The effect of automated landmark identification on morphometric analyses

Morphometric analysis of anatomical landmarks allows researchers to identify specific morphological differences between natural populations or experimental groups, but manually identifying landmarks is time‐consuming. We compare manually and automatically generated adult mouse skull landmarks and subsequent morphometric analyses to elucidate how switching from manual to automated landmarking will impact morphometric analysis results for large mouse (Mus musculus) samples (n = 1205) that represent a wide range of ‘normal’ phenotypic variation (62 genotypes). Other studies have suggested that the use of automated landmarking methods is feasible, but this study is the first to compare the utility of current automated approaches to manual landmarking for a large dataset that allows the quantification of intra‐ and inter‐strain variation. With this unique sample, we investigated how switching to a non‐linear image registration‐based automated landmarking method impacts estimated differences in genotype mean shape and shape variance‐covariance structure. In addition, we tested whether an initial registration of specimen images to genotype‐specific averages improves automatic landmark identification accuracy. Our results indicated that automated landmark placement was significantly different than manual landmark placement but that estimated skull shape covariation was correlated across methods. The addition of a preliminary genotype‐specific registration step as part of a two‐level procedure did not substantially improve on the accuracy of one‐level automatic landmark placement. The landmarks with the lowest automatic landmark accuracy are found in locations with poor image registration alignment. The most serious outliers within morphometric analysis of automated landmarks displayed instances of stochastic image registration error that are likely representative of errors common when applying image registration methods to micro‐computed tomography datasets that were initially collected with manual landmarking in mind. Additional efforts during specimen preparation and image acquisition can help reduce the number of registration errors and improve registration results. A reduction in skull shape variance estimates were noted for automated landmarking methods compared with manual landmarking. This partially reflects an underestimation of more extreme genotype shapes and loss of biological signal, but largely represents the fact that automated methods do not suffer from intra‐observer landmarking error. For appropriate samples and research questions, our image registration‐based automated landmarking method can eliminate the time required for manual landmarking and have a similar power to identify shape differences between inbred mouse genotypes.     

微观社会资本对农转非居民主客观健康认知一致性的影响研究

目的探讨微观社会资本对农转非居民自评健康与客观健康认知一致性的影响。方法两层logistic回归模型分析微观社会资本和人口学因素对健康认知一致性的影响。结果自评健康和客观健康的一致率为63.89%,个体社会资本和年龄对主客观健康一致性产生影响。结论使用自评健康作为健康指标时,应考虑个体社会资本的影响,提高自评健康的预测准确性。     

微血管定量和血管内皮生长因子表达在非小细胞肺癌中的意义

目的 :研究非小细胞肺癌 (NSCL C)的预后与血管内皮生长因子 (VEGF)表达及肿瘤微血管定量间的关系。方法 :对81例行手术治疗的 NSCL C患者运用免疫组织化学的方法检测 VEGF的表达及微血管定量 ,检测 VEGF使用抗 VEGF单克隆抗体 ;检测微血管定量用抗 CD34 单克隆抗体。结果 :在术后半年出现转移的 32例 NSCL C中微血管定量为 (32± 15 .4)根/ mm3比术后未出现转移的 49例患者 (12± 8.6 )根 / mm3明显增高 ,经统计学处理 (P=0 .0 0 1)。在术后半年出现转移的 32例中有 2 4例 VEGF表达阳性 (75 % ) ,在术后未出现转移的 49例中有 2 5例 VEGF表达阳性 (5 1% ) ,经统计学处理 (P=0 .0 31)。结论 :NSCL C的转移形式为血管形成依赖性 ,VEGF是 NSCL C的血管形成的一个重要因素。VEGF的表达是检测NSCL C预后的一个有意义的指标     

沙丁胺醇加布地奈德微量泵吸入治疗小儿毛细支气管炎的疗效观察

目的 :评价沙丁胺醇 (喘乐宁 )加布地奈德 (普米克令舒 )微量泵吸入治疗小儿毛细支气管炎的疗效。方法 :随机将 72例患儿分为两组。对照组在综合疗法基础上单用喘乐宁微量泵吸入治疗 ,治疗组加用喘乐宁及普米克令舒微量泵吸入治疗。观察两组疗效及气急缓解和喘鸣音消失时间。结果 :显效率治疗组为 94.4% ,对照组为 72 .2 % ,两者相比有显著性差异 ( χ2 =4.9,P <0 .0 5 ) ;治疗组气急缓解、喘鸣音消失时间均较对照组短。结论 :喘乐宁加普米克令舒微量泵吸入治疗小儿毛细支气管炎较单用喘乐宁有较好疗效。     

