Langerhans cells proliferation in ectopic micronodular thymoma with lymphoid stroma: a case report

Ectopic micronodular thymoma (MNT) is a rare tumor. We described a 76-year-old woman, who was referred to our institutional for a mass in the left cervical region. The Magnetic Resonance Imaging (MRI) scan showed a 3.7 cm × 1.7 cm × 2.0 cm mass. The neoplasm was composed of epithelial tumor cells arranged in a micronodular growth pattern set in a stroma showing lymphoid hyperplasia with germinal centers. Immunohistochemical studies showed that the neoplastic epithelial cells were reactive for AE1/AE3, CK5/6, P63, and the lymphoid component to be of mixed B- and immature T-cell lineage. Langerhans cells were confirmed within epithelial nodules for the first time with langerin, S-100, CD1a expression. We report a case of cervical ectopic MNT to emphasize the langerhans cells proliferation and the histopathologic features and differential diagnosis of the rare lesion to promote a better and broader understanding of this less understood subject.     

壳聚糖/鞣花酸/红细胞膜脂止血复合海绵的制备与评价

背景：部分文献报道壳聚糖对严重创伤的止血效果有限,因此以壳聚糖为基础止血剂的促凝血活性还有待进一步增强。 目的：制备一种新型的壳聚糖/鞣花酸/红细胞膜脂复合海绵,评价其促凝血活性和细胞毒性。 方法：通过冻干法制备壳聚糖海绵和壳聚糖乙酸盐海绵,然后再通过静电吸附法制备壳聚糖/鞣花酸/红细胞膜脂复合海绵。血浆复钙时间法观察3种海绵的促凝血活性,并检测3种海绵对SD大鼠肝脏的止血效果及对L929细胞的毒性。 结果与结论：壳聚糖/鞣花酸/红细胞膜脂复合海绵组的血浆复钙时间、出血时间、失血量均显著少于壳聚糖海绵组和壳聚糖乙酸盐海绵组(P < 0.01)。细胞实验显示壳聚糖/鞣花酸/红细胞膜脂复合海绵无细胞毒性。说明壳聚糖/鞣花酸/红细胞膜脂复合海绵具有良好的促凝血活性且无细胞毒性。     

Efficacy of Entecavir Treatment for up to 5 Years in Nucleos(t)ide-Na?ve Chronic Hepatitis B Patients in Real Life

Objective: To analyze the efficacy and safety of entecavir (ETV) treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life.Methods: We retrospectively analyzed 230 nucleos(t)ide naïve chronic hepatitis B patients who received ETV 0.5 mg/day monotherapy for at least 3 months, of whom 113 were HBeAg positive and 117 were HBeAg negative. The primary endpoints was cumulative probability of achieving a virological response (undetectable serum HBV DNA, <100IU/mL). Secondary endpoints were rates of ALT normalization (ALT < upper limit of normal), HBeAg seroconversion, resistance, and safety.Results: The median follow-up duration was 27.5 months (3-73 months) and mean age was 42 years. With 230, 214, 180, 142, 88, 42 and 11 patients followed-up for at least 3 months,6 months, 1, 2, 3, 4 and 5 years, respectively. In all, Incremental increases were observed in the rates of undetectable HBV DNA. 67.0%, 85.0%, 89.4%, 94.4%, 95.5%, 97.6%, 100% had undetectable HBV DNA at month 3, month 6, 1 year, 2 years, 3 years, 4 years and 5 years. Proportions of patients achieving normal ALT were 73.9%, 85.5%, 82.8%, 89.4%, 80.7%, 85.7%, 100%, respectively. The rate of HBeAg seroconversion reached 21.4% and 15.4% at year2, 3, respectively. One patient achieved HBsAg seroclearance after 1 year, and achieved anti-HBs seroconversion at year 3. Of 180 patients, HBV DNA was detectable (partial virological response, PVR) in 19 patients at year 1 of follow-up, twelve of 14 (85.7%) patients with PVR need more than 1 year of continuous ETV therapy to achieved VR. At baseline, no ETV-resistance was detected in 25 ETV-naïve patients. One patient developed ETV-resistance mutations due to noncompliance. No serious adverse event was reported.Conclusion: Long-term ETV treatment of nucleos(t)ide-naïve was effective and safe in real life. Adjustment of ETV monotherapy in nucleos(t)ide-naïve patients with a partial virological response at 1 year may be unnecessary.     

