Cognitive impairment and cardiovascular disease: So near,so far

In the spectrum of cognitive impairment, ranging from “pure” vascular dementia to Alzheimer's disease (AD), clinical interest has recently expanded from the brain to also include the vessels, shifting the pathophysiological focus from the leaves of synaptic dysfunction to the sap of cerebral microcirculation and the roots of cardiovascular function. From a diagnostic viewpoint, a thorough clinical evaluation of individuals presenting cognitive impairment might systematically include the assessment of the major cardiovascular rings of the chain linking regional perfusion to brain function: 1) lung (with assessment of asthma, chronic obstructive pulmonary disease, obstructive sleep apnea syndrome); 2) heart function (with clinical examination and echocardiography) and cardiovascular risk factors; 3) orthostatic hypotension (with medical history and measurement of heart rate and blood pressure in supine and upright positions); 4) aorta and large artery stiffness (with assessment of pulse wave velocity); 5) large cerebro-vascular vessel status (with neuroimaging techniques); 6) assessment of microcirculation (with cerebrovascular reactivity testing with transcranial Doppler sonography or MRI perfusion imaging); and 7) assessment of venous cerebral circulation. The apparent difference in approaches to “brain” and “vascular” environmental enrichment with physical, cognitive and sensorial training is conceptually identical to that of a constant gardener caring for an unhealthy tree, watering the leaves (“train the brain”) or simply the roots (“mind the vessel”). The therapeutic difference probably consists in the amount and quality of water added to the tree, rather than by where one pours it, with either a top-down (leaves to roots) or bottom-up (roots to leaves) approach.     

妊娠糖尿病患者血Betatrophin、HbA1c、25-(OH)VitD3的表达水平及其相关性

 目的 探讨妊娠糖尿病(gestational diabetesmellitus, GDM)患者血Betatrophin、HbA1c、25-(OH)VitD₃的表达水平及其相关性。方法 选取2018年1－12月医院收治的80例GDM患者作为研究组,并选取同期80例健康妊娠孕妇作为对照组,检测并比较两组血中Betatrophin、HbA1c、25-(OH)VitD₃的表达水平。结果 研究组孕妇血Betatrophin、HbA1c表达水平明显高于对照组,而25-(OH)VitD₃表达水平明显低于对照组,同时研究组维生素不足发生率(86.25%)明显高于对照组,差异均具有统计学意义(P<0.01);Pearson相关分析结果显示,GDM患者血HbA1c水平与Betatrophin水平呈正相关(r₁=0.452),与25-(OH)VitD₃水平呈负相关(r₂=-0.556),血25-(OH)VitD₃水平与Betatrophin水平呈负相关(r₃=-0.358),相关性均具有统计学意义(P<0.05);非条件Logistic回归分析结果显示,HbA1c和25-(OH)VitD₃分别是GDM发生的危险因素和保护因素(P<0.05)。结论 血Betatrophin、HbA1c及25-(OH)VitD₃水平与GDM有密切联系,妊娠期及时补充维生素D有助于控制血糖,降低GDM的发生率。     

枸地氯雷他定联合维生素D滴剂治疗慢性自发性荨麻疹的疗效观察

 目的 观察枸地氯雷他定联合维生素D滴剂治疗血清25-(OH)维生素D含量缺乏的慢性自发性荨麻疹患者的临床疗效。方法 选取2018-10至2019-09就诊于山西医科大学第一医院皮肤科门诊的血清25-(OH)维生素D含量缺乏的慢性自发性荨麻疹患者108例,按随机数字表法分为两组,每组54例。对照组予口服枸地氯雷他定片,治疗组予口服枸地氯雷他定片联合维生素D滴剂,疗程均为6周,比较两组患者的总有效率及治疗前后的每天发作次数评分、每天发作时间评分、皮肤病生活质量指数评分、血清25-(OH)维生素D含量的差异。结果 治疗后治疗组总有效率83.33%,高于对照组的64.81%,差异有统计学意义(P＜0.05);治疗前两组各项指标差异均无统计学意义,治疗后两组各项指标均较治疗前有改善,差异有统计学意义(P＜0.05);治疗后治疗组每天发作次数评分、每天发作时间评分及DLQI评分均低于对照组,差异均有统计学意义(P＜0.05);治疗组25-(OH)维生素D含量明显高于对照组,差异有统计学意义;治疗后治疗组平均血清25-(OH)维生素D含量[(59.43±10.08)nmol/L]与对照组血清25-(OH)维生素D含量[(30.19±9.60)nmol/L]相比差异有统计学意义(P＜0.05)。结论 血清25-(OH)维生素D含量缺乏的慢性自发性荨麻疹患者口服枸地氯雷他定片联合维生素D滴剂疗效显著,能够改善患者的生活质量,值得推广使用。     

