FHIT基因与HPV联合检测对宫颈癌诊断的意义

目的 通过检测宫颈癌患者DNA中脆性组氨酸三联体基因异常甲基化以及高危人乳头瘤病毒,以探讨二者联合检测在宫颈癌诊断中的意义.方法 采用巢式甲基化特异性PCR方法检测21例宫颈癌患者脆性组氨酸三联体基因的甲基化状态,同时应用HC2法测定高危人乳头瘤病毒,并与32例宫颈上皮内瘤变患者和25例健康者作对照,分析二者联合应用的临床诊断价值.结果 在13例宫颈癌患者标本检测到了脆性组氨酸三联体基因的甲基化,阳性率为66.7%,高危人乳头瘤病毒的阳性率为90.5%;平行联合检测时敏感性增至95.0%.宫颈上皮内瘤变组中脆性组氨酸三联体基因甲基化与高危人乳头瘤病毒阳性率分别为3.1%和28.1%;健康对照者标本中脆性组氨酸三联体基因无异常甲基化,高危人乳头瘤病毒阳性率为12.0%.结论 联合检测患者脆性组氨酸三联体基因甲基化与高危人乳头瘤病毒可提高宫颈癌诊断的敏感性和特异性,对于宫颈癌的早期诊断具有积极意义.     

FHIT基因与结肠癌及关系的研究进展

脆性组氨酸三联体(FHIT)基因是脆性组氨酸三联体基因家族的成员,是一个候选抑癌基因,在嘌呤代谢中参与编码一个AP3A水解酶。该基因在3号染色体上包含常见的脆性部位FRA3B。在多种肿瘤特别是环境致癌物引起的肿瘤中常有FHIT基因的异常改变。FHIT基因可能通过调控细胞周期,诱导细胞凋亡发挥抑制肿瘤的作用,其失活机制主要表现为启动子区域CPG岛甲基化、缺失及异常转录。此文拟就FHIT基因与结肠癌的关系进行综述。     

脆性组氨酸三联体基因在肺癌发病中的研究进展

肺癌是严重威胁人类生命健康的恶性肿瘤之一,其发病机制复杂,细胞癌基因的激活和抑癌基因的失活是近年来在肿瘤研究中的热点,抑癌基因的失活被认为是重要的致癌因素。脆性组氨酸三联体基因（fragile histidine triad,FHIT）定位于染色体3p14．2上,该基因在人类约60％的上皮性肿瘤中表达降低或缺失,对其研究可能为肿瘤的发生机制提供新线索。现就FHIT基因与肺癌发病的有关研究进展综述如下。     

脆性组胺三联体、增殖细胞核抗原蛋白与宫颈上皮内瘤变恶性程度的相关性研究

目的研究脆性组胺三联体（fragile histidine triad，FHIT）蛋白和增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）蛋白在宫颈涂片中的表达及在宫颈癌前病变诊断中的意义。方法选取2004年6月至2005年6月在兰州大学第一医院妇科门诊宫颈计算机辅助细胞学检测涂片（computer—assisted cytology test，CCT）为低度鳞状上皮内病变（low-grade squamous intraepithelial lesion，LSIL）（74例）和高度鳞状上皮内病变（high—grade squamous intraepithelial lesion，HSIL）（40例）的可疑宫颈病变患者114例，采用免疫组化法检测患者宫颈组织中脆性组胺三联体、增殖细胞核抗原蛋白的表达情况。结果脆性组胺三联体蛋白在正常宫颈上皮中表达，在宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）及宫颈癌中表达缺失，在宫颈上皮内瘤变Ⅰ、宫颈上皮内瘤变Ⅱ、宫颈上皮内瘤变Ⅲ及宫颈癌组织中，其表达缺失率分别为13．3％，30．0％，60．0％和71．4％。增殖细胞核抗原蛋白在宫颈上皮内瘤变及宫颈癌中表达升高，在宫颈上皮内瘤变Ⅰ、宫颈上皮内瘤变Ⅱ、宫颈上皮内瘤变Ⅲ及宫颈癌组织中，其阳性表达率分别为44．7％，60．0％．80．0％，85．7％，而且其染色强度明显升高。各组间脆性组胺三联体蛋白、增殖细胞核抗原蛋白表达率比较，差异有显著意义（P=0．0001）。结论脆性组胺三联体蛋白表达缺失，是宫颈癌发生的早期事件，其表达缺失程度与宫颈上皮内瘤变的分级有关，高级别的癌前病变缺失率明显增高；增殖细胞核抗原蛋白的表达，在宫颈癌前病变中逐级增高，可用于评估癌前病变的恶变潜能。     

FHIT蛋白和PCNA在子宫颈病变中的表达

目的研究脆性组氨酸三联体基因(FHIT)蛋白和增殖细胞核抗原(PCNA)在正常宫颈、宫颈上皮内瘤变(CIN)和宫颈癌中的表达情况,探讨两者在宫颈癌早期诊断和发生发展中的临床意义。方法采用免疫组织化学SP法检测20例正常宫颈组织,20例宫颈CINⅠ级,25例CINⅡ/Ⅲ级,60例宫颈癌(均为宫颈鳞癌)组织中的FHIT蛋白和PCNA的表达。结果正常宫颈组、CINⅠ级组、CINⅡ/Ⅲ级组和宫颈癌组中FHIT表达的阴性率和PCNA表达的阳性率均递增,且有统计学意义。FHIT表达的缺失与宫颈癌患者的病理分级和淋巴结转移有关系。PCNA的表达与宫颈癌患者的年龄、肿瘤大小、病理分级、临床分期及淋巴结转移均无明显相关。宫颈癌中FHIT表达的缺失和PCNA的表达呈负相关(r=-0.193)。结论检测宫颈CIN中的FHIT蛋白表达情况,可用作高级别的CIN筛查或预测。FHIT和PCNA对于宫颈癌前期病变和宫颈癌的筛查和早期诊断具有一定的临床参考价值。     

FHTT基因与子宫颈癌关系研究进展

1996年,Ohta等[1]利用外显子捕捉法在人类染色体3p14.2处克隆了一条新基因,此基因编码的蛋白质属于组氨酸三聚体结构(histidine triad,HIT)类蛋白质,该基因跨越人类染色体脆性部位FRA3B,故得名脆性组氨酸三联体基因(fragile histidine triad gene,FHIT).     

