保肺颗粒祛痰、平喘、止咳、抗炎作用的药效学研究

目的:研究保肺颗粒的止咳、平喘、祛痰、抗炎作用。方法:通过小鼠酚红分泌实验观察其祛痰作用、通过磷酸组胺引起豚鼠的哮喘反应,观察其平喘作用、通过SO2引起的小鼠咳嗽反应,观察其止咳作用、通过二甲苯致小鼠耳廓肿法,观察其抗炎作用、通过角叉菜胶致大鼠足趾肿胀法,观察其抗炎作用。结果:对小鼠耳廓肿炎性反应模型的实验表明:保肺颗粒高、中、低剂量均能显著抑制二甲苯引起的小鼠耳肿胀,其肿胀度、肿胀率显著降低。对小鼠的祛痰(气管段酚红法)实验表明:保肺颗粒高、中、低剂量均能增加小鼠酚红排出量。对豚鼠的平喘(喷雾致喘法)实验表明:保肺颗粒高剂量能明显提高磷酸组胺引起的豚鼠哮喘潜伏期延长率,中、低剂量也可提高豚鼠哮喘潜伏期延长率,但差异无统计学意义。对小鼠的止咳(二氧化硫引咳法)实验表明:保肺颗粒高、中、低剂量均能明显延长SO2引起的小鼠咳嗽潜伏期;高、中剂量能明显减少2 min内咳嗽次数;保肺颗粒高、低剂量能明显延长枸橼酸引起的豚鼠咳嗽潜伏期,能明显减少5 min内咳嗽次数,潜伏期延长率有明显提高。结论:保肺颗粒具有较好的祛痰、平喘、止咳、抗炎作用。     

Correlation of Stiffness of Prostate Cancer Measured by Shear Wave Elastography with Grade Group: A Preliminary Study

The aim of study was to explore the correlation between shear wave elastography (SWE) and grade group (GG) of prostate cancer (PCa). This retrospective study involved prostate-specific antigen elevated patients with elevated prostate-specific antigen levels who underwent SWE before transrectal ultrasound-guided needle biopsy. A total of 49 PCa lesions were reviewed after radical prostatectomy; 3–7 regions of interest were placed within the cancerous area on axial view compared with the tumor foci outlined on the slides by pathologist. The maximum SWE value was measured, quantitative SWE parameters (E_max, E_mean, E_min and standard deviation [SD]) were recorded and correlated with GG and then parameters were compared between indolent (≤2) and aggressive (≥3) GGs. The diagnostic value of each parameter was compared with the receiver operating characteristic curve. Forty-nine PCa foci were divided into two groups on the basis of their GGs. All SWE parameters exhibited a significant linear trend with GG. The area under the receiver operating characteristic curve (AUC) was 0.816 for E_max; with a cutoff point of 84 kPa, sensitivity and specificity were 81.3% and 82.4% to differentiate low and high GGs in PCa. The AUC was 0.776 for E_mean; with a cutoff point of 71 kPa, sensitivity and specificity were 78.1% and 76.5%. For E_min, the AUC was 0.739; with a cutoff point of 60 kPa, sensitivity and specificity were 68.8% and 70.6%. For SD, the AUC was 0.681; with a cutoff point of 8.3 kPa, sensitivity and specificity were 46.9% and 94.1%. There were no significant differences between the four SWE parameters (p < 0.05 for all). SWE features were correlated with GGs, and this correlation may have excellent diagnostic performance in predicting high GG in PCa.     

Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

Disrupted white matter functional connectivity in aMCI APOEε4 carriers: a resting-state study

The ε4 allele of the APOE gene is thought to increase risk from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease. Cognitive decline in the condition is increasingly considered to worsen functional disconnections in brain network composed of gray matter and white matter. Nevertheless, Whether APOEε4 targets specific white matter functional connectivity in patients with aMCI remains mostly unexplored, mainly due to the challenges of detecting BOLD signals in white matter. Here, we applied a novel approach to investigate APOEε4-related specific bundles and cortical area alterations in aMCI subjects, in order to characterize white matter-gray matter functional connectivity differences throughout the brain. We analyzed 75 patients with aMCI and 76 demographically matched normal controls. The aMCI APOEε4 carriers showed decreased functional connectivity located at left corticospinal tract, bilateral posterior limb of internal capsule, and right temporopolaris, which was different from the regions of aMCI-related changes. We further found that recognition scores were positively associated with the right temporopolaris in aMCI APOEε4 carriers. Collectively, the data provide new evidence that APOEε4 genotype exerts a negative impact on neural activity in both gray and white matter in aMCI, which potentially contributes to functional disconnection and memory decline. A novel method provides full-scale measuring effect of disease conditions on functional architecture throughout the brain. Trial registration: https://www.ClinicalTrials.gov (Identifier: NCT02225964). Registered January 2014.

