Fetal-maternal microchimerism enhances the survival effect of interleukin-2-activated haploidentical peripheral blood stem cell treatment in patients with advanced solid cancer

Killer immunoglobulin-like receptor (KIR)-ligand incompatibility in the graft-versus-host direction is associated with improved outcome in patients receiving hematopoietic stem cell transplants. Fetal-maternal microchimerism has been suggested to mediate acquired fetal-maternal tolerance. The goal of this study was to determine the clinical efficacy of KIR-ligand incompatibility and fetal-maternal microchimerism for interleukin-2-activated haploidentical peripheral blood stem cells (haplo-PBSCs) treatment for patients with advanced solid cancer. Forty-two (42) patients with advanced stage of solid cancer and refractory to standard chemotherapy were treated with haplo-PBSCs donated by their parents or children. Human leukocyte antigen typing, fetal-maternal microchimerism status, and engraftment were detected. Clinical outcomes including overall survival (OS), progression-free survival (PFS), and Karnofsky Performance Status (KPS) level were evaluated. Patients receiving haplo-PBSCs treatment with KIR-ligand incompatibility in the graft-versus-host direction had higher probability of OS (26.8?±?3.1 months) and PFS (13.4?±?1.3 months) when compared with those with KIR ligand compatibility (OS: 17.4?±?3.0 months, p?相似文献   

CD40L在CD4^＋CIK诱导Fas抵抗乳腺癌细胞凋亡中的机制研究

目的:探讨CD40/CD40L交联在诱导Fas抵抗乳腺癌细胞凋亡中的免疫学机制.方法:体外大规模扩增自体CIKs细胞,利用磁珠分选系统纯化其中CD4+T细胞亚群(CD4+OK).用抗Fas激活性抗体CHll诱导乳腺癌细胞系MDA-MB-231细胞凋亡,比较有无CD4+CIK培养上清预处理对MDA-MB-231细胞凋亡率的影响.MDA-MB-231细胞与CD4+CIK在不同效靶比下共孵育6小时和24小时,分别用流式细胞仪检测凋亡率和膜Fas表达,定量RT-PCR法检测胞浆内Bax、Bcl-2、FADD 和c-FLIP)的mRNA含量.在共培养系统中加入抗FasL、抗CD40L和抗IFN-γ中和抗体,分别比较MDA-MB-231细胞凋亡率、膜Fas表达和四种凋亡相关基因的mRNA含量.结果:MDA.MB-231细胞对CHIl诱导的凋亡有抵抗,但经过CD4+CIK培养上清预处理后,敏感性显著提高.MDA-MB-231细胞与CD4+CIK共孵育24小时后,细胞凋亡率明显升高,并与膜Fas表达量呈正相关(r=0.618,P<0.01).在共培养体系中添加抗FasL和抗CD40L中和抗体可完全清除增加的细胞凋亡,而抗IFN-γ中和抗体只能部分清除,凋亡率分别从(33.70±2.77)%降至(7.57±1.15)%、(7.80±0.26)%和(14.21±1.70)%.但MDA-MB-231细胞膜Fas表达可以等效地被抗CD40L和抗IFN-γ中和抗体封闭,分别从(25.90±2.45)%降至(6.93±1.56)%和(8.73±4.70)%.定量RT-PCR结果显示MDA.MB-231细胞与CD4+CIK共孵育6小时时胞浆中c-FLIP表达下降与凋亡率显著相关(r=0.898,P<0.05),而抗CD40L中和抗体可诱导c-FLIP表达升高.结论:CD40/CD40L交联和IFN-γ刺激均参与了CIM+CIK诱导的MDA-MB-231细胞凋亡,但其Fas抵抗性的逆转主要是通过CD40/CIMOL交联抑制c-FLIP的mRNA合成而实现的.     

Differential maternal responses to a newly developed vaccine information pamphlet

We compared the response to a new vaccine information pamphlet with the current CDC Vaccine Information Statements (VIS) among recently delivered mothers who were screened to identify those with concerns about immunization. Eligible mothers (n = 226) were randomly assigned to one of three equal groups; those reviewing only the new pamphlet, those receiving only VIS, or those receiving both. Among those mothers reviewing both, 61% preferred the new pamphlet for its visual appeal (P < 0.0001) and ease of understanding (P = 0.005). Overall, mothers expressed increased confidence and fewer concerns regarding multiple injections after reviewing the pamphlet. However, older, more-highly educated mothers were less likely to report improved vaccine confidence after reviewing either the pamphlet or the VIS. Mothers in all three groups stated a preference for receiving the vaccine information during pregnancy or prior to the actual immunization visit. These data suggest that early provision of tailored immunization material along with the VIS to new mothers may enhance their overall confidence in vaccines and that additional strategies targeted toward certain mothers may be needed.     

