Effect of high-throughput screening of circRNA01724 on a rat model of myocardial ischemia ventricular arrhythmia

BackgroundIt is considered that circRNA can participate in regulating the occurrence and effects of ventricular arrhythmia (VA) through competing endogenous RNA (ceRNA) mechanism, regulating pre-mRNA and regulating parental gene expression. Therefore, we used animal modeling and high-throughput differential screening to screen out circRNA related to VA and study its possible mechanism of action on VA.MethodsThe rat model of myocardial ischemia VA was established. High-throughput screening of the differentiated circRNA was conducted and verified by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot. Lv-circRNA01724 lentivirus was constructed using molecular biology. Primary isolation of the rat cardiomyocytes, hypoxia modeling, Lv-circRNA01724 transfection, mode of action verification, and dual luciferase detection of circRNA01724 and miR-323-5p was performed.ResultsThrough qRT-PCR verification of circRNA01724, circRNA02230, circRNA02088, miR-323-5p, miR-330-5p, and miR-324-3p expressions, circRNA01724 was selected as the research object. Detection by Western blot showed significantly lower Cx43, ZO-1, and α-catenin expressions in rat myocardial tissue in the model group compared with the control group at 1, 7, 14, and 28 days old. On identification of the isolated primary rat cardiomyocytes by immunofluorescence, the α-SMA characteristic protein expression indicated that the isolation was successful. Verification of rat cardiomyocytes transfected with Lv-circRNA01724 suggested overexpression in cells. The miR-323-5p was also highly expressed in the rat cardiomyocyte hypoxia model following Lv-circRNA01724 transfection. Detection by flow cytometry showed that modeling of the transfected Lv-circRNA01724 had a significant increased apoptotic rate. Detection by Western blot showed that modeling of the transfected Lv-circRNA01724 cells had significantly decreased Cx43, ZO-1, and α-catenin compared with the model group.ConclusionsHigh-throughput screening of circRNA01724 can promote the apoptosis of hypoxic cardiomyocytes, which is related to the rat model of myocardial ischemia VA and may be a potential target for the treatment of VA.     

高频彩超对小体积恶性乳腺叶状肿瘤的诊断价值

目的探讨高频彩超对小体积恶性乳腺叶状肿瘤的诊断价值,提高小体积恶性PTB的术前诊断率。方法回顾分析4例经手术病理确诊的小体积恶性乳腺叶状肿瘤的声像图表现,并与该研究在同一台机器同一探头操作、预设条件一样前提下,病灶大小接近的,患者年龄相仿的,病灶深度差不多的6例纤维腺瘤的声像图进行对比分析。结果肿块最小者2.1cm×1.8 cm,最大者4.6 cm×3.7 cm;小体积恶性乳腺叶状肿瘤的CDFI表现：血供较丰富,Ⅱ级1例,Ⅲ级3例。纤维腺瘤的CDFI表现：血供较稀疏,0级1例,Ⅰ级4例,Ⅱ级1例。结论小体积恶性乳腺叶状肿瘤的CDFI表现具有较高的特异性,容易分辨,对于诊断小体积恶性乳腺叶状肿瘤有较高的实用价值。     

免疫抑制剂细胞内浓度测定的研究进展

细胞外浓度测定作为目前器官移植临床免疫抑制剂治疗药物监测（TDM）的主要手段,与免疫抑制剂药效之间的相关性不理想。随着液相质谱技术的广泛应用,免疫抑制剂细胞内浓度检测技术逐渐成熟。由于细胞内浓度测定可直接检测靶细胞内的药物暴露水平,理论上能更好地反映免疫抑制剂的药效。本文总结了免疫抑制剂细胞内浓度测定的历史与现状,着重介绍免疫抑制剂细胞内浓度的测定方法及其与药效的相关性。免疫抑制剂细胞内浓度测定具有较好的临床应用价值,值得推广。     

High throughput screening of small molecule libraries for modifiers of radiation responses

Purpose:?An unbiased approach of drug discovery through high-throughput screening (HTS) of libraries of chemically defined and bioactive small molecule compounds was used to identify modulators of radiation injury with an emphasis on radioprotectors and mitigators rather than radiosensitisers. Assay system endpoints included radiation-induced genotoxicity and DNA damage in yeast and apoptosis in murine lymphocytes. Large-scale data mining of chemically diverse libraries identified agents that were effective with all endpoints. HTS of bioactive compound libraries against murine lymphocytes profiled tetracycline and fluoroquinolone antibiotics and cyclopiazonic acid as having activity, and structure-activity analysis showed a common pharmacophore. Purine nucleosides, the interferon inducer tilorone, and linoleic acid were also identified as potential mitigators of radiation damage that often were also radioprotective. Many of these compounds enhance DNA repair, have anti-inflammatory activity, and stimulate hematopoiesis. Selected compounds within these initial verified hits from both types of libraries identified potent mitigators of lethal whole body irradiation (WBI) in mice.

