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Objectives To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. Study design The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. Results A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. Conclusions Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.

Aim To investigate the effect of changes in fasting plasma glucose (FPG) variability, as assessed by 2-year trajectories of FPG variability, on mortality risk in patients with type 2 diabetes (T2D). Methods From 2009 to 2012, outpatients with T2D, aged>18 years, were enrolled from a medical centre. FPG was measured every 3 months for 2 years in 3569 people. For each of the eight 3-month intervals, FPG variability and means were calculated, with variability defined as the coefficient of variation of FPG. Also, trajectories of FPG variability and means were determined separately, using group-based trajectory analysis with latent class growth models. These models were fitted using the SAS Proc Traj procedure. The primary outcome was all-cause mortality, which was followed-up to the end of 2014. Results Five distinct trajectories of FPG variability (low, increasing, fluctuating, decreasing and high) and means (well controlled, stable control, worsening control, improving control and poor control) were established. The five trajectories of mean FPG were all associated with the same mortality risk. In contrast, in comparison to the low FPG variability trajectory, the fluctuating, decreasing and high variability trajectories all had significantly higher risks of mortality, with respective hazards ratios of 2.63 (95% CI: 1.40–4.93; P = 0.003), 2.78 (95% CI: 1.33–5.80; P = 0.007) and 4.44 (95% CI: 1.78–11.06; P = 0.001) after multivariable adjustment. Conclusion Changes in FPG variability were independently associated with increased mortality risk in patients with T2D.

A titratable thermoplastic mandibular advancement devices (MAD) is clearly an effective treatment option in some patients with obstructive sleep apnea (OSA). Determining which patients may be more likely to respond to treatment with thermoplastic MADs and to adhere to treatment would be of obvious clinical relevance. This was an experimental descriptive study (N = 60). Patients with OSA were instructed to wear a titratable thermoplastic MAD for 3 months. Treatment success was defined as a ≥50% reduction from baseline in the apnea-hypopnea index (AHI) or AHI

Background: Transcatheter closure of congenital coronary artery fistulas (CCAFs) is an alternative therapy to surgery; however, data regarding transcatheter closure for CCAF with a giant coronary artery aneurysm (CAA) in pediatric patients are still limited due to the rarity of the disease. We aimed to evaluate the efficacy and safety of transcatheter closure for CCAF with a giant CAA in a pediatric population at a single center. Methods: Medical records of pediatric patients (

Background/Purpose Maximal bite force of the jaw can cause thorough food chewing and result in good digestion. Bite force is related to the health of the masticatory muscles. Muscle force is frequently affected by obesity in adolescence, however, little is known about how obesity influences the maximum bite force and the difference between genders. Methods Five hundred and seventy-seven adolescent students (292 girls and 285 boys), aged 13–16 years, from central Taiwan were recruited for a cross-sectional study in 2009. The maximum bite force, hand strength, triceps skin-fold fat thickness, serum level of testosterone, and body mass index (BMI) were measured. Dental health was evaluated based on malocclusion and dental caries. Results Bite force in girls was highest in the obese group (32.49 ± 19.13 kg, mean ± standard deviation), whereas in boys it was higher in the overweight group (41.89 ± 19.3 kg) than in the obese group (33.21 ± 17.12 kg). The prevalence of obesity was twofold higher in boys (14.39%) than in girls (7.88%). The mean serum level of testosterone increased with BMI in girls ( p = 0.0172), whereas it decreased with BMI in boys ( p = 0.0014). The relationships of serum testosterone level and bite force with BMI were similar in the two gender groups. Conclusion The maximum bite force decreased in obese boys but increased in obese girls, which may be due to the sensitivity to testosterone being modulated by the fat level.

This study identified 37,810 patients with anxiety or sleep disorder (mean age=53.2 years, SD=16.0 years) who had zolpidem prescribed for at least 2 months from January 1, 2000 through December 31, 2009. Another non-zolpidem cohort was selected by 1:1 matching with the zolpidem cohort on the estimated probability (propensity score) of being treated. The zolpidem cohort had a higher incidence of benign brain tumors compared with the non-zolpidem cohort, particularly for elderly patients. The matched propensity score analysis showed that the highest risk of benign brain tumors occurred in participants with zolpidem exposure ≥520 mg/year (hazard ratio=1.85, 95% confidence interval=1.21-2.82) compared with those not taking zolpidem.

The pathogenesis of infantile spasms remains unclear. DNA methylation may play a pivotal role in the development of some types of neurological diseases, such as epilepsy. In this study, we aimed to investigate the relationship between global DNA methylation of peripheral blood leukocytes and cryptogenic infantile spasms. DNA from peripheral blood leukocytes was extracted from 20 patients with cryptogenic infantile spasms and 20 gender and age matched healthy controls. Global DNA methylation percentage of peripheral blood leukocytes was measured using a global DNA methylation quantification kit. Global DNA methylation levels of peripheral blood lymphocytes in patients with cryptogenic infantile spasms (23.4 ± 20.0%) were significantly lower than those in healthy controls (46.8 ± 8.4%). Furthermore, we did not find any association between the levels of DNA methylation and effectiveness of Adrenocorticotropic hormone treatment. Our study demonstrates that global DNA hypomethylation of peripheral blood lymphocytes is correlated with infantile spasms. This finding provides information for better understanding of the pathogenesis of infantile spasms.

Background/Purpose: Spaced primary dentition plays a critical role in the eruption of permanent teeth and the establishment of ideal occlusion. A lack of these spaces in deciduous dentition may result in disproportionate jaw and tooth sizes. Additionally, spaced primary dentition is significantly affected by ethnic factors. However, few of these studies have been conducted in Asia. The purpose of this study was to investigate the prevalence of spaced primary dentition in Taiwan. Methods: One hundred and forty-seven 3- to 6-year-old Taiwanese children (58 girls and 89 boys) were recruited for a cross-sectional study. Primate and interdental spaces were recorded by intraoral photos. The prevalence of spaced dentition was evaluated. The interpersonal agreement of spaced dentition between the upper and lower arches was also assessed. Results: Most of the subjects had spaced primary dentition. The prevalence of primate space was 83.7% in the upper arch and 61.2% in the lower arch, whereas the prevalence of interdental space was 44.2% in the upper arch and 53.1% in the lower arch. The prevalence rates of interdental space and upper primate space were significantly higher in boys than in girls. Interdental spaces of the lower arch increased with age. Conclusion: Ethnic factors can affect the ratio of spaced dentition. Most of the 3- to 6-year-old Taiwanese children have spaced dentition. The boys have higher incidence of spaced dentition than the girls. Furthermore, primate space is more frequently found in the upper arch than in the lower arch, whereas interdental space is reversed. Keywords: Spaced dentition, Primary dentition, Interdental space, Primate space, Dental arch

The present study aims to explore the role of stromal cell-derived factor-1α (SDF-1α)/stromal cell-derived factor receptor-4 (CXCR4) signaling pathway to the clinicopathological features and prognosis of patients with nasopharyngeal carcinoma (NPC). From January 2009 to December 2010, 102 patients with NPC and 80 patients with chronic nasopharyngitis were enrolled for the study. Immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting were employed to determine the expressions of SDF-1α and CXCR4 proteins in NPC tissues and chronic nasopharyngitis tissues. Chi-square test was conducted to analyze the associations of the expressions of SDF-1α and CXCR4 proteins with the clinicopathological features of NPC patients. Spearman rank correlation analysis was used to analyze the correlation between the SDF-1α protein expression and CXCR4 protein expression. The mRNA and protein expressions of SDF-1α and CXCR4 in NPC tissues were significantly higher than those in chronic nasopharyngitis tissues. The expressions of SDF-1α and CXCR4 proteins showed associations with T staging, N staging, tumor node metastasis (TNM) staging, skull base invasion, and cervical lymph node metastasis of NPC patients. Compared with NPC patients showing negative expressions of SDF-1α and CXCR4 proteins, those with positive expressions of SDF-1α and CXCR4 proteins had a significantly shorter survival time. SDF-1α protein, CXCR4 protein, EBV-IgG status, T staging, N staging, TNM staging, skull base invasion, and cervical lymph node metastasis were independent risk factors for the prognosis of NPC. The findings indicated that SDF-1α/CXCR4 signaling pathway might be associated with the clinicopathological features and prognosis of patients with NPC.

