Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer, functioning as a metastasis suppressor by regulating epithelial-mesenchymal transition. Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation-specific polymerase chain reaction analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. Our data demonstrated that patients with NKX6.1 methylation presented poorer 5-year overall survival (P = 0.0167) and disease-free survival (P = 0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, these data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival (P = 0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel prognostic biomarker in CRC and that it may be used as a predictor of the response to chemotherapy.

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Currently available fetal echocardiographic reference values are derived mainly from North American and European population studies, and there is a lack of reference z-score for fetal echocardiographic measurement in Asian populations. The aim of this study was to establish normal ranges of echocardiographic measurements and z-scores in healthy Asian fetuses. A total of 575 healthy pregnant Taiwanese with an estimated gestational age from 14 to 38 weeks were enrolled voluntarily for this observational study. Standard two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries of the developing fetuses. In contrast to past studies, our sample was more evenly distributed for estimated gestational age (p<0.001). We present percentile graphs for 13 fetal echocardiographic measurements from the knowledge of estimated gestational age, biparietal distance, head circumference, abdominal circumference, and femur length. Most cardiac structures and developmental markers had linear models as the bestfitting, except for transverse aortic isthmus by estimated gestational age and transverse ductus arteriosus by femur length. Our findings indicate that estimated gestational age was generally the best model for fetal heart development, while head circumferences could be used as an optimal developmental marker to predict left atrium, right atrium, right ventricle, pulmonary annulus, and ductus arteriosus. Lastly, we developed nomograms for each of the 13 fetal heart measurements by each developmental markers. This is the first study providing echocardiographic reference ranges and nomograms for Asian fetuses. Computing z-scores from nomograms helps in standardizing comparisons and adds additional prognostic information to the diagnosis of congenital heart disease.

BackgroundThe human norovirus (NV) circulates worldwide and is a major cause of epidemics, which have increased in Taiwan since 2002. NV in acute gastroenteritis (AGE) and non-acute gastroenteritis (asymptomatic) patients, including children and adults, have not been previously examined in Taiwan; therefore, we examined the epidemiology and phylogeny of NV in AGE and asymptomatic patients of all ages.Methods253 stool samples were collected from August 2011 to July 2012 (including 155 AGE and 98 asymptomatic samples in Taiwan) and analyzed using reverse transcription-polymerase chain reaction (RT-PCR) for NV. Primers targeting the RNA-polymerase gene were used for RT-PCR to allow DNA sequencing of Taiwan NV strains and phylogenetic analyses.ResultsNV was detected in 24 (9.5%) of 253 stool specimens using RT-PCR. NV was isolated from all age groups (1 to 86 y) and those NV-positive samples were major identified from inpatients (79.2%, 19/24). Statistical analysis showed that the NV infectious rate of AGE patients was statistically significant (P < 0.05) for age, season and water type, respectively. Phylogenetic analyses of the RdRp region sequence showed that 24 NV isolates belonged to Genogroup II Genotype 4 (GII.4). They were closely related to the epidemic strain in Taiwan in 2006, the GII.4-2006b pandemic strain in 2006, and the GII.4-New Orleans strain in 2010.ConclusionThis study is the first to examine NV in sporadic AGE and asymptomatic patients in Taiwan. Furthermore, epidemic strains of isolated GII.4 were predominant in Taiwan during 2011 and 2012.

Although aberrant complement activation is involved in the pathogenesis of systemic lupus erythematosus (SLE), the role of complement regulatory proteins in disease activity of SLE remains limited. We enrolled the pediatric-onset SLE patients from our cohort study over 10 years. The clinical and laboratory data including SLEDAI disease activity score, and serum complement factor H (CFH), CFI, CD46, C5a, and C5b-9 in the active and remission phases were determined. Glomerular C5b-9 deposition as a complement activity marker was also examined. Forty patients (35 female and 5 male, aged 13.9 ± 3.8 years) met the criteria of investigation were assessed. Fever and kidney were the most common symptom and organ involved, respectively. Mean SLEDAI in the active and remission phases were 12.6 vs 1.7, respectively. All patients exhibited lower serum C3, C4, CFH and CFI and higher serum anti-dsDNA and CD46 in the active pahse. There was a significant difference in serum CFH, CFI and CD46 between active and remissive phases. Serum CFI but not CFH and CD46 level was negatively correlated with SLEDAI score in active phase. Compared to classical activity markers, serum CFI was superior to C4 and anti-dsDNA in reflecting disease activity and also significantly correlated with white blood count and hemoglobin. Glomerular C5b-9 depositions were detected in patients with nephritis during active phase but not in disease controls. Serum CFI level may not only be a promising biomarker for disease activity of SLE, but also reflects the hematological features of SLE.