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Background: Hepatopulmonary syndrome (HPS) is a complication in biliary atresia (BA) children following hepatoportoenterostomy. Liver transplantation (LT) was the definitive treatment of HPS. However, little was known about the risk factors between HPS and mortalities. We aimed to evaluate the role of HPS and the predictors of complications after LT in BA children., Methods: One hundred and twenty (54 males and 66 females) children with BA receiving LT were retrospectively enrolled. The primary outcome was postoperative biliary/vascular complication rates and the secondary outcome was post-LT mortality rates., Results: Among 120 BA children receiving LT, six (5%) children were diagnosed with HPS before LT. The overall survival rate of LT in BA children was 80% and the overall survival rate of LT in BA children with and without HPS was 17% and 83%, respectively. Vascular complications and HPS were predictors for poor overall survival rates both in univariate logistic regression analyses (hazard ratio [HR], 11.63 and 5.96; P < 0.0001 and P = 0.001, respectively) and multivariate logistic regression analyses (HR, 10.02 and 4.16; P < 0.0001 and P = 0.007, respectively). Kaplan-Meier analysis indicated the predictive role of HPS on poor overall survival rates (P < 0.0001), higher risks of biliary complications (P < 0.0001), and higher risks of jaundice (P < 0.01) post-LT., Conclusion: The present study comprising children over long-term follow-up revealed that the development of pre-LT HPS had a poor impact on overall survival rates and higher risks of biliary complications in BA children receiving LT., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit., Research Methodology/design: A prospective and multicentre study., Setting: This study was conducted in 24 intensive care units in Anhui, China., Main Outcome Measures: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay., Results: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition., Conclusion: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales., Implications for Clinical Practice: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Vascular endothelial growth factor (VEGF) is crucial for follicle development through the regulation of granulosa cell (GC) function in some mammals, but its mechanism is unclear in yak (Bos grunniens). Therefore, the objectives of this study were to investigate the effects of VEGF on the viability, apoptosis and steroidogenesis of yak GCs. First, we investigated the localization of VEGF and its receptor (VEGFR2) in yak ovaries by immunohistochemistry analysis and evaluated the effect of culture medium containing different VEGF concentrations and culture times on the viability of yak GCs by Cell Counting Kit-8. Then, optimal treatment with 20 ng/mL VEGF for 24 h was selected to analyze the effects of this compound on intracellular reactive oxygen species levels by DCFH-DA kit, cell cycle and apoptosis by flow cytometry, steroidogenesis by ELISA kit and the expression of the related genes by RT‒qPCR. The results showed that VEGF and VEGFR2 were highly coexpressed in GCs and theca cells. GCs cultured in medium containing 20 ng/mL VEGF for 24 h significantly improved cell viability, decreased ROS production, promoted the transition from G1 phase to S phase (P < 0.05), increased the expression of the CCND1 (P < 0.05), CCNE1, CDK2, CDK4, and PCNA genes (P < 0.01) and decreased the expression of the P53 gene (P < 0.05). This treatment significantly reduced GC apoptosis (P < 0.05) by promoting the expression of BCL2 and GDF9 (P < 0.01) and inhibiting the expression of BAX and CASPASE3 (P < 0.05). VEGF promoted progesterone secretion (P < 0.05) accompanied by increased expression of HSD3B, StAR and CYP11A1 (P < 0.05). Taken together, our findings highlight the beneficial influence exerted by VEGF in improving GC viability and reducing ROS production and the apoptosis rate through the modulation of related gene expression., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Wounds are in a stressed state, which precludes healing. Trehalose is a stress metabolite that protects cells under stress. Here, we explored whether trehalose reduces stress-induced wound tissue damage. A stress model was prepared by exposing human keratinocytes to hydrogen peroxide (H 2 O 2 ), followed by trehalose treatment. Trehalose effects on expression of the autophagy-related proteins ATG5 and ATG7 and cell proliferation and migration were evaluated. For in vivo verification, a wound model was established in Sprague-Dawley rats, to measure the effects of trehalose wound-healing rate and reactive oxygen species (ROS) content. Histological changes during wound healing and trehalose's effects on ATG5 and ATG7 expression, necrosis, and apoptosis were examined·H 2 O 2 stress increased ATG5 and ATG7 expression in vitro, but this was insufficient to prevent stress-induced damage. Trehalose further increased ATG5/ATG7 levels, which restored proliferation and increased migration by depolymerizing the cytoskeleton. However, trehalose did not exert these effects after ATG5 and ATG7 knockout. In vivo, the ROS content was higher in the wound tissue than in normal skin. Trehalose increased ATG5/ATG7 expression in wound tissue keratinocytes, reduced necrosis, depolymerized the cytoskeleton, and promoted cell migration, thereby promoting wound healing., Competing Interests: Declaration of interest We declare that we have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Supplementation with acetyl-l-carnitine (ALC) during in vitro maturation significantly improves the rates of oocyte cleavage and morula and blastocyst formation in sheep and buffalo; however, the mode of action of ALC in improving oocyte competence is not completely understood. Therefore, the aim of this study was to investigate the effects of ALC on proliferation, antioxidant properties, lipid droplet accumulation and steroid hormone secretion in yak (Bos grunniens) granulosa cells (GCs). Yak GCs were identified using FSHR immunofluorescence. The cells were treated with different concentrations of ALC, cell proliferation was detected by cell counting kit-8, and the optimal concentration and treatment time were determined for subsequent experiments. Then, reactive oxygen species (ROS) were detected by a DCFH-DA probe, and lipid droplet accumulation was observed by oil red O staining. Estradiol (E2) and progesterone (P4) in the medium were detected by ELISA, and the expression of genes related to cell proliferation, apoptosis, the cell cycle, antioxidants and steroid synthesis was determined by RT‒qPCR. The results showed that 1 mM ALC treatment for 48 h was the optimum treatment. It significantly increased cell viability (P < 0.05), significantly decreased the amount of ROS and lipid droplet content, and promoted P4 and E2 secretion (P < 0.05) of yak GCs. RT‒qPCR results verified that GCs treated with 1 mM ALC for 48 h significantly increased the expression of genes related to anti-apoptosis and the cell cycle (BCL-2, PCNA, CCND1 and CCNB1), antioxidants (CAT, SOD2 and GPX1), and E2 and P4 secretion (StAR, CYP19A1 and HSD3B1) (P < 0.05), but it significantly decreased the expression of apoptosis genes (BAX and P53) (P < 0.05). In conclusion, ALC increased the viability of yak GCs, reduced the amount of ROS and lipid droplets, increased P4 and E2 synthesis and affected the expression of related genes in yak GCs., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Synapse loss in medial prefrontal cortex (mPFC) has been implicated in stress-related mood disorders, such as depression. However, the exact effect of synapse elimination in the depression and how it is triggered are largely unknown. Through repeated longitudinal imaging of mPFC in the living brain, we found both presynaptic and postsynaptic components were declined, together with the impairment of synapse remodeling and cross-synaptic signal transmission in the mPFC during chronic stress. Meanwhile, chronic stress also induced excessive microglia phagocytosis, leading to engulfment of excitatory synapses. Further investigation revealed that the elevated complement C3 during the stress acted as the tag of synapses to be eliminated by microglia. Besides, chronic stress induced a reduction of the connectivity between the mPFC and neighbor regions. C3 knockout mice displayed significant reduction of synaptic pruning and alleviation of disrupted functional connectivity in mPFC, resulting in more resilience to chronic stress. These results indicate that complement-mediated excessive microglia phagocytosis in adulthood induces synaptic dysfunction and cortical hypo-connectivity, leading to stress-related behavioral abnormality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Primary sclerosing cholangitis (PSC) is often associated with ulcerative colitis (UC). We investigated the clinical characteristics of pediatric UC patients with and without PSC., Methods: We retrospectively recruited children with UC, with and without PSC, from 2006 to 2017 in a tertiary center in Taiwan. The clinical data of the patients, including clinical and endoscopic UC severity scores, medications, and laboratory parameters, were analyzed., Results: We recruited five children with PSC-UC (PSC-UC group), and 26 with UC alone (non-PSC UC group) in this retrospective analysis. Among the patients with PSC-UC, four (80%) were compatible with definite or probable autoimmune sclerosing cholangitis (ASC). The UC Endoscopic Index of Severity (5.00 vs. 9.00, P = 0.003) and Mayo score (4.00 vs. 8.00, P = 0.014) were significantly lower in the PSC-UC group than the non-PSC UC group. The prevalence of immunomodulator use was significantly higher in the PSC-UC than the non-PSC UC group (100% vs. 42.3%, P = 0.043), but there was no difference regarding steroids, mesalamine, or biologics. At the end of the study, significantly fewer patients were steroid-free in the PSC-UC than the non-PSC UC group (20.0% vs. 84.6%, P = 0.010)., Conclusions: Pediatric patients with PSC-UC had less severe colitis than those with UC alone in terms of the clinical activity index and endoscopic severity index, but they were more likely to need an immunomodulator and less likely to be steroid-free in the long term, for the control of liver disease., Competing Interests: Declaration of competing interest The authors declared no potential, perceived, or real conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Combustion-derived black carbon (BC) is increasingly recognized as a significant pollutant that can have adverse effects on the atmospheric environment, human health, and regional climate. Fossil fuel combustion is the main source of BC, yet understanding of the relative contributions to BC from coal and liquid fuel combustion remains incomplete. Moreover, few studies have assessed the relative contributions based on long-term continuous daily field observations. This study adopted a Bayesian model of a three-dimensional array of a stable carbon isotope and the ratios of non-sea-salt K + to BC and ΔBC/ΔCO of one year's daily observations (from September 1, 2017 to August 31, 2018) to constrain source apportionment of BC in Beijing (China). Results showed that both the BC and the carbon isotope concentrations exhibited strong seasonal variability, and that the annual BC concentration has decreased significantly in recent years. The Bayesian model results also revealed that the relative contributions from the combustion of coal, liquid fuel, and biomass were 42% ± 18%, 42% ± 18%, and 16% ± 11%, respectively, with a larger contribution from coal (liquid fuel) combustion in winter and spring (summer and autumn). The seasonal variation of source appointment was attributed to local and regional fuel combustion coupled with meteorological conditions. With increasing PM 2.5 level, the BC concentration derived from biomass burning increased fastest, followed by that derived from coal combustion. But concentration of secondary inorganic ions increased faster than BC as PM 2.5 increased., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Backgorund: Hepatoblastoma is the most common primary liver malignancy in young children., Methods: To identify predictors of the clinical outcomes of hepatoblastoma, we retrospectively reviewed the medical records of 45 children with hepatoblastoma in the National Taiwan University Hospital from 1998 to 2018. All of the children were classified as high risk according to the pretreatment extent of disease (PRETEXT) staging system. The patients' clinical data (sex, age at diagnosis, PRETEXT status, presence of metastasis or tumor rupture, tumor pathologic type, and clinical outcomes) were analyzed., Results: A total of 45 children with high-risk hepatoblastoma were diagnosed at an average age of 3.2 years. The survival analysis showed that the event-free survival duration was significantly longer in patients aged ≤1.25 years at diagnosis than those >1.25 years (hazard ratio = 2.86, p = 0.036). The absence of initial tumor rupture was associated with longer event-free survival (hazard ratio = 2.74, p = 0.039). Diagnosis at age >1.25 years was correlated with the presence of multifocal liver tumors (p = 0.0002) and tumor rupture at diagnosis (p = 0.02). There was no significant difference in event-free survival between the groups classified as intermediate versus high risk according to the Children's Hepatic tumors International Collaboration hepatoblastoma stratification system (p = 0.13)., Conclusions: Diagnosis at ≤ 1.25 years of age and absence of initial tumor rupture were predictive of a good clinical prognosis in Taiwanese children with hepatoblastoma., (Copyright © 2020. Published by Elsevier B.V.)

