Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension

BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.

缺氧时星形胶质细胞定量mRNA表达的内部参照标准研究

目的 :观察缺氧对脑星形胶质细胞 (AC)守家基因甘油醛 - 3-磷酸 -脱氢酶 (GAPDH)和 β -肌动蛋白 (actin)mRNA表达的影响 ,进一步观察内皮素转换酶 (ECE) - 2mRNA可否作为该条件下的内部参照标准。方法 :从新生小鼠大脑获原代AC培养 ,分别在缺氧和正常氧条件下培养 2 4h ,提取mRNA ,以溴化乙啶染色的 2 8S及 18SrRNA作内部参照 ,用Northernblot杂交技术定量测定GAPDH、β -actin和ECE - 2mRNA水平。 结果 :缺氧 2 4h ,ACGAPDHmRNA的表达显著增加 ,β -actinmRNA表达明显下降 ;缺氧前后ECE - 2的mRNA水平无明显差异。 结论 :在缺氧缺血条件下 ,GAPDH和 β -actin不宜作为AC定量mRNA分析的内部参照标准 ,ECE - 2可作为其替代。

云南汉族高血压病6个候选基因相互作用研究

目的探讨AGT、ACE、eNOS、ET-2、ANP和NPRC等6个基因多态性与高血压病的相关性及其相互作用。方法用基因芯片检测技术,对100例高血压病患者及97例健康对照者进行AGTM235T、ACEI/D、eNOSGlu298Asp、ET-2A985G、ANPT2238C和NPRCA-55C等位点基因多态性检测。结果 NPRCA-55C位点的CC基因型频率(0.540)与对照组(0.237)比较差异有极显著性意义(χ2=18.973,P=0.0000),OddRatio=3.777(95%CI:2.050～6.960);ET-2A985G位点G等位基因频率(0.925)与对照组(0.851)比较,差异有显著性意义(χ2=5.507、P=0.0190),OddRatio=2.648(95%CI:1.073～6.536)。用MDR方法分析以上6个位点基因-基因交互作用,显示两位点ET-2/NPRC模型为最佳模型,该模型的OddRatio为4.002(95%CI:2.1597～7.4159)。结论云南汉族NPRCA-55CCC基因型和ET-2A985GG等位基因可能与高血压病易感性相关。ET-2A985G和NPRCA-55C两个基因多态性之间可能存在基因-基因交互作用。

重症急性胰腺炎微循环障碍的实验研究

目的 :探讨急性出血性坏死性胰腺炎杂种犬胰腺血循环障碍的机制。方法 :用 5 %牛黄胆酸钠溶液胰管注入 ,制备急性出血性坏死性胰腺炎模型。动态观察犬和血管紧张素转化酶两血管活性物质的变化与血浆中血栓素A2 /前列腺素I2 、内皮素 /一氧化氮胰腺血流量的内在联系。结果 :急性出血性坏死性胰腺炎犬胰腺血流量明显持续下降 ,血管紧张素转化酶、血栓素A2 、前列腺素I2 、一氧化氮显著升高 ,且血栓素A2 /前列腺素2 和内皮素 /一氧化氮比值持续增加。结论 :血管紧张素转化酶、血栓素A2 /前列腺素I2 和内皮素 /一氧化氮是介导急性出血性坏死性胰腺炎犬胰腺微循环障碍的重要因素 ,出现急性出血性坏死性胰腺炎时胰腺微循环强烈收缩和微小血栓形成 。

Current therapies and novel approaches for biliary diseases

Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver diseases comprise a large group of conditions in which injury is primarily focused on the biliary system. These include congenital diseases(such as biliary atresia and cystic fibrosis), acquired diseases(such as primary sclerosing cholangitis and primary biliary cirrhosis), and those that arise from secondary damage to the biliary tree from obstruction, cholangitis or ischaemia. These conditions are associated with a specific pattern of chronic liver injury centered on damaged bile ducts that drive the development of peribiliary fibrosis and, ultimately, biliary cirrhosis and liver failure. For most, there is no established medical therapy and, hence, these diseases remain one of the most important indications for liver transplantation.As a result, there is a major need to develop new therapies that can prevent the development of chronic biliary injury and fibrosis. This mini-review briefly discusses the pathophysiology of liver fibrosis and its progression to cirrhosis.We make a special emphasis on biliary fibrosis and current therapeutic options,such as angiotensin converting enzyme-2(known as ACE2) over-expression in the diseased liver as a novel potential therapy to treat this condition.

