High hemoglobin fluctuation was a protective factor for cardiovascular‐related death in peritoneal dialysis (PD) patients: A retrospective analysis of 232 patients with PD

ObjectivesThis study aimed to investigate the effect of hemoglobin (Hb) fluctuation after dialysis on the prognosis of cardiovascular‐related and all‐cause deaths in peritoneal dialysis (PD).MethodsAccording to the Hb fluctuation, patients were divided into low fluctuation group, moderate fluctuation group, and high fluctuation group, and then, the effects of Hb fluctuation after dialysis on the prognosis of cardiovascular‐related and all‐cause death in PD were analyzed by regression analysis.ResultsA total of 232 patients were selected in this study. Compared with the low Hb fluctuation group, the moderate and high fluctuation groups had lower body mass index (BMI), estimated glomerular filtration rate (eGFR), and baseline Hb, and the moderate fluctuation group had less erythropoietin (EPO) and dialysis dose. Compared with survivors, patients with cardiovascular‐related and all‐cause deaths had lower mean Hb and Hb fluctuation (all p < 0.05). Cox regression analysis showed that before and after adjusting for confounding factors, Hb fluctuation was still independently correlated with cardiovascular prognosis, and higher Hb fluctuation was still a protective factor for cardiovascular‐related death in the Hb‐substandard group, but there was no significant correlation between Hb fluctuation and all‐cause death. Multivariate linear regression analysis revealed that Hb fluctuation was positively correlated with Kt/V and EPO dosage, but negatively correlated with the baseline Hb.ConclusionHigh Hb fluctuation was a protective factor for cardiovascular‐related death in PD with substandard Hb. Compared with Hb fluctuation, correction of anemia timely and making Hb reaches the standard level had a greater impact on reducing cardiovascular‐related death in PD.     

Causes of death in primary plasma cell leukemia differ from multiple myeloma: A STROBE-compliant descriptive study based on SEER database

The primary plasma cell leukemia (pPCL) is a rare but aggressive variant of multiple myeloma (MM). Few studies have focused on the differences in the causes of death between pPCL and MM. This study aimed to compare and evaluate the causes of death of patients with pPCL and MM.The data were collected from the Surveillance Epidemiology, and End Results (SEER) database. The demographic characteristics, survival, and causes of death in pPCL and MM patients were evaluated and compared. The competing risk regression model was performed to predict the cause of death.Between 1975 and 2009, the overall mortality rate was 96.13% and 88.71% for pPCL and MM, and the median survival was 9 and 26 months, respectively. In pPCL, leukemia caused 45.05% of the deaths, followed by myeloma (38.83%). In MM, myeloma was the leading cause of death, accounting for 74.89% of the deaths. Older age at diagnosis was a risk factor for dying of leukemia in pPCL patients (HR = 1.49, 95% CI: 1.16–1.91), while older age at death was associated with reduced risk (HR = 0.67, 95% CI: 0.52–0.86). Although the survival of pPCL patients increased with time periods of diagnosis since 1975 to 2009, the risk of dying of leukemia increased with the periods. For MM, most of the demographic characteristics were found to have independently predicting influence on the cause of death.Patients with pPCL and MM had distinct causes of death. Leukemia was the leading and the most serious cause of death in pPCL patients. The demographic factors could not predict the causes of death in pPCL. More large-scale and multi-center studies are needed to evaluate the effect of novel agents in pPCL patients, especially for patients who have progressed to leukemia.     

