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目的 探讨球结膜下注射雷帕霉素对豚鼠形觉剥夺性近视(FDM)的干预作用及相关机制。方法 选取2~3周龄豚鼠80只(80眼),雌雄不限,随机分为4组:空白对照组、FDM组、雷帕霉素组、FDM+雷帕霉素组;空白对照组不做任何处理;FDM组单纯缝合豚鼠右眼眼睑;雷帕霉素组于实验第1天、第7天豚鼠右眼球结膜下注射雷帕霉素50 μg;FDM+雷帕霉素组于实验第1天、第7天豚鼠右眼球结膜下注射雷帕霉素50 μg后再缝合右眼眼睑。记录各组豚鼠实验前及实验第7天、第14天的眼轴长度、屈光度;并取各组豚鼠视网膜行过碘酸-雪夫染色(PAS染色)及透射电镜检查,观察各组豚鼠视网膜形态变化;取各组豚鼠巩膜行RT-PCR检测巩膜组织中mTOR、基质金属蛋白酶-2(MMP-2)、α-平滑肌肌动蛋白(α-SMA)及转化生长因子β1(TGF-β1)的mRNA表达;利用Western blot 检测各组豚鼠巩膜组织中AKT、p-AKT、mTOR、p-mTOR的蛋白表达。结果 FDM组与空白对照组相比,实验第7天、第14天豚鼠的右眼眼轴长度、屈光度增加,形成了相对近视;FDM组巩膜中MMP-2、α-SMA 的mRNA相对表达量与空白对照组相比均增加,TGF-β1 mRNA相对表达量减少,差异均具有统计学意义(均为P<0.05);与空白对照组相比,FDM组豚鼠巩膜中mTOR mRNA和AKT、P-AKT、mTOR、p-mTOR蛋白的相对表达量变化不大,差异均无统计学意义(均为P>0.05),但视网膜变薄,各层结构排列紊乱、疏松。雷帕霉素组与空白对照组相比,实验第7天、第14天豚鼠右眼眼轴长度、屈光度差异均无统计学意义(均为P>0.05),且视网膜形态无明显变化。FDM+雷帕霉素组与FDM组相比,实验第7天豚鼠右眼眼轴长度、屈光度差异均无统计学意义(均为P>0.05),实验第14天右眼眼轴长度和屈光度均减小,差异均有统计学意义(均为P<0.05),TGF-β1 mRNA的相对表达量增多,MMP-2、α-SMA、mTOR 的mRNA和AKT、p-AKT、mTOR、p-mTOR的蛋白相对表达量均减少,差异均有统计学意义(均为P<0.05)。结论 雷帕霉素球结膜下注射可延缓豚鼠FDM的形成,可能是通过抑制PI3K/AKT/mTOR信号通路、调节巩膜中的MMP-2、TGF-β1、α-SMA的表达而发挥作用的,且对正常豚鼠视网膜结构没有影响。 相似文献
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《Journal of stroke and cerebrovascular diseases》2022,31(4):106370
Background and AimsAntiretroviral treatment (ART) era HIV-associated stroke data from Sub-Saharan Africa is limited. We determined the prevalence of HIV in patients presenting with acute symptomatic stroke; and compared risk factors, clinical characteristics, and brain imaging with age-matched stroke patients without HIV.MethodsWe conducted a retrospective study of adults presenting with any type of stroke to a South African tertiary hospital in a 12-month period. Patients living with HIV (PLWH) and HIV-uninfected patients (HIV-) were matched on age group (1:2 ratio).ResultsTheacute stroke prevalence of HIV infection was 9.3% (95%CI: 7.4-11.2%) among 884 stroke patients. Mean age at presentation in PLWH was 46 (±11) years compared to 55 (±14) years in HIV- (p<0.001). Hypertension (p=0.011) and dyslipidaemia (p=0.005) were less prevalent in PLWH. Concurrent infection was more prevalent in PLWH (p=<0.001), largely in patients with low CD4 counts. PLWH with higher CD4 counts had traditional risk factors and less concurrent infection. Among PLWH, 39.3% had been started / restarted on ART within 6-months. Basal ganglia infarcts (p=0.014) and multiple vascular territory involvement (p=0.002) was more common in PLWH. Clinical presentation, ischaemic stroke type, and in-hospital outcomes did not differ between groups.ConclusionStroke patients with HIV were younger, had less traditional cardiovascular risk factors, and more concurrent infections than patients without HIV when CD4 count was low. Recent ART initiation or reinitiation rates were high. Significant differences in CT brain imaging findings were seen. Understanding the multifactorial mechanisms underlying increased stroke risk in this population is crucial. 相似文献
