维生素D受体基因多态性与妊娠期糖尿病关系的病例对照研究

目的 探讨维生素D受体（VDR）基因多态性与妊娠期糖尿病（GDM）之间的关系,为GDM的机制研究提供线索与依据。方法 采用病例对照研究设计,以2012年3月1日至2014年7月30日在山西医科大学第一医院产科分娩的孕妇为研究对象,其中334例被诊断为GDM,按年龄、妊娠时间及居住地1∶1匹配相应健康对照。对研究对象进行DNA基因分型,剔除基因分型缺失率>10%者,最终323例病例和320例对照纳入研究。在共显性、显性、隐性和等位基因遗传模型下,通过非条件logistic回归分析VDR基因位点多态性和GDM之间的关系,并采用Haploview软件分析单倍型与GDM之间的关系。结果 在基因水平上,VDR基因与GDM发病风险有关（P<0.05）。在调整孕前BMI、糖尿病家族史后,rs7967152位点在共显性（AC vs. AA,OR=1.58,95%CI：1.13~2.21）、显性（AC+CC vs. AA,OR=1.58,95%CI：1.15~2.18）和等位基因（C vs. A,OR=1.41,95%CI：1.10~1.82）遗传模型下与GDM风险升高有关;rs2238140位点在共显性（AA vs. GG,OR=2.24,95%CI：1.19~4.20）、显性（GA+AA vs. GG,OR=1.48,95%CI：1.07~2.03）和等位基因（A vs. G,OR=1.43,95%CI：1.11~1.83）遗传模型下与GDM风险升高有关。在共显性和显性遗传模型下,孕妇携带rs2853564位点AG基因型、AG+GG基因型（OR=1.46,95%CI：1.04~2.05;OR=1.45,95%CI：1.05~2.00）与携带AA基因型相比,是GDM的危险因素;孕妇携带rs2853566位点AG基因型、AG+GG基因型（OR=1.43,95%CI：1.03~2.00;OR=1.41,95%CI：1.02~1.94）与携带AA基因型相比,是GDM的危险因素。在VDR基因内由rs1544410、rs7967152组成的单倍型区块,其GC单倍型与是GDM的危险因素（OR=1.50,95%CI：1.15~1.97）。结论 VDR基因rs7967152、rs2238140、rs2853564、rs2853566位点多态性和区块（rs1544410、rs7967152）GC单倍型与GDM的发病风险升高有关。     

全球针对家族史高危人群的结直肠癌筛查指南推荐意见的系统综述

目的 对全球现有结直肠癌家族史高危人群筛查指南的更新进展及推荐意见进行系统总结和评价。方法 以“结直肠癌”“筛查”“指南”“共识”“推荐”“家族史”以及“colorectal cancer”“screening”“guideline”“recommendation”“family history”为关键词,并补充其自由词,系统检索中国知网、万方数据知识服务平台、PubMed、Embase、Cochrane Library、Web of Science,并且同时检索官网刊登的结直肠癌筛查指南/共识作为补充,语种限定为中文和英文。截至2022年5月24日,共20篇有效文献。对纳入文献的基本信息、针对家族史人群的推荐意见等进行摘录整理及汇总描述。结果 在20篇文献中,大多数国家/地区/机构根据结直肠癌家族史人群的亲属关系等级,对筛查起止年龄、筛查方式及筛查周期提出建议。多数指南针对有1例60岁前患结直肠癌一级亲属的人群,推荐筛查起始年龄为40岁或比患病亲属诊断年龄提前10年,推荐的筛查方式多为结肠镜。结论 目前全球多数结直肠癌家族史高危人群筛查指南主要针对一级亲属家族史、以结肠镜作为主要筛查方式。本文将为我国针对结直肠癌家族史高危人群筛查策略的更新提供参考依据,进而完善结直肠癌筛查与早诊早治实践。     

食管癌筛查队列操作流程与建设标准方案探讨

癌症防治工作的重点在于一级预防和二级预防,通过健康教育引起人们对疾病的重视、自觉改变不良行为习惯、主动参加定期体检是防治癌症性价比最高的措施之一。食管癌作为我国疾病负担较重的恶性肿瘤之一,定期筛查和早诊早治是该病防治工作的重点。而队列研究有助于了解食管癌的自然史和危险因素、识别食管癌高危人群。本研究拟从危险因素调查、疾病监测、生物样本信息搜集等方面对食管癌多维动态随访共享队列的建设规范进行探讨,为今后建立规范统一的食管癌筛查队列研究操作流程和建设标准提供参考。     

