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Background Clinical manifestations of enterovirus 71 (EV71) range from herpangina, hand-foot-andmouth disease (HFMD), to severe neurological complications. Unlike the situation of switching genotypes seen in EV71 outbreaks during 1998-2008 in Taiwan, genotype B5 was responsible for two large outbreaks in 2008 and 2012, respectively. In China, by contrast, EV71 often persists as a single genotype in the population and causes frequent outbreaks. To investigate genetic changes in viral evolution, complete EV71 genome sequences were used to analyze the intra-genotypic evolution pattern in Taiwan, China, and the Netherlands. Results Genotype B5 was predominant in Taiwan's 2008 outbreak and was re-emergent in 2012. EV71 strains from both outbreaks were phylogenetically segregated into two lineages containing fourteen non-synonymous substitutions predominantly in the non-structural protein coding region. In China, genotype C4 was first seen in 1998 and caused the latest large outbreak in 2008. Unlike shifting genotypes in Taiwan, genotype C4 persisted with progressive drift through time. A majority of non-synonymous mutations occurred in residues located in the non-structural coding region, showing annual increases. Interestingly, genotype B1/B2 in the Netherlands showed another stepwise evolution with dramatic EV71 activity increase in 1986. Phylogeny of the VP1 coding region in 1971-1986 exhibited similar lineage turnover with genotype C4 in China; however, phylogeny of the 3D-encoding region indicated separate lineage appearing after 1983, suggesting that the 3D-encoding region of genotype B2 was derived from an unidentified ancestor that contributed to intra-genotypic evolution in the Netherlands. Conclusions Unlike VP1 coding sequences long used for phylogenetic study of enteroviruses due to expected host immune escape, our study emphasizes a dominant role of non-synonymous mutations in non-structural protein regions that contribute to (re-)emergent genotypes in continuous stepwise evolution. Dozens of amino acid substitutions, especially in nonstructural proteins, were identified via genetic changes driven through intra-genotypic evolution worldwide. These identified substitutions appeared to increase viral fitness in the population, affording valuable insights not only for viral evolution but also for prevention, control, and vaccine against EV71 infection. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the safety and efficacy of TS-1 adjuvant chemotherapy in Taiwanese patients with gastric cancer. Methods We included in this study patients with locally advanced gastric cancer who received adjuvant TS-1 or 5-fluorouracil chemotherapy after curative surgery and extended lymph node dissection between 1 June 2008 and 31 December 2012 at Chang Gung Memorial Hospital. Patient characteristics, tumor features, safety profiles and compliance with TS-1 treatment were retrospectively analyzed from medical charts. Results Forty patients received adjuvant chemotherapy with TS-1 and 193 with 5-fluorouracil within the study period. The 1- and 2-year overall survival rates were 90.6 % and 87 % in the TS-1 group and 95.4 % and 86.8 % in the 5-fluorouracil group (P = 0.34). The 1- and 2-year disease-free survival rates were 90.6 % and 74.7 % in the TS-1 group and 88 % and 75.7 % in the 5-fluorouracil group (P = 0.66). In the TS-1 group, tumor recurrence was more frequent in those with >15 metastatic lymph nodes than ⩽15. Overall, 78.9 %, 74.3 %, 62.1 % and 56 % of patients underwent TS-1 treatment for at least 3, 6, 9 and 12 months, respectively. The most common adverse events of TS-1 were skin hyperpigmentation (55 %), diarrhea (27.5 %), dizziness (27.5 %) and leucopenia (20 %). Severe adverse events (SAEs; grade III or IV toxicity) were diarrhea (7.5 %), stomatitis (7.5 %), leukopenia (5 %), vomiting (2.5 %), anorexia (2.5 %) and dizziness (2.5 %). Patients who underwent total gastrectomy had a significantly greater risk of TS-1-related SAEs than patients who underwent subtotal gastrectomy (40 % versus 8 %, P = 0.014). Conclusions The incidence of SAEs during TS-1 therapy was more common in Taiwanese patients with gastric cancer who underwent total gastrectomy compared with those who underwent subtotal gastrectomy. Clinicians must be aware of and able to manage these SAEs to maximize patient compliance with adjuvant TS-1. [ABSTRACT FROM AUTHOR]