Alpha-lipoic acid activates eNOS through activation of PI3-kinase/Akt signaling pathway

BackgroundLipoic acid (LA) exerts therapeutic effects on cardiovascular diseases. However, the mechanisms underlying these therapeutic effects remain elusive. Endothelial nitric oxide synthase (eNOS) plays a critical role in cardiovascular homeostasis. LA was shown to potently activate PI3-kinase/Akt pathway, and the latter is critical in the regulation of eNOS activity. In the present study, we test the hypothesis that LA improves endothelial function through PI₃-kinase/Akt-mediated eNOS activation.Methods and ResultsWestern blot analysis showed that LA time- and dose-dependently induced phosphorylation of Akt and eNOS in human umbilical vein endothelial cells (HUVECs). Both PI₃-kinase and Akt inhibitors abolished LA-induced eNOS phosphorylation, indicating that LA induces eNOS phosphorylation through the PI₃-kinase/Akt pathway. This increase in eNOS phosphorylation was paralleled by an increase in NO release by HUVECs, supporting its relevance in eNOS activity regulation. Myograph analysis revealed that LA relaxed phenylephrine-induced contraction. Endothelium removal and NOS inhibition by L-NAME abolished this vasodilator action of LA, and Akt but not AMPK inhibition significantly reduced the vasodilator action of LA, indicating that it is mediated by PI₃-kinase/Akt pathway-dependent activation of eNOS. Consistent with in vitro results, intraperitoneal injection with LA significantly increased plasma nitrite and nitrate levels in C57Bl/6j mice.ConclusionsLA activates eNOS through a PI3-kinase/Akt signaling pathway-dependent mechanism, offering a potential molecular basis for the therapeutic effects of LA on cardiovascular diseases.     

胆囊结石与胆囊黏膜细胞IL-1β成熟分泌的相关性研究

探讨胆囊结石与胆囊组织IL1-SymbolbA@表达及其成熟分泌的相关性。 〖HT5”H〗方法〖HT5”K〗〓收集胆结石胆囊及其胆汁样本21例,其中胆固醇结石4例、色素结石7例、混合结石10例,采用PCR检测细菌感染情况,ELISA检测胆汁中IL1-SymbolbA@, 蛋白印迹杂交方法检测IL1-SymbolbA@蛋白表达,免疫组化检测胆囊黏膜IL1-SymbolbA@表达,并分析临床相关性。结果在排除伴有细菌感染的情况下, 结石患者胆汁IL1-SymbolbA@含量在1.93～11.80ng/ml,混合结石组胆汁IL1-SymbolbA@（4.753±2.651）显著高于胆固醇结石组（2.640±0.167）和色素结石组（2.762±1.081） （P＜0.05）;免疫组化、蛋白印迹杂交检测表明胆囊黏膜proIL1-SymbolbA@、IL1-SymbolbA@高表达,推测是胆汁IL1-SymbolbA@重要来源之一、 并示胆结石患者胆囊黏膜有炎症小体激活。结论胆结石患者在非细菌感染情况下,胆汁IL1-SymbolbA@增加可能与胆囊黏膜细胞炎症小体的激活密切相关。     

