Granulocyte Colony-Stimulating Factor Reduces Cardiomyocyte Apoptosis and Improves Cardiac Function in Adriamycin-Induced Cardiomyopathy in Rats

Background: Cardiomyocyte apoptosis reportedly participates in the occurrence and progression of dilated cardiomyopathy (DCM). Recent studies have shown that granulocyte colony-stimulating factor (G-CSF) enhances bone marrow cells migration to the damaged heart in the DCM model and improves the ultrastructure of the cardiomyocyte in adriamycin (ADR) induced DCM. However, its influence on cardiac pump function and cardiomyocyte apoptosis has not been studied. Methods and materials: Wistar Rats were randomly grouped into control, ADR, ADR+PBS, ADR+G-CSF group (n = 10). ADR (2.5 mg/kg, 6 times for 2 weeks) was administered intraperitoneally in all rats except the control group. After 2 weeks, the rats in ADR+G-CSF group were injected with G-CSF (50 microg/kg/day for 8 days) subcutaneously. Cardiac function was evaluated by echocardiogram and cardiac catheterization after 4 weeks. Cardiomyocytes apoptosis and apoptosis-related protein Fas were detected by in situ terminal deoxynucleotidyl transferase assay (TUNEL method) and Western blot, respectively. Results: The ADR and ADR+PBS groups showed significant deteriorations of left ventricular functions and high cardiomyocyte apoptosis index, as well as high Fas expressions. Meanwhile, the ADR+G-CSF group showed significant improvement in LV function, inhibition of cardiomyocyte apoptosis compared with the ADR and ADR+Phosphate-Buffered Saline PBS group. The Fas protein expression was remarkably attenuated as well. Conclusion: Our results suggest that administration of G-CSF inhibited cardiomyocyte apoptosis and Fas protein expression and contributes to improving cardiac pump function in vivo in ADR induced DCM rat model.     

成人急性髓系白血病189例伴有t(8;21)的遗传学特点及预后分析

目的探讨伴有t（8;21）的成人急性髓系白血病（AML）的细胞遗传学特点及预后意义。方法分析我院检测的189例成人t（8;21）的细胞遗传学和临床预后特点。结果单纯t（8;21）（q22;q22）63例,占33．3％;伴有附加异常的126例,占66．7％;单纯性染色体丢失77例占总数的40．7％,其中-Y占男性患者的46．7％（63／135）,-X占女性患者的25．9％（14／54）。有附加异常的126例中,单纯性染色体丢失77例（61．1％）;9q-16例（12．7％）;＋4者5例（4．0％）;7q-6例（4．8％）;四倍体（4N）2例（1．6％）;变异易位7例（5．6％）。此组患者的缓解率较高（87．0％）,生存期较长（中位生存期21．6个月）。附加异常中＋4和4N组预后较差。荧光原位杂交技术是诊断t（8;21）AML较为准确和可靠的方法,特别是对于变异易位、复杂易位和隐匿变异易位的病例。结论t（8;21）常合并附加异常,附加异常的种类会影响t（8;21）AML患者的预后。     

UGT1A1 G71R 基因多态性对母乳性黄疸程度的影响

目的探讨葡萄糖醛酸转移酶UGT1A1 G71R基因突变对晚发型母乳性黄疸患儿黄疸程度的影响。方法收集晚发型母乳性黄疸患儿56例,用套式PCR后限制性片段长度多态性分析(RFLP)确定UGT1A1 G71R基因型,通过全自动生化分析仪测定胆红素水平。结果UGT1A1 G71R突变纯合子5例,杂合子24例,野生型27例。UGT1A1 G71R等位基因频率为30.36%。UGT1A1 G71R纯合子或杂合子组(n=29)与UGT1A1G71R野生组(n=27)的胆红素水平分别为(237.85±31.92)μmol/L、(214.49±32.48)μmol/L,前者明显高于后者(t=2.7141,P=0.0089)。结论晚发型母乳性黄疸患儿如存在UGT1A1 G71R基因突变,临床上黄疸程度较重。     

Modified Paclitaxel-loaded Nanoparticles for Inhibition of Hyperplasia in a Rabbit Arterial Balloon Injury Model

Purpose This study tested the possibility of localized intravascular infusion of positive charged paclitaxel-loaded nanoparticles (NPs) to better prevent neointimal formation in a rabbit carotid artery injury model. Materials and Methods NPs were prepared by oil–water emulsion/solvent evaporation technique using biodegradable poly (lactide-co-glycolide) (PLGA). A cationic surfactant, didodecyldimethylammonium bromide (DMAB), was absorbed on the NP surface by electrostatic attraction between positive and negative charges. NPs were characterized in such aspects as size, surface morphology, surface charges as well as in vitro drug release profile. Balloon injured rabbit carotid arteries were treated with single infusion of paclitaxel-loaded NP suspension and observed for 28 days. The inhibitory effects of NPs on neointima formation were evaluated as end-point. Results NPs showed spherical shape with a diameter ranging from 200 to 500 nm. Negatively charged PLGA NPs shifted to positive after the DMAB modification. The in vitro drug release profile showed a biphasic release pattern. Morphometric analyses on the retrieved artery samples revealed that the inhibitory effect of intima proliferation was dose-dependent. At a concentration of 30 mg ml⁻¹, NP infusion completely inhibited intima proliferation in a rabbit vascular injury model. Conclusions Paclitaxel-loaded NPs with DMAB modification were proven an effective means of inhibiting proliferative response to vascular injury in a rabbit model.     

