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排序方式: 共有434条查询结果,搜索用时 15 毫秒
1.
Mutations in the Na-K-2Cl co-transporter NKCC2 lead to type I Bartter syndrome, a life-threatening kidney disease. We previously showed that export from the ER constitutes the limiting step in NKCC2 maturation and cell surface expression. Yet, the molecular mechanisms involved in this process remain obscure. Here, we report the identification of chaperone stress 70 protein (STCH) and the stress-inducible heat shock protein 70 (Hsp70), as two novel binding partners of the ER-resident form of NKCC2. STCH knock-down increased total NKCC2 expression whereas Hsp70 knock-down or its inhibition by YM-01 had the opposite effect. Accordingly, overexpressing of STCH and Hsp70 exerted opposite actions on total protein abundance of NKCC2 and its folding mutants. Cycloheximide chase assay showed that in cells over-expressing STCH, NKCC2 stability and maturation are heavily impaired. In contrast to STCH, Hsp70 co-expression increased NKCC2 maturation. Interestingly, treatment by protein degradation inhibitors revealed that in addition to the proteasome, the ER associated degradation (ERAD) of NKCC2 mediated by STCH, involves also the ER-to-lysosome-associated degradation pathway. In summary, our data are consistent with STCH and Hsp70 having differential and antagonistic effects with regard to NKCC2 biogenesis. These findings may have an impact on our understanding and potential treatment of diseases related to aberrant NKCC2 trafficking and expression.  相似文献   
2.
叶鹏  谭兴  冷岳奇  王杨凯  王伟忠 《金属学报》2021,26(12):1335-1343
高血压病是一种危害人类健康的严重疾病,尽管高血压的临床治疗已经取得较好疗效,但仍存在不少药物耐受性等不同类型的顽固性高血压,而且高血压的并发症如心力衰竭、脑卒中等发病率仍居高不下,因此,非药物治疗策略的深入研发与应用已成为高血压治疗的一个重要方面。交感神经系统在高血压发生发展中起着关键性作用,目前大多数高血压防治的非药物治疗技术主要通过靶向调节机体交感神经功能来实现,这些技术主要包括深部脑刺激、肾动脉神经射频消融术、中央髂动静脉吻合术、压力反射激活疗法、血管内压力反射放大疗法、颈动脉体切除术等。本综述重点对上述基于交感神经系统的非药物治疗方法的应用现状和相关优缺点进行回顾总结,为高血压的有效治疗提供新思路和多重选择。  相似文献   
3.
袁己百  马志民  殷攀  张华 《连铸》2021,40(6):85-90
针对国内某特钢厂新上的四流H型双通道感应加热中间包,为改善中间包内流体流动状态,设计了倒八字型与V型两种控流装置。应用数值模拟的方法对两种不同控流装置下的中间包流场、RTD曲线、温度场进行了模拟。结果表明,倒八字型控流装置平均停留时间1 469.6 s,死区体积比5.83%,边部水口与中间水口的最大温差3 K;与V型控流装置相比,平均停留时间延长了41.9 s,死区体积相应降低了4.09%,边部水口与中间水口的最大温差减少了2 ℃。湍流抑制器+倒八字型控流装置设计能更好改善四流大方坯H型双通道感应加热中间包流体流动性。  相似文献   
4.
A cross-sectional study was conducted to investigate the impact of solid fuel use for heating and cooking on blood pressure (BP) and hypertension, using data from the China Health and Retirement Longitudinal Study (CHARLS). The primary fuels used for indoor heating and cooking were collected by questionnaires, respectively. Hypertension was defined based on self-report of physician's diagnosis, and/or measured BP, and/or anti-hypertensive medication use. Multivariate logistic regression models were constructed to assess the associations. Among 10 450 eligible participants, 68.2% and 57.2% used indoor solid fuel for heating and cooking, respectively. Compared with none/clean fuel users, solid fuel for heating was associated with elevated BP (adjusted β: 2.02, 95% CI: 1.04–3.01 for systolic BP; adjusted β: 1.36, 95% CI: 0.78–1.94 for diastolic BP) and increased risk of hypertension (adjusted odds ratio: 1.15, 95% CI: 1.03–1.29). The impact of indoor solid fuel for heating on BP was more evident in rural and north residents, and hypertensive patients. We did not detect any significant associations between solid fuel use for cooking and BP/hypertension. Indoor solid fuel use is prevalent in China, especially in the rural areas. Its negative impact on BP suggested that modernization of household fuel use may help to reduce the burden of hypertension in China.  相似文献   
5.
Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.  相似文献   
6.
ABSTRACT

Background: Many epidemiologic studies have explored the association between famine exposure and the risk of hypertension, but the results remain controversial. Objective: A meta-analysis was performed to determine the association between early life famine exposure, fetal famine exposure, and childhood famine exposure and risk of hypertension. Methods: A literature search was performed in PubMed, Web of science, Embase, and China National Knowledge Infrastructure for relevant articles published up to October 2016. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Sixteen studies from 14 articles for early life famine exposure, 11 studies from 10 articles for fetal famine exposure, and 10 studies from 8 articles for childhood famine exposure were included in our meta-analysis. Compared with unexposed group, the pooled RRs were (1.26; 95% CI, 1.11–1.44), (1.27; 95% CI, 1.08–1.49), and (1.32; 95% CI, 1.15–1.52) for early life famine exposure, fetal famine exposure, and childhood famine exposure, respectively. In subgroup analyses, the above-mentioned associations were consistent in cohort studies, and studies conducted in Asia. Conclusion: This meta-analysis confirmed the association between exposure to famine in early life and increased risk of hypertension in adulthood. Prevention of malnutrition during early life is an appropriate recommendation to prevent hypertension.  相似文献   
7.
目前随着直流输电技术的发展,直流滤波器高压电容器的运行可靠性、经济性逐渐成为研究的重点。本文依据某特高压直流输电工程直流滤波器高压电容器工况,针对直流滤波器高压电容器3种不同H型接线不平衡保护方案,重点从电容器单元间均压问题和电容器内部故障保护问题及经济性方面进行了分析,认为在设计制造水平允许的前提下,特高压直流滤波器高压电容器采用方案1并/臂(带内熔丝电容器)H型接线内部故障不平衡保护方式;在谐波电流较大的情况下,特高压直流滤波器高压电容器内部故障不平衡保护仍然可以采用原来的按元件击穿短路串数来整定原则,但是需要对内熔丝的熔断特性及对应温度进行校验。  相似文献   
8.
9.
《Planning》2019,(2)
目的分析24 h尿钠排泄与难治性高血压(resistant hypertension,RH)患者诊室血压及家庭自测血压(home blood pressure monitoring,HBPM)达标状态的关系。方法通过北京协和医院心内科门诊RH数据库,收集2017年10月至2018年3月间在北京协和医院心内科门诊就诊的RH患者临床资料,进行横断面调查。检测患者24 h尿钠,记录患者同期诊室血压、HBPM水平及临床用药情况,以所有患者24 h尿钠水平四分位数为分界点,将研究对象分为低尿钠、低-中尿钠、中-高尿钠及高尿钠4组。采用多因素Logistic回归,分析影响RH血压达标状态的危险因素。结果共202例RH患者入选本研究,男性107例,女性95例,平均年龄(59. 87±16. 30)岁。24 h尿钠平均水平为(198. 92±96. 59) mmol,年轻患者及体质量指数高者尿钠水平更高(P均<0. 001)。随尿钠升高,降压药物的服用种类显著增多(P=0. 001),早晨及上午的HBPM达标率低(P=0. 040,0. 032)。多因素Logistic回归分析显示,24 h尿钠水平与诊室血压(OR=2. 356,95%CI:1. 004~5. 533,P=0. 049),HBPM早晨血压(OR=2. 408,95%CI:1. 026~5. 650,P=0. 030)及HBPM上午血压(OR=2. 299,95%CI:1. 031~5. 129,P=0. 033)达标状态独立相关,而与下午及夜间HBPM血压达标状态无显著相关(P均>0. 05)。结论 24 h尿钠是RH患者诊室血压及HBPM早晨及上午血压达标的独立相关因素,限制钠盐摄入对减少RH患者血压波动、促进血压达标有重要作用。  相似文献   
10.
《Planning》2019,(2)
2017年,美国心脏病学会和美国心脏协会提出将高血压诊断标准降为130/80 mm Hg (1 mm Hg=0. 133 kPa),这与其他指南有所不同。降压治疗的核心目标在于靶器官的保护,近年来降压治疗与脑小血管病预防的相关问题日益受到临床重视。目前研究结果表明,降压治疗对腔隙性卒中患者的二级预防以及白质病变进展的预防可能有一定积极意义,但确切的降压目标值并未确定。血压与临床结局可能呈现J型关系,血压过低或过高可能均有害,而取得最大获益的降压目标有待进一步探索。  相似文献   
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