular pathway that lead to Taxol-induced peripheral neuropathy, neuronal calcium sensor-1 (NCS-1) and calpain. Prolonged treatment with Taxol induces activation of calpain, degradation of NCS-1, and loss of intracellular calcium signaling. This paper has focused on understanding the molecular basis for prevention of peripheral neuropathy by testing the effects of addition of two candidate compounds to the existing chemotherapeutic drug regime: lithium and ibudilast. We found that the co-administration of either lithium or ibudilast to neuroblastoma cells that were treated with Taxol or vincristine inhibited activation of calpain and the reductions in NCS-1 levels and calcium signaling associated with these chemotherapeutic drugs. The ability of Taxol to alter microtubule formation was unchanged by the addition of either candidate compound. These results allow us to suggest that it is possible to prevent the unnecessary and irreversible damage caused by chemotherapeutic drugs while still maintaining therapeutic efficacy. Specifically, the addition of either lithium or ibudilast to existing chemotherapy treatment protocols has the potential to prevent chemotherapy-induced peripheral neuropathy.     

Systems Analysis of Cancer Cell Heterogeneity in Caspase-dependent Apoptosis Subsequent to Mitochondrial Outer Membrane Permeabilization

Deregulation of apoptosis is a hallmark of carcinogenesis. We here combine live cell imaging and systems modeling to investigate caspase-dependent apoptosis execution subsequent to mitochondrial outer membrane permeabilization (MOMP) in several cancer cell lines. We demonstrate that, although most cell lines that underwent MOMP also showed robust and fast activation of executioner caspases and apoptosis, the colorectal cancer cell lines LoVo and HCT-116 Smac^−/−, similar to X-linked inhibitor of apoptosis protein (XIAP)-overexpressing HeLa (HeLa XIAP^Adv) cells, only showed delayed and often no caspase activation, suggesting apoptosis impairment subsequent to MOMP. Employing APOPTO-CELL, a recently established model of apoptosis subsequent to MOMP, this impairment could be understood by studying the systemic interaction of five proteins that are present in the apoptosis pathway subsequent to MOMP. Using APOPTO-CELL as a tool to study detailed molecular mechanisms during apoptosis execution in individual cell lines, we demonstrate that caspase-9 was the most important regulator in DLD-1, HCT-116, and HeLa cells and identified additional cell line-specific co-regulators. Developing and applying a computational workflow for parameter screening, systems modeling identified that apoptosis execution kinetics are more robust against changes in reaction kinetics in HCT-116 and HeLa than in DLD-1 cells. Our systems modeling study is the first to draw attention to the variability in cell specific protein levels and reaction rates and to the emergent effects of such variability on the efficiency of apoptosis execution and on apoptosis impairment subsequent to MOMP.     

Amyloid β (Aβ) peptide directly activates amylin-3 receptor subtype by triggering multiple intracellular signaling pathways

The two age-prevalent diseases Alzheimer disease and type 2 diabetes mellitus share many common features including the deposition of amyloidogenic proteins, amyloid β protein (Aβ) and amylin (islet amyloid polypeptide), respectively. Recent evidence suggests that both Aβ and amylin may express their effects through the amylin receptor, although the precise mechanisms for this interaction at a cellular level are unknown. Here, we studied this by generating HEK293 cells with stable expression of an isoform of the amylin receptor family, amylin receptor-3 (AMY3). Aβ1-42 and human amylin (hAmylin) increase cytosolic cAMP and Ca(2+), trigger multiple pathways involving the signal transduction mediators protein kinase A, MAPK, Akt, and cFos. Aβ1-42 and hAmylin also induce cell death during exposure for 24-48 h at low micromolar concentrations. In the presence of hAmylin, Aβ1-42 effects on HEK293-AMY3-expressing cells are occluded, suggesting a shared mechanism of action between the two peptides. Amylin receptor antagonist AC253 blocks increases in intracellular Ca(2+), activation of protein kinase A, MAPK, Akt, cFos, and cell death, which occur upon AMY3 activation with hAmylin, Aβ1-42, or their co-application. Our data suggest that AMY3 plays an important role by serving as a receptor target for actions Aβ and thus may represent a novel therapeutic target for development of compounds to treat neurodegenerative conditions such as Alzheimer disease.     

ATP binding site mutagenesis reveals different subunit stoichiometry of functional P2X2/3 and P2X2/6 receptors

The aim of the present experiments was to clarify the subunit stoichiometry of P2X2/3 and P2X2/6 receptors, where the same subunit (P2X2) forms a receptor with two different partners (P2X3 or P2X6). For this purpose, four non-functional Ala mutants of the P2X2, P2X3, and P2X6 subunits were generated by replacing single, homologous amino acids particularly important for agonist binding. Co-expression of these mutants in HEK293 cells to yield the P2X2 WT/P2X3 mutant or P2X2 mutant/P2X3 WT receptors resulted in a selective blockade of agonist responses in the former combination only. In contrast, of the P2X2 WT/P2X6 mutant and P2X2 mutant/P2X6 WT receptors, only the latter combination failed to respond to agonists. The effects of α,β-methylene-ATP and 2-methylthio-ATP were determined by measuring transmembrane currents by the patch clamp technique and intracellular Ca(2+) transients by the Ca(2+)-imaging method. Protein labeling, purification, and PAGE confirmed the assembly and surface trafficking of the investigated WT and WT/mutant combinations in Xenopus laevis oocytes. In conclusion, both electrophysiological and biochemical investigations uniformly indicate that one subunit of P2X2 and two subunits of P2X3 form P2X2/3 heteromeric receptors, whereas two subunits of P2X2 and one subunit of P2X6 constitute P2X2/6 receptors. Further, it was shown that already two binding sites of the three possible ones are sufficient to allow these receptors to react with their agonists.     

