First-Phase Ejection Fraction Is a Powerful Predictor of Adverse Events in Asymptomatic Patients With Aortic Stenosis and Preserved Total Ejection Fraction

Objectives

This study investigated the prognostic value of first-phase ejection fraction (EF1) in patients with aortic stenosis (AS), a condition in which left ventricular dysfunction as measured by conventional indices is an indication for valve replacement.

心宝丸联合米力农治疗终末期心力衰竭的临床研究

目的探讨心宝丸联合米力农治疗终末期心力衰竭的临床效果。方法选取2016年3月—2019年3月延安大学附属医院收治的96例终末期心力衰竭患者,随机分为对照组和治疗组,每组各48例。对照组静脉滴注米力农注射液,负荷量50μg/kg,缓慢静脉注射(10 min);继以0.50μg/(kg?min)静脉点滴维持,每日最大剂量不超过1.13 mg/kg。治疗组在对照组治疗基础上口服心宝丸,6丸/次,3次/d。两组均连续治疗5d。观察两组的临床疗效,比较两组治疗前后心功能指标、血流动力学指标、血清学指标和中性粒细胞(NEUT)与淋巴细胞(LYM)比值(NLR)的变化情况。结果治疗后,对照组和治疗组的总有效率分别是77.1%、91.7%,两组比较差异具有统计学意义(P0.05)。治疗后,两组左心室收缩、舒张末期内径(LVESD和LVEDD)值均显著小于治疗前,而左室射血分数(LVEF)值均显著增高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组LVESD、LVEDD值低于对照组,而LVEF高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组每搏输出量(SV)、心脏收缩力指数(HI)均较治疗前显著增加,而舒张功能指数(O/C)、肺动脉楔压(PAWP)、总外周阻力(TPR)均显著减小,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组SV、HI值高于对照组,而O/C、PAWP、TPR值低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清B型利钠肽(BNP)、可溶性生长刺激表达基因2蛋白(s ST2)、C反应蛋白(CRP)、外周血NLR均较治疗前显著下降,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组血清学指标和NLR均显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论心宝丸联合米力农治疗终末期心力衰竭具有较好的临床疗效,有助于逆转患者心室重塑,增强心脏功能,改善血流动力学状态,减轻机体炎症反应,具有一定的临床推广应用价值。     

Ultrastructural localization of active zone and synaptic vesicle proteins in a preassembled multi-vesicle transport aggregate

Although it has been suggested that presynaptic active zone (AZ) may be preassembled, it is still unclear which entities carry the various proteins to the AZ during synaptogenesis. Here, I propose that aggregates of dense core vesicles (DCV) and small clear vesicles in the axons of young rat hippocampal cultures are carriers containing preformed AZ and synaptic vesicle (SV) components on their way to developing synapses. The aggregates were positively labeled with antibodies against Bassoon and Piccolo (two AZ cytomatrix proteins), VAMP, SV2, synaptotagmin (three SV membrane proteins), and synapsin I (a SV-associated protein). Bassoon and Piccolo labeling were localized at dense material both in the aggregates and at the AZ. In addition to the SV at the synapses, the SV membrane proteins labeled the clear vesicles in the aggregate as well as many other SV-like and pleiomorphic vesicular structures in the axons, and synapsin I labeling was associated with the vesicles in the aggregates. In single sections, these axonal vesicle aggregates were approximately 0.22 by 0.13 microm in average dimensions and contain one to two DCV and five to six small clear vesicles. Serial sections confirmed that the aggregates were not synaptic junctions sectioned en face. Labeling intensities of Bassoon and Piccolo measured from serially sectioned transport aggregates and AZ were within range of each other, suggesting that one or a few aggregates, but not individual DCV, can carry sufficient Bassoon and Piccolo to form an AZ. The present findings provide the first ultrastructural evidence localizing various AZ and SV proteins in a preassembled multi-vesicle transport aggregate that has the potential to quickly form a functional active zone.     

Preventing HIV-1 Tat-induced neuronal apoptosis using antioxidant enzymes: mechanistic and therapeutic implications

HIV-1 proteins, especially gp120 and Tat, elicit reactive oxygen species (ROS) and cause neuron apoptosis. We used antioxidant enzymes, Cu/Zn superoxide dismutase (SOD1) and glutathione peroxidase (GPx1) to study signaling and neuroprotection from Tat-induced apoptosis. SOD1 converts superoxide to peroxide; GPx1 converts peroxide to water. Primary human neurons were transduced with SV40-derived vectors carrying SOD1 and GPx1, then HIV-1 Tat protein was added. Both SV(SOD1) and SV(GPx1) delivered substantial transgene expression. Tat decreased endogenous cellular, but not transduced, SOD1 and GPx1. Tat rapidly increased neuron [Ca(2+)](i), which effect was not altered by SV(SOD1) or SV(GPx1). However, both vectors together blocked Tat-induced [Ca(2+)](i) fluxes. Similarly, neither SV(SOD1) nor SV(GPx1) protected neurons from Tat-induced apoptosis, but both vectors together did. Tat therefore activates multiple signaling pathways, in one of which superoxide acts as an intermediate while the other utilizes peroxide. Gene delivery to protect neurons from Tat must therefore target both.     

Catalytic turnover of STAT1 allows PIV5 to dismantle the interferon-induced anti-viral state of cells

A dynamic model of STAT1 degradation by the V protein of parainfluenza virus 5 (PIV5; formerly SV5) has been proposed. In it, the V protein functions as a bipartite adaptor linking DDB1, a component of a cellular SCF-like ubiquitin E3 ligase complex, to STAT2, which in turn binds STAT1 and presents STAT1 to the E3 ligase complex for ubiquitination and subsequent degradation. Furthermore, it appears that loss of STAT1 from the complex results in decreased affinity of V for STAT2 such that STAT2 either dissociates from V or is displaced by STAT1/STAT2 complexes, facilitating the cycling of the DDB1/PIV5 V containing E3 complex for further rounds of STAT1 ubiquitination and degradation. By determining the approximate number of molecules of V, DDB1, STAT1 and STAT2 present in IFN-treated 2fTGH cells, we provide additional evidence for this dynamic model of STAT1 degradation. These results show that (i) in IFN-treated cells there is approximately 4-fold less STAT2 and 15-fold less DDB1 than STAT1 per cell and thus DDB1 and STAT2 must repeatedly acquire more STAT1 for degradation to go to completion, and (ii) approximately 600 molecules of V protein per cell can target as many as 120,000 molecules of STAT1 for degradation in the absence of either viral or cellular protein synthesis. The importance of this mechanism in terms of the ability of the virus to dismantle the IFN-induced anti-viral state of cells is discussed.     

利福霉素钠与利福平治疗肺结核安全性评价

目的 比较利福霉素钠和利福平在治疗肺结核中的安全性.方法 792例肺结核患者分为利福霉素钠组(393例)和利福平组(399例),治疗2个月后评价其安全性.结果 利福霉素钠不良反应发生率(12.47％),较利福平(18.29％)低,严重不良反应发生率:利福霉素钠为1.78％,利福平为5.76％,差异有统计学意义;主要表现为肝损伤、过敏反应、肾功能损伤、血细胞减少和消化道不适.结论 利福霉素钠的不良反应发生率和严重程度小于利福平,若患者不能耐受利福平,可考虑利福霉素钠作为替代治疗.     

Characterization of angiotensin II-receptor subtypes in podocytes

Glomerular podocytes play a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by angiotensin II (Ang II) through activation of cell-surface receptors. Although studies suggest that podocytes express receptors for Ang II, the Ang II binding site has not been characterized with radioligand binding techniques. We therefore used iodine 125-labeled Ang II to monitor Ang II-receptor density during differentiation of a mouse podocyte cell line. Scatchard analyses of equilibrium binding data revealed a single class of high-affinity binding sites (dissociation constant approximately 3 nmol/L) in both differentiated and nondifferentiated cells. During differentiation, the density of Ang II-receptor sites increased roughly 15-fold in differentiated podocytes (maximal density of specific binding sites 881 fmol/mg protein) compared with that in nondifferentiated cells (52 fmol/mg protein; P<.005). Glomerular podocytes expressed messenger RNA for AT1A, AT1B, and AT2 receptor subtypes, and competitive binding studies found that differentiated podocytes expressed mostly AT1 receptors (approximately 75%) with lesser amounts of AT2 (approximately 25%). Up-regulation of Ang II-receptor number was associated with increased Ang II-receptor responsiveness, as evidenced by enhanced Ang II-stimulated inositol phosphate (IP) generation and incorporation of tritiated thymidine. Both [3H]thymidine incorporation and IP generation were mediated by AT1-receptor activation. These data suggest that glomerular podocytes express a high-affinity binding site for Ang II with pharmacologic characteristics of both AT1 and AT2 receptors. This receptor site is up-regulated during podocyte differentiation, and receptor activation induces both IP generation and DNA synthesis by AT1-dependent mechanisms. We speculate that activation of podocyte Ang II receptors contributes to glomerular damage in disease states.     

利福霉素钠制剂的无菌检查法方法学研究

目的：完善利福霉素钠制剂的无菌检查方法.方法：采用薄膜过滤,选用组氨酸-卵磷脂-聚山梨酯80混合溶液作为冲洗液进行无菌检查.结果：此法能有效消除抑菌成分的干扰,各试验菌生长良好.结论：经过方法学验证,所建立的方法适用于注射用利福霉素钠及利福霉素钠注射液的无菌检查.     

Renal transplantation and polyomavirus infection: recent clinical facts and controversies

Abstract: Although many articles have been published on polyomavirus‐induced pathologies in transplant recipients, our knowledge regarding their clinical aspects remains relatively limited. In fact, the number of questions and controversies on the subject seems even to be increasing as new publications continue to appear. This article presents some of these controversies through a brief review of recent clinical facts about the three polyomaviruses that infect humans – JC virus, simian virus 40, and BK virus – as they relate to renal transplantation.