摘要：Objective: As one of the most popular designs used in genetic research, family-based design has been well recognized for its advantages, such as robustness against population stratification and admixture. With vast amounts of genetic data collected from family-based studies, there is a great interest in studying the role of genetic markers from the aspect of risk prediction. This study aims to develop a new statistical approach for family-based risk prediction analysis with an improved prediction accuracy compared with existing methods based on family history. Methods: In this study, we propose an ensemble-based likelihood ratio(ELR) approach, Fam-ELR, for family-based genomic risk prediction. Fam-ELR incorporates a clustered receiver operating characteristic(ROC) curve method to consider correlations among family samples, and uses a computationally efficient tree-assembling procedure for variable selection and model building. Results: Through simulations, Fam-ELR shows its robustness in various underlying disease models and pedigree structures, and attains better performance than two existing family-based risk prediction methods. In a real-data application to a family-based genome-wide dataset of conduct disorder, Fam-ELR demonstrates its ability to integrate potential risk predictors and interactions into the model for improved accuracy, especially on a genome-wide level. Conclusions: By comparing existing approaches, such as genetic risk-score approach, Fam-ELR has the capacity of incorporating genetic variants with small or moderate marginal effects and their interactions into an improved risk prediction model. Therefore, it is a robust and useful approach for high-dimensional family-based risk prediction, especially on complex disease with unknown or less known disease etiology.

摘要：Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the *** elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains *** this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature ***,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic ***,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the ***,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain *** conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.

摘要：Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are two of the leading causes of chronic intestinal conditions in the world. This issue of World Journal of Gastroenterology (WJG ) presents a series of papers from world experts who discuss the current knowledge and opinions on these important conditions. Although great strides have been made in the diagnosis, treatment and pathology of IBS and IBD; much has yet to be explained. The etiologies and risk factors of these multifactorial conditions remain elusive. Specific diagnostic biomarkers need to be developed and safer treatments developed. The burden of IBS and IBD on the healthcare system is felt with repeated medical care visits and high costs. IBS and IBD patients can account for 30%-50% of office visits at gastroenterology services/clinics. Over one million people have IBD in the United States, with 30 000 new cases being diagnosed every year. One-quarter million people in the UK are afflicted with IBD. The cost of medical care in the United States for IBD is estimated to be $1.8 billion/year.

摘要：The female reproductive system consists of the ovaries,the female gonads,and the reproductive tract organs of the fallopian tubes,uterus,cervix,and *** functions to provide hormonal support and anatomical structure for the production of new offspring.A number of endogenous and exogenous factors can impact female reproductive health and fertility,including genetic vulnerability,medications,environmental exposures,age,nutrition,and *** date,due to the ethical concerns of using human subjects in biomedical research,the majority of studies use in vivo animal models and 2D cell/tissue culture models to study female ***,the complexity and species difference of the female reproductive system in humans make it difficult to compare to those of ***,the monolayered cells cultured on flat plastics or glass lose their 3D architecture as well as the physical and/or biochemical contacts with other cells in ***,all reproductive organs do not work alone but interconnect with each other and also with non-reproductive organs to support female reproductive,endocrine,and systemic *** facts suggest that there is an urgent and unmet need to develop representative,effective,and efficient in vitro models for studying human female *** prodigious advancements of bioengineering(e.g.,biomaterials,3D printing,and organ-on-a-chip)allow us to study female reproduction in an entirely new ***,we review recent advances that use bioengineering methods to study female reproduction,including the bioengineering models of the ovary,fallopian tube,uterus,embryo implantation,placenta,and reproductive disease.

摘要：Thirty years ago, the analysis of longwall pillar stability(ALPS) inaugurated a new era in coal pillar *** was the first empirical pillar design technique to consider the abutment loads that arise from full extraction, and the first to be calibrated using an extensive database of longwall mining case *** was followed by the analysis of retreat mining stability(ARMPS) and the analysis of multiple seam stability(AMSS). These methods incorporated other innovations, including the coal mine roof rating(CMRR), the Mark-Bieniawski pillar strength formula, and the pressure arch loading model. They also built upon ever larger case history databases and employed more sophisticated statistical ***, these empirical methods are used in nearly every underground coal mine in the US. However,the piecemeal manner in which these methods have evolved resulted in some weaknesses. For example,in certain situations, it may not be obvious which program is the best to use. Other times the results from the different programs are not entirely consistent with each other. The programs have also not been updated for several years, and some changes were necessary to keep pace with new developments in mining practice. The analysis of coal pillar stability(ACPS) now integrates all three of the older software packages into a single pillar design framework. ACPS also incorporates the latest research findings in the field of pillar design, including an expanded multiple seam case history data base and a new method to evaluate room and pillar panels containing multiple rows of pillars left in place during pillar *** also includes updated guidance and warnings for users and features upgraded help files and graphics.

