BACKGROUND & AIMS: :Mutations in the senataxin (SETX) gene can cause amyotrophic lateral sclerosis 4 (ALS4), an autosomal dominant form of juvenile onset amyotrophic lateral sclerosis, or result in autosomal recessive ataxia with oculomotor apraxia type 2. Great caution regarding the possible disease causation, especially of missense variations, has to be taken. Here, we evaluated the significance of all previously reported SETX missense mutations as well as six newly identified variations in 54 patients suspected of having ALS4. Yet, epidemiologic and in silico evidence indicates that all newly identified variations and two previously published ALS4-related missense variations (C1554G and I2547T) are most likely non-pathogenic, demonstrating the problems of interpretation of SETX missense alleles in the absence of functional assays.

背景与目标： ：senataxin（SETX）基因的突变可引起肌萎缩性侧索硬化4（ALS4），这是一种常染色体显性形式的青少年发作性肌萎缩性侧索硬化，或导致常染色体隐性共济失调并伴有2型动眼性运动失用。特别是错义的变化，必须采取。在这里，我们评估了54位怀疑患有ALS4的患者中所有先前报道的SETX错义突变以及6个新近发现的变异的重要性。然而，流行病学和计算机病学证据表明，所有新发现的变异和两个先前发布的与ALS4相关的错义变异（C1554G和I2547T）极有可能是非致病性的，这表明在缺乏功能检测的情况下，SETX错义等位基因的解释存在问题。

BACKGROUND & AIMS: :The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38α MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.

背景与目标： ：p38丝裂原活化蛋白激酶（MAPK）抑制剂的抗炎潜能同时扩展到了p38αMAPK和磷酸二酯酶4（PDE4）的双重抑制作用，并且两种炎症相关酶均被阻断产生了潜在的益处调查。给啮齿动物，狗和猴子施用1后，在体外实验以及离体和体内临床前研究中相继评估了最有前途的化合物CBS-3595（1）。所得数据清楚地表明有效抑制了肿瘤坏死因子α的释放。为了确认对健康的人类志愿者给药1时动物研究的结果，进行了I期临床试验。除了有关1的药代动力学和药效学特性的进一步信息外，还证明了对p38αMAPK和PDE4的双重抑制能够协同减弱过度的抗炎反应。

BACKGROUND & AIMS: BACKGROUND:We modified and reconstructed a high image quality portable non-mydriatic fundus camera and compared it with the tabletop fundus camera to evaluate the efficacy of the new camera in detecting retinal diseases. METHODS:We designed and built a novel portable handheld fundus camera with telemedicine system. The image quality of fundus cameras was compared to that of existing commercial tabletop cameras by taking photographs of 364 eyes from the 254 patients. In all 800 fundus images taken by two camera types, 400 images per camera, were graded with the four image clarity classifications. RESULTS:Using the portable fundus camera, 63% (252/400) images were graded as excellent overall quality, 20.5% (82/400) were good, 11.75% (47/400) were fair, and 4.75% (19/400) were inadequate. Using the tabletop fundus camera, 70.75% (283/400) images were graded as excellent overall quality, 20.4% (51/400) were good, 13.25% (53/400) were fair, and 3.25% (13/400) were inadequate. Common retinal diseases were easily identified from fundus images obtained from the portable fundus camera. CONCLUSION:The new type of non-mydriatic portable fundus camera was qualified to have professional quality of fundus images. The revolutionary screening camera provides a foundational platform which can potentially improve the accessibility of retinal screening programmes.

背景与目标： 背景：我们修改并重建了高图像质量的便携式非散瞳眼底照相机，并将其与台式眼底照相机进行比较，以评估新照相机在检测视网膜疾病中的功效。
方法：我们设计并制造了一种新型的带有远程医疗系统的便携式手持眼底照相机。通过拍摄254名患者的364眼照片，将眼底照相机的图像质量与现有商用台式照相机的图像质量进行了比较。在两种相机类型拍摄的全部800张眼底图像中，每台相机400张图像被分为四个图像清晰度分类。
结果：使用便携式眼底照相机，将63％（252/400）的图像评为总体质量优良，20.5％（82/400）的图像质量良好，11.75％（47/400）的图像是良好的，以及4.75％（19/400）的图像）不足。使用台式眼底照相机，将70.75％（283/400）的图像评为总体质量优良，20.4％（51/400）的图像质量良好，13.25％（53/400）的图像质量良好，3.25％（13/400）的图像质量良好不足。从便携式眼底照相机获得的眼底图像很容易识别出常见的视网膜疾病。
结论：新型非散瞳便携式眼底照相机经鉴定具有专业的眼底图像质量。革命性的筛查摄像机提供了一个基础平台，可以潜在地改善视网膜筛查程序的可及性。

BACKGROUND & AIMS: :The prevalence of renal diseases is rising and reaching 5-15% of the adult population. Renal damage is associated with disturbances of body homeostasis and the loss of equilibrium between exogenous and endogenous elements including drugs and metabolites. Studies indicate that renal diseases are influenced not only by environmental but also by genetic factors. In some cases the disease is caused by mutation in a single gene and at that time severity depends on the presence of one or two mutated alleles. In other cases, renal disease is associated with the presence of alteration within a gene or genes, but environmental factors are also necessary for the development of disease. Therefore, it seems that the analysis of genetic aspects should be a natural component of clinical and experimental studies. The goal of personalized medicine is to determine the right drug, for the right patient, at the right time. Whole-genome examinations may help to change the approach to the disease and the patient resulting in the creation of "personalized medicine" with new diagnostic and treatment strategies designed on the basis of genetic background of each individual. The identification of high-risk patients in pharmacogenomics analyses will help to avoid many unwarranted side effects while optimizing treatment efficacy for individual patients. Personalized therapies for kidney diseases are still at the preliminary stage mainly due to high costs of such analyses and the complex nature of human genome. This review will focus on several areas of interest: renal disease pathogenesis, diagnosis, treatment, rate of progression and the prediction of prognosis.

