血红蛋白水平对平板运动试验阳性结果诊断价值的影响

目的研究血红蛋白水平对平板运动试验阳性结果诊断价值的影响。方法选择2010年1月到2016年12月因胸痛或胸闷怀疑冠心病行平板运动试验阳性和冠状动脉造影者300例,造影结果显示主要血管狭窄≥70%的137例(阳性组),<70%163例(阴性组),分析比较临床资料及对运动平板试验阳性结果预测值的影响。结果阳性组的血红蛋白、尿酸、肌酐、甘油三酯、男性比例、吸烟比例和高血压比例明显高于阴性组,红细胞分布密度(RDW)、高密度脂蛋白胆固醇(HDL-C)低于阴性组,差异均有统计学意义(均P<0.05)。单因素和多因素logistic回归分析血红蛋白是平板运动试验阳性患者预测冠心病的独立预测因素。ROC曲线分析,血红蛋白曲线下面积0.702(P<0.01),血红蛋白≥137g/L,其敏感度为60.58%,特异度为74.85%。结论血红蛋白水平会影响平板运动试验阳性结果的诊断价值。     

Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation

BACKGROUND Arachidyl amido cholanoic acid(Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis. In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH), 52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c, an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model [induced with a 0.1% methionine and choline deficient diet(0.1 MCD)] after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20 μmol/L Aramchol or vehicle for 48 h. Subsequently, analyses were performed including Western blot, proteomics by mass spectrometry, and fluxomic analysis with ~(13)C-uniformly labeled glucose. For the in vivo part of the study, male C57 BL/6 J mice were randomly fed a control or 0.1 MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk. Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes. This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA) synthesis and oxidation [PACCα/β(S79), SCD1, CPT1A/B, HADHA, and HADHB], oxidative phosphorylation(NDUFA9, NDUFB11, NDUFS1, NDUFV1, ETFDH, and UQCRC2), tricarboxylic acid(TCA) cycle(MDH2, SUCLA2, and SUCLG2), and ribosome(P-p70S6K[T389] and P-S6[S235/S236]). Flux experiments with ~(13)C uniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes, as indicated by the increase in the number of rounds that malate remained in the TCA cycle. Finally, liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1 MCD fed mice in a dose-dependent manner, showing normalization of glucose, G6P, F6P, UDP-glucose, and Rbl5 P/Xyl5 P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1, which in turn activate FA β-oxidation and oxidative phosphorylation.     

暴发性1型糖尿病5例临床资料分析与讨论

目的 提高临床医师对暴发性1型糖尿病（FT1DM）的认识. 方法 回顾性分析2003年10月至2012年10月我院收治的FT1DM患者的临床资料. 结果 患者年龄21～46岁,起病时随机血糖＞24.0 mmol/L,HbA1c 5.1 ％～7.6％.1～5 d迅速发展至DKA. 结论 FF1DM发病急骤,代谢异常严重,胰岛β细胞功能受损严重,易合并并肾、心脏、肌肉等多脏器的功能损害,须引起临床医师的高度重视.     

Hemoglobin A1c values are affected by hemoglobin level and gender in non‐anemic Koreans

Aims/Introduction

To evaluate whether hemoglobin A1c (HbA1c) levels are affected by hemoglobin level and gender.

Materials and Methods

A cross‐sectional analysis was carried out in a sample of 87,284 non‐diabetic Koreans without anemia who participated in comprehensive health check‐ups between January and December 2009 at the Kangbuk Samsung Hospital Total Healthcare Center in Seoul, Korea. We categorized men and women separately according to fasting plasma glucose and hemoglobin level to carry out the analysis.

Results

HbA1c increased steadily with increasing fasting plasma glucose level. Both men and women with lower hemoglobin had significantly higher HbA1c at a given fasting glucose level, and this result was consistent across the fasting glucose quintiles within the non‐diabetic range. Women had a lower mean hemoglobin value compared with men, and women had higher HbA1c levels at a given fasting glucose level consistently across the fasting glucose deciles. There was also a gender‐specific association between age and HbA1c (P < 0.001 for interaction).

Conclusions

HbA1c values were affected by hemoglobin level and gender in non‐anemic Koreans. Thus, hemoglobin level and gender should be considered in the diagnosis of diabetes using HbA1c.     

Estimated contribution of hemoglobin and myoglobin to near infrared spectroscopy

We calculated the light absorbing potential (LAP) of hemoglobin (Hb) and myoglobin (Mb) in mammalian skeletal muscle at rest based on analysis of published chemical and morphometric data (Part 1), interpreted changes in total[Hb + Mb] from NIRS during exercise (Part 2), and estimated the potential contribution of Hb and Mb to changes in NIRS from rest to exercise (Part 3). Part 1: [Hb] in skeletal muscle was estimated from microvascular volume, systemic blood [Hb], and microvascular hematocrit and saturation at rest and during exercise. Part 2: Changes in total[Hb + Mb] (as t[Hb + Mb]) during cycling or knee extension exercise were interpreted using the results of Part 1. Part 3: Using estimates of mean microvascular PO₂, Hb and Mb contribution at peak exercise was estimated. Across several species, [Mb] contributed ∼50–70% of the total LAP to NIRS at rest in skeletal muscle. With exercise, increases in t[Hb + Mb] of up to 30% could be entirely explained by the predicted increase in microvascular hematocrit with exercise. Finally, Mb was estimated to contribute ∼70% of the changes in NIRS from rest to peak exercise.     

