循环血中microRNAs作为疾病标志物的研究进展

新近研究发现成熟的microRNA能够游离于细胞之外,稳定存在于循环血中,具备疾病分子生物标志物的某些优点,已在多种肿瘤和非肿瘤疾病的早期诊断和预后中显示了独特的价值,同时循环血中microRNA的功能研究也已开始。该文针对近两年循环血中microRNA标志物及功能研究的成果,对microRNA研究中的这一热点问题进行综述。     

病毒致癌相关microRNA的研究进展

microRNA(miRNA)是一类内源性非编码的小RNA,广泛存在于病毒、植物和动物等生物体内。miRNA通过与目标mRNA互补配对,对基因进行转录后的表达调控,在生物体的发育、增殖、分化和凋亡等方面发挥重要的生理作用。最近的研究表明,miRNA与病毒介导的肿瘤之间存在密切关系,尤其在调控乙肝病毒介导的肝癌、人乳头瘤病毒介导的宫颈癌及EB病毒介导的鼻咽癌、淋巴瘤等肿瘤中发挥重要作用。在病毒导致肿瘤的发生与发展过程中,miRNA表达谱出现时间与空间上的改变,其表达调控成为近年来病毒致癌的研究热点。我们简要综述病毒致癌相关mi RNA的研究进展。     

鸡microRNA的研究进展

microRNA (miRNA)是参与基因转录后调控的一类重要的非编码小RNA分子.以下简要总结鸡miRNA的数量与染色体分布,同时概述了鸡miRNA对免疫、胚胎发育和病毒感染的调控作用,最后对鸡miRNA的应用前景也进行了简单探讨,以期为miRNA在禽业生产中的深入研究和应用提供参考.     

microRNA在胰腺癌中的研究进展

胰腺癌是预后很差的恶性肿瘤,其分子机制的研究是治愈胰腺癌的希望.microRNA(miRNA)是一类小分子非编码RNA,通过降解或抑制靶基因mRNA的翻译调节靶基因的功能.近年来,研究发现miRNA在胰腺癌中异常表达,有上调,也有下调.虽然很多miRNA异常表达的机制尚不清楚,但启动子CpG甲基化与在胰腺癌中某些miRNA的下调有关.研究发现miRNA表达谱可用于胰腺癌和单个miRNA表达如miR-21、miR-34、miR-10a、miR-155、miR-196a及miR-200和let-7家族成员等可作为肿瘤标志物用于胰腺癌与正常胰腺、慢性胰腺炎、胰腺内分泌肿瘤等的诊断和鉴别诊断,预测胰腺癌的预后等.研究发现miRNA在胰腺癌中上调或下调参与胰腺癌的增殖、凋亡、侵袭、转移以及对化疗药物的耐药.研究发现miR-34、miR-200c等与胰腺癌干细胞的自我更新有关.这些miRNA研究将为胰腺癌的早期诊断、分子靶向治疗打下坚实的基础.     

microRNA及其应用研究进展

microRNA(miRNA)是在多种真核细胞和病毒中发现的一类内源性非编码单链RNA,长约22个核苷酸,在进化上具有高度的保守性。miRNA可以通过碱基互补与靶基因mRNA的特定位点结合,抑制该蛋白合成或诱导该mRNA降解,在生物体生长、发育和疾病发生等过程中发挥着重要的作用。我们简要叙述了miRNA的特点和作用机制,并对miRNA在基因表达调控、胚胎干细胞调控及免疫调节等方面的最新进展进行了综述。     

EB病毒编码microRNA的靶基因研究进展

EB病毒(EBV)是一种疱疹病毒,与多种肿瘤的发生密切相关。EBV可表达多种病毒microRNA(miRNA),并作用于细胞和病毒基因,参与信号转导、细胞增殖、分化等多种功能,这与EBV的致病机制密切相关。探索EBV编码miRNA相关靶基因及功能有助于进一步了解EBV的致病机制,也将为临床治疗提供新的启示。自EBV编码miRNA被发现以来,一些靶基因已经逐渐被验证。本文将对目前已验证的EBV编码miRNA的靶基因及功能进行综述。     

青岛地区孕妇产前传染性标志物检测结果分析

目的:了解青岛地区的孕妇在2001年-2009年间感传染性疾病的情况。方法:乙型肝炎表面抗原(HBsAg)、丙型肝炎病毒抗体(抗-HCV)、人免疫缺陷病毒抗体(抗-HIV)的检测采用酶联免疫吸附实验(ELISA),梅毒测定采用快速血浆反应素(RPR)环状卡片实验,对青岛地区2001年-2009年门诊收治的39369名孕妇的血液进行HbsAg、抗-HCV、抗-HIV、梅毒的检测,并对检测结果进行统计与分析。结果:2001年-2009年间青岛地区的孕妇产前感染以HBsAg多见,其次是梅毒感染和丙型肝炎病毒感染,阳性率分别为3.94%,0.18%和0.15%,抗-HIV暂未检出。各年间各种传染性疾病感染率无显著性差异(P>0.05)。结论:通过对孕妇产前进行传染性标志物的检测,为临床预防及控制母婴垂直传播传染性疾病的发生提供了依据。     