Conserved epitopes dominate cross‐CD8+ T‐cell responses against influenza A H1N1 virus among Asian populations

Novel strains of influenza A viruses (IAVs) have emerged with high infectivity and/or pathogenicity in recent years, causing worldwide concern. T cells are correlated with protection in humans through cross‐reactive immunity against heterosubtypes of IAV. However, the different hierarchical roles of IAV‐derived epitopes with distinct levels of polymorphism in the cross‐reactive T‐cell responses against IAV remain elusive. In this study, immunodominant epitopes scattered throughout the entire proteome of 2009 pandemic influenza A H1N1 virus and seasonal IAVs were synthesized and divided into different pools depending on their conservation. The overall profile of the IAV‐specific CD8⁺ T‐cell immunity was detected by utilizing these peptide pools and also individual peptides. A dominant role of the conserved peptide‐specific T‐cell immunity was illuminated within the anti‐IAV responses, while the CD8⁺ T‐cell responses against the variable epitopes were lower than the conserved peptides. As previously demonstrated within a Caucasian population, we determined that GL9‐specific T cells, which also utilize Vβ 17 TCR (BV19), play a pivotal role in IAV‐specific T‐cell immunity within an HLA‐A2⁺ Asian population. Our study objectively reveals the different predominant roles of T‐cell epitopes among IAV‐specific cross‐reactive cellular immunity. This may guide the development of vaccines with cross‐T‐cell immunogenicity against heterosubtypes of IAV.     

磁性靶向纳米粒体外多模态成像及对肝星状细胞的靶向作用

文题释义： 多模态成像：随着分子影像学的飞速发展,多模态成像改变了传统单一的成像方式,联合超声、CT、MRI、光声及SPECT等各自独特的成像优势,只使用一种对比剂即可获得多种模态增强显影,同时得到疾病的解剖学、分子学及功能学信息。这对疾病的诊断、受检者的健康及减少医疗资源浪费都有重要意义。 寻靶：通过对微泡外壳进行改建,将特异性配体结合或连接到微泡表面,这些微泡可通过血液循环聚到特定的病变组织上,并长时间停留于靶组织或靶器官,从而达到使病变组织在影像中得到特异性的标记增强或局部靶向治疗作用的目的。背景：近来年,分子成像结合医学影像技术和靶向分子探针逐渐成为研究的热点,其相互结合能够在分子水平对靶组织进行观察,从而实现对疾病的发生、发展实时无创成像。 目的：制备载磁性颗粒靶向纳米粒探针,探讨其体外超声/CT/MRI成像效果,观察其体外对大鼠肝星状细胞的靶向能力。 方法：以高分子材料聚乳酸/羟基乙酸作为外壳、含有精氨酸-甘氨酸-天冬氨酸序列环八肽作为配体,通过双步乳化法制备包载磁性颗粒和全氟辛溴烷的载磁性颗粒靶向纳米粒cRGD-PLGA-Fe₃O₄-PFOB,检测其理化性质。将载磁性颗粒靶向纳米粒以双蒸水稀释为不同质量浓度的混悬液,体外观察其超声、CT、MRI显影效果。通过碳二亚胺法连接精氨酸-甘氨酸-天冬氨酸序列肽与载磁性颗粒靶向纳米粒,验证载磁性颗粒靶向纳米粒的精氨酸-甘氨酸-天冬氨酸序列连接情况和体外靶向能力。细胞毒性实验测定不同质量浓度载磁性颗粒靶向纳米粒对大鼠肝细胞BRL-3A的毒性作用。 结果与结论：①载磁性颗粒靶向纳米粒分散度好,大小较均匀,单个纳米粒呈球形,数个黑色的铁颗粒分布于壳膜上,平均粒径为(221.5±60.3) nm,Fe₃O₄包封率为38%;②随着载磁性颗粒靶向纳米粒质量浓度的降低,样品的超声回声强度、CT值均逐渐降低;随着纳米粒中Fe₃O₄颗粒质量浓度的增加,MRI T2加权信号强度逐渐降低;③流式细胞仪检测显示,含有精氨酸-甘氨酸-天冬氨酸序列环八肽与载磁性颗粒靶向纳米粒的连接率为94.13%;体外靶向实验显示,大部分载磁性颗粒靶向纳米粒聚集于大鼠肝星状细胞细胞HSC-T6周围;④不同质量浓度的载磁性颗粒靶向纳米粒对大鼠肝细胞BRL-3A活力无影响;⑤结果表明,载磁性颗粒靶向纳米粒探针不仅能作为多模态显像剂用于超声、CT、MRI,且在体外实验中对大鼠肝星状细胞有较强的靶向能力,对肝纤维化的早期诊断具有重大应用潜力。 ORCID: 0000-0001-8470-8548(李璇) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Monocytes augment inflammatory responses in human aortic valve interstitial cells via β2-integrin/ICAM-1-mediated signaling

Objective

Inflammatory infiltration in aortic valves promotes calcific aortic valve disease (CAVD) progression. While soluble extracellular matrix (ECM) proteins induce inflammatory responses in aortic valve interstitial cells (AVICs), the impact of monocytes on AVIC inflammatory responses is unknown. We tested the hypothesis that monocytes enhance AVIC inflammatory responses to soluble ECM protein in this study.

