跨膜蛋白16A通过激活表皮生长因子受体信号通路促进乳腺癌细胞增殖的研究

目的探讨跨膜蛋白16A(TMEM16A)在乳腺癌细胞中参与信号通路的富集分析及其对乳腺癌患者预后的影响,探究其对雌激素受体(ER)和孕酮受体(PR)阳性乳腺癌促进增殖作用的机制。方法从公共数据库癌症基因组图谱在线数据库中下载乳腺癌的转录组及临床数据,根据TMEM16A表达的中位值将患者分为高表达组和低表达组,用基因集富集分析进行基因富集和通路分析。用Kaplan-Meier法进行生存分析。用Western Blot方法检测过表达及敲减TMEM16A后ER和PR阳性乳腺癌T47D细胞的TMEM16A蛋白及下游信号通路磷酸化表皮生长因子受体(p-EGFR)和EGFR蛋白的表达情况。用CCK-8细胞增殖实验检测乳腺癌T47D细胞转染过表达TMEM16A质粒及用EGFR通路抑制剂后的细胞增殖能力。结果高表达TMEM16A组乳腺癌患者的基因高度富集于EGFR通路、葡萄糖激酶调节蛋白通路和间质表皮转化因子(MET)等通路。Kaplan-Meier生存分析显示:TMEM16A高表达乳腺癌患者预后生存期显著降低,TMEM16A与EGFR共同高表达组的总生存显著低于共同低表达组。Western Blot结果显示:过表达TMEM16A能够增加p-EGFR蛋白表达,反之敲减TMEM16A后p-EGFR蛋白表达水平降低。CCK-8结果显示:转染空质粒与过表达(TMEM16A OE)的相对增殖力分别为(100.00±0)%和(121.40±5.99)%,并且这种促增殖作用可以被吉非替尼所逆转,TMEM16A OE+吉非替尼为(78.26±4.74)%。结论 TMEM16A可能通过EGFR信号通路促进ER、PR阳性乳腺癌T47D细胞的增殖。     

上海孤独谱系障碍患儿、母亲社交PEERS团体训练效果的研究

目的实施基于证据支持的社交技能干预训练,提高孤独谱系障碍(ASD)患儿社交能力,降低母亲的抑郁、焦虑情绪和不确定感。方法 2017年10-12月采用中文版结构式同伴互助社交训练教育和促进社交技能的项目(PEERS)手册,对ASD患儿和母亲共同进行3个半月的干预。每周一次,每次90 min,儿童以小组训练的形式,母亲以团体形式。同时调整母亲的疾病不确定感、认知、焦虑和抑郁情绪。对干预前后ASD患儿症状、社交行为以及母亲的情绪进行评估,对母亲疾病不确定感半年后随访。结果母亲抑郁情绪贝克抑郁量表(BDI)(t=-4.585,P<0.01)、儿童孤独症症状评定(CARS)(t=-3.945,P<0.01)、孤独症儿童异常行为评定(ABC)(t=-2.068,P<0.05)、儿童社交问卷(t=-2.315,P<0.05)的前后测之间差异有统计学意义,训练组优于对照组。结论中文版PEERS社交训练能帮助ASD患儿提高社交技能,同时降低母亲抑郁情绪。     

多粘类芽孢杆菌对油菜中锶富集和转移的影响

目的：研究根际促生菌——多粘类芽孢杆菌对油菜中锶富集和转移的影响。方法：实验分5组,设置4个不同锶浓度（1、2、3、4 mmol/L）处理组和1个对照组（水培养液）。利用水培方式培育油菜,水培养液中添加多粘类芽孢杆菌（0.333 g/L）,于添加锶和菌后3个时间点（7、14、21 d）收获油菜,用电感耦合等离子体发射光谱仪（ICP-AES）分别测定油菜的根和茎叶中锶含量,并计算转移系数和富集率。结果：与对照组相比,多粘类芽孢杆菌存在时,油菜根部和茎叶中⁸⁸Sr含量随着培养液中锶浓度增高和作用时间的延长而升高（P < 0.05,油菜根部在1 mmol/L锶+菌作用21 d时除外）,且油菜茎叶中的⁸⁸Sr含量大于油菜根部（P < 0.05）;多粘类芽孢杆菌使⁸⁸Sr的转移系数增加、富集率降低（P < 0.05）,可促进⁸⁸Sr从根到茎叶的转移。4个处理组对⁸⁸Sr的转移系数均增加（P < 0.05）,且转移系数均在21 d达到最高。结论：多粘类芽孢杆菌能够影响油菜对锶的转移和富集,可降低油菜根和茎叶部分对⁸⁸Sr的富集率,促进⁸⁸Sr从根到茎叶的转移。     

Identification of Key Candidate Genes and Pathways in Endometrial Cancer by Integrated Bioinformatical Analysis