背景与目标： ：肾脏疾病的患病率正在上升，并达到成年人口的5-15％。肾脏损害与体内稳态紊乱以及包括药物和代谢产物在内的外源性和内源性元素之间失去平衡有关。研究表明，肾脏疾病不仅受环境影响，而且受遗传因素影响。在某些情况下，该疾病是由单个基因的突变引起的，当时的严重程度取决于一个或两个突变等位基因的存在。在其他情况下，肾脏疾病与一个或多个基因内的改变的存在有关，但是环境因素对于疾病的发展也是必不可少的。因此，似乎遗传方面的分析应该是临床和实验研究的自然组成部分。个性化医学的目标是在正确的时间为正确的患者确定正确的药物。全基因组检查可能有助于改变疾病和患者的治疗方法，从而通过根据每个人的遗传背景设计新的诊断和治疗策略来创建“个性化药物”。在药物基因组学分析中识别高危患者将有助于避免许多不必要的副作用，同时优化单个患者的治疗效果。肾脏疾病的个性化治疗仍处于初步阶段，这主要是由于此类分析的高昂费用和人类基因组的复杂性。这项审查将集中在几个感兴趣的领域：肾脏疾病的发病机制，诊断，治疗，进展的速度和预后的预测。

BACKGROUND & AIMS: OBJECTIVE:Genetic susceptibility to inflammatory bowel disease is well recognized. There is also increasing evidence for the activation of the mucosal immune system and the production of inflammatory cytokines, i.e., interleukin (IL)-1ra and IL-1beta in the inflammatory bowel disease. The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease.

METHODS:Two hundred twenty-eight inflammatory bowel disease patients (87 UC and 141 CD) were included in this study and compared with 113 unrelated controls. The IL-1beta and IL-1ra gene polymorphism was studied after specific amplification of variable regions by PCR. A penta-allelic polymorphism, corresponding to a VNTR region located in intron 2 of the IL-1ra gene, was analyzed, whereas bi-allelic RFLPs displayed by two restriction enzymes (TaqI and AvaI) at position -511 of the IL-1beta gene were analyzed.

RESULTS:There was no significant difference of genotype distribution between controls and CD or UC patients. However, surgically treated UC patients were characterized by a higher frequency of genotype IL-1ra 1-2 (39 vs 16%, pc < 0.01) compared with nonoperated UC patients. Moreover, nonoperated UC patients displayed a lower frequency of IL-1ra allele 2 than surgically treated UC patients (14 vs 34%, pc < 0.002) or controls (14 vs 30%, pc < 0.005). Furthermore, simultaneous analysis of the IL-1beta and IL-1ra genes that are located in the same region of chromosome 2 revealed that CD patients carrying the IL-1beta allele 2 were more often noncarriers of IL-1ra allele 2 (p < 0.005). Moreover, UC and CD patients were, characterized by a lower frequency of the association of IL-1ra allele 2 and IL-1beta allele 2 compared with controls (8.3 vs 20.3% and 10.6 vs 20.3%, p < 0.03).

CONCLUSIONS:IL-1ra and IL-1beta gene polymorphism analysis from a clinical standpoint might help in defining UC prognosis. However, functional studies at both the circulating and mucosal level with stratification on allele associations, especially IL-1ra allele 2-IL-1beta allele 2 subgroups must be realized before therapeutic implications.

背景与目标： 目标：人们对炎症性肠病的遗传易感性已广为人知。也有越来越多的证据表明在炎症性肠病中粘膜免疫系统的活化和炎性细胞因子，即白介素（IL）-1ra和IL-1β的产生。这项研究的目的是分析克罗恩病（CD）或溃疡性结肠炎（UC）患者的IL-1beta和IL-1ra基因多态性以及这些基因的不同等位基因之间的连锁不平衡系数。

方法：该研究纳入了288例炎症性肠病患者（87 UC和141 CD），并与113个无关的对照组进行了比较。在通过PCR特异性扩增可变区之后，研究了IL-1β和IL-1ra基因多态性。分析了一个五等位基因多态性，对应于位于IL-1ra基因内含子2的VNTR区，而在IL-1beta基因第-511位的两个限制性酶（TaqI和AvaI）显示的双等位基因RFLP

结果：对照组和CD或UC患者之间的基因型分布没有显着差异。然而，与未手术的UC患者相比，接受手术治疗的UC患者的特征在于基因型IL-1ra 1-2的发生频率更高（39％vs 16％，pc <0.01）。此外，未手术的UC患者显示出IL-1ra等位基因2的频率低于手术治疗的UC患者（14 vs 34％，pc <0.002）或对照组（14 vs 30％，pc <0.005）。此外，同时分析位于2号染色体同一区域的IL-1beta和IL-1ra基因发现，携带IL-1beta等位基因2的CD患者更常为IL-1ra等位基因2的非携带者（p <0.005） 。此外，UC和CD患者的特征是与对照组相比，IL-1ra等位基因2和IL-1β等位基因2的关联频率较低（8.3 vs 20.3％和10.6 vs 20.3％，p <0.03）。
结论：从临床角度分析IL-1ra和IL-1beta基因多态性可能有助于确定UC的预后。但是，必须在循环和粘膜水平上对等位基因关联，特别是IL-1ra等位基因2-IL-1beta等位基因2亚组进行分层的功能研究。