DNA adsorption on nanoscale zeolitic imidazolate framework-8 enabling rational design of a DNA-based nanoprobe for gene detection and regulation in living cells

DNA functionalized nanomaterials have attracted tremendous attention for bioanalytical applications. Owing to exceptional fluorescence quenching ability, most DNA-based nanoprobes were designed with turn-on signals for target gene detection, while only a few of them could simultaneously achieve gene detection and regulation in one system. In this study, we explored the use of nanoscale zeolitic imidazolate framework-8 (ZIF-8) as a building block to construct a DNA-based nanoprobe. We found ZIF-8 could stably adsorb DNA to resist the dissociation by various biological ligands, enabling potential biological applications. However, ZIF-8 was not a nano-quencher to turn off the fluorophore labeling on the adsorbed DNA. We therefore designed a DNAzyme embedded molecular beacon (DMB) to functionalize ZIF-8. After endocytosis, ZIF-8 was disintegrated to release DMB for target mRNA detection, and the co-released Zn²⁺ acted as an effective cofactor to activate the embedded DNAzyme for mRNA regulation. This study provides a versatile nano-platform to realize multiple functions inside cells by using functional nucleic acids, which holds great promise for theranostic applications.

Boosting DNA-based nanotheranostics for gene detection and regulation by ZIF-8.     

黄柳向治疗胃癌前病变经验

介绍黄柳向教授运用益气健脾,柔肝理气,化痰祛瘀法治疗胃癌前病变的经验。黄教授认为,胃癌前病变的根本病机为本虚标实,即脾胃亏虚为本,气滞痰凝血瘀为标;治疗当以益气健脾,柔肝理气,化痰祛瘀为法。临床上采用莪蚕健胃方加减治疗,对胃癌前病变的阻断与逆转效果确切,并附典型案例1则。     

代谢产物在检测阿片类物质滥用中的研究进展

目的对近年来检测阿片类物质滥用的代谢产物进行综述,为加强阿片类物质的管理、确证滥用导致的死亡等提供依据,也可以用于区别滥用和正常摄入。方法通过大量检索检测阿片类物质滥用的代谢产物相关资料,总结归纳阿片类物质体内代谢过程、常用代谢产物检测的优缺点及应用。结果海洛因、含可待因的药物和罂粟类物质等均能代谢生成吗啡,导致假阳性结果。目前尚未有明确统一的金标准用于准确判断阿片类物质的滥用,滥用确证时除了检测常用的代谢产物指标6-单乙酰吗啡和吗啡外,乙酰可待因、可待因、吗啡与可待因浓度比值、蒂巴因与罂粟碱及那可汀的代谢物也可附加检测。结论在确证阿片类物质滥用时,需谨慎判断代谢产物检测结果的可靠性,并详细询问被检测者近期的服药史。     

基于专利数据库中药复方治疗溃疡性结肠炎的用药规律与作用机制分析

目的：研究溃疡性结肠炎专利复方的用药规律和作用机制。方法：从专利数据库中筛选治疗溃疡性结肠炎的中医专利复方,录入数据库,进行频数、聚类和关联分析,再通过中药系统药理学数据库与分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP）筛选排名前十的高频药的活性成分,然后通过DrugBank数据库找到这些成分对应的作用靶点,并通过基因免疫功能和基因通路富集分析找到这些靶点对应的免疫功能和信号通路。结果：总共发现治疗溃疡性结肠炎的专利复方224个,涉及中药387味;排名前十的高频药依次是黄连、甘草、白术、白芍、黄芪、白及、党参、白头翁、地榆、木香,主要使用的是补益药和清热药;发现中药配伍10对、关联规则16条;在排名前十的高频药中筛选出83个活性成分及其146个作用靶点,这些靶点作用于B细胞增殖、T细胞因子分泌等27个免疫功能,以及TNF信号通路、IL-17信号通路等47条信号通路。结论：专利数据库中治疗溃疡性结肠炎的中药复方用药规律符合临床实际,其作用机制和溃疡性结肠炎的病理机制较符合。     

氟非尼酮凝胶的研制及其体外透皮转运

采用HPLC法测定了25℃、100 r/min条件下平衡48 h时氟非尼酮在水性溶剂和非水溶剂中的溶解度。结果表明,氟非尼酮在水及其他水性溶剂中微溶,溶解度约为2.5 mg/ml,溶剂的pH值对溶解度影响小;氟非尼酮易溶于乙醇,可溶于聚乙二醇400、1,2-丙二醇和异丙醇,微溶于甘油。摇瓶法测得氟非尼酮的油水分配系数(logP)值为1.182,略有亲脂性。以乳猪皮肤为模型,采用改良的Franz扩散池法评价不同载药量(0.5%和1%)凝胶及溶液的经皮渗透特性。结果表明,2种载药量的氟非尼酮凝胶的经皮渗透行为均符合零级模型,1%凝胶的24 h单位面积累积渗透量(Q24h)和单位面积皮肤滞留量(Qskin)均比0.5%凝胶增加约1倍;同时,0.5%溶液的Q24h和Qskin结果介于2种载药量凝胶之间。     