Background & Aims: Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF., Methods: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured., Results: One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m 2 , p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm 2 , p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm 2 , p = 0.926)., Conclusions: Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery., Clinical Trial Number: NCT01312012 (ClinicalTrials.gov) LAY SUMMARY: Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Inborn errors of bile acid metabolism (IEBAM) cause rare but treatable genetic disorders that can present as neonatal cholestasis or neurological diseases. Without timely primary bile acid treatment, patients may develop liver failure early in life. This study aimed to analyze the types and treatment outcomes of IEBAM in Taiwanese infants and document the allele frequency of CYP7B1 hot spot mutations in the population., Methods: Urine samples from patients with infantile intrahepatic cholestasis and suspected IEBAM were subjected to urinary bile acid analysis by gas chromatography-mass spectrometry (GC/MS). Genetic diagnoses were made using direct sequencing or next-generation sequencing. We also tested healthy control subjects for a probable hot spot point mutation of CYP7B1., Results: Among the 75 patients with infantile intrahepatic cholestasis tested during 2000 -2016, three had ∆ 4 -3-oxosteroid 5β-reductase deficiency with AKR1D1 mutations, and three had oxysterol-7α-hydroxylase deficiency with CYP7B1 mutation. Two patients with ∆ 4 -3-oxosteroid 5β-reductase deficiency were successfully treated with cholic acid. The three unrelated infants with oxysterol 7α-hydroxylase deficiencies had the same p.R112X homozygous CYP7B1 mutation. Two had mild renal or neurological involvement. Among 608 healthy control subjects, the allele frequency of the heterozygous mutation for p.R112X was 2/1216 (0.16%). The only surviving patient with oxysterol 7α-hydroxylase deficiency recovered from liver failure after chenodeoxycholic acid (CDCA) treatment beginning at 3 months of age., Conclusion: Distinct types of IEBAM disease were found in the Taiwanese population. Patients with early diagnosis and early treatment had a favorable outcome. IEBAM prevalence rates may be higher than expected due to the presence of heterozygous mutations in the general population., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: This study aimed to validate the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for nasopharyngeal carcinoma (NPC) in non-endemic region., Materials and Methods: We recruited 607 patients with histology-proven, previously untreated, non-metastatic NPC treated by intensity-modulated radiotherapy (IMRT) at our center. Harrell's concordance index (c-index) and Akaike information criterion (AIC) were applied to compare the prognostic discrimination between the 7th and 8th edition staging system., Results: For T category, the local recurrence-free survival (LRFS) Kaplan-Meier curves of T1, T2 and T3 were well separated in the 8th edition; however, LRFS did not significantly differ between T3 and T4 (P = 0.166). Moreover, the 7th edition achieved higher c-index (0.702 [95% CI, 0.618-0.787] vs. 0.685 [95% CI, 0.604-0.767]) and lower AIC (766.1 vs. 770.8) than 8th edition for LRFS. With regard to N category, the 8th edition achieved higher c-index (0.796 [95% CI, 0.749-0.843] vs. 0.751 [95% CI, 0.696-0.805]) and lower AIC (1439.4 vs. 1471.9) for distant metastasis-free survival. In terms of overall stage, the 8th edition also had higher c-index (0.798 [95% CI, 0.753-0.844] vs. 0.721 [95% CI, 0.672-0.770]) and lower AIC (1963.9 vs. 2007.2) compared with the 7th edition for overall survival. Furthermore, interval validation by bootstrapping the sample randomly for ~100-1000 times also validated above findings., Conclusion: The 8th edition of AJCC/UICC TNM staging system achieved significantly better prognostic discrimination than the 7th edition with regard to N category and overall stage but not T category., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Three-dimensional printing may play an important role in patients' education. The objective of this study was to assess the effectiveness of personalized 3D printed models for increasing patient understanding of their medical condition and surgical plan., Methods: Forty-five patients with degenerative lumbar diseases were randomized by block design into three groups: educational program presented by CT & MRI imaging (care-as-usual), 3D reconstructions, or personalized 3D printed models. Patients' level of understanding and satisfaction were evaluated by two questionnaires one day after education., Results: Patients educated with personalized 3D printed models demonstrated an expanded level of understanding than patients educated with CT & MRI imaging (care-as-usual) (P ＜ 0.05) and 3D reconstructions (P ＜ 0.05). Personalized 3D printed models also resulted in a higher degree of patient satisfaction (P ＜ 0.05)., Conclusions: Personalized 3D printed models and 3D reconstructions can simplify and enhance understanding of lumbar anatomy, physiology, and patients' disease and surgical plan. Personalized 3D printed models also enhance patients' subjective satisfaction., Practice Implications: Personalized 3D printed models for patient education are feasible and could be generalized for degenerative lumbar diseases., (Copyright © 2019. Published by Elsevier B.V.)

