Analysis of long noncoding RNA-associated competing endogenous RNA network in glucagon-like peptide-1 receptor agonist-mediated protection in β cells

BACKGROUND Long noncoding RNAs(lncRNAs) and mRNAs are widely involved in various physiological and pathological processes. The use of glucagon-like peptide-1 receptor agonists(GLP-1 RAs) is a novel therapeutic strategy that could promote insulin secretion and decrease the rate of β-cell apoptosis in type 2 diabetes mellitus(T2 DM) patients. However, the specific lncRNAs and mRNAs and their functions in these processes have not been fully identified and elucidated.AIM To identify the lncRNAs and mRNAs that are involved in the protective effect of GLP-1 RA in β cells, and their roles.METHODS Rat gene microarray was used to screen differentially expressed(DE) lncRNAs and mRNAs in β cells treated with geniposide, a GLP-1 RA. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed to assess the underlying functions of DE mRNAs. Hub mRNAs were filtered using the STRING database and the Cytoscape plugin, CytoHubba. In order to reveal the regulatory relationship between lncRNAs and hub mRNAs, their co-expression network was constructed based on the Pearson coefficient of DE lncRNAs and mRNAs, and competing endogenous RNA(ceRNA) mechanism was explored through miRanda and TargetScan databases.RESULTS We identified 308 DE lncRNAs and 128 DE mRNAs with a fold change filter of ≥ 1.5 and P value 0.05. GO and KEGG pathway enrichment analyses indicated that the most enriched terms were G-protein coupled receptor signaling pathway, inflammatory response, calcium signaling pathway, positive regulation of cell proliferation, and ERK1 and ERK2 cascade. Pomc, Htr2 a, and Agtr1 a were screened as hub mRNAs using the STRING database and the Cytoscape plugin, CytoHubba. This result was further verified using SwissTargetPrediction tool. Through the co-expression network and competing endogenous(ceRNA) mechanism, we identified seven lncRNAs(NONRATT027738, NONRATT027888, NONRATT030038, etc.) co-expressed with the three hub mRNAs(Pomc, Htr2 a, and Agtr1 a) based on the Pearson coefficient of the expression levels. These lncRNAs regulated hub mRNA functions by competing with six miRNAs(rno-miR-5132-3 p, rno-miR-344 g, rno-miR-3075, etc.) via the ceRNA mechanism. Further analysis indicated that lncRNA NONRATT027738 interacts with all the three hub mRNAs, suggesting that it is at a core position within the ceRNA network.CONCLUSION We have identified key lncRNAs and mRNAs, and highlighted here how they interact through the ceRNA mechanism to mediate the protective effect of GLP-1 RA in β cells.     

分离手术治疗老年脊柱骨转移瘤的临床研究

目的总结分离手术治疗老年脊柱骨转移瘤的临床特征。 方法回顾性分析解放军第九六〇医院2014年1月至2018年12月间所有接受分离手术的老年脊柱骨转移瘤患者的临床资料,按性别、年龄、肿瘤类型、累及部位、脊柱稳定性评分（SINS）、硬膜外脊髓压迫分级（ESCC分级）、神经功能评价（Frankel分级）、肿瘤处理方式、内固定方式、手术时间、出血量、术前合并内科疾病、围手术期并发症分别进行统计,分析其临床特征。 结果33例老年脊柱骨转移瘤患者纳入本研究,其中男14例（42.4%）,女19例（57.6%）,男女比例为0.74∶1。发病年龄为60～75岁,平均年龄65.2岁,Frankel神经功能分级包括：A级2例,B级1例,C级2例,D级19例,E级9例。SINS平均得分为11.6分,最低分8分,最高分16分。ESCC分级,1b2例,1c2例,2级13例,3级16例。术前合并内科疾病患者17例,无内科疾病患者16例,7例患者在椎体肿瘤刮除后行直视下骨水泥填塞,另外26例患者均单纯行肿瘤刮除。所有患者均行椎弓根螺钉固定,平均使用螺钉数为7.2（4～9）个。中位出血量600（150～2500）ml。中位手术时间168（94～277）min。3例患者出现了围手术期并发症。29例（87.9%）患者获得术后症状改善。 结论存在硬膜外压迫的老年脊柱骨转移瘤患者,在做好围手术期准备后,采用分离手术能够在控制创伤的同时获得良好的症状改善。     