宫颈癌并发人乳头瘤病毒感染癌症组织FHIT和C-myc研究

目的探讨宫颈癌并发高危型人乳头瘤病毒(HPV)感染妇女的癌症组织脆性组氨酸三联体基因(FHIT)、癌基因C-myc蛋白表达水平。方法选取内蒙古医科大学附属医院2016年5月-2018年5月收治的宫颈癌患者为宫颈癌组;宫颈上皮内瘤变(CIN)患者为CIN组;因子宫良性病变行子宫切除术的患者为对照组。比较所有标本中FHIT、C-myc蛋白表达情况以及HPV亚型。结果 CIN组和宫颈癌组FHIT阳性率低于对照组(P<0.05),C-myc阳性率高于对照组(P<0.05);宫颈癌组FHIT阳性率低于CIN组(P<0.05)。宫颈癌组高危亚型HPV感染率高于CIN组和对照组(P<0.05)。宫颈癌患者癌组织中FHIT阳性表达与组织分化程度、卵巢癌分期(FIGO)和高危亚型HPV感染有关(P<0.05);C-myc阳性表达与组织分化程度、病理类型、FIGO分期、淋巴结转移和高危亚型HPV感染有关(P<0.05)。结论合并高危亚型HPV感染的宫颈癌患者癌组织中C-myc表达上调,FHIT表达下调,提示可能对于宫颈癌的诊断有一定意义。     

FHIT基因与宫颈癌的关系研究进展

3号染色体短臂一直是许多研究关注的热点，因为它可能是肿瘤抑制基因位点。1996年发生在3p族中一个重要的事件是在一家族性肾癌中观察到与交叉移位（3；8）（p14．2；q24）有关的基因被克隆出来。该基因被命名为脆性组氨酸三联体（fragile histidine triad，FHIT），它编码二核苷酸5’，5＇＇＇-P1，P3三磷酸水解酶。     

宫颈癌合并HPV感染患者HPV不同亚型分布及脆性组氨酸三联体蛋白表达

目的探究宫颈癌合并人乳头瘤病毒(HPV)感染患者HPV不同亚型分布及脆性组氨酸三联体(FHIT)蛋白表达情况。方法选取2015年6月-2018年6月于首都医科大学附属北京同仁医院行手术切除宫颈癌患者45例作为宫颈癌组,同期收治子宫肌瘤行子宫全切、宫颈健康患者30例为对照组。检测HPV基因分型及FHIT蛋白表达水平;比较宫颈癌组织和正常组织聚合酶链反应产物电泳图谱,检测FHIT外显子D3S1234和D3S1300微卫星多态标记杂合性丢失(LOH)和微卫星不稳定性(MI)。结果 45例宫颈癌检出13种HPV亚型,以高危型感染为主。宫颈癌HPV亚型感染检出单一亚型感染31例、双重感染8例、多重感染6例。宫颈癌组FHIT表达阳性率28.89%低于对照组(P<0.05);FHIT表达与宫颈癌病理分级和淋巴结转移关系密切(P<0.05);宫颈癌LOH或MSI出现频率80.00%,外显子D3S1234 MSI频率24.44%、LOH频率51.11%、D3S1300 MSI频率22.22%、LOH频率68.89%,均出现MSI 2例、LOH 13例。结论高危型HPV感染与宫颈癌发生发展密切相关,FHIT基因MSI、LOH及蛋白表达水平与宫颈癌关系密切,为宫颈癌筛查诊断提供参考价值。     

宫颈癌相关基因多态性与患者报告结局和生命质量关系研究进展

整理可能对宫颈癌患者报告结局和生命质量造成影响的相关基因,并探讨这些基因多态性与患者报告结局和生命质量的关系。利用中国知网(CNKI)、万方、PubMed、ScienceDirect 4个数据库,以“宫颈癌、基因、基因多态性、情绪、心理、患者报告结局和生命质量”为中文检索词,“Cervical cancer、gene、polymorphism、emotion、psychology、patient-reported-outcomes和quality of life”为英文检索词,检索1999-01-01-2022-08-30相关文章。纳入标准：(1)基因多态性、基因与宫颈癌的相关性;(2)患者报告结局、生命质量与基因关系。排除标准：(1)年代久远的综述类文献;(2)文章质量差的文献。最终纳入文献125篇。经过专家咨询和核心小组讨论等方法筛选可能与宫颈癌患者报告结局和生命质量相关的基因,同时探讨这些基因的潜在影响机制。结果表明,脆性组氨酸三联体(FHIT)、肿瘤坏死因子(TNF)和微小RNA(miRNA)基因与宫颈癌发生发展相关;宫颈癌组中的FHIT阳性表达率较高,提示在宫颈癌中FHIT基...     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.