Background & aims Patients with cholangitis may exhibit repeated and chronic inflammation of the biliary tract despite successful medical or surgical treatments. This nationwide cohort study examined the association between cholangitis and the subsequent development of acute coronary syndrome (ACS). Methods We identified a cohort of 37 676 patients who were diagnosed with cholangitis between January 1998 and December 2010, and a comparison cohort of 150 704 subjects frequency matched by age, sex, and index year after excluding comorbidities for ACS. Both cohorts were followed until the end of 2010 to measure the incidence of ACS. Both incidence rate ratios and hazard ratios of ACS were estimated by age and sex. Results Sex-specific analysis showed that males were at a higher incidence of ACS than females in both groups with (16.2 vs 11.5 per 10 000 person-years) and without (18.7 vs 12.5 per 10 000 person-years) cholangitis. The incidence of ACS also increased with age no matter having or not having cholangitis. The age stratified analysis revealed that the risk of ACS was significantly higher in patients with cholangitis younger than 65 years old. The multivariable Cox proportional hazard model demonstrated that cholangitis was significantly associated with ACS (adjusted hazard ratio [HR] = 1.18; 95% confidence interval [CI], 1.03–1.35) after adjusting age and sex in the model. Conclusions This study suggests that patients with cholangitis are at an elevated risk of ACS. Awareness of the potential ACS risk for patients with cholangitis is important for patients and clinicians.

This study explored the feasibility effect and safety of the limb stimulation (LS) for the treatment of neonatal apnea (NAP). The cases of 30 eligible premature infants with NAP were included in this retrospective study. These cases were equally divided into an intervention group (n = 15) and a control group (n = 15). The infants in both groups received caffeine treatment. Moreover, cases in the intervention group also received LS for a total 30 hours, while the subjects in the control group did not receive LS during this period. The primary outcome included apnea frequency (number of episodes per 24 hours), and apnea rate. The secondary outcomes consisted of desaturation (number of episodes per 24 hours), and heart rate (beats per minute). Additionally, adverse events were also documented during the treatment period. After treatment, LS did not show better outcomes in apnea frequency (P = .48), apnea rate (P = .33), desaturation (P = .55), and heart rate (P = .41). Furthermore, no significant differences of all adverse events were found between 2 groups. The results of this pilot study demonstrated that LS might be not efficacious for premature infants with NAP.

Background Diabetic neuropathy is a common complication in patients with type 2 diabetes. However, the prevalence of painful diabetic polyneuropathy (PDPN) have been less studied. We examined the prevalence and risk factors of PDPN in outpatients with type 2 diabetes in an ethnic Chinese population. Methods This retrospective study enrolled 2358 outpatients with type 2 diabetes who had completed the Douleur Neuropathique en 4 Questions (DN4) questionnaire from January 2013 to October 2013. Patients with a total score ≥ 4 were defined as having PDPN. Results In all, 179 patients were diagnosed as having PDPN with a score of 4.49 on the DN4 questionnaire, compared with 0.66 for patients without PDPN. After adjusting the possible confounding factors, the risk of painful neuropathy was increased in the group without physical activity (Odds ratio 3.38, 95% CI 1.54–9.79), and in the group with macroalbuminuria (Odds ratio 2.31, 95% CI 1.44–3.73). Besides, there was a joint effect of macroalbuminuria and no physical activity habit on PDPN risk. Conclusions The prevalence of PDPN was 7.6% among our outpatients with type 2 diabetes. Less physical activity and albuminuria, respectively, increased the risk of PDPN and had a joint effect.

Few studies involving human participants have been conducted to investigate the effect of orthodontic treatment on alveolar bone density around the teeth. Our previous study revealed that patients who received 6 months of active orthodontic treatment exhibited an ∼24% decrease in alveolar bone density around the teeth. However, after an extensive retention period following orthodontic treatment, whether the bone density around the teeth can recover to its original state from before the treatment remains unclear, thus warranting further investigation. The purpose of this study was to assess the bone density changes around the teeth before, during, and after orthodontic treatment. Dental cone-beam computed tomography (CBCT) was used to measure the changes in bone density around 6 teeth in the anterior maxilla (maxilla central incisors, lateral incisors, and canines) of 8 patients before and after orthodontic treatment. Each patient underwent 3 dental CBCT scans: before treatment (T0); at the end of 7 months of active orthodontic treatment (T1); after several months (20–22 months) of retention (T2). The Friedman test was applied to evaluate the changes in the alveolar bone density around the teeth according to the 3 dental CBCT scans. From T0 to T1, a significant reduction in bone density was observed around the teeth (23.36 ± 10.33%); by contrast, a significant increase was observed from T1 to T2 (31.81 ± 23.80%). From the perspective of the overall orthodontic treatment, comparing the T0 and T2 scans revealed that the bone density around the teeth was relatively constant (a reduction of only 0.75 ± 19.85%). The results of the statistical test also confirmed that the difference in bone density between T0 and T2 was nonsignificant. During orthodontic tooth movement, the alveolar bone density around the teeth was reduced. However, after a period of bone recovery, the reduced bone density recovered to its previous state from before the orthodontic treatment. However, the bone density around ∼10% of the teeth in this region could not recover to 80% of its state from before the orthodontic treatment.

This study investigated the effects of gender on the three-dimensional (3D) bone mineral density (BMD) and micromorphology of the trabeculae of matured autogenous bone grafts after sinus floor augmentation, and compared them to those of adjacent native bone. Ten bone biopsy samples were removed from the implant placement areas of patients who had received second-stage sinus floor augmentation, and analyzed by microcomputed tomography. BMD phantoms with two calcium hydroxyapatite densities (0.25 and 0.75 g/cm3) were used to determine the BMD of the grafted and native bone samples. The 3D structural parameters of the trabeculae, including percentage of bone volume (bone volume/tissue volume, BV/TV), trabecular thickness (Tb.Th), trabecular number, trabecular separation, trabecular pattern factor (Tb.Pf), and structure model index, were analyzed between males and females and between grafted bone and native bone. No significant gender-specific differences in BMD and 3D trabecular structure of either native or grafted bone were found (P > 0.05). Compared to the adjacent native bone, the autogenous grafted bone exhibited lower BV/TV and Tb.Th as well as a higher Tb.Pf (P

Objective The purpose of this study was to determine the relationships and differences in three-dimensional (3D) bone mineral density (BMD) and microtrabecular structures between autogenous bone grafts and their adjacent native bone after a healing period following maxillary sinus augmentation. Materials and methods Nine rod-shaped human bone biopsy samples were taken from patients receiving two-stage sinus augmentation therapy in implantation areas and analyzed using microcomputed tomography (micro-CT). Before micro-CT scanning, two BMD phantoms were placed near to the bone biopsy samples for executing BMD calculations of the grafted and native bone samples. In addition, 3D structural parameters of the trabeculae were analyzed for both the grafted and native bone, including percentage of bone volume [bone volume (BV)/tissue volume (TV)], bone-specific surface [bone surface (BS)/BV], trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular pattern factor (Tb.Pf), and structure model index (SMI). Results No significant correlations with regard to BMD and trabecular-structure parameters were found between native bone and grafted bone; however, BS/BV and Tb.Pf were higher and Tb.Th and Tb.Sp were 37.35% and 12.74% lower in grafted bone than in native bone. For grafted bone, there were significant correlations (P

The object of this study was to evaluate the relationship between changes in the alveolar bone density around the teeth and the direction of tooth movement by using cone-beam computed tomography (CBCT). CBCT was used to measure the bone densities around six maxilla anterior teeth before and after 7 months of orthodontic treatment in eight patients. Each root was divided into three levels (cervical, intermediate, and apical) to determine whether the bone density change varied with the tooth level. Moreover, each level was divided into four regions (palatal, distal, mesial, and buccal sides). Three-dimensional computer models of the maxilla before and after orthodontic treatment were created to detect the direction of tooth movement. The percentage for all 144 samples [8 (patients) × 6 (teeth) × 3 (levels)] in which the side (palatal, distal, mesial, or buccal sides) of maximum bone density reduction (before and after orthodontic treatment) coincided with the direction of tooth movement was calculated; this was referred to as the "coincidence percentage". The bone density around the teeth reduced by 24.3 ± 9.5%. The average coincidence percentage for the eight patients was 59.0%. The coincidence percentages for the eight patients were 62.5%, 62.5%, and 52.1% at the cervical, intermediate, and apical levels, respectively. The obtained results demonstrate that the direction of tooth movement is associated with the side of maximum bone density reduction, and that CBCT is a useful approach for evaluating bone density changes around teeth induced by orthodontic treatment.

