抗肿瘤多肽类药物的来源及其机制的研究进展

恶性肿瘤已成为严重影响人类健康的一种疾病,其治疗手段一直是人们所探索的内容,药物治疗就是其中一种治疗方法。与传统化疗药物相比,抗肿瘤多肽类药物以其分子量小、特异性强、毒性低等特点作为新的治疗肿瘤药物一直广受人们关注。多肽的来源广泛,有存在于天然动植物及微生物体内,也可以通过蛋白质酶解或人工合成得到。近年来,越来越多的多肽类药物被发现除抗菌外还具有抗肿瘤的作用,其抗肿瘤的机制多种多样但尚未完全清楚,是许多研究者研究的重点。本文从多肽类药物的来源与特点及它们的抗肿瘤机制等方面对多肽类药物的研究进展进行综述。     

心脏磁共振特征追踪技术定量评价肥厚型心肌病患者心肌形变

目的 探讨心脏磁共振（CMR）特征追踪（CMR-FT）技术定量评价肥厚型心肌病（HCM）患者心肌形变的价值。方法 对16例HCM患者（HCM组）及18名健康志愿者（正常对照组）采用CMR-FT技术行CMR检查。比较两组间左心室舒张末期容积（LVEDV）、收缩末期容积（LVESV）、左心室射血分数（LVEF）、左心室质量（LVMASS）及左心室心肌整体径向应变（RS）、环向应变（CS）的差异。并分析HCM患者各节段室壁厚度与节段性RS、CS的相关性及整体RS、CS与LVEDV、LVESV、LVEF、LVMASS间的相关性。结果 HCM组的LVMASS高于正常对照组[（133.74±79.13）g vs（76.87±14.15）g,P=0.01]。两组间LVEDV、LVESV、LVEF差异均无统计学意义（P均>0.05）。HCM组心肌整体RS、CS值均明显低于正常对照组[RS：（27.05±13.35）% vs（40.62±4.92）%,P<0.01;CS：（-8.68±5.56）% vs（-20.73±1.56）%,P<0.01]。HCM患者各节段室壁厚度与节段性RS（r=-0.41,P<0.01）、CS（r=0.28,P<0.01）间无相关性;心肌整体RS（r=-0.36、-0.41、0.22、-0.36）、CS（r=0.34、0.10、0.22、0.42）与LVEDV、LVESV、LVEF、LVMASS间无相关性（P均>0.05）。结论 CMR-FT有助于定量评估HCM患者心肌形变情况。     

Assessment of cardiovascular physiology using dobutamine stress cardiovascular magnetic resonance reveals impaired contractile reserve in patients with cirrhotic cardiomyopathy

Background

Liver cirrhosis has been shown to affect cardiac performance. However cardiac dysfunction may only be revealed under stress conditions. The value of non-invasive stress tests in diagnosing cirrhotic cardiomyopathy is unclear. We sought to investigate the response to pharmacological stimulation with dobutamine in patients with cirrhosis using cardiovascular magnetic resonance.

Methods

Thirty-six patients and eight controls were scanned using a 1.5 T scanner (Siemens Symphony TIM; Siemens, Erlangen, Germany). Conventional volumetric and feature tracking analysis using dedicated software (CMR42; Circle Cardiovascular Imaging Inc, Calgary, Canada and Diogenes MRI; Tomtec; Germany, respectively) were performed at rest and during low to intermediate dose dobutamine stress.

Results

Whilst volumetry based parameters were similar between patients and controls at rest, patients had a smaller increase in cardiac output during stress (p = 0.015). Ejection fraction increase was impaired in patients during 10 μg/kg/min dobutamine as compared to controls (6.9 % vs. 16.5 %, p = 0.007), but not with 20 μg/kg/min (12.1 % vs. 17.6 %, p = 0.12). This was paralleled by an impaired improvement in circumferential strain with low dose (median increase of 14.4 % vs. 30.9 %, p = 0.03), but not with intermediate dose dobutamine (median increase of 29.4 % vs. 33.9 %, p = 0.54). There was an impaired longitudinal strain increase in patients as compared to controls during low (median increase of 6.6 % vs 28.6 %, p < 0.001) and intermediate dose dobutamine (median increase of 2.6%vs, 12.6 % p = 0.016). Radial strain response to dobutamine was similar in patients and controls (p > 0.05).

Conclusion

Cirrhotic cardiomyopathy is characterized by an impaired cardiac pharmacological response that can be detected with magnetic resonance myocardial stress testing. Deformation analysis parameters may be more sensitive in identifying abnormalities in inotropic response to stress than conventional methods.     