Endometrial Cancer is the most common female genital tract malignancy, its pathogenesis is complex, not yetfully described. To identify key genes of Endometrial Cancer we downloaded the gene chip GSE17025 from the GeneExpression Omnibus database. Differentially expressed genes (DEGs) were identified through the GEO2R analysistool. Functional and pathway enrichment analysis were performed for DEGs using DAVID database. The network ofprotein–protein-interaction (PPI) was established by STRING website and visualized by Cytoscape. Then, functionaland pathway enrichment analysis of DEGS were performed by DAVID database. A total of 1000 significant differencesgenes were obtained, contain 362 up-regulated genes and 638 down-regulated genes. PCDH10, SLC6A2, OGN,SFRP4, TRH, ANGPTL, FOSB are down-regulated genes. The gene of IGH, CCL20, ELF5, LTF, ASPM expressionlevel in tumor patients are up-regulated. Biological function of enrichment include metabolism of xenobiotics bycytochrome P450, MAPK signaling pathway, Serotonergic synapse, Protein digestion and absorption, IL-17 signalingpathway, Chemokine signaling pathway, HIF-1 signaling pathway, p53 signaling pathway. All in all, the current studyto determine endometrial differentially expressed genes and biological function, comprehensive analysis of intrauterinemembrane carcinoma pathogenesis mechanism, and might be used as molecular targets and diagnostic biomarkers forthe treatment of endometrial cancer.     

Environmental enrichment alters organizational features of the forepaw representation in the primary somatosensory cortex of adult rats

The cortical forepaw area of young adult rats was mapped by recording the response properties of small clusters of neurons in layer IV of the primary somatosensory (SI) cortex. First we quantitatively analyzed the somatotopic organizational features of the cortical forepaw representation in terms of areal extent and topography, receptive field (RF) sensory modality, size, and location. We also assessed the influence of environmental enrichment, known to induce structural alterations in cortical connectivity, on the representational characteristics of the forepaw maps. Long-Evans rats were housed in environments (standard, SE; enriched, EE) promoting differential tactile experience for 71–113 days from weaning. Within the SI, we found a single and complete topographic map of the cutaneous surfaces of the forepaw consisting of a rostrolateral-caudomedial sequence of digit and pad representational zones. Small islets of noncutaneous responses (NCR; high-threshold, deep-receptor input) within the boundaries of the cutaneous maps were a conspicuous feature of the forepaw map for SE rats. These islets created discontinuities in the representation of contiguous skin territories. In the SE rats, about 79% of the cortical sites activated by light tactile stimulation had a single cutaneous RF, whereas about 21% exhibited multiple RFs. Most single-digit RFs we delineated in the SE rats extended across two or three phalanges. As a result, the representations of the phalangeal skin surfaces were not segregated but formed an overlapping continuum. Moreover, within these regions, as the electrode was displaced in regular steps across the mediolateral axis, RFs did not shift across the digit skin surface in an orderly manner, suggesting a lack of internal topography in the finger representation zones. Tactile experience promoted by environmental enrichment induced alterations in the representational features of the SI cutaneous map of the forepaw. In EE rats, the areal extent of the forepaw cutaneous representation was 1.5 times larger than in SE rats. Indeed, the cutaneous map extended into NCR cortical sectors along its external margins and also into NCR islets found in the forepaw area. Consequently, in EE rats there were fewer representational discontinuities. The areal enlargement was due to a selective increase in the areal extent of the glabrous but not the hairy skin surface representations. Furthermore, protuberant glabrous skin (digit tips, palmar pads) was represented over larger cortical regions than were other glabrous skin territories less likely to be stimulated during object palpation and manipulation. Maps from EE rats were also characterized by a larger proportion of sites with single RFs (88% compared with 79%). In addition, glabrous RFs from EE rats were smaller and more clustered on the digit tips and palmar pads than were RFs in SE rat maps. RF size on hairy skin surfaces remained unchanged. Because the RFs were smaller, the cutaneous maps of EE rats contained distinct representations of digit phalangeal glabrous skin. RFs tended to exhibit more orderliness in their progression across the digit glabrous skin of EE rats than they did in SE rats. The phalanges of EE rats were represented in distinct patches. Neurons in EE rats were more sensitive to light tactile stimulation than were neurons in SE rats. These alterations were presumably mediated by the selective potentiation of cutaneous over deep-receptor activation. More generally, the present study corroborates the view that cortical cutaneous maps are maintained in a permanent state of use-dependent fluctuation. Received: 3 June 1997 / Accepted: 11 November 1997     

Reaping the benefits of meaningful work: The mediating versus moderating role of work engagement