线粒体通路和死亡受体通路在中华眼镜蛇毒组分诱导KG1a细胞凋亡中的作用

目的研究线粒体通路和死亡受体通路在中华眼镜蛇毒组分(naja naja actra venom component,NNAVC)诱导KG1a细胞凋亡过程中的作用。方法以人急性髓系白血病细胞株KG1a细胞为研究对象,采用Annexin V-FITC/PI荧光染色法进行凋亡细胞的形态学观察,流式细胞仪检测细胞凋亡率,分光光度法检测Caspase-9、Caspase-8和Caspase-3的活性,ELISA法检测胞质内细胞色素C的表达水平,流式细胞仪分析TRAIL死亡受体(DR4、DR5)和诱骗受体(DcR1、DcR2)的改变。结果 NNAVC作用后,荧光显微镜下可见明显的凋亡细胞,细胞凋亡率随药物作用浓度的增加而升高;Caspase-9、Caspase-8和Caspase-3蛋白被激活,胞质内细胞色素C的表达明显增加;流式细胞仪检测结果显示,NNAVC具有降低死亡受体DR4和诱骗受体DcR1的表达率,而提高DR5和DcR2的表达水平的作用。结论线粒体凋亡通路和死亡受体通路均参与NNAVC诱导KG1a细胞凋亡的过程,这可能是NNAVC发挥抗白血病作用的机制之一。     

正常人肝细胞和肝癌细胞对力达霉素诱导的有丝分裂性细胞死亡的差异

[摘要]目的：探讨力达霉素（lidamycin, LDM）诱导人肝癌BEL-7402和正常人肝L-02细胞出现的有丝分裂性细胞死亡的差异。方法：采用MTT法观察LDM对BEL-7402和L-02细胞生长曲线的影响;使用Giemsa染色和流式细胞术观察有丝分裂性细胞死亡特征;用Western blot法检测蛋白表达变化。结果：LDM抑制BEL-7402和L-02细胞的生长,二者均表现出有丝分裂性细胞死亡的特征,即细胞体积增大、G2/M期阻滞、出现多核化,但BEL-7402细胞对LDM更敏感。在LDM处理的BEL-7402和L-02细胞中,与凋亡相关的Bax和Smac的蛋白表达水平没有增加,caspase-3和caspase-9未被活化,但L-02细胞的Akt通路被激活。结论：人正常L-02细胞对LDM引起的有丝分裂性细胞死亡明显低于人肝癌BEL-7402细胞,对LDM的反应敏感性存在差异的原因可能与Akt信号通路有关。     

Assessing the selective therapeutic efficacy of superparamagnetic erlotinib nanoparticles in lung cancer by using quantitative magnetic resonance imaging and a nuclear factor kappa-B reporter gene system

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used as the first-line treatment for advanced NSCLC; however, the efficacy of drug delivery remains unknown. Hence, we successfully developed erlotinib-conjugated iron oxide nanoparticles (FeDC-E NPs) as theranostic probe that can potentially provide a new avenue for monitoring drug delivering through noninvasive magnetic resonance imaging. MRI ΔR2* relaxivity measurements offer an opportunity to quantitatively evaluate the uptake of FeDC-E NPs at cellular and tumoral levels. Additionally, NF-κB reporter gene system provides NF-κB activation status monitoring to validate the therapeutic efficiency of FeDC-E NPs. FeDC-E NPs not only inhibit the tumor growth and NF-κB-modulated antiapoptotic mechanism but also trigger extrinsic and intrinsic apoptotic pathways. Taken together, dual functional FeDC-E NPs offer diagnostic and therapeutic benefits against lung cancers, indicating that our presented probe could be applied in clinical.     

Eliciting pyroptosis to fuel cancer immunotherapy: mechanisms and strategies

Immune checkpoint blockade(ICB) therapy has recently shown promise in treating several malignancies. However, only a limited number of patients respond to this treatment, partially because of the “immune cold” condition of the tumor immune microenvironment. Pyroptosis is a type of gasdermin-mediated programmed cell death that often leads to inflammation and immune responses. Many studies on the mechanism and function of pyroptosis have led to increasing recognition of the role of pyroptosis in m...     

