Renin–angiotensin system inhibition is not associated with increased sudden cardiac death,cardiovascular mortality or all-cause mortality in patients with aortic stenosis

Background

Renin–angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS.

Methods

All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses.

Results

769 (41%) patients received RASI. During a median follow-up of 4.3 ± 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95%CI: 0.50–2.83], p = 0.694), cardiovascular (HR: 1.05 [95%CI: 0.62–1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95%CI: 0.55–1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040).

Conclusions

RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression.     

Inhibition of microRNA-17-5p reduces the inflammation and lipid accumulation,and up-regulates ATP-binding cassette transporterA1 in atherosclerosis

Atherosclerosis (AS) is a chronic inflammatory disease of the arterial wall. Macrophages are considered to be closely associated with the development and progression of AS. However, the precise mechanism of miR-17-5p in the macrophages under AS remains incompletely clarified. This study investigated the regulatory effect of miR-17-5p on the inflammation and lipid accumulation in mouse macrophages both in vivo and in vitro. It was found that miR-17-5p was highly expressed with lowered ATP-binding cassette transporterA1 (ABCA1) level in the peripheral blood leucocytes (PBLs) of AS patients. Moreover, the level of miR-17-5p was up-regulated in the macrophages of ApoE^?/? mice fed with a high-cholesterol diet. Furthermore, we injected miR-17-5p antagomir into AS mice or transfected miR-17-5p inhibitors into mouse macrophage RAW264.7 cells. Results showed that downregulation of miR-17-5p significantly reduced the production of inflammatory cytokines, inhibited the lipid accumulation and up-regulated ABCA1, and activated peroxisome proliferator-activated receptor (PPAR) γ/Liver X receptor (LXR) α signaling pathway. Additionally, ABCA1 was found to be a target of miR-17-5p by directly binding to 3′-untranslated region (3′-UTR) of its mRNA. Our study indicates a novel regulatory mechanism for miR-17-5p by interacting with ABCA1, which could be a therapy-target for the treatment of AS.     

中老年人群肝脏脂肪含量与骨密度的相关性研究

目的探讨中老年人群肝脏脂肪含量与腰椎骨密度的相关性。方法2016年3月至6月纳入184名北京社区中老年居民,其中男68名、女116名,对其进行腹部MRI mDIXON-Quant序列扫描和腰椎定量CT(QCT)扫描,测量肝脏脂肪含量和腰1~腰3椎体骨密度。根据肝脏脂肪含量的四分位数分为四组,采用单因素方差分析比较不同肝脏脂肪含量组间骨密度及身高、体重、体质量指数(BMI)、腰围、臀围等变量的差异,并对肝脏脂肪含量和骨密度做Spearman相关性分析和偏相关分析。结果随着肝脏脂肪含量的升高,BMI、腰围呈上升趋势,而腰椎骨密度逐渐降低。肝脏脂肪含量与腰椎骨密度呈低度负相关(r=-0.203,P=0.003),校正年龄、体重之后,仍呈负相关(r=-0.291,P<0.001),男性中r=-0.283(P=0.021),女性r=-0.210(P=0.025)。结论中老年人群肝脏脂肪含量与腰椎骨密度呈低度负相关。     

武警某部2019年入伍战士骨密度与其饮食行为习惯的相关性

 目的 调查了解新兵骨密度与其饮食行为习惯的关系,为降低训练伤风险,推行科学合理的训练方案提供理论依据。方法 对武警某部2019年入伍的1489名战士进行骨密度测定,自行设计调查问卷对他们的膳食营养态度和饮食行为习惯进行现场问卷调查。纳入骨密度正常的和骨密度低下的共计780名战士资料进行相关分析,探讨骨密度的膳食影响因素。结果 膳食营养态度方面,骨密度正常组(476名)关注饮食健康和认为自己每天食物摄入均衡方面优于骨密度低下组(304名),差异有统计学意义(P<0.05)。多因素回归结果显示:不偏食挑食(OR=0.534,95% CI 0.370~0.770),每天鸡蛋(OR=0.603,95% CI 0.412~0.882)、牛奶摄入(OR=0.419,95% CI 0.286~0.615)达到中国居民膳食指南推荐剂量,每天锻炼(OR=0.653,95% CI 0.449~0.949),户外活动时间≥2 h(OR=0.153,95% CI 0.057~0.411)是骨密度的保护因素;但是经常喝碳酸饮料(OR=3.182,95% CI 2.117~4.284)是骨密度的危险因素。结论 本次调查的入伍新兵38.8%为骨密度低下,应制定个体化的训练计划、普及相关知识、树立科学的饮食行为习惯提升骨密度值。     

