Aberrantly expressed long non‐coding RNAs in air pollution‐induced congenital defects

Air pollution has been a serious public health issue over the past few decades particularly in developing countries. Air pollution exposure during pregnancy poses potential threat to offspring as the deleterious substances might pass through placenta to alter foetal development. A growing number of studies have demonstrated that long non‐coding RNAs (lncRNAs) participate in the development of many diseases, including congenital defects. Here, we used RNA sequencing to identify differentially expressed lncRNAs in air pollution‐exposed rat embryos compared with control group. Our data suggested that 554 lncRNAs (216 up‐regulated and 338 down‐regulated) were significantly differentially expressed in the air pollution‐exposed embryos. Moreover, potential cellular functions of these deregulated lncRNAs were predicted via KEGG signal pathway/GO enrichment analyses, which suggested the possible involvements of neurological process, sensory perception of smell and the G‐protein signalling pathway. Furthermore, potential functional network of deregulated lncRNAs and their correlated mRNAs in the development of congenital spinal abnormality was established. Our data suggested that lncRNAs may play a vital role in the pathophysiology of air pollution‐exposed congenital spinal malformation.     

心脏彩超评估高血压左心室肥厚伴左心衰竭患者心功能的临床价值及与NYHA分级的关系研究

目的:探讨心脏彩超评估高血压左心室肥厚(LVH)伴左心衰竭患者心功能的临床价值,分析其超声指标与美国纽约心脏病协会(NYHA)分级的相关性。方法:选择2017年5月至2018年5月我院收治的127例高血压LVH伴左心衰竭患者为观察组,根据NYHA分级将其分为NYHAⅡ级组(41例)、Ⅲ级组(47例)、Ⅳ级组(39例),另选择100例体检的健康志愿者为对照组。所有受试者均接受心脏彩超获得相关参数[左心房内径(LAD)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室短轴缩短率(LVFS)、左心室后壁厚度(LVPWT)、室间隔厚度(IVST)、左心室射血分数(LVEF)、左心室舒张早期充盈峰最大充盈速度/舒张晚期充盈峰最大峰值速度(E/A)比值、Tei指数],分析心脏彩超相关参数与NYHA分级之间相关性。结果:观察组患者LAD、LVEDD、LVESD、LVPWT、IVST、Tei指数高于对照组(P0.05),LVFS、LVEF、E/A比值低于对照组(P0.05)。Tei指数随着NYHA分级增高而增高(P0.05),LVFS、LVEF、E/A比值随着NYHA分级增高而降低(P0.05)。Spearman秩相关分析结果显示,Tei指数与NYHA分级呈正相关(rs=0.398,P0.05),LVFS、LVEF、E/A比值与NYHA分级呈负相关(rs=-0.285,-0.442,-0.305,P0.05)。结论:高血压LVH伴左心衰竭患者发生明显左室肥厚和左心功能降低,心脏彩超可准确评估高血压LVH伴左心衰竭患者的心功能和病情严重程度,且部分心脏彩超相关参数与NYHA分级相关。     

电针对大鼠心肺复苏后脑损伤的保护作用及对海马炎性因子表达的影响

目的:探讨电针对大鼠心肺复苏后脑损伤及海马炎性因子表达的影响。方法:雄性SD大鼠随机分三组:假手术组(Sham)、对照组(Control)、电针组(EA)。大鼠窒息8 min后进行心肺复苏,EA组于复苏同时在水沟、内关穴插入毫针并予以电针刺激,对照组仅在相同穴位插入毫针。计算大鼠复苏成功率,记录自主循环恢复时间,于复苏后24 h及72 h对大鼠进行神经功能缺损评分(NDS),水迷宫检测各组大鼠学习记忆能力,尼氏染色观察海马区神经元形态及存活数量,Western blot检测海马区炎性因子表达。结果:与Sham组相比,对照组与EA组大鼠复苏后24 h、72 h NDS降低,学习记忆能力明显减低,两组海马CA1区细胞排列紊乱、神经元存活数量减少,IL-10表达降低、IL-1与IL-6表达升高(P0.05)。而与对照组相比,EA组大鼠复苏成功率有所提高,但无统计学意义,自主循环恢复时间明显缩短(P0.05);复苏后24 h、72 h NDS评分提高(P0.05);水迷宫第六天逃避潜伏期缩短、空间探索能力显著增强(P0.05);海马CA1区细胞排列紊乱减轻,神经元存活数目增多;海马区炎性因子IL-1、IL-6表达降低,抗炎因子IL-10表达增多(P0.05)。结论:电针能够减轻大鼠心肺复苏后脑损伤,其保护作用可能与抑制炎性因子、促进抗炎因子表达有关。     

Direct Interaction of CaVβ with Actin Up-regulates L-type Calcium Currents in HL-1 Cardiomyocytes

