血必净注射液治疗肾综合征出血热合并急性肾功能衰竭42例临床疗效观察

目的:观察血必净注射液治疗肾综合征出血热(HFRS)合并急性肾功能衰竭(ARF)的临床疗效。方法:将72例ARF患者随机分为治疗组(Ⅰ组,42例)和对照组(Ⅱ组,30例),Ⅰ组在西医综合治疗的基础上加用血必净注射液,Ⅱ组仅采用西医综合治疗。结果:Ⅰ组总有效率为95.24%,Ⅱ组为80.00%,2组比较具有显著性差异(P<0.05);Ⅰ组肾功能恢复正常时间显著短于Ⅱ组(P<0.05)。结论:血必净注射液治疗HFRS合并ARF具有良好疗效。     

阿昔洛韦致不良反应86例文献分析

目的：探讨阿昔洛韦所致不良反应（ADR）的一般规律和特点,为临床合理用药提供参考。方法：对1995-2009年国内医药学术期刊报道的86例阿昔洛韦致不良反应病例进行统计、分析。结果发生ADR的原疾患以单纯性疱疹和带状疱疹患者最多（65例,占75.58％）。静脉滴注（76侧,88.37％）ADR发生率明显高于口服和局部用药;ADR在≤24h发生例数最多（25例,29.07％）。急性肾功能衰竭（Acute renal failure,ARF）是其严重且高发的不良反应,有54例占62.79％,大部分是由于不合理用药所致,一般为非少尿型,停药并经积极对症治疗大多预后良好。结论：临床医生应严格掌握适应证,严格选取药物的用法、用量,使用疗程不宜过长。     

膀胱移行细胞癌和p14ARF基因

目的探讨p14ARF在膀胱癌中的表达及其与膀胱移行细胞癌发生的关系。方法用逆转录聚合酶链反应法（RT-PCR）检测162例膀胱移行细胞癌和20例癌旁正常组织中p14ARF基因mRNA表达情况。结果p14ARF基因mRNA在膀胱癌中的阳性表达率为33．9％（21／62）,在癌旁正常组织中的阳性表达率为100％（20／20）,两者相比差异有统计学意义（P〈0．01）。结论p14ARF基因mRNA在膀胱癌中的失表达可能与膀胱癌的发生有关。     

鼻咽癌组织中P14ARF和P15INK4B基因异常甲基化的研究

目的 通过检测P14肝和P15INK4B基因启动子区甲基化情况,分析其与鼻咽癌发生、发展及临床病理特征的关系,探讨其可能在鼻咽癌临床早期分子生物学诊断和治疗中的作用.方法 运用甲基化特异性聚合酶链式扩增对54例鼻咽癌组织和20例正常鼻咽上皮组织的P14ARF和P15INK4B基因启动子区甲基化状态进行检测,比较两者的差异,并分析鼻咽癌组织中两种基因甲基化与患者临床病理特征的关系,以及两种基因甲基化的相关性.结果 鼻咽癌组织中P14ARF和P15INK4B基因启动子区甲基化阳性率分别为20.4%(11/54)和22.2%(12/54),两者总检出率为27.8%(15/54);而正常鼻咽上皮组织中未检测到P14ARF和P15INK4B基因启动子区甲基化;两组间P14ARF和P15INK4B基因启动子区甲基化阳性率差异有统计学意义(P<0.01).15例甲基化的癌组织同时两种基因同时甲基化为8例,非甲基化39例.P14ARF和P15INK4B基因甲基化与鼻咽癌的临床病理特征均无明显相关性(均P>0.05).结论 P14ARF和P15INK4B基因启动子区甲基化在鼻咽癌的发生、发展中可能存在协同作用,作为鼻咽癌发生的早期事件,有望成为分子生物学早期诊断的标志物,将来还可能作为去甲基化基因治疗的靶点.     

P16INK4a和P14ARF蛋白在喉表达及临床意义鳞癌中的

【摘要】目的探讨P16INK4a和P14ARF蛋白在喉鳞状细胞癌组织中的表达及其临床意义。方法采用免疫组织化学EnVision法检测71例喉鳞状细胞癌组织中P16INK4a和P14ARF蛋白的表达。结果71例喉鳞状细胞癌标本中,35例（49．3％）P16INK4a蛋白阴性,29例（40．8％）P14ARF蛋白阴性,15例（21．1％）P16INK4a和P14ARF蛋白表达均阴性。P16INK4a和P14ARF蛋白阴性间无相关性（P〉O．05）。P16INK4a和P14ARF蛋白阴性率均与患者性别、年龄及临床分期无相关性（P〉0．05）。P14ARF蛋白在Ⅰ—Ⅱ期病例中强阳性占阳性比例为41．7％,在Ⅲ～Ⅳ期中强阳性比例为11．1％。结论P16INK4a和P14ARF在喉鳞状细胞癌发生过程中起重要作用,两种蛋白的失活是各自独立的事件。P14ARF蛋白的缺失发生在喉鳞状细胞癌早期。（中国眼耳鼻喉科杂志,2010,10：218—220）     