硒对碘过量EAT大鼠肝、脑抗氧化水平的影响

目的研究高碘及高碘条件下不同硒摄入水平对实验性自身免疫性甲状腺炎（experimental autoimmunethyroiditis,EAT）大鼠肝、脑SOD、GPX活性的影响。方法选择易感Lewis大鼠建立EAT模型,将动物随机分为5组,即对照组（C组）、模型组（M组）、造模＋高碘高硒组（M＋I＋Se＋组）、造模＋高碘适硒组（M＋I＋Se组）、造模＋高碘低硒组（M＋I＋Se-组）。按照实验设计对各组动物喂以不同硒、碘水平饲料。16周后,对大鼠的甲状腺组织进行病理学检查,测定甲状腺自身抗体（TGAb、TMAb）及大鼠肝、脑组织SOD、GPX活性。结果光镜下观察,M组大鼠甲状腺组织出现散在淋巴细胞浸润;M＋I＋Se＋组及M＋I＋Se组部分小叶受累,有淋巴细胞浸润;M＋I＋Se-组病变严重,几乎所有小叶受累。与C组相比,M组大鼠甲状腺自身抗体（TGAb、TMAb）水平明显升高,肝脏GPX活性显著降低。M＋I＋Se组与M组相比,脑组织GPX活性显著降低。与M＋I＋Se-组相比,M＋I＋Se＋组肝、脑GPX活性显著升高,M＋I＋Se组肝脏GPX活性显著升高。肝、脑GPX及SOD活性均有随硒摄入量增加而增强的趋势。结论EAT时大鼠机体抗氧化能力下降,高碘及低硒均可加重EAT大鼠甲状腺、肝、脑组织的氧化损伤,补硒可以提高组织GPX活性。     

再生障碍性贫血的骨髓和细胞病理

目的：研究再生障碍性贫血（AA）患者骨髓组织病理及有核细胞的超微结构变化。方法：光镜观察20例AA患者骨髓活检病理,透射电镜分析骨髓有核细胞超微结构。结果：光镜下所有患者骨髓脂肪组织增多,造血面积减小,大部分存在血浆渗出、出血和纤维细胞局灶性增生,血窦血管结构紊乱。电镜观察显示原始和早幼红细胞代偿性不典型增生,中晚幼红细胞核损伤。粒细胞呈活化和损伤状态;巨核细胞显著减少,胞浆灶性坏死;单核细胞异常增生、活化、吞噬和坏死。淋巴细胞大部分结构正常。结论：AA患者骨髓造血细胞减少和炎症反应同时存在,单核巨噬细胞活化和吞噬反应与造血细胞损伤相关。     

DVd(T)方案治疗多发性骨髓瘤17例临床疗效分析

目的:观察脂质体阿霉素(PLD)联合长春新碱(VCR)、地塞米松(Dex)士沙利度胺(Thal)治疗多发性骨髓瘤(MM)患者的疗效及毒副反应.方法:17例初治或复发难治MM患者接受DVd(PLD 40 mg·m-2d1、VCR 2 mg d1、Dex 40 mg d1～4)或DVdT(PLD及VCR用法用量同上,Dex:40 mg,d1～4、d9～12;Thal:100 mg,d1～21)治疗,按照EBMT标准评价疗效、WHO标准判断毒副反应.结果:①17例患者共完成了34个周期的治疗,总有效率(ORR=CR+nCR+VGPR+PR)为58.8%,与国外文献报道接近,与历史上我院采用的VAD及其类似方案相比疗效也接近.②采用DVd方案治疗的11例患者的ORR为4/11(36.4%).其中6例初治患者的ORR为2/6(33.3%).采用DVdT方案化疗的6例患者均为初治病例,其ORR为6/6(100%).对于初治患者.DVdT方案的ORR显著好于DVd方案.③多数治疗相关毒副反应为1～2级且可耐受.17例患者中有13例在接受DVd(T)化疗前心电图或心脏B超示不同程度的心律失常或左室舒张功能降低,但均未因化疗增加心脏毒性.DVd组与DVdT组的毒副反应接近.结论:DVd方案具有较好的耐受性,适当延长Dex用量并加入Thal可以在不增加化疗相关毒性的同时显著提高DVd方案疗效.     

骨髓增生异常综合征RAEB、RAEB-T和老年急性髓系白血病的临床对照分析

目的：在WHO分类中,FAB分型中的骨髓增生异常综合征一难治性贫血伴原始细胞增多转化型（MDS—RAEBT）被划分为急性髓系白血病（AML）,本文探讨该划分的合理性。方法：采用病例对照研究比较58例老年AML患者、88例骨髓增生异常综合征-难治性贫血伴原始细胞增多（MDS-RAEB）10％～19％（骨髓原始细胞10％～19％）患者和37例MDS-RAEBT患者在临床和染色体核型及共同累及的染色体异常类型上的区别。结果：MDS-RAEBT和MDS-RAEB在病程、WBC、Hb、肝脾肿大比例、正常核型和复杂核型比例及共同累及的染色体异常类型上差异无统计学意义,而和老年AMI,患者比较差异有统计学意义。结论：MDS-RAEBT应该划分为MDS,该结论有待于前瞻性实验进一步验证。