Methods

Human AVICs isolated from normal aortic valves were cocultured with monocytes and stimulated with soluble ECM protein (matrilin-2). ICAM-1 and IL-6 productions were assessed. YAP and NF-κB phosphorylation were analyzed. Recombinant CD18, neutralizing antibodies against β₂-integrin or ICAM-1, and inhibitor of YAP or NF-κB were applied.

Results

AVIC expression of ICAM-1 and IL-6 was markedly enhanced by the presence of monocytes, although matrilin-2 did not affect monocyte production of ICAM-1 or IL-6. Matrilin-2 up-regulated the expression of monocyte β₂-integrin and AVIC ICAM-1, leading to monocyte-AVIC adhesion. Neutralizing β₂-integrin or ICAM-1 in coculture suppressed monocyte adhesion to AVICs and the expression of ICAM-1 and IL-6. Recombinant CD18 enhanced the matrilin-2-induced ICAM-1 and IL-6 expression in AVIC monoculture. Further, stimulation of coculture with matrilin-2 induced greater YAP and NF-κB phosphorylation. Inhibiting either YAP or NF-κB markedly suppressed the inflammatory response to matrilin-2 in coculture.

Conclusion

Monocyte β₂-integrin interacts with AVIC ICAM-1 to augment AVIC inflammatory responses to soluble matrilin-2 through enhancing the activation of YAP and NF-κB signaling pathways. Infiltrated monocytes may promote valvular inflammation through cell–cell interaction with AVICs to enhance their sensitivity to damage-associated molecular patterns.

     

RXRalpha-regulated liver SAMe and GSH levels influence susceptibility to alcohol-induced hepatotoxicity

Retinoids influence the pathogenesis of alcohol liver disease (ALD). To analyze the impact of retinoid X receptor alpha (RXRalpha) on ALD, alcohol-induced hepatotoxicity was studied using mice fed ethanol intragastrically for 25 days. Alcohol-induced microvesicular fat around the central vein and drug-induced morphological changes (loss of rough endoplasmic reticulum, pinkish cytoplasm, and enlarged hepatocyte) in the pericentral area were observed in the liver of wild-type mice. In the hepatocyte RXRalpha-deficient mouse liver, alcohol induced fat accumulation, mitosis, acute inflammation, and necrosis. The histology score after alcohol treatment was significantly higher in mutant mice than in wild-type mice. However, drug-induced morphological changes were not apparent in alcohol-treated hepatocyte RXRalpha-deficient mice. Northern analysis showed that the basal and alcohol-induced CYP2B, CYP2A, and CYP3A mRNA levels were lower in hepatocyte RXRalpha-deficient mice than in wild-type mice, which in turn may protect mutant mice from morphological changes. Compared with wild-type mice, hepatocyte RXRalpha-deficient mice have significant lower levels of S-adenosylmethionine and glutathione, which is further reduced after alcohol treatment, and that may account for severe liver injury induced by alcohol. The overall result suggests an important role of RXRalpha in preventing alcohol-induced liver injury.     

Expression of pseudorabies virus gE epitopes in Pichia pastoris and its utilization in an indirect PRV gE-ELISA

Pseudorabies virus glycoprotein E (PRV gE) has been recognized as a suitable diagnostic antigen for pseudorabies. In order to produce gE antigen in large quantities and at low cost, a gene fragment encoding PRV gE epitopes was expressed in Pichia pastoris expression system. SDS-PAGE and Western blotting revealed that the expression product was two recombinant proteins, approximately 38 and 32 kDa, in the culture supernatant of P. pastoris integrant 72 h after induction. Protein concentration assay showed the expression product amounted to 106.7 mg/l, accounting for 66.67% of total culture supernatant proteins. An indirect PRV gE-ELISA was then established by using the recombinant expression product as a coating antigen. Cross-reactivity assay showed that this antigen was PRV specific. Reproducibility experiment displayed good consistency. Comparison of detection results of 348 field serum samples between PRV gE-ELISA and a commercially available PRV diagnostic kit showed there was no significant difference between these two methods (P > 0.05).     

蛋白亚细胞定位的预测方法研究

预测蛋白质的亚细胞定位信息对于了解其功能有重要的意义.选择氨基酸组成、氨基酸对组成、位置特异性打分矩阵三种分类特征以及模糊k近邻、支持向量机两种预测方法,分别进行了测试.对预测结果的分析显示,位置特异性打分矩阵可以提高对不同亚细胞器的可区分性;而支持向量机可以更好地利用位置特刎异性打分矩阵特征进行预测.使用氨基酸组成和位置特异性打分矩阵两种特征,并结合支持向量机,是一种有效的亚细胞定位预测方法.