一例X-连锁高IgM综合征合并进行性多灶性脑白质病的基因变异分析

目的对1例临床拟诊为X-连锁高IgM综合征(X-linked hyper-IgM syndrome,XHIM)并发进行性多灶性脑白质病变(progressive multifocal leukoencephalopathy,PML)的患儿CD40L基因及人类嗜神经多瘤病毒(Jamestown Canyon virus,JCV)进行检测,明确致病原因,为临床诊断提供依据。方法采集患儿及父母外周血提取基因组NDA,设计扩增CD40L基因5个外显子及外显子-内含子连接区的特异性引物并进行PCR扩增,产物测序结果与GenBank中CD40L基因序列分析对比确定有无变异。用两对JCV特异性引物对患儿外周血DNA行巢式PCR扩增,目的条带PCR产物测序结果与GenBank中JCV序列对比确定患儿是否存在JCV感染。结果测序结果显示患儿为CD40L c.506 A>C(p.Tyr169Ser)错义变异半合子,该变异位于CD40L肿瘤坏死因子同源区结构域,引起CD40L蛋白疏水作用及结构稳定性丧失,经PolyPhen2及SIFT蛋白功能预测软件预测分别为很可能有害变异(probably damaging,score=1.00)及有害变异(deleterious,score=-8.868),该变异尚未见文献报道。患儿母亲携带CD40L c.506 A>C(p.Tyr169Ser)半合子变异,父亲未检测到该变异。患儿外周血DNA巢式PCR产物经凝胶电泳后发现JCV目的条带,测序结果与GenBank中JCV基因序列比对同源性达到99%,表明患儿外周血DNA中含有JCV,有JCV感染。结论CD40L基因分析及JCV检测结果确诊患儿为XHIGM,其并发的PML与JCV感染有关。     

黑素细胞及相关细胞群参与白癜风发病的研究进展

【摘要】 白癜风发病机制复杂，黑素细胞缺失是核心。目前认为除黑素细胞自身缺陷外，表皮和真皮细胞群的功能异常及其与黑素细胞的交互作用对白癜风的发病同样重要，充分而准确地了解不同病期白癜风皮肤全层细胞、组织的病理生理状态，对认识和治疗白癜风有重要作用。本文旨在综述黑素细胞及相关细胞群在白癜风发病中作用的研究进展。     

急性脑梗死患者血浆CD147水平与神经功能缺损程度的关系

目的探讨急性脑梗死(acute cerebral infarction,ACI)患者血浆CD147的水平及其与神经功能缺损的关系。方法选择2015年6月至2016年6月期间作者医院住院治疗的ACI患者79例(ACI组),另设对照组37例,选自门诊体检者,入选者均无脑血管病证据和(或)头颅MRI/CT检测正常者。以ELISA法检测两组血浆CD147水平,并比较两组CD147水平;以美国国立卫生研究院脑卒中量表(NIHSS)评分评估ACI组神经功能缺损情况;并分析其与CD147水平的关系。结果ACI组血浆CD147水平明显高于对照组〔(635.80±187.63)pg/mL比(352.70±91.32)pg/mL;t=8.693,P=0.000〕。ACI组患者NIHSS评分<8分组明显低于≥8分组〔(526.48±143.02)pg/mL比(761.02±150.56)pg/mL;t=-7.103,P=0.000〕。相关分析显示CD147水平与NIHSS评分成正相关(r=0.749,P=0.000)。结论ACI组患者血浆CD147水平明显升高,并且与神经功能缺损程度成正相关。     

CD200 maintains the region-specific phenotype of microglia in the midbrain and its role in Parkinson's disease

Microglia are a specialized population of tissue macrophages in the mammalian brain. Microglial phenotype is tightly regulated by local environmental factors, although little is known about these factors and their region-preferred roles in regulating local neuroinflammatory responses. We hypothesized that microglia in different brain regions respond differently to neuroinflammatory stimulation and that CD200, an anti-inflammatory protein mainly originated from neurons, acts as a local cue inhibiting microglia activation in the midbrain. We utilized a CD200-deficient mouse line to analyze the phenotypic role of CD200 in the regulation of normal neuron–microglia homeostasis in the midbrain and in the dopaminergic degeneration in an α-synuclein overexpression model of PD. We found that systemic administration of an endotoxin lipopolysaccharide induced a region-preferred change in CD200 expression in the midbrain. Similarly, CD200^−/− mice showed a regional preference in an enhancement of microglia activation and baseline inflammatory levels in the midbrain and dopamine neuron loss in the substantia nigra (SN). In a mouse model of Parkinson's disease (PD) induced by rAAV-hSYN injection into the SN, CD200^−/− mice showed more dopamine neuron loss in the SN than wild type mice. Activation of CD200 receptors with a CD200 fusion protein alleviated the neuroinflammation and neuronal death in the SN of PD mice. These findings demonstrate that CD200 is essential for the midbrain homeostasis and acts as a critical local regulator in controlling microglial properties related to the PD pathogenesis.     

A juvenile case of epilepsy-associated,isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF A598T mutation

Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAF^A598T mutation, the first case reported in a glioma. BRAF^A598T is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention.     

结直肠癌微环境中细胞因子的表达及其与CD16a mRNA表达的相关性研究

目的探讨结直肠癌肿瘤微环境中细胞因子的表达及其与CD16a mRNA表达的关系。方法分别采用实时荧光定量PCR法和流式细胞术微球阵列法(CBA法)检测42例结直肠癌组织及其癌旁组织中CD16a mRNA和8种细胞因子[包括白细胞介素(IL)-2、IL-4、IL-6、IL-10、IL-12、肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)和血管内皮生长因子(VEGF)]的表达水平,分析两者之间的相关性。结果结直肠癌组织中IL-6、TNF-α和VEGF的表达水平高于癌旁组织(P<0.05),而IL-2、IL-4、IL-10、IL-12和IFN-γ在2种组织中的表达水平比较差异均无统计学意义(P>0.05)。术前CEA正常组的IL-6和VEGF的表达水平高于术前CEA升高组(P<0.05)。相关性分析结果显示:结直肠癌组中IL-6的相对表达水平与CD16a mRNA的表达水平呈负相关(P<0.05)。结论结直肠癌组织中IL-6、TNF-α和VEGF的表达水平较癌旁组织明显升高,提示促血管生成作用及免疫抑制增强。此外,结直肠癌肿瘤微环境中CD16a mRNA的表达与IL-6的表达呈负相关。     

Does choice of antiretroviral drugs matter for inflammation?

Introduction: The massive implementation of combination antiretroviral therapy (cART) has forever changed the landscape of HIV infection. This unprecedented success has turned HIV infection into a manageable chronic disease. The increased survival of people living with HIV is, however, shadowed by a high burden of aging-related comorbidities. The pathogenic basis underlying this excess of co-morbid conditions is most likely a persistent inflammatory and immune activation state, despite an optimal control of HIV replication, which in turn has largely been attributed to bacterial or bacterial products translocation from the gut.

Area covered: This review is focused on the relationship between cART and the chronic inflammatory and immune activation status in otherwise virologically well-controlled people living with HIV (PLWH). Particular focus will be placed on the differences, if any, between distinct cART modalities, with emphasis on less-drug cART regimens, and especially on dual therapies.

Expert opinion: Research to address the increased inflammatory and immune activation status of cART-treated, HIV-infected patients, should focus on adjuvant means of therapy, rather than on the cART regime itself. With current antiretrovirals, no difference between dual and triple regimens has been demonstrated, provided that virological and immunological outcomes be non-inferior.