Allelotypic and cytogenetic characterization of chemically induced mouse mammary tumors: High frequency of chromosome 4 loss of heterozygosity at advanced stages of progression

Loss of heterozygosity (LOH) is one of the most common genetic abnormalities in cancer. To define the role of LOH and chromosomal abnormalities at various stages of mouse mammary cancer progression, we analyzed the allelotypes and karyotypes of primary mammary tumors induced in CD2F₁ mice by two basic protocols, the classical multiple-dose 7, 12-dimethylbenz[a]anthracene (DMBA) protocol and a novel protocol of combined medroxyprogesterone acetate (MPA) and DMBA. The advantage of the latter protocol is that its latency for tumor development is much shorter and its tumor incidence is higher than those of DMBA alone. To study more advanced stages of mammary tumor progression, we also analyzed mouse mammary tumors that had acquired autonomous growth and were transplantable into syngeneic hosts. The allelotypic studies were performed by means of microsatellite length polymorphism analysis with a minimum of two simple-sequence repeat markers per chromosome. We observed that MPA-DMBA-induced mammary adenocarcinomas, which in general arose earlier because of the growth promotion exerted by MPA, did not show any significant LOH and were essentially diploid. Tumors induced by DMBA alone, which on average took longer to develop, showed a higher frequency of allelic losses. LOH on chromosome 11 was observed in 30% of the cases. Chromosomes 4 and 8 were affected in 25% and 20% of the tumors, respectively. Interestingly, advanced stages of mammary tumor progression, represented by transplantable mammary tumors, showed a much higher level of genomic instability, specifically a very high frequency (66%) of LOH on chromosome 4. These findings indicate that chromosome 4 harbors a gene whose inactivation may play a role in the acquisition of more aggressive characteristics such as autonomous growth and transplantation ability. © 1996 Wiley-Liss, Inc.     

PTEN/PI3K信号转导相关蛋白在非小细胞肺癌组织中的表达及其意义

背景与目的:PTEN/PI3K信号转导途径能调节细胞的增殖与存活,与多种肿瘤的发生发展密切相关,但在肺癌中所起的作用及其相互关系尚不十分明确。本研究旨在探讨PTEN/PI3K信号转导相关蛋白IGF-1R、PTEN和PI3K在非小细胞肺癌(non-smallcelllungcarcinoma,NSCLC)中的表达及其意义。方法:利用免疫组织化学SP法检测59例NSCLC组织、19例转移的淋巴结组织、16例癌旁增生肺组织和7例正常肺组织中IGF-1R、PTEN和PI3K蛋白的表达。IGF-1R、PTEN和PI3K蛋白阳性率的差异比较采用卡方检验和Fisher确切概率法。结果:59例NSCLC组织中IGF-1R、PTEN和PI3K蛋白阳性率分别为:72.88%、27.12%和84.75%。IGF-1R以及PI3K蛋白的阳性率与NSCLC的临床病理特征无显著相关(P>0.05)。PTEN蛋白的阳性率与NSCLC的组织学类型、细胞分化程度无关(P>0.05),但与淋巴结转移显著相关(P=0.009)。NSCLC组及转移淋巴结组中PI3K、PTEN蛋白的阳性率与正常肺组织和癌旁增生肺组织相比,差异均有显著性(P<0.05)。59例NSCLC组织中IGF和PI3K之间具有显著正相关性(P=0.001),Pearson列联系数为0.432。PTEN和PI3K之间具有显著负相关(P=0.000),Pearson列联系数为0.505。结论:IGF-1R、PI3K蛋白的过表达和PTEN蛋白的低表达与肺癌的发生及浸润转移相关。     

Genetic Polymorphism and Activities of Human Colon Alcohol and Aldehyde Dehydrogenases: No Gender and Age Differences

