小细胞肺癌关键基因及信号通路分析

目的 探究SCLC基因调控机制，为寻找SCLC早期诊断及靶向治疗潜在的生物标志物提供依据。方法 采用生物信息学方法从公共基因芯片数据库获取小细胞肺癌（SCLC）mRNA数据并筛选出差异表达基因（DEGs），对DEGs进行基因本体（GO）和基因组百科全书数据库（KEGG）富集分析，构建蛋白互作网络，筛选出核心基因并利用Kaplan-Meier在线工具进行生存分析。结果 17例SCLC组织样本和19例正常肺组织样本中筛选出248个DEGs，包括172个高表达基因和76个低表达基因（P<0.05）。GO和KEGG富集分析结果显示，DEGs的功能主要涉及细胞周期、DNA复制、错配修复、P53信号通路等，蛋白互作分析网络筛选出6个节点度最高的核心基因：TOP2A、PCNA、RFC4、 FEN1、CCNA2和MCM2，并与患者预后相关。结论 DEGs涉及的分子功能和信号通路可能是SCLC发生的分子机制，而核心基因可能是治疗SCLC的潜在靶点。     

尿道下裂的基因特点及其研究进展

尿道下裂是男性新生儿中常见的先天性泌尿系统畸形。主要是由阴茎和尿道发育异常引起的，是一种多因素疾病，个体差异明显。目前研究发现，多种因素均与尿道下裂有关，包括遗传因素、产前激素不足、母体胎盘因素及环境影响，因此，尿道下裂往往是多因素结合的产物。在过去的十年间，大量研究致力于揭示尿道下裂的遗传基因特点。这些研究包括骨形成蛋白（BMP）、成纤维细胞生长因子（FGF）、同源盒基因A（HOXA）等基因，涵盖了性别基因的转录、性激素的合成及相关基因的信号传导。尽管目前发现了大量尿道下裂相关基因，但仍需大样本病例临床对照研究明确这些基因的诊断效能及生物学意义。同时，随着测序技术的发展，外显子和全基因组测序也将揭示基因与基因、基因与环境的相互作用，更好地探索尿道下裂的分子机制，从而探寻合适分子标记物及治疗干预的靶点。综述这一领域的研究现状，并对一些与尿道下裂有关基因的研究进展进行探讨。     

经典名方物质基准研制的关键技术分析

中药经典名方开发已成为当下中医药界研究的热点之一,而其中经典名方物质基准的成功研制对于整个中药经典名方的申报极为关键。经典名方物质基准既是检测经典名方制剂质量的基准,同时又需反映整方的物质基础。中药成分众多而复杂,单成分的、化药式的研发与质量控制模式难以适用于整体药用的中药制剂的开发,亟需开辟一条中药专属的研发模式。以目前已有的现代科学技术,笔者建议将中药的遗传多态性、提取动力学、指纹图谱总量统计矩(相似度)法、超分子"印迹模板"等结合应用于经典名方物质基准的研制,探讨中药经典名方物质基准的质量控制技术,以期全面、准确地阐明药材-饮片-物质基准的成分群量值的传递规律,为推进中药经典名方的研制进程提供参考。     

The STING activator c-di-AMP exerts superior adjuvant properties than the formulation poly(I:C)/CpG after subcutaneous vaccination with soluble protein antigen or DEC-205-mediated antigen targeting to dendritic cells

