High TRIM44 expression in endometrial carcinoma is associated with a poorer patient outcome

Background

Tripartite motif‐containing protein 44 (TRIM44) has been recently identified as a novel oncogene that is overexpressed in several types of human cancers; however, its role in endometrial cancer (EC) remains unknown. The purpose of the current study was to investigate the TRIM44 protein expression and clinicopathological significance of TRIM44 in EC.

An improved multi-objective optimization-based CICA method with data-driver temporal reference for group fMRI data analysis

Group independent component analysis (GICA) has been successfully applied to study multi-subject functional magnetic resonance imaging (fMRI) data, and the group independent component (GIC) represents the commonality of all subjects in the group. However, some studies show that the performance of GICA can be improved by incorporating a priori information, which is not always considered when looking for GICs in existing GICA methods. In this paper, we propose an improved multi-objective optimization-based constrained independent component analysis (CICA) method to take advantage of the temporal a priori information extracted from all subjects in the group by incorporating it into the computational process of GICA for group fMRI data analysis. The experimental results of simulated and real data show that the activated regions and the time course detected by the improved CICA method are more accurate in some sense. Moreover, the GIC computed by the improved CICA method has a higher correlation with the corresponding independent component of each subject in the group, which means that the improved CICA method with the temporal a priori information extracted from the group can better reflect the commonality of the subjects. These results demonstrate that the improved CICA method has its own advantages in fMRI data analysis.     

Enhanced <Emphasis Type="Italic">AZIN1</Emphasis> RNA editing and overexpression of its regulatory enzyme ADAR1 are important prognostic biomarkers in gastric cancer

Background

Adenosine-to-inosine (A-to-I) RNA editing is catalyzed by adenosine deaminases acting on RNA (ADAR) enzymes. Recent evidence suggests that RNA editing of antizyme inhibitor 1 (AZIN1) RNA is emerging as a key epigenetic alteration underlying cancer pathogenesis.

Methods

We evaluated AZIN1 RNA editing levels, and the expression of its regulator, ADAR1, in 280 gastric tissues from 140 patients, using a RNA editing site-specific quantitative polymerase chain reaction assays. We also analyzed the clinical significance of these results as disease biomarkers in gastric cancer (GC) patients.

Results

Both AZIN1 RNA editing levels and ADAR1 expression were significantly elevated in GC tissues compared with matched normal mucosa (P?<?0.0001, 0.0008, respectively); and AZIN1 RNA editing was positively correlated with ADAR1 expression. Elevated expression of ADAR1 significantly correlated with poor overall survival (P?=?0.034), while hyper-edited AZIN1 emerged as an independent prognostic factor for OS and disease-free survival in GC patients [odds ratio (OR):1.98, 95% CI 1.17–3.35, P?=?0.011, OR: 4.55, 95% CI 2.12–9.78, P?=?0.0001, respectively]. Increased AZIN1 RNA editing and ADAR1 over-expression were significantly correlated with key clinicopathological factors, such as advanced T stage, presence of lymph node metastasis, distant metastasis, and higher TNM stages in GC patients. Logistic regression analysis revealed that hyper-editing status of AZIN1 RNA was an independent risk factor for lymph node metastasis in GC patients [hazard ratio (HR):3.03, 95% CI 1.19–7.71, P?=?0.02]. Conclusions: AZIN1 RNA editing levels may be an important prognostic biomarker in GC patients, and may serve as a key clinical decision-making tool for determining preoperative treatment strategies in GC patients.

     

Clinical and molecular insights into Glanzmann's thrombasthenia in China

Glanzmann's thrombasthenia (GT) is a rare bleeding disorder characterized by spontaneous mucocutaneous bleeding. The disorder is caused by quantitative or qualitative defects in integrin αIIbβ3 (encoded by ITGA2B and ITGB3) on the platelet and is more common in consanguineous populations. However, the prevalence rate and clinical characteristics of GT in non‐consanguineous populations have been unclear. We analyzed 97 patients from 93 families with GT in the Han population in China. This analysis showed lower consanguinity (18.3%) in Han patients than other ethnic populations in GT‐prone countries. Compared with other ethnic populations, there was no significant difference in the distribution of GT types. Han females suffered more severe bleeding and had a poorer prognosis. We identified a total of 43 different ITGA2B and ITGB3 variants, including 25 previously unidentified, in 45 patients. These variants included 14 missense, 4 nonsense, 4 frameshift, and 3 splicing site variants. Patients with the same genotype generally manifested the same GT type but presented with different bleeding severities. This suggests that GT clinical phenotype does not solely depend on genotype. Our study provides an initial, yet important, clinical and molecular characterization of GT heterogeneity in China.     

Novel recessive PDZD7 biallelic mutations in two Chinese families with non‐syndromic hearing loss

Autosomal recessive non‐syndromic hearing loss (ARNSHL) is a highly heterogeneous genetic condition. PDZD7 has emerged as a new genetic etiology of ARNSHL. Biallelic mutations in the PDZD7 gene have been reported in two German families, four Iranian families, and a Pakistani family with ARNSHL. The effect of PDZD7 on ARNSHL in other population has yet to be elucidated. Two Chinese ARNSHL families, each of which had two affected siblings, were included in this study. The families underwent target region capture and high‐throughput sequencing to analyze the exonic, splice‐site, and intronic sequences of 128 genes. Furthermore, 1751 normal Chinese individuals served as controls, and 122 Chinese families segregating with apparent ARNSHL, who had been previously excluded for variants in the common deafness genes GJB2 and SLC26A4, were subjected to screening for candidate mutations. We identified a novel homozygous missense mutation (p.Arg66Leu) and novel compound heterozygous frameshift mutations (p.Arg56fsTer24 and p.His403fsTer36) in Chinese families with ARNSHL. This is the first report to identify PDZD7 as an ARNSHL‐associated gene in the Chinese population. Our finding could expand the pathogenic spectrum and strengthens the clinical diagnostic role of the PDZD7 gene in ARNSHL patients.     

Functional independence of Taiwanese children with Prader–Willi syndrome

Prader–Willi syndrome (PWS) is a genetic disorder with obesity, developmental delay, short stature, and behavioral abnormalities. The study aimed to assess the functional independence in children with PWS. The Functional Independence Measure for Children (WeeFIM) was used to evaluate 81 children with PWS (44 boys and 37 girls) with a median age of 11 years 1 month (range 2 years 8 months to 20 years 2 months) were recruited between January 2013 and December 2016. The mean total WeeFIM score was 103.8 (maximum 126). Sixty‐five patients (80%) had deletion type PWS, 16 (20.0%) had nondeletion type. The scores were 103.6 ± 18.5 for deletion and 104.8 ± 18.3 for nondeletion type (p = .405), 104.8 ± 19.3 in boys and 102.6 ± 17.3 in girls (p = .293). The mean self‐care, mobility, and cognition scores were 47 (maximum 56), 33 (maximum 35), and 24 (maximum 35), respectively. All total scores and 18 subscores in the three functional domains were positively correlated with age (p < .05). Most children required assistance in problem‐solving, comprehension, and expression. The WeeFIM identified the strengths and limitations of children with PWS and confirmed that support and supervision were needed in cognitive and self‐care tasks.     

