Angiotensin (1−7) peptide replacement therapy with plasma transfusion in COVID-19

AimTo determine whether convalescent angiotensin (1?7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection.Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1?7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days.ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment.ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1?7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.     

黄芪甲苷调节PI3K/Akt/FoxO1通路抑制糖尿病大鼠肝糖异生

目的:探讨黄芪甲苷对2型糖尿病(T2DM)大鼠肝损伤保护潜在机制及肝组织磷酯酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/叉头框转录因子1(FoxO1),磷酸烯醇式丙酮酸羧基酶(PEPCK)和葡萄糖6-磷酸酶(G6Pase)蛋白表达的影响。方法:6周高糖高脂饮食后,链脲佐菌素(STZ)一次性腹腔注射(0.035 g·kg^-1)建立T2DM大鼠模型,随机分为正常组、模型组、黄芪甲苷低、中、高剂量组及二甲双胍组。黄芪甲苷低、中、高剂量组灌胃黄芪甲苷0.02,0.04,0.08 g·kg^-1·d^-1,二甲双胍组灌胃二甲双胍0.2 g·kg^-1·d^-1;给药8周后,于末次灌胃24 h禁食不禁水后处死,测血清肝生化指标,肝脏指数等;采用苏木素-伊红(HE)染色观察肝脏组织病理形态学变化;马松(Masson)染色观察纤维化程度;过碘酸希夫(PAS)染色反应观察细胞内糖原等变化;免疫组化及蛋白免疫印迹法(Western blot)检测各组肝中PI3K/Akt/FoxO1信号蛋白及PEPCK,G6Pase蛋白表达水平。结果:与正常组比较,模型组肝脏指数显著升高(P<0.01),肝功能指标丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),总胆固醇(TC),甘油三酯(TG)的含量显著升高(P<0.01),高密度脂蛋白胆固醇(HDL-C)显著降低(P<0.01),大鼠体质量显著减轻(P<0.01),PI3K/Akt/Fox O1信号减弱(P<0.01),PEPCK,G6Pase蛋白表达水平显著增强(P<0.01);与模型组比较,黄芪甲苷中、高剂量组及二甲双胍组肝功能指标ALT,AST,TC,TG的含量明显降低(P<0.05,P<0.01),大鼠体质量明显增加(P<0.05,P<0.01),肝组织Fox O1,PEPCK及G6Pase蛋白水平明显降低(P<0.05,P<0.01),Fox O1的磷酸化水平明显增强(P<0.05,P<0.01)。结论:黄芪甲苷可能通过调节PI3K/Akt/Fox O1信号通路抑制高脂高糖加小剂量STZ诱导T2DM肝糖异生,从而起到延缓T2DM大鼠肝脏损伤作用。     

N‐acetyl‐seryl‐aspartyl‐lysyl‐proline is a valuable endogenous antifibrotic peptide for kidney fibrosis in diabetes: An update and translational aspects

N‐acetyl‐seryl‐aspartyl‐lysyl‐proline (AcSDKP) is an endogenous peptide that has been confirmed to show excellent organ‐protective effects. Even though originally discovered as a modulator of hemotopoietic stem cells, during the recent two decades, AcSDKP has been recognized as valuable antifibrotic peptide. The antifibrotic mechanism of AcSDKP is not yet clear; we have established that AcSDKP could target endothelial–mesenchymal transition program through the induction of the endothelial fibroblast growth factor receptor signaling pathway. Also, recent reports suggested the clinical significance of AcSDKP. The aim of this review was to update recent advances of the mechanistic action of AcSDKP and discuss translational research aspects.     

The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

Backgroundand Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed.MethodsWe systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms “(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)”. The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively.ResultsTotally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I²: 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I²: 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I²: 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I²: 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I²: 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups.ConclusionAdministration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.     

