Synergistic activity of ABT-263 and ONC201/TIC10 against solid tumor cell lines is associated with suppression of anti-apoptotic Mcl-1, BAG3, pAkt,and upregulation of pro-apoptotic Noxa and Bax cleavage during apoptosis

A major underlying cause of the resistance of solid tumor cells to cancer therapy is the evasion of cell death following anti-cancer drug treatment. We explored the combination of TRAIL-inducing compound ONC201/TIC10 and Bcl-xL/Bcl-2 inhibitor ABT-263 to target the extrinsic and intrinsic apoptotic pathways, respectively, in solid tumor cell lines (N = 13) derived from different tissues (colon, prostate, lung, breast, ovary, bladder). We found an IC50 range of 0.83-20.10 μM for ONC201 and 0.06-14.75 μM for ABT-263 among the 13 cancer cell lines. We show that combination of ONC201 and ABT-263 produces a strong synergistic effect leading to tumor cell death, and that the combination is not toxic to human fibroblast cells. In OVCAR-3 ovarian cancer cells, 2.5 μM ONC201 and 1.25 μM ABT-263 yielded 37% and 27% inhibition of viability, respectively, while the combination of the two agents yielded 92% inhibition of viability, resulting in a high synergy score of 52; conversely, the same combination in the HFF-1 human fibroblast cells yielded 2.45% inhibition of viability and a synergy score of 6.92 (synergy scores were calculated using SynergyFinder; scores greater than 10 are considered synergistic). We also found that the combination of these two agents resulted in synergistic caspase activation and PARP cleavage consistent with induction of apoptosis. Combination therapy-induced cell death correlated with decreased levels of Mcl-1, BAG3, pAkt, and upregulation of Noxa along with Bax cleavage during apoptosis at 48 hours, and ATF4, TRAIL, and DR5 induction at 24 hours. There was some heterogeneity in the cell lines with regard to these responses. Our data provide evidence for synergy from the combination of ONC201 and ABT-263 against human solid tumor cell lines associated with alterations in cell death and pro-survival mediators. The combination of ONC201 and ABT-263 merits further exploration in vivo and in clinical trials against a variety of solid malignancies.     

正念在规培医师职业倦怠与社会支持之间的中介作用

目的 探讨正念在规培医师职业倦怠与社会支持之间的中介作用,为提高规培医师的工作热情和医疗服务水平提供科学依据.方法 随机选取2020年5月～6月安徽省内5家有规培资质的三甲医院,采取整群抽样,纳入493名规培医师为调查对象.采用职业倦怠量表(CMBI)、5因素正念量表(FFMQ)、社会支持评定量表(SSRS),分别测量...     

系统性红斑狼疮和类风湿性关节炎T细胞异常调节与免疫功能紊乱的研究

目的 分析系统性红斑狼疮（SLE）和类风湿性关节炎（RA）外周血T细胞亚群表面共刺激信号分子表达,探讨人类SLE和RA中T细胞免疫紊乱状态。方法 采用流式细胞技术检测SLE、RA患者外周血T细胞亚群表面CD28、CDl52、诱导性共刺激因子（ICOS）、CD154、CD30和CD95分子表达。结果 与健康对照组比较,SLE和RA患者组分别为CD3^＋CD8^＋T细胞和CD3^＋CD4^＋T细胞增加（P〈0．05）;SLE患者CD4^＋T细胞和CD8^＋T细胞上CD28和CD152分子表达率均增加,ICOS分子表达减少（P均〈0．05）,CD154和CD30分子表达率均下降;RA患者2类T细胞亚群上CD28分子表达均降低,CD152分子表达率均增加（P均〈0．05）,ICOS分子表达率无明显变化,CD154和CD30分子表达率分别增加或减少;SLE和RA患者CD4^＋T细胞和CD8^＋T细胞上CD95分子表达率均明显增加。结论 SLE和RA有不同的外周T细胞亚群平衡失控;T细胞的异常活化受复杂的细胞其刺激信号网络分子调控。     

