目的 了解我国宫颈癌高发区妇 女生殖道人乳头状瘤病毒 (humanpapillomavirus ，HPV)感染状况 ，研究高危型HPV感染与宫颈癌的关系。方法 应用第二代杂交捕获试验对山西省襄垣县 1997名 35～ 45岁已婚妇女自己采集的阴道细胞和医生采集的宫颈细胞 ，检测 13种高危型HPV脱氧核糖核酸 (DNA)。采用多因素的非条件logistic回归模型分析HPV感染与宫颈癌及宫颈上皮内瘤变 (CIN)的关系。用卡帕 (kappa)系数衡量两种标本HPV检测的符合度。 结果 该人群的高危型HPVDNA总检出率为 2 0 .8%。HPVDNA检出率随病变程度加重呈趋势性增高 (χ2 =44 4.0 4，P =0 .0 0 0 )。两年龄组 (35～ 39岁和 40～ 45岁 )妇女的宫颈HPVDNA检出率几乎一样(2 0 .9%∶2 0 .6 %，χ2 =0 .0 3，P =0 .86 )。非条件logistic回归分析显示 ，HPV感染与宫颈上皮内高度病变及癌症 (≥CINⅡ )和低度病变 (CINⅠ )的发生高度相关 (OR =2 5 4.2和OR =2 6 .4) ，归因危险百分比 (ARP)分别为 98.1%和 83.6 %。自我取样HPV检测的灵敏度低于医生取样HPV检测 (84%∶98%，χ2 =5 .92 ，P =0 .0 15 ) ，特异度差异无显著性 (86 %∶85 %，χ2 =0 .0 0 ，P =0 .997) ，但两种标本HPV检测的符合度较好 (kappa =0 .74)。结论 女性生殖道高危型HPV感染是当地宫颈癌及CIN流
摘 要： 龋齿是儿童最常见口腔疾病，并对儿童身心健康造成严重危害，是目前危害儿童口腔健康的常见病、多发病。儿童患龋齿后不仅会引起疼痛，而且还会影响食欲、咀嚼和消化功能，从而影响儿童的生长发育。世界卫生组织已将其与心血管疾病和肿瘤列为人类三大重点防治疾病。为了解襄垣县儿童患龋病情况，进一步为儿童保健和龋齿防治工作提供依据，我县妇幼保健院儿童保健科于2014年3月至6月对6所幼儿园在园儿童的龋齿情况进行了调查，现报告如下。
Abstract 4281: Oncostatin M renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-fluorouracil by inducing hepatocytic differentiation
Recent evidence suggests that a certain type of () is hierarchically organized by a subset of cells with stem cell features (stem cells; ). Although normal stem cells and are considered to share similar self-renewal programs， it remains unclear whether differentiation programs are also maintained in and effectively used for eradication. In this study， we investigated the effect of oncostatin M ()， an -related cytokine known to induce the differentiation of hepatoblasts into hepatocytes， on liver . receptor expression was detected in the majority of epithelial molecule-positive (EpCAM(+)) with stem/progenitor cell features. treatment resulted in the induction of hepatocytic differentiation of EpCAM(+) cells by inducing signal transducer and activator of 3 activation， as determined by a decrease in stemness-related gene expression， a decrease in EpCAM， alpha-fetoprotein and protein expressions， and an increase in albumin protein expression. -treated EpCAM(+) cells showed enhanced with expansion of the EpCAM-negative non-population. Noticeably， combination of treatment with the chemotherapeutic agent (5-FU)， which eradicates EpCAM-negative non-， dramatically increased the number of apoptotic cells in vitro and suppressed in vivo compared with either saline control， ， or 5-FU treatment alone. Taken together， our data suggest that could be effectively used for the differentiation and active of dormant EpCAM(+) liver ， and the combination of and conventional chemotherapy with 5-FU efficiently eliminates by targeting both and non-.