CircCDR1as Suppresses Bone Microvascular Endothelial Cell Activity and Angiogenesis Through Targeting miR‐135b/ FIH‐1 Axis

ObjectiveThe current study investigated the role of CircCDR1as on angiogenesis of bone microvascular endothelial cells (BMECs) isolated from non‐traumatic ONFH.MethodsForty corticosteroid‐induced ONFH patients received THA were enrolled in our study. Expressions of CircCDR1as, miR‐135b, and FIH‐1 were detected by qRT‐PCR in affected necrosis tissue and non‐affected normal tissue. Bone microvascular endothelial cells (BMEC) were isolated from six patients and treated with 0.1 mg/mL hydrocortisone to establish a GC‐damaged model of BMECs. Circ CDR1as plasmid and miR‐135b mimic were transfected into BMECs. BMEC proliferation was assessed using MTT assays. The migration ability of cells was detected by scratch‐wound assays. Matrigel assay was performed to detect angiogenesis in vitro. Western blot assay was used to detect HIF‐1α, VEGF, and FIH‐1 expressions. FISH, RNA pull down, RIP, and luciferase assay were carried out to determine the interaction of CircCDR1as, miR‐135b, and FIH‐1.ResultsCircCDR1as was upregulated(2.02 ± 0.30 vs. 1.00 ± 0.10,P < 0.001) whereas miR‐135b was downregulated (0.55 ± 0.12 vs. 1.00 ± 0.10,P < 0.001) in affected tissues than in non‐affected tissues. Expression of CircCDR1as and FIH‐1 were negatively associated with miR‐135b in affected tissues (CircCDR1as with miR‐135b: r = −0.506, P < 0.001; FIH‐1 with miR‐135b r = −0.510, P < 0.001). Total blood tubule density was increased when CircCDR1as was silenced compared with NC (P < 0.01 vs. NC). The number of migrated BMECs were significantly increased in CircCDR1as silencing group compared with NC group (P < 0.05 vs. NC). In addition, CircCDR1as plasmids transfection increased the protein expressions of FIH‐1 (P < 0.05 vs. NC) and reduced the HIF‐1α as well as VEGF expression compared with NC group (P < 0.05 vs. NC). FISH, RNA pull down, RIP, and luciferase assay identified that FIH‐1 was a target of miR‐135b and could be modulated by CircCDR1as.ConclusionCircCDR1as decreases angiogenesis and proliferation of BMECs by sponging miR‐135b and upregulate FIH‐1.     

Comprehensive analysis of the lncRNA-miRNA-mRNA regulatory network for bladder cancer

BackgroundLong non-coding RNAs (lncRNAs) are essential regulators for various human cancers. However, these lncRNAs need to be further classified for cancer. In the present study, we identified novel competing endogenous RNA (ceRNA) network for bladder cancer (BC) and explored the gene functions of the ceRNA regulatory network.MethodsDifferential gene expression analysis were performed on The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) datasets to identify differentially expressed messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs). Based on the competing endogenous RNA (ceRNA) hypothesis, a lncRNA-miRNA-mRNA network was constructed using the StarBase database and visualization by Cytoscape software. Functional enrichment analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed via R package ClusterProfiler. The protein-protein interaction network was constructed by STRING database and visualization by Cytoscape. Finally, we used CIBERSORT and the TIMER database to analyze the immune infiltrations for BC.ResultsThe regulatory network was constructed via TCGA BLCA cohort. The differential expressions of lncRNA, miRNA, and mRNA were 186, 200, and 2,661, respectively. There were 106 lncRNA, miRNA, and mRNA included in the ceRNA network. In this network, Calcium Voltage-gated Channel Auxiliary Subunit Alpha2delta1 (CACNA2D1, P<0.001), domain containing engulfment adaptor1 (GULP1, P=0.001), latent transforming growth factor beta binding protein 1 (LTBP1, P=0.006), myosin light chain kinase (MYLK, P=0.001), serpin family E member 2 (SERPINE2, P=0.002), spectrin beta non-erythrocytic 2 (SPTBN2, P=0.047), and hsa-miR-590-3p (P<0.001) significantly affected the prognosis of BC patients. Functional enrichment analyses showed that the biological functions included negative regulation of protein phosphorylation, cell morphogenesis, and sensory organ morphogenesis. Important cancer pathways of KEGG included parathyroid hormone synthesis secretion action, the notch signaling pathway, MAPK signaling pathway, the Rap1 signaling pathway, signaling pathways regulating the pluripotency of stem cells, and the transforming growth factor-β signaling pathway. Our findings demonstrated that the ceRNA network has important biological functions and a significant influence on the prognosis of BC.ConclusionsThe lncRNA-miRNA-mRNA network constructed in the present study could provide useful insight into the underlying tumorigenesis of BC, and can determine new molecular biomarkers for the diagnosis and therapeutical treatment of BC.     