     

胰高血糖素样肽1受体激动剂类降糖药致2型糖尿病患者头疼和眩晕的网状Meta分析

摘 要 目的：使用网状Meta分析系统评价胰高血糖素样肽1受体激动剂（GLP-1 RAs）类降糖药对2型糖尿病（T2DM）患者头疼和眩晕的影响。方法：系统检索Medline、Embase、Clinical trials和Cochrane数据库中（截止2017年6月23日）比较GLP-1 RAs与传统降糖药或安慰剂对头疼和眩晕发生风险影响的随机对照试验（RCT）,采用贝叶斯网状Meta分析对纳入的研究进行分析。结果：共纳入100项RCTs,包括15种干预措施：8种GLP-1 RAs类降糖药（艾塞那肽、艾塞那肽缓释剂、利拉鲁肽、利西拉来、他司鲁肽、阿必鲁肽、杜拉鲁肽、索玛鲁肽）、安慰剂、2种二肽基肽酶-4（DPP-4）抑制剂（西格列汀和维格列汀）和4种传统降糖药（胰岛素、二甲双胍、磺脲类、噻唑烷二酮类）。网状Meta分析结果显示：与胰岛素相比,艾塞那肽（OR=1.35,95%CI：1.13~1.60）、利拉鲁肽（OR=1.35,95%CI：1.12~1.62）、利西拉来（OR=1.59,95%CI：1.22~2.06）和他司鲁肽（OR=1.78,95%CI：1.33~2.37）致T2DM患者发生头疼的风险增加;与安慰剂、胰岛素及噻唑烷二酮相比,艾塞那肽和利拉鲁肽显著增加了眩晕发生的风险（OR的取值范围为1.56~2.56）。此外,后验概率显示,致T2DM患者发生头疼风险最高的前三位为艾塞那肽缓释剂、二甲双胍、他司鲁肽;致T2DM患者发生眩晕风险最高的前三位为利拉鲁肽、利西拉来和艾塞那肽。结论：艾塞那肽缓释剂和他司鲁肽显著增加了头疼的发生风险,利拉鲁肽显著增加了眩晕的发生风险,但仍建议开展相应的大型前瞻性研究加以验证。     

阿卡波糖与2型糖尿病患者冠心病发病风险的回顾性队列研究

摘 要 目的：探究使用阿卡波糖对新发2型糖尿病（T2DM）人群冠心病发病风险的影响。 方法：使用2012~2015年北京市城镇职工基本医疗保险数据库进行回顾性队列研究,共1 627例新发T2DM患者纳入分析。以患者首次诊断为糖尿病的时间为随访起点,直到出现研究结局、或最后一次就诊日期为观察终点。按照随访期间有无使用阿卡波糖将研究对象分为暴露组与对照组,使用时间依赖的Cox比例风险回归模型分析阿卡波糖用药对冠心病发病的影响;并根据累积暴露水平（累积用药时间/剂量）进行亚组分析。 结果：对研究对象随访4年,发生冠心病共计918例（56.42%）,其中暴露组379例（47.55%）,对照组539例（64.94%）,差异有统计学意义（P<0.05）。与对照组相比,累积用药天数＜60 d、60~180 d和＞180 d组发生冠心病的调整后HR（95%CI）分别为2.08（1.77,2.45）、0.79（0.65,0.97）和0.29（0.22,0.39）;累积用药剂量＜14 000 mg、14 000~48 000 mg和＞48 000 mg组发生冠心病的调整后HR（95%CI）分别为2.02（1.73,2.37）、0.72（0.58,0.89）和0.23（0.17,0.32）。 〖HTH〗结论：〖HTK〗长期使用阿卡波糖（累积用药达一定的天数或者剂量）可以降低新发T2DM患者冠心病的发病风险。     

基于电子医疗数据库的药品不良反应信号挖掘方法概述

摘 要随着电子医疗记录的不断发展和完善,基于大规模电子医疗数据库开展药品安全主动监测成为可能。本文对基于电子医疗数据库的药品不良反应（ADR）信号挖掘方法进行了综述,并对评价这些方法的研究进行了总结。综述的信号挖掘方法包括比值失衡法、传统药物流行病设计、处方序列对称分析、序贯统计检验、时序关联规则、有监督的机器学习和树状扫描统计量方法。从评价这些方法的研究结果可以看出,自身对照设计、处方序列对称分析和有监督机器学习方法的性能较好。当考虑使用信号挖掘方法开展常规药品安全主动监测时,方法原理容易理解有利于结果的解释。此外,方法能否给出信号强度以及方法是否易于实现,都是影响其实际应用的关键因素。     

多元化教学在《药事管理与法规》课程中的应用

目的：为提高学生的综合学习能力和课堂教学质量,对《药事管理与法规》课程的教学方式进行创新探索。方法：采用多种教学方法相融合的多元化教学方式,如案例教学法、拓展训练法、对点习题法、时事跟踪等,并在本校药物制剂专业《药事管理与法规》课程教学中进行实践。结果：多元化教学方式在该课程教学中的应用取得了很好的效果和反响,极大地激发了学生的学习兴趣,增强了学生服务社会的意识,提高了学生的专业认知程度。结论：多元化教学方式是适应当今多元化社会发展的必须模式,也是改变传统课堂教学方式的一种创新尝试。     

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy_7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy_7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy_7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy_7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy_7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.