Shu-shui Wang , Jiao Rao , Yu-fen Li , Zhi-wei Zhang ⁎, Guo-hong Zeng ⁎⁎ a Department of Pediatric Cardiology, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Science/Guangdong General Hospital, No. 96, Dongchuan Rd, Guangzhou City, Guangdong Province 510100, PR China b Department of Heart Center, Guangdong Women and Children Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Science/Guangdong General Hospital, PR China

Over the last 25 years, asthma has emerged as an increasingly important public health problem (Anderson et al. 1994; Rappaport and Boodram 1998). The pathogenesis and etiology of asthma is complex and not fully understood. Although a rapid rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic, genetic susceptibility to environmental stressors is also likely to influence the occurrence of asthma (Blumenthal 2005; Cookson 2002; Hemminki et al. 2007). Evidence suggests that members of the glutathione S-transferase (GST) superfamily contribute to asthma pathogenesis. We have previously reported that GSTM1 is associated with asthma risk in children exposed to tobacco smoke (Gilliland et al. 2002b). The GST superfamily includes a number of additional candidate susceptibility genes for asthma because several members, including GSTP1, are expressed in the respiratory tract and function in processes implicated in asthma pathogenesis, including oxidant defenses, xenobiotic metabolism, and detoxification of hydroperoxides (Strange et al. 2001). DNA sequence variants in the GSTP1 locus may contribute to susceptibility to oxidative stress and airway inflammation, which are key processes in asthma pathogenesis. A functional sequence variant in GSTP1 at codon 105 (Ile105Val) has been associated with asthma and susceptibility to the adverse effects of tobacco smoke and ambient air pollution in several studies (Aynacioglu et al. 2004; Ercan et al. 2006; Fryer et al. 2000; Gilliland et al. 2002a, 2004; Hemmingsen et al. 2001; Lee et al. 2004, 2005; Mapp et al. 2002; Palmer et al. 2006; Spiteri et al. 2000; Tamer et al. 2004). Although evidence indicates a role of the GSTP1 Ile105Val variant in asthma, the effect of other common variants in GSTP1 coding and promoter region and the joint effects with tobacco-smoke exposure have yet to be fully determined. The human genome is characterized by regions of strong linkage disequilibrium (LD) that have been labeled as haplotype blocks by Gabriel et al. (2002). The common genetic variation across the region can be predicted using only a subset of all single nucleotide polymorphisms [haplotype tagging SNPs (htSNPs)] (Stram et al. 2003). These can be used to impute haplotypes and provide an indirect assessment of potential common causal variants that may not have been genotyped. To further investigate the effect of common GSTP1 variants to asthma occurrence and susceptibility to tobacco smoke, we examined associations between common GSTP1 haplotypes, tobacco-smoke exposure, childhood asthma, and related symptoms among participants in the Children’s Health Study.

BACKGROUND: Organophosphorus pesticides are widely used throughout the world. Because of their ease of availability, organophosphorus compounds are commonly used for self-poisoning in developing countries. The acute effects of exposure to organophosphorus pesticides are well known, but the chronic effects are unclear. Recent studies suggest that abnormalities of the central and peripheral nervous systems persisted for up to 5 years after acute poisoning due to a single large dose of organophosphates (OPs). However, the long-term effects on cardiovascular diseases are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: An OPs-exposed cohort (N = 7,561) and an age- and gender-matched control cohort (N = 30,244), both identified from the National Health Insurance Research Database, were compared. We utilized the multivariable Cox proportional model to estimate the risks of developing arrhythmia, coronary artery disease (CAD) and congestive heart failure (CHF). The patients with acute poisoning from OPs had higher incidence rates of arrhythmia (5.89 vs. 3.61 per 1,000 person-years), CAD (9.10 vs. 6.88 per 1,000 person-years), and CHF (3.89 vs. 2.98 per 1,000 person-years) compared with that of the non-OPs poisoning cohort, with a crude subhazard ratio (SHR) of 1.40, 1.13, and 1.12, respectively. Additionally, a significantly higher risk of arrhythmia was observed in the OPs poisoning cohort (adjusted SHR = 1.25) compared with the non-OPs poisoning cohort, particularly in male patients (adjusted SHR = 1.33) and those under 49 years of age (adjusted SHR = 3.16). After accounting for the competing risks of death, there was a higher risk of arrhythmia and CAD during a three year follow-up period (adjusted SHR = 1.50 for arrhythmia; adjusted SHR = 1.10 for CAD). We also found an adjusted SHR of 1.36 associated with developing CHF after 6 years of follow-up for OPs poisoning cohort. CONCLUSIONS: Acute OPs poisoning may continuously impact human health through mechanisms that are unclear. Any supportive measurements that could contribute to a reduction in the risk of heart disease may be beneficial in cases of OPs poisoning survivors. Language: en

Oral squamous cell carcinoma (OSCC) constitutes >90% of oral cancers and is the sixth most common malignancy among males worldwide and the fourth leading cause of death due to cancer among males in Taiwan. However, most patients do not receive a diagnosis of OSCC until the late stages, which have a lower survival rate. The use of molecular marker analysis to identify early-stage OSCC would permit optimal timing for treatments and consequently prolong survival. The aim of this study was to identify biomarkers of OSCC using the Illumina GoldenGate Methylation Cancer Panel, which comprised a total of 1,505 CpG sites covering 807 genes. Samples of buccal mucosa resected from 40 OSCC patients and normal tissue samples obtained from 15 patients (normal mucosa from OSCC patients or from patients undergoing surgery unrelated to OSCC) were analyzed. Fms-related tyrosine kinase 4 (FLT4) methylation exhibited a perfect specificity for detecting OSCC, with an area under the receiver operating characteristic curve of 0.91 for both all-stage and early-stage OSCC. Methylation of 7 genes (ASCL1, FGF3, FLT4, GAS7, KDR, TERT, and TFPI2) constitutes the top-20 panels for detecting OSCC. The top-20 panels for detecting early-stage OSCC contain 8 genes: ADCYAP1, EPHA7, FLT4, GSTM2, KDR, MT1A, NPY, and TFPI2. FLT4 RNA expression and methylation level were validated using RT-PCR and a pyrosequencing methylation assay. The median level of FLT4 expression was 2.14-fold for normal relative to OSCC tissue samples (P < 0.0001). Among the 8 pyrosequenced FLT4 CpG sites, methylation level was much higher in the OSCC samples. In conclusion, methylation statuses of selected genes, and especially FLT4, KDR, and TFPI2, might be of great potential as biomarkers for early detection of buccal OSCC.

Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is usually estimated by the Friedewald formula (FF) calculated from three parameters, namely, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). We aimed to develop a new and simple formula (NF) for LDL-C estimation.This cross-sectional study enrolled two study populations (a testing group, n=16,749, and a validation group, n=4940). Linear regression analysis was used in the testing group to investigate the association between measured LDL-C (mLDL-C) and TC concentration, and was verified in the validation group.The NF yielded an estimated LDL-C (eLDL-C) equal to 0.75×total cholesterol–0.6465 (mmol/L). For the subjects with TC between 2.58 and 7.74 mmol/L, the difference between mLDL-C and eLDL-C using the NF was less than that from the FF (testing group: –0.04 to –0.20 vs. –0.28 to –0.38 mmol/L; validation group: 0.01 to –0.12 vs. –0.23 to –0.30 mmol/L; p7.74 mmol/L, respectively.In the Chinese population, the accuracy of eLDL-C measurement with the NF was better than that with the FF, especially in subjects with TC levels between 2.58 and 7.74 mmol/L. The NF is simple and may be used for screening as well as for follow-up of patients on lipid lowering agents.