A nationwide post-marketing survey of knowledge,attitude and practice toward human papillomavirus vaccine in general population: Implications for vaccine roll-out in mainland China

BackgroundHuman papillomavirus (HPV) vaccine has been increasingly discussed in mainland China since its first approval in 2016. To date, nearly all studies assessing HPV vaccine perceptions and attitudes were implemented during pre-licensure period. Therefore, the nationwide post-marketing survey was conducted to update knowledge, attitudes and practice on HPV vaccine among general population in mainland China.MethodsParticipants aged 18–45 years living in mainland China were recruited in April 2019 by multi-stage non-randomized sampling. Sociodemographic factors, HPV and HPV vaccine related awareness, knowledge, attitudes, vaccine uptake and potential obstacles were assessed in questionnaires. Bivariate analysis and multivariate regression were used to identify disparity among subgroups with different sociodemographic characteristics.Results4,000 women (32.1 ± 7.81y) and 1,000 men (31.8 ± 7.96y) were included in final analysis. Less than one third of participants had heard of HPV (female: 31%; male: 22%) and HPV vaccine (female: 34%; male: 23%). Knowledge score was also unfavorable on HPV (female: 3 out of 13; male: 1.8 out of 13) and HPV vaccine (female: 3 out of 6; male: 2 out of 5). Only 3% females had been vaccinated three years after HPV licensure in China, although willingness to get vaccinated among those unvaccinated were high (mean willingness score ± SD: female: 3.3 ± 0.97; male: 3.0 ± 0.98). Industry of employment and household income were the major factors related to awareness and knowledge of vaccine, whereas HPV and HPV vaccine awareness were key influential factors for willingness. The main obstacles of vaccination were safety concerns, lack of knowledge, and high price of HPV vaccines.ConclusionsFindings highlight a lack of vaccine awareness, knowledge, and poor uptake in mainland China and underscore the necessity of health education campaigns. The identified priority groups, contents to be delivered and practical obstacles could furthermore provide insight into health education to reduce disparities and accelerate HPV vaccine roll-out in China.     

Biochemical interactions between methotrexate and 1-β-d-arabinofuranosylcytosine in hematopoietic cells of children: a Pediatric Oncology Group study

Summary Children with acute lymphocytic leukemia (ALL) in remission were treated with overlapping sequential infusions of methotrexate (MTX) and 1--d-arabinofuranosylcytosine (araC) as part of continuation therapy. The doses and the sequence were chosen to mimic conditions that produced greater than additive antineoplastic activity with these two drugs in preclinical studies. To assess the potential for the drug combination to exhibit greater than additive effect in vivo, we investigated several biochemical parameters that had been associated with synergism in vitro. Because the patients were in remission, the intracellular parameters could only be measured in cytologically normal hematopoietic cells. We observed that (1) the mean plasma concentrations of MTX and araC were above those required to obtain a greater than additive cytotoxicity with the two drugs in tissue culture; (2) MTX did not have a significant antipurine effect in bone marrow mononuclear cells; (3) the mean intracellular concentration of deoxycytidine triphosphate (dCTP) was significantly lower after treatment with the drug combination than after therapy with araC alone; and (4) the ratio of araC triphosphate (araCTP) to dCTP was 2.6 times higher after treatment with the combination than after araC alone. These results indicate that it is possible to achieve in patients the biochemical conditions associated with the greater than additive antineoplastic activity of MTX and araC in vitro.Abbreviations ALL acute lymphocytic leukemia - araC 1--d-arabinofuranosyluracil - araCTP araC triphosphate - araU 1--d-arabinofuranosyluracil - dNTPs deoxyribonucleoside triphosphates - MTX methotrexate - TCA trichloroacetic acid Supported in part by grants from the National Cancer Institute, National Institutes of Health (CA-38 053; CA-33572, CA-32278, CA-38 859, CA-29 691, and CA-30 969). Preliminary reports on the biochemical data were published by E. M. N., A. M. T., and D. P. inProc Am Assoc Cancer Res 24: 133 (1983) and those on the clinical data, by R. A K., E. M. N., D. P. R. B. R., M. B. H., Y. R., and A. I. F. inProc Am Soc Clin Oncol 3: 201 (1984)