Heme Oxygenase-1 Regulates Myeloid Cell Trafficking in AKI

Renal ischemia-reperfusion injury is mediated by a complex cascade of events, including the immune response, that occur secondary to injury to renal epithelial cells. We tested the hypothesis that heme oxygenase-1 (HO-1) expression, which is protective in ischemia-reperfusion injury, regulates trafficking of myeloid-derived immune cells in the kidney. Age-matched male wild-type (HO-1^+/+), HO-1–knockout (HO-1^−/−), and humanized HO-1–overexpressing (HBAC) mice underwent bilateral renal ischemia for 10 minutes. Ischemia-reperfusion injury resulted in significantly worse renal structure and function and increased mortality in HO-1^−/− mice. In addition, there were more macrophages (CD45⁺ CD11b^hiF4/80^lo) and neutrophils (CD45⁺ CD11b^hi MHCII⁻ Gr-1^hi) in HO-1^−/− kidneys than in sham and HO-1^+/+ control kidneys subjected to ischemia-reperfusion. However, ischemic injury resulted in a significant decrease in the intrarenal resident dendritic cell (DC; CD45⁺MHCII⁺CD11b^loF4/80^hi) population in HO-1^−/− kidneys compared with controls. Syngeneic transplant experiments utilizing green fluorescent protein–positive HO-1^+/+ or HO-1^−/− donor kidneys and green fluorescent protein–negative HO-1^+/+ recipients confirmed increased migration of the resident DC population from HO-1^−/− donor kidneys, compared to HO-1^+/+ donor kidneys, to the peripheral lymphoid organs. This effect on renal DC migration was corroborated in myeloid-specific HO-1^−/− mice subjected to bilateral ischemia. These mice also displayed impaired renal recovery and increased fibrosis at day 7 after injury. These results highlight an important role for HO-1 in orchestrating the trafficking of myeloid cells in AKI, which may represent a key pathway for therapeutic intervention.     

p19ARF is a critical mediator of both cellular senescence and an innate immune response associated with MYC inactivation in mouse model of acute leukemia

MYC-induced T-ALL exhibit oncogene addiction. Addiction to MYC is a consequence of both cell-autonomous mechanisms, such as proliferative arrest, cellular senescence, and apoptosis, as well as non-cell autonomous mechanisms, such as shutdown of angiogenesis, and recruitment of immune effectors. Here, we show, using transgenic mouse models of MYC-induced T-ALL, that the loss of either p19ARF or p53 abrogates the ability of MYC inactivation to induce sustained tumor regression. Loss of p53 or p19ARF, influenced the ability of MYC inactivation to elicit the shutdown of angiogenesis; however the loss of p19ARF, but not p53, impeded cellular senescence, as measured by SA-beta-galactosidase staining, increased expression of p16INK4A, and specific histone modifications. Moreover, comparative gene expression analysis suggested that a multitude of genes involved in the innate immune response were expressed in p19ARF wild-type, but not null, tumors upon MYC inactivation. Indeed, the loss of p19ARF, but not p53, impeded the in situ recruitment of macrophages to the tumor microenvironment. Finally, p19ARF null-associated gene signature prognosticated relapse-free survival in human patients with ALL. Therefore, p19ARF appears to be important to regulating cellular senescence and innate immune response that may contribute to the therapeutic response of ALL.     

GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1

GB virus type C (GBV-C) glycoprotein E2 protein disrupts HIV-1 assembly and release by inhibiting Gag plasma membrane targeting, however the mechanism by which the GBV-C E2 inhibits Gag trafficking remains unclear. In the present study, we identified ADP-ribosylation factor 1 (ARF1) contributed to the inhibitory effect of GBV-C E2 on HIV-1 Gag membrane targeting. Expression of GBV-C E2 decreased ARF1 expression in a proteasomal degradation-dependent manner. The restoration of ARF1 expression rescued the HIV-1 Gag processing and membrane targeting defect imposed by GBV-C E2. In addition, GBV-C E2 expression also altered Golgi morphology and suppressed protein traffic through the secretory pathway, which are all consistent with a phenotype of disrupting the function of ARF1 protein. Thus, our results indicate that GBV-C E2 inhibits HIV-1 assembly and release by decreasing ARF1, and may provide insights regarding GBV-C E2''s potential for a new therapeutic approach for treating HIV-1.     

缬沙坦 卡维地洛 多巴胺联合治疗流行性出血热急性肾功能衰竭疗效观察

目的：探讨缬沙坦、卡维地洛及多巴胺联合治疗流行性出血热（ EHF ）急性肾功能衰竭的效果。方法将116例EHF急性肾功能衰竭患者随机分为对照组和治疗组各58例。对照组常规采用抗病毒、止血、维持内环境平衡,及早使用利尿剂、导泻等综合治疗;治疗组在常规综合治疗的基础上加用缬沙坦、卡维地洛及多巴胺。观察两组患者的疗效。结果治疗组尿蛋白消失快,进入多尿期早,尿素氮降至正常时间短,各种并发症低,透析病人数减少,能改善透析病人的预后,提高治愈率。结论缬沙坦、卡维地洛及多巴胺联合治疗EHF急性肾功能衰竭疗效显著。