An unexpected asymptomatic epiglottal site of Kimura disease

Introduction

Kimura disease (KD) is a chronic lymphoproliferative disorder of unknown etiology that affects the skin and lymph nodes, mostly observed in males of Asian descent. The natural history of asymptomatic epiglottal KD remains unknown. This rare site of KD is often only diagnosed when tumor growth starts to obstruct the upper airways.

瘦素在肥胖成人慢性鼻-鼻窦炎伴鼻息肉发病中的作用

1007 1520.202003008·论著· 目的初步探讨瘦素（Leptin）在肥胖成人慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）发病中的作用及机制。方法按照体重指数（BMI）随机选取肥胖CRSwNP患者40例，体重正常CRSwNP患者30例，选取同期肥胖鼻中隔偏曲患者30例为对照组。通过酶联免疫吸附法（ELISA）测定3组患者血清中Leptin及其受体水平、EOS相关因子IL 4、IL 13的水平；RT PCR及免疫组织化学方法检测3组患者局部鼻黏膜中Leptin及其受体水平表达；苏木精-伊红染色法观察3组患者组织中EOS细胞浸润程度。另Pearson相关性分析Leptin水平与EOS相关指标及浸润程度的关系。结果与对照组比较，两组CRSwNP患者的血清与局部Leptin及其受体水平表达均升高，血清中EOS相关因子IL 4、IL 13的水平表达均显著升高，差异具有统计学意义（P<0.05）；两组CRSwNP患者中肥胖患者的各项检测指标均显著高于体重正常患者（P<0.05），且Leptin及其受体水平与EOS相关指标、EOS浸润程度均呈正相关（P<0.05）。结论Leptin在CRSwNP患者中水平显著升高，且肥胖患者组更高，并与EOS浸润及其促进因子显著相关，提示Leptin可能通过促进EOS增殖浸润参与肥胖成人CRSwNP发病。     

嗜酸性粒细胞在肿瘤免疫微环境中的作用研究进展

近年来,对恶性肿瘤发生发展过程及治疗策略的研究扩展到肿瘤组织与肿瘤免疫微环境（TIME）的联合作用,TIME由肿瘤细胞、肿瘤相关成纤维细胞及其分泌的基质蛋白、血管内皮细胞、免疫细胞,以及一系列细胞因子、趋化因子、细胞外基质组成。TIME的组成及表型会影响肿瘤的发展及疗效,针对TIME各组分的充分了解有助于治疗方案的制定和预后的预测。嗜酸性粒细胞（EOS）是TIME的重要组分,由骨髓中的多能干细胞分化而来,成熟后释放入血,随后迁移到组织中,该过程受多种细胞因子、趋化因子、黏附分子调控,EOS自身及肥大细胞、成纤维细胞等组分分泌一系列介质起趋化作用。成熟EOS含初级颗粒和特殊颗粒,包含一系列细胞毒性碱性蛋白,如主要碱性蛋白（MBP）、嗜酸性粒细胞源性神经毒素（EDN）、嗜酸性粒细胞阳离子蛋白（ECP）和嗜酸性粒细胞过氧化物酶（EPX）等,并可分泌神经营养因子、白细胞介素及趋化因子等可溶成分。目前针对EOS的研究多集中于EOS水平对预后的影响分析、EOS与TIME其他组分的相互作用,而EOS促肿瘤或抗肿瘤的相关信号通路和确切机制尚不明确,相关组织学实验和临床试验较少,有待进一步研究和完善。     

No strict requirement for eosinophils for bone marrow plasma cell survival

Lasting antibody responses are maintained by long‐lived plasma cells, which are thought to lodge in the BM in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought to provide pro‐survival signals to nearby plasma cells. Recent study shows that many BM plasma cells are recently generated and chiefly short‐lived cells, raising the possibility that rare plasma cell–eosinophil interactions are a rate‐limiting step needed to establish lasting humoral immunity. To address these issues, we examined the impact of eosinophil depletion on short‐ and long‐lived BM plasma cells in the context of antibody responses induced by both T‐cell dependent and T‐cell independent antigens. Surprisingly, our results failed to support a role for eosinophils in either plasma cell generation or survival. These studies included examination of plasma cell frequencies in mice lacking eosinophils either after antibody‐mediated depletion, or due to mutation of the GATA1 locus.     

XE-2100血细胞分析仪嗜酸粒细胞异常散点图报警筛选疟原虫感染的研究

目的 利用Sysmex XE-2100血细胞分析仪提示的嗜酸粒细胞增高或无嗜酸粒细胞分类结果及异常散点图信息,探索能够快速、简便地检出疟原虫的方法.方法 用XE-2100血细胞分析仪进行血常规检测,对嗜酸粒细胞比值增高或无嗜酸粒细胞分类结果的标本进行显微镜检查,当镜检未发现嗜酸粒细胞异常时,继续镜检红细胞,查找疟原虫.结果 在1 501份仪器报警提示嗜酸粒细胞比值增高或无嗜酸粒细胞分类结果的标本中,经显微镜镜检发现有9份嗜酸粒细胞结果正常,与仪器报警不符.其中6份仪器报警提示嗜酸粒细胞增高,分类散点图中的嗜酸粒细胞与中性粒细胞间的间距变小;另外3份仪器报警提示白细胞分类散点图异常,嗜酸粒细胞与中性粒细胞间无间距,从而无分类结果.但9份标本均在红细胞中检出疟原虫的滋养体、裂殖体或配殖体.结论 当SysmexXE-2100血细胞分析仪提示嗜酸粒细胞增高或无嗜酸粒细胞分类结果,而未得到显微镜镜检证实时,则高度提示有疟原虫感染.此方法不仅能快速、简便地筛查疟原虫,而且对于防止漏检疟原虫有重要临床实用价值.     

