焦亡的分子机制及其在血液肿瘤中的研究进展

焦亡是一种新的程序性细胞死亡类型,它不同于凋亡和坏死,可以由各种细胞内或细胞外刺激引发.焦亡主要由Caspase-1/3/4/5/11和Gasdermin蛋白家族介导产生,具有细胞肿胀、胞膜溶解和炎症因子释放的特点.血液肿瘤亦称恶性血液病,包括急/慢性白血病、淋巴瘤、多发性骨髓瘤、骨髓增生异常综合征等,以恶性转化的造血...     

Has hyperglycemia a different prognostic role in STEMI patients with or without diabetes?

Background and aimsHyperglycemia at hospital admission is a common finding in patients with STEMI. However, whether elevated acute glycemia in these patients may have a direct impact on worsening prognosis or is just a marker of a greater neurohormonal activation in response to the infarction is still unsettled.We sought to investigate the prognostic impact of hyperglycemia at hospital admission in patients undergoing primary PCI (pPCI) for STEMI, and the influence of the presence of diabetes mellitus (DM) on its prognostic impact.Methodsand Results, We enrolled 2958 consecutive STEMI patients treated by pPCI. Hyperglycemia was defined as plasma glucose >198 mg/dL (or >11 mmol/L). Patients with hyperglycemia showed a greater risk-profile; they also experienced a higher mortality both at univariable (17.6% vs 5.2%, p < 0.001) and multivariable (HR 1.9, 95%IC 1.5–2.9, p = 0.001) analysis. However, after stratification for DM presence, hyperglycemia resulted as an independent predictor of mortality only in patients without DM (HR 2, 95%IC 1.2–3.4, p = 0.01).ConclusionHyperglycemia in the setting of myocardial infarction treated with primary PCI in an independent predictor of all-cause mortality in patients without diabetes; in patients with diabetes, its prognostic impact seems attenuated.     

两种方法治疗急性脑梗死疗效比较

目的 探讨灯盏花注射液治疗急性脑梗死的疗效。方法 急性脑梗死患者124例分为2组，在常规治疗基础上，治疗组62例加用灯盏花注射液，对照组62例加用低分子右旋糖酐和丹参注射液，治疗4周，对比两组神经功能缺损评分情况及有效率。结果 治疗组神经功能缺损评分低于对照组，有效率高于对照组（P〈0．01）。结论 灯盏花注射液治疗急性脑梗死疗效优于低分子右旋糖酐和丹参注射液。     

急性冠脉综合征患者循环miR-208b-3p与心室重构的关系研究

目的 探究急性冠脉综合征患者循环miR-208b-3p表达水平与心室重构的关系。方法 收集140例西安市第九医院心血管内科2015年11月至2016年12月确诊为急性冠脉综合征患者,实时定量PCR（quantification PCR,qPCR）检测样本miR-208b-3p的表达水平,根据miR-208b-3p表达水平高低以每组同样患者数分为四组,分别比较四组住院及出院1年随访超声测量结果,并对测量值变化率做进一步对比分析。结果 住院期间各超声测量组患者例数之间差异无统计学意义（p>0.05）,出院1年各左心室舒张末期内径（left ventricular end-diastolic dimension,LVDd）组和各左心室射血分数（left ventricular ejection fraction,LVEF）组患者例数的差异具有统计学意义（p=0.046;p=0.036）,各左心室短轴缩短率（fraction shortening,FS）组差异无统计学意义（p>0.05）。变化率分析显示各组LVDd变化率分别为（-0.410±0.125、0.024±0.156、0.082±0.152、0.004±0.078）（p=0.326）;各组FS变化率分别为（0.081±0.379、0.074±0.209、0.061±0.258、0.123±0.310）（p=0.896）;各组LVEF变化率分别为（0.082±0.035、0.046±0.035、0.022±0.037、-0.082±0.052）（p=0.034）。对各组LVEF测量值变化率进行两两对比显示高危组分别与低危组及中低危组差异具有统计学意义（p=0.010;p=0.042）。结论 循环miR-208b-3p与远期心室重构相关,并且对LVEF值的影响最大。     

Characteristics, outcomes, and predictors of 1-year mortality in patients hospitalized for acute heart failure.

