Prognostic factors for early relapse in non-metastatic triple negative breast cancer — real world data

BackgroundTriple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse.Materials and methodsSingle-centre retrospective analysis of 127 women with TNBC, stage II–III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse.ResultsAfter 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3–22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2–6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1–1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively).ConclusionsIn this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up.     

犬脑内动脉构筑的显微X线解剖学研究

犬脑11只,经生理盐水冲洗脑血管后,注入20％钡胶液,切成0.2～1.0厘米的厚片,用显微X线法研究犬脑内各级动脉的构筑,其结果:1.皮质动脉的管径平均为25.9±0.005微米,平均长度为888.0±0.241微米。其形态与发出部位有关,分别呈栅状和瓶刷状。2.髓质动脉的管径平均为49.9±0.007微米。呈直线或孤形向心走行。3.皮质下动脉的管径平均为38.7±0.009微米。呈新月形或蟹钳状分布。4.豆纹动脉和内囊动脉的平均管径为70.0±0.021微米。呈锐角、反血流方向发自母干,再呈“S”形上升。5.丘脑动脉的平均管径为63.7±0.019微米,主要从下方进丘脑,呈树枝状分支。     

Splash seed dispersal by raindrops

Splash seed dispersal by raindrops was investigated for plants in southern Japan. Nine families, 10 genera and 19 species were confirmed as raindrop-dispersed plants. The 10 genera were Gentiana, Gratiola, Chrysosplenium, Mazus, Mitella, Ophiorrhiza, Sagina, Sedum, Trigonotis and Veronica. The method of splash rain dispersal in these species was clarified. Raindrop-dispersed species were all small herbaceous plants with a vertical pedicel and an apically opening fresh capsule when the seeds mature. Open capsules were cup-shaped or boat-shaped and can accommodate raindrops easily. The raindrops splashed the seeds from the capsule. In general, the seeds weighed very little, but they were heavier than powder or dust seeds dispersed by wind. A strong negative correlation was found between seed weight and the number of seeds per capsule. In the case of Trigonotis brevipes (Maxim.) Maxim., raindrops were received into the cup-shaped calyx-tube and dispersed the fruitlets. Some species, such as Gentiana thunbergii (G. Don) Griseb., Gentiana zollingeri Fawcett and Ophiorrhiza japonica Blume, had hydroscopic movement capsules that opened widely only when wet. Raindrop-dispersed plants were found in various habitats. For example, some plants grew together on rocks along the mountain torrents where splash water could easily be caught. The results of the laboratory and field experiments indicated that the dispersal distance of seeds by raindrops was 1m or less. For small herbaceous plants, splash dispersal by rain might be an effective and advantageous method of seed dispersal because dispersal is not affected by plant height.     

天香胶囊对晕动病模型大鼠行为学与前庭核c-fos蛋白表达的影响

目的:观察中药复方天香胶囊对晕动病模型大鼠行为学与前庭核c-fos蛋白表达的影响。方法:选择雄性SD大鼠并将其随机分为正常组、模型组、阳性药组、天香胶囊低、中、高剂量组。灌胃预给药3天后,采用双轴旋转刺激法建立大鼠晕动病模型,通过晕反应指数评分、自发活动实验、异嗜高岭土实验检测各组大鼠行为学变化,Western blotting法与免疫组化法检测各组大鼠前庭核c-fos蛋白的表达。结果:与正常组大鼠相比,模型组大鼠晕反应指数和高岭土摄入量均显著增高,自发活动总路程与次数均显著减少,前庭核c-fos蛋白表达水平显著增高;与模型组相比,天香胶囊可显著降低晕动病模型大鼠晕反应指数与高岭土摄入量,提高自发活动总路程与活动次数,降低大鼠前庭核组织c-fos蛋白表达。结论:天香胶囊可有效改善晕动病模型大鼠的行为学变化,其作用机制可能与下调前庭核c-fos表达有关,提示降低前庭核兴奋性可能是天香胶囊抗晕动病的内在机制之一。     

A small-molecule activator induces ULK1-modulating autophagy-associated cell death in triple negative breast cancer

ULK1 (unc-51 like autophagy activating kinase 1) is well known to be required to initiate the macroautophagy/autophagy process, and thus activation of ULK1-modulating autophagy/autophagy-associated cell death (ACD) may be a possible therapeutic strategy in triple negative breast cancer (TNBC). Here, our integrated The Cancer Genome Atlas (TCGA) data set, tissue microarray-based analyses and multiple biologic evaluations together demonstrate a new small-molecule activator of ULK1 for better understanding of how ULK1, the mammalian homolog of yeast Atg1, as a potential drug target can regulate ACD by the ULK complex (ULK1-ATG13-RB1CC1/FIP200-ATG101), as well as other possible ULK1 interactors, including ATF3, RAD21 and CASP3/caspase3 in TNBC. Moreover, such new inspiring findings may help us discover that this activator of ULK1 (LYN-1604) with its anti-tumor activity and ACD-modulating mechanisms can be further exploited as a small-molecule candidate drug for future TNBC therapy.     