Background: This study investigated the prognostic parameters and beneficial effects of repeat plasma exchange in children with acute liver failure (ALF)., Methods: Twenty-three patients under 18 years of age admitted to National Taiwan University Hospital due to ALF from 2003 to 2016 were included in this retrospective analysis., Results: Among the patients, 11 (48%) had native liver recovery (NLR), 9 (39.1%) died without liver transplant, and 3 (12.9%) received liver transplantation. The NLR group showed a lower proportion of idiopathic cases, lower peak ammonia level, higher peak alpha fetoprotein (AFP) level, and they had plasma exchange fewer times than the other groups. Receiver operating characteristic curve analyses yielded optimal cutoff values of plasma exchange (≤6 times), peak ammonia level (<190 μmol/L), and peak AFP level for predicting NLR in children with ALF., Conclusion: Pediatric ALF with idiopathic etiology, high peak ammonia level, and low peak AFP level are associated with fewer cases of NLR. Plasma exchange for more than six times probably offers little benefit with regard to patient survival if liver transplantation is not performed promptly., (Copyright © 2018. Published by Elsevier B.V.)

Objective: C1-C2 pedicle screw fixation has become popular for providing excellent bony purchase and avoiding neurovascular complications. However, it may be technically challenging in children. The objective of this study is to investigate the safety and efficacy of C1-C2 pedicle screw fixation for atlantoaxial dislocation (AAD) in pediatric patients younger than 5 years and to evaluate the preliminary clinical and radiographic results., Methods: During a 7-year period, 15 patients with a mean age of 3.4 years (range, 2-5 years) underwent C1-C2 pedicle screw fixation for AAD; at least 1 C1 pedicle screw was incorporated as part of the posterior atlantoaxial fusion construct. The cause, surgical technique, instrumentation, and clinical and radiographic results were analyzed., Results: Five patients had preoperative neurologic deficits and no neurovascular injury occurred during surgery. Anterior release using a retropharyngeal approach was performed in 4 cases. Fixation of 55 C1 and C2 pedicle screws was performed successfully without neurovascular complications. Anatomic and partial reductions occurred in 12 and 3 cases, respectively. Solid fusion was achieved in 14 patients (96.9%) during a mean follow-up of 37.6 months (range, 12-111 months). Two patients (13%) experienced complications: one had prolonged immobilization for a loose C1 pedicle screw, and one had unintended fusion caused by allograft absorption. All patients showed radiographic stability and symptom resolution., Conclusions: C1-C2 pedicle screw fixation for AAD is safe and effective even in children younger than 5 years., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Intensity-modulated radiotherapy (IMRT) has been applied in nasopharyngeal carcinoma (NPC) for nearly twenty years, while little is known about the ten-year survival outcomes. This study aimed at evaluating the 10-year survival outcomes for patients with NPC receiving IMRT., Materials and Methods: Data on 614 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2004 and 2008 were retrospectively reviewed. Survival outcomes stratified by tumor stage were compared., Results: The median follow-up duration was 112.7months (range, 7.6-156.8months) for the entire cohort. The 10-year local relapse-free survival rates for T1, T2 and T3 were 94.2%, 92.5% and 91.4% (P>0.05), respectively, and significantly higher than that of T4 disease (79.3%, P<0.05 for all rates). As N category increased from N0 to N3, the 10-year distant metastasis-free survival rates significantly decreased accordingly (P<0.01 for all rates). Furthermore, the 10-year overall survival rates were 100%, 87.1%, 75.5% and 55.6% for stage I, II, III and IV, respectively (P<0.05 except stage I and II). Multivariate analysis established tumor stage and age as independent prognostic factors. Late toxicities were assessable for 495 (80.6%) patients and most were Grade I/II damages. Xerostomia (387 of 489, 79.1%) and hearing impairment (212 of 495, 42.8%) remained the most troublesome., Conclusion: IMRT could achieve satisfactory survival outcomes for NPC patients with acceptable late toxicities. However, distant control still remains poor, especially for patients with N3 disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Tetrahydroxy bile acids (THBAs) are hydrophilic and are present at minimal or undetectable levels in healthy human adults, but are present at high levels in bile salt export pump ( abcb11 )-knockout mice. The roles of THBAs in human cholestatic diseases are unclear. We aimed to investigate the presence of THBAs in patients with infantile intrahepatic cholestasis and its correlation with outcome. Urinary bile acids (BAs) were analyzed by GC-MS. Data were compared between good (n = 21) (disease-free before 1 year old) and poor prognosis groups (n = 19). Good prognosis patients had a higher urinary THBA proportion than poor prognosis patients [25.89% (3.45-76.73%) vs. 1.93% (0.05-48.90%)]. A urinary THBA proportion >7.23% predicted good prognosis with high sensitivity (95.24%), specificity (84.21%), and area under the curve (0.91) ( P < 0.0001). A THBA proportion 7.23% was an independent factor for decreased transplant-free survival (hazard ratio = 7.16, confidence interval: 1.24-41.31, P = 0.028). Patients with a confirmed ABCB11 or tight junction protein 2 gene mutation (n = 7) had a minimally detectable THBA proportion (0.23-2.99% of total BAs). Three patients with an ATP8B1 mutation had an elevated THBA proportion (7.51-37.26%). In conclusion, in addition to disease entity as a major determinant of outcome, a high THBA level was associated with good outcome in the infantile intrahepatic cholestasis patients., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background: Gastroesophageal reflux (GER) is the retrograde flow of gastric contents into the esophagus and may induce a variety of complications. Endoscopically visible breaks in the distal esophageal mucosa are the most reliable evidence of reflux esophagitis. Combined multichannel intraluminal impedance and pH-metry (MII-pH) is a technique that enables monitoring of GER independent of its acidity. The aim of this study is to investigate the GER patterns in children with the aid of MII-pH monitoring and determine the correlation between endoscopically proven reflux esophagitis and reflux types by MII-pH monitoring., Methods: One hundred and twenty children were enrolled from January 2010 to October 2011 for MII-pH monitoring. We studied the GER patterns by means of pH (acid and nonacid reflux) and composition (liquid, mixed, and gas reflux) by the esophageal MII-pH signals. Meanwhile, 34 (28.3%) patients received esophagogastroduodenoscopy examination at the same time. The severity of reflux esophagitis was graded with Los Angeles classification., Results: MII-pH monitoring significantly increased the detection of numbers of reflux compared with traditional 24-hour pH monitoring (p < 0.001). The significant cutoff value of MII-pH parameters including DeMeester score ≥ 21, duration of longest acid reflux ≥ 17 minutes, and occurrence of acid reflux for more than 5 minutes showed good correlation in the prediction of the presence of endoscopic reflux esophagitis. The odds ratios of the above mentioned parameters were 12.6, 8.94, and 7.5, respectively (p = 0.02, p = 0.01, and p = 0.01). Furthermore, ≥ 3 episodes per day of acid reflux for more than 5 minutes can predict the occurrence of severe reflux esophagitis (odds ratio 12.78, p = 0.009)., Conclusion: MII-pH monitoring not only raised the diagnostic yield in identifying GER, but it also showed significant correlation with the presence of endoscopically proven reflux esophagitis in children., (Copyright © 2015. Published by Elsevier B.V.)

