ELAM-1在鼻咽癌裸鼠移植瘤中的表达及其与转移的关系

目的 建立裸鼠鼻咽癌转移模型并探讨 E-选择素（ELAM-1）与鼻咽癌转移的相关性。方法 将鼻咽癌5-8F细胞悬液注射于裸鼠左后肢爪垫，观察裸鼠状态、成瘤情况并测量裸鼠体重及移植瘤长短径；采用连续病理切片苏木精-伊红染色观察移植瘤及转移情况，将16只人鼻咽癌荷瘤裸鼠分为转移组和非转移组；采用免疫组织化学法检测两组移植瘤组织中ELAM-1的表达。 结果 16只裸鼠均成瘤，成瘤率为100.0%，其中10只裸鼠出现转移瘤，转移率为62.5%。建模前，两组裸鼠体重差异无统计学意义［（13.83±0.56）g vs （14.62±0.30） g，t=1.026，P=0.071］。建模后4~7周，裸鼠瘤体体积呈指数增长，且转移组移植瘤增长速度较非转移组快，非转移组裸鼠瘤体体积小于转移组［（198.91 ± 163.29） mm³ vs （268.76 ±174.31） mm³，t=4.376，P=0.005］。ELAM-1在鼻咽癌裸鼠移植瘤、淋巴结转移灶及远处转移灶中的表达均为阳性，主要表达于细胞膜。转移组移植瘤光密度值高于非转移组（0.4497±0.0705 vs 0.0435±0.0082，t=4.388，P＝0.001）。结论 本研究成功构建稳定性好、转移率高的鼻咽癌裸鼠移植瘤转移模型，且ELAM-1在裸鼠移植瘤中高表达，可促进鼻咽癌裸鼠移植瘤生长和转移。     

A new mouse model for the neurodevelopmental ciliopathy Joubert syndrome

Recent recognition of the key role of primary cilia in orchestrating human development and of the dire consequences of their dysfunction on human health has placed this small organelle in the spotlight. While the causal link between mutations in ciliary genes and central nervous system malformations and dysfunction is well established, the mechanisms by which primary cilia dysfunction acts on development and function of the CNS remain partly unknown. The recent article by Bashford and Subramanian in The Journal of Pathology describes a new mouse model for the neurodevelopmental ciliopathy Joubert syndrome, supporting a role for ciliary-mediated Hedgehog signaling on proliferation, survival, and differentiation of cerebellar granule cell progenitors. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Insights into the regeneration of skin from Acomys,the spiny mouse

Members of the Acomys genus, known as spiny mice, are unique among mammals in being perfectly capable of regenerating large areas of skin that have been removed. During this regenerative process hairs, sebaceous glands, erector pili muscles, adipocytes and the panniculus carnosus all regenerate and the dermis does not scar. We review here the processes that the epidermis and the individual components of the dermis undergo during spiny mouse regeneration as well as the molecules that have been identified as potentially important in regeneration. We then relate this to what has been proposed as playing a role in studies from the laboratory mouse, Mus musculus. Differences in the immune systems of spiny mice and laboratory mice are also highlighted as this is suggested to play a part not only in the perfect wound healing that embryos display but also in regeneration in lower vertebrates.     