骨髓间充质干细胞移植在哮喘小鼠肺组织中的作用

目的：探讨外源性骨髓间充质干细胞（MSCs）移植后在哮喘小鼠肺组织中的分布及对气道炎症的影响,为以MSCs为基础的哮喘疾病的防治提供实验依据.方法：取30只雌性BALB/c 小鼠随机分成空白对照组、哮喘组和MSCs处理组.在无菌条件下取绿色荧光蛋白（GFP）转基因小鼠骨髓MSCs,体外扩增并鉴定.哮喘组和MSCs处理组应用卵白蛋白（OVA）腹腔注射（第0、7、14天）和雾化吸入（第15~21天）制备慢性哮喘模型.第14天通过尾静脉注射将表达GFP的MSCs移植入MSCs处理组小鼠.于末次激发哮喘后24h,取3组动物支气管肺泡灌洗液（BALF）和外周血,计数细胞总数和嗜酸粒细胞数,取肺组织行病理切片,HE染色观察肺部气道炎症情况,并通过荧光显微镜观察MSCs在哮喘小鼠肺组织中的分布,Image-proplus图像分析软件测量支气管壁厚度和平滑肌厚度.结果：GFP转基因小鼠骨髓中分离的MSCs表达MSC特异性标志物并表达GFP.MSCs处理组和哮喘组小鼠BALF中细胞总数以及外周血和BALF嗜酸粒细胞百分比均高于空白对照组,但MSCs处理组上述指标明显低于哮喘组,差异有统计学意义（P〈0.05）.与哮喘组比较,MSCs处理组小鼠肺组织病理学变化改善,支气管壁厚度和平滑肌厚度均显著降低（P〈0.05）.结论：外源性MSCs体内移植能集中分布于哮喘小鼠肺组织并通过减少哮喘气道嗜酸粒细胞侵润等方式抑制哮喘小鼠的气道炎症.     

Primary care of asthma: new options for severe eosinophilic asthma

Objective: Asthma is a common heterogeneous disease characterized by airway inflammation and bronchoconstriction. Current treatment guidelines provide recommendations for categorizing disease severity, asthma control and management. This paper reviews asthma assessment in primary care and describes the pathophysiology, clinical characteristics and new targeted treatments available for patients with severe eosinophilic asthma.

Methods: A non-systematic PubMed literature search was conducted and articles, primarily from the last 5?years, were selected based on relevance to primary care practice, asthma pathophysiology and biologic therapies.

Results: Despite optimal therapy including high-dose inhaled corticosteroids (ICS), long-acting β2-agonists and tiotropium, ～4–10% of all patients with severe asthma continue to have poor asthma control. These patients have impaired quality of life, frequent exacerbations and are exposed to the side effects of repeated courses of oral steroids. Approximately 50% of patients with severe uncontrolled asthma have eosinophilic asthma, with increased airway expression of type 2 cytokines IL-4, IL-5 and IL-13. Eosinophilic asthma is identified in primary care by having eosinophils ≥150–300 cells/μL on a complete blood count with differential.

Conclusions: A new class of agents is available for patients with moderate to severe eosinophilic asthma. Four biologic therapies – mepolizumab, reslizumab, benralizumab and dupilumab – that interfere with the regulation and activity of eosinophils have been approved by the FDA for patients with moderate to severe asthma with an eosinophilic phenotype. Primary care physicians should be familiar with these medications to explain part of the rationale for referral to specialist care and manage patient expectations for treatment.     

Gastric eosinophils are detrimental for Helicobacter pylori vaccine efficacy

Helicobacter pylori (Hp) colonizes the human gastric mucosa with a high worldwide prevalence. Currently, Hp can be eradicated by the use of antibiotics. Due to the increase of antibiotic resistance, new therapeutic strategies need to be devised: one such approach being prophylactic vaccination. Pre-clinical and clinical data showed that a urease-based vaccine is efficient in decreasing Hp infection through the mobilization of T helper (Th)-dependent immune effectors, including eosinophils. Preliminary data have shown that upon vaccination and subsequent Hp infection, eosinophils accumulate in the gastric mucosa, suggesting a possible implication of this granulocyte subset in the vaccine-induced reduction of Hp infection.In our study, we confirm that activated eosinophils, expressing CD63, CD40, MHCII and PD-L1 at their cell surface, infiltrate the gastric mucosa during vaccine-induced reduction of Hp infection. Strikingly, we provide evidence that bone marrow derived eosinophils efficiently kill Hp in vitro, suggesting that eosinophils may participate to the vaccine-induced reduction of Hp infection. However, conversely to our expectations, the absence of eosinophils does not decrease the efficacy of this Hp vaccine in vivo. Indeed, vaccinated mice that have been genetically ablated of the eosinophil lineage or that have received anti-Sialic acid-binding immunoglobulin-like lectin F eosinophil-depleting antibodies, display a lower Hp colonization when compared to their eosinophil sufficient counterparts. Although the vaccine induces similar urease-specific humoral and Th responses in both eosinophil sufficient and deficient mice, a decreased production of anti-inflammatory cytokines, such as IL-10, TGFβ, and calgranulin B, was specifically observed in eosinophil depleted mice.Taken together, our results suggest that gastric eosinophils maintain an anti-inflammatory environment, thus sustaining chronic Hp infection. Because eosinophils are one of the main immune effectors mobilized by Th2 responses, our study strongly suggests that the formulation of an Hp vaccine needs to include an adjuvant that preferentially primes Hp-specific Th1/Th17 responses.