山东半岛地区汉族人群HLA-A、B、DRB1高分辨等位基因及单体型多态性的研究

目的研究山东半岛地区汉族人群HLA-A、B、DRB1等位基因多态性的分布特征。方法应用聚合酶链反应-直接测序分型(polymerase chain reaction sequence-based typing,PCR-SBT)法和序列特异性寡核苷酸探针杂交技术(Polymerase chain reaction and sequence-specific olignucleotide probe hybridizations,PCR-SSOP)高分辨试剂,对山东半岛地区865名无血缘关系的汉族健康人群HLA-A、B、DRB1进行基因分型。结果检出HLA-A、B、DRB1等位基因分别有33、73、43种,经统计分析这3个基因座分布均符合Hardy-Weinberg平衡定律(P>0.05),A*3001-B*1302-DRB1*0701(7.61%)和A*3303-B*4403-DRB1*1302(1.674%)单体型是山东半岛地区汉族人群最常见单体型。结论山东半岛地区汉族人群HLA-A、B、DRB1基因座单体型分布具有高度的遗传多态性且有其自身分布特点。本研究获得的的HLA-A、B、DRB1基因座单体型分布数据及相关遗传参数资料,为HLA在人类学、免疫遗传学、法医学和其它的组织器官移植方面的应用和科学研究提供和积累了基础资料。     

四种杀虫剂对雷州半岛灭蚤地区印鼠客蚤的毒性观察

目的 观察四种杀虫剂(奋斗呐、氯菊酯、敌敌畏、马拉硫磷)对灭蚤地区印鼠客蚤的毒性.方法 将用丙酮配制的药液100 μl加在φ35mm的滤纸药膜上,20 min后放入50 ml离心管盖中,接15匹成蚤于离心管(底部有20个φ0.5 mm小孔以通气)中,旋紧盖子并倒置.在温度(25±1)℃,相对湿度(85±5)%的培养箱中接触药膜24 h,检查死虫数,计算LC50及95%可信区间范围.结果 雷州平步、遂溪洋青、廉江营仔和潮洲饶平(对照点)的印鼠客蚤对奋斗呐、氯菊酯、敌敌畏、马拉硫磷相应的LC50分别为510.51 mg/L、923.63 mg/L、10.40mg/L、1224.62 mg/L;293.22 mg/L、349.95 mg/L、9.11 mg/L、775.00 mg/L;255.27 mg/L、219.99 mg/L、8.27 mg/L、559.37 mg/L;176.81 mg/L、199.66 mg/L、5.73 mg/L、583.31 mg/L.雷州平步、遂溪洋青、廉江营仔各自相应的LC50与潮洲饶平(对照点)的LC50的比值分别为2.89、4.63、1.82、2.10;1.66、1.75、1.59、1.33;1.44、1.10、1.44、0.96.结论 除了廉江营仔印鼠客蚤对马拉硫磷毒性敏感外,4种杀虫剂对雷州半岛灭蚤地区的印鼠客蚤的毒性降低,并以雷州平步的情况较为明显.     

Urothelial carcinoma associated with Balkan endemic nephropathy. A worldwide disease

Balkan endemic nephropathy (BEN), a familial chronic tubulo-interstitial disease with a slow progression to terminal renal failure, affects people living in the alluvial plains along the tributaries of the Danube River. One of its most peculiar characteristics is a strong association with upper urothelial cancer. An increased incidence of upper urinary tract (UUT) transitional cell cancer (TCC) was discovered among the inhabitants of endemic settlements and in families affected by BEN. In areas where BEN is endemic, the incidence of upper tract TCC is significantly higher, even 100 times, than in non-endemic regions. A high incidence of urothelial cancer in end-stage BEN patients strongly suggests preventive nephro-ureterectomy in all end-stage patients with BEN treated with either transplantation or dialysis. Better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression, has provided a large number of molecular markers of TCC, with a potential diagnostic and prognostic value. Markers that distinguish among TCC, normal urothelium, and benign urothelial conditions are potentially diagnostic, prognostic, and therapeutic targets. The geographic correlation and presence of AA-DNA adducts in both BEN and associated urothelial cancer, support the speculation that these diseases share a common etiology. Dietary exposure to AA is a significant risk factor for BEN and its attendant transitional cell cancer. These are cases of well-known AA induced urothelial carcinoma, and could be detected worldwide. The presence of more than one risk factors is possible and it is important to test etiological hypotheses in different endemic foci, preferably as a multicentric research.     

2005 - 2009年浙江省象山半岛地区出生缺陷监测

目的 进一步了解象山县出生缺陷发生情况,以利于实施出生缺陷干预工程。 方法 监测2005年1月1日至2009年12月31日所有产妇分娩的胎儿在孕期和产后7 d内发现的出生缺陷的相关情况,统一上报,并进行调查、分析。 结果 2005 - 2009年共出生24 863名胎儿,出生缺陷发生率为147.61/万;发生死胎170例,其中缺陷儿死胎占65.88%;孕28周后发现的出生缺陷占88.01%,孕28周前发现的占11.99%;按系统分类排在前5位的分别为循环系统先天性畸形,肌肉骨骼系统先天性畸形和变形,眼、耳、面和颈部先天性畸形,神经系统先天性畸形,唇裂和腭裂。 结论 5年出生缺陷发生率总体呈逐年上升趋势,死胎出生缺陷发生率明显高于活胎发生率,孕28周前发现的出生缺陷所占的比例逐年增大,做好三级预防措施是关键。     

