Lin Y.-C.,Far Eastern Memorial Hospital |
Lin Y.-C.,Oriental Institute of Technology |
Chang P.-F.,Far Eastern Memorial Hospital |
Chang M.-H.,National Taiwan University Hospital |
Ni Y.-H.,National Taiwan University Hospital
American Journal of Clinical Nutrition | Year: 2014
Background: A genome-wide association study identified variants in or near patatin-like phospholipase domain-containing-3 (PNPLA3), neurocan (NCAN), lysophospholipase-like 1 (LYPLAL1), glucokinase regulatory protein (GCKR), and protein phosphatase 1 regulatory subunit 3b (PPP1R3B) that were strongly associated with nonalcoholic fatty liver disease (NAFLD) in adults of European ancestry. Objective: We examined these genetic variants in obese children and tested whether their effects on NAFLD are significant in the Taiwanese Han Chinese population. Design: We genotyped PNPLA3 rs738409, NCAN rs2228603, LYPLAL1 rs12137855, GCKR rs780094, and PPP1R3B rs4240624 in 797 obese children aged 7-18 y. NAFLD was identified by liver ultrasonography. We analyzed the effect of these genetic variants on NAFLD. Results: NAFLD was identified in 24% of the recruited obese children. We found significant associations with NAFLD at variants in PNPLA3 and GCKR but not in NCAN, LYPLAL1 , and PPP1R3B. Multiple logistic regression analysis showed that, after control for the effects of age- and sex-adjusted body mass index, waist-to-hip ratio, sex, and PNPLA3 rs738409 polymorphism, the variant GCKR rs780094 TT genotype independently increased the OR of NAFLD by 1.997 (95% CI: 1.196, 3.335; P = 0.008) compared with the CC genotype. Subjects with the variant GCKR rs780094 TT genotype had a higher mean serum alanine aminotransferase concentration than did those with the CC genotype (30.8 ± 34.7 compared with 22.2 ± 18.6 IU/L; P = 0.01). Conclusions: By studying the genetic variants of obese Taiwanese children, we confirmed that the genetic variants in GCKR rs780094 and PNPLA3 rs738409, but not in NCAN rs2228603, LYPLAL1 rs12137855, and PPP1R3B rs4240624, are associated with an increased risk of NAFLD. GCKR and PNPLA3 variants are the common genetic factors that may confer susceptibility to NAFLD in obese individuals across multiple ethnic groups. This trial was registered at clinicaltrials.gov as NCT00274183. © 2014 American Society for Nutrition.
Chen H.-F.,Far Eastern Memorial Hospital |
Chen P.,Central Medicine Hospital Group |
Li C.-Y.,China Medical University at Taichung
Hepatology | Year: 2010
We prospectively investigated 615,532 diabetic patients and 614,871 age-matched and sex-matched control subjects selected from National Health Insurance claims for malignant neoplasms of liver and biliary tract (International Statistical Classification of Diseases and Related Health Problems, 9th edition, codes 155 and 156, respectively) between 2000 and 2006. The person-year approach with Poisson assumption was used to estimate the hazard rates. We also evaluated the age-specific and sex-specific relative risks of these two malignancies in relation to diabetes with Cox proportional hazard regression model with adjustment for potential confounders. The overall hazard rate of malignant neoplasm of the liver was 32.76 and 17.41 per 10,000 patient-years, respectively, for diabetic men and women; the corresponding figures for biliary tract neoplasm were much lower at 1.42 and 1.60 per 10,000 patient-years. Compared with control subjects, diabetic patients had a two-fold increased risk of malignant neoplasm of the liver, but this risk was attenuated by adjusting for selected clinical risk factors (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.17-1.25). Additionally, diabetic patients were associated with increased risk of biliary neoplasms with an approximate magnitude of 20%-30%, but the HR was attenuated and became insignificant after adjustment for clinical risk factors (HR 1.07; 95% CI 0.95-1.21). Diabetic patients with cirrhosis had the highest relative risk of liver neoplasm (HR 85.25; 95% CI 76.84-94.58), whereas those with cholangitis had the highest risk of biliary tract neoplasm (HR 70.30; 95% CI 51.95-95.12) compared with control subjects without any clinical risk factors. Conclusion: This population-based study confirms the association of diabetes with liver neoplasm and suggests that diabetic patients with certain clinical risk factors should be educated for strict adherence of liver neoplasm screening. Copyright © 2010 by the American Association for the Study of Liver Diseases.