肺硬化性血管瘤的CT征象与临床病理研究

目的研究肺硬化性血管瘤(PSH)的CT征象与临床病理特征,提高对PSH的认识水平。方法收集2007—2013年我院经手术病理证实的PSH 20例。分别回顾性总结分析其CT影像资料及PSH病理资料。CT的评价征象包括病变形态、密度、边缘、分布位置及增强前后CT值的差值。PSH病理资料包括组织形态结构与细胞学形态。结果 20例PSH的CT均表现为单发、边缘清楚的圆形或是类圆形肿块,12例行增强扫描者均表现均匀显著强化。20例PSH均未发现肺门及纵隔淋巴结肿大,肺内亦未见转移灶。显微镜下,PSH主要由实体型、乳头型、硬化型和血管瘤型4种组织学形态,单个瘤体包括至少2种或2种以上组织形式。结论了解PSH的CT与病理特征,有利于提高对PSH的认识与诊断正确率。     

Decoding the processing of lying using functional connectivity MRI

Background

Previous functional MRI (fMRI) studies have demonstrated group differences in brain activity between deceptive and honest responses. The functional connectivity network related to lie-telling remains largely uncharacterized.

Methods

In this study, we designed a lie-telling experiment that emphasized strategy devising. Thirty-two subjects underwent fMRI while responding to questions in a truthful, inverse, or deceitful manner. For each subject, whole-brain functional connectivity networks were constructed from correlations among brain regions for the lie-telling and truth-telling conditions. Then, a multivariate pattern analysis approach was used to distinguish lie-telling from truth-telling based on the functional connectivity networks.

Results

The classification results demonstrated that lie-telling could be differentiated from truth-telling with an accuracy of 82.81% (85.94% for lie-telling, 79.69% for truth-telling). The connectivities related to the fronto-parietal networks, cerebellum and cingulo-opercular networks are most discriminating, implying crucial roles for these three networks in the processing of deception.

Conclusions

The current study may shed new light on the neural pattern of deception from a functional integration viewpoint.

Electronic supplementary material

The online version of this article (doi:10.1186/s12993-014-0046-4) contains supplementary material, which is available to authorized users.     

胰腺癌干细胞研究进展

胰腺癌干细胞（PCSC）在胰腺癌的发生、发展过程中起着重要作用,且与胰腺癌的耐药、转移机制关系密切。PCSC的表面标志物、分离、鉴定、信号通路、微环境、耐药、转移和靶向治疗等方面的研究,将为临床胰腺癌的治疗提供新的方向。     

CD26 a cancer stem cell marker and therapeutic target

Cancer stem cells (CSCs) comprise a tumor subpopulation responsible for tumor maintenance, resistance to chemotherapy, recurrence and metastasis. The identification of this cell group is very important, but there is still no consensus on its characterization. Several CSC markers have been described, like CD133, CD24, CD44 and ALDH1, but more research to identify new markers to facilitate the identification of CSC in a heterogeneous tumoral mass is required. Thus, this article describes the CD26 expression as a CSC marker and the role that it plays in different types of cancer. CD26 expression correlates with some characteristics of CSCs, like the formation of spheres in vitro, formation of new tumors, and resistance to chemotherapy. CD26 is therefore suggested as an auxiliary marker for CSC in different types of cancer, and as a potential therapeutic target.     

Genome-wide pathway-based association study implicates complement system in the development of Kashin-Beck disease in Han Chinese

Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of KBD remains unknown. To identify relevant biological pathways for KBD, we conducted a genome-wide pathway-based association study (GWPAS) following by replication analysis, totally using 2743 Chinese Han adults. A modified gene set enrichment algorithm was used to detect association between KBD and 963 biological pathways. Cartilage gene expression analysis and serum complement measurement were performed to evaluate the functional relevance of identified pathway with KBD. We found that the Complement and Coagulation Cascades (CACC) pathway was significantly associated with KBD (P value = 3.09 × 10^− 5, false-discovery rate = 0.042). Within the CACC pathway, the most significant association was observed at rs1656966 (P value = 1.97 × 10^− 4) of KNG1 gene. Further replication study observed that rs1656966 (P value = 0.037) was significantly associated with KBD in an independent validation sample of 1026 subjects. Gene expression analysis observed that CFD (ratio = 3.39 ± 2.68), A2M (ratio = 3.67 ± 5.63), C5 (ratio = 2.65 ± 2.52) and CD46 (ratio = 2.29 ± 137) genes of the CACC pathway were up-regulated in KBD articular cartilage compared to healthy articular cartilage. The serum level of complement C5 in KBD patients were significantly higher than that in healthy controls (P value = 0.038). Our study is the first to suggest that complement system-related CACC pathway contributed to the development of KBD.