Clinical Presentations,Antiplatelet Strategies and Prognosis of Patients with Stent Thrombosis: An Observational Study of 140 Patients

Background

Until now there has been scarce evidence regarding an optimal antiplatelet strategy and clinical outcomes for patients who had suffered from stent thrombosis (ST).

Methods and Results

140 patients who suffered from stent thrombosis were prospectively registered. Patients received dual (aspirin and 150 mg clopidogrel, N = 66) or triple (additional cilostazol, N = 74) antiplatelet therapy at the physician’s discretion. Thereafter platelet reactivity and one year clinical outcomes were analyzed. The primary outcome included the composite of cardiac death, non-fatal myocardial infarction (MI) or stroke at one year,which developed in 41 (29.3%) patients, consisting of 31 (22.1%) cardiac death, 9 (6.4%) non-fatal MI and 1 (1.4%) stroke. Recurrent definite and probable ST according to ARC definition was observed in 8 (5.7%) and 14 (10.0%) patients, respectively. Triple therapy was associated with significantly lower platelet reactivities (50.2±17.8, % vs. 59.6±17.2, %, P = 0.002) compared to high dose dual antiplatelet therapy. However, the incidence of primary events (24.3% vs. 34.8%, P = 0.172) did not differ between triple and dual antiplatelet therapies. High on-treatment platelet reactivity (HR: 8.35, 95% CI: 2.234∼30.867, P = 0.002) and diabetes (HR: 3.732, 95% CI: 1.353∼10.298, P = 0.011) were independent predictors of primary events.

Conclusions

Patients who suffered from stent thrombosis have a poor prognosis even after revascularization with intensive antiplatelet therapy. Triple antiplatelet therapy was more effective in reducing on-treatment platelet reactivity, compared to high dose dual antiplatelet therapy.     

Lys842 in Neuronal Nitric-oxide Synthase Enables the Autoinhibitory Insert to Antagonize Calmodulin Binding, Increase FMN Shielding, and Suppress Interflavin Electron Transfer

Neuronal nitric-oxide synthase (nNOS) contains a unique autoinhibitory insert (AI) in its FMN subdomain that represses nNOS reductase activities and controls the calcium sensitivity of calmodulin (CaM) binding to nNOS. How the AI does this is unclear. A conserved charged residue (Lys⁸⁴²) lies within a putative CaM binding helix in the middle of the AI. We investigated its role by substituting residues that neutralize (Ala) or reverse (Glu) the charge at Lys⁸⁴². Compared with wild type nNOS, the mutant enzymes had greater cytochrome c reductase and NADPH oxidase activities in the CaM-free state, were able to bind CaM at lower calcium concentration, and had lower rates of heme reduction and NO synthesis in one case (K842A). Moreover, stopped-flow spectrophotometric experiments with the nNOS reductase domain indicate that the CaM-free mutants had faster flavin reduction kinetics and had less shielding of their FMN subdomains compared with wild type and no longer increased their level of FMN shielding in response to NADPH binding. Thus, Lys⁸⁴² is critical for the known functions of the AI and also enables two additional functions of the AI as newly identified here: suppression of electron transfer to FMN and control of the conformational equilibrium of the nNOS reductase domain. Its effect on the conformational equilibrium probably explains suppression of catalysis by the AI.     

Regulation of emotional memory by hydrogen sulfide: role of GluN2B‐containing NMDA receptor in the amygdala

As an endogenous gaseous molecule, hydrogen sulfide (H₂S) has attracted extensive attention because of its multiple biological effects. However, the effect of H₂S on amygdala‐mediated emotional memory has not been elucidated. Here, by employing Pavlovian fear conditioning, an animal model widely used to explore the neural substrates of emotion, we determined whether H₂S could regulate emotional memory. It was shown that the H₂S levels in the amygdala of rats were significantly elevated after cued fear conditioning. Both intraamygdala and systemic administrations of H₂S markedly enhanced amygdala‐dependent cued fear memory in rats. Moreover, it was found that H₂S selectively increased the surface expression and currents of NMDA‐type glutamate receptor subunit 2B (GluN2B)‐containing NMDA receptors (NMDARs) in lateral amygdala of rats, whereas blockade of GluN2B‐containing NMDARs in lateral amygdala eliminated the effects of H₂S to enhance amygdalar long‐term potentiation and cued fear memory. These results demonstrate that H₂S can regulate amygdala‐dependent emotional memory by promoting the function of GluN2B‐containing NMDARs in amygdala, suggesting that H₂S‐associated signaling may hold potential as a new target for the treatment of emotional disorders.