急性阑尾炎患者术中寒战的临床研究

目的 探讨长托宁对急性阑尾炎患者术中寒战的预防作用。方法 蛛网膜下腔阻滞麻醉下行急性阑尾炎手术患者120例,随机分为3组: Ⅰ组(对照组),Ⅱ组(长托宁组),Ⅲ组(哌替啶组)。观察三组患者术中寒战的发生率及严重分级;记录静脉注药前1min(T₀)、静脉注药后3min(T₁)、5min(T₂)、10min(T₃)、15min(T₄)、20min(T₅)、30min(T₆)的血氧饱和度(SPO₂)、平均动脉压(MAP)、心率(HR)的变化情况;用药后不良反应的发生情况;注药前1min(T₀)、注药后30min(T₆)、麻醉后30min(T₇)和手术结束时(T₈)体温变化情况。结果 Ⅱ组、Ⅲ组的寒战发生率分别为10％、7.5％,显著低于Ⅰ组的65％(P<0.01),Ⅱ组和Ⅲ组之间比较差异无显著性(P>0.05);Ⅱ组、Ⅲ组寒战严重程度分级显著低于Ⅰ组(P<0.05),Ⅱ组和Ⅲ组之间比较差异无显著性(P>0.05)。血氧饱和度(SPO₂)的变化,Ⅲ组用药后下降明显,与Ⅰ组和Ⅱ组比较有显著性差异(P<0.01)。平均动脉压(MAP)、心率(HR)、体温,三组变化比较差异均无统计学意义(P>0.05)。Ⅲ组静脉注药后,发生恶心呕吐6例(15％),嗜睡5例(12.5％),明显高于Ⅱ组和Ⅰ组(P<0.05)。结论 麻醉前预防性静脉注射长托宁(0.01mg/kg)具有预防术中寒战发生的作用,效用与预防性静脉注射哌替啶(0.5mg/kg)相似,但长托宁无类似哌替啶的呼吸抑制作用,且无哌替啶高发生率的恶心呕吐、嗜睡不良反应,对血压、心率、体温无影响,在临床预防术中寒战的应用中优于哌替啶。     

糖尿病合并不同程度冠状动脉粥样硬化患者外周血EMP及EPC水平的研究

目的探讨糖尿病患者EMPs、EPCs与不同程度冠状动脉粥样硬化病变及糖代谢异常的关系。方法117例糖尿病患者,根据临床症状、心肌标记物水平以及冠状动脉造影及冠脉内血管超生(IVUS)结果,将患者分为急性冠脉综合症组(A组,n=45)、稳定型心绞痛组(B组,n=27)、冠状动脉病变组(狭窄＜50%,C组,n=45)。采用流式细胞术检测3组患者外周血中CD144⁺/Annexin V+的内皮微颗粒以及CD34⁺/CD39⁺内皮祖细胞的水平,并检测血脂、血糖、糖化血红蛋白、炎性指标、心肌标记物、肝肾功能等各项指标。结果 3组相比,年龄、性别、血压、吸烟、体质量指数、血脂等组间差异均无统计学意义。超敏C反应蛋白、CK-MB、HsTnT均在A组中较高,与其余两组相比差异有统计学意义(P＜0.001)。3组之间空腹血糖、餐后血糖及糖化血红蛋白差异无统计学意义。外周血的CD144⁺/Annexin V+EMPs水平3组间差异有统计学意义,其中A组显著高于B组(P＜0.05),且A、B组CD144⁺/Annexin V+EMPs水平显著高于C组(P＜0.05),EMPs水平与糖化血红蛋白不相关。A、B组外周血CD34⁺/CD39⁺EPCs水平显著低于C组(P＜0.05),而A、B组间无差异,且EPCs水平与糖化血红蛋白呈负相关。结论 糖尿病患者冠脉病变加重是导致外周血CD144⁺/Annexin V+EMPs水平升高的主导损伤因素。糖代谢异常对内皮功能的损伤主要是通过损伤内皮修复功能因素实现的。     

TKA术中假体旋转力线控制的研究进展

近年来,全膝关节置换术(total knee arthroplasty, TKA)作为治疗严重膝关节疼痛、畸形、功能障碍的一种有效的临床术式,在国内外得到了广泛的开展。但其术后并发症的发生率也相对较高,对手术后远期效果和膝关节假体的长期生存率会产生较大的影响。随着对膝关节旋转力线的重视程度的提高和研究技术的发展,笔者查阅近几年有关控制旋转力线的文献,阐述其与术后功能的相关性,综合新技术在旋转控制方面的应用进展,以期为临床进一步研究提供参考。     

Activation status of CD56dim natural killer cells is associated with disease activity of patients with systemic lupus erythematosus

Clinical Rheumatology - Decreased natural killer (NK) cells have been reported in systemic lupus erythematosus (SLE) patients. However, the role of NK cells in the pathogenesis of SLE is not well...     

