新疆地区HPV16型变异体及E6、E7、LCR基因变异分析

目的 探讨新疆地区感染HPV16变异体谱系分布及E6、E7、LCR基因突变研究. 方法 对HPV16阳性的宫颈癌及癌前病变患者,提取基因组DNA,利用PCR扩增HPV16 DNA E6、E7基因及LCR区核苷酸片段,正反向测序.与HPV16基因序列分析比对,确定HPV16谱系分布,分析核苷酸突变位点. 结果 E6基因突变率为80.00％,主要突变位点为T350G(59.78％)和T178G(18.48％);E7突变率为54.78％,主要突变位点为A647G(33.33％)和T846C(26.98％);LCR突变率为23.48％,主要突变位点为C24T(74.07％)和C13T(18.52％).新疆维吾尔族妇女与汉族妇女之间比较,维吾尔族妇女T350G突变率(72.00％)显著高于汉族(45.24％),汉族妇女A647G(33.33％)、T846C(31.25％)、C24T(78.95％)三个突变率均显著高于维吾尔族(依次为20.00％、13.33％、62.50％),差异具有统计学意义.新疆汉族妇女中感染的HPV16主要为亚洲型,新疆维吾尔族妇女感染的HPV16主要为欧洲型. 结论 T350G突变可能是新疆维吾尔族妇女宫颈癌高发的原因之一,新疆汉族妇女中感染的HPV16型主要为亚洲型,新疆维吾尔族妇女感染的HPV16型主要为欧洲型.     

FARVATX: Family‐Based Rare Variant Association Test for X‐Linked Genes

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X‐linked variants have been reported for complex traits. For instance, dosage compensation of X‐linked genes is often achieved via the inactivation of one allele in each X‐linked variant in females; however, some X‐linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X‐linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X‐linked variant genetic association analysis of dichotomous phenotypes with family‐based samples. The proposed methods are computationally efficient and can complete X‐linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare‐variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X‐linked genes were identified, illustrating the practical importance of the proposed methods.     

Impact of pathological response after preoperative transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion and early tumor recurrence in hepatocellular carcinoma: a multicenter propensity score matching analysis

BackgroundTo study the influence of pathological responses (PR) after transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion (MVI) and early recurrence in hepatocellular carcinoma (HCC) patients.MethodsBetween 2013 to 2015, consecutive HCC patients who underwent liver resection with “curative” intent at three hospitals were enrolled in this study. Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI, early recurrence rates and patterns of recurrence before and after propensity score matching (PSM).ResultsOf 1,970 patients, 737 patients who received preoperative TACE were divided into three groups according to the areas of PR: ≥90% (n=226), 60–90% (n=447), and <60% (n=64). PR ≥90% was an independent protective factor of incidences of MVI [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.082–0.245, P<0.001) and early recurrence (HR, 0.742; 95% CI, 0.561–0.963, P=0.032); while PR<60% was an independent risk factor of incidences of MVI (OR, 6.076; 95% CI, 3.004–11.728, P<0.001) and early recurrence (HR, 1.428; 95% CI, 1.095–1.929; P=0.009). Furthermore, patients with PR <60% were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.ConclusionsThis study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence. Patients with PR <60% were at significantly higher risks of having more MVI, early and multiple tumor recurrences     

Survivin及其剪接变异体survivin-△Ex3,survivin-2B mRNA在乳腺癌中的表达和临床意义

目的观察乳腺癌组织中survivin及其剪接变异体survivin-△Ex3,survivin-2B mRNA表达情况,并探讨其与临床病理学指标的关系。方法以逆转录-聚合酶链反应(RT-PCR)法检测50例乳腺癌及癌旁5cm正常乳腺组织标本中的凋亡抑制因子survivin及其剪接变异体survivin-△Ex3、survivin-2B mRNA表达,半定量分析电泳结果。免疫组化法检测乳腺癌石蜡标本中的雌激素受体(ER)、孕激素受体(PR)和HER-2基因。结果50例乳腺癌标本中survivin及其剪接变异体survivin-△Ex3、survivin-2B mRNA均高表达,与癌旁正常乳腺组织中差异有统计学意义(P<0.01),survivin mRNA与survivin-△Ex3,survivin-2B mRNA在乳腺癌组织中的高表达呈正相关(P<0.05),survivin-△Ex3,survivin-2B mRNA的表达与淋巴结转移有关(P<0.05)。结论Survivin及其剪接变异体survivin-△Ex3、survivin-2B系重要的凋亡蛋白抑制因子,与其他预后指标联合检测可望对患者的治疗以及预后作出更准确的预测。     

The Divergent Pattern of SARS-CoV-2 Variant Predominance and Transmission Dynamics in the Brazilian Island of Ilhabela

