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51.
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.  相似文献   

52.

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.

Methods

In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.

Results

AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.

Conclusions

These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium.  相似文献   
53.
目的探讨心理护理在ICU重症护理中的效果。方法选定本科于2017年6月-2019年8月收诊的ICU重症患者86例,等距抽样法分为对照组(43例,传统式护理)与观察组(43例,心理护理联合传统式护理)2组,比较2组ICU重症患者的护理满意率、情绪评分(SAS/SDS)指标。结果观察组ICU重症患者干预结束后的满意率高于对照组(P<0.05);观察组ICU重症患者干预结束后的SAS评分(32.52±3.26)分、SDS评分(30.09±3.45)分均低于对照组(P<0.05)。结论心理护理应用于ICU重症患者,可对其满意度、安全性进行保证。  相似文献   
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《Vaccine》2016,34(50):6316-6322
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 PM2.5 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.  相似文献   
57.
《Annals of hepatology》2019,18(3):514-516
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.  相似文献   
58.
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.  相似文献   
59.
目的分析新生儿重症监护病房(NICU)中重症肺炎新生儿多种菌感染危险因素。方法回顾分析2014年1月至2019年5月收入NICU的1 057例重症细菌肺炎新生儿的临床资料,分析其多种菌感染的危险因素。结果单因素分析显示,胎龄(37周)、出生体质量(2 500 g)、发病日龄(7 d)、羊水污染(Ⅱ、Ⅲ度)、感染类型(医院感染)、住院时间(≥14天)、机械通气、Apagar评分(7分)、胎膜早破、抗菌药物使用天数(≥10天)、更换抗菌药物(≥3种)、联合使用抗菌药物(≥3种)12个因素是NICU中重症肺炎新生儿多种菌感染的危险因素,差异有统计学意义(P均0.05)。多因素分析显示,更换抗菌药物(≥3种)、Apagar评分(7分)、感染类型(医院感染)、机械通气、羊水污染(Ⅱ、Ⅲ度)是NICU中重症肺炎新生儿多种菌感染的独立危险因素(P0.05)。结论临床应针对主要危险因素采取综合防控措施,减少NICU新生儿重症肺炎多种菌感染。  相似文献   
60.
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