目的 在宫颈癌高发区调查其危 险因素 ，为现阶段宫颈癌的防治工作提供依据。方法在宫颈癌高发区山西省襄垣县 ，对 1997名妇女采用 6种宫颈癌检查方法筛查后 ，进行问卷调查。问卷内容包括 ：基本信息、月经婚孕史、性行为及卫生习惯、避孕史、既往疾病和肿瘤家族史等。进行高危型人乳头瘤病毒 (HPV)检测。病理学诊断为宫颈高度鳞状上皮病变以上者 86例 ;非癌及非鳞状上皮病变者共 1784例作为对照。结果 高危型HPV感染率为 2 0 8% ( 4 15 / 1997)。病例组HPV感染率为 97 7% ，而对照组为 14 2 %。单因素分析后 ，具有显著统计意义的变量有 ：高危型HPV感染、初次性交年龄、流产史、性伴侣数、怀孕治疗史及肿瘤家族史等。logistic回归分析结果表明 ，高危型HPV感染、性伴侣数和肿瘤家族史与宫颈癌的发生呈显著关联。此外 ，HPV感染与男、女婚外性行为均有显著的统计学联系 ，且随性伴侣数呈趋势性增高。结论 襄垣县妇女子宫颈癌高发的主要危险因素是高危型HPV感染。HPV感染与该地区性生活、月经期及产褥期卫生不洁有直接 关联
摘 要： 目的：通过对2006—2009年山西省襄垣县宫颈癌筛查早诊早治结果分析，评价醋酸或碘染色肉眼观察法（visual inspection with acetic acid/Lugol’s iodine，VIA/VILI）宫颈癌筛查方案在农村高发区推广应用的可行性。方法2006—2009年在山西省襄垣县对30-59岁的妇女进行宫颈癌筛查。用VIA和VILI作为初筛方法，VIA/VILI阳性者进行阴道镜检查，阴道镜异常者在病变处取活检进行病理诊断。对VIA和VILI阴性、VIA/VILI阳性但阴道镜检查正常、VIA/VILI阳性同时阴道镜检查异常且病理活检结果为轻度宫颈上皮内瘤样病变（cervical intraepithelial neoplasia grade 1，CIN1）或正常的妇女一年后用与初筛同样的方法进行复查。结果2006—2010年累计筛查16703人次，其中初筛9618人，复查7085人。4年初筛人群累计阴道镜转诊率、中度CIN及以上（CIN2＋）检出率、重度CIN及以上（CIN3＋）检出率分别为4.6%（438/9618）、0.9%（82/9618）、0.5%（44/9618）；复查人群上述指标分别为3.1%（221/7085）、0.6%（42/7085）、0.2%（19/7085）；筛查人群累计（包括初筛和复查）上述指标分别为4.0%（659/16703）、1.3%（124/9618）、0.7%（63/9618）。初筛人群阴道镜转诊率、CIN2＋检出率和CIN3＋检出率均随方案的持续开展呈升高趋势（P〈0.001）；复查阴道镜转诊率、CIN2＋检出率则呈下降趋势（P〈0.001）。结论随着VIA/VILI筛查方案在示范基地的推广，筛查效果越来越显著。VIA/VI-LI是一种经济有效的宫颈癌及其癌前病变筛查方法，适宜在资源有限、经济欠发达的农村地区推广。持续的培训和实践是VIA/VILI筛查方案有效实施的关键措施。
Human aquaporin 4281-300 is the immunodominant linear determinant in the context of HLA-DRB1*03:01: relevance for diagnosing and monitoring patients with neuromyelitis optica.
