他汀类药物在糖尿病血管病变应用的新进展

糖尿病诱发的动脉粥样硬化是引起患者死亡的主要原因。他汀类药物属糖尿病血管病变常见防治药物。本文,旨在分析他汀类药物对2型糖尿病大血管相关并发症、1型糖尿病大血管相关并发症、微血管病变、血管内皮功能的影响,为临床糖尿病血管病变的预防及治疗提供可靠依据。     

他汀类药物的临床应用

他汀类药物。即羟甲戊二酰辅酶A(HMG-COA)还原酶抑制剂是一类新型降血脂药物,具有调整血脂,降低冠状动脉疾病,逆转动脉粥样硬化等作用,疗效确切、不良反应较少,已广泛用于临床。本文结合近年的文献将其临床应用进展综述如下。     

他汀类药物治疗骨质疏松的研究进展

骨质疏松症(osteoporosis,OP)是一种涉及到多学科的疾病.特别是进入21世纪,人类寿命的延长和人口老龄化日趋严重,由骨质疏松引起骨折的发生率也明显增加,伴随骨折而出现的并发症、伤残率和病死率均上升,对中老年人的生存造成极大的威胁,已引起世界卫生组织及各国医学界的重视.     

他汀类药物治疗丙型肝炎的研究进展

他汀类药物作为羟甲基戊二酸单酰辅酶A还原酶的抑制剂,除具降血脂效应外,还具有不依赖于调脂作用的多效性.新近的研究表明其具有抗丙型肝炎的作用,但也有相反的结论报道.当此类药物与聚乙二醇干扰素和利巴韦林联合用药治疗HCV感染时,他汀类药物显示出了很强的协同作用,可能是临床治疗丙型肝炎的新途径.本文就近几年他汀类药物与丙型肝炎治疗的研究新进展作一综述.     

他汀类药物在2型糖尿病综合治疗中的研究进展

2型糖尿病的患病率正在世界范围内逐年增加,同时与之相关的微血管并发症和大血管并发症发生率也显著增加.他汀类药物除了调脂作用以外,还可通过抑制炎症因子、保护血管内皮细胞功能及抗氧化应激等途径延缓糖尿病并发症发生发展,显著减少心血管事件.总体而言,及时启动他汀类药物对2型糖尿病的治疗是有益的,尤其是伴有心血管危险因素的糖尿病患者.     

他汀类药物治疗冠心病房颤临床分析

观察发现长期服用他汀类药物的老年冠心病患者,新发房颤率或房颤复发率明显降低。对我科2002年1月~2013年12月100例>60岁冠心病患者连续追踪,其中服用他汀类药物患者,发生房颤率或既往有阵发性房颤患者的房颤复发率明显低于不服用他汀类。应用他汀类药物后新发房颤率或房颤复发率明显降低,且预防复发的有益效应可能比房颤的一级预防更为明显。     

他汀类药物（Statins）在防治前列腺癌中的应用及存在的问题

前列腺癌(PCa)是男性泌尿生殖系常见恶性肿瘤,其发病机制虽然至今不完全明确,但研究发现高胆固醇血症患者更易患PCa或高级别PCa,PCa向去势难治性前列腺癌(CRPC)转变过程中常伴有癌细胞胆固醇调节机制的改变。他汀类药物(Statins)是3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂,临床用于治疗高脂血症和预防心血管不良事件的发生。最近研究发现,Statins可能抑制PCa的发生发展,降低PCa总发病率。因此,抑制胆固醇介导的细胞生长作用成为预防和治疗PCa和CRPC的新策略。     

肿瘤坏死因子样凋亡微弱诱导剂在肿瘤研究中的进展

肿瘤坏死因子样凋亡微弱诱导剂(TWEAK)作为肿瘤坏死因子超家族的新成员可表达在多种细胞表面,也表达在多种肿瘤细胞和组织中,可诱导人肠腺癌细胞系HT29、人口腔鳞状细胞癌HSC3等肿瘤细胞凋亡,介导HepG2、HLE和SK-Hep-1等肿瘤细胞增殖,诱导巨噬细胞在肿瘤浸润区的杀伤活性,潜在介导肿瘤血管。     

他汀类药物临床应用的安全性

大量研究表明他汀类药物在心血管疾病一级预防和二级预防中具有显著疗效,并且与低密度脂蛋白胆固醇(LDL-C)降低的幅度密切相关,强化调脂的概念已经受到广泛重视。尽管他汀类药物具有很高的安全性,但大剂量药物治疗对肝脏和肌肉潜在的不良影响倍受关注,如何在强调调脂的同时注意用药的安全性,是目前该领域的重要话题。     