     

白鱀豚饲养池水质某些理化因子的变动规律

自来水中的低量余氯对白暨豚无明显的刺激作用。豚池水温的变化情况与长江中、下游相似,极温对豚有不利影响。不同温度下,池水中磷酸盐含量的日增加率有显著差异,铵氮和硝酸盐氮的日增加系数相近,分别为0.327和0.2468,而亚硝酸盐氮的日增加系数在0.397—0.539之间,受温度的影响较大。池水有机物耗氧量增加不显著,含量与时间的相关式符合Y=aX~b型。缺少阳光照射是池水无机氮化合物增加较快、有机物分解较慢的原因之一。     

Crystallization Control of Ternary‐Cation Perovskite Absorber in Triple‐Mesoscopic Layer for Efficient Solar Cells

Controlling the crystallization of organic–inorganic hybrid perovskite is of vital importance to achieve high performing perovskite solar cells. The growth mechanism of perovskites has been intensively studied in devices with planar structures and traditional structures. However, for the printable mesoscopic perovskite solar cells, it is difficult to study the crystallization mechanism of perovskite owing to the complicated mesoporous structure. Here, a solvent evaporation controlled crystallization method to achieve ideal crystallization in the mesoscopic structure is provided. Combining results of scanning electron microscope and X‐ray diffraction, it is found that adjusting the evaporation rate of solvent can control the crystallization rate of perovskite and a model for the crystallization process during annealing in mesoporous structures is proposed. Finally, a homogeneous pore filling in the mesoscopic structure without any additives is successfully achieved and a stabilized power conversion efficiency of 16.26% using ternary‐cation perovskite absorber is realized. The findings will provide better understanding of perovskite crystallization in printable mesoscopic perovskite solar cells and pave the way for the commercialization of perovskite solar cells.     

Effects of rapid cooling on articular cartilage

In order to improve the technique and protocols of cryopreservation of articular cartilage, a study was carried out to assess the effects of rapid cooling on the intact articular cartilage. Cartilage slices with a thickness ranging from 0.2 to 0.5 mm taken from bovine metacarpal-phalangeal joints were subjected to rapid cooling by immersing them in liquid nitrogen with and without treatment of the VS55 cryoprotective agent (CPA). The ultrastructure, chondrocyte viability, swelling property, and glycosaminoglycan (GAG) content were then examined before and after cryopreservation to give qualitative and quantitative evaluation on the functional state of both chondrocytes and extracellular matrix. The transmission electron microscopy study demonstrated that damage to chondrocytes without CPA was far more pronounced than those with VS55 protection while the structure of the extracellular matrix altered little in either group. The cell viability assay showed that although the exposure to VS55 led to about 36% chondrocytes losing membrane integrity, the VS55 could provide protection to chondrocytes during rapid cooling and thawing, with approximately 51% of the cells having survived rapid cooling compared to fewer than 5% in the absence of CPA. There were no significant differences in degrees of swelling or the GAG contents of cartilage slices after cryopreservation indicating rapid freezing caused little damage to the matrix. Future research activities include searching improved CPA formulation, optimising the treatment protocol and investigating the long-term effects of rapid cooling on articular cartilage.     

Effects of phenolic compounds on adventitious root formation and oxidative decarboxylation of applied indoleacetic acid in <Emphasis Type="Italic">Malus</Emphasis> ‘Jork 9’

Stem slices (1-mm thick) cut from apple microshoots were cultured on a modified Murashige-Skoog medium with indole-3-acetic acid (IAA) or α-naphthaleneacetic acid (NAA), and increasing concentrations of various phenolic compounds. Both auxins were added at a concentration suboptimal for rooting. Indole-3-acetic acid is metabolized through oxidation and conjugation but NAA through conjugation only; which might have affected the results. With IAA, all tested orthodiphenols, paradiphenols and triphenols promoted adventitious root formation from the stem slices. Ferulic acid (FA, a methylated orthodiphenol) had the largest effect and increased the number of adventitious roots from 0.9 to 5.8. With NAA there was little or no promotion after addition of phenolics. Phloroglucinol (a triphenol) and FA were examined in detail. Their effects on the dose–response curve of IAA and the timing of their action indicated that both acted as antioxidants protecting IAA from decarboxylation and the tissue from oxidative stress. Experiments with carboxyl-labelled IAA showed that IAA was massively decarboxylated by the slices and that decarboxylation was strongly reduced by phenolics. Decarboxylation was to a great extent attributable to the wound response and did not occur to such an extent in non-wounded plant tissues. In shoots, FA promoted little rooting. Slices were cultured on top of the medium and shoots were stuck into the medium. Possibly, the anaerobic conditions in the medium near the basal part of the stem of shoots reduced the wound response and consequently decarboxylation of IAA. The monophenolic compound salicylic acid (SA) promoted IAA decarboxylation. Accordingly, SA reduced rooting when added during the initial days of the rooting process (the period during which auxin enhances rooting), and promoted outgrowth of root primordia later on (the period during which auxin inhibits rooting).