儿科病房抗生素相关性腹泻的临床观察

目的观察儿科病房抗生素相关性腹泻(antibiotic associated diarrhea,AAD)的临床表现。方法对983例使用抗生素的患儿进行分析,根据是否发生AAD分为两组,AAD组共有76例患儿,未发生AAD的对照组有907例患儿。分析AAD组患儿使用抗生素的情况,并对两组患儿的基本情况进行比较分析。结果对AAD患儿抗生素使用种类进行分析,发现导致AAD的抗生素主要有三类,其中美洛西林/舒巴坦使用率最高,为18.4%,其次为美洛西林、头孢哌酮/舒巴坦和阿奇霉素,均为14.5%。并且,AAD的发生与性别无关(P0.05)。但是AAD在体重较轻、低龄、抗生素使用时间较长和抗生素联用患儿中多发(P0.05)。这些因素均会导致患儿住院时间延长并出现重要器官损伤现象。结论儿科病房中抗生素的使用要合理科学,尽量减少AAD的发生。     

Multifaceted Roles of Interleukin-6 in Adipocyte–Breast Cancer Cell Interaction

Breast cancer is the most common malignancy in women worldwide, with a developmental process spanning decades. The malignant cells recruit a variety of cells including fibroblasts, endothelial cells, immune cells, and adipocytes, creating the tumor microenvironment. The tumor microenvironment has emerged as active participants in breast cancer progression and response to treatment through autocrine and paracrine interaction with the malignant cells. Adipose tissue is abundant in the breast cancer microenvironment; interactions with cancer cells create cancer-associated adipocytes which produce a variety of adipokines that influence breast cancer initiation, metastasis, angiogenesis, and cachexia. Interleukin (IL)-6 has emerged as key compound significantly produced by breast cancer cells and adipocytes, with the potential of inducing proliferation, epithelial-mesenchymal phenotype, stem cell phenotype, angiogenesis, cachexia, and therapeutic resistance in breast cancer cells. Our aim is to present a brief knowledge of IL-6’s role in breast cancer. This review summarizes our current understanding of the breast microenvironment, with emphasis on adipocytes as key players in breast cancer tumorigenesis. The effects of key adipocytes such as leptin, adipokines, TGF-b, and IL-6 are discussed. Finally, we discuss the role of IL-6 in various aspects of cancer progression.     

A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed an exhaustive analysis of immunogenic signatures in TNBC based on 2 large-scale breast cancer (BC) genomic data. We compared enrichment levels of 26 immune cell activities and pathways among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features. We found that almost all analyzed immune activities and pathways had significantly higher enrichment levels in TNBC than non-TNBC. Elevated enrichment of these immune activities and pathways was likely to be associated with better survival prognosis in TNBC. This study demonstrated that TNBC likely exhibits the strongest immunogenicity among BC subtypes, and thus warrants the immunotherapeutic option for TNBC.     

Behavioural responses of female Neogobius melanostomus to odours of conspecifics

The behavioural responses of reproductive and non‐reproductive female round gobies Neogobius melanostomus to water conditioned by reproductive and non‐reproductive males and females were tested. The behavioural responses of reproductive female round gobies exposed to odour of reproductive males included increased time spent near the source of the odour, elevated swimming velocities and directed movement to and around the odour source when compared with their responses to control water. These results suggested that pheromones released from reproductive males may induce spawning behaviour in reproductive females. Non‐reproductive females exposed to reproductive female odour spent significantly more time near the odour source of reproductive females compared with control water. Non‐reproductive females also showed directed movement towards and around the odour source when exposed to reproductive female odour. These results suggested that round gobies use inter‐sexual and intra‐sexual pheromones and that both sex and reproductive status are important in the detection and release of these pheromones.     

骨髓移植后的白血病患者环境微生物控制与感染关系研究

白血病患者骨髓移植后,易引起各类微生物感染而死亡。通过F_1鼠9Gy^(60)Co照射(最大致死量)骨髓移植后,行环境微生物控制,将其数据结合临床特点,设计的白血病患儿骨髓移植,环境微生物监控的层流病房。自1989～1993年12例患儿行骨髓移植无一例感染。     

Assays for the Identification of Novel Antivirals against Bluetongue Virus

To identify potential antivirals against BTV, we have developed, optimized and validated three assays presented here. The CPE-based assay was the first assay developed to evaluate whether a compound showed any antiviral efficacy and have been used to screen large compound library. Meanwhile, cytotoxicity of antivirals could also be evaluated using the CPE-based assay. The dose-response assay was designed to determine the range of efficacy for the selected antiviral, i.e. 50% inhibitory concentration (IC₅₀) or effective concentration (EC₅₀), as well as its range of cytotoxicity (CC₅₀). The ToA assay was employed for the initial MoA study to determine the underlying mechanism of the novel antivirals during BTV viral lifecycle or the possible effect on host cellular machinery. These assays are vital for the evaluation of antiviral efficacy in cell culture system, and have been used for our recent researches leading to the identification of a number of novel antivirals against BTV.     

