Monitoring stroke progression: in vivo imaging of cortical perfusion,blood–brain barrier permeability and cellular damage in the rat photothrombosis model

Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood–brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood–brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.     

三七总皂苷治疗脑梗死作用机制的网络药理学研究

三七总皂苷（PNS）是从三七中将其主要药理活性成分提纯出来,三七总皂苷近年来在治疗与研究脑梗死方面取得了较佳的效果,而网络药理学是一种网络分析生物系统的新学科,基于系统生物学理论,从生物网络平衡学和系统生物学的角度来对疾病的发生发展过程进行阐释。本文就三七总皂苷治疗脑梗死作用机制的网络药理学进行研究,具有一定的参考价值。     

Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles

Engineered nanoparticles (NPs) are widely used in different technologies but their unique properties might also cause adverse health effects. In reviewing recent in vitro and in vivo genotoxicity studies we discuss potential mechanisms of genotoxicity induced by NPs. Various factors that may influence genotoxic response, including physico-chemical properties and experimental conditions, are highlighted. From 4346 articles on NP toxicity, 112 describe genotoxicity studies (94 in vitro, 22 in vivo). The most used assays are the comet assay (58 in vitro, 9 in vivo), the micronucleus assay (31 in vitro, 14 in vivo), the chromosome aberrations test (10 in vitro, 1 in vivo) and the bacterial reverse mutation assay (13 studies). We describe advantages and potential problems with different methods and suggest the need for appropriate methodologies to be used for investigation of genotoxic effects of NPs, in vitro and in vivo.     

Advances and novel developments in allergic rhinitis

Allergic rhinitis (AR) is an upper airway disease with high prevalence in the world, and therefore needs to be thoroughly investigated and treated accordingly. Although the mechanisms underlying the pathology and treatment of AR have been widely studied, many aspects of AR are still unclear and warrant further investigations. The purpose of the present review was therefore to report recently published papers, which highlight the novel mechanisms and treatments of AR. These include role of environment, important proteins and cells, and some other factors in the pathogenesis of AR; as well as the role of immunotherapy and biologics in the treatment of AR.     

Chalcone hybrids as potential anticancer agents: Current development,mechanism of action,and structure-activity relationship

The continuous emergency of drug-resistant cancers and the low specificity of anticancer agents have been the major challenges in the control and treatment of cancer, making an urgent need to develop novel anticancer agents with high efficacy. Chalcones, precursors of flavonoids and isoflavonoids, exhibit structural heterogeneity and can act on various drug targets. Chalcones which demonstrated potential in vitro and in vivo activity against both drug-susceptible and drug-resistant cancers, are useful templates for the development of novel anticancer agents. Hybridization of chalcone moiety with other anticancer pharmacophores could provide the hybrids which have the potential to overcome drug resistance and improve the specificity, so it represents a promising strategy to develop novel anticancer agents. This review emphasizes the development, the mechanisms of action as well as structure-activity relationships of chalcone hybrids with potential therapeutic application for many cancers in recent 10 years.     

Sublingual immunotherapy alters expression of IL‐4 and its soluble and membrane‐bound receptors

Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which results from an inappropriate T helper cell, type 2 (Th2) response to pollen. Specific immunotherapy (SIT) involves repeated treatment with small doses of pollen and can result in complete and lasting reversal of SAR. Here, we assayed the key Th2 cytokine, IL‐4, and its soluble and membrane‐bound receptor in patients with SAR before and after SIT. Using allergen‐challenge assays, we found that SIT treatment decreased IL‐4 cytokine levels, as previously reported. We also observed a significant decrease in the IL‐4 membrane‐bound receptor (mIL4R) at the level of both mRNA and protein. SIT treatment resulted in a significant increase in the inhibitory soluble IL‐4 receptor (sIL4R). Reciprocal changes in mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a novel explanation for the positive effects of immunotherapy with potential basic and clinical research implications.     