This study examined whether meaningful work may improve one's quality of life outside of the workplace (i.e., work‐to‐life enrichment). More importantly, we proposed and tested competing hypotheses regarding the role of work engagement in the relationship between meaningful work and work‐to‐life enrichment. Specifically, we investigated whether work engagement served as a mediator of this relationship, as suggested by the job demands‐resources model, or instead a moderator, as suggested by conservation of resources theory. Two‐wave survey data were collected from 194 respondents recruited via Amazon Mechanical Turk. Analyses showed that meaningful work was positively related to work‐to‐life enrichment over time (i.e., 3 months later). Additionally, work engagement mediated but did not moderate the relationship between meaningful work at Time 1 and work‐to‐life enrichment at Time 2. We suggest that organizations foster a sense of meaningfulness in employees to facilitate engagement and in turn enrich employees' lives beyond the workplace. Therefore, not only organizations, but individuals as well may reap the benefits of meaningful work.     

Point estimation in adaptive enrichment designs

Adaptive enrichment designs are an attractive option for clinical trials that aim at demonstrating efficacy of therapies, which may show different benefit for the full patient population and a prespecified subgroup. In these designs, based on interim data, either the subgroup or the full population is selected for further exploration. When selection is based on efficacy data, this introduces bias to the commonly used maximum likelihood estimator. For the situation of two‐stage designs with a single prespecified subgroup, we present six alternative estimators and investigate their performance in a simulation study. The most consistent reduction of bias over the range of scenarios considered was achieved by a method combining the uniformly minimum variance conditionally unbiased estimator with a conditional moment estimator. Application of the methods is illustrated by a clinical trial example.     

我国动物环境丰富研究论文的文献计量分析

目的对我国动物环境丰富研究文献进行计量分析,以期为我国环境丰富研究和应用提供一定参考。方法基于中国知网和万方数据库,检索环境丰富相关文献,分别对论文发表年代、期刊、作者、机构及学科分布和应用环境丰富的动物等进行统计分析。结果 2016年之前共检索出环境丰富相关文献422篇,其中期刊273篇,分布于126种期刊。总体发文量稳步上升,特别是在2006年之后呈快速增长。载文量前3的期刊为《野生动物学报》、《中国康复医学杂志》、《中华行为医学与脑科学杂志》。发文量最多的机构是第三军医大学新桥医院(18篇)和福建医科大学附属协和医院(14篇),而来自此2家单位的陈燕惠、赵聪敏是此方向的高产作者。涉及17个学科,其中神经病学、精神病学、生物学和儿科学是主要学科。应用环境丰富的动物可分3类,最多的是实验动物(占69.6%),其次是动物园动物(22.9%),最后是农场经济动物(7.5%)。结论目前环境丰富的研究相对集中于神经学、精神病学等方面,对于改善动物福利的研究主要在动物园动物上,实验动物此方向的研究还较少,需要加强此方面的工作。     

Pneumococcal carriage among children after four years of routine 10-valent pneumococcal conjugate vaccine use in Brazil: The emergence of multidrug resistant serotype 6C

BackgroundIn 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced free of charge in Brazil as part of the public immunization program. Here we investigated the carriage prevalence, colonization risk factors, capsular types, and antimicrobial resistance among pneumococcal isolates obtained from children in Brazil four years after routine PCV10 use.MethodsBetween September and December 2014, we conducted a cross-sectional study among children < 6 years old who attended one public and two private clinics in Niterói, RJ, Brazil to evaluate pneumococcal nasopharyngeal carriage. Antimicrobial susceptibility and capsular types were determined for all isolates.ResultsOf 522 children, 118 (22.6%) were pneumococcal carriers. Being ≥ 2 years old, attending childcare center, presenting with any symptoms, having acute or chronic respiratory disease, and residing in a slum were associated with pneumococcal carriage. The most prevalent capsular types were 6C (14.5%), 15B/C (11.5%), 11A/D (9.2%), and 6A (7.6%). PCV10 serotypes represented 2.5%. All isolates were susceptible to levofloxacin, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) comprised 39%, with penicillin and ceftriaxone MICs ranging from 0.12–8.0 μg/ml and 0.012–1.0 μg/ml, respectively. The 33 (28%) erythromycin-resistant isolates (MICs of 1.5 to >256 μg/ml) displayed the cMLS_B (72.7%) or M (27.3%) phenotypes, harboring the erm(B) and/or mef(A/E) genes. High non-susceptibility rates (>20%) to clindamycin, erythromycin, penicillin, and tetracycline were largely explained by the prevalence of multidrug resistant (MDR) serotype 6C isolates.ConclusionsEffects of universal childhood PCV10 use on carriage were evident, with the near elimination of PCV10 serotypes. The emergence of MDR serotype 6C isolates, however, is a concern. Ongoing surveillance to monitor serotype 6C increase in invasive diseases is warranted.