Expression of the β-subunit (Ca_Vβ) is required for normal function of cardiac L-type calcium channels, and its up-regulation is associated with heart failure. Ca_Vβ binds to the α₁ pore-forming subunit of L-type channels and augments calcium current density by facilitating channel opening and increasing the number of channels in the plasma membrane, by a poorly understood mechanism. Actin, a key component of the intracellular trafficking machinery, interacts with Src homology 3 domains in different proteins. Although Ca_Vβ encompasses a highly conserved Src homology 3 domain, association with actin has not yet been explored. Here, using co-sedimentation assays and FRET experiments, we uncover a direct interaction between Ca_Vβ and actin filaments. Consistently, single-molecule localization analysis reveals streaklike structures composed by Ca_Vβ₂ that distribute over several micrometers along actin filaments in HL-1 cardiomyocytes. Overexpression of Ca_Vβ₂-N3 in HL-1 cells induces an increase in L-type current without altering voltage-dependent activation, thus reflecting an increased number of channels in the plasma membrane. Ca_Vβ mediated L-type up-regulation, and Ca_Vβ-actin association is prevented by disruption of the actin cytoskeleton with cytochalasin D. Our study reveals for the first time an interacting partner of Ca_Vβ that is directly involved in vesicular trafficking. We propose a model in which Ca_Vβ promotes anterograde trafficking of the L-type channels by anchoring them to actin filaments in their itinerary to the plasma membrane.     

Regulation of the Sarcoplasmic Reticulum Calcium Pump by Divergent Phospholamban Isoforms in Zebrafish

The sarcoplasmic reticulum calcium pump (SERCA) is regulated by the small integral membrane proteins phospholamban (PLN) and sarcolipin (SLN). These regulators have homologous transmembrane regions, yet they differ in their cytoplasmic and luminal domains. Although the sequences of PLN and SLN are practically invariant among mammals, they vary in fish. Zebrafish (zf) appear to harbor multiple PLN isoforms, one of which contains 18 sequence variations and a unique luminal extension. Characterization of this isoform (zfPLN) revealed that SERCA inhibition and reversal by phosphorylation were comparable with human PLN. To understand the sequence variations in zfPLN, chimeras were created by transferring the N terminus, linker, and C terminus of zfPLN onto human PLN. A chimera containing the N-terminal domain resulted in a mild loss of function, whereas a chimera containing the linker domain resulted in a gain of function. This latter effect was due to changes in basic residues in the linker region of PLN. Removing the unique luminal domain of zfPLN (⁵³SFHGM) resulted in loss of function, whereas adding this domain to human PLN had a minimal effect on SERCA inhibition. We conclude that the luminal extension contributes to SERCA inhibition but only in the context of zfPLN. Although this domain is distinct from the SLN luminal tail, zfPLN appears to use a hybrid PLN-SLN inhibitory mechanism. Importantly, the different zebrafish PLN isoforms raise the interesting possibility that sarcoplasmic reticulum calcium handling and cardiac contractility may be regulated by the differential expression of PLN functional variants.     

Constitutive Phosphorylation of Cardiac Myosin Regulatory Light Chain in Vivo

In beating hearts, phosphorylation of myosin regulatory light chain (RLC) at a single site to 0.45 mol of phosphate/mol by cardiac myosin light chain kinase (cMLCK) increases Ca²⁺ sensitivity of myofilament contraction necessary for normal cardiac performance. Reduction of RLC phosphorylation in conditional cMLCK knock-out mice caused cardiac dilation and loss of cardiac performance by 1 week, as shown by increased left ventricular internal diameter at end-diastole and decreased fractional shortening. Decreased RLC phosphorylation by conventional or conditional cMLCK gene ablation did not affect troponin-I or myosin-binding protein-C phosphorylation in vivo. The extent of RLC phosphorylation was not changed by prolonged infusion of dobutamine or treatment with a β-adrenergic antagonist, suggesting that RLC is constitutively phosphorylated to maintain cardiac performance. Biochemical studies with myofilaments showed that RLC phosphorylation up to 90% was a random process. RLC is slowly dephosphorylated in both noncontracting hearts and isolated cardiac myocytes from adult mice. Electrically paced ventricular trabeculae restored RLC phosphorylation, which was increased to 0.91 mol of phosphate/mol of RLC with inhibition of myosin light chain phosphatase (MLCP). The two RLCs in each myosin appear to be readily available for phosphorylation by a soluble cMLCK, but MLCP activity limits the amount of constitutive RLC phosphorylation. MLCP with its regulatory subunit MYPT2 bound tightly to myofilaments was constitutively phosphorylated in beating hearts at a site that inhibits MLCP activity. Thus, the constitutive RLC phosphorylation is limited physiologically by low cMLCK activity in balance with low MLCP activity.     