Prediction of Proteins Associated with COVID-19 Based Ligand Designing and Molecular Modeling

Current understanding about how the virus that causes COVID-19 spreads is largely based on what is known about similar coronaviruses.Some of the Natural products are suitable drugs against SARS-CoV-2 main protease.For recognizing a strong inhibitor,we have accomplished dock-ing studies on the major virus protease with 4 natural product species as anti COVID-19(SARS-CoV-2),namely“Vidarabine”,“Cytarabine”,“Gem-citabine”and“Matrine”which have been extracted fromGillan’s leaves plants.These are known as Chuchaq,Trshvash,Cote-Couto and Khlvash in Iran.Among these four studied compounds,Cytarabine appears as a suitable com-pound with high effectiveness inhibitors to this protease.Finally by this work we present a method on the Computational Prediction of Protein Structure Associated with COVID-19 Based Ligand Design and Molecular Modeling.By this investigation,auto dock software(iGEM-DOCK)has been used and via this tool,the suitable receptors can be distinguished in whole COVID-19 component structures for forming a complex.“iGEMDOCK”is suitable to define the binding site quickly.With docking simulation and NMR inves-tigation,we have demonstrated these compounds exhibit a suitable binding energy around 9 Kcal/mol with various ligand proteins modes in the bind-ing to COVID-19 viruses.However,these data need further evaluation for repurposing these drugs against COVID-19 viruses,in both vivo&vitro.

云南省汉族健康人群六个原发性高血压候选基因多态性分布

目的探讨肾素血管紧张素系统（RAS）、血管内皮和钠肽系统中AGT、ACE、eNOS、ET-2、ANP和NPRC等6个原发性高血压候选基因多态性在云南汉族健康人群中的分布，为进一步研究其在原发性高血压等心血管疾病发生中的作用提供本地信息。方法用基因芯片检测技术，对97例健康者进行AGTM235T（MM、MT、TT）、ACE I／D（II、ID、DD）、eNOS Glu298Asp（EE、ED、DD）、ET-2A985G（AA、AG、GG）、ANP T2238C（TT、TC、CC）和NPRC A-55C（AA、AC、CC）等位点基因多态性检测。结果①云南汉族97例健康人群中AGT M235T位点的MM、MT、TT基因型频率分别为0．052、0．381、0．567；M和T的等位基因频率分别为0．242、0．758。②ACE I／D突变的II、ID、DD基因型频率分别为0．340、0．598、0．062；I和D等位基因频率分别为0．680、0．320。③eNOS Glu298Asp位点的EE、ED、DD基因型频率分别为0．845、0．144、0．011；E和D等位基因频率分别为0．918、0．082。④ET-2 A985G位点的AA、AG、GG基因型频率分别为0．020、0．258、0．722；A和G等位基因频率分别为0．149、0．851。⑤ANP T2238C位点的TT、TC基因型频率分别为0．959、0．041，未检出CC基因型；T和C等位基因频率分别为0．979、0．021。⑥NPRC A-55C的AC、CC基因型频率分别为0．763、0．237，未检出AA基因型；A和c等位基因频率分别为0．381、0．619。结论云南汉族健康人群AGT M235T、ACE I／D、eNOS Glu298Asp（E298D）、ET-2 A985G、ANP T2238C和NPRC A-55C等6个位点基因多态性有地区特征。

丹红化瘀口服液对视网膜中央静脉阻塞症关键靶点的调节作用

目的采用G蛋白偶联受体及酶活检测实验方法,探究丹红化瘀口服液对视网膜中央静脉阻塞症关键靶点的调节作用,明确其作用机制。方法选取磷酸二酯酶3A(phosphodiesterase 3A,PDE3A)、凝血酶(Thrombin)、内皮素转化酶1(endothelin converting enzyme 1,ECE1)、血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)、α1A肾上腺素受体(α1A adrenergic receptor,ADRA1A)为研究载体,通过胞内钙离子荧光检测和酶抑制剂检测技术评价丹红化瘀口服液及14个主要单体成分对PDE3A、Thrombin、ECE1、VEGFR2酪氨酸激酶和ADRA1A的抑制活性。结果丹红化瘀口服液对以上5个靶点均有显著的抑制作用(P<0.001);丹酚酸D、丹酚酸B、丹参素、迷迭香酸和柚皮苷对PDE3A有显著的抑制作用(P<0.05、0.001);14个化合物对Thrombin均有显著的抑制活性(P<0.05、0.01、0.001);丹酚酸D、丹酚酸B、丹参素、迷迭香酸、阿魏酸、羟基红花黄色素A对ECE1有显著的抑制活性(P<0.05、0.01、0.001);丹酚酸D、丹酚酸B、丹参素、迷迭香酸、柠檬苦素对VEGFR2酪氨酸激酶有显著的抑制效果(P<0.01、0.001);柴胡皂苷a可显著抑制ADRA1A活性(P<0.001)。结论 ADRA1A、VEGFR2、PDE3A、Thrombin和ECE1可能为丹红化瘀口服液治疗中央静脉阻塞症的关键作用靶点,其药效物质基础可能为丹参酮IIA、丹酚酸B、丹酚酸D、丹参素、迷迭香酸、原儿茶醛、阿魏酸、川芎嗪、洋川芎内酯I、羟基红花黄色素A、苦杏仁苷、柴胡皂苷a、柚皮苷和柠檬苦素。