定量CT分析年龄、腹部脂肪与骨密度的关系

目的采用定量CT(QCT)探讨腹部脂肪及骨密度(BMD)随年龄变化的规律及腹内脂肪(VAT)与BMD的相关性。资料与方法选取行低剂量胸部CT联合QCT检查的健康体检者2442例,其中男1522例,女920例,根据年龄分为5个年龄段:30~39、40~49、50~59、60~69、70~90岁。采用QCT测量L2中心层面腹部总脂肪(TAT)、VAT、皮下脂肪(SAT)及腰椎BMD。分析不同性别各年龄段间TAT、VAT、SAT、BMD的差异及TAT、VAT、SAT与BMD的相关性。结果50岁以上男性各年龄段TAT、VAT高于30~39岁男性(P均<0.01),而SAT低于30~39岁男性(P均<0.05)。50岁以上女性各年龄段TAT、VAT、SAT高于30~39岁女性(P均<0.001)。50岁以上男性及女性各年龄段间TAT、VAT、SAT比较,差异均无统计学意义(P均>0.05),40~49、50~59岁年龄段分别较上一年龄段VAT明显增多(P均<0.01),BMD随年龄增长逐渐减低(P均<0.001)。多元逐步回归分析显示,VAT是女性BMD的独立影响因素(β=-0.089,P=0.007),TAT、SAT不是BMD的独立影响因素(P均>0.05)。结论腹部脂肪和BMD随年龄发生变化,男性和女性均在40~59岁出现VAT明显增多。VAT可能是女性BMD的独立负性影响因素。     

Scaffold implantation in the omentum majus of rabbits for new bone formation

Restoration of the mandible after defects caused by ablative surgery remains challenging. Microvascular free flaps from the scapula, fibula or iliac crest remain the ‘gold standard’. A drawback of these methods is donor-side morbidity, availability and the shape of the bone. Former cases have shown that prefabrication of a customized bone flap in the latissimus dorsi muscle may be successful; however, this method is still associated with high donor-side morbidity. Osteogenesis in the omentum majus of rabbits by wrapping the periosteum into it was confirmed recently and is particularly interesting for bone endocultivation.Twelve adult male New Zealand white rabbits were used. In each, two hydroxyapatite blocks were implanted in the greater omentum with autologous bone or autologous bone + rhBMP-2.Bone density measurements were performed by CT scans. Fluorochrome labelling was used for new bone formation detection. The animals were sacrificed at week 10, and the specimens were harvested for histological and histomorphometric analysis. In histological and fluorescence microscopic analysis, new bone formation could be found, as well as new blood vessels and connective tissue. No significant differences were found regarding the histological analysis and bone density measurements between the groups.It could be demonstrated that the omentum majus is a practical way to use one's own body as a bioreactor for prefabrication of tissue-engineered bony constructs. Regarding the influence and exact dose of rhBMP-2, further research is necessary. To establish and improve this method, further large-animal experimental studies are also necessary.     

Osteocytes and mechanical loading: The Wnt connection

Bone adapts to the mechanical forces that it experiences. Orthodontic tooth movement harnesses the cell‐ and tissue‐level properties of mechanotransduction to achieve alignment and reorganization of the dentition. However, the mechanisms of action that permit bone resorption and formation in response to loads placed on the teeth are incompletely elucidated, though several mechanisms have been identified. Wnt/Lrp5 signalling in osteocytes is a key pathway that modulates bone tissue's response to load. Numerous mouse models that harbour knock‐in, knockout and transgenic/overexpression alleles targeting genes related to Wnt signalling point to the necessity of Wnt/Lrp5, and its localization to osteocytes, for proper mechanotransduction in bone. Alveolar bone is rich in osteocytes and is a highly mechanoresponsive tissue in which components of the canonical Wnt signalling cascade have been identified. As Wnt‐based agents become clinically available in the next several years, the major challenge that lies ahead will be to gain a more complete understanding of Wnt biology in alveolar bone so that improved/expedited tooth movement becomes a possibility.     

血管紧张素转换酶2基因转染对内皮细胞的保护作用

目的：探讨血管紧张素转换酶2（ACE2）基因转染对内皮细胞血凝素样氧化型低密度脂蛋白受体-1(LOX-1)表达的影响及意义。方法：实验包括体外实验与体内实验。体外实验,首先进行人脐静脉内皮细胞（HUVEC）的培养,然后应用蛋白质印迹法检测ACE2转染对血管紧张素II刺激HUVEC产生的LOX-1蛋白表达的影响。体内实验,首先建立载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化模型。然后将20只ApoE-/-小鼠随机分为ACE2组及增强型绿色荧光蛋白组（EGFP组）,每组10只。ACE2组经尾静脉注射ACE2的复制缺陷重组腺病毒（Ad-ACE2）(2.5×109 pfu/ml),EGFP组注射等量EGFP的复制缺陷重组腺病毒(Ad-EGFP)。注射一个月后处死动物,做腹主动脉的油红O及LOX-1表达的检测。结果：体内实验与体外实验均证实ACE2基因转染抑制了内皮细胞LOX-1的表达,体内实验中ACE2组斑块内脂质含量明显低于EGFP组水平。结论：ACE2通过抑制LOX-1的表达进而抑制了动脉粥样硬化斑块的进展。