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。     

Impact of repaired aortic coarctation in left ventricular myocardial work

AimsMyocardial strain analysis enables more precise assessment of cardiac performance but is relatively load dependent. New tools have been developed with afterload adjustment. Our objective was to assess myocardial work (MW) in patients with repaired aortic coarctation (rACo).MethodsProspective study of consecutive patients with rACo who underwent a routine transthoracic echocardiogram in 2018 and 2019 at our center. Patients with significant aortic valve disease, pacemaker, or other congenital heart diseases (except for mild bicuspid aortic valve disease) were excluded. Global longitudinal strain with two dimensional speckle tracking analysis and MW were obtained (GWI:Global Work Index; GCW: Global Constructive Work; GWW: Global Wasted Work; GWE: Global Work Efficiency). Blood pressure was measured in the patient's right arm.ResultsWe included 42 patients in the analysis, mean age of 37±10 years, 38% males. In this group, 52% had hypertension and 64% had a concomitant bicuspid aortic valve. In comparison to previously published reference values, patients with rACo had significantly lower GWI (1807 vs. 1896 mmHg%) and GCW (2173 vs. 2232 mmHg%) (p<0.001), particularly in males. Systolic blood pressure is an independent predictor for GWI (β=0.432) and for GCW (β=0.534) and GLS an independent predictor of all MW parameters (β>0.594). Neither age nor gender were independent predictors.ConclusionsIn patients with rACo, there are some signs of left ventricular dysfunction with a reduction in GCW and GWI and with preserved GWE, despite normal ejection fraction and strain.     

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.     

Restless legs syndrome in children and adolescents with attention-deficit/hyperactivity disorder: prevalence,mimic conditions,risk factors,and association with functional impairment

ObjectivesTo determine the prevalence of restless legs syndrome (RLS) and RLS-mimic conditions, the risk factors for RLS, and whether RLS contributes to functional impairment in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).MethodsADHD children and adolescents were prospectively studied at the outpatient psychiatric clinic. A trained registered nurse used the 2012 Revised International Restless Legs Syndrome Study Group diagnostic criteria to diagnose RLS. Sociodemographic data and medical records were reviewed. Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) Thai version was used to identify association between RLS and 6 domains of function [family, school (learning), school (behavior), life skills, child self-concept, social activities, and risky activities].ResultsA total of 217 patients were included. Of those, 23 (11%) patients met the criteria for RLS, and 49 (23%) had RLS-mimic conditions. Those conditions included myalgia (30/49), habitual foot tapping (23/49), positional discomfort (20/49), leg ulcer/bruise (1/49), and arthralgia/arthritis (1/49). Binary logistic regression revealed first-degree relative having RLS symptom to be significantly associated with RLS in study patients (OR: 5.06, p < 0.01). Multivariate linear regression showed RLS to be independently associated with school (behavior) (Β = 1.18, p = 0.05) and life skills (Β = 2.36, p = 0.05) impairment.ConclusionsRLS was found to be common in ADHD children and adolescents. RLS-mimic conditions were found in two-thirds of patients who previously met 4 essential RLS criteria. First-degree relative with RLS symptom was associated with RLS, and RLS was associated with functional impairment in the life skills and school (behavior) domains.