Secondhand tobacco smoke (SHS) and traffic-related air pollutants are associated with asthma and allergy. Diesel exhaust particles (DEPs) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species. Glutathione S-transferases (GSTs) metabolize reactive oxygen species and detoxify electrophilic xenobiotics present in SHS and DEPs.We tested the hypotheses that functional GSTM1-null genotype and GSTP1 codon 105 variants (Ile105 and Val105) are determinants of allergic responses to SHS, and that responses to SHS and DEPs are correlated.In a randomized, placebo-controlled crossover trial, 19 ragweed allergen-sensitive subjects who had previously participated in a DEP trial were challenged intranasally with allergen after having been exposed to either clean air or SHS at separate visits. Nasal allergen-specific IgE, histamine, IL-4, and IFN-gamma levels were measured before and after allergen challenge.Individuals with GSTM1-null or GSTP1 Ile105 genotypes showed larger nasal responses to allergens with SHS compared with clean air. GSTM1-null subjects had a larger increase in IgE than GSTM1-present subjects (median, 173.3 vs. 46.7 U/ml; p = 0.03), and the Ile105 GSTP1 genotype subjects had increased histamine (median, 10.2 vs. 4.6 nM; p = 0.01) after SHS plus allergen challenge. Responses to SHS and DEPs were correlated. Enhancement of IgE and histamine was greatest in the subjects with both the GSTM1-null and GSTP1 Ile/Ile genotypes.GSTM1 and GSTP1 are important cytoprotective factors that reduce SHS and DEP exacerbation of allergic responses.

Rationale: Tumor necrosis factor (TNF) mediates a spectrum of airway inflammatory responses, including those to air pollutants, and is an asthma candidate gene. One TNF promoter variant (G–308A) affects expression of TNF and has been associated with inflammatory diseases; however, studies of asthma have been inconsistent. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the −308 TNF polymorphism with asthma may vary by ozone exposure and variants of oxidant defense genes glutathione-S-transferase (GST) M1 and GSTP1. Objectives: To investigate the association of TNF G–308A with asthma and wheezing and to determine whether these associations vary with ozone exposure and GSTM1 and GSTP1 genotype. Methods: We studied associations of TNF–308 genotype with lifetime and current wheezing and asthma among 3,699 children in the Children's Health Study. We examined differences in associations with community ozone and by GSTM1 null and GSTP1 105 Ile/Val (A105G) genotype. Results: Children with TNF–308 GG had decreased risk of asthma (odds ratio, 0.8; 95% confidence interval, 0.7–0.9) and lifetime wheezing (odds ratio, 0.8; 95% confidence interval, 0.7–0.9). The protective effects of GG genotype on wheezing outcomes were of greater magnitude in lower compared with higher ozone communities. These findings were replicated in the two cohorts of fourth-grade children recruited in 1993 and 1996. The reduction of the protective effect from the −308 GG genotype with higher ozone exposure was most marked in the GSTM1 null and GSTP1 Ile/Ile groups. Conclusions: The TNF–308 GG genotype may have a protective role in asthma pathogenesis, depending on airway oxidative stress levels.

It remains unclear whether long-term daily icodextrin use can decrease technique failure and improve survival in peritoneal dialysis (PD) patients. The aim of the present study was to investigate whether icodextrin use, once daily, can decrease technique failure and prolong patient survival in incident PD patients.Incident PD patients who survived more than 90 days were recruited from the China Medical University Hospital, Taiwan, between 1 January 2007 and 31 December 2011. All patients were followed until transfer to haemodialysis (HD), renal transplantation, transfer to another centre, death, or 31 December 2011.A total of 306 incident PD patients (89 icodextrin users, 217 icodextrin non-users) were recruited during the study period. Icodextrin users were more likely to have hypertension, diabetes and high or high-average peritoneal transport compared with non-users. During the follow-up period, 43 patients were transferred to HD: seven (7.87%) of the icodextrin group, and 36 (16.59%) of the non-icodextrin group. Thirty-two patients died during the follow-up period: five (5.62%) of the icodextrin group, and 27 (12.44%) of the non-icodextrin group. Icodextrin use was significantly associated with a better prognosis, in terms of technique failure (adjusted HR = 0.32; 95% CI = 0.14-0.72). With regard to patient survival, icodextrin use (adjusted HR = 0.33; 95% CI = 0.12-0.87) was associated with a significantly lower risk of death.The use of icodextrin once daily may decrease technique failure and improve survival in incident PD patients.

We investigated the role of intercellular adhesion molecule-1 in childhood asthma by examining associations of functional variants at codons 29 (A --> T), 241 (G --> A), and 469 (A --> G) in Children's Health Study participants. Among African-Americans, 469G carriers had lower risk for asthma (ever asthma OR = 0.4, 95% CI 0.2-0.9) but increased risk among 29T carriers (early onset active asthma OR = 2.2, 95% CI 1.0-4.9). Protective associations with the 241A allele were observed among non-Hispanic and Hispanic whites (ever asthma OR = 0.7, 95% CI 0.6-0.9; early onset active asthma OR = 0.5, 95% CI 0.4-0.8), and these associations were not confounded by population stratification. To gauge the potential impact of confounding by population stratification, we performed analyses by ethnic group and in an independent family-based sample. Regional associations were stable across analyses. Haplotype associations of the four common haplotypes (29A/241G/469A, AGG, TGA, and AAG) with asthma showed that Hispanics with the AAG haplotype had lower asthma risk compared to carriers of two copies of AGA haplotype (OR = 0.6, 95% CI 0.4-0.9). Among non-Hispanic whites, the AAG haplotype was associated with reduced risk for active asthma. For African-Americans, who had a low frequency of the AAG haplotype, carrying one copy of the AGG haplotype was associated with a lower risk of asthma (OR = 0.3, 95% CI 0.1-0.8), as compared with two copies of the AGA haplotype. Consistent with information on variant function, the 241A and 469G variants may indicate haplotypes that are associated with reduced risk for asthma.

Exposures to ambient air pollutants have been associated with adverse birth outcomes. We investigated the effects of air pollutants on birth weight mediated by reduced fetal growth among term infants who were born in California during 1975-1987 and who participated in the Children's Health Study. Birth certificates provided maternal reproductive history and residence location at birth. Sociodemographic factors and maternal smoking during pregnancy were collected by questionnaire. Monthly average air pollutant levels were interpolated from monitors to the ZIP code of maternal residence at childbirth. Results from linear mixed-effects regression models showed that a 12-ppb increase in 24-hr ozone averaged over the entire pregnancy was associated with 47.2 g lower birth weight [95% confidence interval (CI), 27.4-67.0 g], and this association was most robust for exposures during the second and third trimesters. A 1.4-ppm difference in first-trimester carbon monoxide exposure was associated with 21.7 g lower birth weight (95% CI, 1.1-42.3 g) and 20% increased risk of intrauterine growth retardation (95% CI, 1.0-1.4). First-trimester CO and third-trimester O3 exposures were associated with 20% increased risk of intrauterine growth retardation. A 20-microg/m3 difference in levels of particulate matter < or = 10 microm in aerodynamic diameter (PM10) during the third trimester was associated with a 21.7-g lower birth weight (95% CI, 1.1-42.2 g), but this association was reduced and not significant after adjusting for O3. In summary, O3 exposure during the second and third trimesters and CO exposure during the first trimester were associated with reduced birth weight.