Conclusion:?In spite of the fact that in vitro HTS has limitations and is unable to fully recapitulate all aspects of the complex in vivo acute radiation response, it identified several classes of molecules that had activity as radioprotectors and radiomitigators of the hematopoietic system in vivo. In the future, addition of 3-dimensional (3-D) or stem cell cultures or pathway analysis, may improve the power of HTS, but our findings indicate that common, evolutionary conserved, canonical pathways can be identified that could be exploited to mitigate radiation-induced defects.     

A New High Affinity Variant Hb Aurillac (β141Leu→Val)

Hemoglobin (Hb) variant β141(H19)Leu→Val (HBB:c.424C>G), one of the two mutations defining Hb Kochi [the other one being β144(HC1)Lys-Tyr-His→0 (HBB:c.433A>T)], was found as an isolated mutation. In contrast to what was suggested for Hb Kochi, the new variant was not clinically silent. It displayed increased oxygen affinity and was associated with mild erythrocytosis.     

A blinded,randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock

Background. High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. Methods. This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. Results. 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. Conclusion. HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.     

肝癌高强度聚焦超声消融的增效方法

本文从肝癌高强度聚焦超声（HIFu）治疗的优势与不足出发,探讨肝癌HIFU增效剂的临床价值。通过改变肝癌组织声环境,增加靶区能量沉积,即肝癌组织内引入高声阻抗物质,改变肝癌组织声学特性及血供状态,引入微泡造影剂等,阐述HIFU增效剂的原理及应用。     

心血管疾病患者高密度脂蛋白心脏保护功能的改变

高密度脂蛋白胆固醇（high density lipoprotein cholesterol,HDL-C）水平是心血管疾病风险的独立预测因素,与心血管事件发生风险呈负相关。但是单纯增加HDL-C的浓度并不能减少心血管疾病的发生率,过高浓度的HDL-C可能促进心血管疾病发生,所以HDL-C与心血管疾病发生和进展是否有因果关系仍不明确。在某些疾病内环境下,组成HDL的蛋白或脂类和参与HDL代谢的酶等成分发生改变,这些因素将导致HDL心血管保护功能下降。所以,在研究HDL与心血管疾病关系时,评估它的功能和质量,可能比评估它的数量更重要。     

高原肺水肿大鼠模型的建立与研究

 目的 模拟高原环境,研究大鼠急性低氧复合运动高原肺水肿的发生及低氧习服后的改变.方法 健康SD-大鼠分为常氧对照组(n=10)、5 000 m急性低氧组(n=10)及3 000 m低氧习服组(n=10).对比研究大鼠的肺血流动力学、肺水肿程度及肺组织病理形态学改变.结果 与常氧对照组相比,急性低氧组大鼠动脉血氧分压及氧饱合度显著降低,肺体指数及肺含水率升高,病理学显示肺间质充血,肺泡隔增宽等间质性肺水肿表现.低氧习服组明显改善.结论 成功建立高原间质性肺水肿模型及低氧习服模型,有利于进一步研究高原肺水肿低氧习服机制.     

高原低氧环境对人体生长发育和营养状况的影响

目的:研究高原低氧环境对人体发育和营养状况的影响。方法:依照中华人民共和国国家军用标准(GJB1102-91)《中国人民解放军战士身体发育测量及评价》对驻守在海拔4300m某地的277名战士进行身体发育指标的测量并计算派生出其他指标,与120名平原战士比较。同时按高原居住不同时间对277名高原战士进行组内对照。结果:与平原战士比较,高原战士的体重、上臂围、上臂肌围、三头肌部皮褶厚度、肩胛下皮褶厚度、体脂含量、体质指数、比体重等均低于平原战士,相差非常显著(P<0.01)。高原居住时间越长,营养缺乏越严重。结论:高原低氧环境由于营养供給不足,加之缺氧状态机体营养代谢紊乱,致使人体体质量下降、肌消瘦、营养缺乏等,进而导致机体免疫力下降,患病率增高。