Syncytin和GCMa在特发性胎儿生长受限胎盘中的表达

目的探讨Syncytin及glial cells missing(GCMa)在特发性胎儿生长受限(idiopathic fetal growth restriction,IFGR)患者胎盘组织中的表达及意义。方法选取剖宫产分娩的IFGR孕妇32例为研究组,同期因社会因素剖宫产分娩的健康足月孕妇30例作为健康对照组。采用免疫组化S-P法和逆转录聚合酶链反应(RT-PCR)检测2组胎盘组织中Syncytin和GCMa的表达。结果免疫组化及RT-PCR结果均显示Syncytin和GCMa在研究组胎盘组织中表达水平低于健康对照组,差异均具有显著统计学意义(P<0.01)。Syncytin及GCMa在研究组胎盘组织中表达均降低,两者呈正相关(r=0.537,P<0.05)。结论 Syncytin与GCMa在IFGR胎盘组织中均低表达,提示可能在该疾病的发生、发展过程中起重要作用。     

1例肥胖症患者腹腔镜下行可调节胃束带减容术的护理

对1例肥胖症患者腹腔镜下行可调节胃束带减容术，结果手术效果满意。提出术前正确评估患者病情，加强心理护理，完善术前准备，术后严密监测生命体征，预防脑梗死、肺栓塞等并发症发生，是保证手术成功的关键。     

Protective Effect of Extract of Folium Ginkgo on Repeated Cerebral Ischemia-Reperfusion Injury

Protective Effect of Extract of Folium Ginkgo on Repeated Cerebral Ischemia-Reperfusion Injury@周兰兰 @明 亮 @江 勤 @马传庚     

Differential metabolic responses in three life stages of mussels <Emphasis Type="Italic">Mytilus galloprovincialis</Emphasis> exposed to cadmium

Cadmium (Cd) is one of the most important metal contaminants in the Bohai Sea. In this work, NMR-based metabolomics was used to investigate the toxicological effects of Cd at an environmentally relevant concentration (50?µg L^?1) in three different life stages (D-shape larval, juvenile and adult) of mussels Mytilus galloprovincialis. Results indicated that the D-shape larval mussel was the most sensitive life stage to Cd. The significantly different metabolic profiles meant that Cd induced differential toxicological effects in three life stages of mussels. Basically, Cd caused osmotic stress in all the three life stages via different metabolic pathways. Cd exposure reduced the anaerobiosis in D-shape larval mussels and disturbed lipid metabolism in juvenile mussels, respectively. Compared with the D-shape larval and juvenile mussels, the adult mussels reduced energy consumption to deal with Cd stress.     

综合护理对改善慢阻肺患者肺功能及生活质量的作用研究

目的 探讨综合护理对慢阻肺患者肺功能及生活质量的影响。方法 选取我院2019年1月至2021年3月期间收治的100例慢阻肺患者,随机分为对照组(n=50)和观察组(n=50)。对照组实施常规基础护理,研究组实施综合护理。比较两组患者的肺功能指标(FVC、 PEF、 FEV₁/FVC)及生活质量评分。结果 干预后,研究组的FVC、 PEF、 FEV₁/FVC明显高于对照组(P<0.05)。干预后,研究组功能、症状及整体健康状况评分均高于对照组(P<0.05)。结论 综合护理可有效改善慢阻肺患者的肺功能,提高其生活质量,值得临床推广。     

远隔缺血预处理对肺损伤患者预后的临床研究Meta分析

目的 系统性评价远隔缺血预处理(remote ischemic preconditioning,RIPC)对各种原因导致的肺损伤的影响.方法 通过检索PubMed、Embase、Medline、中国知网(CNKI)、维普中文期刊全文数据库、中国生物医学文献数据库、中国生物医学期刊引文数据库,根据纳入标准和排除标准,检索出相关随机对照临床研究文献,并提取主要评估指标(ICU停留时间及机械通气时间)和次要评估指标[术后24 h血清IL-6、TNF-α、IL-8浓度及肺泡动脉氧分压差(alveolar-arterial oxygen tension gradient,A-aDO2)、氧合指数(oxgension index,PaO2/FiO2)、呼吸指数(respiratory index,RI)],采用RevMan5.3和STATA 12.0软件进行Meta分析. 结果 共纳入前瞻性随机对照研究8篇,476例患者,其中RIPC组237例,对照组239例.与对照组相比,RIPC可以减少患者术后ICU停留时间及机械通气时间,并降低术后24 h血清TNF-α浓度(P＜0.05),其标准均数差(standard mean difference,SMD)和95％CI分别为-0.03(-0.41,-0.05)、-0.2(-0.39,-0.01)、-0.85(-1.35,0.34). 结论 RIPC可以减少患者术后ICU停留时间和机械通气时间,改善肺损伤患者的临床预后.