m7FLIPI and targeted sequencing in high‐risk follicular lymphoma

Patients with follicular lymphoma (FL) refractory to front‐line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high‐risk FL. Twenty‐five patients with FL refractory to front‐line ICT and 10 non‐refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three‐year progression‐free survival (PFS) and OS probabilities were 25% (95% CI, 13%‐41%) and 53% (34%‐69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0‐3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non‐refractory). In conclusion, in this study, patients with high‐risk follicular lymphoma were genetically heterogeneous.     

Evoked potentials predict psychomotor development in neonates with normal MRI after hypothermia for hypoxic-ischemic encephalopathy

Objectives

To assess the prognostic role of evoked potentials (EP) in neonates with normal magnetic resonance imaging (MRI) after therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE).

胎盘异铁蛋白在异常妊娠中作用的研究进展

胎盘异铁蛋白是一种免疫抑制因子 ,主要抑制妊娠过程中母体淋巴细胞对胎儿的同种异体免疫 ,使妊娠得以顺利进行 ,其低水平表达 ,不仅与一些肿瘤发生有关 ,而且与许多异常妊娠 ,如早产、流产、异位妊娠、胎儿宫内发育迟缓、妊高征、滋养细胞肿瘤以及多种妊娠合并症关系密切。对胎盘异铁蛋白的研究将促进妇产科多种疾病的诊治进展。     

Evidence that PGE2 in the dorsal and median raphe nuclei is involved in LPS-induced anorexia in rats

Anorexia is an element of the acute-phase immune response. Its mechanisms remain poorly understood. Activation of inducible cyclooxygenase-2 (COX-2) in blood-brain-barrier endothelial cells and subsequent release of prostaglandins (e.g., prostaglandin E2, PGE2) may be involved. Therefore, we sought to relate the effects of prostaglandins on the anorexia following gram-negative bacterial lipopolysaccharide treatment (LPS) to neural activity in the dorsal and median raphe nuclei (DRN and MnR) in rats. COX-2 antagonist (NS-398, 10 mg/kg; IP) administration prior to LPS (100 μg/kg; IP) prevented anorexia and reduced c-Fos expression the DRN, MnR, nucleus tractus solitarii and several related forebrain areas. These data indicate that COX-2-mediated prostaglandin synthesis is necessary for LPS anorexia and much of the initial LPS-induced neural activation. Injection of NS-398 into the DRN and MnR (1 ng/site) attenuated LPS-induced anorexia to nearly the same extent as IP NS-398, suggesting that prostaglandin signaling in these areas is necessary for LPS anorexia. Because the DRN and MnR are sources of major serotonergic projections to the forebrain, these data suggest that serotonergic neurons originating in the midbrain raphe play an important role in acute-phase response anorexia.     

The soluble EP2 receptor FuEP2/Ex2 suppresses endometrial cancer cell growth in an orthotopic xenograft model in nude mice

Endometrial cancer is one of the most common gynecologic malignancies and many factors influence in its growth and development. As in many other types of cancer, prostaglandin E(2) (PGE(2)) is thought to be an accelerator of cell proliferation and endometrial cancer progression. In this study, we examined the effect of FuEP2/Ex2, a soluble decoy receptor for PGE(2) on growth of endometrial cancer cells. A stable transfectant expressing FuEP2/Ex2 was established from human endometrial cancer Ishikawa cells (Ish-FuEP2/Ex2). Ish-FuEP2/Ex2 cells expressed FuEP2/Ex2 mRNA and protein. Expression levels of E-prostanoid receptor 1 (EP1), EP2, EP3, EP4, and F-prostanoid receptor (FP) were almost the same in Ish-FuEP2/Ex2 and vector control cells. Growth rates of Ish-FuEP2/Ex2 under normal culture conditions were also similar to vector control cells, although PGE(2)-induced growth stimulation was completely inhibited in Ish-FuEP2/Ex2 or by Ish-FuEP2/Ex2 culture medium. Moreover, phosphorylation of extracellular signal-regulated kinase (ERK) and induction of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), cyclin D1, and c-fos mRNA by PGE(2) were not observed in Ish-FuEP2/Ex2 and Ish-FuEP2/Ex2 culture medium-treated vector control cells, although they were found when treated with prostaglandin F(2α). An orthotopic xenograft model in athymic nude mice revealed that Ish-FuEP2/Ex2-injected mice had significantly decreased mean tumor area. The proportion of Ki-67-positive cells in the tumor lesion was also significantly lower in Ish-FuEP2/Ex2-injected mice. These findings suggest that an EP-targeting strategy using FuEP2/Ex2 may be of use in the treatment of endometrial cancer.     