成人先天性主动脉缩窄临床特征分析

目的总结成人先天性主动脉缩窄患者的临床特征。资料与方法回顾分析2009年1月至2012年11月在阜外心血管病医院住院治疗的85例年龄大于14岁的先天性主动脉缩窄患者的临床特征。结果平均年龄(25.9±9.9)岁,其中74.1%患者既往有高血压病史,最高血压达到(191.0±26.8/101.7±22.4)mmHg(1mmHg=0.133kPa),合并其他先天性心血管疾病的占69.4%,39.5%的患者接受了外科手术治疗。37.2%的患者接受了介入治疗。结论成人主动脉缩窄患者多因不明原因的高血压而发现,易造成多种高血压并发症,且多合并其他先天性心血管异常,详细的体格检查,测量四肢血压有助于尽早诊断,自然预后差,一旦发现,应尽早进行介入或外科治疗。     

一个半综合征──附6例报道

一个半综合征是一种具有特征性的眼球运动障碍，也是一个具有重要定位意义的临床休征。本文报道６例思考并结合文献资料，对该综合征的临床表现、病变部位和病因进行了讨论。     

Failure of colour and contrast polarity identification at threshold for detection of motion and global form

We used identification at threshold to systematically measure binding costs in two visual modalities. We presented a conjunction of two features as a signal stimulus and concurrently measured detection and identification performance as a function of three threshold variables: duration, contrast and coherence. Discrepancies between detection and identification sensitivity functions demonstrated a consistent processing cost to visual feature binding. Our findings suggest that feature binding is indeed a genuine problem for the brain to solve. This simple paradigm can transfer across arbitrary feature combinations and is therefore suitable to use in experiments addressing mechanisms of sensory integration.     

GMDH-based feature ranking and selection for improved classification of medical data

Medical applications are often characterized by a large number of disease markers and a relatively small number of data records. We demonstrate that complete feature ranking followed by selection can lead to appreciable reductions in data dimensionality, with significant improvements in the implementation and performance of classifiers for medical diagnosis. We describe a novel approach for ranking all features according to their predictive quality using properties unique to learning algorithms based on the group method of data handling (GMDH). An abductive network training algorithm is repeatedly used to select groups of optimum predictors from the feature set at gradually increasing levels of model complexity specified by the user. Groups selected earlier are better predictors. The process is then repeated to rank features within individual groups. The resulting full feature ranking can be used to determine the optimum feature subset by starting at the top of the list and progressively including more features until the classification error rate on an out-of-sample evaluation set starts to increase due to overfitting. The approach is demonstrated on two medical diagnosis datasets (breast cancer and heart disease) and comparisons are made with other feature ranking and selection methods. Receiver operating characteristics (ROC) analysis is used to compare classifier performance. At default model complexity, dimensionality reduction of 22 and 54% could be achieved for the breast cancer and heart disease data, respectively, leading to improvements in the overall classification performance. For both datasets, considerable dimensionality reduction introduced no significant reduction in the area under the ROC curve. GMDH-based feature selection results have also proved effective with neural network classifiers.     

Diagnosing Aortic Valve Stenosis by Parameter Extraction of Heart Sound Signals

The objective of this study was to develop an automatic signal analysis system for heart sound diagnosis. This should support the general practitioner in discovering aortic valve stenoses at an early stage to avoid or decrease the number of surgical interventions. The applied analysis method is based on classification of heart sound signals utilising parameter extraction. From the wavelet decomposition of a representative heart cycle as well as from the Short Time Fourier Transform (STFT) and the Wavelet Transform (WT) spectra new time series were derived. In several segments, parameters were extracted and analysed. In addition, features of the Fast Fourier Transform (FFT) of the raw signal were examined. In this study, 206 patients were enrolled, 159 with no heart valve disease or any other heart valve disease but aortic valve stenosis and 47 suffering from aortic valve stenosis in a mild, moderate or severe stage. To separate the groups, a linear discriminant function analysis was applied leading to a reduced parameter set. The introduced two classification stage (CS) system for automatic detection of aortic valve stenoses achieves a high sensitivity of 100% for moderate and severe aortic valve stenosis and a sensitivity of 75% for mild aortic valve stenosis. A specificity of 93.7% for patients without aortic valve stenosis is provided. The developed method is robust, cost effective and easy to use, and could, therefore, be a suitable method to diagnose aortic valve stenosis by general practitioners.     

What goes through the gate? Exploring interference with visual feature binding

A series of experiments explored the mechanisms determining the encoding and storage of features and objects in visual working memory. We contrasted the effects of three types of visual suffix on cued recall of a display of colored shapes. The suffix was presented after the display and before the recall cue. The latter was either the color or shape of one of the objects and signaled recall of the object's other feature. In Experiments 1 and 2, we found a larger effect of ‘plausible’ suffixes comprising features (color and shape) drawn from the experimental set, relative to the effect of ‘implausible’ suffixes comprising features outside the experimental set. Experiment 3 extended this pattern by showing that ‘semi-plausible’ suffixes containing only one feature (either color or shape) from the experimental set had an equivalent effect to those with both features from the set. Reduction in accuracy was mainly due to an increase in recall of suffix features, rather than within-display confusions. The findings suggest a feature-based filtering process in visual working memory, with any stimuli that pass through this filter serving to directly overwrite existing object representations.     

Automatic recognition of five types of white blood cells in peripheral blood

This paper proposes image processing algorithms to recognize five types of white blood cells in peripheral blood automatically. First, a method based on Gram-Schmidt orthogonalization is proposed along with a snake algorithm to segment nucleus and cytoplasm of the cells. Then, a variety of features are extracted from the segmented regions. Next, most discriminative features are selected using a Sequential Forward Selection (SFS) algorithm and performances of two classifiers, Artificial Neural Network (ANN) and Support Vector Machine (SVM), are compared. The results demonstrate that the proposed methods are accurate and sufficiently fast to be used in hematological laboratories.