白芍对酒精性肝损伤肝阴虚证的保护功效和机制

目的研究白芍对小鼠酒精性肝损伤肝阴虚证的保护功效和机制。方法将ICR小鼠随机分为空白组、模型组、一贯煎组、白芍组,每组10只,除空白组外,用Lieber-DeCarli酒精液体饲料加甲状腺激素灌胃制备小鼠酒精性肝损伤肝阴虚证模型。造模期第1天开始给药,一贯煎组灌胃一贯煎水提液9.07 g/kg,白芍组灌胃白芍水提液4.3 g/kg,空白组和模型组灌胃等量生理盐水。28 d后观察各组小鼠状态,测定体重、体温、心率,测定血清及肝组织转氨酶活性、细胞因子水平、乙醇及脂肪代谢相关酶活性、抗氧化酶活性并取肝脏进行冰冻油红、HE病理切片检查。结果与空白组相比,模型组小鼠体重明显减轻,体温升高,心率加快,且出现毛发无光泽、疲倦易困、烦躁易怒等症状;血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)、环磷酸腺苷(cAMP)水平及肝组织丙二醛(MDA)、细胞色素P450同工酶E1(CYP2E1)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)水平明显升高;血清中环磷酸鸟苷(cGMP)水平及肝组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、乙醇脱氢酶(ADH)、乙醛脱氢酶2(ALDH2)、白细胞介素10(IL-10)、白细胞介素1Ra(IL-1Ra)水平明显降低;肝脏出现脂质沉积及肝细胞坏死情况。与模型组相比,白芍组小鼠血清中ALT、AST、TG、TC、cAMP水平均明显降低(P<0.05),cGMP水平明显升高(P<0.05);肝组织中CYP2E1、TNF-α、IL-1β、IL-6水平明显降低(P<0.05),SOD、CAT、ADH、ALDH2、IL-10、IL-1Ra水平明显升高(P<0.05);肝组织脂质占比显著降低(P<0.05),肝细胞坏死程度改善。结论白芍具有明显的保护酒精性肝损伤肝阴虚证的作用,其机制与调节cAMP/cGMP水平及细胞因子水平、使肝细胞功能与代谢恢复平衡、增强肝组织中乙醇代谢关键酶及抗氧化酶活性、同时抑制脂质过氧化反应、减少脂质沉积有关。     

FGF13 promotes metastasis of triple-negative breast cancer

Triple-negative breast cancer (TNBC) represents 10–20% of all human ductal adenocarcinomas and has a poor prognosis relative to other subtypes, due to the high propensity to develop distant metastases. Hence, new molecular targets for therapeutic intervention are needed for TNBC. We recently conducted a rigorous phenotypic and genomic characterization of four isogenic populations of MDA-MB-231 human triple-negative breast cancer cells that possess a range of intrinsic spontaneous metastatic capacities in vivo, ranging from nonmetastatic (MDA-MB-231_ATCC) to highly metastatic to lung, liver, spleen and spine (MDA-MB-231_HM). Gene expression profiling of primary tumours by RNA-Seq identified the fibroblast growth factor homologous factor, FGF13, as highly upregulated in aggressively metastatic MDA-MB-231_HM tumours. Clinically, higher FGF13 mRNA expression was associated with significantly worse relapse free survival in both luminal A and basal-like human breast cancers but was not associated with other clinical variables and was not upregulated in primary tumours relative to normal mammary gland. Stable FGF13 depletion restricted in vitro colony forming ability in MDA-MB-231_HM TNBC cells but not in oestrogen receptor (ER)-positive MCF-7 or MDA-MB-361 cells. However, despite augmenting MDA-MB-231_HM cell migration and invasion in vitro, FGF13 suppression almost completely blocked the spontaneous metastasis of MDA-MB-231_HM orthotopic xenografts to both lung and liver while having negligible impact on primary tumour growth. Together, these data indicate that FGF13 may represent a therapeutic target for blocking metastatic outgrowth of certain TNBCs. Further evaluation of the roles of individual FGF13 protein isoforms in progression of the different subtypes of breast cancer is warranted.     

Membrane-associated mucins of the ocular surface: New genes,new protein functions and new biological roles in human and mouse

The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.     

2017年泰州市重点职业病危害因素接触人员职业健康风险评估分析

依据《江苏省重点职业病监测与职业健康风险评估工作实施方案》要求，分析泰州市职业健康检查、职业病诊断与鉴定、职业病患者工伤保险待遇落实及职业病报告信息。结果显示，2017年职业健康检查共16759人，检出职业病10例，疑似职业病23例，职业禁忌证22人。职业病患者均已享受工伤保险待遇。泰州市重点职业病危害因素为电焊烟尘、矽尘和噪声，应进一步加强职业健康监护工作。