川芎嗪联合阿托伐他汀治疗肺动脉高压的临床疗效分析

目的:观察川芎嗪联合阿托伐他汀治疗肺动脉高压的临床疗效及安全性。方法:将96例肺动脉高压患者随机分成两组,其中治疗组48人,对照组48人。治疗组患者在常规治疗基础上采川芎嗪联合阿托伐他汀治疗,对照组患者在常规治疗基础上单采用阿托伐他汀治疗,通过检测平均动脉压(mAP)、平均肺动脉压(mPAP)、肺血管阻力(PVR)、心脏指数(CI)、左心室射血分数(LVER)、Borg呼吸困难指数(Borg dyspnea)、6分钟步行距离(6TWD)以及肺功能升级(WHO FC)等指标评价其疗效。结果:两组患者经过6个月的治疗后,mPAP、PVR与治疗前相比显著降低,而CI、LVEF和6MWD均显著升高,差异均有统计学意义(P<0.05),治疗前后两组mAP与Borg呼吸困难指数均没有统计学差异(P>0.05),治疗组的mAP、LVEF以及6TWD与对照组相比差异有统计学意义(P<0.05)。结论:川芎嗪联合阿托伐他汀治疗充肺动脉高压临床疗效优于单纯应用阿托伐他汀。     

不同剂量阿伐他汀联合阿司匹林治疗原发性高血压并动脉粥样硬化的临床研究

目的:探讨不同剂量阿托伐他汀联合阿司匹林治疗原发性高血压并动脉粥样硬化的临床疗效。方法:选取2015年1月-2016年12月在我院治疗的原发性高血压并动脉粥样硬化患者80例,随机分为对照组和实验组,每组40例。实验组给予口服高剂量阿托伐他汀(40 mg/d)联合阿司匹林肠溶片(100 mg/d)治疗,对照组给予口服高剂量阿托伐他汀(20 mg/d)联合阿司匹林肠溶片(100 mg/d)治疗,疗程均为3个月。观察和比较两组患者治疗前后的总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high-density lipoproteincholesterol,HDL-C)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、收缩压(systolic blood pressure,SBP)、舒张血压(diastolic blood pressure,DBP)以及颈动脉斑块分级。结果:两组治疗后的SBP、DBP、血清TC、TG和LDL-C水平均较治疗前显著降低,血清HDL-C水平较治疗前明显升高,且实验组SBP、DBP、血清TC、TG和LDL-C水平均显著低于对照组(P0.05),血清HDL-C水平明显高于对照组(P0.05)。实验组颈动脉斑块0-Ⅰ级的比例显著高于对照组(P0.05)。结论:口服高剂量阿托伐他汀(40 mg/d)联合阿司匹林肠溶片(100 mg/d)治疗原发性高血压并动脉粥样硬化较低剂量阿托伐他汀(20 mg/d)联合阿司匹林肠溶片(100 mg/d)疗效更好,可以有效降低血压,调节血脂并改善患者预后。     

缬沙坦联合阿托伐他汀钠对尿毒症维持性血液透析患者炎症因子及营养状况的影响

目的:探讨缬沙坦联合阿托伐他汀钠对维持性血液透析患者炎症因子及其营养状况的影响.方法:将120例维持性血液透析患者随机分为对照组与观察组,每组各60例.给予对照组患者口服阿托伐他汀,观察组患者给予缬沙坦联合阿托伐他汀钠口服.比较两组治疗前后C-反应蛋白(CRP)、IL-6、肿瘤坏死因子(TNF-α)、抵抗素及血清白蛋白(ALb)、血红蛋白(Hb)的变化情况.结果:治疗后6月两组患者hs-CRP、TNF-α、IL-6及抵抗素水平均显著下降(P＜0.05),但观察组患者上述指标显著低于对照组(P＜0.05);观察组治疗后Alb及Hb水平显著高于对照组,差别具有统计学意义(P＜0.05).结论:缬沙坦联合阿托伐他汀钠用于维持性血液透析患者,可显著减少炎症因子水平,改善患者营养状况.     

