多西紫杉醇联合替吉奥治疗蒽环类耐药晚期乳腺癌的疗效观察

目的 观察多西紫杉醇联合替吉奥治疗蒽环类耐药晚期乳腺癌的疗效和不良反应。方法 21例蒽环类耐药晚期乳腺癌患者采用多西紫杉醇（75mg／m²静滴 d₁）联合替吉奥（80mg／m²／天,分2次口服,d_l～d₁₄）治疗,3周为1周期,2周期后按WHO标准评价疗效及不良反应。结果 21例患者均可评价疗效和不良反应,其中获CR 3例,PR 9例,SD 5例,PD 4例,有效率为57.2％,临床获益率为81.0％。中位疾病进展时间为9.5个月,1年生存率为81.0%。主要不良反应为血液学毒性和消化道反应,以1、2级为主,均可耐受。结论 多西紫杉醇联合替吉奥治疗蒽环类耐药晚期乳腺癌疗效肯定,不良反应较小,耐受性好,值得临床进一步研究。     

Research on Fall Prevention and Protection from Heights in Japan

The high frequency of fall accidents is a serious problem in Japan. Thus, morestringent countermeasures for preventing falls from scaffolds were developed andincorporated into institutional guidelines. These countermeasures aim to decrease deathscaused by falls from scaffolds. Despite the improvements in such measures, however, therate of accidental fall deaths remains high in Japan’s construction industries. To improvethe rigor of the countermeasures, a committee was established in our institute by theJapan Ministry of Health, Labour, and Welfare. This committee investigated the regulationsapplied in other countries and evaluated construction industry compliance with existingfall prevention guidelines. After considerable research and discussion, the OccupationalSafety and Health Regulations and Guidelines were amended in 2009. The effects of theamended regulations have recently been investigated on the basis of accident reports. Thispaper describes the investigation and its results. The paper also discusses other researchand workplace safety countermeasures for preventing falls and ensuring fall protectionfrom heights.     

FOLFIRI方案二线治疗23例晚期胃癌临床观察

目的：评价FOLFIRI方案二线治疗晚期胃癌的疗效及不良反应。方法23例晚期胃癌患者采用伊立替康150 mg/m^2,静脉滴注90 min, d1;甲酰四氢叶酸（CF）200 mg/m^2,静脉滴注2 h, d1-2;5-FU 2400 mg/m^2静脉滴注46 h,每2周重复,3周期后评定疗效。结果完全缓解（CR）0例,部分缓解（PR）8例,稳定（SD）4例,进展（PD）11例,总有效率为34.7%,疾病控制率52.2%。中位PFS为3.8个月,中位OS为14.1个月,1年生存率39.1%,常见的不良反应为白细胞减少、腹泻和恶心呕吐。结论 FOLFIRI方案二线治疗晚期胃癌具有较高的疗效,不良反应可耐受且可控制。     

Vicenin 2 isolated from Artemisia capillaris exhibited potent anti-glycation properties

Vicenin 2, isolated from a traditionally used medicinal plant Artemisia capillaris, is a 6,8-di-C-glucoside of apigenin which has been previously reported to possess a wide variety of pharmacological activities including antioxidant, anti-inflammatory, anti-cancer, and hepatoprotective. However, there have not been any reports concerning its anti-diabetic potential until now. Therefore, in the present study, we evaluated the anti-diabetic potential of vicenin 2 via α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), rat lens aldose reductase (RLAR), and advanced glycation end products (AGE) formation inhibitory assays. Vicenin 2 strongly inhibited α-glucosidase, PTP1B, and RLAR in the corresponding assays. In addition, vicenin 2 inhibited the formation of both fluorescent AGE and nonfluorescent AGE, e.g., CML, as well as the level of fructosamine in glucose–fructose-induced bovine serum albumin (BSA) glycation. In the test system, vicenin 2 suppressed glycation-induced protein oxidation by attenuating the formation of protein carbonyl groups as well as by inhibiting the modification of protein thiol groups. Moreover, vicenin 2 was found to be a potent inhibitor of glycation-induced formation of amyloid cross-β structures in BSA. Taken together, vicenin 2 might be a useful lead for the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-associated complications.     

