重组人心钠肽治疗急性心力衰竭的临床研究

目的：探讨重组人心钠肽治疗急性心力衰竭疗效。方法：对自2011年5月～2013年2月我院收治的急性心力衰竭患者应用重组人心钠肽治疗,于用药前后监测患者的血流动力学参数。结果：66例患者59例症状缓解,显效27例,有效32例,无效7例,有效率89．39％。结论：重组人心钠肽是治疗急性心力衰竭疗效可靠的药物,安全性高。     

人血白蛋白在原发性肝癌肝切除术后的应用分析

目的 对东方肝胆外科医院原发性肝癌行肝切除术后使用人血白蛋白的情况进行合理性评价。 方法 回顾分析2012年6月至2013年6月期间150例原发性肝癌患者行肝切除术后应用人血白蛋白治疗的临床资料,比较患者术后应用人血白蛋白前后临床指标、生化指标,及人血白蛋白用药剂量相关因素分析,评价该院人血白蛋白的用药合理性。 结果 在统计的150份病历中,白蛋白总用量11 212.5 g(897瓶),总金额527 744元,占药品总费用的近20%,占住院总费用的近10%。患者在术后使用人血白蛋白后肝功能异常指标阳性率降低(P<0.05),人血白蛋白的使用剂量与患者用药前肝功能的Child-Pugh评分存在正相关(P<0.05)。 结论 该院原发性肝癌肝切除术后使用人血白蛋白较为合理,可达到预期的治疗效果。     

重楼活性单体PP-22对人结肠癌SW620细胞增殖和凋亡的影响

目的 探讨重楼活性单体PP-22对人结肠癌SW620细胞增殖和凋亡的影响及其联合5-氟尿嘧啶(5-FU)和洛铂的抗肿瘤效果。方法 采用噻唑蓝(MTT)法和克隆形成抑制实验观察不同浓度PP-22对人结肠癌SW620细胞增殖的抑制作用;分别观察PP-22联合5-FU和洛铂对人结肠癌SW620细胞增殖的抑制作用;碘化丙锭单染流式细胞术检测细胞周期变化及细胞凋亡水平;Western blot法检测PP-22作用后细胞凋亡相关蛋白的表达。结果 重楼单体PP-22能显著抑制SW620细胞的生长,作用呈剂量-效应关系;随着PP-22浓度的增加,细胞克隆形成逐渐减少,与细胞对照组和DMSO组相比有显著差异;PP-22联合不同浓度的5-FU和洛铂作用于SW620细胞48 h,可提高SW620细胞对5-FU和洛铂的敏感性;不同浓度PP-22作用于SW620细胞后,细胞周期阻滞于S期;PP-22作用后存在Caspase-3和Caspase-9蛋白的活化和降解,抗凋亡蛋白Bcl-2、Bcl-xL减少,促凋亡蛋白Bax的表达增加。结论 PP-22能显著抑制人结肠癌SW620细胞增殖,诱导细胞凋亡,提高SW620细胞对5-FU和洛铂的敏感性。     

重组人白介素-11联合环孢素治疗糖皮质激素无效ITP的临床研究

目的 探讨重组人白介素-11(rhIL-11)联合环孢素治疗糖皮质激素无效的原发免疫性血小板减少症(ITP)的远期临床疗效及其安全性。方法 选取糖皮质激素治疗无效的ITP患者60例,患者随机分为治疗组(40例)和对照组(20例)。治疗组应用rhIL-11和环孢素治疗,对照组长春新碱和静脉注射用免疫球蛋白治疗,分别在治疗前、后检测两组血小板计数,观察两组临床疗效和不良反应。结果 治疗组第1个月、3个月、5个月、12个月末的有效率分别为82.5%、80.0%、72.5%和52.5%,对照组的有效率分别为55.0%、50.0%、40.0%和25.0%,治疗组均优于对照组,差异有统计学意义(P<0.05)。治疗组、对照组不良反应轻微,大多数患者耐受良好。结论 rhIL-11联合环孢素治疗糖皮质激素无效的ITP的中远期疗效满意,安全性良好,可作为理想的二线方案。     

Prevalence and correlates of dyslipidemia in HIV positive and negative adults in Western Kenya: A cross-sectional study

There is increasing morbidity and mortality from cardiovascular diseases (CVD) in sub-Saharan Africa (SSA). Dyslipidemia is a well-known CVD risk factor which has been associated with human immunodeficiency virus (HIV) infection and its treatment in high-income countries. Studies in SSA that have examined the relationship between HIV and dyslipidemia have reported mixed results. In this study, we sought to determine the prevalence of dyslipidemia in HIV positive and negative adults (>=30 years old) and evaluate for association in Western Kenya with a higher prevalence expected among HIV positive individuals.HIV positive adults receiving antiretroviral therapy (ART) and HIV negative individuals seeking HIV testing and counseling services were recruited into a cross-sectional study. Demographic and behavioral data and fasting blood samples were collected. Dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III. Associations between baseline demographic and clinical variables and dyslipidemia were analyzed using logistic regression.A total of 598 participants, 300 HIV positive and 298 HIV negative adults were enrolled. Dyslipidemia data was available for 564 (94%) participants. In total, 267 (47%) had dyslipidemia. This was not significantly different between HIV positive and HIV negative individuals (46% vs 49%, P = .4). In a multivariate analysis including both HIV positive and negative individuals, adults 50 to 59 years of age had a 2-fold increased risk of dyslipidemia (Odds ratio [OR] 2.1, 95% confidence interval (1.2–3.5) when compared to 30 to 39-years-old participants. Abdominal obesity (OR 2.5), being overweight (OR 1.9), and low fruit and vegetable intake (OR 2.2) were significantly associated with dyslipidemia. Among HIV positive participants, time since HIV diagnosis, ART duration, use of (PI) protease inhibitor-based ART, viral load suppression, current cluster of differentiation (CD4) count and nadir CD4 did not have significant associations with dyslipidemia.The prevalence of dyslipidemia is high in Western Kenya, with nearly half of all participants with lipid abnormalities. Dyslipidemia was not significantly associated with HIV status, or with HIV-specific factors. Older age, being overweight, abdominal obesity, and low fruit and vegetable intake were associated with dyslipidemia and may be targets for public health interventions to lower the prevalence of dyslipidemia and CVD risk in sub-Saharan Africa.     

