Idarubicin-intensified BUCY2 regimens may lower relapse rate and improve survival in patients undergoing allo-SCT for high-risk hematological malignancies: a retrospective analysis

We conducted a retrospective study to evaluate the outcome of 94 consecutive patients with high-risk hematological malignancies who received allo-PBSCT, following idarubicin (IDA)-intensified BUCY2 (IDA-BUCY2) myeloablative conditioning regimens (n=53) and BUCY2 conditioning regimens (n=41). IDA 15?mg/m(2) once daily was administered by continuous infusion on days -11 to -9, followed by BU, 3.2?mg/kg in divided doses daily, on days -6 to -4, and i.v. injection of CY, 1.8?g/m(2) once daily on days -3 to -2 in the IDA-BUCY2 group. The relapse rate in patients in the IDA-BUCY2 and BUCY2-conditioning regimens group was 18.9 and 39%, respectively (P=0.030). There was no significant difference in terms of TRM. The cumulative probabilities of OS and disease-free survival at 2 years for patients conditioned with the IDA-BUCY2 and BUCY2 regimens were 65.3% vs 46.8% (P=0.038), and 63.5% vs 43.4% (P=0.025), respectively. Multivariate analysis showed that IDA-BUCY2 regimens and limited chronic GVHD were the only two factors resulting in improved survival and reduced relapse rate. This retrospective study suggests that IDA-intensified BUCY2 may be substituted for BUCY2 as conditioning regimen for patients with high-risk hematological malignancies.     

Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study

Objective Patients with primary aldosteronism (PA) who are suitable for surgery should undergo adrenal computerised tomography (CT) and adrenal venous sampling (AVS). A retrospective study was performed of 100 patients with PA. We determined the optimal AVS lateralisation ratio for unilateral disease and reviewed adrenalectomy outcomes evaluating which characteristics predicted hypertension cure. Methods AVS was performed in 93 patients. Lateralisation criteria were assessed using ROC curve analysis. The outcome of adrenalectomy was reviewed in 39 patients and predictive factors for cure determined using univariate and multivariate analysis. Results Of previously published criteria, ROC curve analysis found a cortisol corrected aldosterone affected to unaffected (Aldo/Cort A:U) cut‐off of 2·0 was the best predictor of adenoma identifying 80·4% of patients. A novel ratio calculated by dividing the affected to unaffected ratio by the unaffected to peripheral ratio [(Aldo/Cort A:U)/(Aldo/Cort U:IVC)] was successful in identifying 87·0% of patients. Cure rate for blood pressure after adrenalectomy was 38·5% with improvement in 59·0%. On univariate analysis, predictors of post‐operative hypertension were increased weight, raised creatinine, left ventricular hypertrophy (LVH) and male sex. On multivariate analysis, male sex and higher pre‐operative systolic blood pressure were predictive. Conclusions Patients with PA should have CT scanning and AVS. Aldo/Cort A:U >2·0 is the most accurate of previously published ratios in predicting unilateral disease. When patients were carefully selected for surgery, 97% had cure or improvement in blood pressure control. Further confirmatory work is required on a novel ratio which was even more predictive in our series.     

Melatonin protects against rotenone-induced cell injury via inhibition of Omi and Bax-mediated autophagy in Hela cells

Parkinson's disease is the second most common neurodegenerative disease, and environmental toxins such as rotenone play an important role in causing degeneration of dopaminergic neurons. Melatonin, a major secretory product of pineal, is recently reported to protect against rotenone-induced cell death in animal models. Yet, the mechanism involved in this protection needs to be elucidated. Here, we report that rotenone treatment (0-100 μM) decreased cell survival of Hela cells in a dose-dependent manner. At concentrations ranging from 0.1 to 100 μM, rotenone induced a dose-dependent increase in the expression of microtubule-associated protein 1 light chain 3 (LC3)-II, a protein associated with the autophagosomal membrane. Knockdown of Bax or Omi using shRNA inhibited 1 μM rotenone-induced autophagy. To determine whether melatonin would protect cells against rotenone-induced cell death and autophagy, we pretreated Hela cells with 250 μM melatonin for 24 hr in the presence of rotenone. Melatonin inhibited Bax expression and the release of the omi/HtrA2 into the cytoplasm induced by 1 μM rotenone. Melatonin 250 μM treatment also suppressed cell death induced by 0.1-100 μM rotenone and protected against the formation of LC3-II in cells exposed to 1 μM rotenone. This work demonstrates a novel role for melatonin as a neuroprotective agent against rotenone.     