Our effort in SARS-CoV-2 genomic surveillance in Brazil has detected the Alpha Variant of Concern with a predominance higher than 75% in the population of Ilhabela island (São Paulo State) at a time when the Gamma VOC was already predominating the mainland raised concerns for closer surveillance on this island. Therefore, we intensified the surveillance for 24 weeks by generating data from 34% of local positive cases. Our data show that the patterns of VOC predominance dynamics and infection rates were in general distinct from the mainland. We report here the first known case of Alpha predominance in a Brazilian population, a delay greater than 3 months for the Gamma to dominate the previous variants compared to the mainland, and a faster dispersion rate of Gamma and Delta VOCs compared to the mainland. Phylogenetic analysis revealed the SARS-CoV-2 transmission dynamics in Ilhabela were characterized by multiple independent introduction events of Gamma and Delta, with a few events of Alpha introduction, two of them followed by community transmission. This study evidenced the peculiar behavior of SARS-CoV-2 variants in an isolated population and brought to light the importance of specific programs for SARS-CoV-2 genomic surveillance in isolated populations.     

睾丸混合性生殖细胞肿瘤临床病理分析

目的:探讨原发性睾丸混合性生殖细胞肿瘤(MGCT)的临床病理特征。方法:对我院13例原发性睾丸MGCT患者的临床病理资料进行回顾性分析,并结合相关文献进行讨论。结果:睾丸MGCT占我院同期睾丸生殖细胞肿瘤的24.1%(13/54),患者年龄2~53岁,平均28.3岁。全部病例均发生于单侧睾丸,左侧6例,右侧7例,左右侧比为0.86∶1。睾丸MGCT病理形态多样,肿瘤成分包括胚胎性癌(11例,84.6%)、精原细胞瘤(8例,61.5%)、畸胎瘤(6例,46.2%)、绒毛膜癌及卵黄囊瘤(均为4例,23.1%)。其中9例(69.2%)包含2种不同的生殖细胞肿瘤成分,3例(30.8%)包含3种不同的肿瘤成分,1例(7.7%)包含5种不同的肿瘤成分。结论:睾丸MGCT非常少见,好发于青壮年男性,不同的肿瘤成分其生物学行为、临床治疗和预后不同,因此准确的病理诊断非常必要,免疫组化标记对病理诊断与鉴别诊断具有重要作用。     

静脉注射三乙醇胺对SD大鼠的病理性损伤作用

目的 观察静脉注射三乙醇胺后SD大鼠的组织病理学改变及其可逆性。方法 60只SD大鼠,随机分为对照组和300 mg/kg剂量组,连续30 d给药和恢复4周,分别进行大体解剖和组织病理学检查。结果 连续给药30 d,SD大鼠肝细胞嗜酸性变,肾髓质肾小管上皮细胞变性,脾小体生发中心增大,白髓边缘带增宽,淋巴结内淋巴滤泡数量增多,生发中心增大;恢复4周,肝脏、脾脏和淋巴结病变恢复不明显。结论 静脉注射一定剂量的三乙醇胺,对SD大鼠肝脏、肾脏、脾脏和淋巴结有一定的损伤作用,其中,肾脏的损伤可逆,脾脏、淋巴结和肝脏的损伤有一定程度的恢复。     

Inhibition of Pathological Angiogenesis of Chinese Medicine against Liver Fibrosis

Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells (LSECs) and formation of new vascular, is a crucial mechanism responsible for origination and development of liver fifibrosis and closely involves in the development of cirrhosis and hepatic cancer. Anti-neovascularization medicine such as sorafenib can decrease portosystemic shunts, improve splanchnic hyperdynamic circulation, lower portal hypertension, while it can not be applied in clinic due to its serious toxic and side reactions. Chinese herbal formula can effectively inhibit pathological angiogenesis of liver, improve microcirculation of liver, and decrease the probability of gastrointestinal hemorrhage in cirrhotic patients. Different Chinese herbal formula are of different characteristics on inhibiting pathological angiogenesis in liver fifibrosis, which partly explains synergistic effect of different compatibility of Chinese materia medica and opens up good vista for Chinese medicine against liver fifibrosis through inhibiting angiogenesis.     

水通道蛋白-9在肝脏的表达及其意义

水通道蛋白-9(aquaporin-9,AQP9)是一种在肝组织中表达的跨膜转运蛋白。肝组织细胞内AQP9定位于细 胞质膜。AQP9除可通透水,还可以通透甘油、尿素等其他多种小分子。大量研究证明AQP9参与肝组织多种生理和 病理过程。AQP9在肝脏上的表达对肝脏生理和病理过程有多种影响,肝脏AQP9的研究可为肝脏疾病的诊断和治疗 提供新的靶点。