AIMS: Acute heart failure (AHF) is associated with poor prognosis and requires recurrent hospitalizations. However, studies on AHF characteristics, treatment, and prognostic factors are few. Our aim was to investigate the characteristics, treatment, and 1-year prognosis of AHF and identify prognostic factors in different clinical groups. METHODS AND RESULTS: We conducted a prospective multicentre study with 620 patients hospitalized due to AHF; mean age 75.1 (10.4) years, 50% male. Half of the patients had new-onset heart failure. Acute congestion (63.5%) and pulmonary oedema (26.3%) were the most common clinical presentations. Left ventricular ejection fraction (LVEF) was reported in two-thirds of patients. Half of these had preserved systolic function (LVEF> or =45%). At discharge, 86% of patients had beta-blockers and 76% either ACE-inhibitors or angiotensin receptor blockers in use. The 12-month all-cause mortality was 27.4%. We identified several clinical and biochemical prognostic risk factors in univariate analysis. Independent predictors of 1-year mortality were older age, male gender, lower systolic blood pressure (SBP) on admission, C-reactive protein, and serum creatinine >120 micromol/L. CONCLUSION: We present the characteristics and prognosis of an unselected population of AHF patients. One-year mortality is high, and independent clinical risk factors include age, male gender, lower SBP on admission, C-reactive protein, and renal dysfunction.     

A quantitative evaluation of ST-segment changes on the 18-lead electrocardiogram during acute coronary occlusions

This study determined quantitative ST segment changes on the 18-lead electrocardiogram (ECG) during occlusions in each of the coronary arteries.

Methods

Continuous 18-lead ECGs, including standard 12 leads, posterior (V_7-9), and right ventricular (RV) leads (V_3-5R) were recorded for 155 subjects undergoing percutaneous coronary occlusions, the maximum intervention.

Results

During 58 left anterior descending (LAD) coronary occlusions, the maximum ST elevation and depression were in V₃ (4.2mm) and III (−0.9mm), respectively. During 44 right coronary artery (RCA) occlusions, the maximum ST elevation and depression were in III (2.2mm) and aVL (−1.4mm), respectively. During 53 left circumflex (LCX) occlusions, the maximum ST elevation and depression were in V₇ (0.8mm) and V₂ (−1.6mm), respectively.

Conclusions

ST elevation often occurred in the anteroapical (V₁-V₆), lateral (I, aVL), and RV lead V_3R during LAD occlusions; in the inferior, RV, and posterior leads during RCA occlusions; and in the posterior, inferior, and apical leads (V₅-V₆) during LCX occlusions.     

Mechanism of acute pancreatitis Cellular and subcellular events

A membrane-bound system through which secretory and lysosomal proteins travel in a vectorial fashion is essential for the preserved integrity of pancreatic acinar cells. This system is composed of an ordered array of compartments, such as the rough endoplasmic reticulum, the Golgi complex, lysosomes, and secretory granules. As a principle, in acute pancreatitis the final steps of this transport seem to be disturbed. Caerulein-induced pancreatitis is a valuable experimental model for studying altered intracellular transport, and compartmentation of lysosomal and digestive enzymes. The formation of enlarged secretory vacuoles containing lysosomal and digestive enzymes is paralleled by the activation of lysosomes and degradation of cellular organelles in autophagosomes. On the level of secretory and autophagic vacuoles, activation of serine proteases occurs, which in addition to increasing lysosomal enzyme activities can represent the initial stage for acinar cell destruction and the development of pancreatitis.     

脂质运载蛋白-2在急性心肌梗死发病过程中的变化及临床意义

目的探讨脂质运载蛋白-2(lipocalin-2,Lcn-2)在急性心肌梗死(AMI)过程中的变化及其临床意义。方法分别采集100例AMI患者行经皮冠状动脉介入(PCI)治疗前及PCI治疗后24 h、72 h外周血,30例健康受试者外周血作为对照。分离血浆及中性粒细胞;分别采用酶联免疫吸附法(ELISA)及RT-q PCR法检测血浆及中性粒细胞中Lcn-2水平。选取12周龄25~30 g的C57BL/6雄性小鼠(北京维通利华) 16只用于制备AMI模型。通过开胸结扎左冠状动脉前降支建立小鼠AMI模型(n=8)。分别取模型组小鼠结扎前及结扎1 h、24 h外周血,检测血浆及外周血中性粒细胞Lcn-2水平。此外,采用Lcn-2抗体对该模型进行干预,对结扎24 h后小鼠进行心功能检测,并采用TUNEL法和免疫荧光检测心脏梗死区心肌凋亡情况及中性粒细胞浸润情况。结果与健康受试者比较[血浆Lcn-2(20.35±8.51) ng/m L,中性粒细胞Lcn-2(1.03±0.16)倍],AMI患者PCI治疗前Lcn-2水平[血浆(113.55±22.73) ng/m L,中性粒细胞(16.81±3.83)倍]明显升高,PCI治疗后24 h[血浆(74.26±14.36) ng/m L,中性粒细胞(10.86±2.71)倍]、72 h[血浆(46.81±12.83) ng/m L,中性粒细胞:(6.15±1.92)倍]依次明显下降。在小鼠模型上,与结扎前比较[血浆Lcn-2(8.14±2.33) ng/m L,中性粒细胞Lcn-2(1.01±0.08)倍],小鼠结扎1 h Lcn-2水平[血浆(17.33±6.19) ng/m L,中性粒细胞(12.86±5.66)倍]、24 h[血浆(35.15±10.44) ng/m L,中性粒细胞(20.17±7.14)倍]依次明显升高。与模型组比较[左心室舒张末期容积(LVEDV)(143.25±10.29)μL,左室射血分数(LVEF)(40.35±5.10)%,左室缩短分数(LVFS)(20.16±2.64)%],Lcn-2抗体干预明显改善了小鼠的心功能[LVEDV(123.25±9.35)μL,LVEF(49.37±6.69)%,LVFS(24.79±3.40)%]。此外,Lcn-2抗体干预明显抑制心肌细胞凋亡。结论血浆及中性粒细胞中Lcn-2水平与AMI发生相关,靶向抑制Lcn-2对AMI有明显的保护作用。     