Both in utero exposures to maternal smoking and asthma are associated with chronic deficits in lung function. We hypothesized that in utero exposure affects lung function in children without asthma and synergistically affects children with early onset asthma. To investigate effects of in utero exposure and age at asthma diagnosis on lung function, we examined longitudinal medical history, tobacco smoke exposure, and lung function data from 5,933 participants in the Children's Health Study. We found that children exposed in utero, but without asthma, showed decreased FEV1/FVC, FEF25-75, and FEF25-75/FVC ratio. Among children without in utero exposure, early asthma diagnosis was associated with larger decreases in FEV1, FEF25-75, and FEV1/FVC ratio compared with later diagnosed asthma. Children with in utero exposure alone and early onset asthma showed deficits in FEV1 (-13.6%; 95% confidence interval [CI], -18.9 to -8.2) and FEF25-75 (-29.7%; 95% CI, -37.8 to -20.5) among boys; and FEF25-75 (-26.6%; 95% CI, -36.4 to -15.1) and FEV1/FVC (-9.3%; 95% CI, -12.9 to -5.4) among girls. The absolute differences in FEF25-75 associated with in utero exposure increased with age in children with early onset asthma. We found little evidence for effects from environmental tobacco smoke exposure alone. In summary, deficits in lung function were largest among children with in utero exposure and early onset asthma.

Background. The aim of the study is to describe the overall diet and potential effects of gender, ethnicity, family income, and parents' education on dietary patterns in adolescents aged 11 to 20 years who participated in a cohort study in 12 Southern California communities. Methods. A validated 131-item youth/adolescent food frequency questionnaire was administrated among 3,201 participants in the Children's Health Study at follow-up visits between 1998 and 2000. Sociodemographic characteristics included ethnicity, family income, and parents' education. Stratified analysis and analysis of covariance were used to describe the intakes of selected nutrients and food groups. Results. Mean intakes for all nutrients except calcium met 100% of the Recommended Dietary Allowances. Average daily food intakes were below the minimum recommended number of servings for all major food groups. The majority of subjects had an excessive intake of added sugar. A gender difference was found in intakes of energy, total fat (TF), saturated fat (SF), monounsaturated fat (MUSF), and calcium (P < 0.05). Non-Hispanic Whites had the lowest intakes of fruits while Blacks and Asians had significantly higher intakes of vegetables (P < 0.05). Subjects from higher income families had significantly higher intakes of polyunsaturated fat, protein, calcium, and folate and more frequently consumed dairy products. Intakes of TF, SF, MUSF, and cholesterol decreased as parents' education levels increased. Subjects from families with parents who had higher educational attainment were more likely to meet the recommendations of dairy products, fruits, and vegetables. Conclusion. Overall, subjects in our study did not have healthy eating habits. Dietary patterns varied by sex, ethnicity, income, and education.

The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S -transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functions in pathways involved in asthma pathogenesis such as xenobiotic metabolism and antioxidant defenses. Effects of GSTM1 genotype, maternal smoking during pregnancy, and childhood environmental tobacco smoke (ETS) exposure on asthma and wheezing were investigated in 2,950 children enrolled in 4th, 7th, and 10th grade classrooms in 12 Southern California communities. The effects of in utero exposure to maternal smoking on asthma and wheezing occurrence were largely restricted to children with GSTM1 null genotype. Among GSTM1 null children, in utero exposure was associated with increased prevalence of early onset asthma (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.0‐2.5), asthma with current symptoms (OR 1.7, 95% CI 1.1‐2.8), persistent asthma (OR 1.6, 95% CI 1.1‐2.4), lifetime history of wheezing (OR 1.8, 95% CI 1.3‐2.5), wheezing with exercise (OR 2.1, 95% CI 1.3‐ 3.3), wheezing requiring medication (OR 2.2, 95% CI 1.4‐3.4), and emergency room visits in the past year (OR 3.7, 95% CI 1.9‐7.3). Among children with GSTM1 ( � ) genotype, in utero exposure was not associated with asthma or wheezing. Our findings indicate that there are important long-term effects of in utero exposure in a genetically susceptible group of children.

Sleep-disordered breathing (SDB) and Eustachian tube disorders (ETDs) share the same risk factors. The specific aim of this study was to determine the correlation between these 2 conditions and to determine whether treatments for SDB reduce the risk of ETD. This is a retrospective and large population-based cohort study. According to Taiwan's National Health Insurance Research Database, out of 1,000,000 insured patients, 24,251 patients were newly diagnosed with SDB from year 2000 through 2009. The control group for this study comprised 96,827 patients without SDB who were randomly selected from the same database at a ratio of 1:4, frequency matched for sex, age, and index year of SDB. The incidence of developing ETD was compared between these 2 groups; the main covariates were demographic data, interventions, and medical comorbidities. There was an increased risk of developing ETD among the SDB cohort compared with the control group (hazard ratio = 1.51, 95% confidence interval = 1.41–1.63). Compared with SDB patients who did not receive treatment, those who received the treatment, that is, pharyngeal or nasal surgery, CPAP, or multiple modalities (both surgery and CPAP), had a significantly reduced risk of developing ETD. This study showed that patients with SDB are at an increased risk of developing ETD and other comorbidities. The risk of developing ETD can be reduced by implementing prompt treatment for SDB. Multidisciplinary evaluation including ETD should be conducted in the management of patients presenting with SDB.

Although clinical and immunological studies have shown a possible link between allergy and idiopathic nephrotic syndrome (INS), the nature of the relationship remains unclear. Asthma is the most common chronic allergic airway inflammation. However, no study has used a longitudinal design with a population cohort to investigate INS in children with asthma.Using nationwide claims data from 2000 through 2007, we randomly selected 251,698 asthma cases and 1,006,791 frequency-matched controls. Incidence rates of INS and hazard ratios (HRs) were calculated.The INS incidence was 3.36-fold greater in the asthma cohort than in the nonasthma control (9.26 vs. 2.76 per 100,000 person-years; 95% confidence interval (CI): 2.65-4.26). The HR for INS increased for those with more asthma-related medical visits per year, from 1.49 (95% CI: 1.06-2.11) for3 visits to 15.7 (95% CI: 11.5-21.5) for ≥6 visits (trend test, P0.0001). The HR for INS slightly decreased during the follow-up period, from 3.41 (95% CI: 2.66-4.38) for ≤5.5 y to 2.90 (95% CI: 1.33-6.30) for5.5 y.We conclude that children with asthma had an increased incidence rate of INS, and increased incidence rate correlated with asthma-related medical visits.

Asthma is a chronic disease that is particularly common in children. The association between polymorphisms of the gene encoding intercellular adhesion molecule 1 (ICAM1) and gene-environment interactions with childhood asthma has not been fully investigated. A cross-sectional study was undertaken to investigate these associations among children in Taiwan. The effects of two functional single-nucleotide polymorphisms (SNPs) of ICAM1, rs5491 (K56M) and rs5498 (K469E), and exposure to environmental tobacco smoke (ETS) were studied. Two hundred and eighteen asthmatic and 877 nonasthmatic children were recruited from elementary schools. It was found that the genetic effect of each SNP was modified by the other SNP and by exposure to ETS. The risk of asthma was higher for children carrying the rs5491 AT or TT genotypes and the rs5498 GG genotype (odds ratio = 1.68, 95% confidence interval 1.09–2.59) than for those with the rs5491 AA and rs5498 AA or AG genotypes (the reference group). The risk for the other two combinations of genotypes did not differ significantly from that of the reference group (p of interaction = 0.0063). The two studied ICAM1 SNPs were associated with childhood asthma among children exposed to ETS, but not among those without ETS exposure (p of interaction = 0.05 and 0.01 for rs5491 and rs5498, respectively). Both ICAM1 and ETS, and interactions between these two factors are likely to be involved in the development of asthma in childhood.