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《Journal of stroke and cerebrovascular diseases》2022,31(4):106216
ObjectivesIntracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variations remain unknown. Our study reports updated trends of ICH incidence, mortality, and mortality to incidence ratio (MIR) across the US.Materials and MethodsObservational study to evaluate the incidence and mortality from ICH across the US. Data was obtained from Global Burden of Disease (GBD) database. Age-Standardized Incidence (ASIRs) and Death (ASDRs) Rates, as well as the Mortality- to-Incidence ratios (MIRs) for ICH in the US overall and state-wise from 1990-2017. Joinpoint regression analysis was used, with presentation of estimated annual percentage changes (EAPCs).ResultsOverall decrease in ASIRs, ASDRs, and MIRs in the US for both sexes. The 2017 mean ASIR was 25.67/100,000 for men and 19.17/100,000 for women, whereas mean ASDR was 13.96/100,000 for men and 11.35/100,000 for women. District of Columbia had greatest decreases in ASIR EAPCs for both men and women at -41.25% and -40.58%, respectively, and greatest decreases in ASDR EAPCs for men and women at -55.38% and -48.51%, respectively. MIR between 1990-2017 decreased in men by -12.12% and women by -7.43%. MIR increased in men from 2014-2017 (EAPC +2.2%) and in women from 2011-2017 (EAPC +1.0%).ConclusionDecreasing trends in incidence, mortality, and MIR. No significant trends in mortality were found in the last 6 years of the study period. MIR worsened in males from 2014-2017 and females from 2011-2017, suggesting decreased ICH-related survival lately. 相似文献
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糖基化终末产物(AGEs)体内多种组织中累积,通过调节相关因子表达及激活信号通路等诱发一系列生物学反应,引起年龄相关性疾病及神经退行性病变,如阿尔茨海默病、帕金森病、动脉粥样硬化。青光眼是一种视神经退行性病变,最终导致不可逆的视野缺失,是全球仅次于白内障导致视力丧失的主要原因。青光眼患者视网膜等眼组织中过多AGEs累积,通过激活信号通路、引发生物反应,对组织、细胞的结构及功能造成损伤,参与青光眼发生发展的病理过程。本文主要阐述AGEs在青光眼发病机制、治疗、筛查等相关研究中的最新进展,为青光眼的防治提供新的思路和研究方法。 相似文献
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目的:探讨综合护理干预在下肢骨折并发深静脉血栓形成患者中的应用效果。方法:将100例下肢骨折并发深静脉血栓形成的患者随机分为观察组和对照组各50例,对照组患者采用常规健康教育、饮食指导、运动指导等措施,观察组在常规护理基础上实施综合护理干预,比较两组患者依从性、满意度及生活质量改善情况。结果:观察组患者总依从率98%,对照组总依从率72%,两组比较差异有统计学意义(P<0.05);观察组总满意率96%,对照组总满意率70%,两组比较差异有统计学意义(P<0.05);观察组患者生活质量评分高于对照组(P<0.05)。结论:综合护理干预应用于下肢骨折并发深静脉血栓形成患者,可以改善患者的生活质量,提高其依从性及满意度,临床应用价值较高。 相似文献