Purification and in vitro toxicity of gamma amanitin

We aimed to obtain gamma amanitin with high purity through a purification process and compare toxic effects of alpha, beta, and gamma amanitin. Specific concentrations of the toxins (25, 10, 1, and 0.1?μg/mL) were applied to the C3A human hepatocytes. A MTT test was performed to determine the level of toxicity. Alpha amanitin showed a higher toxicity in 48?h while the lowest toxicity was observed in beta amanitin. The toxicity level of gamma amanitin was found between the alpha and beta amanitin toxicity. Our method is suitable for obtaining gamma amanitin with high purity (>99%) as well as for obtaining alpha amanitin and beta amanitin. Gamma amanitin has been shown to have equal responsibility for toxicity as alpha amanitin in amanita poisoning.     

静脉给予两次低剂量重组人脑利钠肽治疗顽固性心衰的疗效及安全性

目的:观察冻干重组人脑利钠肽(新活素,recombinant human brain natriuretic peptide,rhBNP)治疗顽固性心衰(refractory heart failure,RHF)的疗效与安全性.方法:2013年2月至2014年5月第二军医大学长海医院心血管内科收治的RHF病人78例,随机分为对照组和rhBNP组,每组39例.在常规抗心衰治疗的基础上,rhBNP组给予rhBNP治疗,先在10 min内匀速静脉注射负荷剂量1.5 μg/kg,随后以0.01μg·kg-1·min-1维持静脉泵入(至少10h泵入),每次总量0.5 mg,隔3d再重复给药1次.第2次用药后7d,比较两组病人的心功能分级、脑利钠肽(BNP)和肌酐水平、左室射血分数(LVEF)、左室舒张末内径(LVEDD),并记录不良反应.结果:rhBNP组心功能改善36例,总有效率为92.31％,显著高于对照组的28例(71.79％,P＜0.05).两组病人用药后心率减慢,舒张压、肌酐和BNP降低,LVEF提高,LVEDD减小,与用药前比较差异有极显著意义(P＜0.001),且rhBNP组心率、舒张压、LVEDD、血肌酐和BNP水平的降低,和LVEF的提高比对照组更明显(P＜0.001).rhBNP组发生1例低血压和1例低血钾,对照组发生2例低血压和1例室性心律失常,两者不良事件无显著差异(P＞0.05).结论:在常规抗心衰治疗基础上再静脉给予两次rhBNP(间隔3d),可以进一步改善RHF病人的心功能和血流动力学,降低血浆BNP和血清肌酐水平,使疗效提高,但并不增加不良反应.     

Nutlin-3-induced redistribution of chromatin-bound IFI16 in human hepatocellular carcinoma cells in vitro is associated with p53 activation

Aim:

Interferon-γ inducible protein 16 (IFI16), a DNA sensor for DNA double-strand break (DSB), is expressed in most human hepatocellular carcinoma cell (HCC) lines. In this study we investigated the re-localization of chromatin-bound IFI16 by Nutlin-3, a DNA damage agent, in HCC cells in vitro, and the potential mechanisms.

Methods:

Human HCC SMMC-7721 (wild-type TP53), Huh-7 (mutant TP53), Hep3B (null TP53) and normal fetal liver L02 cell lines were examined. DSB damage in HCC cells was detected via γH2AX expression and foci formation assay. The expression of IFI16 and IFNB mRNA was measured using RT-PCR, and subcellular localization and expression of the IFI16 protein were detected using chromatin fractionation, Western blot analysis, and fluorescence microscopy.

Results:

Treatment of SMMC-7721 cells with Nutlin-3 (10 μmol/L) or etoposide (40 μmol/L) induced significant DSB damage. In SMMC-7721 cells, Nutlin-3 significantly increased the expression levels of IFI16 and IFNB mRNA, and partially redistributed chromatin-bound IFI16 protein to the cytoplasm. These effects were blocked by pretreatment with pifithrin-α, a p53 inhibitor. Furthermore, Nutlin-3 did not induce ectopic expression of IFI16 protein in Huh-7 and Hep3B cells. Moreover, the association of IFI16 with chromatin and Nutlin-3-induced changes in localization were not detected in L02 cells.

Conclusion:

Nutlin-3 regulates the subcellular localization of IFI16 in HCC cells in vitro in a p53-dependent manner.     

A study of the sequential treatment of acute heart failure with sacubitril/valsartan by recombinant human brain natriuretic peptide: A randomized controlled trial

This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, β receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.