Stochastic Multiscale Heat Transfer Analysis of Heterogeneous Materials with Multiple Random Configurations

This study presents a new stochastic multiscale analysis approach to analyze the heat transfer performance of heterogeneous materials with random structures at different length scales. The heterogeneities of the materials are taken into account by periodic layouts of unit cells, consisting of randomly distributed inclusion dispersions and homogeneous matrix on the microscale and mesoscale. Based on the reiterated homogenization, a novel unified micro-meso-macro stochastic multiscale formulation is established and the scale gap is correlated by means of two-scale asymptotic expansions. Also, the stochastic multiscale formulae for computing the effective thermal property and temperature field are derived successively. Then, the stochastic prediction algorithm coupled with the finite element method is brought forward in details. The accuracy of the implemented stochastic multiscale analysis is verified by comparing the results against the experimental data for three scales heterogeneous materials with several different material combinations. The comparison demonstrates the usability of the proposed stochastic multiscale method for the determination of the thermal behaviors. This study offers a unified multiscale framework that enables heat transfer behavior analysis of heterogeneous materials with multiple random configurations.     

Expression and clinical implications of leucine-rich repeat containing 15 (LRRC15) in osteosarcoma

Leucine-rich repeat containing 15 (LRRC15) is a member of the leucine-rich repeat superfamily that is overexpressed in various cancers and associated with higher tumor grade and aggression. Despite its known tumorigenicity, its roles within osteosarcoma are unknown, prompting us to evaluate its expression and clinical significance within this rare yet aggressive cancer. Western blots showed differential expression of LRRC15 in the osteosarcoma cell lines MNNG/HOS, KHOS, 143B, MG63, Saos-2, and U2OS. We additionally validated this positive expression, as well as sublocalization to the cell membrane, with immunofluorescence. A tissue microarray constructed from 69 osteosarcoma patient tissues was immunohistochemically stained for LRRC15 expression, stratified, and used for clinicopathological analysis. Publicly available databases on LRRC15 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2) were also analyzed. We found 63 of the 69 (91.3%) patient tissues exhibited some degree of LRRC15 immunostaining, including no staining (6 of 69, 8.7%), 1+ staining (12 of 69, 17.4%), 2+ staining (25 of 69, 36.2%), and 3+ staining (26 of 69, 37.7%). The patients with osteosarcomas having elevated LRRC15 expression demonstrated comparatively increased metastasis, chemoresistance, and shorter 5-year survival rates. Our analysis of the TARGET-OS and GENT2 databases also showed increased LRRC15 gene expression in osteosarcoma. Taken together, our study supports LRRC15 as a prognostic biomarker and emerging therapeutic target in osteosarcoma.     

Optimal linear quadratic Gaussian control for discrete time-varying system with simultaneous input delay and state/control-dependent noises

This article focuses on the problem of linear quadratic Gaussian (LQG) control for discrete time-varying system with input delay and state/control-dependent noises. When the state variables can be exactly observed, first, we obtain the maximum principle by applying the method of variation. Second, a nonhomogeneous relationship between the state and the costate is developed in virtue of the obtained maximum principle and the mathematical induction. It is noted that the nonhomogeneous relationship is the solution to the forward and backward stochastic difference equations (FBSDEs). Finally, based on the solution to the FBSDEs, a necessary and sufficient condition for the optimal LQG control is derived in terms of coupled Riccati equations. Moreover, the analytical expression of the optimal controller is presented. The derived results are applied in networked control systems with packet dropout. Numerical examples are shown to illustrate the effectiveness of the proposed algorithm.