阿托伐他汀治疗高血压并颈动脉粥样硬化的临床疗效观察

目的:观察阿托伐他汀治疗高血压并颈动脉粥样硬化的临床疗效。方法:选择高血压并颈动脉粥样硬化患者64例,按照自愿的原则分为对照组和观察组,对照组给予常规治疗,观察组在常规治疗的基础上给以阿托伐他汀治疗。治疗6个月后,比较两组患者血压、血脂及颈动脉斑块分级情况。结果:治疗6周后,两组患者在上述方面比较,差异均具有统计学意义,观察组优于对照组。结论:在高血压并颈动脉粥样硬化患者药物治疗过程中,应加行阿托伐他汀治疗,可提高临床疗效。     

银杏内酯注射液联合阿托伐他汀钙片对急性脑梗死患者神经功能、血脂、抗氧化能力和TLR4/NF-κB信号通路的影响

摘要 目的：探讨银杏内酯注射液联合阿托伐他汀钙片对急性脑梗死（ACI）患者神经功能、血脂、抗氧化能力和Toll样受体4（TLR4）/核因子-κB（NF-κB）信号通路的影响。方法：选择2019年6月~2020年6月期间来重庆医科大学附属永川医院接受治疗的152例ACI患者,采用随机数字表法分为两组,分别为研究组（n=76）,接受银杏内酯注射液联合阿托伐他汀钙片治疗;对照组（n=76）,接受阿托伐他汀钙片治疗。两组均治疗14 d,对比两组疗效、神经功能情况、血脂、抗氧化能力和TLR4/NF-κB信号通路变化情况,观察两组用药安全性。结果：研究组的临床总有效率明显高于对照组（P<0.05）。两组治疗后美国国立卫生院神经功能缺损评分（NIHSS）、神经元特异烯醇化酶（NSE）、S100β蛋白下降,且研究组低于对照组（P<0.05）。两组治疗后总胆固醇（TC）、低密度脂蛋白（LDL-C）、甘油三酯（TG）下降,且研究组低于对照组（P<0.05）,两组高密度脂蛋白（HDL-C）升高,且研究组高于对照组（P<0.05）。两组治疗后过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、总抗氧化能力（TAC）升高,且研究组高于对照组（P<0.05）。两组治疗后血清TLR4、NF-κB水平下降,且研究组低于对照组（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：银杏内酯注射液联合阿托伐他汀钙片治疗ACI,有利于减轻神经功能损伤,调节血脂,提高抗氧化能力,可能与调节TLR4/NF-κB信号通路有关。     

阿托伐他汀对急性冠状动脉综合征介入患者血清ox-LDL、hs-CRP及slCAM-1水平以及心功能的影响

目的:探讨阿托伐他汀对急性冠状动脉综合征(ACS)介入患者血清氧化低密度脂蛋白(ox-LDL)、高敏C反应蛋白(hs-CPR)及可溶性细胞间黏附分子-1(slCAM-1)水平以及心功能的影响。方法:选取2015年2月-2016年4月在我院接受治疗的ACS患者120例作为研究对象,采用乱数表法将所有患者分为观察组和对照组,两组均60例。在常规治疗基础上,观察组患者给予大剂量阿托伐他汀口服,对照组给予小剂量阿托伐他汀口服,对比两组患者治疗前后ox-LDL、hs-CRP及slCAM-1水平以及治疗后的心功能指标,观察两组患者治疗后的不良反应。结果:两组患者治疗2周后ox-LDL、hs-CRP及slCAM-1较治疗前均有明显下降,且观察组治疗2周后ox-LDL、hs-CRP及slCAM-1明显低于对照组(P0.05)。治疗2周后观察组的E峰与A峰流速比值(E/A)、左心室射血分数(LVEF)均显著高于对照组,而收缩指数、舒张指数和Tei指数均显著低于对照组(P0.05)。两组患者均未出现严重不良反应。结论:大剂量阿托伐他汀治疗ACS介入患者能有效降低患者术后ox-LDL、hs-CRP及slCAM-1ACS水平,抑制炎症反应,改善患者心功能,药物安全性与小剂量相当,值得临床推广应用。     