Fifty Years of Balkan Endemic Nephropathy: Challenges of Study Using Epidemiological Method

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease associated with urothelial cancer, which affects people living in the alluvial plains along the tributaries of the Danube River. Challenges of studying BEN using the epidemiological method are multiple. The natural history from exposure to occurrence of the disease may take many years. The early stages of BEN are not easily detectable clinically, as the disease is asymptomatic until a significant decline in function occurs, and even then symptoms are usually non-specific. The natural history of BEN is complex, possibly with multiple risk factors operating both at the stage of initiation of renal damage and in its progression. In BEN, genetic susceptibility is due to multiple genes of small effects, gene-gene interactions, and gene-environment interactions of complex nature that are difficult to assess with current study designs. BEN is now kidney disease of the old people, and many risk factors for disease such as smoking, alcohol consumption, obesity, and diabetes could contribute to the kidney damage. Evidence is presented that environmental rather than genetic factors play a decisive role in the etiopathogenesis of BEN. Aristolochic acid, described as a culprit of BEN in 1959, is confirmed in 2007 by the molecular biology methods. Mycotoxins and polycyclic aromatic hydrocarbons, leached from lignites and found in the vicinity of endemic settlements, deserve further investigation. Despite advances in understanding the epidemiology of BEN, more research is needed on the patterns of BEN over time and between places, and on identifying the contributions of modifiable risk factors in initiating and hastening progression of BEN in order to improve the scope for preventing BEN. Primary prevention is still at the beginning. Knowledge accumulated in the fifty years of BEN research and new data about prevention and treatment of chronic kidney disease reveal several effective methods in secondary and tertiary prevention of BEN. Genetic epidemiology could establish the relative size of the genetic effect in relation to other sources of variation in disease risk (i.e., environmental effects such as intrauterine environment, physical and chemical effects, as well as behavioral and social aspects). Public health authorities in the several countries having aristolochic acid nephropathy should take immediate measures for reducing dietary exposure of residents to Aristolochia.     

Experimental infection of sheep,goats and cattle with a bluetongue virus serotype 4 field strain from Bulgaria, 2014

In 2014, a new bluetongue virus serotype 4 (BTV ‐4) strain was detected in southern Greece and spread rapidly throughout the Balkan Peninsula and adjacent countries. Within half a year, more than 7,068 outbreaks were reported in ruminants, particularly in sheep. However, the reported morbidity and case fatality rates in ruminants varied. The pathogenesis of a Bulgarian BTV ‐4 strain isolated from sheep during the BTV ‐4 epizootic was studied in different species. Therefore, four sheep, three goats and three cattle were experimentally infected with the isolate BTV ‐4/BUL 2014/15 and monitored for clinical signs up to several weeks. Serum and whole‐blood samples were collected at regular intervals and subjected to serological and virological analyses. In this context, BTV ‐4‐specific real‐time RT ‐PCR assays were developed. The infection kinetics were similar to those known for other traditional BTV serotypes, and only mild BT ‐like clinical signs were observed in goats and sheep. In cattle, no obvious clinical signs were observed, except a transient increase in body temperature. The study results contrast with the severe clinical signs reported in sheep experimentally infected with an African BTV ‐4 strain and with the reports of BT ‐like clinical signs in a considerable proportion of different ruminant species infected with BTV ‐4 in the Balkan region and Italy. The discrepancies between the results of these animal trials and observations of BTV ‐4 infection in the field may be explained by the influence of various factors on the manifestation of BT disease, such as animal breed, fitness and virus strain, as described previously.     

E-cadherin expression in upper urothelial carcinoma in Balkan Endemic Nephropathy and non-endemic regions

There is a high incidence of upper urothelial carcinoma (UUC) in regions affected by Balkan Endemic Nephropathy (BEN). The aim of this study was to compare E-cadherin expression in UUC, in regions affected by BEN, and in control rural and city populations free of BEN. Another aim was to determine the influence of some morphological parameters on the E-cadherin status. In the samples of 85 UUC patients, of whom 40 lived in BEN settlements and 45 served as control subjects, immunoreactions were performed using monoclonal anti-human E-cadherin antibody. Aberrant expression of E-cadherin was more frequent in BEN tumors than in control tumors (p<0.01). Decreased E-cadherin expression was linked to high grade and solid growth in control and BEN tumors (p<0.0001 and <0.05 versus p<0.05 and <0.05, respectively), and to the stage in control tumors (p<0.01). However, BEN low grade and low stage tumors showed aberrant expression more often than did control tumors (p<0.05 and <0.005, respectively). In control tumors, using univariate analysis, E-cadherin status was found to be influenced by grade, stage, and tumor growth (p=0.001, 0.017, 0.015, respectively). In the same group, only the grade was significant according to multistep logistic regression analysis (Wald=6.429 and p=0.011). The growth pattern had a predominant influence on E-cadherin expression in BEN tumors (p=0.005). A significant influence on normal membranous or abnormal cytoplasmic expression of E-cadherin in UUC is exerted by tumor grade, stage, growth, and metaplastic change (p=0.002, 0.048, 0.019, 0.011, respectively), but only by tumor grade in the multistep logistic regression model. These results suggest that decreased expression of E-cadherin in BEN tumors may be linked to tumor growth, while expression of E-cadherin in control tumors may be associated with tumor grade.