微滴式数字PCR和实时荧光定量PCR对新型冠状病毒肺炎患者不同时间血便尿中核酸检测结果初步探讨

目的 分析微滴式数字PCR(droplet digital PCR, ddPCR)和实时荧光定量PCR(quantitative real-time PCR,qPCR)的核酸检测结果,比较两种方法检测各类样本的差异性,为改进新型冠状病毒核酸检测方案提供数据支持。 方法 利用ddPCR和qPCR技术对已经确诊的3例新型冠状病毒肺炎患者发病不同时间的全血、尿液、粪便共22份标本进行新型冠状病毒核酸检测。 结果 两种方法对人保守区域基因扩增结果一致:全血标本信号最强,尿液次之,粪便最少;ddPCR在1份全血,1份尿液,5份粪便中检出ORF-1ab和N基因的阳性微滴,qPCR仅在3份粪便中检出上述基因,漏检的3个标本基因拷贝数平均浓度为128 copies/ml;ddPCR在发病<5、5~15、>15 d的各类标本中都有检出,qPCR检出以中晚期为主;重症病例用ddPCR均可测到阳性微滴,qPCR检测的各类标本均为阴性;轻症病例的各类标本中qPCR只有粪便核酸检测阳性,ddPCR检出率高于qPCR。 结论 ddPCR可以有效克服qPCR 灵敏度不足的难题,是对qPCR 的有益补充,尤其是针对病毒载量比较低的血液、尿液和可疑的粪便或肛拭子标本,适用于早期感染的判断及患者治愈后出院诊断。     

Ebola Virus RNA Stability in Human Blood and Urine in West Africa’s Environmental Conditions

We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa’s environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

Same-Day Yttrium-90 Radioembolization: Feasibility with Resin Microspheres

Purpose

To evaluate the feasibility of a same-day yttrium-90 (⁹⁰Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.

Same-Day Repeat Hepatopulmonary Shunt Measurement during Planning Angiography for Hepatic Radioembolization

This report describes a technique for measuring lung shunt fraction (LSF) twice in a single session during planning arteriography for radioembolization using low and standard dose technetium-99m macroaggregated albumin (^99mTc-MAA). A patient with a 16.0 cm hepatocellular carcinoma and LSF of 70% was treated with lenvatinib for 4 weeks. Planning arteriography with administration of 0.5 millicuries of ^99mTc-MAA was then performed. Arterial access was maintained while the LSF was calculated, which was persistently elevated at 54%. Embolization of arteriovenous shunts was performed during the same session and 5.0 millicuries of ^99mTc-MAA were administered. The repeat LSF was 29%. Successful radioembolization was subsequently performed.     

缺血修饰性白蛋白在急性缺血性胸痛中的诊断价值

目的 评价缺血修饰性白蛋白（ischemia modified albumin，IMA）对急性缺血性胸痛（ICP）的早期诊断价值。方法 时206例发病〈12h、表现为急性胸痛的患者立即行12导联心电图（ECG）检查，并抽血进行IMA、肌钙蛋白I（cTnI）、肌酸激酶同工酶MB（CK-MB）测定。将ECG、IMA、cTnI、CK-MB的结果单独或结合与最终诊断为非缺血性胸痛（NICP）及ICP的相互关系进行比较。结果 最后诊断为ICP98例，NICP108例，ICP发病〈3h和3-6h组IMA水平明显升高，与NICP组比较差异有统计学意义（P〈0．001）；ICP发病〉6h组IMA水平与NICP组比较差异无统计学意义（P〉0．05）。IMA诊断发病〈3hICP的敏感性和阴性预测值（NPV）为89．1％和88．8％，明显高于ECG、cTnI和CK-MB，四者结合为97．6％和96．9％；IMA诊断发病3～6hICP的敏感性和NPV为71．7％和74．5％，也高于ECG、cTnI、CK-MB，四者结合为95．5％和94．2％；但IMA对于发病〉6h的ICP则无诊断作用。结论 IMA是诊断ICP的早期敏感生化指标，对于发病〈6h（尤其是〈3h）的ICP诊断具有较高的敏感性和NPV，优于ECG、CK-MB、cTnI；将IMA与其他指标结合，可进一步提高对ICP的诊断价值。     

Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.     

对血清蛋白白球比值参考范围的修改及其临床应用

目的探讨血清蛋白白球比值(A／G)的参考范围和A／G在计算过程中产生的误差对临床应用的影响。方法①选取健康查体人员统计其A／G参考范围；②从理论上分析A／G计算误差的存在。结果①以统计结果的2s置信区间作为A／G的参考范围是1.1～2.2；②A／G计算值的误差会远大于相应总蛋白和白蛋白的测定误差。结论A／G较合适的参考范围为1.1～2.2,并且在临床应用中仍可根据实际情况降低其范围的下限。