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  • 简介:AbstractDespite overwhelming evidence from large randomized clinical trials supporting a clear benefit of low-density lipoprotein cholesterol (LDL-C) lowering therapy on the primary and secondary prevention of atherosclerotic cardiovascular disease, data from epidemiological and clinical observations demonstrated an increased incidence of hemorrhagic stroke in patients with low LDL-C exposure (<70 mg/dL), especially among East Asians. Meanwhile, emerging studies have reported a paradoxical phenomenon in which hypercholesterolemia is associated with better short-term outcomes in acute coronary syndrome patients, the "lipid paradox." The underlying mechanism for these two closely connected clinical observations is not clear. This review aimed to summarize the evolution and clinical implications of these two low LDL-C related concepts, and proposed a "double-hit" hypothesis that may help explain these phenomena. It is worth noting that in the era of increasing use of high-intensity LDL-C lowering and dual antiplatelet strategies in atherosclerotic cardiovascular disease in patients receiving percutaneous coronary intervention, balancing the risk of thrombosis with bleeding complication should be a priority in clinical practice. Our hypothesis may raise clinicians’ awareness to identify potential high risk patients with low LDL-C (<70 mg/dL), especially among East Asians.

  • 标签: acute coronary syndrome bleeding hemorrhagic stroke lipid paradox risk factor
  • 简介:一个模拟模型一电子地控制了二个螺线管阀门燃料注射系统因为一台柴油机引擎在AMESim环境被建立。模型的精确性与试验性的数据通过比较被验证。在不同控制模式下面的主要注射的数量上的注射前控制参数的影响被分析。在喷洒控制阀门模式,主要注射的燃料数量逐渐地减少然后因为多注射居住时间的增加,到达稳定的水平。在针控制阀门模式,主要注射的燃料数量与升起的多注射居住时间增加;这效果在高速度的革命和大主要注射的脉搏宽度变得更明显。注射前脉搏宽度没在二个控制模式下面在主要注射的数量上有明显的影响;在主要注射的数量的变化在1mm3的范围。

  • 标签: 燃油喷射系统 控制参数 预喷射 电磁阀 柴油机 燃油量
  • 简介:在优核质,有DExD/Hhelicase家庭,的至少60个成员许多哪个能察觉到病毒的nucleic酸。由屏蔽所有已知的家庭成员,我们在myeloid作为一个新奇双strandedRNA(dsRNA)传感器识别了helicaseDHX33树枝状的房间(mDCs)。用小heteroduplexRNA(shRNA)的DHX33击倒堵住了mDCs的能力生产类型我干扰素(IFN)响应poly我:C和reovirus。DHX33的HELICc领域被显示poly绑我:C。在DHX33和IPS-1之间的相互作用被DHX33和IPS-1的C终端领域的HELICc区域调停(也指了MAVS和维萨卡)。由RNA干扰的DHX33表示的抑制堵住了poly我:地图kinases的导致C的激活,NF-κ;B和IRF3。在helicaseDHX33和IPS-1之间的相互作用独立于RIG-I/MDA5并且可以是为poly察觉到的一条新奇小径我:在mDCs的C和RNA病毒。

  • 标签: RNA病毒 双链RNA 树突状细胞 相互作用 解旋酶 检测
  • 简介:ThetransportpropertiesintheLa2/3(Ca1-xSrx)1/3MnO3(x=0,1/3,2/3)filmspreparedusingtheRFmagnetronsputteringmethodwereinvestigated.TheeffectoftheCa,Srdouble-dopingattheApositionintheLa2/3A1/3MnO3onthestructureofthetargetsandtransportofthefilmshasbeenstudied.Withtheincreaseofx,thestructuresofthetargetstransformfromtherhombohedralphasetothecubicphase;themetal-insulatorphasetransitiontemperature(Tp)ofthefilmsincreases;andthecorrespondingpeakresistivitydecreases.Allthephenomenacanbequalitativelyexplainedbythelatticeeffect.

  • 标签: 格子效应 传输性质 氧化锰薄膜 电子喷射 磁致电阻
  • 简介:AbstractBackground:The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD.Methods:A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency.Results:In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785).Conclusions:As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD.Trial registration:chictr.org.cn, No. ChiCTR-TRC-12003513

  • 标签: MUSKARDIA Stable coronary artery disease Angina Major adverse cardiovascular event
  • 简介:AbstractBackground:Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.Methods:A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.Results:V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95% CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.Conclusions:The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx? proj=124702).

  • 标签: COVID-19 Phase II Clinical trial Recombinant fusion protein vaccine Safety Immunogenicity
  • 简介:AbstractBackground:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.Methods:Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx? proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

  • 标签: Immunogenicity Safety SARS-CoV-2 Inactivated vaccine Neutralizing antibody
  • 简介:摘要:我国“十四五”规划中强调要保证制造业比重稳定,实现制造强国,纺织业制造业中占有重要的地位,同时为适应当下中国国情提出了双循环新发展格局,这对中国纺织业的发展有重大意义。本文收集整理对中国纺织业发展现状及发展趋势研究的文献,总结归纳中国纺 织业在双循环新发展格局下实现产业升级和高质量发展的建议和路径,为更多学者研究相关问题提供参考。

  • 标签: 纺织业 双循环新发展格局 产业升级 高质量发展
  • 简介:主题摘要:加强项目全过程管理,通过科学决策、合规管理、优化建设、严控风险,达到项目实施的预期目标,实现多方共赢。

  • 标签: 科学决策 过程管理 风险管控