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzyme patterns from 69 (men, 47; women, 22) surgical colon mucosal specimens were identified by agarose isoelectric focusing. γ-ADH was found to be the predominant form in the mucosa, whereas only β-ADH was detectable in the muscle layer. ALDH1, ALDH2, and ALDH3 were detectable in the mucosa, with cytosolic ALDH1 being the major form. At pH 7.5, the ADH activities in the colon mucosae with the homozygous phenotype (exhibiting γ₁γ₁) and the heterozygous phenotype (exhibiting γ₁γ₁, γ₁γ₂, γ₂γ₂) were determined to be 183 ± 13 and 156 ± 30 nmol/min/g tissue, respectively. The ALDH activities in the ALDH2-active and ALDH2-inactive phenotypes were determined to be 40.2 ± 2.3 and 34.6 ± 2.0 nmol/min/g tissue, respectively. The lack of significant difference in the ALDH activities between these two phenotypic groups can be attributed to the very low expression of the mitochondrial ALDH2 in the colon mucosa. No significant differences in the ADH or the ALDH activities were found between the men and women studied and between the three age groups (20–40, 49–70, and 72–83 years). The ascending, transverse, descending, and sigmoid colons exhibited similar ADH and ALDH activities. The isoenzyme patterns of ADH and ALDH remained unaltered in colon carcinomas, except that a significant reduction of the enzyme activities was found in the cancer tissue as compared with the adjacent normal portions. it is concluded that human colon mucose exhibits significant amounts of ethanol- and acetaldehyde-oxidizing activities.     

老年住院患者复合跌倒风险评分表的构建及应用研究

目的 构建老年住院患者复合跌倒风险评分表,提高老年住院患者跌倒风险评估准确性。方法 整合约翰霍普金斯跌倒评定量表和HendrichⅡ跌倒风险模型作为初始条目;采用前瞻性研究,收集42 490例老年住院患者跌倒发生情况及相关风险因素,通过χ2检验和logistic回归分析确定跌倒的影响因素,构建老年住院患者复合跌倒风险评分表。将复合跌倒风险评分表在1 663例老年住院患者中进行验证。结果 logistic回归分析得到18项危险因素,将各危险因素的风险比值比（OR）进行赋值,总分为100分。验证结果显示,老年住院患者复合跌倒风险评分表的ROC曲线下面积为0.825（95%CI：0.798~0.852）,最佳截断值为7.5分,灵敏度为0.736,特异度为0.771。结论 老年住院患者复合跌倒风险评分表能有效预测老年住院患者的跌倒风险,有助于临床护理人员及时筛查出高危患者,从而进行有针对性的预防干预。     

Construction of Baculovirus-Inducible CRISPR/Cas9 Antiviral System Targeting BmNPV in Bombyx mori

The silkworm Bombyx mori is an economically important insect. The sericulture industry is seriously affected by pathogen infections. Of these pathogens, Bombyx mori nucleopolyhedrovirus (BmNPV) causes approximately 80% of the total economic losses due to pathogen infections. We previously constructed a BmNPV-specific CRISPR/Cas9 silkworm line with significantly enhanced resistance to BmNPV. In order to optimize the resistance properties and minimize its impact on economic traits, we constructed an inducible CRISPR/Cas9 system for use in transgenic silkworms. We used the 39k promoter, which is induced by viral infection, to express Cas9 and the U6 promoter to express four small guide RNA targeting the genes encoding BmNPV late expression factors 1 and 3 (lef-1 and lef-3, respectively), which are essential for viral DNA replication. The system was rapidly activated when the silkworm was infected and showed considerably higher resistance to BmNPV infection than the wild-type silkworm. The inducible system significantly reduced the development effects due to the constitutive expression of Cas9. No obvious differences in developmental processes or economically important characteristics were observed between the resulting transgenic silkworms and wild-type silkworms. Adoption of this accurate and highly efficient inducible CRISPR/Cas9 system targeting BmNPV DNA replication will result in enhanced antivirus measures during sericulture, and our work also provides insights into the broader application of the CRISPR/Cas9 system in the control of infectious diseases and insect pests.     

耳内镜与显微镜下鼓室成形术手术效果的比较分析

目的 比较耳内镜与传统显微镜下鼓室成形术的安全性和疗效.方法 回顾性分析2018年12月-2019年12月在清远市人民医院耳鼻喉科接受鼓室成形术患者的病历资料.根据手术方式将患者分为经耳内镜鼓室成形术组(耳内镜组)和经显微镜鼓室成形术组(显微镜组).比较两组患者手术引起感音神经性耳聋的风险(骨导听阈上升)、手术对听觉的...