Background: The aim of this study was to investigate the treatment response of entecavir (ETV) in children and adolescents with chronic hepatitis B (CHB) who acquired infection perinatally or during early childhood., Methods: A total of nine treatment-naïve patients [median aged 12.2 years (range: 2.6-18.0); five girls and four boys], with hepatitis B e antigen (HBeAg) seropositive > 6 months, alanine aminotransferase (ALT) > 2 times of upper limit of normal value (30 IU/L), were enrolled for ETV therapy. They received ETV therapy with a dose of 0.015 mg/kg/d, with a maximal dose of 0.5 mg daily for at least 52 weeks. Another 27 untreated CHB patients matched for age, sex, ALT levels, and HBeAg status were recruited as the control group. A complete response at 48-52 weeks was defined as follows: (1) normalization of ALT; (2) undetectable hepatitis B virus DNA; and (3) HBeAg/anti-HBe seroconversion. All 36 patients were retrospectively reviewed for their biochemical, serological, and virologic responses., Results: ETV-treated patients achieved rapid ALT normalization (all before 8 months of treatment) compared with the control group (p < 0.001) and they had a greater chance of achieving undetectable HBV DNA levels at Week 52 after treatment (55.6% vs. 11.1%, p = 0.013). The cumulative incidence rates of HBeAg seroconversion were similarly high in both groups (ETV group 44% at 1 year 78% at 2 years; control group 37% at 1 year 63% at 2 years, respectively). The ETV group also had a trend of better complete response than the control group (22.2% vs. 0%, p = 0.057). None of the ETV-treated patients reported significant adverse effects., Conclusion: Entecavir for pediatric CHB treatment is safe and shows clinical benefits in short-term biochemical and virologic responses. Further studies to determine long-term remission and drug resistance are required., (Copyright © 2015. Published by Elsevier B.V.)

Background: Hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were conventionally determined by enzyme immunoassays. We aimed to apply a rapid, simple, and accurate method to detect HBsAg and its antibody., Methods: We collected 1463 serum samples from healthy volunteers, hepatitis B carriers, and children of HBsAg-positive mothers. The test card that we examined is a chromatographic immunoassay for the qualitative detection of either HBsAg or anti-HBs. We then compared the results of the test card to the results of the conventional enzyme-immunoassay method, which is regarded as a standard., Results: In the use of the test card to check HBsAg, the sensitivity was 88.8% and the specificity was 100%. The median hepatitis B virus viral load was significantly higher in the true-positive group [10(3.71) copies/mL (range, 10(2)-10(9.03) copies/mL)] than in the false-negative group [10(2) copies/mL (range, 10(2)-10(3.26) copies/mL)] (p = 0.005). In those who were younger than 2 years, the diagnostic accuracy of the HBsAg test card was 100%. Then, 1272 samples were tested for anti-HBs rapid test card. The sensitivity was 91.8% and the specificity was 96.5%. The median anti-HBs titer was significantly higher in the true-positive group (295.8 mIU/mL) than in the false-negative group (42.3 mIU/mL; p < 0.001)., Conclusion: Because of (1) the limited amount of blood sample required and (2) most of the young hepatitis B virus carriers having high viremia, and no concerns of false negativity, the test card is a good rapid screening tool for the detection of HBsAg and anti-HBs in pediatric group., (Copyright © 2015. Published by Elsevier B.V.)