Vaccination is the most efficient strategy to protect from infectious diseases and the induction of a protective immune response not only depends on the nature of the antigen, but is also influenced by the vaccination strategy and the co-administration of adjuvants. Therefore, the precise monitoring of adjuvant candidates and their immune modulatory properties is a crucial step in vaccine development. Here, one central aspect is the induction of appropriate humoral and cellular effector mechanisms.In our study we performed a direct comparison of two promising candidates in adjuvant development, the STING activator bis-(3,5)-cyclic dimeric adenosine monophosphate (c-di-AMP) and the Toll-like receptor ligand formulation poly(I:C)/CpG. These were evaluated in C57BL/6 mice using the model antigen ovalbumin (OVA) in subcutaneous vaccination with soluble protein as well as in a dendritic cell (DC) targeting approach (αDEC-OVA). Strikingly, c-di-AMP as compared to poly(I:C)/CpG resulted in significantly higher antigen-specific IgG antibody levels when used in immunization with soluble OVA as well as in antigen targeting to DC. In vaccination with soluble OVA, c-di-AMP induced a significantly stronger CTL, Th1 and IFNγ-producing CD8⁺ memory T cell response than poly(I:C)/CpG. The response was CTL and Th1 cell dominated, a profile shared by both adjuvants. In the context of targeting OVA to DC, c-di-AMP induced significantly increased Th1 and Th2 cell responses as compared to poly(I:C)/CpG. Interestingly, the Th1 response dominated the overall T cell response only when c-di-AMP was used, indicating a distinct modulatory property of c-di-AMP when the DC targeting immunization approach was exploited.Taken together, we describe superior properties of c-di-AMP as compared to poly(I:C)/CpG in subcutaneous vaccination with soluble antigen as well as antigen targeting to DC. This indicates exceptionally effective adjuvant properties for c-di-AMP and provides compelling evidence of its potential for further adjuvant development, especially also when using DC targeting approaches.     

儿童呼吸道卡他莫拉菌分离株产β-内酰胺酶情况和耐药性以及菌株BRO酶基因特征

目的研究儿童呼吸道卡他莫拉菌分离株产β-内酰胺酶情况和耐药性以及菌株BRO酶基因特征。方法选择2016年2月-2019年1月因呼吸道感染就诊且从痰液标本中分离得到卡他莫拉菌的患儿,测定抗生素敏感性、产β-内酰胺酶情况、BRO酶基因表达情况。结果产酶菌株对氨苄西林、阿莫西林、头孢克洛、头孢呋辛、头孢吡肟、左氧氟沙星、克拉霉素产生耐药的发生率高于非产酶菌株,BRO-1基因阳性菌株对氨苄西林、阿莫西林、头孢克洛、头孢呋辛、头孢吡肟、左氧氟沙星、克拉霉素产生耐药的发生率高于BRO-2基因阳性菌株;产酶菌株和非产酶菌株、BRO-1基因阳性和BRO-2基因阳性菌株均对亚胺培南敏感,未发生耐药。结论儿童呼吸道卡他莫拉菌产β-内酰胺酶比例高,且BRO-1基因阳性菌株的耐药性强于BRO-2基因阳性菌株。     

公立医院收支管理风险量化评价的两种方法比较分析

目的:构建科学合理的收支管理风险量化评价指标体系,为识别公立医院收支管理环节存在的风险提供依据。方法:分别采用传统描述性统计方法和熵值法对收支风险指标进行赋权。结果:"备用金年底是否及时收回""支出申请与内部审批是否分离"等风险点在两种方法下其权重排序差异较大。结论:在传统医院收支风险管理领域,实务界关注收入支出的数量真实性、合法合规性,而以差异化为导向的熵值法更关注的是不同被试之间的差异性,即易被忽视的风险点,这与近几年审计实务中发现的问题基本吻合,医院财务管理人员应予以重点关注。     

