Outbreak of serogroup W135 meningococcal disease after the Hajj pilgrimage,Europe, 2000

The 2000 Hajj (March 15-18) was followed by an outbreak of Neisseria meningitidis W135 2a: P1.2,5 in Europe. From March 18 to July 31, 2000, some 90 cases of meningococcal infection were reported from nine countries, mostly the United Kingdom (UK) and France; 14 cases were fatal. Although most early cases were in pilgrims, the outbreak spread to their contacts and then to those with no known pilgrim contact. In France and the UK, the outbreak case-fatality rate was compared with the rate reported from national surveillance. The risk of dying during this outbreak was higher in France and the UK, although the difference was not statistically significant. Prophylaxis for all pilgrims and their household contacts was offered in France; in the UK and other European countries, prophylaxis was recommended only for close contacts. No difference in transmission rates following intervention was detected between France and the UK.     

Long-term prognosis in biliary atresia after hepatic portoenterostomy: analysis of 35 patients who survived beyond 5 years of age

The long-term prognosis in 35 patients with biliary atresia, who had undergone successful hepatic portoenterostomy and survived beyond 5 years of age, was studied. Eighteen (51%) patients developed ascending cholangitis after surgery. Jaundice recurred or increased in half of the patients, mainly as a result of ascending cholangitis. Another serious problem was the development of portal hypertension. Esophageal varices developed in 16 (46%) patients, with rupture and massive hemorrhage in seven. Leukopenia resulting from hypersplenism was common. Eighteen patients had WBC counts less than 5000/microliter. Thrombocytopenia was less common than leukopenia. Height was slightly below normal, although weight was within the normal range. Three patients died of hepatic failure; all had previously had ascending cholangitis. These observations indicate that ascending cholangitis is critical in the long-term and short-term prognoses in patients who have undergone successful repair of biliary atresia.     

Emergence of W135 meningococcal meningitis in Ghana

Neisseria meningitidis serogroup W135, well known for a long time as a cause of isolated cases of meningococcal meningitis, has recently increasingly been associated with disease outbreaks of considerable magnitude. Burkina Faso was hit by W135 epidemics in the dry seasons of 2002-2004, but only four W135 meningitis cases were recorded between February 2003 and March 2004 in adjoining Ghana. This reconfirms previous findings that bottlenecks exist in the spreading of new epidemic N. meningitidis clones within the meningitis belt of sub-Saharan Africa. Of the four Ghanaian W135 meningitis patients one died and three survived, of whom one had profound neurosensory hearing loss and speech impairment. All four disease isolates were sensitive to penicillin G, chloramphenicol, ciprofloxacin and cefotaxime and had the multi-locus sequence type (ST) 11, which is the major ST of the ET-37 clonal complex. Pulsed-field gel electrophoresis (PFGE) profiles of the Ghanaian disease isolates and recent epidemic isolates from Burkina Faso were largely identical. We conducted meningococcal colonization surveys in the home communities of three of the patients and in the Kassena Nankana District located at the border to Burkina Faso. W135 carriage rates ranged between 0% and 17.5%. When three consecutive surveys were conducted in the patient community with the highest carrier rate, persistence of W135 colonization over a period of 1 year was observed. Differences in PFGE profiles of carrier isolates taken at different times in the same patient community were indicative of rapid microevolution of the W135 bacteria, emphasizing the need for innovative fine typing methods to reveal the relationship between W135 isolates.     

Methyl-group dietary intake and risk of breast cancer among African-American women: a case–control study by methylation status of the estrogen receptor alpha genes

OBJECTIVES: Recent molecular studies show that the absence of estrogen receptor (ER) alpha gene expression in breast cancer is associated with methylation of the CpG island located in the 5' region and the first exon of the ER alpha gene. Because CpG island methylation is an early event in carcinogenesis and because a methyl-deficient diet may lead to abnormal DNA methylation including CpG island methylation, we hypothesized that a methyl-deficient diet is more likely to be associated with breast cancer with methylated ER alpha gene CpG islands. This study aimed to test this hypothesis in African-American women using a case-control design. METHODS: Cases were 304 African-American women pathologically diagnosed with breast cancer during 1995-1998 who lived in three Tennessee counties. Controls were 305 African-American women without breast cancer, who were selected through random-digit dialing and frequency matched to cases by 5-year age range and county of residence. Information on dietary intake and other risk factors was collected through telephone interviews. Dietary methyl-components were defined based on folate and methionine intakes and alcohol consumption. Tumor tissue samples were collected for measuring methylation status of the ER alpha gene. RESULTS: Our results showed that the odds ratio (OR) estimates for lower dietary folate intake were 2.0 (95% confidence interval, CI: 0.8-4.8) for cases with a methylated ER alpha gene, 0.6 (95% CI: 0.3-1.5) for cases with an unmethylated ER alpha gene, and 1.6 (95% CI: 0.7-3.8) for cases with unknown methylation status (presumably including cases with both methylated and un-methylated genes). However, low methionine intake appeared more likely to be associated with tumors with unknown methylation status and high level of alcohol consumption seemed more likely to be related to tumors with un-methylated genes. CONCLUSIONS: These results did not show a pattern consistent with the study hypothesis that methyl-deficient diets are more likely related to breast cancer with a methylated ER gene.     