纳洛酮对心搏骤停患者心肺复苏后氧化应激反应及缺血缺氧性脑病的影响

目的:探讨纳洛酮对心搏骤停患者心肺复苏(CPR)后氧化应激反应及缺血缺氧性脑病的影响。方法:将我院收治的78例骤停时间≤10 min的心搏骤停患者随机分为治疗组和对照组,每组各39例。两组均按照美国心脏学会心肺复苏指南进行标准的心肺复苏,治疗组在此基础上静脉注射纳洛酮2 mg,复苏后用纳洛酮0.4 mg/(kg·d)微量注射泵24h持续泵入。比较两组的CPR成功率、血浆丙二醛(MDA)含量和谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)活性,监测其不同时点脑氧摄取量(CEO2)的变化。结果:与对照组比较,治疗组自主循环恢复成功率、复苏后24 h存活率均显著升高(P<0.05)。自主循环恢复后,治疗组SOD、GSH-PX活性较对照组明显增加(P<0.05);复苏后24 h,两组MDA含量均显著升高,SOD、GSH-PX活性明显减弱,而治疗组各氧化应激指标明显优于对照组(P<0.05)。两组患者在复苏早期CEO2迅速升高,但在复苏后24 h开始下降,48~72 h处于相对稳定的水平,治疗组各时间点CEO2均明显高于对照组(P<0.05)。结论:纳洛酮可减轻心搏骤停患者CPR后体内氧化应激损伤和缺血缺氧性脑病,改善患者的预后。     

心脏手术围术期的血糖波动与术后急性肾损伤

心脏手术围术期高血糖与术后并发症的关系已经得到大量研究,高血糖与术后肾功能损伤的关系存在着不同的观点,但是对于围术期血糖水平的波动与术后肾损伤的研究甚少。本文概述了心脏手术围术期血糖水平波动对术后肾功能损伤的影响,简要分析其损伤机制。研究表明,多种因素可以增加围术期血糖水平的波动,对多项围术期高血糖是否增加术后肾功能损伤的研究争议分析发现,围术期血糖水平的波动对术后肾损伤的发生起到潜在作用,其损伤机制主要在于引起氧化应激和血流动力学的波动。相信围术期血糖水平的波动对术后肾功能损伤的影响的进一步的研究,将有助于降低心脏手术后急性肾损伤患者术后并发症的发生率。     

STAT蛋白在心脏疾病中作用的研究进展

细胞信号转导途径JAK-STAT通路是细胞因子由细胞膜外向细胞核内传递信号的主要途径,参与了介导细胞生长,增殖分化,炎症反应,细胞凋亡等多种病理生理过程。STAT蛋白是JAK-STAT通路的核心分子,且所有的STAT蛋白在心脏中均有表达,改变其分子结构能调节STAT蛋白的生物学活性。目前,已有大量文献报道了STAT1、STAT3在心脏疾病中的作用,缺血性心脏疾病、缺血再灌注引起心肌损伤、心肌肥大、心肌梗塞后的心脏衰竭以及缺血预/后处理介导的心脏保护作用等均与STAT蛋白密切相关。本文主要就近年来STAT蛋白在心脏疾病中作用的研究进展进行了综述。     

七氟烷联合利多卡因对全身麻醉患者心功能影响研究

目的:通过观察七氟烷联合利多卡因对全身麻醉患者心功能影响,探究七氟烷联合利多卡因诱导全身麻醉的临床价值。方法:选取我院外科收治的需行非心脏手术并进行全身麻醉诱导的患者70例,随机分为两组,其中对照组35例,予单纯七氟烷诱导全身麻醉行非心脏手术;实验组35例,予以七氟烷联合利多卡因进行全身麻醉诱导。分别于全身麻醉诱导前(T1)、诱导插管后30分钟(T2)、诱导插管后1小时(T3)3个时间点对患者心功能进行观察和监测,对比观察各个时间点的外周血管阻力(SVR)、每搏输出量(SV)、每分输出量(CO)、峰值速度(Vp K)、心率(HR)、净射血时间百分比(ET%)等指标。结果:1实验组和对照组患者在T1时SVR、SV、CO、Vp K、HR、ET%水平均无明显变化,差异无统计学意义(P0.05);2与T1相比,实验组和对照组患者在T2和T3的SVR、SV、CO、Vp K、HR水平均明显下降,差异有统计学意义(P0.05),ET%升高明显,差异有统计学意义(P0.05);3实验组在T2和T3时SVR、SV、CO、Vp K、HR水平均明显高于对照组,差异有统计学意义(P0.05),ET%较对照组明显下降,差异有统计学意义(P0.05)。结论:单纯七氟烷诱导和七氟烷联合利多卡因诱导全身麻醉对心功能均有影响,但与单纯七氟烷组相比,七氟烷联合利多卡因组对心功能的影响更小,更适合于外科手术的全身麻醉诱导,对临床具有指导意义,值得临床推广。