他汀类药物抗感染作用的研究进展

他汀类药物（statins）除有降脂作用外,还具有多效性,包括抗氧化、抗炎抗感染、免疫调节、改善血管内皮细胞功能和抑制血栓形成、稳定粥样硬化斑块等作用。目前对statins的抗微生物感染作用研究越来越多,包括实验室的研究和人群的流行病学研究,本文收集了statins抗细菌感染、抗病毒作用、抗真菌及其他微生物感染的实验室及流行病学证据并进行了分析。     

Statin effects on regulatory and proinflammatory factors in chronic idiopathic urticaria

Immunological dysfunction has been described to occur in chronic idiopathic urticaria (CIU), most notably in association with an inflammatory process. Some pharmacological agents as statins--drugs used in hypercholesterolaemia--display a broad effect on the immune response and thus should be tested in vitro in CIU. Our main objectives were to evaluate the effects of statins on the innate and adaptive immune response in CIU. Simvastatin or lovastatin have markedly inhibited the peripheral blood mononuclear cells (PBMC) proliferative response induced by T and B cell mitogens, superantigen or recall antigen. Simvastatin arrested phytohaemaglutinin (PHA)-induced T cells at the G0/G1 phase, inhibiting T helper type 1 (Th1), Th2, interleukin (IL)-10 and IL-17A cytokine secretion in both patients and healthy control groups. Up-regulation of suppressor of cytokine signalling 3 (SOCS3) mRNA expression in PHA-stimulated PBMCs from CIU patients was not modified by simvastatin, in contrast to the enhancing effect in the control group. Statin exhibited a less efficient inhibition effect on cytokine production [IL-6 and macrophage inflammatory protein (MIP)-1α] induced by Toll-like receptor (TLR)-4, to which a statin preincubation step was required. Furthermore, statin did not affect the tumour necrosis factor (TNF)-α secretion by lipopolysaccharide (LPS)-stimulated PBMC or CD14+ cells in CIU patients. In addition, LPS-activated PBMC from CIU patients showed impaired indoleamine 2,3-dioxygenase (IDO) mRNA expression compared to healthy control, which remained at decreased levels with statin treatment. Statins exhibited a marked down-regulatory effect in T cell functions, but were not able to control TLR-4 activation in CIU patients. The unbalanced regulatory SOCS3 and IDO expressions in CIU may contribute to the pathogenesis of the disease.     

Prognostic factors in laryngeal carcinoma: the role of apoptosis,p53, proliferation (Ki-67) and angiogenesis

Even though the roles of different known or suggested prognostic factors in laryngeal cancer have been studied in detail, clinical stage at time of diagnosis and anatomic subsite of the tumour remain the only practical predictors of clinical outcome and offer the only guidelines in the planning of treatment. In this study, the relative roles of known demographic and clinical prognostic factors, in addition to four histopathological factors, were evaluated in a sample of 100 laryngeal carcinoma patients with multivariate analysis using the Cox regression model. In addition to advanced stage (stage III-IV) (relative hazard of death (HR) 8.9, p=0.01) and supraglottic disease (HR 5.6, p=0.02), high apoptotic index (HR 11.1, p=0.05) was significantly associated with poor survival. Cell proliferation, p53 and angiogenesis did not significantly affect the prognosis. In the future, high degree of apoptosis could be used to identify patients with poor prognosis in laryngeal cancer.     

Mcl-1表达沉默对肺癌细胞生长的抑制作用

目的：研究Mcl?1对肺癌细胞PC?9增殖和凋亡的影响。方法利用Western印迹检测人正常肺上皮细胞及4种肺癌细胞株中Mcl?1的表达; CCK8细胞增殖实验、平板克隆形成实验观察Mcl?1表达沉默对PC?9细胞增殖的影响;并运用流式细胞仪观察Mcl?1沉默对PC?9细胞凋亡的影响。结果 Mcl?1在肺癌细胞株A549和PC?9中的表达水平较高;干扰Mcl?1表达能抑制PC?9细胞的生长（ P＜0?05）;经Mcl?1 siR?NA处理后PC?9细胞克隆形成率显著低于阴性对照组,差异有统计学意义（ P＜0?05）。流式细胞仪检测细胞凋亡结果显示,下调Mcl?1的表达水平可以明显提高PC?9肺癌细胞的凋亡比例。结论在肺癌细胞中沉默Mcl?1的表达,能够抑制肺癌细胞的增殖并促进肺癌细胞的凋亡,提示Mcl?1可能成为潜在的肺癌治疗靶点。     

Statin use and clinical outcomes among pneumonia patients

It was suggested that statin may improve the outcomes of pneumonia patients. However, there are sparse data regarding this topic in ethnic Chinese populations. In the present study, we investigated associations between previous statin use and pneumonia outcomes in Taiwan with a large-scale matched cohort study. A total of 11 576 patients with pneumonia were selected, comprising 2894 patients with previous statin use and 8682 matched patients. We used a separate conditional logistic regression to explore relationships between statin use and each clinical outcome, including ‘intensive care unit admission,’ ‘use of mechanical ventilation,’ ‘acute respiratory failure’ and ‘in-hospital death’. We found that patients who were statin users were 0.81 (95% CI 0.74–0.89), 0.80 (95% CI 0.71–0.89), 0.84 (95% CI 0.75–0.94) and 0.69 times (95% CI 0.57–0.85) less likely to be admitted to the intensive care unit, to have acute respiratory failure, to need mechanical ventilation, and to die in the hospital, respectively, than patients who were not statin users. In addition, it consistently revealed that compared with patients who were not statin users, regular statin users had lower ORs of intensive care unit admission, acute respiratory failure, the use of mechanical ventilation and in-hospital death. However, there were no significant differences in the above adverse outcomes between irregular users of statin and non-statin users. We concluded that patients with regular previous statin use were significantly associated with favourable outcomes during admission for pneumonia in Taiwan.     

The role of statins in lung cancer

Lung cancer is one of the most common causes of cancer-related mortality in the 21^st century. Statins as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase not only reduce the cholesterol levels in the blood and decrease the risk of cardiovascular disease but may also play an important role in the prevention and treatment of lung cancer. Statins have several antitumor properties including the ability to reduce cell proliferation and angiogenesis, decrease invasion and synergistic suppression of lung cancer progression. Statins induce tumor cell apoptosis by inhibition of downstream products such as small GTP-binding proteins, Rho, Ras and Rac, which are dependent on isoprenylation. Statins reduce angiogenesis in tumors by down-regulation of pro-angiogenic factors, such as vascular endothelial growth factor. In this review, the feasibility and efficacy of statins in the prevention and treatment of lung cancer are discussed.     

Cancer immunotherapy of targeting angiogenesis

Tumor growth and metastasis are angiogenesis-dependent. Anti-angiogenic therapy may be a useful approach to cancer therapy. This review discussed tumor angiogenesis and immunotherapy of targeting tumor angiogenesis from two main aspects: (1) active vaccination to induce effective anti-angiogenesis immunity; (2) passive immunotherapy with anti-pro-angiogenic molecules relevant antibody. Evidence from the recent years suggested that anti-angiogenic therapy should be one of the most promising approaches to cancer therapy.     

Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer

AIMS: Recent studies have drawn attention to intratumoral microvessel density (MVD) as a prognostic factor in invasive breast cancer. Various methods have been applied to assess MVD and the prognostic value of MVD in different studies varies considerably. Counting of microvessels in the most highly vascularized area (hot spot) of a tumour is the method most widely used. In this study we compared three counting methods. METHODS AND RESULTS: To assess MVD in 112 cases of invasive breast cancer with long-term follow-up we performed microvessel counting in the hot spot of the tumour in four and 10 fields of vision (HS-MVD4 and HS-MVD10) and microvessel counting in 10 fields of vision distributed systematically over the whole tumour area (global MVD). The HS-MVD4, HS-MVD10 and global MVD showed good correlations with each other. HS-MVD4 provided the highest number of microvessels (median value 71) followed by HS-MVD10 and global MVD, with median values of 58 and 39, respectively. HS-MVD4 showed the best prognostic value for overall survival (P = 0.0001) whereas HS-MVD10 showed less (P = 0.01) and the global MVD showed no (P = 0.75) prognostic value. In univariate analysis, the HS-MVD4 was the second strongest prognostic factor after tumour size. In multivariate survival analysis, the HS-MVD4, mitotic activity index (MAI), lymph node status and tumour size were found to be independent prognostic factors. When combining MVD4 and MAI in lymph node negative patients, none of the patients with low MVD (< 71/mm2) and a low MAI (< 10 per 10 HPF) died, in contrast to patients with a high MVD or high MAI who have a 10-year survival of 57%. CONCLUSIONS: These data suggest that the hot spot MVD in four fields of vision is a major independent prognostic factor for overall survival in invasive breast cancer. For the first time, it is shown that hot spot MVD provides additional prognostic information to well established factors like lymph node status and the MAI, and may therefore be useful for designing treatment strategies in invasive breast cancer.     

Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia

Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable.