矽肺大鼠肺组织let-7d-3p和miRNA-21-5P差异表达及其初步分析

目的探索let-7d-3p和miRNA-21-5p在二氧化硅(SiO_2)诱导的大鼠纤维化肺组织中的差异表达及其意义。方法 SPF级Wistar雄性大鼠随机分为对照组和模型组,每组30只,采用一次性气管内灌注1 ml SiO_2悬浊液建立大鼠矽肺模型,对照组大鼠相同方法灌注1ml灭菌生理盐水。分别于染尘后1、7、14、21、28 d采集各组大鼠肺组织,每组取6只,对3只大鼠肺组织进行病理学观察,另外3只采用miRNA微阵列芯片技术筛选肺组织中差异表达的miRNA,通过miRNA芯片筛选结合反转录定量聚合酶链式反应(RT-qPCR)验证let-7d-3p和miRNA-21-5p在两组间的表达水平,对let-7d-3p和miRNA-21-5p进行靶基因预测并进行GO(gene ontology)富集分析和KEGG(kyoto encyclopedia of genes and genomes)通路分析。结果对照组大鼠1、7、14和21 d Masson染色均可见正常肺组织,未发现胶原纤维,28 d大鼠肺间质和支气管周围仅有少量纤细的胶原分布;模型组大鼠1 d和7 d未发现胶原纤维,14 d染色可见较多以淋巴细胞为主的炎症细胞浸润,未见明显纤维组织,21 d和28 d模型组大鼠肺间质内可见大片状密集的胶原纤维沉积,在肉芽组织、支气管及血管壁周围胶原蛋白增生明显。模型组中let-7d-3p的表达水平均显著下调,miRNA-21-5p表达水平均显著上调,与对照组相比差异均有统计学意义(P0.05)。结论模型组中let-7d-3p和miRNA-21-5p表达变化明显,可能与早期矽肺的发生发展有关。     

An inducible transgenic mouse breast cancer model for the analysis of tumor antigen specific CD8+ T-cell responses

In Simian virus 40 (SV40) transgenic BALB/c WAP-T mice tumor development and progression is driven by SV40 tumor antigens encoded by inducible transgenes. WAP-T mice constitute a well characterized mouse model for breast cancer with strong similarities to the corresponding human disease. BALB/c mice mount only a weak cellular immune response against SV40 T-antigen (T-Ag). For studying tumor antigen specific CD8⁺ T-cell responses against transgene expressing cells, we created WAP-T_NP mice, in which the transgene additionally codes for the NP_118–126-epitope contained within the nucleoprotein of lymphocytic choriomeningitis virus (LCMV), the immune-dominant T-cell epitope in BALB/c mice. We then investigated in WAP-T_NP mice the immune responses against SV40 tumor antigens and the NP-epitope within the chimeric T-Ag/NP protein (T-Ag_NP). Analysis of the immune-reactivity against T-Ag in WAP-T and of T-Ag_NP in WAP-T_NP mice revealed that, in contrast to wild type (wt) BALB/c mice, WAP-T and WAP-T_NP mice were non-reactive against T-Ag. However, like wtBALB/c mice, WAP-T as well as WAP-T_NP mice were highly reactive against the immune-dominant LCMV NP-epitope, thereby allowing the analysis of NP-epitope specific cellular immune responses in WAP-T_NP mice. LCMV infection of WAP-T_NP mice induced a strong, LCMV NP-epitope specific CD8⁺ T-cell response, which was able to specifically eliminate T-Ag_NP expressing mammary epithelial cells both prior to tumor formation (i.e. in cells of lactating mammary glands), as well as in invasive tumors. Elimination of tumor cells, however, was only transient, even after repeated LCMV infections. Further studies showed that already non-infected WAP-T_NP tumor mice contained LCMV NP-epitope specific CD8⁺ T-cells, albeit with strongly reduced, though measurable activity. Functional impairment of these ‘endogenous’ NP-epitope specific T-cells seems to be caused by expression of the programmed death-1 protein (PD1), as anti-PD1 treatment of splenocytes from WAP-T_NP tumor mice restored their activity. These characteristics are similar to those found in many tumor patients and render WAP-T_NP mice a suitable model for analyzing parameters to overcome the blockade of immune checkpoints in tumor patients.     

子宫动静脉畸形大出血2例文献复习

子宫动静脉畸形( uterine arteriovenous malformations, UAVMs)在临床上是较为少见的疾病,但常常导致不明原因阴道流血,有时可出现大出血,危及生命。现对在金华市中心医院诊治的2例UAVMs病例进行回顾性分析,并复习相关文献,报道如下。     

Microcystic adnexal carcinoma—diagnostic criteria and therapeutic methods: case report and review of the literature

Microcystic adnexal carcinoma (MAC) is a rare, infiltrating, locally aggressive cutaneous neoplasm of combined follicular and eccrine/apocrine histogenesis, usually presenting on the upper lip or face. Differentiation from other adnexal tumours is very important because the clinical management of these tumours is radically different, and misdiagnosis may lead to incorrect treatment. A case of recurrent MAC in the upper lip, treated with multiple excisions and postoperative radiation therapy (PORT), is presented herein. There have been no signs or symptoms of recurrence since the subsequent reconstructive surgery and PORT. Based on reports in the literature it appears that although immunohistochemistry can be helpful in distinguishing between MAC and other adnexal tumours, careful histopathological examination is essential for an accurate diagnosis. Perineural and intramuscular invasion strongly suggest the diagnosis of MAC. Its predilection for the facial area often limits the width of surgical excision. In such cases, PORT may be considered.     

Dedifferentiated endometrial cancer: an atypical case diagnosed from cerebellar and adrenal metastasis: case presentation and review of literature

Dedifferentiated endometrial cancer (DEC) is microscopically characterized by the presence of high-grade areas emerging from low-grade tumour. DEC is an aggressive tumour even when the dedifferentiated component represents only 20% of the entire neoplasm. A proper histological diagnosis is essential to define the most appropriate therapeutic approach for these tumors, since they are characterized by a particularly aggressive trend and by an extremely poor prognosis. We report a single case of DEC associated with dedifferentiated and adrenal metastasis, for which the patient underwent both abdominal-pelvic and cerebellar surgery. Dedifferentiated carcinoma of the endometrium is a poorly recognized neoplasm since they have not been clearly defined the histological features discriminating this neoplasm from high-grade endometrioid adenocarcinoma. Revising existing literature we found 79 described cases of central nervous system secondary involvement and 13 cases where the onset of the disease was characterized by neurological signs and symptoms. We could only find two reported cases of adrenal metastases originating from endometrial neoplasia but in no case of dedifferentiated endometrial carcinoma previously described has been reported the concomitant adrenal-cerebellar involvement.