Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Use of different combination diphtheria-tetanus-acellular pertussis vaccines does not increase risk of 30-day infant mortality. A population-based linkage cohort study using administrative data from the Australian Childhood Immunisation Register and the National Death Index.

Objective

To determine whether differences in combination DTaP vaccine types at 2, 4 and 6?months of age were associated with mortality (all-cause or non-specific), within 30?days of vaccination.

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

工作坊模式在护生压疮护理带教中的应用效果分析

目的探讨工作坊模式在护生压疮护理带教中的应用效果,为临床护理带教提供参考。方法选取2018年7月—2019年6月在医院实习的120名护生作为研究对象,随机分为对照组和观察组,各60名护生。对照组采用传统带教法进行压疮培训,观察组采用工作坊教学模式进行培训。培训结束后比较两组护生压疮知识的掌握程度即理论考核、技能操作成绩,教学效果满意度。结果观察组护生对压疮知识的掌握程度即理论考核成绩、技能操作考核成绩远远高于对照组,两组差异具有统计学意义(P<0.05)。95%的观察组护生对工作坊教学模式的效果表示满意,认为工作坊教学模式能够提高学习的兴趣、主动性和临床实践能力,对临床工作有很大帮助。结论工作坊教学模式应用于压疮护理的临床带教,能让护生亲身体验压疮护理的过程,并参与其中,将理论与实践相结合,更好地活跃课堂气氛,启发护生思考,提高护生对压疮理论和技能的掌握,为临床实际工作中压疮护理质量的提高奠定基础。