正中开胸上腔静脉人工血管置换的程序化处理在胸部肿瘤外科治疗中的应用

背景与目的 上腔静脉系统受累是局部晚期胸部肿瘤较常见的一种情况,手术可能获益,但风险极高.本研究针对正中开胸入路,提出一种程序化的手术方案,旨在优化流程,使得这一类以往认为风险极高的手术能够更加安全地实施.方法 35例胸部疾患累及上腔静脉系统,经正中开胸进行人工血管置换的患者资料,分期检查明确为局部晚期.包括肺部肿瘤16例,纵隔肿瘤19例.手术方法采用从左至右的单向推进,先游离左无名静脉起始部,阻断后切断,掀起瘤体,打开心包,用人工血管桥接左无名静脉和右心耳.游离上腔静脉近心端未受侵部分后,向尾侧牵拉肿瘤,剪开右侧纵隔胸膜,结扎切断右侧乳内血管,可以充分显露右无名静脉.向左上方牵拉瘤体,于肺门上方结扎切断奇静脉,此时可以阻断右无名静脉和上腔静脉,切除中间受侵的血管,以人工血管行右无名静脉-上腔静脉桥接,完成受侵的上腔静脉系统全部替换.结果 全组病例均顺利完成手术.术后并发症包括:心律失常6例,低氧血症5例,肌无力危象1例,心脏疝1例,真菌感染2例.2例患者死亡,死亡率5.12%,分别死于心梗和肺部感染.其余33例顺利出院.平均术后住院日15 d.在10例术前出现上腔静脉综合征的患者中,除2例术中即出现人工血管内血栓形成的患者,其余8例症状均明显改善.结论 上腔静脉人工血管置换手术经程序化的处理,规范治疗的细节,在手术操作过程中可降低手术风险,本组病例手术能够安全实施的实践也支持这一点.     

程序性死亡配体-1及其抑制剂在非小细胞肺癌中的研究进展

程序性死亡配体-1（PD-L1）以细胞膜型 PD-L1和可溶性 PD-L1两种形式在 NSCLC 中高表达,通过与其受体结合参与肿瘤免疫逃逸。目前 PD-L1抑制剂已进入 NSCLC 的Ⅰ期临床试验并反应良好,其治疗敏感性与肿瘤组织 PD-L1的表达状态显著相关,因而 PD-L1有望成为预测其药物疗效的生物学标志物。     

三阴性乳腺癌中PD-1、PD-L1的表达与肿瘤浸润性淋巴细胞及临床病理指标的相关性

目的:分析三阴性乳腺癌样本中PD-1、PD-L1的表达水平及其与肿瘤浸润性淋巴细胞及临床病理指标的相关性,探讨其临床意义。方法:免疫组织化学法检测132例乳腺浸润性导管癌患者样本中PD-1、PD-L1、CD4及CD8的表达情况;苏木精-伊红染色后计数癌间质中肿瘤浸润性淋巴细胞个数;回顾性分析病理报告中各项临床病理指标并随访患者预后。分析PD-1、PD-L1在三阴组和非三阴组中表达的差异,以及其与各指标之间的相关性。结果:相较于非三阴组,三阴性乳腺癌中PD-1（P=0.034）及PD-L1（P=0.037）高表达;三阴性乳腺癌中PD-1的表达与肿瘤浸润性淋巴细胞个数（P=0.015）、CD4表达（P=0.001）、ki-67指数（P=0.012）、淋巴结转移（P=0.027）、脉管癌栓（P=0.009）呈正相关,与月经初潮时间（P=0.031）呈负相关;PD-L1的表达与肿瘤浸润性淋巴细胞个数（P=0.022）、CD4表达（P=0.004）、 CD8表达（P=0.037）、ki-67指数（P=0.013）、体质量指数（P=0.004）、乳腺手术史或外伤史（P=0.029）呈正相关。结论:PD-1及PD-L1在三阴性乳腺癌中的表达水平显著高于非三阴组,其表达与肿瘤浸润性淋巴细胞的数目及分型相关,并与多种临床病理指标具有明确的相关性,提示PD-1、PD-L1及肿瘤浸润性淋巴细胞可以作为三阴性乳腺癌的诊断及预后评估的重要指标。