1,25(OH)2D3干预糖尿病肾病模型大鼠肾脏组织MicroRNA-130b及转化生长因子β1的变化

文题释义： 1,25(OH)₂D3：维生素D3是胆固醇的衍生物,其活性形式有25-羟维生素D3[25(OH)D3]和1,25-二羟维生素D3[1,25(OH)₂D3]两种,其中1,25-二羟维生素D3活性更高。体内的维生素D3无生物活性,它首先在肝脏被25-羟化酶催化为具有一定生物活性的25(OH)D3,然后在肾近端小管1α-羟化酶的催化下生成活性更高的1,25(OH)₂D3,1,25(OH)₂D3在肾脏具有促进肾小管对钙、磷的重吸收,尿钙、磷排出量减少等方面作用。MicroRNA-130b：microRNA(miRNA)是一种内源性小分子RNA,由21-25个核苷酸组成,可通过与靶基因mRNA的3’UTR或者CDS序列配对,促进mRNA的降解或抑制其翻译,从而抑制靶基因的表达,其中MicroRNA-130b与多脏器的多种病变有关,在糖尿病的进程中MicroRNA-130b与早期肾脏损伤具有一定的关系,可能成为糖尿病患者早期肾脏损害以及肾脏损害严重程度的新的生物学标志。 背景：1,25(OH)₂D3在糖尿病肾病的发展过程中发挥着重要调节作用。 目的：探索1,25(OH)₂D3对糖尿病肾病大鼠肾脏组织MicroRNA-130b及转化生长因子β1表达的影响作用。 方法：实验方案经新疆医科大学动物实验中心动物实验伦理委员会批准。将25只清洁级SD大鼠随机分为正常对照组、糖尿病肾病+1,25(OH)₂D3组、糖尿病肾病+花生油组,后2组分别给予骨化三醇(即1,25(OH)₂D3,活性维生素D3) 0.03 μg/(kg • d)治疗、花生油对照处理。37 d后采集标本,以实时聚合酶链式反应(RT-PCR)、Western blot及免疫组织化学方法检测大鼠肾脏组织转化生长因子β1的表达;RT-PCR检测MicroRNA-130b的表达;采用苏木精-伊红及Masson染色对大鼠肾脏形态结构及纤维化程度进行分析。 结果与结论：①RT-PCR结果显示,糖尿病肾病+1,25(OH)₂D3组及糖尿病肾病+花生油组MicroRNA-130b的表达明显低于正常对照组(P < 0.01),糖尿病肾病+1,25(OH)₂D3组明显高于糖尿病肾病+花生油组(P < 0.01);②RT-PCR、Western blot、免疫组织化学及病理结果显示,糖尿病肾病+1,25(OH)₂D3组及糖尿病肾病+花生油组转化生长因子β1 mRNA和蛋白的表达、大鼠肾脏组织结构紊乱及纤维化程度明显高于正常对照组(P < 0.01),糖尿病肾病+1,25(OH)₂D3组明显低于糖尿病肾病+花生油组(P < 0.01);③结果说明,糖尿病肾病大鼠肾脏MicroRNA-130b表达水平下降,转化生长因子β1 mRNA及蛋白表达水平升高,肾脏组织结构紊乱及纤维化程度严重;1,25(OH)₂D3可上调糖尿病肾病大鼠肾脏MicroRNA-130b的表达水平,同时还可下调糖尿病肾病大鼠肾脏转化生长因子β1的表达水平,改善肾脏组织结构紊乱及纤维化程度。ORCID: 0000-0002-5676-5016(刘玥彤) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Accelerating the clearance of mutant huntingtin protein aggregates through autophagy induction by europium hydroxide nanorods

