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.     

杭州市下城区中老年人对社区中医药卫生服务的需求与影响因素

目的:探究中老年人对对社区中医药卫生服务的需求及影响因素,为促进中医药在社区卫生服务中心的开展提供科学依据。方法:于2018~2019年随机抽取杭州市下城区石桥街道社区卫生服务中心诊治的40岁以上中老年人作为研究对象。采用问卷调查的方法对中老年人进行社区中医药卫生服务的需求及影响因素分析。结果:研究共纳入569例中老年人,中老年人对中医药卫生服务总体需求度为75.75%,对中医药技术服务、中医用药、中医药膳指导服务、腧穴保健指导、中医康复、情志疏导需求度分别为84.53%、75.92%、81.72%、88.75%、71.18%、65.38%。对中医药卫生服务有需求和无需求的两组研究对象中,年龄、性别、BMI、婚姻状况、学历、家庭人均年收入、是否患有慢性病的构成情况差异明显(P<0.05),高年龄、男性、高BMI、丧偶或离异或其他、高学历、高收入及患有慢性病的中老年人对中医药卫生服务需求度较高。结论:中老年人对社区中医药卫生服务的需求度较高,尤其是高年龄、女性、高收入及患有慢性病的人群。     

Measuring Psychological Inflexibility of Suicidal Thoughts: The Acceptance and Action Questionnaire for Suicidal Ideation (AAQ-SI)

Cognitive Therapy and Research - Despite interest in psychological inflexibility as a marker of suicide risk, no measure of psychological inflexibility specific to SI exists. The present study...     

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.     

中药治疗哮喘-慢阻肺重叠的Meta分析＊

目的 系统评价中药治疗哮喘-慢阻肺（ACO）的疗效与安全性。方法 全面检索PubMed、Cochrane Library、Web of Science、中国知网、万方、维普、中国医学文献数据库，纳入有关中医药治疗ACO的随机对照试验（RCT），运用Cochrane手册对纳入研究的方法学质量进行评估，采用Review Manager 5.3进行Meta分析。结果 共纳入32项RCT，包括2688例ACO患者，其中试验组1361例，对照组1327例。Meta分析结果显示，中医药可以显著改善ACO患者的中医证候疗效［RR=1.19，95% CI（1.13，1.25），P<0.00001］、CAT评分［MD=-3.62，95% CI（-4.37，-2.87），P<0.00001］、ACT评分［MD=3.42，95% CI（2.23，4.62），P<0.00001］，、中医证候总积分［MD=-3.61，95% CI（-4.83，-2.39），P<0.00001］、FEV₁［MD=0.59，95% CI（0.08，1.10），P=0.02］、FEV₁%［MD=8.61，95% CI（5.20，12.1），P<0.00001］、FEV₁/FVC［MD=6.52，95% CI（4.24，8.80），P<0.00001］、6 min步行实验［MD=41.18，95% CI（22.15，60.21），P<0.0001］、急性发作次数［MD=-2.46，95% CI（-3.62，-1.13），P<0.0001］。所有研究均未报道严重不良反应。结论 中药治疗ACO，可以显著提高临床疗效，改善患者的肺功能且具有较好安全性，但是需要更高质量、多样本、多中心的随机对照试验进一步确认。     

基于标准化患者法评价四川农村基层医生两种慢性病诊断准确性及其影响因素

目的 运用标准化患者法评估四川农村地区基层医生不稳定型心绞痛和2型糖尿病两种慢性病诊断准确性现状,探讨基层医生两种慢性病诊断准确性的主要影响因素,为提升基层医生两种慢性病诊断准确性提供科学依据。方法 采用多阶段随机整群抽样方法,抽取四川省自贡市5个区/县50个乡镇100个村为研究现场,以调查当日在岗的全科及内科医生作为研究对象。共进行两轮数据采集,第1轮采集样本乡镇卫生院和村卫生室医生的基本信息;第1轮调查完成1个月后,运用标准化患者法开展第2轮调查,收集农村基层医生对不稳定型心绞痛和2型糖尿病诊断结果信息。运用Logistic回归分析农村基层医生不稳定型心绞痛和2型糖尿病诊断准确性的影响因素。结果 共纳入172名农村基层医生,完成186次标准化患者访问,正确诊断率为48.39%。其中不稳定型心绞痛的正确诊断率为18.68%(17/91),2型糖尿病的正确诊断率为76.84%(73/95)。Logistic回归分析显示,具有执业医师资质的农村基层医生更有可能做出正确诊断(OR=4.857,95%CI=1.076~21.933,P=0.040)。农村基层医生在诊断过程中涉及的必要问诊和检查条目越多,做出正确诊断的概率越高(OR=1.627,95%CI=1.065~2.485,P=0.024)。与不稳定型心绞痛相比,农村基层医生对2型糖尿病做出正确诊断的可能性更高(OR=6.306,95%CI=3.611~11.013,P<0.001)。结论 四川农村基层医生不稳定型心绞痛和2型糖尿病诊断准确性整体较差,建议以基层医生慢性病诊断过程质量改善为突破口,提升基层医生执业水平,进而提高慢性病诊断准确性。