Kuo H.-C.,Tzu Chi University |
Liao C.-H.,Fu Jen Catholic University |
Chung S.-D.,Far Eastern Memorial Hospital
European Urology | Year: 2010
Background: Intravesical injection of botulinum toxin type A (BoNTA) provides effective treatment for detrusor overactivity and overactive bladder (OAB). However, the high rates of treatment-related adverse events (AEs) prevent its more widespread use. Objective: To investigate the risk factors of increasing AEs after BoNTA injection for idiopathic detrusor overactivity (IDO). Design, setting, and participants: This study included a total of 217 patients receiving their first intravesical BoNTA injection for refractory IDO in a tertiary university hospital from 2004 to 2009. Measurements: AE incidence was analyzed according to gender, age, comorbidities, prostate condition in men, OAB subtype, BoNTA dose, injection site, and baseline urodynamic parameters. Successful outcome was determined based on patient perception of improvement of bladder condition at 3 mo. Results and limitations: Successful outcomes were reported by 144 (66.3%) patients. By multivariable analysis, male gender (p = 0.013) and baseline postvoid residual (PVR) ≥100 ml (p = 0.003) were independent predictors of acute urinary retention (AUR). Baseline PVR ≥100 ml (p = 0.007) and receiving >100 U BoNTA (p = 0.029) were predictors of straining to void. The incidence of large PVR after treatment was associated with comorbidity (p = 0.011). Urinary tract infection occurred more frequently in women (p = 0.003) and in men with retaining prostate (p = 0.008). No AUR developed after bladder base/trigonal injection. Nevertheless, the occurrence of AUR or large PVR did not affect therapeutic outcome. This study is limited by nonconsecutive enrollment of patients. Conclusions: Male gender, baseline PVR ≥100 ml, comorbidity, and BoNTA dose >100 U are risk factors for increasing incidence of AEs after intravesical BoNTA injection for IDO. © 2010 European Association of Urology.
Su L.-H.,Far Eastern Memorial Hospital |
Chen T.H.-H.,National Taiwan University
British Journal of Dermatology | Year: 2010
Background Several previous studies have investigated the association between factors related to metabolic syndrome, which is known to increase the risk of type 2 diabetes mellitus and cardiovascular disease, and androgenetic alopecia (AGA). However, the results of these studies have been inconsistent. Objectives To determine if there is an association between metabolic syndrome and AGA after adjustment for potential confounders. Methods A population-based cross-sectional survey was conducted in Tainan, Taiwan. A total of 740 subjects aged 40-91 years participated in the survey between April and June 2005. The Norwood classification was used to assess the degree of hair loss. Information on components of metabolic syndrome together with other possible risk factors was collected. Results A statistically significant association was found between AGA and the presence of metabolic syndrome [odds ratio (OR) 1·67, 95% confidence interval (CI) 1·01-2·74] as well as between AGA and the number of fulfilled metabolic syndrome components (OR 1·21, 95% CI 1·03-1·42) after controlling for age, family history of AGA and smoking status. Among metabolic syndrome components, high-density lipoprotein cholesterol (HDL-C) (OR 2·36, 95% CI 1·41-3·95; P = 0·001) was revealed as the most important factor associated with AGA. Conclusions Our population-based study found a significant association between AGA and metabolic syndrome; among the components of metabolic syndrome, HDL-C was found to be of particular importance. This finding may have significant implications for the identification of metabolic syndrome in patients with moderate or severe AGA. Early intervention for metabolic syndrome is critical to reduce the risk and complications of cardiovascular disease and type 2 diabetes mellitus later in life. © 2010 British Association of Dermatologists.
Wu C.-Y.,Far Eastern Memorial Hospital |
Tsai Y.-P.,National Yang Ming University |
Wu M.-Z.,National Yang Ming University |
Teng S.-C.,National Taiwan University |
Wu K.-J.,National Yang Ming University
Trends in Genetics | Year: 2012
The epithelial-mesenchymal transition (EMT) is a developmental process that is important for organ development, metastasis, cancer stemness, and organ fibrosis. The EMT process is regulated by different signaling pathways as well as by various epigenetic and post-transcriptional mechanisms. Here, we review recent progress describing the role of different chromatin modifiers in various signaling events leading to EMT, including hypoxia, transforming growth factor (TGF)-β, Notch, and Wnt. We also discuss post-transcriptional mechanisms, such as RNA alternative splicing and the effects of miRNAs in EMT regulation. Furthermore, we highlight on-going and future work aimed at a detailed understanding of the epigenetic and post-transcriptional mechanisms that regulate EMT. This work will shed new light on the cellular and tumorigenic processes affected by EMT misregulation. © 2012 Elsevier Ltd.