TNF-α对肺微血管内皮细胞ERM蛋白表达的研究

目的 观察肿瘤坏死因子-α(TNF-α)对大鼠肺微血管内皮细胞(PMVEC)表达埃兹蛋白-根蛋白-膜突蛋白(ezrin-radixin-moesin,ERM)及磷酸化ERM蛋白(p-ERM)的影响,并初步探讨Rho激酶(ROCK)与ERM蛋白磷酸化的关系.方法 体外培养大鼠PMVEC,随机(随机数字法)分为TNF-α量效组(0、0.1、1、10 μg/L TNF-α与PMVEC孵育60 min)、TNF-α时效组(10 μg/LTNF-α分别与PMVEC孵育0、15、30、60、90、120、180 min)和ROCK抑制剂(Y-27632)干预组:分别以10μg/L的TNF-α和30 μmol/L Y-27632+ 10 μg/LTNF-α与PMVEC孵育60min.Western印迹检测ERM蛋白及p-ERM相对表达量.采用SPSS 16.0软件进行分析,多组变量间比较采用单因素方差分析,以P＜ 0.05为差异具有统计学意义.结果 Western印迹检测到大鼠PMVEC均表达ERM蛋白和p-ERM,量效组p-ERM表达量随TNF-α浓度(0、0.1、1、10 μg/L)增加逐渐升高,分别为0.648±0.102、0.728±0.082、0.926±0.121、1.245±0.134(均P=0.000).时效组p-ERM相对表达量于15 min开始上升(0.777±0.151),90 min达高峰(1.295±0.176),之后渐下降,120 min (0.802±0.139),180 min仍维持较高水平(0.769±0.128),分别与未刺激0 min组(0.631±0.123)比较,P=0.004,0.000,0.001,0.016.ROCK抑制剂预处理PMVEC后再给予TNF-α刺激,p-ERM相对表达量(0.634±0.112)较单独TNF-α刺激组(0.875±0.164)显著减少(P =0.002),而较单独ROCK抑制剂组(0.661±0.108)和未处理组(0.654±0.125)差异无统计学意义(分别为P=0.973,P=0.900).结论 TNF-α诱导大鼠PMVEC中的ERM蛋白磷酸化表达增加,ROCK参与其磷酸化调控.     

心理干预对康复期脑卒中伴焦虑抑郁障碍患者情绪及幸福感的影响

目的：探讨心理干预对康复期脑卒中伴焦虑抑郁障碍患者情绪及幸福感的影响。方法将120例康复期脑卒中伴抑郁焦虑障碍患者随机分为两组,每组60例。两组均予以神经内科常规治疗及训练,研究组联合心理干预,观察12个月。于干预前后采用焦虑自评量表、抑郁自评量表评定焦虑抑郁情绪,症状自评量表评定心理健康状况,总体幸福感指数量表评定幸福感, Barthel指数量表评定日常生活活动能力;干预12个月评估两组患者的治疗依从性。结果干预前两组各量表评分比较差异无显著性（ P＞0．05）;干预12个月两组焦虑自评量表、抑郁自评量表及症状自评量表评分较干预前显著降低（P＜0．01）,研究组显著低于对照组（P＜0．01）;干预后各时间点两组Barthel指数量表评分和研究组总体幸福感指数量表评分较干预前显著升高（P＜0．01）,研究组显著高于对照组（P＜0．01）。干预后研究组依从率为96．7％,对照组为81．7％,研究组显著高于对照组（ P＜0．01）。结论心理干预能有效缓解或消除脑卒中患者的焦虑抑郁情绪,提高其心理健康水平、总体幸福感及日常生活活动能力,有利于疾病的预后。