Background: Several studies discussed the relations between asthma and rheumatoid arthritis (RA) but the results were controversial. These studies were either questionnaire based or with small study populations. We aimed to examine the risk of asthma among RA patients in a nationwide population. Methods: We conducted a cohort study using data from the National Health Insurance system of Taiwan. The RA cohort included 27 602 patients who were newly diagnosed and recruited between 1998 and 2008. Each patient was randomly frequency-matched with three people without RA on age group, sex and the year of index date from the general population. The occurrence of asthma was followed up until the end of 2010. The relative risks of asthma were estimated using Cox proportional hazard models after adjusting for age and comorbidities. Result: The overall incidence rate of asthma was 2.07-fold greater in the RA cohort than in the non-RA cohort (4.56 vs. 2.22 per 1000 person-years, 95% CI = 1.99–2.15). Stratified analyses by gender, age group and comorbidity revealed that the risk of asthma associated with RA was higher in females (adjusted hazard ratio (HR) = 2.18, 95% CI = 1.97–2.41), individuals younger than 40 years old (adjusted HR = 3.26, 95% CI = 2.09–5.11) and without comorbidity (adjusted HR = 2.17, 95% CI = 1.97–2.39). Conclusion: Patients with RA had a significantly higher risk of developing asthma than healthy people in all sex and age subgroups. Stratified analyses indicated that there was a higher risk in women with RA than in men with RA when compared to their counterpart. Similarly, the HR of asthma associated with RA was higher in younger subjects, although the incidence rate increased with age.

Paroxysmal or persistent tachycardia in pediatric patients is a common disease. Certain circulating microRNAs (miRNAs) have been associated with arrhythmia. The present study investigated miRNAs in the plasma of pediatric patients with tachycardia. Forty pediatric subjects were included retrospectively: 24 with recurrent sustained tachycardia [seven cases of ventricular tachycardia (VT) and 17 cases of supraventricular tachycardia (SVT)] and 16 healthy controls. Circulating miR-1 and miR-133 in the plasma were detected by fluorescent quantitative polymerase chain reaction. miR-1 levels were significantly decreased in the arrhythmia group compared with those in the controls (P=0.004) whilst miR-133 expression levels were not significantly different between the two groups (P=0.456). Both miR-1 and miR-133 levels showed significant differences between the SVT and VT groups (P=0.004 and P=0.046, respectively), and a significant decrease in miR-1 levels was observed in the SVT group as compared with the controls (P

Chemical analysis of the Chinese marine sponge Xestospongia testudinaria afforded a library of brominated polyunsaturated lipids including eight new compounds, named xestonarienes A–H ( 3 – 10 ) and thirteen known analogues ( 11 – 23 ). The structures of the new compounds were elucidated by detailed spectroscopic analysis and by comparison with literature data. The isolated lipids were evaluated for their inhibitory activity against pancreatic lipase (PL), an essential enzyme for efficient fat digestion and the major metabolite, 14 , exhibited a marked inhibitory activity (IC 50 = 3.11 μM), similar to that of the positive control Orlistat (IC 50 = 0.78 μM). The preliminary structure–activity relationships on the series of compounds clearly evidenced that a terminal ( E )-enyne functionality, a diyne within the chain, and methyl ester group are all key functional groups for the activity of this class of PL inhibitors. Further biological investigation on compound 14 revealed a significant decrease in the plasma triglyceride level following an oral lipid challenge in C57BLKS/J male mice. Acute toxicology study demonstrated that compound 14 was non-toxic up to 1600 mg/kg p.o in mice. This is the first report of the PL inhibitory activity for brominated polyunsaturated lipids and the obtained results qualify compound 14 as a potent and bioavailable drug candidate for a mild and safe treatment to prevent and reduce obesity.

To assess the safety and efficacy of transcatheter intervention for critical pulmonary stenosis (CPS) and pulmonary atresia with intact ventricular septum (PA/IVS) in neonates.From June 2006 to September 2011, 27 neonates including CPS in 19 patients and PA/IVS in 8 patients underwent transcatheter intervention. All patients had membranous stenosis or atresia without severe Ebstein's anomaly and severe right ventricle and pulmonary valve hypoplasia, without right ventricle-dependent coronary circulation in PA/IVS. The mean age was (16.8 ± 9.9) d. The mean weight was (3.3 ± 0.5) kg. Two of them were premature neonates, the weight was 2.3 kg and 2.5 kg, respectively. The procedural success, early outcome, complication rates, midterm results and pulmonary regurgitation were retrospectively studied.Twenty-six patients were successfully treated with transcatheter intervention. Right ventricular pressure fell from (112.0 ± 21.0) mm Hg (1 mm Hg = 0.133 kPa) to (50.4 ± 15.9) mm Hg (P0.001). The ratio of right ventricular pressure and aortic pressure fell from 1.7 ± 0.1 to 0.7 ± 0.3 (P0.001). One patient died early of PA/IVS. Complication occurred in 5 patients. Hemopericardium occurred in 3 patients, tachyarrhythmia in 2 patients. Five patients needed prolonged prostaglandin E(1) infusion for 3 to 14 days because of desaturation after the procedure. No patient needed surgery in neonatal period. At a mean follow-up of (33.5 ± 18.3) months (from 6 months to 5 years), 21 patients had no further transcatheter or surgical intervention. Four patients with CPS had moderate to severe residual pulmonary stenosis after the procedure, 3 of them underwent a second balloon dilation at 3 months of follow-up, the other one was waiting for the second balloon dilation. One patient with PA/IVS was waiting for a bidirectional Glenn procedure because of chronic right ventricular failure. Mild pulmonary regurgitation occurred in 18 patients (69.2%), and moderate pulmonary regurgitation in 8 patients (30.8%).Transcatheter intervention for CPS and PA/IVS in neonates is safe and effective. It can avoid neonatal surgery. Some patients may require repeat balloon valvuloplasty in infant period. In most patients surgical or transcatheter intervention could be avoided and mild pulmonary regurgitation was the common finding in midterm follow-up.

Background: This case-control study investigates the role of xenobiotic-metabolizing genes, including glutathione S-transferases (GSTs) and cytochrome P450 1A1 (CYP1A1) and 2E1 (CYP2E1), in the susceptibility to oral potentially malignant disorders (OPMDs).Methods: The genotypes of GSTM1, GSTT1, GSTP1, CYP1A1∗2C, and CYP2E1 PstI/RsaI polymorphisms were determined for 217 OPMD cases and 492 age- and sex-matched controls from a Taiwanese penitentiary.Results: Compared to the GSTM1-present genotype, the GSTM1-null genotype was significantly associated with increased risk of leukoplakia (odds ratio [OR]=1.46, 95% l [CI]=1.01–2.10). Similarly, compared to the CYP1A1∗2C A/G+G/G genotype, the CYP1A1∗2C A/A genotype was significantly associated with increased risk of leukoplakia (OR=1.64, 95% CI=1.12–2.40), particularly for smokers consuming > 13 pack-years of cigarettes (OR=2.40, 95% CI=1.40–4.11) (Interaction P=0.039). In addition, participants with 4–5 risk genotypes (OR > 1) experienced higher risks for leukoplakia than those with 0-1 risk genotypes (OR=3.19, 95% CI=1.65–6.15) (Trend test P=0.001).Conclusions: Our findings suggest that the CYP1A1∗2C A/A genotype may increase the risk of leukoplakia, especially for heavy smokers. Xenobiotic-metabolizing genes may simultaneously modulate this disease risk. These observations require further confirmation with larger samples.

