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Road traffic injuries (RTIs) are among the leading causes of injury and fatality worldwide. RTI casualties are continually increasing in Taiwan; however, because of a lack of an advanced method for classifying RTI severity data, as well as the fragmentation of data sources, road traffic safety and health agencies encounter difficulties in analyzing RTIs and their burden on the healthcare system and national resources. These difficulties lead to blind spots during policy-making for RTI prevention and control. After compiling classifications applied in various countries, we summarized data sources for RTI severity in Taiwan, through which we identified data fragmentation. Accordingly, we proposed a practical classification for RTI severity, as well as a feasible model for collecting and integrating these data nationwide. This model can provide timely relevant data recorded by medical professionals and is valuable to healthcare providers. The proposed model's pros and cons are also compared to those of other current models., (© The Author(s) 2018. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128., (© 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The network of stemness genes and oncogenes in human patient-specific reprogrammed cancer stem cells (CSCs) remains elusive, especially in liver cancer. HepG2-derived induced pluripotent stem cell-like cells (HepG2-iPS-like cells) were generated by introducing Yamanaka factors and the knockdown vector shTP53. They exhibited features of stemness and a higher tumorigenesis after xenograft transplantation compared with HepG2 cells. The cancerous mass of severe combined immunodeficiency (SCID) mice derived from one colony was dissected and cultured to establish reprogrammed HepG2-derived CSC-like cells (designated rG2-DC-1C). A single colony exhibited 42% occurrence of tumors with higher proliferation capacities. rG2-DC-1C showed continuous expression of the OCT4 stemness gene and of representative tumor markers, potentiated chemoresistance characteristics, and invasion activities. The sphere-colony formation ability and the invasion activity of rG2-DC-1C were also higher than those of HepG2 cells. Moreover, the expression of the OCT4 gene and the c-JUN oncogene, but not of c-MYC, was significantly elevated in rG2-DC-1C, whereas no c-JUN expression was observed in HepG2 cells. The positive-feedback regulation via OCT4-mediated transactivation of the c-JUN promoter and the c-JUN-mediated transactivation of the OCT4 promoter were crucial for promoting cancer development and maintaining cancer stemness in rG2-DC-1C. Increased expression of OCT4 and c-JUN was detected in the early stage of human liver cancer. Therefore, the positive feedback regulation of OCT4 and c-JUN, resulting in the continuous expression of oncogenes such as c-JUN, seems to play a critical role in the determination of the cell fate decision from iPS cells to CSCs in liver cancer. Stem Cells 2016;34:2613-2624., (© 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background: Conjunctival and corneal calcification (CCC) is the most common form of metastatic calcification in patients with chronic renal failure. The aim of this study is to investigate if severity of CCC correlates with vascular calcification and mortality in maintenance haemodialysis (MHD) patients., Methods: One hundred and nine MHD patients were recruited. CCC was evaluated by external eye photographs, and was graded and scored according to modified Porter and Crombie classification system described by Tokuyama et al. Chest X-ray examination was used to evaluate aortic arch calcification. Geographic, haematological, biochemical and dialysis-related data were obtained. The patients were analysed for traditional and non-traditional risk factors for cardiovascular disease stratified by severity of CCC. All patients were followed up for 1 year to investigate the risks for mortality., Results: Forty-three, 35 and 31 patients had mild (scores ≤ 4), moderate and severe (scores ≥ 9) CCC at baseline, respectively. With trend estimation, patients with severe CCC had a significantly higher percentage of severe aortic arch calcification. Multiple linear regression analysis showed that hypertension, haemodialysis duration and corrected calcium level were associated with scores of CCC in MHD patients. Moreover, age, corrected calcium-phosphate level, and moderate and severe CCC were associated with grades of aortic arch calcification. At 1-year follow-up, 11 of 109 (10.1%) patients had died. Multivariate Cox proportional hazards model showed that age, corrected calcium and severe CCC were significant risk factors for all-cause 1-year mortality in MHD patients. Each increment of one score of CCC is associated with a 26.4% increased risk for all-cause mortality., Conclusions: Severity of CCC, which is easily obtained at bedside, acts as an independent predictor for all-cause 1-year mortality in MHD patients.

To verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non-muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non-muscle-invasive bladder urothelial tumors.