青岛地区孕妇产前传染性标志物检测结果分析

目的：了解青岛地区的孕妇在2001年-2009年间感传染性疾病的情况。方法：乙型肝炎表面抗原（HBsAg）、丙型肝炎病毒抗体（抗-HCV）、人免疫缺陷病毒抗体（抗-HIV）的检测采用酶联免疫吸附实验（ELISA）,梅毒测定采用快速血浆反应素（RPR）环状卡片实验,对青岛地区2001年-2009年门诊收治的39369名孕妇的血液进行HbsAg、抗-HCV、抗-HIV、梅毒的检测,并对检测结果进行统计与分析。结果：2001年-2009年间青岛地区的孕妇产前感染以HBsAg多见,其次是梅毒感染和丙型肝炎病毒感染,阳性率分别为3.94%,0.18%和0.15%,抗-HIV暂未检出。各年间各种传染性疾病感染率无显著性差异（P〉0.05）。结论：通过对孕妇产前进行传染性标志物的检测,为临床预防及控制母婴垂直传播传染性疾病的发生提供了依据。     

主要禽源病毒相关microRNA的研究进展

近年来,禽类病毒性疾病已经成为研究病毒感染和致病机制的重要模型之一,而且病毒与micro RNA的调控关系和机制研究也成为人们关注的焦点。本文简要总结禽源疱疹病毒编码micro RNA的概况,以及禽源疱疹病毒的致瘤性与micro RNA的表达调控关系,同时探讨了利用micro RNA靶向调控机制在病毒疾病(如传染性法氏囊病毒、禽白血病病毒、禽流感病毒等)防治中的可能应用。     

野生鸟类传染性疾病研究进展

由于具有独特的飞行能力和极强的地理扩散能力,鸟类活动为某些传染性疾病的快速传播和扩散带来了潜在风险.自20世纪以来,以禽霍乱、禽波特淋菌病、西尼罗河热、禽流感等为代表的鸟类疾病频繁暴发,导致为数众多的野生鸟类、家禽甚至人类死亡,给社会造成巨大的经济损失.因此,有关鸟类传染性疾病的研究已引起了国内外学者的广泛关注.从鸟类传染性疾病的生态学特征、疾病对鸟类与人类社会的影响、鸟类对疾病的传播、鸟类疾病的监测、预警和防控等方面对野生鸟类的传染性疾病研究进展进行了综述.不同疾病导致的鸟类死亡量、易感物种数量、暴发频率和地理扩散等特征差异显著.20世纪以来,疾病已成为全球生物多样性的七大威胁因子之一.疾病可能造成鸟类大量死亡,从而对鸟类种群,特别是濒危鸟类种群造成严重影响.其中,人畜共患病还会导致家禽家畜甚至人类的死亡,从而对社会产生严重的影响.野生鸟类作为多种疾病传播的媒介,其移动和迁徙可能会导致疾病的传播与扩散.开展全面的监测活动和建立疾病预警体系,对于疾病的防控具有重要意义.     

新形势下的传染病医院医疗应急后勤保障工作

传染病因其不可预测性和突发性,已经成为人类生存的大敌。随着气候的变化和环境的破坏,新老传染病（SARS、甲型H1N1流感、禽流感、TB等）相继出现及复燃,人民的健康不时受到威胁,传染病医院肩负着防治疾病的重任并面临巨大挑战。因此如何做好医疗应急后勤保障工作是当今新形势下传染病医院工作的重中之重。     

综合性传染病医院运行机制新尝试

目的：对综合性传染病医院运行机制进行新的尝试,旨在探讨传染病医院的现代化建设与综合发展方向。方法：对我院近五年（2008-2012年）进行改革前后的一系列相应指标采取回顾性对比分析,对新的运行机制进行经验总结。结果：新的运行机制明显加强了医院内部的现代化建设、激发了医院活力,满足了人民群众就医需求、提高了医院的综合竞争力。结论：综合性传染病医院的新的运行机制不断趋于完善,取得的成效显著,得到了广泛的肯定,使传染病医院告别原有模式而走向现代化、人性化、综合化之路。     

Urinary Biomarkers of Brain Diseases

Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood,there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.     