替吉奥联合奈达铂对比多西他赛单药二线治疗晚期肺鳞癌的疗效观察

目的 探讨替吉奥（S-1）联合奈达铂与多西他赛单药二线治疗晚期肺鳞癌的疗效和安全性。方法 收集本院2012年12月至2014年12月一线含铂双药化疗方案治疗失败或缓解后再进展的晚期肺鳞癌患者共87例,其中43例接受S-1联合奈达铂治疗（观察组）,44例接受多西他赛单药治疗（对照组）,两方案均为21天1个周期。化疗2个周期后采用RECIST 1.1 版标准评价客观疗效,采用美国国立癌症研究所毒性判定标准（NCI-CTCAE）4.0评价毒性反应,同时随访生存情况并评价两组生活质量的改善程度。结果 87例患者均可评价疗效。观察组和对照组的有效率分别为23.3％和18.2％,差异无统计学意义（P＞0.05）;观察组的疾病控制率为65.1％,高于对照组的40.9％,差异有统计学意义（P＜0.05）;两组中位无疾病进展生存期分别为3.6个月（95%CI：2.44～4.76个月）和2.9个月（95%CI：2.54～3.26个月）,差异有统计学意义（P＜0.05）;两组治疗后生活质量均有相应改善,差异无统计学意义（P＞0.05）。观察组主要的毒副反应为血液学毒性和消化道反应,对照组主要的毒副反应为血液学毒性和口腔黏膜炎,两组不良反应经对症治疗均可缓解。结论 S-1联合奈达铂二线治疗晚期肺鳞癌疗效更佳,不良反应可耐受。     

Advanced technologies applied to physiopathological analysis of central nervous system aneurysms and vascular malformations

While depiction and definition of morphological and architectural characteristics of CNS vascular disorders remains the first step of an MR analysis, emerging imaging techniques offer new functional information that might help to characterize rupture risk of CNS vascular disorders. Two main orientations are suggested by recent studies: inflammation of the vessel wall and analysis of physical constraints of blood flow using 4D flow imaging (shear parietal). This paper will focus on radiological application of 4D flow imaging and inflammation imaging, in the characterization of potential prognostic markers of CNS vascular disorders. We will review the basic technical considerations of 4D flow MRA, inflammation imaging and discuss their applications in CNS vascular disorders: aneurysms, arteriovenous malformation, dural arteriovenous fistulas. We will illustrate their potential in the development of individual rupture risk criteria in brain vascular disorders.     

Toremifene in the treatment of breast cancer

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier (SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase III trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events and it has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.     

Impact of extracted urinary proteins and advanced glycation end product on autophagy pathway in renal tubular epithelial cells

Objective To investigate the effect of urinary proteins extracted from minimal change nephritic syndrome (MCNS) and advanced glycation end products (AGEs) on autophagy activity in renal tubular epithelial cells (TECs). Methods Kidney tissue specimens of patients with MCNS and DN were obtained from the kidney pathology library of the Affiliated Hospital of Guangdong Medical College. The kidney tissue from patients with hematuria and proven to be minimal change by pathology examination were used as control. The expression of LC3-Ⅱ in kidney was examined by immune histochemistry in vivo. Expression of LC3-Ⅱ was also studied after exposing HK-2 cells to 8 g/L urinary proteins and 100 mg/L AGE-BSA respectively. LC3-Ⅱ turnover was examined after exposure to urinary proteins in presence of Lysosomal inhibitors leupeptin (200 mg/L) or chloroquine(10μmol/L) by western blot assay. In addition, the autophagosome or autolysosome formation was assessed after transfecting a tandem mRFP-GFP tagged LC3 (tfLC3) plasmid into HK-2 cells. Finally, the production of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were measured by ELISA after exposure of cells to autophagy enhancer rapamycin (10 μmol/L) and autophagy inhibitor chloroquine (10 μmol/L) in addition to urinary proteins. Results (1)In comparison with the control group, the expression of LC3-Ⅱ was significantly increased in TECs from patients with MCNS and DN(P＜0.01). (2)The expression of LC3-Ⅱwas enlarged after exposed to urinary proteins(P＜0.01), and further increased after leupeptin (autophagy inhibitor) addition. (3) Exposure to urinary proteins increased the autophogosomes and autolysosomes when observed by transfection of tfLC3 plasmid(P＜0.01). (4)The expression of LC3-Ⅱ was also elevated after treatment with AGE-BSA(P＜0.01), but no further increase after chloroquine (autophagy inhibitor) addition. (5) Only the autophogosome formation(P＜0.01), but not autolysosome formation, was found increased by transfection of tfLC3 plasmid after exposure to AGE-BSA. (6) Pre-treatment of HK-2 cells with autophagy enhancer rapamycin reduced the productions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), while blocking autophagy with autophagy inhibitor chloroquine exerted an opposite effect. Conclusions Autophagy was activated by urinary proteins, but inactivated by AGE-BSA. Autophagy activation may play a key role in protecting TECs in the progression of primary and secondary kidney diseases.