某校园鼠密度调查及防鼠策略

目的了解校园鼠患情况,为在校园中进行科学灭鼠提供相应的参考依据。方法采用粉迹法对整个校园的鼠密度进行测定。结果共布粉块712块,其中阳性粉块为135块,鼠迹率19.4%,学生旧宿舍区鼠患最严重,其次是食堂区。结论加强学生防鼠意识,改善校园特别是宿舍区卫生状况,从根本上加强校园鼠害防治已刻不容缓。     

Protocatechuic acid promotes cell proliferation and reduces basal apoptosis in cultured neural stem cells

Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of Alpinia oxyphylla, showed anti-oxidant neuroprotective property in our previous study. However, it is still unknown whether PCA have effects on the cultured neural stem cells (NSCs). In this study, we investigated the roles of PCA in the survival and apoptosis of rat NSCs under normal conditions. NSCs obtained from 13.5-day-old rat embryos were propagated as neurospheres and cultured under normal conditions with or without PCA for 4 and 7 days. The cell viability was determined by the cell counting kit-8 (CCK-8) test, while cell proliferation was assayed by bromodeoxyuridine (BrdU) labeling. PCA increased the cellular viability of NSCs and stimulated cell proliferation in a dose- and time-dependent manner. Apoptotic cells were detected after 4 days by observing the nuclear morphological changes and flow cytometric analysis. Compared with the control on both culture days, treatment with PCA effectively reduced the levels of apoptosis of NSCs. At the same time, the reactive oxygen species (ROS) level in NSCs was depressed. In addition, PCA also significantly decreased the activity of elevated caspase-3, indicating that PCA may inhibit apoptosis of NSCs via suppression of the caspase cascade. These results suggest that PCA may be a potential growth inducer and apoptosis inhibitor for NSCs.     

后程超分割调强放疗联合化疗治疗中晚期鼻咽癌的临床研究

目的:评价后程超分割放疗联合化疗治疗Ⅲ～Ⅳa鼻咽癌的疗效.方法:60例Ⅲ～Ⅳa期鼻咽癌采用随机分组为常规组、后程超分割同步化疗组.均先采用面颈联合野常规分割对穿照射40 Gy,20次4周完成.后超组缩野后改用后程超分割调强放疗,1.2Gy/次,2次/天,共14-15天完成.鼻咽病灶总DT 73.6～76Gy/7周.且在放疗同时给予PF方案治疗.对照组缩野后给予常规照射2Gy/次,鼻咽病灶DT 70～74Gy/35～37次/7～7.5周.结果:后程超分割调强放疗同步化疗组与常规组肿瘤消退率分别为96.6%(29/30)、93.3%(28/30)(P＞0.05),1、3年肿瘤局部控制率分别为93.1%、89.6%和82.1%、67.8%.1、3年生存率分别为96.5%、93.1%和92.8%、71.4%(P＜0.05).后程超分割调强放疗同步化疗组的急性放疗反应显著高于常规分割放疗组.远期不良反应如口干及颈部软组织纤维化低于常规分割放疗组.结论:后程超分割调强放疗可提高局部晚期鼻咽癌的局控率及生存率,放化疗结合可降低远处转移率,毒副反应可耐受.     

原发性肝癌患者调节性T细胞与预后的关系

目的:探讨肝细胞肝癌(HCC)患者T淋巴细胞亚群对其预后的影响.方法:对138例HCC患者的临床病理资料进行回顾性分析,采用流式细胞技术(FCM)检测早晚期HCC患者外周血T淋巴细胞不同分群占外周血单个核细胞(PBMC)的比例,Kaplan-Meier法检验T淋巴细胞亚群对HCC患者生存的影响.结果:138例HCC患者的1年生存率为61%,2年生存率为39%,早晚期HCC患者的中位生存时间分别为28、12个月.晚期HCC患者的CD4+T细胞比例低于早期患者,调节性T细胞(Treg)与NK细胞比例高于早期患者,并且差异均有统计学意义(P<0.05).单因素分析显示T淋巴细胞亚群中Treg是影响HCC患者预后的相关因素.在进一步分析影响Treg的因素时发现有肝硬化的HCC患者外周血Treg比例及绝对数高于无肝硬化的HCC患者(P=0.029),铁蛋白(Ferr)正常的HCC患者外周Treg绝对数高于Ferr水平高的HCC患者(P=0.027).结论:HCC患者的Treg在一定程度上影响其预后,Treg比例>7%是影响晚期肝硬化HCC患者预后的独立危险因素.     