Identification of side arm-modified DOTA scaffolds as multi-site binding ligands for cancer cells over normal cells

The metal-chelated 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-tetraamide (DOTA) scaffold has been widely used as a contrast agent for diagnostic purposes in positron emission tomography (PET) and magnetic resonance imaging (MRI), but not as a biomarker targetable ligand. While the oxygen atoms at the stem of the four arms of the DOTA scaffold are needed for metal chelation, we previously introduced various physiochemical properties to extend these arms in a chemical library fashion to enhance the imaging contrast mechanism. We developed two such on-bead libraries, with 80 and 76 DOTA derivatives, where one arm was used to attach the DOTA scaffold onto resin beads and the other three arms were chemically modified. We now hypothesized that the chemical moieties used to modify these three arms can also recognize biomarkers on a cell surface. Therefore in this current study, we used such 76 derivatives of DOTA library to screen against HeLa cervical cancer cells. We found that two of the four ‘hits’ identified displayed higher binding towards HeLa cells than the unmodified parent DOTA. Furthermore, one of those ‘hits’ displayed better binding towards cervical and prostate cancer cells than lung and breast cancer cells and normal HBEC-3KT and RWPE1 cells. This indicates that this derivative can recognize a biomarker specific for certain types of cancer cells. If the compound has intrinsic activity, this can be used as a theranostic agent for real time therapy monitoring applications in the future. We believe that our DOTA derivative-based library approach can be applied to other types of cell and protein screens on various disease types in the future.     

桂林岩溶石山青冈群落数量分类与排序

植物群落的数量分类和排序可以客观地揭示植物群落与环境之间的关系,从而能为植被恢复与重建、森林经营与管理和生物多样性保护等提供理论依据。基于群落学调查和环境因子测定数据,采用Ward聚类、双向指示种分析(TWINSPAN)和多元回归树(MRT)对桂林岩溶石山青冈群落进行数量分类,选用冗余分析(RDA)进行排序,分析其与环境因子之间的关系。结果表明:(1)3种分类方法所得结果基本一致,可将桂林岩溶石山青冈群落划分为3个群丛类型,分别为青冈-粗糠柴+龙须藤+红背山麻杆-三穗薹草群丛(Ass.Cyclobalanopsis glauca-Mallotus philippensis+Bauhinia championi+Alchornea trewioides-Carex tristachya)、青冈-龙须藤+红背山麻杆+干花豆-宽叶沿阶草+三穗薹草群丛(Ass.Cyclobalanopsis glauca-Bauhinia championi+Alchornea trewioides+Fordia cauliflora-Ophiopogon platyphyllus+Carex tristachya)、青冈-粗糠柴+干花豆-三穗薹草群丛(Ass.Cyclobalanopsis glauca-Mallotus philippensis+Fordia cauliflora-Carex tristachya);(2)冗余分析结果较好地反映出各群丛类型的分布格局及其与环境梯度的相互关系,在10个环境因子中,岩石裸露率、土壤含水量、pH值、全氮、全磷、全钾、速效钾这7个环境因子对群落的分布影响显著。土壤含水量和全钾含量可能是影响该植物群落物种组成与分布的重要生态因子。     

Structure-based rational design of staurosporine-based fluorescent probe with broad-ranging kinase affinity for kinase panel application

Selectivity profiling of compounds is important for kinase drug discovery. To this end, we aimed to develop a broad-range protein kinase assay by synthesizing a novel staurosporine-derived fluorescent probe based on staurosporine and kinase-binding related structural information. Upon structural analysis of staurosporine with kinases, a 4′-methylamine moiety of staurosporine was found to be located on the solvent side of the kinases, to which several linker units can be conjugated by either alkylation or acylation. However, such conjugation was suggested to reduce the binding affinities of the modified compound for several kinases, owing to the elimination of hydrogen bond donor moiety of NH-group from 4′-methylamine and/or steric hindrance by acyl moiety. Based on this structural information, we designed and synthesized a novel staurosporine-based probe without methyl group in order to retain the hydrogen bond donor, similar to unmodified staurosporine. The broad range of the kinase binding assay demonstrated that our novel fluorescent probe is an excellent tool for developing broad-ranging kinase binding assay.     

Development of 99mTc radiolabeled A85380 derivatives targeting cerebral nicotinic acetylcholine receptor: Novel radiopharmaceutical ligand 99mTc-A-YN-IDA-C4

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (^99mTc) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent α4β2-nAChR agonist, we prepared A85380 derivatives labeled with ^99mTc using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a ^99mTc analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at α4β2-nAChR in both the docking simulation (?19.3 kcal/mol) and binding assay (Ki = 0.4 ± 0.04 nM). Further, ^99mTc-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that ^99mTc-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy.