Drug discovery strategies for acute radiation syndrome

Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach.

Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims.

Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a ‘hybrid’ strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS.     

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.

Influenza vaccination and the endurance against air pollution among elderly with acute coronary syndrome

ObjectiveAir pollution, weather condition and influenza are known risk factors of acute coronary syndrome (ACS) among elderly people. The influenza vaccine (IV) has been shown to reduce major cardiovascular events. The purpose of this study was to compare resistance to air pollution and weather factors causing ACS between vaccinated and less-vaccinated elderly people.MethodsA case–crossover design was applied to 1835 elderly ACS patients who were obtained from the 1-million sample of Taiwan National Health Insurance Research Data with inclusion criteria: (1) the first diagnosis of ACS was in cold season and at age 68 or more, (2) had received the free IV program at least once during the period 3 years before the ACS. They were stratified into two groups: 707 had received flu vaccinations for all the 3 years and the remaining 1128 had not. The measurements of air pollutants, temperature, and humidity corresponding to each of the 3 days prior to the ACS diagnosis date were retrieved from the data banks of the Taiwan Environmental Protection Administration and Central Weather Bureau.FindingsIncreases in air pollution concentrations of CO, NO₂, PM₁₀ or PM_2.5 and decreases in temperature significantly influenced the risk of ACS for the non-continuously vaccinated elderly population; however, less significant effects were observed for the continuously vaccinated population.ConclusionConsecutive influenza vaccination may potentially offer resistance against the detrimental effects of air pollution and changes in temperature in frail elderly adults with ACS. Future studies are needed to directly assess the interaction effect between the vaccination and environmental factors on ACS.     

Acute liver injury,acute liver failure and acute on chronic liver failure: A clinical spectrum of poisoning due to Gyromitra esculenta

Gyromitra esculenta, also known as “false morel” is one of the most poisonous mushrooms. This species is found all over the world, growing in coniferous forest in early spring time. Common manifestation of poisoning includes gastrointestinal symptoms which include varied degrees of liver impairment.We describe three cases: acute liver injury, acute liver failure and acute-on-chronic liver failure due to G. esculenta poisoning. At admission patients presented with encephalopathy and features of liver failure. Two of them recovered completely following supportive management while the remaining patient who also had preexisting liver disease developed multiorgan failure and subsequently died.Although a rare occurrence, G. esculenta poisoning should be considered in the differential diagnosis of acute liver failure.     

A new era of immuno-oncology in acute myeloid leukemia - antibody-based therapies and immune checkpoint inhibition

Acute myeloid leukemia (AML) remains a therapeutically challenging malignancy with high rate of relapse and poor outcomes. There has been increased understanding of the molecular characteristics of AML and the various roles of the immune system in its pathogenesis, the result of which has led to the study and development of multiple immune-based approaches for this disease. In this review, we aim to provide an overview of the recent advancements made in antibody-based approaches to the treatment of AML including monoclonal antibodies, antibody-drug conjugates, and immune checkpoint inhibition. In addition, we provide insight and discuss the promise of these agents, some of which may soon enter the therapeutic armamentarium we currently employ against this lethal disease.     

SWIM技术治疗后循环大血管闭塞所致急性缺血性卒中的有效性和安全性观察

目的 观察SWIM技术治疗后循环大血管闭塞所致急性缺血性卒中的有效性及安全性。 方法 回顾性分析2017年2月-2018年11月于大连市中心医院采用SWIM技术治疗的后循环大血管闭 塞所致急性缺血性卒中患者的临床资料，评价该技术的疗效和安全性，并分析影响患者预后的因素。 观察指标为术后即刻成功再通（mTICI≥2b）、90 d良好预后（mRS评分≤2分），以及术后24 h任何颅内 出血、90 d全因死亡。 结果 共纳入35例患者，平均年龄66.1±12.1岁，男性26例（74.3%），基线NIHSS评分22（15～34）分。 术后即刻成功再通率为94.3%（33/35），90 d良好预后率为45.7%（16/35），24 h颅内出血率为17.1% （6/35），90 d全因死亡率为37.1%（13/35）。单因素分析显示，基线NIHSS评分较低（P =0.001）、基 线后循环ASPECTS评分较高（P =0.016）、发病至到院时间较短（P =0.039）、发病至再通时间较短 （P =0.047）、血管成功再通率较高（P =0.036）以及饮酒比例较低（P =0.042）与良好预后相关。 结论 使用SWIM技术治疗后循环急性缺血性卒中相对安全、有效。     

自拟温润方治疗风寒袭肺型急性咳嗽病的临床观察

目的 观察自拟温润方治疗风寒袭肺型急性咳嗽病的临床疗效。方法 64例风寒袭肺型急性咳嗽病患者,随机分为对照组(31例)和治疗组(33例)。对照组患者给予复方甘草口服溶液治疗,治疗组患者给予温润方治疗。比较两组患者治疗前和治疗3、6 d后的中医症状评分以及临床疗效。结果 治疗3、6 d后,两组患者咳嗽、咯痰、恶风、咽痒、鼻塞、流涕、鼻干、口干咽燥症状评分均低于治疗前,差异均具有统计学意义(P<0.05)。治疗组患者治疗3 d后咳嗽、咽痒、鼻干、口干咽燥症状评分分别为(2.18±0.98)、(1.15±0.81)、(0.60±0.61)、(0.81±0.71)分,均低于对照组的(3.04±1.62)、(1.68±0.96)、(0.96±0.67)、(1.37±0.86)分,差异均具有统计学意义(P<0.05);治疗组患者治疗6 d后咳嗽、咽痒、鼻干、口干咽燥症状评分分别为(0.54±0.51)、(0.42±0.48)、(0.40±0.46)、(0.47±0.51)分,均低于对照组的(1.12±0.76)、(1.11±0.98)、(0.88±0.98)、(1.01±0.92)分,差异均具有统计学意义(P<0.05)。两组患者治疗3、6 d后咯痰、恶风、鼻塞、流涕症状评分比较,差异无统计学意义(P>0.05)。治疗3 d后,治疗组治疗总有效率90.9%高于对照组的71.0%,差异具有统计学意义(P<0.05)。治疗6 d后,治疗组患者治疗总有效率93.9%与对照组的90.3%比较,差异无统计学意义(P>0.05)。结论 在风寒袭肺型急性咳嗽病治疗中,温润方在缓解咳嗽以及部分次症方面明显优于复方甘草口服溶液,起效更快。