不同剂量阿托伐他汀对稳定性心绞痛患者TNF-α 和LDL-C 水平的影响

目的:观察不同剂量阿托伐他汀对冠心病稳定性心绞痛患者血清肿瘤坏死因子a(TNF-α)和低密度脂蛋白胆固醇(LDL-C)水平的影响。方法:用酶联免疫吸附法和生化发光分析法测定40例正常对照组和40例阿托伐他汀10mg组及39例阿托伐他汀20mg组冠心病患者治疗前后血清TNF-α和LDL-C水平的变化。结果:阿托伐他汀10mg及20mg组患者治疗12周后血清TNF-α和LDL-C水平明显降低,并且阿托伐他汀20mg组比阿托伐他汀10mg组血清TNF-α下降更明显,差异有显著性(P<0.05),但两组间LDL-C水平降低无显著性差异(P>0.05)。结论:阿托伐他汀可以降低冠心病患者血清LDL-C和TNF-α水平,减轻冠心病的炎症反应,并且这种机制独立于降脂作用以外。     

瑞舒伐他汀与阿托伐他汀治疗冠心病效果的对比分析

目的:对比观察瑞舒伐他汀与阿托伐他汀治疗冠心病的效果。方法:选取在我部诊治的冠心病患者64例,随机分为两组。观察组(32例)给予瑞舒伐他汀10mg/d治疗,对照组(32组)给予阿托伐他汀10mg/d治疗,共治疗4周。结果:治疗后,两组血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇均较治疗前降低。治疗组低密度脂蛋白胆固醇水平、血清总胆固醇水平较观察组下降明显(p0.05)。所有患者对两种药物能很好耐受,未发现严重不良反应。结论:在同等剂量下,瑞舒伐他汀调脂效果优于阿托伐他汀,二者安全性相同。     

双歧三联活菌胶囊联合阿托伐他汀对高脂血症患者肠道乳酸杆菌数量的影响及疗效观察

目的探讨双歧三联活菌胶囊联合阿托伐他汀对高脂血症患者肠道乳酸杆菌数量的影响及疗效观察。方法选取心内科就诊治疗的高脂血症患者86例,随机将其分为观察组(n=43例)和对照组(n=43例)。观察组患者予以双歧三联活菌胶囊联合阿托伐他汀治疗8周,其中双歧三联活菌胶囊420 mg/次,3次/d;阿托伐他汀片10 mg/次,1次/d。对照组患者予以单纯的阿托伐他汀治疗,剂量、方法及疗程同观察组。观察并记录两组患者治疗前后血脂总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平及肠道乳酸杆菌数量的变化。结果治疗8周后,两组患者TC、TG和LDL-C较前均有不同程度下降,HDL-C水平较前均有不同程度上升(P0.05),且观察组下降或上升幅度较对照组更明显(P0.05);同时两组患者肠道乳酸杆菌数量较前均有不同程度上升(P0.05),且观察组上升幅度较对照组更明显(P0.05)。结论双歧三联活菌胶囊联合阿托伐他汀治疗高脂血症能更明显降低TC、TG和LDL-C水平,升高HDL-C水平,具有良好的调脂效应,可能与其能调整肠道内的微生物菌群,大幅提升肠道乳酸杆菌数量密切相关。     

尼可地尔联合阿托伐他汀对冠状动脉慢血流患者炎症反应、血管内皮功能的影响及安全性分析

目的:探讨尼可地尔联合阿托伐他汀对冠状动脉慢血流患者炎症反应、血管内皮功能的影响及安全性。方法:选取2016年2月至2017年2月在我院就诊并经冠状动脉造影确诊为冠状动脉慢血流的患者63例,并将其随机分为3组,每组21人,分别为尼可地尔组、阿托伐他汀组、联合药物组(尼可地尔联合阿托伐他汀)。尼克地尔组在常规药物治疗的基础上给予尼克地尔片剂,阿托伐他汀组在常规药物治疗的基础上给予阿托伐他汀钙片,联合药物组在常规药物治疗的基础上给予尼克地尔片剂和阿托伐他汀钙片。治疗前后,检测和比较三组血浆超敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)、白细胞介素-6(interleukin-6,IL-6)、内皮素(endothelin-1,ET-1)、一氧化氮(nitric oxide,NO)、血常规、肝肾功能指标水平的变化及患者心绞痛的改善。结果:与治疗前相比,3组患者治疗后血浆hs-CRP、IL-6、ET-1水平均显著下降,NO水平明显升高,联合用药组血浆hs-CRP、IL-6、ET-1水平明显低于尼可地尔组和阿托伐他汀组,而NO水平显著高于尼可地尔组和阿托伐他汀组。治疗后,联合药物组心绞痛改善的有效率显著优于阿伐他汀组及尼可地尔组。治疗前后,三组患者血常规、肝肾功能均在正常范围内。结论:尼克地尔和阿托伐他汀联合应用可安全有效改善冠状动脉慢血流患者的血管内皮功能,抑制炎性反应,可能与降低患者血浆hs-CRP、IL-6、ET-1水平,升高血浆NO水平有关。     