冠心病患者血清对氧磷酶1活性与糖化血红蛋白水平及冠状动脉病变的关系

目的探讨冠心病患者血清对氧磷酶1(PON1)活性与糖化血红蛋白(HbA1c)水平及冠状动脉病变严重程度的关系。方法入选心内科入院拟诊冠心病患者133例,根据冠状动脉造影结果分为冠心病组101例及对照组32例,冠心病组再依据HbA1c水平分为三个亚组:HbA1c<6.5%组31例、6.5%≤HbA1c<9%组41例、HbA1c≥9%组29例。分光光度法测定PON1活性,冠状动脉病变结果采用Gensini积分。比较各组PON1活性及Gensini积分,分析PON1活性与HbA1c水平及冠状动脉病变程度的相关性。结果血清PON1活性在冠心病组(2.17±0.18)较对照组(2.49±0.19)明显降低(P<0.01);冠心病三个亚组间比较,HbA1c≥9%组较HbA1c<6.5%组PON1活性明显下降(P<0.01)且冠状动脉狭窄Gensini积分显著升高(P<0.01),HbA1c≥9%组较6.5%≤HbA1c<9%组PON1活性有所下降(P<0.05)而冠状动脉狭窄Gensini积分升高(P<0.05)。相关分析表明,血清PON1活性对数值与HbA1c水平呈负相关(r=-0.534,P<0.01),与冠状动脉造影Gensini积分呈负相关(r=-0.742,P<0.01)。结论冠心病患者血清PON1活性明显降低并与HbA1c水平升高及冠状动脉狭窄严重程度密切相关。     

血红蛋白、胆红素在预测心衰患者全因死亡风险中的作用

目的研究血红蛋白浓度（Hb）及总胆红素水平（Tbil）是否能预测慢性心衰患者全因死亡。方法对入选的1197例慢性心力衰竭（CHF）患者进行随访,全因死亡为随访终点。先比较不同Hb及Tbil水平其他临床指标分布的差异;再应用Kaplan-Meier曲线及Log-rank检验进行不同水平生存描述及比较;单因素Cox回归判断各影响因素与心衰死亡的关系,将有统计学意义的指标引入多元Cox回归,以明确低Hb、高Tbil是否为心衰死亡的独立预测因子。结果完成随访1025例（失访率14.4%）,死亡360例（35.1%）。随访中位数44个月。不同Hb及BMI水平的心衰患者在合并症、血压、左室射血分数（LVEF）、多种检验项目及用药方面存在显著差异。随着Hb减低及Tbil增高,死亡率增加。单因素分析显示,总胆红素（Tbil）、肌酐、尿酸（UA）升高以及血红蛋白（Hb）、血钠（Na）降低均可增加心衰患者死亡风险。校正其他影响因素后,Hb、Tbil、Scr和UA与心衰死亡独立相关,Hb减低（HR1.142）及Tbil〉19umol/L（HR1.312）均为心衰患者死亡的独立预测因素。结论 Hb、Tbil和UA与心衰死亡独立相关,Hb降低和Tbil升高均为心衰死亡的独立预测因素。     

The antioxidant tempol decreases acute pulmonary thromboembolism-induced hemolysis and nitric oxide consumption

Introduction

Acute pulmonary thromboembolism (APT) is a critical condition associated with acute pulmonary hypertension. Recent studies suggest that oxidative stress and hemolysis contribute to APT-induced pulmonary hypertension, possibly as a result of increased nitric oxide (NO) consumption. We hypothesized that the antioxidant tempol could attenuate APT-induced hemolysis, and therefore attenuate APT-induced increases in plasma NO consumption.

Materials and Methods

APT was induced in anesthetized sheep with autologous blood clots. The hemodynamic effects of tempol infused at 1.0 mg/kg/min 30 min after APT were determined. Hemodynamic measurements were carried out every 15 min. To assess oxidative stress, serum 8-isoprostanes levels were measured by ELISA. Plasma cell-free hemoglobin concentrations and NO consumption by plasma samples were determined. An in vitro oxidative AAPH-induced hemolysis assay was used to further validate the in vivo effects of tempol.

Results

APT caused pulmonary hypertension, and increased pulmonary vascular resistance in proportion with the increases in 8-isoprostanes, plasma cell-free hemoglobin concentrations, and NO consumption by plasma (all P < 0.05). Tempol attenuated the hemodynamic alterations by approximately 15-20% and blunted APT-induced increases in 8-isoprostanes, in cell-free hemoglobin concentrations, and the increases in NO consumption by plasma (P < 0.05). Tempol dose-dependently attenuated AAPH-induced in vitro hemolysis (P < 0.05).

Conclusions

Our findings are consistent with the idea that antioxidant properties of tempol decrease APT-induced hemolysis and nitric oxide consumption, thus attenuating APT-induced pulmonary hypertension.