Rationale: Previous studies have shown that apolipoprotein-1 (apoA-1) binding protein (AIBP) is highly associated with the regulation of apoA-1 metabolism, suggesting its role in the treatment of atherosclerosis. However, how AIBP regulates foam cell formation remains largely unexplored., Objective: To investigate the mechanisms underlying AIBP inhibition of foam cell formation from macrophages., Methods and Results: THP-1-derived macrophages were incubated without or with apoA-1 and AIBP, followed by assessing the formation of foam cells and the potential mechanisms. Our results showed that AIBP and apoA-1 enhanced cholesterol efflux, altered the levels of cellular free cholesterol and cholesterol ester and prevented lipid accumulation so as to reduce the formation of foam cells. Meanwhile, lack of AIBP 115-123 amino acids resulted in the loss of AIBP binding to apoA-1. Moreover, our chemiluminescent analysis showed that AIBP promoted biotin-labeled apoA-1 binding to macrophages. Besides with AIBP, more apoA-1 bound to ABCA1, a key transporter responsible for cholesterol efflux to apoA-1, as indicated by our co-immunoprecipitation assay. Our results also showed that AIBP did not regulate ABCA1 mRNA expression, but stabilized its protein from CSN2-mediated degradation., Conclusions: AIBP promotes apoA-1 binding to ABCA1 on the cell membrane of macrophages and prevents ABCA1 protein from CSN2-mediated degradation so as to prevent foam cell formation. AIBP 115-123 amino acids is at least partially responsible for its binding to apoA-1., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells., Methods: HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo., Results: Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1+RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb+RT group., Conclusion: The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The gastroesophageal reflux disease (GERD) questionnaire (GerdQ) is a validated questionnaire that was developed recently to help identify GERD patients. The sensitivity and specificity of GerdQ for the diagnosis of GERD in adult patients were 65% and 71%, respectively. Because the application of GerdQ in pediatric population is largely unknown, the aim of this study is to establish the endoscopic correlation between Chinese GerdQ and grades of erosive esophagitis (EE) in Taiwanese children., Methods: Seventy-four children (aged 9-18 years) were evaluated by our version of the Chinese GerdQ prior to receiving esophagogastroduodenoscopy for warning upper gastrointestinal symptoms. Grades of EE were assessed blindly, according to the Los Angeles classification. The sensitivity and specificity of GerdQ for detecting endoscopic EE were analyzed., Results: In 74 patients, the male to female ratio was 1:1.1 and the mean age was 14.2 ± 2.3 years (age range: 9.2-17.9 years). Thirty-nine percent of the enrolled patients had EE. The sensitivity and specificity of GerdQ (with a cutoff score of ≥7) to identify EE patients were 65.5% and 80%, respectively. The odds ratio of GerdQ for a cutoff score of 7 to identify EE was 7.6 (95% confidence interval = 2.6-21.9, p < 0.001)., Conclusion: For the identification of EE in children, the Chinese GerdQ had similar sensitivity and specificity to that used for adults. This questionnaire may be applied as a noninvasive screening tool., (Copyright © 2014. Published by Elsevier B.V.)

Objective: Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages., Methods and Results: Cultured THP-1 macrophages were treated with U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively., Conclusion: Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Rationale: Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis., Objective: We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis., Methods and Results: In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages., Conclusion: These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of this study was to determine whether ATP-binding cassette transporter A1 (ABCA1) was up-regulated by growth differentiation factor-15 (GDF-15) via the phosphoinositide 3-kinase (PI3K)/protein kinase Cζ (PKCζ)/specificity protein 1 (SP1) pathway in THP-1 macrophages., Methods and Results: We investigated the effects of different concentrations of GDF-15 on ABCA1 expression in THP-1 macrophages. The results showed that GDF-15 dramatically increased cholesterol efflux and decreased cellular cholesterol levels. In addition, GDF15 increased ABCA1 mRNA and protein levels. The effects of GDF-15 on ABCA1 protein expression and cellular cholesterol efflux were abolished by wither inhibition or depletion of PI3K, PKCζ and SP1, respectively, suggesting the potential roles of PI3K, PKCζ and SP1 in ABCA1 expression. Taken together, GDF-15 appears to activate PI3K, PKCζ and SP1 cascade, and then increase ABCA1 expression, thereby promoting cholesterol efflux and reducing foam cell formation., Conclusion: Our results suggest that GDF-15 has an overall protective effect on the progression of atherosclerosis, likely through inducing ABCA1 expression via the PI3K/PKCζ/SP1 signaling pathway and enhancing cholesterol efflux., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Atherosclerosis is a lipid disorder disease characterized by chronic blood vessel wall inflammation driven by the subendothelial accumulation of macrophages. Studies have shown that lipoprotein lipase (LPL) participates in lipid metabolism, but it is not yet known whether post-transcriptional regulation of LPL gene expression by microRNAs (miRNAs) occurs in vivo. Here, we tested that miR-467b provides protection against atherosclerosis by regulating the target gene LPL which leads to reductions in LPL expression, lipid accumulation, progression of atherosclerosis and production of inflammatory cytokines in apolipoprotein E knockout (apoE(-/-)) mice. Treatment of apoE(-/-) mice with intra-peritoneal injection of miR-467b agomir led to decreased blood plasma levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β and monocyte chemotactic protein-1 (MCP-1). Using Western blots and real time PCR, we determined that LPL expression in aorta and abdominal cavity macrophages were significantly down-regulated in the miR-467b agomir group. Furthermore, systemic treatment with miR-467b antagomir accelerated the progression of atherosclerosis in the aorta of apoE(-/-) mice. The present study showed that miR-467b protects apoE(-/-) mice from atherosclerosis by reducing lipid accumulation and inflammatory cytokine secretion via downregulation of LPL expression. Therefore, targeting miR-467b may offer a promising strategy to treat atherosclerotic vascular disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Percutaneous endoscopic gastrostomy (PEG) is widely accepted as the preferred procedure to establish long-term enteral feeding., Objective: To learn the long-term outcomes of the patients who have undergone PEG placement, we reviewed our experience with children who underwent this procedure in our institute., Methods: A total of 83 pediatric patients (42 males and 41 females), who were aged from 3 months to 20 years, underwent PEG insertion in National Taiwan University Hospital from January 2000 to April 2011. The underlying diseases of the patients receiving PEG were neurological dysfunction (n = 67), metabolic disorders (n = 9), gastrointestinal disease (n = 2), and congenital heart disease (n = 1). This procedure was performed under intravenous sedation or under general anesthesia. Prophylactic antibiotics were administered for 1 day. Tube feeding began 24 hours after the PEG placement. The body weight of the patients was recorded 1 day before PEG placement and at least 6 months after PEG placement., Results: The weight-for-age Z-score before and at 6 months after PEG placement were -1.5 ± 2.0 and -0.9 ± 2.1, respectively, which was statistically significant (paired t test, p = 0.006). The catch-up growth was recorded after PEG placement. Complications of PEG in our patients included cellulitis at the gastrostomy wound (n = 14), dislodgement of the tube (n = 17), and persistent gastrocutaneous fistula (n = 3). The PEG tube was removed permanently in seventeen patients because they resumed an adequate oral intake. During the follow-up period, 14 patients died of an underlying disease or infection., Conclusion: Our experience confirmed that PEG placement is a good long-term route for nutritional supply with no serious complications in children., (Copyright © 2013. Published by Elsevier B.V.)