大豆异黄酮抑制大鼠前列腺增生及其作用机制

目的观察大豆异黄酮(SI)对良性前列腺增生(BPH)大鼠体内性激素、生长因子及细胞凋亡相关基因的影响,探讨SI对BPH的防治及作用机制。方法选择SPF级健康成年雄性SD大鼠100只,随机分为正常对照(NC)组、BPH模型组、低剂量[6 mg/(kg·d)]SI组、中剂量[12 mg/(kg·d)]SI组及高剂量[24 mg/(kg·d)]SI组,每组各20只。灌胃给药4周后麻醉处理大鼠,腹主动脉取血,制备血清;完整摘取大鼠前列腺组织。称重测定前列腺组织湿质量,计算前列腺指数(PI);酶联免疫吸附法(ELISA)测定大鼠血清雌二醇(E2)、睾酮(T)水平;免疫质印迹法(Western blotting)检测前列腺组织Fas、Fas L、Bax、Bcl-2、表皮生长因子(EGF)及其受体EGFR的表达。结果与NC组比,BPH组前列腺组织湿质量及PI均较明显增加(P<0.05);血清E2及T水平均显著升高(P<0.05);前列腺组织中Fas L、Bcl-2、EGF及EGFR表达水平均显著升高(P<0.05),而Fas和Bax表达水平均显著降低(P<0.05)。与BPH组比,中、高剂量SI组前列腺组织湿质量及PI均明显减少(P<0.05);血清E2及T水平均显著下降(P<0.05);前列腺组织中Fas L、Bcl-2、EGF及EGFR表达水平均显著降低(P<0.05),而Fas和Bax表达水平显著升高(P<0.05);其中,中剂量SI组各指标变化较低、高剂量组更显著(P<0.05)。结论 SI对BPH具有较好的抑制作用,其中中剂量SI作用效果更佳,其作用机制可能与调节机体性激素水平,下调生长因子及其受体表达以及调控细胞凋亡基因表达有关。     

Downregulating osteopontin reduces angiotensin II-induced inflammatory activation in vascular smooth muscle cells

Objective:  Atherosclerosis is considered as a chronic inflammatory response in arterial blood vessels. The function of osteopontin (OPN), a proinflammatory cytokine, in the Ang II-induced inflammatory activation in vascular smooth muscle cells (VSMCs) remains poorly understood. Methods:  In the present study, the role of OPN was investigated by knocking down OPN using small interfering RNA (siRNA). VSMCs from human saphenous vein were divided into three groups according to RNAi treatment: OPN siRNA group, sham (un-transfected) treated group, and control siRNA group. RNAi effect was investigated by real time PCR, western blotting analysis and ELISA. Then all groups were stimulated with Ang II. The inflammatory activation was assessed by determining the activation of NFκB and activator protein-1 (AP-1), and the release of interleukin-6 (IL-6) and IL-1β. Results:  OPN was knocked down effectively in OPN RNAi group. Inflammatory activations, such as NFκB and AP-1 activation and IL-6 accumulation, were induced by Ang II in sham treated group and control siRNA group. However, it was abolished in OPN siRNA group by the downregulation of OPN compared to sham treated group and control siRNA group. Conclusions:  This result suggested that OPN plays an important role in Ang II-induced inflammatory activation in VSMCs. The finding further supports OPN as a potential target for atherosclerotic therapy. Received 21 February 2008; returned for revision 6 May 2008; received from final revision 16 May 2008; accepted by S. Stimpson 21 August 2008 The first three authors contributed equally to this work.     

Sectional anatomy of the fetal brain in uterus at term on the sagittal plane

ObjectiveTo provide sectional anatomic data for the precise localization of developmental malformation of fetal brain in sagittal magnetic resonance imaging (MRI).MethodAfter abdominal and pelvic MRI scanning, the gravid specimen was cut into serial sagittal slices in correspondence with MRI in a low temperature laboratory to demonstrate the structures of fetal brain.Result(1) Directional determination of the sloping and rotating fetal head. From the serial sagittal sections of pregnant cadaver at term, we concluded that, the longitudinal lying and cephalic presentation fetal had run into maternal pelvis, and rotated and sloped to right. Anteroposterior position and median sagittal plane of the fetal was in correspondence with his mother’s. (2) Seven serial sagittal sections of the fetal brain were obtained through lateral surface of the right cerebral hemisphere, lateral sulcus, internal capsule, median sagittal plane, middle cerebellar peduncle, brainstem, and lateral surface of the left cerebral hemisphere.ConclusionThrough the comparison study between sagittal sections and corresponding MRI of fetal brain at term, we could obtain morphological anatomic structures and MRI of fetal brain, providing morphological demonstration of the intrauterine development of fetal brain and auxiliary diagnosis of ultrasound and MRI in pregnant woman.