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1.
目的 探讨脆性组氨酸三联体(FHIT)与甲基-CpG-结合蛋白2(MeCP2)异常表达在宫颈癌变中的交互作用。方法 选择经病理学确诊的宫颈鳞状细胞癌(SCC)患者73例,宫颈上皮内瘤样变(CIN)患者113例(CINⅠ45例;CINⅡ/Ⅲ68例)和宫颈正常(NC)妇女60人作为研究对象,分别采用荧光定量PCR和Western blot检测宫颈组织中FHIT及MeCP2 mRNA和蛋白的表达量,甲基化特异性PCR(MSP)检测FHIT基因CpG岛甲基化状态。利用SPSS 20.0软件进行相关资料的Kruskal-Wallis H检验、χ2检验、χ2趋势检验和Spearman秩相关分析,应用广义多因子降维模型(GMDR)评价交互作用。结果 随着宫颈癌变的进展,FHIT基因CpG岛甲基化率(χ2=18.64,P<0.001,趋势检验χ2=18.08,P<0.001)逐渐升高,FHIT mRNA(H=27.32,P<0.001;趋势检验χ2=12.65,P<0.001)与蛋白(H=47.10,P<0.001;趋势检验χ2=29.79,P<0.001)表达量逐渐降低,且FHIT基因CpG岛甲基化率与FHIT蛋白表达量呈负相关(r=-0.226,P<0.001)。MeCP2 mRNA(H=26.19,P<0.001;趋势检验χ2=11.81,P=0.001)与蛋白(H=69.02,P<0.001;趋势检验χ2=47.44,P<0.001)表达量均逐渐升高。MeCP2蛋白表达量与FHIT mRNA Ct比值呈正相关(r=0.254,P<0.001),与FHIT蛋白表达量呈负相关(r=-0.213,P=0.001)。GMDR交互作用分析表明,在CINⅡ/Ⅲ组,MeCP2蛋白高表达、FHIT基因CpG岛甲基化及mRNA和蛋白低表达存在交互作用;在SCC组,MeCP2 mRNA和蛋白高表达、FHIT基因CpG岛甲基化及mRNA和蛋白低表达存在交互作用。结论 MeCP2 mRNA和蛋白高表达、FHIT基因CpG岛甲基化及mRNA和蛋白低表达,均可增加宫颈癌变的风险,且在宫颈癌变中具有协同作用。  相似文献   

2.
目的 探讨脆性组氨酸三联体(FHIT)基因甲基化及蛋白表达异常与HPV16感染在宫颈癌变中的作用及其交互效应。方法 选择2009年9月至2011年3月在山西省肿瘤医院、山西医科大学第二医院妇科、太原市妇幼保健院和介休市妇幼保健院就诊的宫颈鳞状细胞癌(SCC)新发患者100例,宫颈上皮内瘤样变(CIN)患者142例(72例CIN1,70例CIN2+)和正常宫颈(NC)妇女108例为研究对象。采用多重PCR法检测HPV16感染状况,应用甲基化特异性PCR(MSP)和Western Blot法分别检测FHIT基因甲基化状态和蛋白的表达水平。利用SPSS 20.0软件进行相关资料的t检验、方差分析、χ2检验、因素与疾病关联效应分析(OR值及其95%CI),应用相加效应模型进行交互作用评价。结果 HPV16感染率在CIN1组(45.8%)、CIN2+组(68.6%)和SCC组(73.0%)均高于NC组(28.7%),差异均有统计学意义(P<0.001);在NC、CIN1、CIN2+和SCC组,FHIT基因甲基化率分别为3.7%、13.9%、21.4%和38.0%,蛋白表达水平分别为1.255±0.130、1.184±0.172、1.133±0.126和1.099±0.148,各组的差异均有统计学意义(P<0.001);随宫颈病变程度的加重,HPV16感染率逐渐升高(趋势检验χ2=47.623,P<0.001),FHIT基因甲基化率逐渐升高(趋势检验χ2=40.147,P<0.001),FHIT蛋白低表达率也逐渐升高(趋势检验χ2=65.098,P<0.001);FHIT基因高甲基化、FHIT蛋白低表达与HPV16感染在不同宫颈病变组均存在正相加交互效应。结论 FHIT基因高甲基化和FHIT蛋白低表达与HPV16感染均可增加宫颈癌及其癌前病变的发生风险,FHIT基因高甲基化和FHIT蛋白低表达与HPV16感染在宫颈癌变中均具有协同作用。  相似文献   