In this study, a poly(methyl methacrylate) chip-based photocatalyst-assisted reduction device (PMMA chip-based PCARD) was developed as a reactor based on its excellent optical properties and ease of fabrication. Its transmittance of ultraviolet light at 365nm (UV365) was found to be as high as 92% using a PMMA of 2mm thickness. To optimize the vaporization efficiency, the effect of varying the depth of the geometry trenched on the PMMA-based chip was investigated. After optimization, it required only 29s of UV365 irradiation to vaporize the selenium (Se) species of interest. The PMMA-based chip was successfully used as an interfacing device for the hyphenation of high performance liquid chromatography (HPLC) separation and inductively coupled plasma-mass spectrometry (ICP-MS) detection. Additionally, under the optimized conditions for vaporization, using 1gL(-1) titanium dioxide nanoparticles (nano-TiO2) at pH 5, we found that Se(IV) and Se(VI) were converted quantitatively into volatile Se products. In addition, the optimized vaporization efficiency of the Se species of interest for the online HPLC/PMMA chip-based PCARD/ICP-MS system enabled us to achieve detection limits for Se(IV) and Se(VI) in the nanogram-per-liter range (based on 3σ). A series of validation experiments indicated that our proposed methods could be applied satisfactorily to the determination of inorganic Se species in environmental water samples., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background & Aims: Immunoprophylaxis reduces but does not completely eradicate hepatitis B virus (HBV) transmission. This prospective study aims at assessing the rate and risk factors of maternally transmitted HBV infection., Methods: We enrolled 303 mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg) under current immunization program. Maternal viral load was determined by a real-time PCR-based assay. The children were tested for HBsAg at 4-8 months and/or 1-3 years of age. Rates of HBV infection were estimated using a multivariate logistic regression model., Results: HBeAg-positive mothers (81/303, 26.7%) had higher viral loads than HBeAg-negative mothers (7.4 ± 1.9 vs. 2.7 ± 1.4 log10 copies/ml, p<0.0001). Ten children, born to HBeAg-positive mothers with high viral load (median, 8.4; range, 6.5-9.5 log₁₀ copies/ml), were chronically infected. After adjustment for maternal age, birth type, factors related to maternal-fetal hemorrhage, gestational age, infant gender, birth weight, timeliness of vaccination, and feeding practice, maternal viral load was significantly associated with risk of infection (adjusted odds ratio for each log₁₀ copy/ml increase, 3.49; 95% confidence interval (CI), 1.63-7.48; p=0.001). The predictive rates of infection at maternal viral load levels of 7, 8, and 9 log₁₀ copies/ml were 6.6% (95% CI, 0.5-12.6%; p=0.033), 14.6% (95% CI, 5.6-23.6%; p=0.001), and 27.7% (95% CI, 13.1-42.4%; p<0.001), respectively., Conclusions: Additional strategies to further reduce transmission should be considered in mothers with a viral load above 7-8 log₁₀ copies/ml., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the prognosis of three subgroups of locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy and platinum-based chemotherapy., Patients and Methods: Hundred and eighty-one consecutive patients with locoregionally advanced untreated nasopharyngeal carcinoma were retrospectively divided into three subgroups: locally advanced group (T3-4N0-1M0), regionally advanced group (T1-2N2-3M0) and the mixed group (T3-4N2-3M0). They were all treated with definitive intensity-modulated radiotherapy and platinum-based chemotherapy. Their prognosis were investigated and compared. Multivariate analysis was applied to identify the independent risk factors of study endpoints., Results: The 3-year locoregional control rates for locally advanced group, regionally advanced group, and the mixed group were 91.5%, 90.6% and 84.3% respectively, no significant difference was observed (P=0.656, P=0.429). The 3-year distant metastasis-free survival rates were 89.6%, 75.7% and 76.3%, respectively. The distant metastasis-free survival rate of the locally advanced group was significantly higher than the other two subgroups (P=0.028, P=0.028). The 3-year progression-free survival rates were 85.5%, 67.9% and 67.1% respectively with significance also favoring the locally advanced group (P=0.043, P=0.023). Nodal stage and the performance status were the independent risk factors of distant metastasis in the observed period., Conclusions: In the context of intensity-modulated radiotherapy and platinum-based chemotherapy, the locally advanced group had a better prognosis compared with the regionally advanced group and the mixed group. Treatment stratification may be based on nodal stage., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background & Aims: Hepatitis B virus (HBV) infection was hyperendemic in Taiwan before the implementation of the universal infant hepatitis B immunization program, which was launched in 1984. Five previous seroepidemiologic surveys were conducted at 0, 5, 10, 15, and 20 years after the launch of the vaccination program., Methods: We enrolled 3332 subjects younger than 30 years of age, with approximately 100 of them in each age cohort. Subjects were recruited voluntarily from schools and other institutions in Taipei, as in previous surveys. HBV seromarkers included hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). HBV DNA levels were measured in anti-HBc positive/HBsAg negative subjects (anti-HBc only)., Results: The HBsAg, anti-HBs, and anti-HBc seropositive rates were very different between subjects born after the program in 2009 and the baseline group in 1984 (0.9% vs. 10%, 55.9% vs. 24.5%, and 7.0% vs. 28%, respectively). In this 6th survey, we showed that HBsAg prevalence further decreased in the vaccinated cohorts. A positive maternal HBsAg status was found in 86% of vaccine failures. Serum HBV DNA was detected in 4.2% (6/142) of anti-HBc positive/HBsAg negative subjects, with a low level of HBV DNA. All of these six subjects' HBV were genotype C., Conclusions: The universal infant HBV immunization program in Taiwan has completed its 25-year follow-up and its efficacy in young adults is clear. The continued decrease in HBsAg prevalence suggests that the elimination of HBV infection is becoming a reality., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Mitochondrial DNA (mtDNA) deletion is a rare occurrence that results in defects to oxidative phosphorylation. The common clinical presentations of mtDNA deletion vary but include mitochondrial myopathy, Pearson syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. Here, we report the case of a 10-year-old boy who presented with progressive deterioration of his clinical status (which included hypoglycemia, short stature, sensorineural hearing loss, retinitis pigmentosa, and chronic gastrointestinal dysmotility) that progressed to acute deterioration with pancreatitis, Fanconi syndrome, lactic acidosis, and acute encephalopathy. Following treatment, the patient was stabilized and his neurological condition improved. Through a combination of histological examinations and biochemical and molecular analyses, mitochondrial disease was confirmed. A novel 3670-base pair deletion (deletion of mtDNA nt 7,628-11,297) was identified in the muscle tissue. A direct repeat of CTACT at the breakpoints was also detected., (Copyright © 2012. Published by Elsevier B.V.)