Background: Adenosine triphosphate-binding cassette (ABC) transporters ABCG5 and ABCG8 are sterol export pumps regulating biliary cholesterol excretion. The formation of gallstones, supersaturated with cholesterol in bile, is determined by genetic and environmental factors. The interaction of susceptible gene polymorphisms with age, sex and body mass index in gallstone disease is unclear., Methods: In a cross-sectional study, 979 subjects (880 men and 99 women, mean(s.d.) age 47.7(10.4) years) were recruited from a hospital-based population. Of these, 74 were diagnosed with gallstone disease by abdominal ultrasonography. Five non-synonymous polymorphisms, E604Q (ABCG5), D19H, C54Y, T400K and A632V (ABCG8), were analysed using the TaqMan genotyping assay., Results: The serum total cholesterol and both low- and high-density lipoprotein cholesterol levels were significantly lower in subjects with gallstones than in those without. 604Q (CC) and D19H (GC) genotypes were significantly associated with gallstone disease, even when adjusted for age, sex and body mass index. The genetic risk of developing gallstone disease was further stratified by age. The risk was greatly increased in subjects younger than 50 years with the D19H genotype and those of 50 years or more with the 604Q genotype., Conclusion: Carriers of ABCG5 604Q or ABCG8 D19H polymorphisms have an increased risk of gallstone disease independent of age, sex and body mass index., ((c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Introduction: There have been limited multiregional studies in Asia examining the parameters of men's general and sexual health and quality of life in the general population vs. those in clinical cohorts of patients with erectile dysfunction (ED)., Aims: The aims of the Asian Men's Attitudes to Life Events and Sexuality (Asian MALES) study were to investigate the prevalence of ED, associated health conditions, and ED treatment-seeking patterns in the general male population in five regions of Asia (China, Japan, Korea, Malaysia, and Taiwan)., Main Outcome Measure: Standardized questionnaire previously used in a similar multiregional study and modified to ensure culturally appropriate content for Asia., Methods: Phase I of the study involved 10,934 adult men, aged 20-75 years, who were interviewed using the standardized questionnaire. Phase II of the study involved men with self-reported ED recruited from Phase I and via physician referral, invitations in general practitioner offices, and street interception (total Phase II sample, N = 1,209)., Results: The overall prevalence of self-reported ED in the Phase I study population was 6.4%. ED prevalence varied by region and significantly increased with age (P < 0.01). Men with ED reported significantly greater rates of comorbid illness (P < 0.0001) and a reduced quality of life (P = 0.0001), compared with men without ED. Phase II of the study revealed that fewer than half of men with self-reported ED had sought treatment for their problem. Men were more likely to seek help for erection difficulties from Western doctors than from traditional medicine practitioners (P = 0.0001). A man's partner/spouse was the most common influencer of treatment seeking in all regions except Malaysia., Conclusion: The findings confirm those of existing research on ED in both Asian and non-Asian males: ED is a prevalent condition; the prevalence of ED increases with age and is strongly associated with comorbid conditions; and the majority of men have never sought treatment for their condition. This study highlights a substantial need for the evaluation and treatment of ED in Asian men.

Introduction: Previous clinical studies assessing the efficacy and safety of vardenafil, an oral phosphodiesterase type 5 inhibitor, in men with erectile dysfunction (ED) have consisted mostly of Caucasian patients., Aim: The aim of this article is to describe the efficacy and safety of vardenafil in men of East Asian ethnicity with ED., Methods: Data were pooled from two 12-week, double-blind studies that included 306 East Asian men randomized to placebo or 10 mg of vardenafil., Main Outcome Measures: Efficacy variables included the International Index of Erectile Function-erectile function (IIEF-EF) domain score, questionnaires of Sexual Encounter Profile (SEP2 and SEP3), and a Global Assessment Question (GAQ). Safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse events., Results: A total of 306 East Asian men with ED were treated with placebo (N = 151) or vardenafil (N = 155). Mean baseline IIEF-EF domain scores (placebo, 13.4; vardenafil, 14.2) were consistent with moderate ED. At end point, the patients treated with vardenafil had a significantly greater increase in IIEF-EF domain score compared with placebo (24.2 vs. 15.9; P < 0.0001). The average per patient penetration (SEP2) success rate was significantly higher in the vardenafil group compared with placebo (88% vs. 58%; P < 0.0001). Moreover, the average per patient intercourse completion (SEP3) success rate was significantly higher in the vardenafil group compared with placebo (69% vs. 23%; P < 0.0001). Positive GAQ responses were reported by 85% of patients receiving vardenafil, compared with 33% of those receiving placebo. The most frequent adverse events were vasodilatation (primarily facial flushing), rhinitis, and headache, all of which were of mild intensity., Conclusions: Vardenafil is an effective, well-tolerated oral drug for the treatment of East Asian men with moderate ED of broad-spectrum etiology.

Introduction: Tadalafil is a phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction (ED). Past clinical trials have assessed its efficacy and safety in western populations. Tadalafil has not been investigated in a large clinical trial with a South-east Asian population., Aim: To assess the efficacy and safety of on-demand tadalafil for the treatment of ED in a 12-week, double-blind, placebo-controlled study in Taiwan., Methods: Men with mild to severe ED of various etiologies were randomized to receive placebo, tadalafil 10 mg, or tadalafil 20 mg, taken as needed (maximum once daily). Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ)., Results: Tadalafil significantly improved erectile function compared with placebo (P < 0.005, all measures). At endpoint, the patients receiving tadalafil reported a greater mean per-patient percentage of successful intercourse attempts (SEP question 3: 70.0%, 10 mg; 78.0%, 20 mg) than placebo-treated patients (42.8%) and a greater proportion of improved erections (GAQ: 92.3% and 84.6% vs. 54.5%). Most treatment-emergent adverse events were mild or moderate. The most common adverse events were back pain, dyspepsia, and myalgia., Conclusions: Tadalafil was an effective, well-tolerated therapy for men in Taiwan with ED of broad-spectrum severity and etiology.