miR-135b-5p通过靶向下调XBP1增强MCF-7/DOXR 细胞对阿霉素敏感性的机制

【摘要】 目的 探讨miR 135b 5p通过调控X盒结合蛋白（XBP1）对MCF-7/DOXR细胞阿霉素敏感性的机制。方法 采用Westernblot检测XBP1的表达水平;RT-qPCR法检测XBP1 mRNA在乳腺癌细胞MCF 7和乳腺癌阿霉素耐药MCF-7/DOXR细胞中的表达水平以及miR-135b 5p的表达水平;CCK-8检测MCF 7/DOXR细胞的增殖情况;Annexin-V-FITC双染流式细胞术检测MCF-7/DOXR细胞的凋亡情况;双荧光素酶报告基因验证miR-135b-5p与XBP1的调控关系。结果 XBP1在乳腺癌细胞MCF-7和MCF-7/DOXR细胞中均高表达（P＜0.05）,敲降XBP1可显著抑制MCF-7/DOXR细胞增殖并促进了细胞凋亡（P＜0.05）。双荧光素酶报告基因证实,XBP1是miR-135b-5p的潜在靶基因,miR-135b-5p靶向下调XBP1的表达水平（P＜0.05）。实验进一步证实,过表达miR-135b-5p下调XBP1进而显著抑制MCF-7/DOXR细胞增殖并诱导细胞凋亡（P＜0.05）。结论 miR-135b-5p通过下调XBP1增强MCF-7/DOXR细胞对阿霉素的敏感性。     

"一箭双星法"构建Flt3转基因细胞株

目的构建稳定表达Flt3分子的转基因细胞株。方法将Flt3基因重组入逆转录病毒载体pEGZ-term,通过293T细胞的包装获得具有感染能力的完整重组病毒载体,进而采用“一箭双星法”即同时感染BaF和L929细胞,构建Flt3转基因细胞株。结果成功获得稳定表达Flt3的转基因细胞株BaF/Flt3和L/Flt3。结论采用“一箭双星法”成功构建Flt3转基因细胞株,为以Flt3为靶分子的研究奠定了物质基础,也为类似的高难度的转基因细胞株的构建提供了有价值的经验。     

MicroRNA-135b regulates apoptosis and chemoresistance in colorectal cancer by targeting large tumor suppressor kinase 2

Colorectal cancer remains the third most common cause of death from cancer worldwide. MicroRNA emerges as a good area of research for current cancer therapy. Here, we identified miR-135b to be a contributor to anti-apoptosis and chemoresistance in colorectal cancer. We observed high levels of miR-135b in colorectal cancer cell lines and clinical tissues, compared to colorectal epithelium cell line and noncancerous tissues. Furthermore, enforced expression of miR-135b attenuated doxorubicin-induced apoptosis in colorectal cells. (Doxorubicin alone can trigger significant apoptosis). In elucidating the molecular mechanism by which miR-135b participate in the regulation of apoptosis and chemoresistance in colorectal cancer, we discovered that large tumor suppressor kinase 2 (LATS2) is a direct target of miR-135b. The role of miR-135b was confirmed in colorectal tumor xenograft models. The growth of established tumors was suppressed by an inhibition of miR-135b expression and enhanced apoptosis was further assessed by TUNEL assay. Taken together, our results reveal that miR-135b and LATS2 axis may be a novel therapeutic target for colorectal cancer.     

Global epidemiology of capsular group W meningococcal disease (1970–2015): Multifocal emergence and persistence of hypervirulent sequence type (ST)-11 clonal complex

Following an outbreak in Mecca Saudi Arabia in 2000, meningococcal strains expressing capsular group W (W) emerged as a major cause of invasive meningococcal disease (IMD) worldwide. The Saudi Arabian outbreak strain (Hajj clone) belonging to the ST-11 clonal complex (cc11) is similar to W cc11 causing occasional sporadic disease before 2000. Since 2000, W cc11 has caused large meningococcal disease epidemics in the African meningitis belt and endemic disease in South America, Europe and China. Traditional molecular epidemiologic typing suggested that a majority of current W cc11 burden represented global spread of the Hajj clone. However, recent whole genome sequencing (WGS) analyses revealed significant genetic heterogeneity among global W cc11 strains. While continued spread of the Hajj clone occurs in the Middle East, the meningitis belt and South Africa have co-circulation of the Hajj clone and other unrelated W cc11 strains. Notably, South America, the UK, and France share a genetically distinct W cc11 strain. Other W lineages persist in low numbers in Europe, North America and the meningitis belt. In summary, WGS is helping to unravel the complex genomic epidemiology of group W meningococcal strains. Wider application of WGS and strengthening of global IMD surveillance is necessary to monitor the continued evolution of group W lineages.     

血清miR-135、miR-601、CA72-4及CA19-9的表达水平与胃癌诊断的相关性

目的探究血清miR-135、miR-601、糖类抗原72-4(CA72-4)及糖类抗原19-9(CA19-9)的表达水平与胃癌(GC)诊断的相关性。方法选取2015年1月至2020年10月本院106例GC患者作为观察组,健康人群45例作为对照组,检测并比较两组血清miR-135、miR-601、CA72-4及CA19-9表达水平;Pearson相关系数分析各指标与GC发生相关性;受试者工作特征(ROC)曲线评价各指标对GC诊断效能。结果与对照组比较,观察组血清miR-135、miR-601、CA72-4及CA19-9表达水平升高差异有统计学意义(P<0.05);血清miR-135、miR-601、CA72-4及CA19-9与GC的发生呈正相关(P<0.05);血清miR-135、miR-601、CA72-4及CA19-9联合诊断GC灵敏度、特异性、准确度,阳性预测值、阴性预测值、ROC曲线下面积(area under curve,AUC)显著高于单一指标(P<0.05)。结果血清miR-135、miR-601、CA72-4及CA19-9的表达水平与GC的发生呈正相关。