Method development of immunoglobulin G purification from micro-volumes of human serum for untargeted and targeted proteomics-based antibody repertoire studies

Immunoglobulins (Igs) are major serum proteins which play important roles in immunity. Both untargeted and targeted proteomic workflows can be applied to investigate antigen-binding sites and the glycosylation profiles of Igs. For a more-comprehensive picture of IgG from human serum, we developed an IgG purification process and coupled the standardized method to untargeted and targeted proteomic workflows for IgG investigations. Parameters such as the type of purification beads, volume of the bead slurry, incubation conditions, and binding capacities were evaluated in this study. Only 2 μL of human serum was required for each sample. The performance of coupling the purification process to untargeted proteomics in the IgG analysis was evaluated by comparing normalized abundances of IgG subclass-specific peptides with quantification results from an ELISA. Pearson's correlation values were all >0.82. Targeted proteomic workflow was applied to serum samples from patients with autoimmune pancreatitis and from healthy controls, and the results corresponded to clinical findings that IgG4-related peptides/glycopeptides showed higher abundances in the diseased group. The developed IgG purification process is simple and requires small sample volume, and it can be coupled to targeted and untargeted proteomic workflows for clinical investigations in the future.     

多层螺旋CT定量评估慢性阻塞性肺疾病病情的价值

目的探讨多层螺旋CT(MSCT)定量评估慢性阻塞性肺疾病病情的价值。方法选取2017年8月～2018年7月在湖州市第一人民医院就诊的73例慢性阻塞性肺疾病(COPD)患者作为研究对象,按照病情轻重分为Ⅰ组(轻度患者17例)、Ⅱ组(中度患者32例)、Ⅲ组(重度患者24例),并选取同期于该院体检的健康者20例为对照组。所有研究对象均行MSCT低剂量扫描,观察比较各组管腔面积(Ai)、支气管壁面积百分比(WA%)、管壁厚度与体表面积比值(T/BSA)、壁厚度与直径比值(TDR),同时予以肺功能检查,采用定量CT气道分析软件分别测量气道相关参数,并用Siemens Pulmo软件Pearson定量分析其相关性。结果对照组、Ⅰ组、Ⅱ组、Ⅲ组的FEV1均呈逐渐下降趋势,FEV1/FVC呈逐渐上升趋势,差异均有统计学意义(P0.05)。对照组、Ⅰ组、Ⅱ组、Ⅲ组的WA%、T/BSA、TDR比较,均呈逐渐上升趋势,Ai呈下降趋势,差异均有统计学意义(P0.05)。FEV1与WA%、TDR之间呈负相关(r=-0.291,P=0.000;r=-0.473,P=0.000),FEV1/FVC与WA%、TDR之间呈正相关(r=0.285,P=0.000;r=0.472,P=0.000)。结论 MSCT扫描及定量分析可为COPD患者气道病变情况提供可靠的评估信息。     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

The relationships among monocyte subsets,miRNAs and inflammatory cytokines in patients with acute myocardial infarction

Background

Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.

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.