健脾消癌方通过PI3K/Akt信号通路抑制结肠癌血管生成的研究＊

目的 观察结肠癌HCT116细胞健脾消癌方的条件培养液对HUVEC细胞管腔形成的影响，从PI3K/Akt生物轴调控角度探讨其作用机制。方法 培养HCT116细胞，细胞设3组：对照组，健脾消癌方组（加入15%健脾消癌方含药血清）及人参皂苷Rg3组；制备HCT116细胞健脾消癌方条件培养液（分组及制备方法见实验方法），用条件培养液干预HUVEC（脐静脉内皮细胞，Human Umbilical Vein Endothelial Cells），Matrigel基质胶法检测HCT116细胞健脾消癌方条件培养液对HUVEC小管形成的影响。随后采用蛋白免疫印迹法（Western blot）检测各组HCT116细胞磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、p-Akt、VEGF（血管内皮生长因子，Vascular endothelial growth factor）蛋白表达。最后在结肠癌HCT116荷瘤小鼠中验证健脾消癌方对肿瘤生长速度的影响，并经瘤组织VEGF蛋白表达、CD31免疫组化染色检测肿瘤内血管生成情况。结果 模型组HUVEC细胞管腔形成较空白血清组显著增加（P<0.05）；健脾消癌方组及人参皂苷Rg3组较模型组HUVEC细胞管腔形成显著减少（P<0.01）。p-Akt和VEGF蛋白表达水平模型组高于空白血清组（P<0.05），健脾消癌方组及人参皂苷Rg3组显著低于模型组（P<0.01）；PI3K、Akt蛋白表达量组间差异无统计学意义。与对照组比较，模型组荷瘤小鼠肿瘤体积显著性增大，瘤组织内VEGF表达、CD31阳性面积显著性增加，差异有统计学意义（P<0.05）；与模型组比较，健脾消癌方组及人参皂苷Rg3组荷瘤小鼠肿瘤体积显著减小，瘤组织内VEGF表达、CD31阳性面积降低，差异有统计学意义（P<0.05）。结论 健脾消癌方可抑制肿瘤的血管生成和生长，其作用机制可能与PI3K/Akt生物轴调控VEGF表达有关。     

丹参酮生物合成相关SmERF108转录因子的鉴定及其靶基因分析＊

目的 鉴定与丹参酮合成相关转录因子AP2/ERF家族中SmERF108转录因子，并分析转录因子SmERF108的靶基因。方法 利用生物信息学在线分析平台如NCBI、PFAM等分析SmERF108的序列特征；MEGA-X软件用于构建SmERF108与不同功能转录因子的系统进化树；拟南芥原生质体转化法鉴定SmERF108蛋白的亚细胞定位；通过实时荧光定量PCR（Real-time qPCR）对SmERF108基因在丹参不同器官和组织差异表达进行检测；利用酵母体系对SmERF108的转录激活活性进行探究并用酵母单杂技术确定其靶基因。结果 SmERF108具有典型的AP2/ERF保守结构域，属于ERF-B3亚组，系统进化树和保守基序分析显示SmERF108与丹参中SmERF128、青蒿中AaERF2亲缘关系较近且保守基序分布一致；亚细胞定位显示SmERF108蛋白定位于细胞核；SmERF108基因在周皮中表达最高，且呈现周皮（R1）>韧皮部（R2）>木质部（R3）的规律；酵母自激活验证SmERF108具有转录激活活性，同时酵母单杂交确认其能与关键酶基因SmCPS1启动子结合。结论 鉴定到丹参中一个新转录因子SmERF108，生物信息学分析及差异表达分析预测与丹参酮合成相关，分子互作初步证实靶基因为SmCPS1二萜环化酶。     

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.     

Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Moral Distress and Burnout in NICU Nurses

The objectives of this study were to factor analyze the Moral Distress Scale–Revised (MDS-R) in NICU nurses and to evaluate the relationships among dimensions of the MDS-R and the demoralization, exhaustion, and loss of motive dimensions of the Burnout Measure (BM). A total of 142 NICU nurses completed modified pen-and-paper versions of the MDS-R and BM. Exploratory and confirmatory factor analyses showed that the MDS-R-14 was a relatively good fit for the data. The compromised care dimension predicted BM demoralization (β = 0.24) and exhaustion (β = 0.22), the futile care dimension predicted BM exhaustion (β = 0.18), and the untruthful care dimension predicted BM demoralization (β = .25). Strategies to mitigate moral distress and resulting burnout in NICU nurses should address futile care, compromised care, and untruthful care.     

老年人生命晚期获知疾病信息意向及影响因素CSCD

目的了解老年人生命晚期获知疾病相关信息意向及影响因素。方法2016年10月至2017年6月,采用生命晚期疾病信息意向问卷,利用方便抽样法对福州市中心城区7所养老机构及15个社区的414例年龄≥60岁的老年人进行横断面调查,采用单因素分析、多元线性回归与有序多分类logistic回归分析老年人对疾病相关信息的需求水平、获知程度意向及其影响因素。结果414例老年人疾病相关信息需求得分为(17.1±4.9)分;48.8%(202/414)希望详尽知晓,30.7%(127/414)希望选择性了解,20.5%(85/414)不想知道任何信息;多元线性回归分析显示,年龄、文化程度、是否接受/见过其他生命维持治疗(LSTs)是影响老年人疾病相关信息需求水平的主要因素(标准化回归系数分别为-0.141、0.116、0.115,均P<0.05);有序多分类logistic分析显示,年龄(以60~69岁为参照,70~79岁:OR=0.544,95%CI:0.310~0.957;80~89岁:OR=0.526,95%CI:0.289~0.956)、文化程度(以小学及以下为参照,大专及以上:OR=2.166,95%CI:1.093~4.290)、主要生活费来源(以其他补贴为参照,家人支持:OR=7.303,95%CI:1.157~46.108;退休金:OR=9.288,95%CI:1.502~57.415;公积金/储蓄:OR=15.676,95%CI:2.122~115.793)、是否接受/见过其他LSTs(以是为参照,OR=1.985,95%CI:1.150~3.425)是影响老年人疾病相关信息获知程度意向的主要因素。结论老年人生命晚期获知疾病相关信息的意向程度较高,年龄、文化程度、主要生活费来源、是否接受/见过其他生命维持治疗等是其主要影响因素。     

Management of sagittal craniosynostosis: morphological comparison of eight surgical techniques

The aim of this study was to carry out a retrospective multicentre study comparing the morphological outcome of 8 techniques used for the management of sagittal synostosis versus a large cohort of control patients. Computed tomographic (CT) images were obtained from children CT-scanned for non-craniosynostosis related events (n = 241) and SS patients at preoperative and postoperative follow-up stages (n = 101). No significant difference in morphological outcomes was observed between the techniques considered in this study. However, the majority of techniques showed a tendency for relapse. Further, the more invasive procedures at older ages seem to lead to larger intracranial volume compared to less invasive techniques at younger ages. This study can be a first step towards future multicentre studies, comparing surgical results and offering a possibility for objective benchmarking of outcomes between methods and centres.