LINE-1编码蛋白L1-ORF1的原核表达纯化和多克隆抗体制备

目的: 制备具有肿瘤组织特异性表达的L1-ORF1蛋白多克隆抗体并进行初步应用研究。方法:采取基因工程表达方法制备L1-ORF1蛋白,免疫家兔制备多克隆抗体,间接ELISA检测抗体效价,Western blot和细胞免疫荧光方法检测抗体特异性,免疫检测验证其识别肿瘤细胞内L1-ORF1蛋白的特异性。结果:制备的抗L1-ORF1蛋白多克隆抗体具有很高的敏感性与特异性,免疫学检测表明该抗体不仅能检测出正常细胞中瞬时表达的L1-ORF1蛋白,而且可检测出肿瘤细胞中天然表达的L1-ORF1蛋白。结论:制备的多克隆抗体具有较高的敏感性与特异性,为以后该抗体的进一步应用奠定了基础。     

Comparative CYP1A1 and CYP1B1 substrate and inhibitor profile of dietary flavonoids

CYP1A1 and CYP1B1 are two extrahepatic enzymes that have been implicated in carcinogenesis and cancer progression. Selective inhibition of CYP1A1 and CYP1B1 by dietary constituents, notably the class of flavonoids, is a widely accepted paradigm that supports the concept of dietary chemoprevention. In parallel, recent studies have documented the ability of CYP1 enzymes to selectively metabolize dietary flavonoids to conversion products that inhibit cancer cell proliferation. In the present study we have examined the inhibition of CYP1A1 and CYP1B1-catalyzed EROD activity by 14 different flavonoids containing methoxy- and hydroxyl-group substitutions as well as the metabolism of the monomethoxylated CYP1-flavonoid inhibitor acacetin and the poly-methoxylated flavone eupatorin-5-methyl ether by recombinant CYP1A1 and CYP1B1. The most potent inhibitors of CYP1-EROD activity were the methoxylated flavones acacetin, diosmetin, eupatorin and the di-hydroxylated flavone chrysin, indicating that the 4'-OCH(3) group at the B ring and the 5,7-dihydroxy motif at the A ring play a prominent role in EROD inhibition. Potent inhibition of CYP1B1 EROD activity was also obtained for the poly-hydroxylated flavonols quercetin and myricetin. HPLC metabolism of acacetin by CYP1A1 and CYP1B1 revealed the formation of the structurally similar flavone apigenin by demethylation at the 4'-position of the B ring, whereas the flavone eupatorin-5-methyl ether was metabolized to an as yet unidentified metabolite assigned E(5)M1. Eupatorin-5-methyl ether demonstrated a submicromolar IC(50) in the CYP1-expressing cancer cell line MDA-MB 468, while it was considerably inactive in the normal cell line MCF-10A. Homology modeling in conjunction with molecular docking calculations were employed in an effort to rationalize the activity of these flavonoids based on their CYP1-binding mode. Taken together the data suggest that dietary flavonoids exhibit three distinct modes of action with regard to cancer prevention, based on their hydroxyl and methoxy decoration: (1) inhibitors of CYP1 enzymatic activity, (2) CYP1 substrates and (3) substrates and inhibitors of CYP1 enzymes.     

DEC1 and MIC-1

Comment on: Qian Y, et al. Proc Natl Acad Sci USA 2012; 109:11300-5.     