To investigate the effects of sIL-5Rα and sIL-13Rα2 on VCAM-1 and IFN-γ in allergic rhinitis rats.A total of 50 Wistar rats were randomly divided into 5 groups: the normal group (group A), the allergic rhinitis model group (group B), the sIL-5Rα treatment group (group C), the sIL-13Rα2 treatment group (group D), the combination of sIL-5Rα and sIL-13Rα2 treatment group (group E or the combined treatment group). Rats in the latter 4 groups were sensitized with ovalbumin (OVA) and Al(OH)(3), and challenged with OVA to establish allergic rhinitis models, while rats in the normal group were treated with saline. Rats in the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group were absorbed on day 31 to day 38 once daily once nasal cavity with sIL-5Rα(100 µg), sIL-13Rα2 (100 µg) and the combination of sIL-5Rα (100 µg) and sIL-13Rα2 (100 µg) 30 min before challenged, while rats in the allergic rhinitis model group received PBS(50 µl). Then the levels of VCAM-1 and IFN-γ in serum and nasal lavage fluid (NLF) were measured by ELISA.Compared with the normal group, the levels of VCAM-1 in the allergic rhinitis model group were higher, while IFN-γ were lower (all P0.01). Compared with the allergic rhinitis model group, the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group could effectively reduced serum and NLF VCAM-1 level [group E: (283.5 ± 5.7) µg/L, (101.8 ± 4.8) µg/L; group C: (311.5 ± 12.6) µg/L, (133.9 ± 5.8) µg/L; group D: (304.7 ± 6.6) µg/L, (128.5 ± 7.7) µg/L], and increased IFN-γ level [group E: (874.7 ± 9.6) pg/ml, (349.2 ± 12.1) pg/ml; group C: (600.2 ± 16.1) pg/ml, (195.5 ± 16.1) pg/ml; group D: (577.9 ± 9.6) pg/ml, (196.7 ± 9.9) pg/ml ]; compared with single treatment, the combined treatment group also had significant differences(P0.01).Combined treatment with sIL-5Rα and sIL-13Rα2 to treat the allergic rhinitis rats can significantly reduce VCAM-1 levels in serum and NLF, and increase IFN-γ levels, thus, to achieve the purpose of mitigation and treatment of allergic rhinitis.

Background Previous research has shown variation in the effects of patient factors, including hepatic necroinflammatory activity, on liver stiffness measurement (LSM). This prospective study attempts to identify explanatory factors for LSM in patients with chronic hepatitis C (CHC) using acoustic radiation force impulse (ARFI) technology. Methods A cohort of 127 Taiwanese patients with CHC underwent ARFI LSM and immediate percutaneous liver biopsy. This study compares the concurrent diagnostic performances of LSM and FibroTest using receiver operating characteristic (ROC) curves. Three multiple linear regression models were used to evaluate the significance of concurrent patient factors in explaining LSM. Results To classify METAVIR fibrosis (F) stages, the areas under ROC curves (AUCs) were ARFI LSM, 0.847 (95% confidence interval (CI), 0.779-0.914) and FibroTest, 0.823 (95% CI, 0.748-0.898), for F1 versus F2-4; ARFI LSM, 0.902 (95% CI, 0.835-0.970) and FibroTest, 0.812 (95% CI, 0.735-0.888), for F1-2 versus F3-4; ARFI LSM, 0.831 (95% CI, 0.723-0.939) and FibroTest, 0.757 (95% CI, 0.648-0.865), for F1-3 versus F4. After adjusting for other demographic and biological covariates, biochemical and histological necroinflammatory factors consistently explained LSM. Factors included serum alanine aminotransferase (ALT)/upper limit of normal (ULN) categories (model R2 = 0.661, adjusted R2 = 0.629), ActiTest A scores (R2 = 0.662, adjusted R2 = 0.636), and METAVIR activity (A) grades (R2 = 0.651, adjusted R2 = 0.620). METAVIR F stages, body mass index, and platelet count were also independently associated with LSM. Necroinflammatory degrees, including ALT/ULN, ActiTest A scores, and METAVIR A grades, explained the false positivity of liver fibrosis staging using ARFI LSM. Conclusions The degree of hepatic necroinflammatory activity independently and significantly exaggerated liver fibrosis evaluation using ARFI LSM. However, comparisons with concurrent FibroTest indicate that ARFI LSM may be a promising alternative, or adjunctive single indicator, for liver fibrosis evaluation in patients with CHC.

To evaluate the adrenocortical function in children with severe and critical enterovirus 71 infection by using a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. And to at provide experimental basis for glucocorticoid in the treatment of hand-foot-and-mouth disease (HFMD).This was a prospective multi-center study which was carried out in PICUs of Beijing Children's Hospital, Zhengzhou Children's Hospital, Kaifeng Children's Hospital and Linyi People's Hospital in Shandong province. Children with severe and critical hand-foot-mouth disease admitted to PICUs of the four hospitals from June 2009 to April 2010 were enrolled in this study, and EV71 virus nucleic acid test and high-dose (250 µg) ACTH stimulation started at the same time. EV71 virus nucleic acid positive 51 cases were eventually enrolled in the study. Cortisol test was performed at baseline (T0) and after high-dose (250 µg) ACTH stimulation at 30 minutes (T30), 60 minutes (T60) in the first 6 hours after admission, but before glucocorticoid was given. The adrenocortical function was evaluated according to ΔTmax [ΔTmax=(T30, T60 maximum)-T0]. Diagnostic criteria of adrenal insufficiency (AI) is increment (ΔTmax)≤9 µg/dl.The incidence of AI in 51 cases was 52.94% (27/51). The incidence of AI in severe group was 44.74% (17/38), which was significantly higher in critical group 76.92% (10/13), P0.05. Of the cases with a pediatric critical illness score (PCIS)≤70, 81.82% (9/11) had adrenal insufficiency, and it was 28.57% (4/14) when PCIS≥90. The incidence of AI was 75% (6/8) and 48.84% (21/43) in death and survivor group respectively, but there were no significant difference between the two groups (P0.05). Baseline (T0) cortisol in death group was higher than survivor group (P0.05).AI may occur in children with enterovirus 71 infection. The critical enterovirus 71 infection had a high incidence of AI. AI may affect the prognosis of patients with severe and critical enterovirus 71 infection. Exogenous glucocorticoids administration may be considered when AI is identified or highly suspected. The timing, dosage and regimen of glucocorticoid are still unclear. Further animal experiments and clinical trials are needed.

To report the results of transcatheter interventional therapy (TIT) of congenital heart disease (CHD) register from 23 medical centers in China.In this retrospective multicenter registry study, clinical data from 5808 patients who underwent TIT between January 2008 to December 2010 in 23 Chinese medical centers in 14 cities were analyzed.Procedure was successful in 5720 cases (98.5%), success rate was 99.5% for PDA, 98.8% for ASD, 97.4% for VSD and 98.5% for pulmonary stenosis (PS). Multivariate regression analysis showed that PDA size and procedure time, age and procedure time, distance from VSD to AV were significantly associated with the procedure success rate of PDA, ASD and VSD closure, respectively. Early complications occurred in 306 cases (5.3%), 36 cases (0.6%) experienced major complications including device embolization in 7 cases, serious aorta regurgitation in 5 cases, serious tricuspid regurgitation in 4 cases, tricuspid stenosis in 2 cases, heart block (HB) in 13 cases (2 in ASD and 11 in VSD), cardiac tamponade in 2 cases (1 ASD and 1 PS) and hemolysis in 3 cases. Procedure time and PDA size, ASD size, device size, age and PS degree were risk factors related to the occurrence of the early complications for PDA, ASD and VSD closure and PBPV respectively. The median follow-up time was 15 months (range 1-36 months). The complete closure rate during follow up was 100% for ASD, PDA and VSD and the pressure gradient in PS decreased to normal range in all PS patients. Late complications occurred in 15 cases (0.2%), of which 3 cases needed surgery intervention and permanent pacemaker was implanted in 1 patient. There was no death during procedure and at follow-up period.TIT of CHD offers encouraging results in China. Follow up is warranted to monitor the occurrence of serious complications, especially late complications.

Previous studies have suggested that diabetes mellitus (DM) is a risk factor for gallbladder cancer; however, it remains unclear whether DM with or without gallstones increases the risk of gallbladder cancer. The aim of this study was to evaluate the risk factors for gallbladder cancer, including sex, hypertension, hyperlipidemia, gallstones, and DM.The study cohort consisted of 214,179 subjects newly diagnosed with diabetes (cases) collected from the claims data of the Health Insurance Program of Taiwan from 2000 to 2001 who were retrospectively enrolled. The control group consisted of 206,860 subjects without diabetes, matched with the cases for sex, age, and index year. The subjects were followed up until the end of 2008. The effects of the risk factors on the incidence of gallbladder cancer were evaluated with Cox's proportional hazard regression models.The risk of gallbladder cancer was higher in the DM group than in the non-DM group, with a hazard ratio (HR) of 1.53 [95 % confidence interval (CI) 1.22-1.90]. Gallstones were also a risk factor for gallbladder cancer, with an HR of 2.52 (95 % CI 1.11-5.73). DM and gallstones were synergistic risk factors for gallbladder cancer (p 0.0001), with an HR of 5.37 (95 % CI 3.17-9.10) for subjects with both diseases in relation to those with neither of these conditions.In the present long-term cohort study, DM with or without gallstones increased the risk of gallbladder cancer. Gallstones were independently related to gallbladder cancer, and DM and gallstones were synergistic risk factors for gallbladder cancer.