基因芯片分析NTD小鼠细胞周期和凋亡相关基因表达的变化

目的 筛选神经管缺陷(NTD)发生过程中与正常组织差异表达的细胞周期和细胞凋亡相关基因并作初步功能分析.方法 用含有1 100余个已知基因的中密度芯片比较了胚胎9.5d、10.5 d正常与同期NTD小鼠神经管组织的基因表达差异.结果 通过比较正常E9.5d与E10.5 d获得138个差异表达基因,E9.5 d-NTD获得20个差异,El0.5 d-NTD获得29个差异表达基因,根据基因功能分类包括细胞周期与凋亡相关基因,信号转导基因,转录与翻译调控,能量与代谢基因,热休克基因,基质与骨架蛋白等多种种类.而细胞周期和凋亡相关基因分别占差异基因的25.80％(32/124),45.00％(9/20)及28.57％(8/28).结论 实验证实多类基因参与了NTD的发生、发展过程,细胞周期和凋亡相关基因在神经管异常发育中具有重要作用,对该相关基因群的进一步研究有助于阐释NTD的发病机制.     

血浆ox-LDL在阿尔茨海默病患者中的临床研究

目的探讨氧化低密度脂蛋白(oxidized Low density lipoprotein,ox-LDL)与阿尔茨海默病(Alzheimer’s dis-ease,AD)患者认知功能损害的关系。方法运用简易精神状态检查量表(mini mental state examination,MMSE)检测入组患者认知功能,将其分为3组,即正常组(NC组,37例)、血管性痴呆组(VD组,41例)、阿尔茨海默病组(AD组,48例),分别用酶联免疫吸附试验(enzyme-linked immunosorbnent assay,ELSIA)测定3组患者血浆ox-LDL的浓度。结果 NC组、VD组、AD组患者血浆ox-LDL浓度分别为(47.46±10.04)μg/L、(60.95±11.78)μg/L、(112.25±17.81)μg/L,AD组患者血浆ox-LDL浓度显著高于VD组,差异有统计学意义(P<0.01);相关分析显示,AD患者血浆ox-LDL浓度与MMSE得分呈负相关(r=-0.574,P<0.01);对AD患者各个认知领域的分值与血浆ox-LDL水平进行多元线性回归分析显示,血浆ox-LDL水平与AD患者记忆力、定向力、注意力和计算能力呈负相关。结论血浆ox-LDL浓度测定有可能作为判断AD患者认知功能损害的生化指标,亦可作为AD与VD鉴别诊断的生物学指标。     

缺血性卒中患者血清同型半胱氨酸与脑白质病变体积相关性研究

目的本文顾性横断面研究旨在探讨脑卒中患者脑白质病变体积与血清同型半胱氨酸(Hcy)水平的关系。方法回顾性收集87例急性脑梗死患者的人口学、临床、实验室及器械检查资料。Hcy的测定采用荧光偏振免疫分析法。应用半自动测量软件对所有患者颅脑MRI冠状位液体衰减反转回复序列(FLAIR)上脑白质病变进行体积测量。应用多元线性回归法对脑白质病变的体积(平方根值)进行相关因素的分析。结果共87例患者纳入研究,男54例(62.1%),平均年龄(62.2±11.2)岁,76例(87.4%)有高血压,18例(20.7%)有糖尿病,18例(20.7%)既往有脑卒中史。在多元线性回归显示,年龄、既往卒中史、腔隙性梗死数目、血清Hcy水平及颅内动脉狭窄均为脑白质病变体积(平方根值)的独立相关因素。结论脑卒中患者的血清Hcy水平是其脑白质病变体积的独立危险因素。血清Hcy可作为脑部小血管病变的生物学标记。     

Chloride channel blocker 4,4-diisothiocyanatostilbene-2,2’-disulfonic acid inhibits nitric oxide-induced apoptosis in cultured rat hippocampal neurons

Apoptosis in cultured rat hippocampal neurons was induced using the nitric oxide donor 3-morpholinosydnonimine, and cells were treated with the chloride channel blocker, 4,4-diisothiocyanatostilbene-2,2’-disulfonic acid. Results showed that the survival rate of neurons was significantly increased after treatment with 4,4-diisothiocyanatostilbene-2,2’-disulfonic acid, and the rate of apoptosis decreased. In addition, the expression of the apoptosis-related proteins poly(adenosine diphosphate-ribose)polymerase-1 and apoptosis-inducing factor were significantly reduced. Our experimental findings indicate that the chloride channel blocker 4,4- diisothiocyanatostilbene-2,2’-disulfonic acid can antagonize apoptotic cell death of hippocampal neurons by inhibiting the expression of the apoptosis-related proteins poly(adenosine diphosphate-ribose)polymerase-1 and apoptosis-inducing factor.     

Effect of minocycline on cerebral ischemia- reperfusion injury

Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-reperfusion (22.5 mg/kg, initially 45 mg/kg) at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein expression.