冠心病合并甲状腺功能减退症冠状动脉搭桥术围术期治疗

目的:分析总结冠心病合并甲状腺功能减退症外科治疗围术期处理方法。方法:回顾性分析20例冠心病合并甲状腺功能减退患者外科治疗围术期临床资料。结果:全组患者手术效果良好,19例患者经治疗后痊愈出院,围术期死亡1例。术前甲减确诊者均服用左旋甲状腺素片,剂量为12.5～200μg/d,平均(85±11.9)μg/d,(1.15±0.14)μg/kg,术后3d内服用剂量为25～200μg/d,平均(113±11.3)μg/d,(1.56±0.13)μg/kg;术前漏诊6例,术后确诊后立即行激素替代治疗,左旋甲状腺素片最大剂量为250μg/d,最小剂量为75μg/d,平均179.17μg/d,(2.38±0.66)μg/kg;术后机械通气时间14～146 h,平均(38±21)h,ICU停留时间16～67 h,平均(35±14.5)h;术后使用2～5μg.kg-1.min-1多巴胺改善心功能,其中使用肾上腺素维持心功能者4例,剂量在0.02～0.08μg.kg-1.min-1,行IABP辅助治疗者1例,5 d后顺利撤除。结论:冠心病合并甲状腺功能减退症外科治疗增加患者术后机械通气时间、ICU停留时间,术后恢复较甲状腺功能正常者慢,积极有效的围术期处理,术后并发症的发生率、围术期病死率并无明显增高,可安全耐受手术。     

Mirabegron Ameliorated Atherosclerosis of ApoE−/− Mice in Chronic Intermittent Hypoxia but Not in Normoxia

Cardiovascular Drugs and Therapy - It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates...     

Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers

B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE.     

人核因子κBp65核定位信号缺失突变对A549细胞恶性表型的影响

目的鉴定人核因子κB(NF-κB)p65核定位信号(NLS)缺失突变质粒即pc DNA3.1(+)-NF-κBp65ΔNLS(简称NF-κBp65ΔNLS)的表达功能,以及其对低表达NF-κBp65的A549细胞株即A549/NF-κBp65 shRNA细胞增殖、迁移和粘附能力的影响。方法培养人A549/NF-κBp65 shRNA细胞株,分为对照组、转染pc DNA3.1(+)组、转染NF-κBp65ΔNLS组。应用间接免疫荧光、实时荧光定量-PCR和Western blot技术检测NF-κBp65的细胞内定位及mRNA、蛋白表达水平的变化;应用MTT、Transwell和细胞粘附实验分析转染NF-κBp65ΔNLS质粒对A549/NF-κBp65 shRNA细胞增殖、迁移、粘附能力的影响。结果成功构建人NF-κBp65ΔNLS真核表达质粒。转染NF-κBp65ΔNLS质粒的A549/NF-κBp65 shRNA细胞与对照组及转染pc DNA3.1(+)组比较,NF-κBp65 mRNA表达水平明显上调(10.63±0.84比1.04±0.21和1.23±0.22,P0.01),NF-κBp65蛋白表达水平明显升高(1.07±0.06比0.53±0.02和0.59±0.04,P0.01),且NF-κBp65蛋白主要位于细胞浆内,在肿瘤坏死因子α刺激后NF-κBp65蛋白并未明显进入细胞核。与对照组及转染pc DNA3.1(+)组比较,转染NF-κBp65ΔNLS质粒的A549/NF-κBp65 shRNA细胞的增殖、迁移和粘附能力均有不同程度增强。结论通过基因突变技术构建无NLS的NF-κBp65真核表达质粒,可明显增强A549/NF-κBp65shRNA细胞株内NF-κBp65 mRNA和蛋白的表达水平,并使NF-κBp65蛋白定位于细胞浆内;同时,细胞浆内过表达NF-κBp65ΔNLS蛋白可明显增强A549/NF-κBp65 shRNA细胞的增殖、迁移和粘附能力,提示滞留于细胞浆内的NF-κBp65仍可通过影响NF-κB信号通路相关蛋白参与调节肺癌细胞的生物学行为。     

建立同时测定大鼠血浆中丹参素钠与原儿茶醛和咖啡酸、迷迭香酸和丹酚酸A含量的液质联用方法

目的建立HPLC-MS/MS法测定丹参素钠、原儿茶醛、咖啡酸、迷迭香酸和丹酚酸A在大鼠血浆中浓度的方法。方法用乙腈蛋白沉淀法处理血浆样本,色谱柱为Synergi Hydro-RP 80 A(150 mm×2 mm,4μm),流动相为乙腈-0.1%甲酸水溶液,梯度洗脱,0~2 min,10%~60%乙腈;2~3 min,60%~95%乙腈;3~6.5 min,95%乙腈;6.5~7 min,95%~10%乙腈;7~12 min,10%乙腈,流速为0.4 m L·min-1;电喷雾电离(ESI)离子源离子化,采用多重反应监测(MRM)方式进行负离子检测。结果丹参素钠、原儿茶醛、咖啡酸、迷迭香酸和丹酚酸A的线性范围分别为10~1000,5~500,2~200,5~500,10~1000ng·m L-1;定量下限分别为10,5,2,5,10 ng·m L-1。日内精密度(RSD)均小于8.31%,日间RSD均小于12.73%,提取回收率均大于50%。结论本检测方法专属性高,操作简便,稳定性好,可以同时准确地检测丹参素钠、原儿茶醛、咖啡酸、迷迭香酸和丹酚酸A的血药浓度。     

Safety and Efficacy of Intracoronary Thrombolysis as Adjunctive Therapy to Primary PCI in STEMI: A Systematic Review and Meta-analysis

BackgroundPrimary percutaneous coronary intervention (PPCI) is the preferred method of reperfusion in ST-elevation myocardial infarction. However, microvascular perfusion is often impaired due to distal embolization of thrombus. Intracoronary (IC) thrombolysis may attenuate thrombotic burden. We conducted a meta-analysis comparing the benefits and risks of IC thrombolytic therapy as an adjunct to PPCI.MethodsRandomized controlled trials (RCTs) were identified through search of Medline, EMBASE, Scopus, Web of Science, Cochrane Library (Cochrane Reviews and Cochrane Protocols), PROSPERO, and clinicaltrials.gov from 1946 to January 2019. Studies included patients with ST-elevation myocardial infarction undergoing primary PCI receiving IC thrombolytic agents. Both safety and efficacy outcomes were explored. Data were combined using a fixed-effects model.ResultsOf 1278 citations identified, 6 RCTs (890 patients; 519 IC thrombolytic and 371 IC placebo) were included. Post-PCI thrombolysis in myocardial infarction (TIMI) flow grade 2/3 occurred in 97.1% of the IC thrombolytic group vs 95.1% of the IC placebo group (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.28-1.17; P = 0.13). Complete ST-segment resolution was more common with IC thrombolysis (OR, 0.29; 95% CI, 0.15-0.57; P = 0.0003). There was a strong trend favouring fewer in-hospital major adverse cardiac events with IC thrombolysis when compared with IC placebo (OR, 0.64; 95% CI, 0.41-1.01; P = 0.05). There was no difference in bleeding (TIMI major, TIMI minor, and Bleeding Academic Research Consortium [BARC] 3-5 bleeds) between the 2 groups (OR, 1.36; 95% CI, 0.38-3.54; P = 4.84).ConclusionsGiven the limited studies to date, our meta-analysis suggests that a targeted IC thrombolytic approach is safe and potentially effective to augment PPCI. However, these findings deserve confirmation in a larger RCT.