This study describes the relationship between symptoms and quality of life in patients with malignant fungating wounds.Malignant fungating wounds are complex wounds that can bleed, become malodorous due to infection and are painful causing physical and psychological distress. However, there is a lack of literature on the impact that such wounds can have on quality of life.This was a descriptive, cross-sectional multi-centre study of patients with malignant fungating wounds. Participants were recruited from the palliative care, hospice, outpatient clinic and oncology units of three medical centres in Taiwan. Data were collected from February 2008 to August 2009. A structured questionnaire obtained socio-demographic information, medical details, wound assessment information and the Taiwanese version of the McGill quality of life questionnaire was administered by interview. McGill quality of life scores indicated that the participants had the lowest quality of life. The participant's age, dressing change frequency, pain, wound dressing comfort, wound symptom, bleeding and malodour had statistically significant negative correlations with quality of life. Multiple regression analysis showed that age, malodour, pain issues and psychological issues explained 87% of the total variance in quality of life. This study contributes to our understanding of the impact of malignant fungating wounds and how correct assessment and management is necessary to improve quality of life. Educational intervention research is needed for patients and caregivers in countries where this has not yet been performed. Further research should also identify whether nursing competence has a direct impact on quality of life.

Summary Background The roles remain unclear of early on-treatment quantitative serum HBsAg and hepatitis B virus (HBV) DNA levels in the prediction of a sustained response (SR) to peginterferon alfa-2a therapy in HBeAg-negative chronic hepatitis B (CHB) patients infected with genotype B or C. Aims To determine their roles in HBeAg-negative CHB patients infected with genotype B or C. Methods Sixty-one patients were treated with peginterferon alfa-2a for 48 weeks. Serum HBsAg levels were quantified using the Abbott Architect HBsAg QT assay throughout treatment. Multiple regression analyses were performed to identify independent predictors of SR. Results Nineteen patients (31%) achieved SR with serum HBV DNA levels

Objective: Linkage between allergy and increased immune response activation in Tourette syn- drome (TS) has been reported. We performed a matched case-control study to evaluate correlation between allergic diseases and TS. Methods: Data in this case-control study were from the Taiwan National Health Insurance Research Database. The sample comprised 845 2- to 18-year-old patients with newly diagnosed TS in 2003-2007 and 3378 controls frequency matched with cases on age, sex, and urbanization level. Uncon- ditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) of the association between allergic disease (e.g., allergic rhinitis, atopic dermatitis, asthma, and allergic conjunctivitis), the number of allergic comorbidities, and TS. Results: The majority (76.0%) of incident TS cases were boys; the 4 allergic diseases strongly correlated with higher risk of TS. In a model simultaneously considering all 4 allergic diseases, subjects with allergic rhinitis showed double the risk of TS (adjusted OR 2.18, 95%CI 1.83-2.59; p < 0.0001); adjusted ORs were 1.82, 1.61, and 1.33, respectively, for asthma (95% CI 1.47-2.24; p < 0.0001), dermatitis (95%CI 1.32-1.95; p < 0.0001), and allergic conjunctivitis (95% CI 1.13-1.57; p < 0.001). Risk increased with number of comorbidities (p < 0.0001); this association was positively modified by age (p < 0.0001). Conclusions: Our data showed significant correlation between allergic diseases and TS. Risk also increased with number of allergic comorbidities and with age. Further studies on the mechanism of neuro- immunology of TS are required.

To simplify the methods of transcatheter mapping and ablation in the pediatric patients with left posterior fascicular tachycardia.While in sinus rhythm, the fascicular potential can be mapped at the posterior septal region (1 - 2 cm below inferior margin of orifice of coronary sinus vein), which display a biphasic wave before ventricular wave, and exist equipotential lines between them. When the fascicular potential occurs 20 ms later than the bundle of His' potential, radiofrequency was applied. Before applying radiofrequency, catheter position must be observed using double angle viewing (LAO 45°RAO 30°), and it should be made sure that the catheter is not at His' bundle. If the electrocardiogram displays left posterior fascicular block, the correct region is identified and ablation can continue for 60 s. Electrocardiogram monitoring should continue for 24 - 48 hours after operation, and notice abnormal repolarization after termination of ventricular tachycardia. Aspirin [2 - 3 mg/(kg·d)] was used for 3 months, and antiarrhythmic drug was discontinued. Surface electrocardiogram, chest X-ray and ultrasound cardiography were rechecked 1 d after operation. Follow-up was made at 1 month and 3 months post-discharge. Recheck was made half-yearly or follow-up was done by phone from then on.Fifteen pediatric patients were ablated successfully, and their electrocardiograms all displayed left posterior fascicular block after ablation. None of the patients had recurrences during the 3 to 12 months follow-up period. In one case, the electrocardiogram did not change after applying radiofrequency ablation and the ventricular tachycardia remained; however, on second attempt after remapping, the electrocardiogram did change. The radiofrequency lasted for 90 seconds and ablation was successful. This case had no recurrences at 6 months follow-up.Transcatheter ablation of the fascicular potential in pediatric patients with left posterior fascicular tachycardia can simplify mapping, reduce operative difficulty and produce a distinct endpoint for ablation.

To evaluate the efficacy of interventional therapy for complex congenital heart defects patients with un-repaired or postoperative residual lesions.Between March 1998 and April 2009, 42 patients (12 females), mean age 6 years (5 months to 30 years) received interventional therapy, 17 cases underwent occlusion of major aorto-pulmonary collateral arteries (MAPCAs), 15 underwent device closure of residual ventricular or atrial septal shunting, 12 underwent balloon angioplasty (n = 10) and stenting (n = 2) for stenosis of the anastomosis of vessels or branched pulmonary arteries.Twenty-three MAPCAs were performed in 17 patients without residual shunting. One patient died of multiple organ failure after intervention therapy and the remaining patients discharged without complication, successful device closure was performed in 15 patients and there was minimal residual shunting in 1 patient. There were no severe arrhythmias such as complete atrio-ventricular block during and post procedure. Exercise capacities were significantly improved in 12 patients underwent balloon angioplasty or stenting. Pressure gradients were significantly decreased and there was no aneurysmal or thromboembolic formation post procedure.Interventional therapy is a safe and effective therapy option for treating complex congenital heart defects patients with un-repaired or postoperative residual lesions.

To summarize the experience in diagnosis and treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) in children.A total of 14 children (7 females and 7 males) with ARVC were involved. The cases underwent electrocardiography, echocardiography, cardiac CT or MRI examinations. All cases were treated with sotalol or amiodarone in combination with propranolol. In 2 cases with drug-refractory ventricular extrasystoles, catheter ablation treatment was performed. In 6 cases with obvious impaired ventricular function, additional pharmacological therapy including vasodilators, diuretics, and digitalis were given.Ventricular extrasystoles occurred in all 14 cases and ventricular tachycardia in 8 cases. Ten cases showed Epsilon wave on electrocardiography. All 14 cases had enlarged right ventricle and reduced right ventricular ejection fraction. CT or MRI examination showed right ventricular dilatation and a thinned wall of right ventricle in 10 cases. Ventricular extrasystoles or tachycardia disappeared in 7 cases and was reduced in 4 cases after treatment. The two children receiving catheter ablation treatment did not present ventricular extrasystoles or tachycardia in a 3-month follow-up. The heart function was improved in the 6 children with obvious impaired ventricular function after pharmacological therapy.The clinical manifestations are diverse in children with ARVC. A definite diagnosis of ARVC should be based on a combination of electrocardiography and echocardiography examinations. Pharmacological therapy is effective partially. Catheter ablation treatment appears to be a promising option in patients with drug-refractory ventricular extrasystoles.