糖皮质激素在脓毒症治疗中免疫调节机制的生物信息学探索

目的探索糖皮质激素用于脓毒症患者引起的差异表达基因。方法从GEO数据库下载基因芯片数据集,按照糖皮质激素治疗前后分为两组,通过数据处理后筛选出差异基因,再经过功能通路富集(GO、KEGG、GSEA)及蛋白相互作用网络(PPI)筛选出关键基因。结果两组数据共筛选出685个差异基因,GO、KEGG、GSEA与PPI主要富集到粒细胞活化及免疫应答通路等,基因FPR2、RETN、HMA1、UBB、TFRC、RUMX1参与广泛的基因间调节作用。结论生物信息学技术有助于对脓毒症免疫药物治疗机制的认识。     

中药在抗新型冠状病毒肺炎（COVID-19）引起的细胞因子风暴中的应用分析

2019年12月底新型冠状病毒肺炎(COVID-19)在我国爆发,截止2020年2月23日已感染超7万人,感染者遍布全球28个国家和地区。其传染性强,传播迅速广泛,重症患者可出现急性呼吸窘迫综合征、多器官衰竭等严重并发症。而病毒感染引起的免疫过度激化导致的"细胞因子风暴"是重症患者产生严重并发症的重要原因。目前《新型冠状病毒感染的肺炎诊疗方案》中采用糖皮质激素作为免疫抑制剂,用于遏制重症患者的免疫激化反应,但是糖皮质激素的使用可能会造成二次感染、病程延长等不良预后,且存在严重后遗症风险。而中药在整体免疫调控方面具有明显优势,目前在COVID-19临床治疗中,中西医结合治疗也收到了积极效果。从免疫调控作用入手,分析了单味中药及中药方剂在遏制COVID-19引起的免疫过度激化及细胞因子风暴、抗急性肺损伤的潜在应用价值,有望对现有的诊疗方案中药临床应用做有益补充,发挥抗击疫情的重要作用。     

Differential expression of a stress‐regulated gene Nr4a2 characterizes early‐ and late‐born hippocampal granule cells

Neural progenitors acquire GFAP expression during the perinatal period and continue to generate granule cells (GCs) in the hippocampal dentate gyrus throughout adulthood. Cellular characteristics of GFAP+ progenitor‐derived late‐born GCs in comparison with early‐born GCs remain unknown. Using genetic fate mapping in mice, we show that early‐ and late‐born GCs are concentrated in the outer and inner side of the GC layer, respectively. We then identify that a nuclear orphan receptor Nr4A2 is preferentially expressed by early‐born GCs. Nr4a2 expression is dynamically regulated in response to restraint stress and glucocorticoid levels, indicating that Nr4a2 is a stress‐regulated gene in GCs. Acute stress suppresses but chronic stress conversely induces Nr4a2 expression in GCs. The survival of newly generated GCs is impaired by chronic restraint stress and long‐term stress after middle age decreases the proportion of late‐born GCs in aged mice. Thus, early‐ and late‐born GCs exhibit characteristic anatomical distribution, differential gene expression, and distinct response to environmental stress.     

Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.     

糖皮质激素类联合肾上腺素能β激动剂对慢性阻塞性肺疾病急性加重期患者的疗效分析

目的 探讨糖皮质激素类联合肾上腺素能β激动剂对慢性阻塞性肺疾病急性加重期(AECOPD)患者的疗效.方法 选取AECOPD患者100例,依据随机数字表法分为联合用药组和对照组,每组50例.对照组给予常规对症和布地奈德雾化吸入治疗,联合用药组在此基础上加用沙丁胺醇雾化吸入治疗.调查所有患者治疗前后肺功能、血清肿瘤坏死因子-α、白细胞介素-8、C-反应蛋白、不良反应、病情严重程度和生活质量情况.结果 联合用药组治疗后1秒用力呼气量、肺总量、1秒用力呼气量用力肺活量百分比显著高于对照组(P<0.05);联合用药组治疗后血清肿瘤坏死因子-α、白细胞介素-8、C-反应蛋白水平低于对照组(P<0.05),治疗后1个月、3个月慢性阻塞性肺疾病评估测试评分和St George呼吸疾病问卷得分低于对照组,差异有统计学意义(P<0.05);两组治疗期间不良反应发生率、治疗后6个月慢性阻塞性肺疾病评估测试评分和St George呼吸疾病问卷得分差异无统计学意义(P>0.05).结论 糖皮质激素类联合肾上腺素能β激动剂治疗可有改善AECOPD患者的肺功能、炎症状态、病情、生活质量和提高疗效,且具有良好的安全性.