磷脂酰肌醇蛋白聚糖3和泛素D基因在肝细胞癌中的异常表达及其相互作用

目的 利用基因组学和表观遗传组学分析工具,分析磷脂酰肌醇蛋白聚糖3（GPC3）和泛素D（UBD）在肝细胞癌（HCC）中的异常表达情况,以及两者对HCC患者预后的影响。 方法 利用ULCAN（http://ualan.path.uab.edu）和Gene Expression Profiling Interative Analysis(GEPIA)数据库,分析UBD和GPC3在正常肝组织和HCC组织的异常表达情况和甲基化水平,以及对HCC患者生存的影响。利用GeneCards数据库分析UBD和GPC3的定位。利用STRING数据库对UBD和GPC3分别构建蛋白质互相作用（PPI）网络,并对UBD和GPC3进行基因注释。基于皮尔森相关系数,计算UBD和GPC3在HCC发生发展中的关联。 结果 UBD和GPC3在HCC组织中表达上调,启动子甲基化水平下降。UBD位于6p22.1,主要表达于细胞核;GPC3位于Xq26.2,主要表达于细胞膜、细胞外基质、内质网、溶酶体和高尔基体。富集分析显示,UBD主要与蛋白酶体活动相关：翻译后蛋白修饰、泛素化和去泛素化;GPC3主要参与黏多糖的生物合成和分解过程,介导的生物通路主要涉及癌症多聚糖、细胞外基质受体相互作用和细胞黏附分子。关联分析显示,UBD和GPC3成线性正相关,共同调控HCC的发生发展。预后分析显示,GPC3对HCC的预后有明显的影响。 结论 UBD和GPC3在HCC的表达均上调,甲基化水平均降低,GPC3对HCC的预后影响较大,或许可以作为预后评估的生物标志。     

Mutations and polymorphisms of the skeletal muscle α‐actin gene (ACTA1)

The ACTA1 gene encodes skeletal muscle α‐actin, which is the predominant actin isoform in the sarcomeric thin filaments of adult skeletal muscle, and essential, along with myosin, for muscle contraction. ACTA1 disease‐causing mutations were first described in 1999, when a total of 15 mutations were known. In this article we describe 177 different disease‐causing ACTA1 mutations, including 85 that have not been described before. ACTA1 mutations result in five overlapping congenital myopathies: nemaline myopathy; intranuclear rod myopathy; actin filament aggregate myopathy; congenital fiber type disproportion; and myopathy with core‐like areas. Mixtures of these histopathological phenotypes may be seen in a single biopsy from one patient. Irrespective of the histopathology, the disease is frequently clinically severe, with many patients dying within the first year of life. Most mutations are dominant and most patients have de novo mutations not present in the peripheral blood DNA of either parent. Only 10% of mutations are recessive and they are genetic or functional null mutations. To aid molecular diagnosis and establishing genotype–phenotype correlations, we have developed a locus‐specific database for ACTA1 variations ( http://waimr.uwa.edu.au ). Hum Mutat 30:1–11, 2009. © 2009 Wiley‐Liss, Inc.     

术后放疗在声门上型喉鳞状细胞癌治疗中的价值

目的：评估手术后辅助放疗（postoperative radiotherapy,PORT）在声门上型喉鳞状细胞癌治疗中的作用。方法：搜集美国监测、流行病学和最终结果（Surveillance,Epidemiology,and End Results,SEER）数据库中2004年至2015年接受手术治疗的831例声门上型喉鳞状细胞癌患者的临床资料,根据术后是否接受放疗分为PORT（-）组及PORT（+）组,应用倾向性评分匹配法（propensity score matching,PSM）均衡2组间变量的差异,采用Kaplan-Meier及log-rank检验进行生存分析并进行亚组分析,比较2组间总生存（overall survival,OS）和肿瘤特异性生存（cancer specific survival,CSS）的差异,分析PORT在声门上型喉鳞状细胞癌患者治疗中的价值及获益人群。结果：倾向性评分匹配前,PORT（-）组及PORT（+）组的OS无统计学差异,而PORT（+）组的CSS较PORT（-）组更差（P=0.022）。对阳性淋巴数的亚组分析显示,阳性淋巴结数为0和1的患者,PO...     

Selecting an Appropriate Medication for Treating Neuropathic Pain in Patients with Diabetes: A Study Using the U.K. and Germany Mediplus Databases

Objective:   To evaluate the appropriateness of prescribing select neuropathic pain medications to diabetes patients based on the potential for drug–drug interactions with medications diabetes patients were prescribed continuously for ≥ 3 months (chronic use).
Methods:   Medical records of patients with a diagnosis of diabetes or use of antidiabetic medications between January 1, 2002 and September 30, 2005 in the U.K. and Germany Mediplus databases were obtained.
Patients:   Medication use profiles were evaluated between April 2004 and September 2005. The metabolic pathways associated with medications that were prescribed chronically to at least 10% of study patients were compared with the metabolic pathways of neuropathic pain medications to identify potential drug–drug interactions.
Results:   A total of 40,448 patients in the U.K. (63.6 ± 16.6 years, 51% male) and 31,930 patients in Germany (68.9 ± 12.7 years, 46% male) were identified. Frequently prescribed medications in the U.K. included aspirin (33.7%), metformin (32.7%), simvastatin (25.5%), atorvastatin (19.4%), atenolol (18.1%), and in Germany hydrochlorothiazide (35.8%), aspirin (25.2%), metformin (21.6%), metoprolol (20.3%), and simvastatin (18.3%). Several neuropathic pain medications have potential for drug–drug interactions with medications prescribed to diabetes patients. Examples include (neuropathic pain medications vs. diabetes medications): duloxetine, paroxetine, and methadone (CYP2D6 inhibitors) and oxycodone HCL, hydrocodone (CYP2D6 substrates) vs. metoprolol and bisoprolol (CYP2D6 substrates); and carbamazepine (CYP3A4 inducer) vs. simvastatin, and atorvastatin (CYP3A4 substrates).
Conclusions/Interpretation:   Our findings underscore the need for medical vigilance when selecting medications for treating neuropathic pain in diabetes patients. ▪