Inherited Platelet Disorders: An Updated Overview

Platelets play a major role in hemostasis as ppwell as in many other physiological and pathological processes. Accordingly, production of about 10¹¹ platelet per day as well as appropriate survival and functions are life essential events. Inherited platelet disorders (IPDs), affecting either platelet count or platelet functions, comprise a heterogenous group of about sixty rare diseases caused by molecular anomalies in many culprit genes. Their clinical relevance is highly variable according to the specific disease and even within the same type, ranging from almost negligible to life-threatening. Mucocutaneous bleeding diathesis (epistaxis, gum bleeding, purpura, menorrhagia), but also multisystemic disorders and/or malignancy comprise the clinical spectrum of IPDs. The early and accurate diagnosis of IPDs and a close patient medical follow-up is of great importance. A genotype–phenotype relationship in many IPDs makes a molecular diagnosis especially relevant to proper clinical management. Genetic diagnosis of IPDs has been greatly facilitated by the introduction of high throughput sequencing (HTS) techniques into mainstream investigation practice in these diseases. However, there are still unsolved ethical concerns on general genetic investigations. Patients should be informed and comprehend the potential implications of their genetic analysis. Unlike the progress in diagnosis, there have been no major advances in the clinical management of IPDs. Educational and preventive measures, few hemostatic drugs, platelet transfusions, thrombopoietin receptor agonists, and in life-threatening IPDs, allogeneic hematopoietic stem cell transplantation are therapeutic possibilities. Gene therapy may be a future option. Regular follow-up by a specialized hematology service with multidisciplinary support especially for syndromic IPDs is mandatory.     

A Multi-Strategy Sequencing Workflow in Inherited Retinal Dystrophies: Routine Diagnosis,Addressing Unsolved Cases and Candidate Genes Identification

The management of unsolved inherited retinal dystrophies (IRD) cases is challenging since no standard pipelines have been established. This study aimed to define a diagnostic algorithm useful for the diagnostic routine and to address unsolved cases. Here, we applied a Next-Generation Sequencing-based workflow, including a first step of panel sequencing (PS) followed by clinical-exome sequencing (CES) and whole-exome sequencing (WES), in 46 IRD patients belonging to 42 families. Twenty-six likely causal variants in retinal genes were found by PS and CES. CES and WES allowed proposing two novel candidate loci (WDFY3 and a X-linked region including CITED1), both abundantly expressed in human retina according to RT-PCR and immunohistochemistry. After comparison studies, PS showed the best quality and cost values, CES and WES involved similar analytical efforts and WES presented the highest diagnostic yield. These results reinforce the relevance of panels as a first step in the diagnostic routine and suggest WES as the next strategy for unsolved cases, reserving CES for the simultaneous study of multiple conditions. Standardizing this algorithm would enhance the efficiency and equity of clinical genetics practice. Furthermore, the identified candidate genes could contribute to increase the diagnostic yield and expand the mutational spectrum in these disorders.     

继承性构造与新生构造并存的时空发育特征——“盆”“山”耦合理论指导油气勘探的一个切入点

研究继承性构造与新生构造并存的时空发育特征是"盆""山"耦合理论指导油气勘探的一个切入点。文章从超大陆旋回,成盆动力学和含油气构造带研究3方面展开论述,强调"寻根溯源",在具体分析每一阶段的新生构造时注意基底/先存构造的影响,从含油气盆地的研究深入到含油气构造带的研究,从盆地的运动学研究发展到动力学(包括外动力和内动力)研究。在分析新生构造演化的2种趋势的基础上指出了海相油气勘探的3类主要靶区。以新生构造的演化为主线,结合"源""运""聚""藏"的研究,借鉴石油地质学研究的其它新思想,"盆""山"耦合将成为指导油气勘探尤其是海相油气勘探的创新思路之一。     

Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies

Inherited neuropathies known as Charcot-Marie-Tooth (CMT) disease are genetically heterogeneous disorders affecting the peripheral nerves, causing significant and slowly progressive disability over the lifespan. The discovery of their diverse molecular genetic mechanisms over the past three decades has provided the basis for developing a wide range of therapeutics, leading to an exciting era of finding treatments for this, until now, incurable group of diseases. Many treatment approaches, including gene silencing and gene replacement therapies, as well as small molecule treatments are currently in preclinical testing while several have also reached clinical trial stage. Some of the treatment approaches are disease-specific targeted to the unique disease mechanism of each CMT form, while other therapeutics target common pathways shared by several or all CMT types. As promising treatments reach the stage of clinical translation, optimal outcome measures, novel biomarkers and appropriate trial designs are crucial in order to facilitate successful testing and validation of novel treatments for CMT patients.     