Ion Torrent ™ Genexus ™ Integrated Sequencer and ForeNGS Analysis Software—An automatic NGS-STR workflow from DNA to profile for forensic science

The Ion Torrent ™ Genexus ™ Sequencer (Genexus) is a highly integrated instrument that can automate library construction, templating, and sequencing in a single-instrument run. By programing the ForeNGS Analysis Software (FNAS), we bridged the gap between sequencing and genotyping without manual intervention. FNAS can automatically transfer sequencing output files from Genexus, analyze the repeat and flanking regions aligned to the GRCh38 assembly, name the alleles according to the ISFG guidelines, and generate user-friendly interactive profiles. Genexus and FNAS can accomplish the fully automatic DNA-to-Profile workflow in forensics. Based on our experiences, the optimal assay parameters on Genexus were validated as follows: 24 cycles of target amplification for library construction; 40 μL of library and 400 bp of template size for templating; 852 flows of dNTPs by order of Ion samba HID2 for sequencing; and 750,000 reads per sample at minimum for 16 samples multiplexed on a lane. By developmental validations of the Precision ID Globalfiler ™ NGS STR Panel v2, Genexus presented competitive performance at the optimal assay parameters qualified to detect commonly used forensic STR markers. It could produce repeatable and reproducible results, and human profiles could be easily separated from nonhuman profiles. Additionally, Genexus was sensitive enough to detect samples with 100 pg of input DNA, and it was suitable for various types of case samples, especially for low copy number samples and degraded samples. Moreover, minor contributors could be detected between the 4:1 and 1:4 mixtures with an analysis threshold of 50 × . The Genexus workflow is a robust and labor-effective solution enabling forensic scientists to obtain NGS-STR profiles within a single day and with only the need to prepare DNA extracts, then set up Genexus, and finally interpret profiles on FNAS.     

64层螺旋CT冠状动脉血管成像与冠状动脉造影对照研究

目的评价64层螺旋CT诊断冠状动脉粥样硬化性心脏病的临床应用价值。方法40例临床诊断或可疑冠心病患者行64层螺旋CT心电门控平扫及增强扫描,并以冠状动脉造影结果作为对照。得出64层螺旋CT冠状动脉CT血管成像(CTA)诊断冠状动脉狭窄的准确性、敏感性、特异性。结果64层螺旋CT冠状动脉血管成像用于诊断冠心病的敏感性为87.1%,特异性为67.5%,准确性为80.0%。结论①64层螺旋CT检查是一种无创、快捷的冠状动脉血管检查方法,对冠心病的诊断有较高的准确性。②与冠状动脉造影术相比,64层螺旋CT冠状动脉血管成像对冠状动脉血管狭窄程度判断仍有一定差异。     

Effects of dietary supplementation with vitamin E and selenium on rat hepatic stellate cell apoptosis

AIM: To evaluate the effects of dietary supplementation with vitamin E and selenium on proliferation and apoptosis of hepatic stellate cells (HSCs), in acute liver injury induced by CCl4, and to explore their role in the recovery from hepatic fibrosis phase. METHODS: An acute liver damage model of rats was established by intraperitoneal injection of carbon tetrachloride (0.3 mL/100 g body weight) twice a week, then the rats were killed at 6, 24, 48, and 72 h after the first and third injection, respectively. A liver fibrosis model was established by the same injection for 8 wk. Then three rats were killed at 3, 7,14, and 28 d after the last injection, respectively. The rats from the intervention group were fed with chow supplemented with vitamin E (250 mg/kg) and selenium (0.2 mg/kg), and the rats in the normal control group and pathological group were given standard chow. Livers were harvested and stained with hematoxylin and eosin, Sirius red. Activated HSCs were determined by α-smooth muscle actin immunohistochemistry staining. Apoptotic HSCs were determined by dual staining with the terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL) and α-smooth muscle actin immunohistochemistry. Serum alanine aminotransferase and aspartate aminotransferase were also analyzed. RESULTS: In the acute liver damage model, the degree of liver injury was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, while the number of apoptotic HSCs was more in the intervention group than in the pathological group. In the liver fibrosis model, the degree of liver fibrosis was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, and the number of apoptotic HSCs was more in the intervention group than in the pathological group. CONCLUSION: Vitamin E and selenium supplementation at the given level can inhibit CCl4-induced activation and proliferation of HSCs and promote the apoptosis of activated HSCs in acute damage phase. Vitamin E and selenium can also effectively decrease the degree of hepatic fibrosis and promote the recovery process.