两种不同方法学检测PSA、CA125、CA15-3、CA19-9的比对研究

为探讨不同检测方法测定PSA、CA125、CA15-3、CA19-9结果的可比性,参考EP9-A2文件的规定,使用RIA和微粒子酶免疫方法(MEIA)测定PSA、CA125、CA15-3及CA19-9并进行方法学比对试验,两种方法各项结果间均呈良好的线性关系,其相关系数R2均大于0.95;PSA和CA15-3系统误差均...     

奥林巴斯AU5400全自动生化分析仪检测尿素氮临床可报告范围的建立与评价

目的建立奥林巴斯AU5400全自动生化分析仪检测尿素氮的临床可报告范围。方法参考美国临床检验标准化协会(CLSI)EP6-A文件和相关文献,在奥林巴斯AU5400全自动生化分析仪上进行尿素氮功能灵敏度验证实验、分析测量范围验证实验、最大允许稀释度验证实验,并由此建立其临床可报告范围。结果 BUN的分析测量范围为0.84～47.01mmol/L,最大允许稀释度为1:50,其临床可报告范围为0.66～2350.5mmol/L。结论奥林巴斯AU5400对BUN检测结果可靠准确,线性范围宽,适合常规检测。     

Cognitive evoked potentials in narcolepsy: a review of the literature

Subtle cognitive deficits have been described in narcolepsy. They have been hypothesised to be related to changes in the hypocretin system. Event-related potential (ERP) paradigms are known to be useful tools in the investigation of information processing and seem to be sensitive to subtle neuropsychological changes. We review empirical articles on ERPs in narcolepsy in order to contribute to clarify the pattern of cognitive deficits that are specific to this disease and, possibly, to identify specific cognitive domains that improve with treatment. Fourteen peer-reviewed articles were selected for this review. These studies were conducted with passive and active oddball paradigms and support the existence of changes in cognitive attentive processing in narcolepsy, possibly in association with altered functioning of the prefrontal cortex. ERP low-resolution electromagnetic tomography revealed that modafinil improved information processing speed and increased energetic resources in prefrontal cortical areas. These findings suggest that it is worthwhile to further evaluate the usefulness of ERPs in the detection of cognitive dysfunction in this disorder before and after treatment.     

Association study of EP1 gene polymorphisms with suicide completers in the Japanese population

Background

Both environmental and genetic factors have been reported to be involved in suicidal behaviors. Considerable evidence indicates that impulsive aggression is one of the important risk factors that contribute to suicide. A recent study has shown that prostaglandin E2 type 1 receptor (EP1) signaling regulates impulsive-aggressive behaviors in mice under both social and environmental stresses. To test the possible involvement of the EP1 gene in suicide, we carried out an association study of EP1 gene polymorphisms with suicide completers in the Japanese population.

Methods

We studied 5 SNPs including one SNP in exon 2 (rs3745459) and four SNPs in the potential promoter region of the EP1 gene (rs3810255, rs3810254, rs3810253 and rs10416814) in 374 healthy control and 287 completed suicide victims using standard Taqman probe genotyping assays.

Results

No significant differences of the genotypic distribution, allelic frequency or haplotype distribution between controls and suicide completers were found. Gender based analysis revealed that genotypic, allelic and haplotypic distributions of rs3810255, rs3810254, rs3810253 and rs10416814 SNPs were significantly different between the female control and female suicide groups, although the differences did not withstand correction for multiple comparisons.

Conclusion

We could not find an association of EP1 gene with suicide in the Japanese population. Because several SNPs in the promoter region of the EP1 gene were nominally significantly associated with suicide in the female, further studies with a larger sample size and different population are needed to confirm this result.