论平顶山煤田锅底山断层

研究表明，平顶山煤田锅底山断层是１个同沉积、继承性控煤断层。它在聚煤期就已活动。从断层落差、岩性、厚度、含煤性等方面论证了同沉积性质，聚煤期后又发生了继承性的活动。锅底山断层的这一发现，对指导煤矿开采、深入研究平顶山煤田构造乃至华北板块的构造演化，均具有重要的理论和实际意义。     

川中乐山—龙女寺古隆起震旦系天然气成藏条件分析

认为四川盆地中部乐山—龙女寺古隆起震旦系含油气系统属多源多期成藏的复合含油气系统，烃源主要来自下寒武统筇竹寺组底部腐泥型暗色泥岩，其次为震旦系灯影组三段暗色藻白云岩和页岩；最有利的储盖组合是以灯影组四段、三段为储集层和以下寒武统黑色页岩为盖层的组合，其次是灯影组三段中部的白云岩段储盖组合。灯三段烃源岩在奥陶纪末—志留纪进入大量生烃期，生成的液态烃在古隆起顶部形成古油藏，志留纪末的抬升终止了第一期成烃作用，晚二叠世以来进入二次生烃期；三叠纪—中侏罗世，筇竹寺组烃源岩进入主要生烃期，在古隆起顶部灯影组风化壳形成古油气藏；晚侏罗世—早白垩世，筇竹寺组烃源岩处于生气高峰期，古油气藏的液态烃热裂解成气态烃，这些气态烃聚集形成现今的气藏。乐山—龙女寺古隆起震旦系储盖和保存条件较好，高石梯—磨溪潜伏构造带及华蓥山构造带是有利勘探区。     

SOS显色法在供水工程水源水遗传毒性研究中的应用

本文介绍一种最为快速简便的检测遗传毒物的方法－ＳＯＳ显色法；并用该法对广东某供水工程水源水的有机提取进行了研究。进一步证明了前Ａｍｅｓ法的结果。     

数据挖掘算法研究与综述

信息化的到来导致数据急剧膨胀，从大量的数据中提取有用信息并非易事，数据挖掘就是为了满足这种需要而产生的。论文介绍了数据挖掘的相关理论知识和算法，算法有关联规则、遗传算法和决策树，对这些算法进行了分析研究，并找出其局限性。     

求解双资源约束车间调度问题的继承式双目标遗传算法

针对双资源约束作业车间调度的双目标优化问题,提出一种继承式遗传算法,通过分支种群继承父辈种群的进化经验．该算法面向双资源约束特点,采用4维染色体编码方式,基于时间窗口比较实现活动化调度,通过资源进化算子提高算法全局搜索能力;基于个体Pareto指数的锦标赛选择策略,有效削弱了染色体Pareto排序级别对个体存活概率的影响以保持群体多样性,并利用精英保留策略提高了解的收敛性．仿真实验与分析结果表明了所提算法具有优良性能．     

串联质谱在新生儿遗传代谢性疾病筛查中的应用

遗传代谢性疾病是一类由于单基因缺陷而引起代谢途径阻断的疾病.许多遗传代谢性疾病对新生儿危害极大,因此是新生儿筛查的主要内容.串联质谱用于新生儿筛查是自Guthrie将细菌抑制法用于苯丙酮尿症筛查以来,新生儿筛查史上最重要的技术革新.近年来,串联质谱已成为新生儿遗传代谢性疾病筛查中最具发展潜力的"朝阳"技术.本文介绍串联...