The role of an Ommaya reservoir in the management of children with cryptococcal meningitis

Cryptococcal meningitis is the most common life-threatening fungal infection and is associated with high mortality in children. Amphotericin B plus flucytosine and fluconazole is the optimal current therapy. Implantation of an Ommaya reservoir for intraventricular infusion of medication and aspiration of cerebrospinal fluid (CSF) for the treatment of increased intracranial pressure (ICP) has been reported. Intraventricular injection of amphotericin B through an Ommaya reservoir in children with cryptococcal meningitis has not been reported previously. We report two children who had cryptococcal meningitis and associated increased intracranial pressure, and were treated with an Ommaya reservoir. Both patients experienced rapid reversal of symptoms. At the time of discharge both patients had recovered and have remained asymptomatic.     

Genetic polymorphisms of glutathione S-transferase T1 and bladder cancer risk: a meta-analysis

In recent years, there have been numerous papers emphasizing the relationship between Glutathione S-transferases polymorphisms and bladder cancer risk, but the findings have not reached a consensus. The relationship between glutathione S-transferase T 1 null genotype and bladder cancer susceptibility is now even more disputable. Therefore, we present a meta-analysis of (nested) case–controlled, genotype-based studies (including 37 studies, 6,986 cases and 9,166 controls) examining this association. Using a fixed-effect model, statistically significant increase was observed between glutathione S-transferase T 1 deletion and bladder cancer risk for the overall studies (OR = 1.12; 95% confidence interval (CI): 1.04–1.21; P = 0.004 for Z test; I ² = 47.43 for heterogeneity). After adjusting the result using trim-and-fill method, the outcome still had significant difference with little downgrade (OR = 1.10, 95% CI = 1.02–1.18). Three potential sources of heterogeneity including ethnicity, source of control and smoking status were also assessed. Minor increased correlation was found only in population-based studies (OR = 1.16; 95% CI = 1.03–1.30; I ² = 47.16). Our analysis suggests that glutathione S-transferase T 1 null status is associated with a modest increase in the risk of bladder cancer and the difference exiting in source of control has been confirmed. Due to limited sample size, various confounding variables as well as discrepancy in study design, a valid conclusion still cannot be confirmed.     

Relation between soluble intercellular adhesion molecule-1, statin therapy, and long-term risk of clinical cardiovascular events in patients with previous acute coronary syndrome (from PROVE IT-TIMI 22)

High levels of adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1), are associated with long-term risk of cardiac events in patients with and without stable coronary artery disease. The relation between sICAM-1 and long-term risk after acute coronary syndromes (ACSs) and the influence of statin treatment has not been explored. Using a nested case-control design, patients with ACS who were enrolled in the PROVE IT-TIMI 22 trial were matched for age, gender, smoking, diabetes, type of ACS presentation, and revascularization for index event (583 patients with recurrent events vs 581 controls). Patients with recurrent events were identified as such by death, myocardial infarction, or hospitalization for recurrent ACS. Soluble ICAM-1 was measured at study entry (approximately 7 days after ACS). After adjusting for statin regimen and other risk factors, patients in quartiles 2 to 4 were at a higher risk of clinical events compared with those in quartile 1 (odds ratio 1.6 for quartile 4 vs 1, 95% confidence interval 1.1 to 2.3, p = 0.02). The risk of adverse events in patients with sICAM-1 levels in quartiles 2 to 4 was most marked in subjects who were allocated to standard dose statin therapy, even after adjusting for low-density lipoprotein cholesterol and C-reactive protein at day 30. The risk in quartiles 2 to 4 was somewhat attenuated in the intensive therapy group. In conclusion, in this large study of patients with ACS, we provide evidence that increased endothelial activation after ACS is independently associated with increased long-term risk of death, myocardial infarction, or recurrent ACS.