哮喘相关基因与治疗药物的生物信息学分析

目的:通过生物信息学技术比较哮喘患者与健康人的基因芯片数据,初步鉴定与哮喘相关的基因以及治疗哮喘的潜在药物。方法:从基因表达数据库下载GSE74986基因芯片,使用GEO2R分析得出差异表达基因,采用Morpheus制作差异表达基因的热图;通过DAVID 6.8对差异表达基因进行基因本体及京都基因与基因组百科全书分析,使用String 10.5构建蛋白质-蛋白质相互作用网络,筛选核心基因。进一步使用Cytoscape 3.6.1的插件MCODE对差异表达基因进行模块分析。通过医学本体信息检索平台筛选治疗哮喘的小分子药物。结果:筛选出510个差异表达基因,包括29个上调基因和481个下调基因。差异表达基因生物过程与通路主要富集在染色质沉默、核糖核酸聚合酶Ⅱ启动子的转录调节、蛋白质转运、信使核糖核酸加工、核糖核酸剪接以及泛素介导的蛋白水解、内质网中的蛋白质加工、核糖核酸转运、髓样分化因子依赖性Toll样受体信号通路、血小板激活、核苷酸结合寡聚化结构域样受体信号通路等。共得出9个核心基因,包括T-复合蛋白1θ亚基(CCT8),T复合物蛋白1α亚单位(TCP1),26S蛋白酶调节亚单位S10B(PSMC6),热休克蛋白90α(HSP90A) A1,细胞周期蛋白C(CCNC),HSP90AB1,26S蛋白酶体非ATP酶调节亚基6(PSMD6),泛素特异性蛋白酶14(USP14),真核细胞翻译起始因子4E(EIF4E)。得出2个重要模块,模块里的基因主要涉及剪接体和泛素介导的蛋白水解、蛋白修饰以及核糖核酸修饰等生物过程。治疗哮喘的潜在小分子药物有茴香霉素和金雀异黄素等。结论:差异表达基因和核心基因促进了对哮喘发病分子机制的理解,为哮喘的诊治提供了潜在的基因靶标与治疗药物。     

Thrombosis and infections of peripherally inserted central catheters in burn patients: A 3-year retrospective study and a systematic review

AimsPeripherally inserted central catheters (PICCs) are becoming common and effective in acute and critical care settings recently. Burn patients need special considerations because of restricted insertion sites, burn wounds, hyper coagulation, high infection rates and others. However, the safety of PICCs in burn patients are not well elucidated and no related protocol has been formed. This study aims to investigate the thrombosis and infections of PICCs in burn patients.MethodsThis was a single center retrospective study and a systematic review. All the burn patients with PICCs between January 1, 2018 and December 31, 2020 were included. A systematic search of Medline, PubMed, EMBASE and Web of Science was performed from inception to 4 June 2021 following PRISMA guidelines. Upper extremity vein thrombosis (UEVT) and central line-associated bloodstream infection (CLABSI) were the main outcome.ResultsA total of 85 successful PICCs in 78 patients were included. Most patients were male (79.5%), adults(80.8%) and injured by flame(74.4%). The mean TBSA was 50.3% and 76.9% of patients had TBSA more than 30%. Most PICCs were punctured once (60.0%) and inserted less than 30 days after injury (80.0%) through basilar vein (70.6%). The overall line days were 2195 days and the mean line days was 25.8 ± 18.3 days. Six PICCs were complicated by UEVT (7.1%) in 21.2 ± 17.3 days after insertion. Patients with UEVT had significantly higher rate of bacteremia and later insertions than those without UEVT. One patient developed CLABSI and the CLABSI rate was 1.2% and 0.5 per 1000 line days. Six PICCs had catheter colonization. No significant risk factors were identified. Five articles involving 293 patients and 319 PICCs were ultimately evaluated in systematic review. The overall incidence of UEVT was 3.2% and CLABSI was 6.9% in burn populations.ConclusionPICCs in burn patients had acceptable incidence of UEVT and CLABSI with relative long line durations. A standardized PICC guideline for burn patients is required to further improve the feasibility and safety of PICCs.     

中药调节黏膜免疫系统用于防治COVID-19的思路探索

机体免疫功能低下患者,极易出现新型冠状病毒感染,与中医所说正气不足、邪毒侵扰一致。目前集中在抗病毒药物研发是必须的,但对于调节机体免疫系统制剂的研究也较为迫切。黏膜组织是人体免疫系统的一道重要屏障,具有独特功能和结构的独立免疫体系,是机体抵抗感染的第一道防线,与外界抗原(比如食物、共生菌、病毒等)直接接触。其在抵抗病毒、抗感染方面,黏膜免疫(如呼吸道黏膜、肠道黏膜等)起着极其重要的作用,可以消灭外来病原微生物或其他外来抗原,不至于病毒侵入机体组织而对机体造成损伤。中药通过黏膜免疫系统发挥治疗作用的研究报道日益增多,该文拟针对黏膜免疫系统与新型冠状病毒肺炎(COVID-19)的关系以及中药的干预机制展开探讨,以期为COVID-19的防治提供可借鉴的研究方法与治疗思路。