Purification and characterization of KpsT,the ATP-binding component of the ABC-capsule exporter of Escherichia coli K1

The K1 capsule, an alpha(2,8)-linked polymer of sialic acid, is an important virulence determinant of invasive Escherichia coli. The 17-kb kps gene cluster of E. coli K1 encodes the information necessary for capsule expression at the cell surface. Two proteins, KpsM and KpsT, play a role in the transport of capsular polysaccharide across the cytoplasmic membrane, utilizing the energy from ATP hydrolysis. They belong to the ATP-binding cassette superfamily of transport proteins. In this study, we purified KpsT in its native form and show that the purified protein is able to bind ATP, undergo an ATP-dependent conformational change and hydrolyze ATP. Protease accessibility studies demonstrate the in vivo interaction between KpsM and KpsT.     

薄层扫描法测定保元肠疡胶囊中人参皂苷Rg_1的含量

本文报道了用双波长薄层扫描法测定中成药制剂保元肠疡胶囊中微量人参皂苷Ｒｇ１的含量．方法稳定、检测灵敏度高,变异系数小于５％．可作为该成药制剂的质量控制标准．     

芪苈强心胶囊辅助治疗老年慢性心力衰竭的临床研究

目的：探讨芪苈强心胶囊辅助治疗老年慢性心力衰竭的临床疗效及其安全性。方法：选择我科2012年1月．6月收治的102例老年慢性心力衰竭患者为研究对象,并将其随机分为两组,对照组42例,给予西医常规治疗及地高辛0．125mg／d;观察组60例,在对照组基础上将地高辛用量改为O．0625mg／d,并予芪苈强心胶囊,每次4粒,每日3次12服,2个月为1个疗程,治疗3个疗程后观察和比较两组心功能的变化。结果：观察组和对照组的治疗总有效率分别为95．0．％和78．6％,观察组显著高于对照组,两组比较差异有统计学意义（P〈0．05）;观察组的平均住院时间明显短于对照组（P〈0．05）。治疗后,两组心输出量（cO）、每搏输出量（SV）、左室射血分数（LVEF）舒张晚期与舒张早期充盈速度比（～E）均较治疗前明显升高（P〈0．05）,而脑钠肽（BNP）水平较治疗前显著降低（P〈O．05）,且观察组CO、SV水平均明显高于对照组（P〈0．05）,BNP水平明显低于对照组（P〈0．05）。治疗过程中,对照组发生洋地黄中毒3例,观察组无不良事件发生。结论：芪苈强心胶囊辅助治疗老年慢性心力衰竭可有效改善其心功能,并减少地高辛用量和洋地黄中毒的发生,值得临床推广应用。     

Luminescence enhancement of the catalytic 19 kDa protein (KAZ) of Oplophorus luciferase by three amino acid substitutions

To characterize the luminescence properties of nanoKAZ, a 16 amino acid substituted mutant of the catalytic 19 kDa protein (KAZ) of Oplophorus luciferase, the effects of each mutated amino acid were investigated by site-specific mutagenesis. All 16 single substituted KAZ mutants were expressed in Escherichia coli cells and their secretory expressions in CHO-K1 cells were also examined using the signal peptide sequence of Gaussia luciferase. Luminescence activity of KAZ was significantly enhanced by single amino acid substitutions at V44I, A54I, or Y138I. Further, the triple mutant KAZ-V44I/A54I/Y138I, named eKAZ, was prepared and these substitutions synergistically enhanced luminescence activity, showing 66-fold higher activity than wild-KAZ and also 7-fold higher activity than nanoKAZ using coelenterazine as a substrate. Substrate specificity of eKAZ for C2- and/or C6-modified coelenterazine analogues was different from that of nanoKAZ, indicating that three amino acid substitutions may be responsible for the substrate recognition of coelenterazine to increase luminescence activity. In contrast, these substitutions did not stimulate protein secretion from CHO-K1 cells, suggesting that the folded-protein structure of KAZ might be different from that of nanoKAZ.     

步长稳心颗粒治疗功能性早搏60例疗效分析

目的:观察步长稳心颗粒(简称稳心颗粒)治疗功能性早搏的临床疗效及安全性。方法:选择功能性早搏60例病人,随机分为治疗组及对照组,每组各30例。治疗组给予稳心颗粒一包(9克),每日三次,温开水冲服;对照组给予倍他乐克25毫克,每日二次口服,一个月为一疗程。结果:四周后治疗组显效11例,有效16例,总有效率90%。对照组显效8例,有效18例,总有效率86.7%,p>0.05,两组比较无显著性差异。对血压、心率影响方面稳心颗粒明显优于倍他乐克结论:稳心颗粒治疗功能性早搏疗效显著,且效果稳定,安全无明显不良反应,值得临床推广应用。