3.
目的 探讨叶酸与人乳头瘤病毒16型(HPV16)E6/E7 mRNA表达在宫颈癌变中的交互作用。方法 选取经病理学确诊的宫颈鳞状细胞癌(SCC)患者64例、低度宫颈上皮内瘤样变(CIN1)患者55例、高度宫颈上皮内瘤样变(CIN2+)患者55例和正常宫颈(NC)者80例作为研究对象。采用微生物法测定血清叶酸和红细胞叶酸水平,应用real-time PCR法检测HPV16 E6/E7 mRNA表达水平。利用SPSS 16.0软件进行相关资料的χ2检验、方差分析、Welch检验、Kruskal-Wallis H检验、有序logistic回归和Spearman秩相关分析,应用相加模型进行交互作用分析。结果 随着宫颈癌变的进展,血清叶酸和红细胞叶酸水平均呈逐渐降低趋势(χ2=32.71,P<0.001; χ2=16.32,P<0.001),且血清叶酸和红细胞叶酸含量呈正相关(r=0.41,P<0.001);HPV16 E6/E7 mRNA表达水平随着宫颈癌变的进展呈逐渐升高趋势(χ2=30.11,P<0.001; χ2=38.99,P<0.001);红细胞叶酸含量与HPV16 E6/E7 mRNA表达量呈负相关(E6:r=-0.14,P=0.009;E7:r=-0.21,P=0.001),红细胞叶酸缺乏与HPV16 E6/E7mRNA高表达在CIN1、CIN2+和SCC组均存在正相加交互作用。结论 叶酸缺乏和HPV16 E6/E7 mRNA高表达均可增加宫颈癌及癌前病变发生的风险,两者在宫颈癌变进展中存在协同作用。  相似文献   

4.
目的 探讨叶酸与p16蛋白在宫颈癌变中的作用及其相互效应。方法 选取经病理学确诊的80例正常宫颈(NC)妇女、55例低度宫颈上皮内瘤样变(CINⅠ)患者、55例高度宫颈上皮内瘤样变(CINⅡ/Ⅲ)患者、64例宫颈鳞状细胞癌(SCC)患者为研究对象。分别采用微生物法和Western-blot方法检测其血清叶酸水平和p16蛋白的表达量。同时采用体外细胞实验研究方法,对HPV阴性的宫颈癌细胞C33A和HPV16阳性的宫颈癌细胞Caski进行不同浓度叶酸干预,检测两种宫颈癌细胞的增殖和凋亡情况,以及p16蛋白的表达。结果 NC组、CINⅠ组、CINⅡ/Ⅲ组和SCC组血清叶酸含量分别为(5.96±3.93) ng/ml、(5.08±3.43) ng/ml、(3.92±2.59) ng/ml、(3.18±2.71) ng/ml,p16蛋白表达水平分别为0.80±0.32、1.33±0.52、1.91±0.77、2.09±0.72;随着宫颈病变的进展,血清叶酸含量逐渐降低(趋势检验 χ2=32.71,P<0.001),p16蛋白表达量逐渐升高(趋势检验 χ2=56.06,P<0.001)。在CINⅠ、CINⅡ/Ⅲ、SCC组中血清叶酸缺乏与p16蛋白高表达均存在正相加交互作用。体外实验结果显示,随着叶酸浓度的增加,宫颈癌细胞的增殖抑制率(C33A:r=0.928,P=0.003;Caski:r=0.962,P=0.001)和凋亡率(C33A:r=0.984,P<0.001;Caski:r=0.986,P<0.001)均上升,p16蛋白表达量逐渐降低(C33A:r=-0.817,P=0.025;Caski:r=-0.871,P=0.011),且p16蛋白表达量与宫颈癌细胞的增殖抑制率(C33A:r=-0.935,P=0.002;Caski:r=-0.963,P=0.001)和凋亡率(C33A:r=-0.844,P=0.017;Caski:r=-0.898,P=0.006)均呈负相关关系。结论 血清叶酸缺乏与p16蛋白高表达均可增加宫颈癌和癌前病变的发病风险,两者在宫颈癌和癌前病变中存在正相加交互作用。补充叶酸可逆转p16蛋白的异常表达,有效抑制宫颈癌细胞的增殖,促进凋亡。  相似文献   

5.
目的 探讨多环芳烃与p16FHIT基因CpG岛甲基化在宫颈上皮内瘤变(CIN)中的作用及其交互效应。方法 利用2014年6-12月建立的山西省阳曲县宫颈病变研究队列。包括经病理学确诊的CIN患者169例(CINⅠ86例,CINⅡ/Ⅲ 83例)和正常宫颈(NC)妇女91例。全部研究对象采用高效液相色谱法检测尿液中的1-羟基芘(1-OHP)浓度,甲基化特异性PCR法检测抑癌基因p16FHIT CpG岛甲基化状态。应用SPSS 20.0软件进行相关资料的Kruskal-Wallis H检验、χ2检验、趋势χ2检验,应用logistic回归模型计算因素与宫颈疾病之间关联强度的OR值及其95%CI,应用广义多因子降维模型(GMDR)评价交互作用。结果 随着CIN程度加重,1-OHP水平逐渐上升(H=50.743,P<0.001),1-OHP高暴露率逐渐升高(趋势检验χ2=20.146,P<0.001)。CINⅠ、CINⅡ/Ⅲ组p16FHIT CpG岛甲基化率均高于NC组;随着CIN程度的加重,p16基因CpG岛甲基化率(趋势检验χ2=9.75,P=0.002)、FHIT基因CpG岛甲基化率(趋势检验χ2=10.39,P=0.001)均逐渐升高。GMDR交互作用分析显示,在CINⅠ和CINⅡ/Ⅲ组,1-OHP高暴露与p16FHIT基因CpG岛甲基化呈交互作用。结论 1-OHP高暴露和p16FHIT CpG岛甲基化均可增加CIN的风险,且在病变中具有协同作用。  相似文献   

6.
目的 探讨叶酸和甲基-CpG-结合蛋白2(MeCP2)表达在宫颈癌变中的交互作用。方法 选择经病理学确诊的宫颈鳞状细胞癌(SCC)患者41例,宫颈上皮内瘤样变(CIN)患者71例(34例CIN1和37例CIN2+)及61名宫颈正常(NC)妇女为研究对象。采用微生物法检测血清叶酸和红细胞叶酸水平,Western blot法和荧光定量PCR法检测宫颈组织中MeCP2蛋白和mRNA的表达量。利用SPSS 20.0软件进行相关资料的Kruskal-Wallis H检验、χ2检验、χ2趋势检验和Spearman秩相关分析,应用广义多因子降维模型(GMDR)评价交互作用。结果 随着宫颈病变程度的加重,血清叶酸(H=44.71,P<0.001;趋势检验 χ2=24.48,P<0.001)和红细胞叶酸(H=5.28,P<0.001;趋势检验 χ2=3.83,P<0.05)水平均呈逐渐降低趋势,且血清叶酸和红细胞叶酸水平呈正相关(r=0.270,P<0.001);MeCP2蛋白(H=33.72,P<0.001;趋势检验χ2=14.74,P<0.001)和mRNA (H=19.50,P<0.001;趋势检验χ2=10.74,P<0.001)表达量随着宫颈病变的进展均呈逐渐升高趋势;叶酸水平与MeCP2蛋白表达量呈负相关(血清叶酸:r=-0.226,P=0.003;红细胞叶酸:r=-0.164,P=0.004)。GMDR交互作用分析表明,在SCC组和CIN2+组,血清叶酸和红细胞叶酸缺乏,MeCP2蛋白高表达与MeCP2mRNA高表达呈现交互作用。结论 叶酸缺乏和MeCP2基因异常高表达可增加宫颈癌及其癌前病变的风险,血清叶酸缺乏、红细胞叶酸缺乏、MeCP2蛋白高表达和MeCP2mRNA高表达在宫颈癌变的发展过程中具有协同作用。  相似文献   

7.
目的 探讨DNA甲基转移酶1(DNMTl)和甲基-CPG-结合蛋白2(MecP2)与宫颈癌发生发展的关系及其在宫颈癌变中的相互作用。方法 选择经病理学确诊的宫颈鳞状细胞癌(SCC)患者74例、低度宫颈上皮内瘤样变(CIN I)患者52例、高度宫颈上皮内瘤样变(CINⅡ一Ⅲ)患者60例和宫颈炎(CI)患者58例为研究对象。在收集全部对象人口学特征、人乳头瘤病毒感染、生殖因素等相关资料同时,检测DNMTl和MeCP2蛋白(Western blot法)和mRNA(real-time PCR法)的相对表达量。采用SPSS 17.0分析软件,计算相关资料的t检验、X2检验、因素与疾病之间关联强度指标(0R值及其95%CI)及其交互作用。结果 随着宫颈病变的加重,DNMTl和MeCP2蛋白表达水平逐渐增高(H=94.33,PF=21.580,P<0.001),DNMTl和MeCP2 mRNA的表达水平亦逐渐增高(F=4.758,P=0.003;F=7。804,Pr=0.287,P<0.001)和mRNA(r=0.179,P=0.005)表达均存在正相关关系。交互作用分析显示,DNMTl与MeCP2蛋白和mRNA高表达在SCC组和CINl/-Ⅲ组存在正相加交互作用。结论 DNMTl及MeCP2高表达可增加宫颈癌和癌前病变发生的风险,两者在C1N II-Ⅲ组和SCC组存在正相加交互作用。  相似文献   

8.
目的探讨宫颈癌细胞中叶酸对DNA甲基转移酶1(DNMTl)和甲基化CpG岛结合蛋白2(MeCP2)表达的调节作用。方法采用体外实验研究方法,对宫颈癌细胞casl(i(HPVl6阳性)和C33A(HPV阴性)进行不同浓度(10、50、100、500、750、1000 I.tg/m1)叶酸干预,分别采用Western blot和real-time PCR方法检测两种细胞中DNMTl和MeCP2蛋白的表达量和mRNA水平。结果随着叶酸水平的升高,两种细胞的生长抑制率(C33A:r=0.984,Pr=0.978,P=0.002)和凋亡率(C33A:r=0.989,P<0.001;Caski:r=0.994,Pr=0.914,Pr=0.859,P=0.003)及MeCP2蛋白表达(C33A:r=0.830,P=0.005;Caski:r=0.981,P<0.001)均呈逐渐降低趋势,而DNMTl和MeCP2 mRNA的Ct比值在两种细胞中的变化均无统计学意义(P>O.05)。相同叶酸浓度下,DNMTl蛋白和mRNA表达水平在Caski细胞均较C33A细胞为高,而MeCP2蛋白和mRNA表达水平则在C33A细胞较Caski细胞普遍为高。结论补充叶酸可有效抑制宫颈癌细胞的增殖,促进凋亡,逆转DNMTl和MeCP2蛋白的异常表达;HPVl6感染与DNMTl功能异常对宫颈癌的发生可能有协同效应。  相似文献   

9.
目的 探讨hnRNP K与HPV16感染在宫颈上皮内瘤样变(CIN)中的作用及其交互效应。方法 选取2014年6月至2015年6月在山西省介休市建立的社区队列中经病理学确诊的正常宫颈(NC)女性67例和CIN患者137例(CINⅠ患者69例、CINⅡ/Ⅲ患者68例)为研究对象。采用结构式问卷收集研究对象人口学资料及宫颈病变相关因素的基础上,采集宫颈脱落细胞和宫颈活检或手术组织,应用分子导流杂交法检测HPV16感染状况,并采用Western blot技术检测宫颈组织中hnRNP K蛋白表达水平。采用SPSS 23.0软件对资料进行整理分析,研究对象的人口学特征、相关因素、hnRNP K蛋白和HPV16感染在NC组、CINⅠ和CINⅡ/Ⅲ组的差异通过χ2检验、趋势χ2检验、Kruskal-Wallis H检验进行比较;hnRNP K蛋白表达量的组间两两多重比较采用Bonferroni法;采用非条件logistic回归模型计算hnRNP K蛋白、HPV16感染与CIN的关联强度OR值及其95% CI,采用相加交互模型及交互效应指标评价hnRNP K蛋白和HPV16感染两因素在CIN中的交互效应。结果 CINⅡ/Ⅲ组HPV16感染率(41.2%)高于NC(10.4%)、CINⅠ(14.5%),差异有统计学意义(P<0.001),且随着CIN程度加重,HPV16的感染率呈上升趋势(趋势χ2=18.512)。hnRNP K蛋白表达量在NC组、CINⅠ组和CINⅡ/Ⅲ组间差异有统计学意义(H=48.138,P<0.001),且随着CIN程度加重呈上升趋势(趋势χ2=21.765,P<0.001)。交互效应分析显示,hnRNP K蛋白高表达与HPV16感染在CINⅡ/Ⅲ组存在正相加交互作用(API=0.639,95% CI:0.083~1.196),在CINⅠ组尚未发现存在类似交互作用。结论 hnRNP K蛋白高表达、HPV16感染均可能增加CIN的发生风险,且在高度CIN发生中存在正相加交互作用。  相似文献   

10.
目的探讨叶酸缺乏和抑癌基因p16 CpG岛甲基化异常与宫颈癌变的关系,以及两者在宫颈癌变中的相互作用。方法选择经病理学确诊的宫颈鳞状细胞癌(squamous cell carcinoma,SCC)患者85例,宫颈上皮内瘤样变(cervical intraepithelial neoplasm,CIN)患者60例和宫颈组织正常(normal cervix,NC)妇女103例为研究对象,采用放射免疫法检测其血清叶酸水平,宫颈组织中p16基因CpG岛甲基化状况采用甲基化特异PCR检测。结果在NC、CIN和SCC组,血清叶酸的平均水平依次为2.64 ng/ml、2.07 ng/ml和1.72 ng/ml,随着宫颈病变程度的增加,血清叶酸含量逐渐降低,p16基因CpG岛甲基化率逐渐升高(2趋势=32.22,P<0.001)。交互作用分析显示,叶酸缺乏和p16基因CpG岛甲基化异常在宫颈癌的发生发展中存在正相加交互作用。结论叶酸缺乏与p16基因CpG岛甲基化异常均可增加宫颈癌变的风险,且二者在宫颈癌变中存在正相加交互作用。  相似文献   

11.
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.  相似文献   

12.
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).  相似文献   

13.

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.  相似文献   

14.
15.
Occupational health hazards in mining: an overview   总被引:1,自引:0,他引:1  
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.  相似文献   

16.
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.  相似文献   

17.
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.  相似文献   

18.
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.  相似文献   

19.
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.  相似文献   

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