Nucleic acid binding and unfolding properties of ribosomal protein S1 and the derivatives S1-F1 and m1-S1.

The nucleic acid binding and unwinding properties of wild-type Escherichia coli ribosomal protein S1 have been compared to those of a mutant form and a large trypsin-resistant fragment, both reported recently [J. Mol. Biol. 127, 41-45 (1979) and J. Biol. Chem. 254, 4309-4312 (1979). The mutant (m1-S1) contains 77% and the fragment (S1-F1) 66% of the polypeptide chain length (approximately 600 amino acid residues) of protein S1. The mutant is active in protein synthesis in vitro; the fragment, although retaining one or more of the functional domains of S1, is inactive in protein synthesis. We find that m1-S1 is is almost as effective as S1 in binding to poly(rU), phage MS2 RNA and simian virus 40 (SV40) DNA, and in unfolding poly(rU) and the helical structures present in MS2 RNA and phi X174 viral DNA. S1-F1, however, binds to poly(rU) and denatured SV40 DNA, but not to MS2 RNA. It unfolds neither poly(rU), nor the residual secondary structure of MS2 RNA or phi X174 viral DNA. Thus, there appears to be a correlation between the loss in ability of S1 to unwind RNA and the loss in its ability to function in protein synthesis.     

Regulation of PCTAIRE1 protein stability by AKT1, LKB1 and BRCA1

PCTAIRE1, also known as CDK16, is a cyclin-dependent kinase that is regulated by cyclin Y. It is a member of the serine-threonine family of kinases and its functions have primarily been implicated in cellular processes like vesicular transport, neuronal growth and development, myogenesis, spermatogenesis and cell proliferation. However, as extensive studies on PCTAIRE1 have not yet been conducted, the signaling pathways for this kinase involved in governing many cellular processes are yet to be elucidated in detail. Here, we report the association of PCTAIRE1 with important cellular proteins involved in major cell signaling pathways, especially cell proliferation. In particular, here we show that PCTAIRE1 interacts with AKT1, a key player of the PI3K signaling pathway that is responsible for promoting cell survival and proliferation. Our studies show that PCTAIRE1 is a substrate of AKT1 that gets stabilized by it. Further, we show that PCTAIRE1 also interacts with and is degraded by LKB1, a kinase that is known to suppress cellular proliferation and also regulate cellular energy metabolism. Moreover, our results show that PCTAIRE1 is also degraded by BRCA1, a well-known tumor suppressor. Together, our studies highlight the regulation of PCTAIRE1 by key players of the major cell signaling pathways involved in regulating cell proliferation, and therefore, provide crucial links that could be explored further to elucidate the mechanistic role of PCTAIRE1 in cell proliferation and tumorigenesis.     

Antagonism between Cry1Ac1 and Cyt1A1 Toxins of Bacillus thuringiensis

Most strains of the insecticidal bacterium Bacillus thuringiensis have a combination of different protoxins in their parasporal crystals. Some of the combinations clearly interact synergistically, like the toxins present in B. thuringiensis subsp. israelensis. In this paper we describe a novel joint activity of toxins from different strains of B. thuringiensis. In vitro bioassays in which we used pure, trypsin-activated Cry1Ac1 proteins from B. thuringiensis subsp. kurstaki, Cyt1A1 from B. thuringiensis subsp. israelensis, and Trichoplusia ni BTI-Tn5B1-4 cells revealed contrasting susceptibility characteristics. The 50% lethal concentrations (LC₅₀s) were estimated to be 4,967 of Cry1Ac1 per ml of medium and 11.69 ng of Cyt1A1 per ml of medium. When mixtures of these toxins in different proportions were assayed, eight different LC₅₀s were obtained. All of these LC₅₀s were significantly higher than the expected LC₅₀s of the mixtures. In addition, a series of bioassays were performed with late first-instar larvae of the cabbage looper and pure Cry1Ac1 and Cyt1A1 crystals, as well as two different combinations of the two toxins. The estimated mean LC₅₀ of Cry1Ac1 was 2.46 ng/cm² of diet, while Cyt1A1 crystals exhibited no toxicity, even at very high concentrations. The estimated mean LC₅₀s of Cry1Ac1 crystals were 15.69 and 19.05 ng per cm² of diet when these crystals were mixed with 100 and 1,000 ng of Cyt1A1 crystals per cm² of diet, respectively. These results indicate that there is clear antagonism between the two toxins both in vitro and in vivo. Other joint-action analyses corroborated these results. Although this is the second report of antagonism between B. thuringiensis toxins, our evidence is the first evidence of antagonism between toxins from different subspecies of B. thuringiensis (B. thuringiensis subsp. kurstaki and B. thuringiensis subsp. israelensis) detected both in vivo and in vitro. Some possible explanations for this relationship are discussed.     

