Genetic association of CHEK2, GSTP1, and ERCC1 with glioblastoma in the Han Chinese population

Glioblastoma (GBM), a deadly brain tumor, is the most malignant glioma. It mainly occurs in adults and occurs significantly more in males than in females. We genotyped 19 tag single nucleotide polymorphisms (tSNPs) from 13 genes in a case–control study of the Han Chinese population to identify genetic factors contributing to the risk of GBM. These tSNPs were genotyped by Sequenom MassARRAY RS1000. Statistical analysis was performed using χ ² test and SNPStats, a website software. Using χ ² test, we found that the distribution of two tSNPs (rs2267130 in checkpoint kinase 2 (CHEK2), p?=?0.040; rs1695 in GSTP1, p?=?0.023) allelic frequencies had significant difference between cases and controls. When we analyzed all of the tSNPs using the SNPStats software, we found that rs1695 in GSTP1 decreased the risk of GBM in log-additive model (OR?=?0.56, 95 % CI, 0.34–0.94, p?=?0.022). Besides, we found that there is an interaction between rs3212986 in excision repair cross-complementing group 1 (ERCC1) and gender under codominant and recessive models. The gene polymorphisms in CHEK2, GSTP1, and ERCC1 may be involved in GBM in the Han Chinese population. Since our sample size is small, further investigation needs to be performed.     

枕下三角的超声解剖学研究

目的探讨枕下三角境界及内容物的检查方法与超声解剖学特点,为临床检查枕下三角提供超声影像学资料。方法对100例健康成年人枕下区进行超声检查,描述枕下三角境界的超声判定及解剖关系;阐述枕大神经的走行特点,测量头下斜肌表面枕大神经的横截面积;记录椎动脉V3段管腔内径(D)、收缩期峰值流速(PSV)、舒张期末流速(EDV)、阻力指数(PI)。结果 (1)寰椎后结节左侧约1 cm处纵切声像图显示寰椎后弓呈"短弧形"强回声,其后上方为头后大直肌、后下方为头下斜肌,三者分别构成枕下三角的底、内上界和外下界。(2)寰椎侧块处纵切声像图显示侧块为"平台样"强回声结构,其后方为椎动脉V3段、下方紧接寰椎后弓;后弓后方为头下斜肌、后上方为头上斜肌,头上斜肌构成三角的外上界,后弓与椎动脉V3段之间为枕下神经所在区域。(3)枕大神经长轴声像图显示神经从头下斜肌下缘发出后向内上走行于头下斜肌及头后大直肌与头半棘肌之间;不同性别头下斜肌表面枕大神经横截面积两侧比较,差异均无统计学意义(P>0.05)。(4)寰椎侧块处横切声像图显示椎动脉V3段呈"倒U形"绕侧块进入枕骨大孔,排除发育不良者,测V3段D为(3.52±0.39)mm、PSV及EDV分别为(43.33±9.05)、(21.87±5.86)cm/s、RI为(0.49±0.11)。结论超声是检查枕下三角及其内容物的理想方法。     

新生儿急性肾损伤生物标志物研究现状

新生儿急性肾损伤(AKI)是指由于各种原因引起的肾功能在短时间内受到损害,新生儿呈现血容量减少性休克、缺氧、低体温等多种病理状态,血清肌酐水平急性和可逆性增高,伴或不伴尿量减少,水和电解质紊乱、酸碱失衡和代谢废物堆积。AKI表现隐匿,该病新生儿易被临床漏诊。由于AKI新生儿特殊的病理生理特点,使其与成年人AKI患者差异较大,目前临床不断改进的成年人AKI诊断标准,并不适用于临床诊断新生儿AKI。因此,临床需要新型肾损伤生物标志物,对新生儿AKI进行早期预测和诊断。目前可反映肾小管及肾小球损伤,有助于新生儿AKI诊断的新型生物标志物包括:胱抑素C(Cys-C)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾脏损伤分子(KIM)-1、β2微球蛋白(β2-MG)、α1微球蛋白(α1-MG)、N-乙酰-β-D氨基葡萄糖苷酶(NAG)、肝型脂肪酸结合蛋白(L-FABP)、神经轴突导向因子(Netrin)-1、表皮生长因子(EGF)、白细胞介素(IL)-18、谷胱甘肽-S-转移酶(GST)及β-微量蛋白(BTP)等。在众多预测新生儿AKI的新型生物标志物中,应用相对较多及预测效果较佳的生物标志物是尿、血清Cys-C,尿、血清NGAL和尿KIM-1等,在对AKI新生儿进行早期预测、辅助诊断等方面,均优于血清肌酐及尿量检测。但是,上述新型生病标志物的“正常值”大多受新生儿出生胎龄、体重及其检测时日龄与是否合并全身感染等多种因素影响。这些因素均可降低其预测新生儿AKI的敏感度和特异度。联合检测多种生物标志物预测新生儿AKI,虽然降低了预测特异度,但是可以提高预测敏感度。     

Melatonin attenuates postmyocardial infarction injury via increasing Tom70 expression

Mitochondrial dysfunction leads to reactive oxygen species (ROS) overload, exacerbating injury in myocardial infarction (MI). As a receptor for translocases in the outer mitochondrial membrane (Tom) complex, Tom70 has an unknown function in MI, including melatonin‐induced protection against MI injury. We delivered specific small interfering RNAs against Tom70 or lentivirus vectors carrying Tom70a sequences into the left ventricles of mice or to cultured neonatal murine ventricular myocytes (NMVMs). At 48 h post‐transfection, the left anterior descending coronary arteries of mice were permanently ligated, while the NMVMs underwent continuous hypoxia. At 24 h after ischemia/hypoxia, oxidative stress was assessed by dihydroethidium and lucigenin‐enhanced luminescence, mitochondrial damage by transmission electron microscopy and ATP content, and cell apoptosis by terminal deoxynucleotidyl transferase dUTP nick‐end labeling and caspase‐3 assay. At 4 weeks after ischemia, cardiac function and fibrosis were evaluated in mice by echocardiography and Masson's trichrome staining, respectively. Ischemic/hypoxic insult reduced Tom70 expression in cardiomyocytes. Tom70 downregulation aggravated post‐MI injury, with increased mitochondrial fragmentation and ROS overload. In contrast, Tom70 upregulation alleviated post‐MI injury, with improved mitochondrial integrity and decreased ROS production. PGC‐1α/Tom70 expression in ischemic myocardium was increased with melatonin alone, but not when combined with luzindole. Melatonin attenuated post‐MI injury in control but not in Tom70‐deficient mice. N‐acetylcysteine (NAC) reversed the adverse effects of Tom70 deficiency in mitochondria and cardiomyocytes, but at a much higher concentration than melatonin. Our findings showed that Tom70 is essential for melatonin‐induced protection against post‐MI injury, by breaking the cycle of mitochondrial impairment and ROS generation.     

A four-protein metabolon assembled by a small peptide protein creates the pentacyclic carbonate ring of aldgamycins

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII–UV) assembled by a small peptide protein (AlmUV) appends a reactive N-hydroxylcarbamoyl moiety to the decarboxylated aldgamycins followed by a non-enzymatic condensation to give the pentacyclic carbonate ring. Our results have documented an unprecedent mechanism for carbonate formation.KEY WORDS: Aldgamycins, Biosynthesis, N-hydroxylcarbamoyl, Organic carbonate, Protein complex