DNA methyltransferase 3a rs1550117 genetic polymorphism predicts poor survival in gastric cancer patients

DNA methyltransferase 3a (DNMT3a) have been suggested to play a crucial role in human cancer prognosis. Single nucleotide polymorphisms (SNPs) in DNMT3a genes may have an impact on the prognosis of cancers. This study aimed to investigate the association between SNPs of DNMT3a gene and prognosis of gastric cancer (GC). Two sites of DNMT3a SNPs, rs1550117 and rs13420827 were selected and genotyped using TaqMan assay in 447 GC patients who received gastrectomy. Effects of genotypes on clinical outcomes of GC were calculated by Kaplan-Meier survival analysis and Cox regression model. We found that the AG or AA genotype of rs1550117 was associated with significantly poorer survival and increased death risk of GC compared with GG genotype (dominant model: HR=1.35, 95% CI=1.01-1.80, P=0.043). Further multivariate Cox regression analysis revealed that in addition to the known factors including male, larger tumor sizes and high clinical stage, rs1550117 variant was an independently predictive factor for survival in GC patients. No significant association was found between rs13420827 genetic variants and GC prognosis. Our findings first demonstrated that DNMT3a rs1550117 polymorphism may be a potential biomarker in predicting overall survival of GC patients.     

Typical or atypical progressive supranuclear palsy: a comparative clinicopathologic study of three Chinese cases

Progressive supranuclear palsy (PSP) is an atypical parkinsonism, which is the third most common geriatric neurodegenerative disease. We reported three pathology-confirmed Chinese PSP cases with special focus on the pathological accumulations of tau, a-synuclein and A-beta in the three PSP brains. Cases 1 and 2 initiated with extrapyramidal signs and gait disorders, while case 3 suffered behavioral abnormalities with cognitive decline at the beginning. In neuropathology, PSP-changes such as tau-positive tufed astrocytes, oligdendrocytes with the tau-positive coiled-body and threads and globose NFTs were widely seen in the basal ganglia, isocortex and allocortex, as well as in brainstem, cerebellum and spinal cord. In addition, numerous AGs were found in the hippocampus of cases 1 & 2, while Aβ amyloid depositions were found in hippocampus and leptomeningeal vessels of case 1 and in neocortex, entorhinal cortex, hippocampus, cingulate gyrus and amygdale of case 3. Vessel infarcts were observed in cases 1. Cortical laminar III necrosis in case 1 suggested the ischemic damage. Cervical spinal cords in cases 2 & 3 were obtained with tau-positive globose NFTs, tufted astrocytes and neuropil threads were respectively found in the neurons of anterior horn and surrounding white matters. In summary, pathological examination is crucial for the ambiguous cases to exclude other neurodegenerative diseases. Furthermore, cervical spinal cord should be routinely examined in the PSP autopsy.     

LOXL4 is downregulated in hepatocellular carcinoma with a favorable prognosis

Lysyl oxidase like 4 (LOXL4), a member of the secreted copper-dependent amine oxidases that contribute to the assemble and maintenance of the extracellular matrix (ECM), was found to be up-regulated or down-regulated in different cancer types, suggesting its paradoxical roles in cancer. The specific role of LOXL4 in hepatocellular carcinoma (HCC), however, is still yet to be defined. Twenty-eight pairs of HCC specimens were used for LOXL4 mRNA expression analysis. The mRNA expression in HCC cell lines was examined, and HepG2 was selected for LOXL4 small interfering RNA (siRNA) interference to investigate the biological function of LOXL4, LOXL4 immunohistochemical staining was performed using a tissue microarray containing 298 HCC patients. The prognostic and diagnostic value of LOXL4 was evaluated using Cox regression and Kaplan-Meier analysis. LOXL4 mRNA or protein expression was significantly lower in HCC tissues than peritumoral tissues (LOXL4 mRNA expression, P = 0.018; LOXL4 protein expression, P < 0.001). Low LOXL4 expression was associated with lower overall survival (OS) rates and higher cumulative recurrence rates. Multivariate analysis indicated that LOXL4 was an independent prognostic indicator for OS and time to recurrence (TTR). Our results revealed that LOXL4 was down-regulated in HCC and correlated with aggressive tumors and a worse clinical outcome. LOXL4 may be a potential biomarker to identify the HCC patients with a higher risk of recurrence.     

Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis

Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy.     

Association of Genetic Variants of SIRT1 With Type 2 Diabetes Mellitus

SIRT1 has been demonstrated in nutrient-sensing and insulin-signaling pathways in in vivo and in vitro experiments, but there is minimal information concerning the association between gene polymorphisms of SIRT1 and type 2 diabetes mellitus (T2DM) in a Chinese Han population. Using case-control design, we recruited 310 unrelated T2DM patients from inpatients at Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, while 301 healthy controls were volunteers from the community for regular medical checkup. All participants were genotyped within the SIRT1 region. The following five SNPs rs10509291, rs12778366, rs10997870, rs10823112, and rs4746720 cover 100% of common genetic variations (minor allele frequency ≥ 0.05) within the SIRT1 gene (r ² ≥ 0.8). The genotypes of SIRT1 gene polymorphisms were analyzed by the Snapshot assay and DNA sequencing. The resulting data show that there was significant genetic differentiation in rs10823112 [p = 0.003; OR (95% CI) = 1.515 (1.152–1.994) for genotype], rs4746720 [p = 0.024; OR (95% CI) = 1.37 (1.037–1.674) for genotype], and rs10509291 [p = 0.002; OR (95% CI) = 1.551 (1.179–2.04) for genotype] between T2DM and control subjects. However, the result of rs4746720 was no longer significant after correction for multiple testing (p after Bonferroni correction = 0.12); the results of rs10509291and rs10823112 were still significantly different between the two groups (p after Bonferroni correction = 0.01 and 0.015, respectively). Linear regression analyses adjusting for age, gender, and body mass index (BMI) showed that HbA1c and HOMA-IR in subjects with rs10509291 AA genotype were higher than those with TT genotype in T2DM group (p = 0.045, p = 0.035, respectively). Together, our data show that genetic variation of the SIRT1 gene is related to insulin resistance and increase risk of T2DM in Chinese Han population. The risk allele A at SIRT1 rs10509291 was closely associated with T2DM, and subjects who were homozygous of the A allele were more likely to develop T2DM.Key words: Type 2 diabetes, Genetic variants, SIRT1, Chinese Han population     