Abstract OBJECTIVE To identify linear determinants of human aquaporin 4 (hAQP4) in the context of HLA-DRB1*03：01. DESIGN In this controlled study with humanized experimental animals， HLA-DRB1*03：01 transgenic mice were immunized with whole-protein hAQP4 emulsified in complete Freund adjuvant. To test T-cell responses， lymph node cells and splenocytes were cultured in vitro with synthetic peptides 20 amino acids long that overlap by 10 amino acids across the entirety of hAQP4. The frequency of interferon γ， interleukin (IL) 17， granulocyte-macrophage colony-stimulating factor， and IL-5-secreting CD4+ T cells was determined by the enzyme-linked immunosorbent sport assay. Quantitative immunofluorescence microscopy was performed to determine whether hAQP4281-300 inhibits the binding of anti-hAQP4 recombinant antibody to surface full-length hAQP4. SETTING Academic neuroimmunology laboratories. SUBJECTS Humanized HLA-DRB1*03：01+/+ H-2b-/- transgenic mice on a B10 background. RESULTS Peptide hAQP4281-300 generated a significantly (P <.01) greater TH1 and TH17 immune response than any of the other linear peptides screened. This 20mer peptide contains 2 dominant immunogenic 15mer peptides. hAQP4284-298 induced predominantly an IL-17 and granulocyte-macrophage colony-stimulating factor TH cell phenotype， whereas hAQP4285-299 resulted in a higher frequency of TH1 cells. hAQP4281-300 did not interfere with recombinant AQP4 autoantibody binding. CONCLUSIONS hAQP4281-330 is the dominant linear immunogenic determinant of hAQP4 in the context of HLA-DRB1*03：01. Within hAQP4281-330 are 2 dominant immunogenic determinants that induce differential TH phenotypes. hAQP4 determinants identified in this study can serve as diagnostic biomarkers in patients with neuromyelitis optica and may facilitate the monitoring of treatment responses to pharmacotherapies.
目的通过分析为国家宫颈癌和乳 腺癌筛查提供基本评价数据。方法 2009～2010年山西省襄垣县妇幼保健院对该县30～59岁妇女通过醋酸/碘染色后肉眼观察方法开展宫颈癌筛查，阳性者转诊阴道镜，镜下有病变时取活 检，以病理诊断为金标准。对35～59岁的妇女开展乳腺癌筛查，以临床检查法为初筛方法，怀疑阳性者通过超声或乳腺X线进行诊断。结果 2009年完成1993名妇女的宫颈癌筛查，其中宫颈上皮内瘤变2级(CIN2)及以上病变的患病率为1.6%，早诊率为100%，第2年复查率为 91%，仅查出1例CIN2，未查出更高病变，早诊率达100%。完成1819名妇女的乳腺癌筛查，乳腺良性病变9例(4.02%)，良性肿瘤3例 (1.34%);2010年完成2026名妇女的乳腺癌筛查，良性病变103例(13.57%)，良性肿瘤14例(1.84%)，可疑恶性1例。结论该县 宫颈癌的筛查效果明显，乳腺癌筛查仍需加强技术培训。筛查体系和技术队伍建设是基层单位承担农村妇女健康保健服务的关键。
Abstract 4281: Determination of the Relative Potency of a Selective Agonist of the Intermediate-Affinity IL-2 Receptor on Lymphocytes from Human, Cynomolgus Monkey and Mouse
RDB 1450 is an engineered fusion protein designed to selectively activate the intermediate-affinity IL-2 receptor versus the high-affinity IL-2 receptor. The potencies of RDB 1450 and IL-2 for activation of distinct subsets of effector and regulatory lymphocytes from murine， non-human primate and human donors were determined. Splenocytes isolated from mice or leukocytes isolated from human or cyno blood were stimulated with either RDB 1450 or IL-2. Multicolor flow cytometry was used to identify distinct subpopulations and the extent of phosphorylation of STAT5 was measured. Whereas IL-2 is 2-3 orders of magnitude more potent on immunosuppressive T regs relative to NK cells and memory CD8 T cells， RDB 1450 induces activation of NK cells， memory CD8 T cells and T regs at comparable concentrations within each species. The non-differentiated potency of RDB 1450 on the lymphocyte subpopulations examined suggests that its effects are mediated through the intermediate affinity receptors even on CD25-expressing T regs . The preferential activation of T regs by IL-2 may lead to immunosuppression and limit its antitumor efficacy. In contrast， RDB 1450 does not exhibit the same preference for T reg activation and is expected to be more effective in driving antitumor immune responses. These results highlight the differentiated immunological profile of RDB 1450 and support its potential as a novel human immunotherapy.Citation Format： Emily E. Rosentrater， Heather Flick， Jared E. Lopes， Heather C. Losey， Chunhua Wang， Juan C. Alvarez. Determination of the Relative Potency of a Selective Agonist of the Intermediate-Affinity IL-2 Receptor on Lymphocytes from Human， Cynomolgus Monkey and Mouse. [abstract]. In： Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia， PA. Philadelphia (PA)： AACR; Cancer Res 2015;75(15 Suppl)：Abstract nr 4281. doi：10.1158/1538-7445.AM2015-4281