Formation of 1-Deoxy-d-fructose, 1-Deoxy-d-sorbose, 1-Deoxy-d-tagatose and 1-Deoxy-erythrulose by Cell-free Extracts of Bacteria and Actinomycetes

In order to investigate the effect of the spacer in pepstatin-Sepharose on adsorption and elution of acid protease (AcP) in raw shoyu (unpasteurized soy sauce), a homologous pepstatin-aminoalkyl agarose series, (pepstatin-NH₂(CH₂)_n-Sepharose), that varied as to the length of the hydrocarbon chains was synthesized. When raw shoyu containing many kinds of proteases was subjected to affinity chromatography on these pepstatin-C_n-Sepharoses (n = 2, 4, 6, 8, 10 and 12), all of them adsorbed AcP. With increasing length of the spacer up to 6, more and more AcP became adsorbed onto the pepstatin-C_n-Sepharose, whereas with decreasing length of the spacer, more and more AcP was eluted with 0.05 M acetate buffer (pH 3) containing 2 M urea. The AcP was purified in one step from raw shoyu and did not have any carboxypeptidase activity. Some properties of the major component of the eluted AcPs were as follows: molecular weight, 6.7 × 10⁴, on gel filtration with TSK-G3000SW, optimum pH for activation of trypsinogen, 3.5, optimum pH for hydrolysis of hemoglobin, 2.75, and the Ki value toward pepstatin, 1.0 × 10⁸ m.     

Antagonism between Cry1Ac1 and Cyt1A1 toxins of bacillus thuringiensis

Most strains of the insecticidal bacterium Bacillus thuringiensis have a combination of different protoxins in their parasporal crystals. Some of the combinations clearly interact synergistically, like the toxins present in B. thuringiensis subsp. israelensis. In this paper we describe a novel joint activity of toxins from different strains of B. thuringiensis. In vitro bioassays in which we used pure, trypsin-activated Cry1Ac1 proteins from B. thuringiensis subsp. kurstaki, Cyt1A1 from B. thuringiensis subsp. israelensis, and Trichoplusia ni BTI-Tn5B1-4 cells revealed contrasting susceptibility characteristics. The 50% lethal concentrations (LC50s) were estimated to be 4,967 of Cry1Ac1 per ml of medium and 11.69 ng of Cyt1A1 per ml of medium. When mixtures of these toxins in different proportions were assayed, eight different LC50s were obtained. All of these LC50s were significantly higher than the expected LC50s of the mixtures. In addition, a series of bioassays were performed with late first-instar larvae of the cabbage looper and pure Cry1Ac1 and Cyt1A1 crystals, as well as two different combinations of the two toxins. The estimated mean LC50 of Cry1Ac1 was 2.46 ng/cm2 of diet, while Cyt1A1 crystals exhibited no toxicity, even at very high concentrations. The estimated mean LC50s of Cry1Ac1 crystals were 15.69 and 19.05 ng per cm2 of diet when these crystals were mixed with 100 and 1,000 ng of Cyt1A1 crystals per cm2 of diet, respectively. These results indicate that there is clear antagonism between the two toxins both in vitro and in vivo. Other joint-action analyses corroborated these results. Although this is the second report of antagonism between B. thuringiensis toxins, our evidence is the first evidence of antagonism between toxins from different subspecies of B. thuringiensis (B. thuringiensis subsp. kurstaki and B. thuringiensis subsp. israelensis) detected both in vivo and in vitro. Some possible explanations for this relationship are discussed.