The roles of furin and intrahepatic cytokines in chronic heptatitis B virus (HBV) infection remain largely unknown. Here, we examined the relations between furin, IL-10, IL-12β, interferon (IFN)-γ, programed death (PD)-1, programed death ligand (PD-L)1, and the suppression of hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) biosynthesis. Liver biopsies were performed on 20 chronically HBV-infected (15 HBeAg-positive and 5 HBeAg-negative) patients to assess liver inflammation/fibrosis, and mRNA levels of furin, IL-10, IL-12β, IFN-γ, PD-1, and PD-L1 were assessed by quantitative real-time PCR. IFN-γ mRNA abundance was associated with lower furin mRNA levels and higher PD-1 and PD-L1 mRNA levels in liver tissue from HBeAg-positive patients. IL-10 and IL-12β mRNA levels positively correlated with IFN-γ expression levels (P < 0.05). PD-L1 and furin mRNA levels were further assessed in IFN-γ-stimulated hepatoma cell lines with (HepG2.2.15 cells) and without (HepG2 and Huh7 cells) HBV replication. IFN-γ enhanced PD-L1 expression in hepatoma cells. In HepG2.2.15 cells, IFN-γ further suppressed furin and HBeAg expression. Furin inhibition and knockdown in HepG2.2.15 cells also down-regulated HBeAg and HBsAg biosynthesis. These data suggest that IFN-γ modulates the inflammatory response to avoid excessive hepatocyte damage through the enhancement of PD-1/PD-L1 expression, whereas furin suppression may contribute to a reduction in HBeAg/HBsAg biosynthesis., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Initial poor graft function (IPGF) following orthotopic liver transplantation is a major determinant of postoperative survival and morbidity. Lactate clearance is a good marker of liver function. In this study, we investigated the clinical utility of early lactate clearance as an early and accurate predictor for IPGF following liver transplantation., Methods: This was a prospective observational study of 222 patients referred to the surgical intensive care unit (SICU) after orthotopic liver transplantation. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1500 IU/L within 72 hours after orthotopic liver transplantation. Early lactate clearance was defined as lactate at SICU presentation (hour 0) minus lactate at hour 6, divided by lactate at SICU presentation. The model for end-stage liver disease (MELD) score, Child-Pugh score and laboratory data including AST, ALT, total bilirubin (TB) and prothrombin time (PT) were recorded at SICU presentation and compared between the non-IPGF and IPGF groups. Receiver operating characteristic (ROC) curves were plotted to measure the performance of early lactate clearance, MELD score, Child-Pugh score, TB and PT., Results: IPGF occurred in 45 of the 222 patients (20.3%). The early lactate clearance in the non-IPGF group was markedly higher than that in the IPGF group (43.2+/-13.8% vs 13.4+/-13.7% P<0.001). The optimum cut-off value for early lactate clearance predicting IPGF was 24.8% (sensitivity 95.5%, specificity 88.9%). The area under the curve of the ROC was 0.961, which was significantly superior to MELD score, Child-Pugh score, TB and PT. Patients with early lactate clearance ≤24.8% had a higher IPGF rate (OR=169) and a higher risk of in-hospital mortality (OR=3.625)., Conclusions: Early lactate clearance can serve as a prompt and accurate bedside predictor of IPGF. Patients with early lactate clearance less than 24.8% are associated with a higher incidence of IPGF.

Objective: The increasing incidence of pediatric Crohn's disease (CD) is well known in Western countries in the last two decades. This study was conducted to delineate the trends of incidence during this period and clinical patterns of pediatric CD in Taiwan., Methods: All children admitted to National Taiwan University Hospital between 1990 and 2009 who met the Porto Criteria for CD were included. Annual enrollment and clinical characteristics were retrospectively reviewed. The incidence was calculated by dividing the number of index cases by total hospitalized pediatric cases to minimize the bias caused by the growing number of hospitalized patients there. We quoted data and statistics from the Department of Health, Executive Yuan, Taiwan, and Accounting and Statistics, Executive Yuan, Taiwan, to present the social-economic changes in Taiwan in the recent decades., Results: The cumulative hospital-based incidence of CD rose from 13.2 per 100,000 to 25.4 per 100,000 children admitted to this hospital in the past two decades. The median age of diagnosis in the first decade of this study was less than that of the second decade. The other study parameters, including gender, disease activity at diagnosis, duration from disease onset to diagnosis, anatomic location and disease behavior, and symptoms at diagnosis, were not different., Conclusions: This study showed that the hospital-based incidence of pediatric CD has been increasing in Taiwan in recent decades. Factors contributing to such an increase could be physicians' awareness of the disease, easier access to health care, and environmental factors., (Copyright © 2011. Published by Elsevier B.V.)

Background: Clinical features and treatment responses in pediatric patients with eosinophilic gastroenteritis are rarely reported. This study aimed to evaluate the clinical manifestations and outcome of eosinophilic gastroenteritis in children of Asian background., Methods: Between 1997 and 2009, 14 Taiwanese patients (nine boys and five girls), with median age of 8.3 years (range, 1.4-14.3 years), were diagnosed with eosinophilic gastroenteritis. The diagnosis was confirmed by the presence of gastrointestinal symptoms, peripheral eosinophilia, and a histology-proved biopsy. The clinical data and responses to medical treatment were analyzed., Results: Initial symptoms included abdominal pain (43%), anemia (36%), hypoalbuminemia (14%), recurrent vomiting (7%), bloody stool (7%), and growth failure (7%). Peripheral eosinophilia was present in 10 patients (71.4%) and positive stool occult blood in seven patients (50%). Endoscopic examination revealed ulcer disease in four patients (28.6%). The treatment included steroid alone, montelukast alone, steroid+montelukast, and steroid+montelukast+ketotifen. Among the patients treated with steroid, two (two of nine, 22%) had successfully tapered off steroid without recurring symptoms. Three patients (three of nine, 33%) had relapses after discontinuing steroid, three (three of nine, 33%) still required low-dose steroid, and one lost to follow-up. There was no relapse in the four patients treated with montelukast alone., Conclusions: A high percentage of patients presented with gross or occult gastrointestinal bleeding with or without abdominal pain. Endoscopic biopsy is necessary for diagnosis. Steroid was the mainstay treatment for active diseases; montelukast was also effective for the disease or as a maintenance therapy in this study., (Copyright © 2011. Published by Elsevier B.V.)

Background: Untreated autoimmune hepatitis (AIH) can develop into liver cirrhosis, with potentially fatal outcomes. Viral hepatitis in children was endemic in Taiwan before universal hepatitis B vaccination, but AIH has rarely been reported in Taiwanese children. We performed this retrospective study to characterize the clinical features of AIH in Taiwanese children., Methods: We enrolled children with AIH, based on the revised scoring system of the International Autoimmune Hepatitis Group (IAIHG) from 383 children hospitalized with hepatitis from January 2000 to April 2008. Other etiologies of hepatitis were excluded., Results: There were three definite and six probable AIH cases. The incidence of AIH among children hospitalized with hepatitis was 2.3%. Eight children had other autoimmune diseases, including systemic lupus erythematosus (SLE) (6), discoid lupus erythematosus (DLE) (1), and autoimmune polyendocrinopathy syndrome type 1 (1). Another had biliary atresia, and AIH developed after cadaveric liver transplantation. Antinuclear antibodies ranged from 1:160-1:2560. Peak alanine aminotransferase (ALT) values were 546 +/- 188 U/L (mean +/- SD). Jaundice occurred in four patients. Liver histology in the three definite AIH patients showed chronic hepatitis with predominantly lymphoplasmacytic infiltrates in portal areas, with prominent interface activity. Treatment included prednisolone, azathioprine, and/or cyclosporine. All patients survived. ALT fell to <60 U/L after treatment. Hepatitis relapse occurred in one patient., Conclusion: AIH in Taiwanese children is commoner than previously thought. It is associated with other autoimmune diseases and may occur before, simultaneously with, or after other autoimmune diseases. Children with liver transplants are also at risk of AIH.