血清Lp-PLA2,BDNF及Ang1-7表达水平与血管性痴呆患者病情严重程度的相关性

目的 探讨血管性痴呆(VD)患者血清脂蛋白相关磷脂酶A2(Lp-PLA2)、脑源性神经营养因子(BDNF)及血管紧张素1-7(Ang1-7)表达水平及其与VD患者病情严重程度的相关性。方法 选取本院2017年10月-2019年10月收治的120例VD患者,依照简易精神状态检查量表(MMSE)分为轻度组、中度组和重度组,各40例,比较各组相关危险因素,颈动脉超声检测颈动脉内膜中层厚度(IMT),检测血清生化指标[低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、三酰甘油(TG)、糖化血红蛋白(GHb)、空腹血糖(GLU)]、血清指标[Lp-PLA2,BDNF,Ang1-7、神经元特异性烯醇化酶(NSE)、C反应蛋白(CRP)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、同型半胱氨酸(Hcy)]水平, 分析Lp-PLA2,BDNF及Ang1-7水平之间的相关性,也分析血清Lp-PLA2,BDNF及Ang1-7水平与MMSE评分的相关性。结果 3组患者年龄、受教育程度、高血压病史、高血脂症史、饮酒、吸烟等临床资料比较均无明显差异(P>0.05),冠心病史、糖尿病史、IMT比较均有明显差异(P<0.05); 3组患者血清LDL-C,HDL-C,TC,TG,GHb,GLU水平比较均无明显差异(P>0.05),血清Lp-PLA2,BDNF,Ang1-7,NSE,CRP,IL-6,TNF-α及Hcy水平比较均有明显差异(P<0.05)。相关性分析显示,血清Lp-PLA2,BDNF及Ang1-7与冠心病史、糖尿病史、血清NSE,CRP,IL-6,TNF-α,LDL-C,TC水平及MMSE评分存在明显相关性。结论 血清Lp-PLA2、BDNF及Ang1-7水平与血管性痴呆患者血清因子水平及VD患者的病情严重程度存在明显相关性,检测血清Lp-PLA2,BDNF及Ang1-7水平有助于VD患者的预防和治疗     

沙库巴曲缬沙坦在心力衰竭治疗中的应用

心力衰竭是一种慢性疾病，是心脏无法泵出足够的血液为其他身体器官提供氧气，从而引发呼吸短促、疲劳和水肿等症状。目前其治疗包括病因治疗、一般治疗、药物治疗及非药物治疗等，其中血管紧张素受体脑啡肽酶抑制剂（ARNI）是当前新研发出的一类抗心衰药物，沙库巴曲缬沙坦是其代表药物，具有阻断肾素-血管紧张-醛固酮系统（RAAS）及抑制脑啡肽酶（NEP）的双重作用，新的欧美指南均推荐用于射血分数降低心力衰竭（HFrEF）的治疗。本文现就沙库巴曲缬沙坦在心力衰竭治疗中的作用机理、临床试验、药物安全性作一综述，旨在为该病的临床治疗提供参考。     

某校大学生饮食习惯对肠易激综合征的影响

目的 了解饮食对肠易激综合征的影响。方法 对2018年10月—2019年4月来校医院就诊的1 207名在校本科生进行问卷调查,问卷依据罗马Ⅳ诊断标准,数据分析采用SPSS 22.0卡方检验、单因素分析、Logistic多因素回归分析。结果 来校医院就诊的在校大学生中,肠易激综合征的患病率为5.1%(60/1207)。在单因素分析中,进食生冷(P=0.070)、高纤维(P=0.367)、乳制品(P=0.414)、果蔬(P=0.784)与肠易激综合征的患病差异无统计学意义。进食辛辣(P=0.002)、高脂饮食(P<0.001)与肠易激综合征的患病差异有统计学意义。进一步Logistic多因素回归分析显示,高频率进食高脂食物比低频率(≤1次/周)进食高脂食物更容易引起肠易激综合征。P值为0.003,OR:1.545。结论 本调查样本中,肠易激综合征的患病率为5.1%。肠易激综合征的患病与进食辛辣、高脂饮食有关。高频率的进食高脂食物是肠易激综合征患病的危险因素。基层医生应着重做好相关病人的饮食指导,尽量减少肠易激综合征被诱发。     

Progression of hypertension and kidney disease in aging fawn-hooded rats is mediated by enhanced influence of renin–angiotensin system and suppression of nitric oxide system and epoxyeicosanoids

The fawn-hooded hypertensive (FHH) rat serves as a genetic model of spontaneous hypertension associated with glomerular hyperfiltration and proteinuria. However, the knowledge of the natural course of hypertension and kidney disease in FHH rats remains fragmentary and the underlying pathophysiological mechanisms are unclear. In this study, over the animals’ lifetime, we followed the survival rate, blood pressure (telemetry), indices of kidney damage, the activity of renin–angiotensin (RAS) and nitric oxide (NO) systems, and CYP450-epoxygenase products (EETs). Compared to normotensive controls, no elevation of plasma and renal RAS was observed in prehypertensive and hypertensive FHH rats; however, RAS inhibition significantly reduced systolic blood pressure (137 ± 9 to 116 ± 8, and 159 ± 8 to 126 ± 4 mmHg, respectively) and proteinuria (62 ± 2 to 37 ± 3, and 132 ± 8 to 87 ± 5 mg/day, respectively). Moreover, pharmacological RAS inhibition reduced angiotensin (ANG) II and increased ANG 1–7 in the kidney and thereby may have delayed the progression of kidney disease. Furthermore, renal NO and EETs declined in the aging FHH rats but not in the control strain. The present results, especially the demonstration of exaggerated vascular responsiveness to ANG II, indicate that RAS may contribute to the development of hypertension and kidney disease in FHH rats. The activity of factors opposing the development of hypertension and protecting the kidney declined with age in this model. Therefore, therapeutic enhancement of this activity besides RAS inhibition could be attempted in the therapy of human hypertension associated with kidney disease.