Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology

Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.

Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.

Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.     

中医药干预新型冠状病毒肺炎临床研究方案分析

对中医药防治新型冠状病毒肺炎临床研究方案注册情况进行分析,为提高相关研究设计质量提供参考和建议。检索中国临床试验注册中心网站(www.chictr.org.cn)以及美国临床试验注册中心网站(clinicaltrials.gov),以新型冠状病毒肺炎、2019-nCoV等为检索词,检索新型冠状病毒肺炎中医药相关临床研究方案。按照纳入排除标准筛选文献,并提取研究注册时间、研究目的、研究类型、申办单位、研究对象、样本量、干预措施、评价指标等数据,采用描述性分析方法。共纳入新型冠状病毒肺炎中医药相关研究方案49个,研究负责单位以湖北、北京、浙江等地医院或高等院校为主。研究具体实施单位属地集中在湖北、广东、浙江、河南等地医院。研究设计以干预性试验研究为主(共40个),其中随机平行对照研究30个,非随机对照试验7个,单臂研究2个,连续入组1个;观察性研究6个;卫生服务研究2个;预防性研究1个。总样本量30562例,单个研究样本量最大20000例,最小30例。49个方案的研究对象包括健康人群(3个)、隔离观察人群(1个)、疑似病例(10个)、确诊病例(31个)、康复期病例(4个)。31个拟纳入确诊病例的研究方案中,有16个研究未明确病情分级,3个研究明确排除危重症,4个研究纳入普通型,2个研究纳入轻型、普通型或重型,1个研究纳入轻型和普通型,1个研究纳入普通型或重型,3个研究纳入重型,1个研究纳入重症或危重症。评价的干预措施包括中成药(连花清瘟胶囊/颗粒、藿香正气滴丸/口服液、八宝丹、固表解毒灵、金蒿解热颗粒、复方鱼腥草合剂、金叶败毒颗粒、疏风解毒胶囊、双黄连口服液、痰热清注射液、血必净注射液、热毒宁注射液、喜炎平注射液)、汤药、太极拳疗法。主要疗效指标以退热时间、临床症状缓解、新型冠状病毒核酸转阴、重症转化率、胸部CT影像为主。结果表明中医药防治新冠肺炎的临床研究响应快速,当前注册方案涵盖了疾病预防、治疗和康复全过程。但存在人群定义不清,研究目标不明确,干预方案需要细化,疗效评价指标需要优化等问题;另外,需要考虑疫情救治的实际困难和工作负担,在符合医学伦理条件下,优化流程,提高研究方案的可操作性。     

Biomedical microelectromechanical systems (BioMEMS): Revolution in drug delivery and analytical techniques

Advancement in microelectromechanical system has facilitated the microfabrication of polymeric substrates and the development of the novel class of controlled drug delivery devices. These vehicles have specifically tailored three dimensional physical and chemical features which together, provide the capacity to target cell, stimulate unidirectional controlled release of therapeutics and augment permeation across the barriers. Apart from drug delivery devices microfabrication technology’s offer exciting prospects to generate biomimetic gastrointestinal tract models. BioMEMS are capable of analysing biochemical liquid sample like solution of metabolites, macromolecules, proteins, nucleic acid, cells and viruses. This review summarized multidisciplinary application of biomedical microelectromechanical systems in drug delivery and its potential in analytical procedures.     

高渗盐水和甘露醇在动脉瘤性蛛网膜下腔出血患者降低颅内压中的应用

目的比较3%高渗盐水和20%甘露醇治疗重症动脉瘤性蛛网膜下腔出血所致颅内压增高的疗效.方法25例动脉瘤性蛛网膜下腔出血患者出现颅内压增高事件时, 随机交替接受等渗透剂量的160 mL 3%高渗盐水与150 mL 20%甘露醇进行降低颅内压治疗, 连续监测患者颅内压、平均动脉压、脑灌注压及中心静脉压.记录有效降低颅内压持续时间、颅内压最大降幅及其时间, 用药前及用药后1 h、3 h血钠水平及血浆渗透压.结果3%高渗盐水和20%甘露醇均可降低颅内压(均 P < 0.01), 两者的降低颅内压作用持续时间及颅内压降幅差异均无统计学意义(均 P >0.05).患者脑灌注压较用药前均上升(均 P < 0.01), 平均动脉压先上升后下降, 但差异无统计学意义( P >0.05).患者中心静脉压稍有波动, 但差异均无统计学意义(均 P >0.05).20%甘露醇治疗后患者血钠下降, 3%高渗盐水治疗后患者血钠值上升, 变化均有统计学意义(均 P < 0.05).20%甘露醇及3%高渗盐水治疗后患者血浆渗透压均先上升后下降, 变化均有统计学意义(均 P < 0.01). 结论3%高渗盐水可作为治疗动脉瘤性蛛网膜下腔出血所致颅内压增高患者的一线治疗药物.     

《艾滋病诊疗指南第三版(2015版)》更新解读

2015年中华医学会感染病学分会艾滋病学组发布了第三版《艾滋病诊疗指南》。新版指南强调抗病毒治疗时点前移:一旦成人确诊感染人类免疫缺陷病毒(HIV), 若无禁忌宜尽早启动抗HIV治疗。对于合并机会性感染的HIV感染者, 在感染控制、病情稳定后也应及早开始抗病毒治疗。尤其强调HIV合并结核患者在CD4阳性淋巴细胞数少于200/μL的情况下, 建议抗结核两周内即开始抗病毒治疗。在抗HIV治疗用药中, 淘汰了一些毒副作用大、依从性较差的药物, 如司他夫定、去羟肌苷、茚地那韦等, 优选抗病毒效力强、服药方便的组合, 如拉米夫定、替诺福韦、依非韦伦组合。对于HIV感染的婴幼儿, 亦主张及早抗HIV治疗。对于五岁以内的幼儿, 主张确诊后即启动抗病毒治疗。对于HIV感染的孕产妇, 建议尽快予以全程、联合抗HIV治疗, 寓防于治。     

Are primary care physicians ill equipped to evaluate and treat childhood physical inactivity?

ABSTRACT

Objective

To investigate primary care physician clinical practice patterns, barriers, and education surrounding pediatric physical activity (PA), and to compare practice patterns by discipline.