Two non-self-complementary 17-mer double-stranded DNA (dsDNA) with four different central base pairs were designed to systematically investigate the binding affinity and sequence specificity of berberine with dsDNA by capillary zone electrophoresis (CZE). The data analysis with the Kenndler model proved only low affinity between dsDNA and berberine and suggested some weak binding preference of berberine for AATT-containing to GGCC-containing dsDNA. The binding constant, Ka, between berberine and dsDNA(AB) was about (1.0 +/- 0.7) x 10(3) M(-1). In addition, the separation of single-stranded DNA (ssDNA) from dsDNA under simple electrophoretic conditions enabled CZE to be a potentially alternative tool to check the extent of DNA annealing, which is usually done by the time-consuming and labor-intensive slab electrophoresis.

A binuclear complex [(phen)Cu(mu-bipp)Cu(phen)](ClO(4))(4), where phen=1,10-phenanthroline and bipp=2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10-phenanthroline, has been synthesized and its interaction with calf-thymus DNA in the buffer containing 5mM Tris and 50mM NaCl has been studied by means of electronic absorption titration, luminescence titration and viscometric measurements. The absorbance of the complex in the range of 320-400 nm, which is mainly based on bipp showed no obvious change upon addition of DNA, while the peak at 270 nm, which is determined by both phen and bipp decreased by up to 18%. The emission band of the complex around 360 nm decreased remarkably in presence of DNA. The emission quenching of this complex by [Fe(CN)(6)](4-) was depressed greatly when bound to DNA. The relative viscosity of DNA was increased by this complex more significantly than a bipp directed intercalating reagent. These results suggest that this complex binds to calf thymus DNA by intercalation of the two phenanthrolinecopper terminals. The apparent intrinsic binding constant of the complexes with DNA was 1.6 x 10(4)M(-1) as determined by UV-visible titration.

All-trans retinoic acid (ATRA) affects cell proliferation, differentiation and apoptosis through its receptors, RARs and RXRs. Besides these, other receptors such as orphan receptor TR3, are also involved in the regulatory process of ATRA. However, how different receptors function in response to ATRA is still largely unknown. In the present study, we found that formation of TR3/RXRalpha heterodimers in the nucleus and their subsequent translocation into the cytoplasm, in association with regulation of apoptosis-related proteins Bcl-2, Bcl-xl and Bax, was critical for apoptosis induction by ATRA in breast cancer cells MCF-7. When such translocation was blocked by Leptomycin B (LMB), ATRA-induced apoptosis was consequently abolished. However, in ATRA-induced gastric cancer cells MGC80-3, RXRalpha heterodimerised with RARalpha but not with TR3, and remained in the nucleus exerting its effect on cell cycle regulation. When transfected with antisense-RARalpha, MGC80-3 cells changed from ATRA-sensitive to ATRA-resistant and most cells were arrested in the S phase, implying the importance of RARalpha in cell cycle regulation. Furthermore, we demonstrated that the effects of ATRA depend on the relative levels of TR3, RARalpha and RXRalpha expression in cancer cells. In ATRA-induced MCF-7 cells, highly expressed TR3 favours the formation of TR3/RXRalpha and promotes the TR3/RXRalpha signalling pathway causing apoptosis; while in ATRA-induced MGC80-3 cells, high expression of RARalpha favours the formation of RARalpha/RXRalpha and promotes the RXRalpha/RARalpha signalling pathway in mediating cell cycle regulation. In conclusion, these results reveal the novel mechanism that cellular expression and location of protein is associated with diverse signalling transduction pathways and the resultant physiological process.

A simple and robust flow injection on-line microdialysis system for multivessel drug dissolution testing is described. Microdialysis probes were used for sampling from the dissolution media. A stopped-flow dialysis mode with a 50-s stopped-flow period followed by 10-s injection at a perfusion rate of 2.8 ml min(-1) for each probe was used to achieve high resolution of dissolution events using relatively simple equipment and operation. The precisions obtained for simultaneous monitoring of dissolution profiles for six tablets were all better than 0.9% (RSD n=80) and the overall sampling frequency of the system was 360 and 60 h(-1) for each test vessel. The dissolution profiles of isoniazid fast-release tablet from three sources were determined to demonstrate the performance of the system.

A sequential injection system for the determination of mercury by vapor generation atomic absorption spectrometry (VGAAS) using tetrahydoborate reductant was developed, characterized by prevention of sample and reagent mixing in the holding coil using small air segments and initiation of the vapor generation in a flow-through gas-liquid separator. Extremely small volumes of reductant of 15-30 mul (0.2-1.0% NaBH(4)) and sample acidity as low as 0.05 mol l(-1) HCl were sufficient for achieving performance similar to flow injection (FI) VGAAS systems. A sample throughput of 90 h(-1) was achieved with 400 mul samples with a precision of 2.0% RSD at 10 mug l(-1)Hg, and a detection limit of 0.1 mug l(-1) (3sigma). Reagent consumption was reduced by a factor of 25 in comparison to the FI-VGAAS system. Good agreement with the certified value was obtained for the determination of mercury in seawater in a standard reference sample.

Preparation of some new mono- and bishydrazones which possess the ferroin chromophoric group is described, together with results of spectrophotometric studies of their chelation reactions with iron(II), copper(I), cobalt(II), nickel(II) and zinc(II). Several of the new compounds show promise as chromogenic reagents for these metals. The results are also of interest with regard to structure-reaction relationships.

Sixty-one primiparous Sprague-Dawley female rats were fed an adequate diet containing 5% protein (experiment 1) or 8% protein (experiment 2) throughout gestation. Low dietary protein reduced individual pup birth weight in both experiments (P less than .01 in experiment 1 and P less than .10 in experiment 2) and drastically decreased early postnatal survival in experiment 1. Weaning weight of survivors was reduced by gestation protein deprivation in experiment 1 but no in experiment 2. Male and female progeny surviving to weaning in experiment 1 and randomly selected progeny from each maternal treatment in experiment 2 were caged individually and fed ad libitum and nutritionally adequate corn-soybean meal-type diet throughout the entire life span. Body weight were recorded monthly beginning in young adulthood and continuing until death. Life span (in days) was recorded for each rat. Mature body weight of male and female progeny of dams fed restricted protein during gestation was less in both experiments than that of offspring from dams fed an adequate diet (P less than .01). There was no effect of prenatal nutrition on life span in either experiment, but females lived significantly longer than males in both experiments (p less than .05). It is concluded that maternal protein restriction during gestation of a magnitude large enough to reduce pup birth weight causes a significant reduction in mature body size of the progeny without affecting longevity in the rat.

Preparation and metal-ion chromogenic properties of five new 2,4,6-trisubstituted pyrimidines containing pyridyl and methyl or phenyl groups are described. All five exhibit specific chromogenic reactions with copper(I), and two possess suitable characteristics for use as sensitive spectrophotometric copper reagents. The results obtained are also of interest in designing related chromogenic reagents.