Background： To provide a systematic analysis of formalin fixation artifacts on Illumina sequencing libraries and results， we generated two complementary sequencing libraries (target enrichment sequencing and whole exome sequencing) from 11 pairs of matched formalin-fixed paraffin-embedded (FFPE) and fresh-frozen (FF) tumor samples and two pairs of matched FFPE and FF germline samples. We also generated whole genome sequencing data from a single pair of FF/FFPE tumor samples. Results： The results indicate minimal variations in library fragment size， coverage， and PCR duplicates within FF/FFPE paired samples that are less than 1 year old; whereas， a large variation in these parameters were observed in FF/FFPE pairs in samples that are approximately 2 years old. No significant increase in global mismatch rates and C•G>T•A substitutions were observed in FFPE samples from the former group; whereas， a discernible increase in mismatch rates and C•G>T•A substitutions were observed in FFPE samples from the latter group. However， over 99.7% and 99.5% of concordant calls were observed between matched FF and FFPE pairs at reference and non-reference positions within the targeted regions， respectively. Although an increased rate of global mismatches and C•G>T•A substitutions were observed in some FFPE samples， discordant rates were low (T•A substitutions are comparable in non-reference positions in paired FF and FFPE samples. Conclusions： We developed upfront quality assessment and library preparation method that use low input DNA from FFPE samples to perform next-generation sequencing. The results from our studies indicate the suitability of FFPE samples in sequencing studies. Citation Format： Sarah Munchel， Yen Hoang， Yue Zhao， Joseph Cottrell， Brandy Klotzle， Andrew Godwin， Janelle Noel， Brooke Fridley， Peter Beyerlein， Jian-Bing Fan， Marina Bibikova， Jeremy R. Chien. Targeted or whole genome sequencing of formalin-fixed tissue samples. [abstract]. In： Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego， CA. Philadelphia (PA)： AACR; Cancer Res 2014;74(19 Suppl)：Abstract nr 4281. doi：10.1158/1538-7445.AM2014-4281
The ubiquitin ligase Nedd4 is an ubuiquitin ligase (E3) which belongs to the HECT family. Like other member of this family members， such as Itch and Smurf， Nedd4 has been proposed to regulate a number of signaling pathways， as well as the traffic of several cell surface molecules， however， its physiological role in mammals has not been well characterized. Former reports identified reduction in the mitogenic activity and increase of the adaptor protein Grb10， aberrant IGF-1， VEGF and FGF receptor localization and / or signaling. In the present study， we performed an analysis of Nedd4-null murine embryonal fibroblastoid cells (MEFs) to show that loss of Nedd4 may affect any additional growth factor signaling. Surface expression of PDGF receptor was significantly increased in homozygous mutant mouse embryonic fibroblasts. Accordingly， PDGF-BB stimulation induced enhanced signaling as judged by MAP kinase p42/44 and Akt phosphorylation. Knockdown of Nedd4 in cell lines also induced similar phenotype. Nedd4， when transiently expressed， ubiquitinated PDGF receptor， which lead to degradation. Under the presence of lysosome inhibitors， PDGF receptor down regulation was at least partially blocked， suggesting its lysosome-dependent degradation. Subcellular localization of the PDGF receptor was also analyzed， but apparent difference was not observed. In the scratch assay， Nedd4 knockout cells showed enhanced migration activity， suggesting their active movement. Thus， Nedd4 appears to negatively control PDGF signaling partly through the regulation of its lysosome dependent degradation.Citation Format： Nobuyuki Tanaka， Kyoko Oyama， Keiichi Tamai. Nedd4 controls cell migration by regulating PDGF receptor signaling. [abstract]. In： Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington， DC. Philadelphia (PA)： AACR; Cancer Res 2013;73(8 Suppl)：Abstract nr 4281. doi：10.1158/1538-7445.AM2013-4281