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21.
A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca2+ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.  相似文献   
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目的 通过阿霉素(Dox)复制大鼠慢性心力衰竭(CHF)模型,观察Liguzinediol对CHF大鼠心功能的影响。方法 通过血流动力学观察Liguzinediol对Dox(腹腔注射,2 mg/kg)诱导的CHF大鼠左心室内压最大上升/下降速率(±dp/dtmax)、左心室内压(LVSP)、动脉收缩压(ASP)、动脉舒张压(ADP)和心率(HR)的变化;观察Liguzinediol对血清一氧化氮(NO)、一氧化氮合成酶(NOS)、超氧化物歧化酶(SOD)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)以及血浆中丙二醛(MDA)的影响。结果 Liguzinediol能增加LVSP、+dp/dtmax、ASP、ADP、AP、HR,降低-dp/dtmax(P<0.05~0.01);降低NO、iNOS以及MDA的浓度,同时增强了SOD的活性(P<0.05~0.01);抑制IL-6和TNF-α的生成(P<0.05~0.01)。结论 Liguzinediol可明显改善Dox诱导的CHF大鼠血流动力学指标,减少模型大鼠炎症因子的释放以及抑制氧自由基的生成。   相似文献   
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目的 了解医学生学习《健康教育》课程的满意度、需求度现状及差异,为《健康教育》课程优化提供参考。方法 以某医科大学在校临床医学生为研究对象,分析医学生对课程内容的需求度和满意度及二者差异。课程内容包括服药依从性、戒烟干预、合理膳食、心理压力管理、中医康复技术、慢性传染病健康教育、急性传染病健康教育、移动健康技术教育、运动康复指导及健康促进理论。采用频数和构成比指标进行统计描述,采用卡方检验进行健康教育课程学习情况与专业/ 学制之间、相关课程内容学习的需求度与学制的差异,相关课程内容学习需求度与满意度的关联比较采用秩和检验。以P < 0.05 为差异具有统计学意义。结果 戒烟干预、合理膳食、心理压力管理、中医康复技术、慢性传染病健康教育、急性传染病健康教育、移动健康技术教育及健康促进理论八项的学习需求度在长学制医学生与五年制医学生中的总体分布位置不同(U = 2.4、2.2、2.5、2.3、2.4、2.4、2.3、2.0,P 均< 0.05);服药依从性、戒烟干预、合理膳食、心理压力管理、慢性传染病健康教育、急性传染病健康教育、移动健康技术教育及运动康复指导八项的满意度与需求度之间的总体位置分布不同(U = 6.2、5.2、7.2、9.2、5.9、6.1、2.1、3.2,P 均< 0.05);不同学制的医学生对于慢性病人、老年人、孕产妇、传染病人、高危人群和职业暴露人群的健康教育重点关注人群侧重有所不同,其差异具有统计学意义(χ2 = 8.9、14.2、9.9、6.9、23.9、17.8,P 均< 0.05);在教学方式上,不同学制的医学生对于教师课堂讲授和小组讨论的偏好上的差异具有统计学意义(χ2=6.3、9.5,P 均< 0.05)。结论 当前健康教育课程的教学内容和结构未能完全满足不同学制、年级医学生的学习需求,需要对课程教学内容、教学方式和开设时间进行进一步的优化设计。  相似文献   
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彭瑶  胡立  蒲虹 《中国热带医学》2019,19(7):696-699
目的 分析HBV患者YKL-40、CA19-9、GP73水平差异及与患者病情轻重程度的相关性,探讨HBV患者病情的判定指标。方法 选取2015年5月—2018年5月收治的100例HBV患者,其中慢性HBV感染组40例、慢性乙型肝炎组36例、HBV相关肝硬化组24例,同期选择我院健康体检的健康者50例作为健康对照组;检测患者血中YKL-40、CA19-9、GP73水平;分析HBV感染患者血清YKL-40、CA19-9、GP73水平与病情轻重程度的相关性。结果 慢性HBV感染、慢性乙型肝炎及HBV相关肝硬化患者血中YKL-40水平分别为(36.38±4.19)ng/mL 、(49.02±4.32)ng/mL、(65.14±5.21)ng/mL ,CA19-9分别为(12.03±1.03)KU/L、(13.84±0.98)KU/L、(16.94±0.81)KU/L,GP73分别为(47.22±5.38)ng/mL 、(98.53±10.24)ng/mL 、(229.85±12.19)ng/mL,均明显高于对照组的(28.19±3.27)ng/mL 、(7.34±0.92)KU/L 、(30.93±3.89)ng/mL,均P=0.000 0。随着慢性HBV感染者、慢性乙型肝炎患者和不同HBV相关肝硬化患者肝脏炎症及纤维化程度加重,患者血中YKL-40、CA19-9和GP73也随之显著增加,均P=0.000 0;YKL-40、CA19-9和GP73均是影响HBV感染患者体内炎症坏死及肝脏纤维化的独立性影响因素,差异有统计学意义(P<0.05)。结论 HBV感染患者血清中YKL-40、CA19-9、GP73水平是HBV感染患者病情轻重程度的独立性影响因素。  相似文献   
28.

Introduction/Hypothesis

Recruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014–2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study.

Methods

An online survey which included participants’ prior experience with clinical trials, motivations to participate (including financial incentives), and demographic information was developed to examine the motivations of healthy participants in two phase 1 clinical vaccine trials conducted at the Canadian Center for Vaccinology in Halifax, Nova Scotia. Participants were invited via email to complete the online survey. Readability and clarity were assessed through pilot testing.

Results

A total of 49 (55.7%) of 88 participants of the two studies completed the survey (22 [55%] of 40 participants from the Ebola vaccine study and 27 [56.3%] of 48 from the adjuvanted influenza vaccine study). Motivations that were most frequently ranked among participants' top three in both trials were (1) wanting to contribute to the health of others, (2) wanting to participate in something important, (3) wanting to contribute to the advancement of science, and (4) wanting to receive an incentive such as money or a tablet.

Conclusions/Recommendations

Although media attention and financial compensation were more often cited by Ebola vaccine trial participants as a reason to participate, both altruistic and self-interested factors were important motivations for participants in their decision to participate in a phase 1 vaccine clinical trial.  相似文献   
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Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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