胫骨延长柄在重度肥胖患者初次全膝关节置换术中的应用及疗效观察

目的：探讨胫骨延长柄在重度肥胖的终末期膝骨性关节炎患者初次全膝关节置换术（ TKA)中的应用及疗效。方法回顾性分析河南省人民医院骨科2009年5月—2012年5月在初次TKA中应用胫骨延长柄治疗的19例（23膝)终末期膝骨性关节炎患者的临床资料,其中男4例、女15例,年龄53~78岁,BMI （37．7±1．75) kg/m2。单侧置换15例（左侧9例、右侧6例),双侧置换4例。应用美国膝关节学会评分（ KSS)系统,记录患者手术前后KSS膝评分及膝功能评分,采用SPSS 17．0进行统计学分析,以评价临床疗效及假体生存率。结果17例（21膝)获得随访,平均随访44个月（27~65个月);2名患者失访。术后下肢力线良好,关节稳定,随访患者均无假体松动等相关并发症。17例患者末次随访时,21膝评分从术前的（20．8±4．5)分提高到（90．7 ± 3．4)分,膝功能评分从术前的（25．7 ± 4．8)分提高到（87．0 ± 3．7)分,差异均有统计学意义（P值均<0．01);经侧方应力试验,17例患者均未出现内翻和外翻类型的关节不稳;未出现假体周围骨折、感染、无菌性松动、髌骨骨折等并发症,假体生存率为100%。结论重度肥胖的终末期膝骨性关节炎患者接受初次TKA治疗时,应用胫骨延长柄可以分散应力,增强假体稳定性,降低术后并发症,可获得良好的临床疗效。     

建立CT三维重建头影测量模型的研究

目的建立一套运用CT三维重建影像研究颅颌面部骨骼形态的三维头影测量分析法。方法采用Mimics软件对头颅CT数据进行骨骼三维重建,由同一研究者标识29个标志点,以颅颌面内在标志点定义基准平面,建立以鼻根点为原点的三维坐标系,将X线头影测量中的测量平面在三维头颅模型中重新定义,建立测量模板并对颅面部骨骼进行三维测量分析。结果运用CT三维重建影像,进行三维头影测量分析,筛选出32个测量项目,在同一坐标系内获得X线头影正、侧位测量的数据。结论本研究建立了一套全面、准确评估颅面部骨骼形态的三维头影测量法,适合临床中对颅颌面骨骼畸形的量化评估。     

miR-580对乳腺癌细胞系中Twist1的调节作用

目的：探讨miR-580在MCF-10A细胞系中对Twist1的调节。方法：本实验利用生物信息学方法预测Twist1的靶miRNA是miR-580。首先,采用qPCR法检测在MCF-10A系列细胞系中Twist1及miR-580的表达。然后,在MCF-10A细胞系中分别转染miR-580类似物和miR-580抑制物后,利用RT-PCR、Western blot、t检验分析Twist1的表达及细胞迁移能力的变化。最后利用荧光素酶实验验证miR-580通过结合在Twist1的3'UTR调节其表达。结果：1)在MCF-10A细胞系中Twist1与miR-580的表达呈负相关;2)在MCF-10A细胞系中转染miR-580类似物后,Twist1的表达下调;在MCF-10A细胞系中转染miR-580抑制物后Twist1的表达上调;3)在MCF-10A细胞系中引入miR-580类似物后细胞迁移能力降低;4)miR-580直接结合在Twist1的3'UTR。结论：miRNA-580在MCF-10A细胞系中通过结合在Twist1的3'UTR负向调节Twist1的表达从而克制细胞的迁移。     

Basal cell adenoma of the parotid gland: clinical and pathological findings in 29 cases

Objective: To determine the clinical and pathological features of basal cell adenoma (BCA) of the parotid gland. Methods: This is a retrospective study of 29 parotid BCAs in 28 patients who underwent surgery at the Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between October 2000 and June 2013. The tumors were categorized according to their location in the parotid gland as superior superficial lobe, inferior superficial lobe and deep lobe. Results: The mean age was 57.0 years (range, 32-83 years). The clinical manifestations of parotid BCAs were consistent with those of other benign parotid tumors. There were no significant differences in age, average disease duration and tumor size among the three tumor groups. There were 11 deep tumors (11/29, 37.9%), and five of them exhibited cystic degeneration (5/11, 45.5%). A total of 15 patients underwent FNAB examination, and the results were positive in seven patients (7/15, 46.7%). Mild facial nerve function impairment occurred in five patients (House-Brackmann grade II), of whom, three had recovered by the 6-month follow-up. No cases of local recurrence or malignant transformation were observed during follow-up. Conclusion: The clinical features of BCA are consistent with those of other benign tumors. The deep lobe of the parotid gland is more likely to develop BCAs, and thus, this diagnosis should be considered in patients with deep-lobe tumors, especially when accompanied with cystic degeneration. FNAB can increase the rate of preoperative diagnoses.