摘要：Varicocele repair in adolescent remains controversial. Our aim is to identify and combine clinical trials results published thus far to ascertain the efficacy of varicocelectomy in improving testis volume and semen parameters compared with nontreatment control. A literature search was performed using Medline, Embase and Web of Science, which included results obtained from meta-analysis, randomized and nonrandomized controlled studies. The study population was adolescents with clinically palpable varicocele with or without the testicular asymmetry or abnormal semen parameters. Cases were allocated to treatment and observation groups, and testis volume or semen parameters were adopted as outcome measures. As a result, seven randomized controlled trials （RCTs） and nonrandomized controlled trials studying bilateral testis volume or semen parameters in both treatment and observation groups were identified. Using a random effect model, mean difference of testis volume between the treatment group and the observation group was 2.9 ml （95% confidence interval [CI]： 0.6, 5.2; P 〈 0.05） for the varicocele side and 1.5 ml （95% CI- 0.3, 2.7; P 〈 0.05） for the healthy side. The random effect model analysis demonstrated that the mean difference of semen concentration, total semen motility, and normal morphology between the two groups was 13.7 x 106 ml-1 （95% CI： -1.4, 28.8; P= 0.075）, 2.5% （95% CI：-3.6, 8.6; P= 0.424）, and 2.9% （95% CI： -3.0, 8.7; P= 0.336） respectively. In conclusion, although varicocelectomy significantly improved bilateral testis volume in adolescents with varicocele compared with observation cases, semen parameters did not have any statistically significant difference between two groups. Well-planned, properly conducted RCTs are needed in order to confirm the above-mentioned conclusion further and to explore whether varicocele repair in adolescents could improve subsequently spontaneous pregnancy rates.

摘要：Interstitial cells of Cajal (ICC) are important players in the symphony of gut motility. They have a very signif icant physiological role orchestrating the normal peristaltic activity of the digestive system. They are the pacemaker cells in gastrointestinal (GI) muscles. Absence, reduction in number or altered integrity of the ICC network may have a dramatic effect on GI system motility. More understanding of ICC physiology will foster advances in physiology of gut motility which will help in a future breakthrough in the pharmacological interventions to restore normal motor function of GI tract. This mini review describes what is known about the physiologic function and role of ICCs in GI system motility and in a variety of GI system motility disorders.

摘要：Dear Editor, Diseases of the genitourinary system were the fifth most common disease of inpatients in Chinese city hospitals in 2011 （6.0%）.1 Andrology in China has grown rapidly within the last decade, however, little is known about the scientific publications by Chinese authors in andrology. We, therefore, sought to reveal the contributions of Chinese authors in three major regions of China-the Mainland （ML）, Taiwan （TW）, and Hong Kong （HK）-to the research in the fields of andrology.

摘要：The differential distribution between cancer cells and normal adult tissues makes survivin a very attractive cancer drug target. We have previously reported a series of novel selective survivin inhibitors with the most potent compound MX 106 reaching nanomolar activity in several cancer cell lines. Further optimization of the MX 106 scaffold leads to the discovery of more potent and more selective survivin inhibitors. Various structural modifications were synthesized and their anticancer activities were evaluated to determine the structure activity relationships for this MX 106 scaffold. In vitro anti-proliferative assays using two human melanoma cell lines showed that several new analogs have improved potency compared to MX 106. Very interestingly, these new analogs generally showed significantly higher potency against P-glycoprotein overexpressed cells compared with the corresponding parental cells, suggesting that these compounds may strongly sensitize tumors that have high expressions of the Pglycoprotein drug efflux pumps. Western blotting analysis confirmed that the new MX 106 analogs maintained their mechanism of actions by selectively suppressing survivin expression level among major inhibitors of apoptotic proteins and induced strong apoptosis in melanoma tumor cells.

摘要：Validity and reliability,as we all learned in our first research methods class,are two of the most important qualities of any test,measurement or *** compared with validity, reliability is actually more important since without it, there would be no *** reliability is so important, almost all research journals today have some articles related to ***,many of these articles fail to