Autophagy is one of the well-known pathways to accelerate the clearance of protein aggregates, which contributes to the therapy of neurodegenerative diseases. Although there are numerous reports that demonstrate the induction of autophagy with small molecules including rapamycin, trehalose and lithium, however, there are few reports mentioning the clearance of aggregate-prone proteins through autophagy induction by nanoparticles. In the present article, we have demonstrated that europium hydroxide [Eu^III(OH)₃] nanorods can reduce huntingtin protein aggregation (EGFP-tagged huntingtin protein with 74 polyQ repeats), responsible for neurodegenerative diseases. Again, we have found that these nanorods induce authentic autophagy flux in different cell lines (Neuro 2a, PC12 and HeLa cells) through the expression of higher levels of characteristic autophagy marker protein LC3-II and degradation of selective autophagy substrate/cargo receptor p62/SQSTM1. Furthermore, depression of protein aggregation clearance through the autophagy blockade has also been observed by using specific inhibitors (wortmannin and chloroquine), indicating that autophagy is involved in the degradation of huntingtin protein aggregation. Since [Eu^III(OH)₃] nanorods can enhance the degradation of huntingtin protein aggregation via autophagy induction, we strongly believe that these nanorods would be useful for the development of therapeutic treatment strategies for various neurodegenerative diseases in near future using nanomedicine approach.     

Association between serum vitamin D levels and venous thromboembolism (VTE): A systematic review and meta-analysis of observational studies

ObjectiveAlthough many studies have attempted to unravel the relationship between vitamin D deficiency and the incidence of VTE, the results remained inconsistent. To address this discrepancy, we performed a systematic review and meta-analysis to precisely disentangle the relationship between serum vitamin D levels and VTE risk.MethodsThe Web of Science, Scopus, PubMed/Medline, Embase, and Google Scholar databases were searched for all available observational studies that reported the risk of venous thromboembolism (VTE) based on serum vitamin D levels categories. The search was performed up to March 2020.ResultsSeven studies were included. The overall analysis showed a significantly increased risk of VTE in subjects with low levels of serum vitamin D compared with those with normal vitamin D levels (RR = 1.34; 95% CI: 1.07–1.69; P = 0.011). In a sensitivity analysis, we did not observe a significant effect of any individual study on the combined effect sizes. Nevertheless, significant heterogeneity was present among the studies (Cochrane Q test, p = 0.018, I² = 61%). In the stratified analysis, low vitamin D levels were positively associated with an increased risk of VTE in prospective population-based studies (RR = 1.31; 95% CI: 1.06–1.61; P = 0.010) and in subjects below 60 years old (RR = 1.28; 95% CI: 1.07–1.54; P = 0.060).Conclusionour systematic review and meta-analysis showed that a low serum vitamin D level was indeed associated with an increased risk of VTE.     

1,25(OH)2D3对应用糖皮质激素治疗的肾病患者骨代谢的影响

目的观察1,25(OH)2D3对应用糖皮质激素治疗的原发性肾脏病患者骨代谢的影响。方法将16例原发性肾脏病患者随机分为治疗组和对照组。治疗组在应用糖皮质激素治疗的同时给予0.25μg的1,25(OH)2D3,每日1次口服,碳酸钙0.75,每日3次口服。对照组单纯给予碳酸钙0.75,每日3次口服。所有患者在治疗前及治疗12周时应用双能X线吸收法骨密度仪测定腰椎和股骨颈的骨密度,同时测定有关骨代谢指标,包括血全段甲状旁腺素,骨钙素,尿脱氧吡啶啉,血钙、磷以及血清白蛋白,24小时尿蛋白定量、尿钙和尿磷。结果治疗12周时两组患者的腰椎和股骨颈骨密度均下降,两组间比较无显著性差异(P>0.05);治疗12周时对照组患者的骨钙素较治疗前明显下降(P<0.05),而治疗组无明显差异;尿脱氧吡啶啉在两组中均下降,但治疗组下降明显(P<0.05);两组患者血全段甲状旁腺素、24小时尿钙和尿磷治疗前后及组间比较均无显著性差异(P>0.05);应用1,25(OH)2D3治疗者无1例出现高钙血症。结论应用糖皮质激素治疗12周的原发性肾脏病患者其腰椎及股骨颈骨密度下降明显。1,25(OH)2D3可促进骨形成,抑制骨的吸收。