Production of 5–15 µm Diameter Alginate-Polylysine Microcapsules by an Air-Atomization Technique

A novel method of preparing small-sized microcapsules using a Turbotak air-atomizer is reported. Alginate-polylysine microcapsules containing Bacillus Calmette Guérin vaccine have been prepared by an adaptation of the method of Lim (1) which allows the manufacture of small-sized microcapsules. A Turbotak is used to spray sodium alginate solution into calcium chloride solution to form temporary calcium alginate microgel capsules. These temporary microgel droplets are subsequently cross-linked with polylysine to form permanent membranes. Microcapules in the size range of 5–15 µm have been produced which can be compared to an average diameter of 300 µm obtained by the method reported by Lim. The microcapsule size is dependent on the conditions of operation of the Turbotak and the concentration of the sodium alginate solution. Particles within the size range 5–15 µm can be reproducibly manufactured using the conditions of operation reported here. Other size ranges below the minimum of 300 µm reported by Lim are also feasible using this technique.     

微细药物表面包覆技术在制剂中的应用

新型药物开发制备过程中，需要对药物颗粒进行粒子设计，通过多层微胶囊化而得到复合包覆药物颗粒。药物包覆、微胶囊制备方法很多，可分为化学法、物理化学法、物理法。本文着重介绍了制备复合多层包覆药物颗粒的几种物理机械方法：复合杂化系统，高速椭圆转子混合法、喷流床包覆法。简要分析了该技术用于中药现代化加工的可能性。     

自体微小颗粒骨复合碱性成纤维细胞生长因子修复节段性骨缺损的实验研究

目的 探讨自体微小颗粒骨复合碱性成纤维细胞生长因子(basic fibroblast growth factor，bFGF)治疗骨缺损的效果，为其临床应用提供实验依据。方法 将36只新西兰白兔双侧桡骨中上段制成骨缺损模型，分别植入自体微小颗粒骨、bFGF和自体微小颗粒骨与bFGF的复合物，同时设空白对照组，分别手术后第2、4、8周进行大体观察，X检查及组织学检查。术后第8周进行骨密度测定，比较修复骨缺损的疗效。结果 经大体观察、组织学及X线检查发现，术后第8周自体微小颗粒骨复合bFGF能更有效地修复节段性骨缺损，对照组无骨愈合迹象。术后第8周骨密度测定证明自体微小颗粒骨复合bFGF组骨密度值明显高于对照组。结论 自体微小颗粒骨复合bFGF组成骨速度快，成骨量多，修复骨缺损的能力明显强于自体微小颗粒骨组及单纯bFGF组。     

葛根素降低2型糖尿病微量白蛋白初步观察

葛根素是从豆科多年生落叶藤木植物的干燥根中提取的单体———异黄酮化合物。本研究以葛根素注射液治疗２型糖尿病早期肾脏病变，现报道如下。１临床资料依１９９７年ADA标准确诊２型糖尿病患者７０人，男４１例，女２９例；年龄４４～７２岁；病程６～１８a。其２４h尿微量白蛋白（UAE）均波动于３０～３００mg/２４h，所有患者均无急慢性肾炎、高血压病、尿路结石、感染、阴道炎、发热及近期内应用肾毒性药物史。并随机分为治疗组３２例；对照组３８例。２方法待空腹血糖控制于≤７．０mmol/L，治疗组患者除按原剂量使用降糖药外，采…