MicroRNAs: Potential diagnostic markers and therapeutic targets for EBV-associated nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a highly malignant cancer with local invasion and early distant metastasis. NPC is highly prevalent in the Southern China and South-eastern Asia. The genetic susceptibility, endemic environment factors, and Epstein-Barr virus (EBV) infection are believed to be the major etiologic factors of NPC. Once metastasis occurs, the prognosis is very poor. It is urgently needed to develop biomarkers for early clinical diagnosis/prognosis, and novel effective therapies for nasopharyngeal carcinoma. In this paper, we systematically reviewed the current progress of miRNA studies in NPC. It has been shown that both host encoded miRNAs and EBV encoded miRNAs play key roles in almost all the steps of epithelia cell carcinogenesis, including epithelial-mesenchymal to stem-like transition, cell growth, migration, invasion, and tumorigenesis. More importantly, some miRNAs could be secreted out and play a role in the microenvironments. The level of sera miRNAs is correlated with the copy numbers of host miRNAs in tumor biopsies. Promising results of gene therapy have been also achieved by lentiviral delivered miRNAs. Taken together, cell free miRNAs would be potential biomarkers of early clinical diagnosis/prognosis; while some miRNAs could be further developed into therapeutic agents in the future.     

Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus

The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.     

Rare Circulating MicroRNAs as Biomarkers of Colorectal Neoplasia

Background

MicroRNAs (miRNAs) are regulatory RNAs, stable in circulation, and implicated in colorectal cancer (CRC) etiology and progression. Therefore they are promising as early detection biomarkers of colorectal neoplasia. However, many circulating miRNAs are highly expressed in blood cells, and therefore may not be specific to colorectal neoplasia.

Methods

We selected 7 miRNA candidates with previously reported elevated expression in adenoma tissue but low expression in blood cells (“rare” miRNAs), 2 previously proposed as adenoma biomarkers, and 3 implicated in CRC. We conducted a colonoscopy-based case-control study including 48 polyp-free controls, 43 advanced adenomas, 73 non-advanced adenomas, and 8 CRC cases. miRNAs from plasma were quantified by qRT-PCR. Correlations between miRNA expression levels, adjusted for age and sex, were assessed. We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals quantifying the association between expression levels of miRNAs and case groups. We also conducted nonparametric receiver operating characteristic (ROC) analyses and estimated area under the curve (AUC).

Results

miRNAs with high expression levels were statistically significantly correlated with one another. No miRNAs were significantly associated with non-advanced or advanced adenomas. Strong (ORs >5) and significant associations with CRC were observed for 6 miRNA candidates, with corresponding AUCs significantly >0.5.

Conclusions

These candidate miRNAs, assayed by qRT-PCR, are probably unsuitable as blood-based adenoma biomarkers. Strong associations between miRNAs and CRC were observed, but primarily with miRNAs highly expressed in blood cells. These results suggest that rare miRNAs will require new detection methods to serve as circulating biomarkers of adenomas.     

加强传染病管理与医院感染管理

目的:探讨传染病防治管理措施的应用价值与效果.方法:以2009年1月至2010年6月间的院内管理为对照组;以2010年7月至2011年12月间的院内管理措施为研究组,采用传染病防治管理措施.结果:两组管理方法传染病患者发生率无显著差异(P＞0.05);研究组传染病预防管理措施院内感染发生率明显低于对照组,数据经统计学比较具有显著差异(P＜0.05).研究组管理方法下患者临床满意度明显高于对照组,数据经统计学比较具有显著差异(P＜0.05).结论:传染病预防管理措施有利于有效阻断院内感染源的传播,进而减少交叉感染发生率,提高患者满意度.     

传染病医院血液净化中心的医院感染管理

目的：探讨传染病医院血液净化中心的医院感染管理方法。方法：我院血液净化中心自2010年1月～2012年1月加强医院感染管理,制定了相关的制度及规范,现对感染管理措施进行总结分析,并统计医院感染发生率。结果：通过加强血液净化中心的医院感染管理,可有效防止医院感染的发生,医院感染的发生率为11.68%。结论：完善医院管理制度和规范,制定严格的管理措施,提高医务人员风险意识等可有效提高医院感染的管理水平,预防医院感染的发生。     

Comprehensive analysis of pathogen-specific antibody response in vivo based on an antigen library displayed on surface of yeast

Host antibody response is a crucial defense against pathogenic infection. Here, we report a novel technique allowing quantitative measurement of polyclonal antibody response in vivo. This involves expression of a combinatorial library of target proteins from a candidate pathogen on the surface of yeast Saccharomyces cerevisiae. After mixing with serum/plasma from infected or immunized subjects, positive yeast clones were isolated via fluorescence-activated cell sorting (FACS). Using this technique, we have studied mouse immunized serum with recombinant hemagglutinin (HA) protein from a human influenza H5N1 strain (A/Anhui/1/2005) and convalescent plasma from an infected human in China. Our technique has identified novel antigenic domains targeted by serum/plasma and allowed calculation of the relative proportion of the antibody response against each domain. We believe such systematic measurement of an antibody response is unprecedented, and applying this method to different pathogens will improve understanding of protective immunity and guide development of vaccines and therapeutics.