Reinforced reasoning in medicine

Some philosophers have argued that evidence of underlying mechanisms does not provide evidence for the effectiveness of a medical intervention. One such argument appeals to the unreliability of mechanistic reasoning. However, mechanistic reasoning is not the only way that evidence of mechanisms might provide evidence of effectiveness. A more reliable type of reasoning may be distinguished by appealing to recent work on evidential pluralism in the epistemology of medicine. A case study from virology provides an example of this so‐called reinforced reasoning in medicine. It is argued that in this case study, the available evidence of underlying mechanisms did in fact play a role in providing evidence in favour of a medical intervention. This paper therefore adds a novel and recent case study to the literature in support of evidential pluralism in medicine.     

2018年度某三甲综合医院常见多重耐药菌的科室分布特点及耐药性分析

目的分析陆军军医大学第二附属医院2018年度多重耐药菌(MDRO)的临床分布及其对常用抗菌药物的耐药性,为医院感染的防控及临床合理利用抗菌药物提供依据。方法采用回顾性分析方法,抽取该院2018年1-12月的5368例住院患者送检标本中多重耐药菌检测情况和细菌药敏试验数据,统计分析多重耐药菌的临床分布特点及其耐药情况。结果2018年度本院共检出多重耐药菌848株,检出菌株量排前5位的分别是鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌、大肠埃希菌;多重耐药菌在痰液标本中的检出率为最高,其次为血液标本、伤口标本和尿标本;检测出的耐甲氧西林金黄色葡萄球菌(MRSA)对糖肽类、硝基呋喃类、恶唑酮类抗菌药物极其敏感,对于氨基糖苷类和喹诺酮类抗菌药物的敏感率≥75%,而对于青霉素类、大环内酯类和林可霉素类抗菌药物的耐药率极高;耐碳青霉烯类大肠埃希菌对碳青霉烯类抗菌药物耐药率极低,而对青霉素类、头孢菌素类、氨基糖苷类、氟喹诺酮类抗菌药物均显示出较高的耐药率耐碳青酶烯类铜绿假单胞菌(CR-PAE)对多黏菌素B极为敏感,对氨基糖苷类的阿米卡星与喹诺酮类的环丙沙星耐药率相对较低,对β-内酰胺酶类、头孢菌素类、碳青霉烯类等抗菌药物的耐药率较高,而对于β-内酰胺类与酶抑制剂复合物的耐药率较低。结论医院多重耐药菌感染日益严重,应该加强对多重耐药菌株的监控,根据送检药敏结果合理选用抗菌药物治疗,加强医护人员多重耐药菌预防控制知识和手卫生培训,严格落实消毒隔离措施,从而有效预防和控制多重耐药菌的感染和暴发。     

丙戊酸钠通过激活内源性凋亡途径诱导乳腺癌细胞凋亡的实验研究

目的探讨丙戊酸钠（VPA）诱导乳腺癌细胞凋亡的作用。方法乳腺癌细胞株MCF-7细胞分为0.75～4.0 mmoL/L VPA实验组、对照组（不加VPA）及VPA与caspase抑制剂共同作用组。Annexin V-PI双染法流式细胞术检测细胞凋亡,间接免疫荧光法定量分析及分光光度法检测caspase- 3、caspase-8、caspase-9蛋白丰度和活性,探讨VPA诱导凋亡的机制,同时检测VPA与caspase-3、caspase- 8、caspase-9特异性抑制剂协同作用后细胞凋亡的变化来加以验证。结果各浓度VPA干预MCF-7细胞48 h后,细胞凋亡率显著增加,caspase-3、caspase-9活性升高、蛋白表达明显上调,与对照组相比有显著差异（F=552.1、610.9、312.8、222.8、70.3,均P〈0.001）;而caspase-8活性及蛋白表达未见明显改变;1.5、3.0 mmol/L VPA与caspase-3、caspase-9相应特异性抑制剂共同作用组,细胞凋亡率均较VPA组显著降低（t=109.0、28.7、18.7、32.3,均P〈0.005）;VPA与caspase-8特异性抑制剂共同作用组细胞凋亡率与VPA组比较无明显改变（t=1.03、2.32,均P〉0.05）。结论VPA可通过激活caspase-9介导的内源性凋亡途径,明显诱导乳腺癌细胞凋亡,具有较好的临床应用价值。