Formyl Peptide Receptors from Immune and Vomeronasal System Exhibit Distinct Agonist Properties

The formyl peptide receptor (Fpr) family is well known for its contribution to immune defense against pathogens in human and rodent leukocytes. Recently, several structurally related members of these receptors were discovered in sensory neurons of the mouse vomeronasal organ (VNO), key detectors of pheromones and related semiochemicals. Although the biological role of vomeronasal Fprs is not yet clear, the known contribution of other Fprs to host immune defense suggested that they could contribute to vomeronasal pathogen sensing. Precise knowledge about the agonist properties of mouse Fprs is required to determine their function. We expressed all seven mouse and three human Fprs using an in vitro system and tested their activation with 32 selected compounds by conducting high throughput calcium measurements. We found an intriguing functional conservation between human and mouse immune Fprs that is most likely a consequence of closely similar biological constraints. By contrast, our data suggest a neofunctionalization of the vomeronasal Fprs. We show that the vomeronasal receptor mFpr-rs1 can be activated robustly by W-peptide and structural derivatives but not by other typical ligands of immune Fprs. mFpr-rs1 exhibits a stereo-selective preference for peptides containing d-amino acids. The same peptide motifs are contained in pathogenic microorganisms. Thus, the ligand profile of mFpr-rs1 is consistent with a role in vomeronasal pathogen sensing.     

编者按: 脑成像与脑网络

揭示脑的奥秘是人类面临的最大挑战之一。神经元是构成神经系统结构与功能的基本单位。神经元与神经元之间通过突触实现信息交互,并构成神经环路或神经网络。神经环路有局部的,也有跨脑区或长程的,甚至全脑尺度的。神经环路则是脑实现神经信息处理的基本单元。若干神经环路构成脑网络。脑网络研究已经成为脑功能与脑疾病研究领域的热点。 在国家自然科学基金委员会和科技部“973计划”等项目的支持下,我国科学家在这一领域已经开展了卓有成效的工作。2011年第393次香山科学会议“脑网络组及其临床应用的前沿科学问题”曾对此进行过比较深入的研讨。为促进对该领域现状及发展的了解,本期汇集了2篇述评和2篇研究论文,作为脑成像与脑网络专题发表,以飨读者。 利用9.4T功能磁共振成像(fMRI)获得轻度麻醉状态下大鼠静息状态及刺激激活的数据,通过互相关分析构建节点之间的相关系数矩阵并计算相应的网络参数,赖永秀等人报道了大鼠感觉运动系统静息态脑网络的研究成果,发现感觉运动系统在静息态时的脑网络具有小世界属性。 扩散磁共振成像(dMRI)的出现为大脑结构与功能研究提供了全新的检测手段,雷皓等报道了小动物高分辨扩散磁共振成像数据分析方法,为小动物脑dMRI研究提供了统一图像模板与完善的计算方法,对于检测神经纤维微观结构的变化,以及临床诊断,将具有极其重要的意义。 神经环路功能变化的实时在体监测是研究脑网络不可或缺的手段,曾绍群等评述了基于声光偏转器的快速无惯性随机扫描双光子显微成像技术的研究进展及发展趋势,指出该技术的进一步发展将为神经活动观测提供一种全新的方法,从而极大地推动脑科学研究的发展。 针对哺乳动物全脑的神经元网络成像,龚辉等从空间分辨率、探测范围、数据配准和成像速度等方面评述了光学显微水平全脑成像方法的研究进展,并讨论所面临的挑战。他们指出,要在全脑尺度获取突起水平分辨率的结构与功能数据,光学成像方法最为成熟。华中科技大学研制的MOST系统,率先获得了一系列高分辨率的完整大脑解剖数据集,该成果将在神经元网络的构建和脑功能与疾病研究中发挥重要作用。 我们期待更多、更好的有关脑成像与脑网络的论文发表,以更广泛和深入地促进我国脑科学研究领域的学术交流。     

Novel dermaseptins from Phyllomedusa hypochondrialis (Amphibia)

Six new antimicrobial peptides structurally related to the dermaseptin family have been isolated from the skin secretion of the amphibian Phyllomedusa hypochondrialis. The primary structures of these molecules named as DShypo 01, 02, 03, 04, 06, and 07 were determined by de novo MS/MS experiments, Edman degradation, and cDNA sequencing. The fifth peptide was found to be precisely the same DS 01 from Phyllomedusa oreades previously described by our group. The majority of the peptides purified from the crude skin secretion could be directly localized and mapped onto a freshly dissected dorsal skin fragment using mass spectrometry-imaging techniques. Comparisons between peptides and commercial drugs on their antibacterial and anti-Leishmania amazonensis efficiencies, associated with peptide lytic effects on mammalian blood cells and surface plasmon resonance interaction studies on immobilized DMPC vesicles, were also performed.