Chen H.-F.,Far Eastern Memorial Hospital |
Chen H.-F.,University of Taipei |
Chen P.,Central Medicine Hospital Group |
Li C.-Y.,National Cheng Kung University
Diabetes Care | Year: 2011
OBJECTIVE - We prospectively assessed the age- and sex-specific incidence and relative risk of malignant neoplasm of the pancreas in Taiwan's diabetic population. RESEARCH DESIGN AND METHODS - A total of 615,532 diabetic patients and 614,871 age- and sex-matched control subjects were linked to inpatient claims (2000-2006) to identify the admissions for malignant neoplasm of the pancreas (ICD-9: 157). The Cox proportional hazards regression model was used to estimate the age- and sex-specific relative risk of pancreatic neoplasm. RESULTS - Compared with the control group, the diabetic patients had a significantly increased risk of pancreatic cancer (hazard ratio [HR] 1.54 [95% CI 1.39-1.71]). The higher and significant age-specific HRs were observed in diabetic men (1.91) and women (1.80) aged 45-65 years. CONCLUSIONS - Middle-aged diabetic men and women were associated with the most increased risk of malignant neoplasm of the pancreas. © 2011 by the American Diabetes Association.
Wu H.Y.,Far Eastern Memorial Hospital
BMJ (Clinical research ed.) | Year: 2013
To assess the effects of different classes of antihypertensive treatments, including monotherapy and combination therapy, on survival and major renal outcomes in patients with diabetes. Systematic review and bayesian network meta-analysis of randomised clinical trials. Electronic literature search of PubMed, Medline, Scopus, and the Cochrane Library for studies published up to December 2011. Randomised clinical trials of antihypertensive therapy (angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), α blockers, β blockers, calcium channel blockers, diuretics, and their combinations) in patients with diabetes with a follow-up of at least 12 months, reporting all cause mortality, requirement for dialysis, or doubling of serum creatinine levels. Bayesian network meta-analysis combined direct and indirect evidence to estimate the relative effects between treatments as well as the probabilities of ranking for treatments based on their protective effects. 63 trials with 36,917 participants were identified, including 2400 deaths, 766 patients who required dialysis, and 1099 patients whose serum creatinine level had doubled. Compared with placebo, only ACE inhibitors significantly reduced the doubling of serum creatinine levels (odds ratio 0.58, 95% credible interval 0.32 to 0.90), and only β blockers showed a significant difference in mortality (odds ratio 7.13, 95% credible interval 1.37 to 41.39). Comparisons among all treatments showed no statistical significance in the outcome of dialysis. Although the beneficial effects of ACE inhibitors compared with ARBs did not reach statistical significance, ACE inhibitors consistently showed higher probabilities of being in the superior ranking positions among all three outcomes. Although the protective effect of an ACE inhibitor plus calcium channel blocker compared with placebo was not statistically significant, the treatment ranking identified this combination therapy to have the greatest probability (73.9%) for being the best treatment on reducing mortality, followed by ACE inhibitor plus diuretic (12.5%), ACE inhibitors (2.0%), calcium channel blockers (1.2%), and ARBs (0.4%). Our analyses show the renoprotective effects and superiority of using ACE inhibitors in patients with diabetes, and available evidence is not able to show a better effect for ARBs compared with ACE inhibitors. Considering the cost of drugs, our findings support the use of ACE inhibitors as the first line antihypertensive agent in patients with diabetes. Calcium channel blockers might be the preferred treatment in combination with ACE inhibitors if adequate blood pressure control cannot be achieved by ACE inhibitors alone.
Chen H.F.,Far Eastern Memorial Hospital
The Tohoku journal of experimental medicine | Year: 2012
Diabetes has been reported to increase the risk of colorectal neoplasm in most but not all studies. However, the data on age- and sex-specific incidence rates and relative risks associated with diabetes are limited. We carried out this population-based cohort study to investigate the overall sex- and age-specific risks of colorectal cancer in association with diabetes. Diabetic patients (n = 615,532) and age- and sex-matched control individuals (n = 614,871), selected from the claim datasets, were followed up from 2000 to 2006. The rates of admission due to colon and rectum cancers were estimated using the person-years approach, and the age- and sex-specific hazard ratio (HR) for both the malignancies were determined using the Cox regression model. The overall incidence rate of colon cancer was 9.94 per 10,000 patient-years for the diabetic patients, as opposed to 7.84 per 10,000 patient-years for the control-group patients. The corresponding observation for rectal cancer was 7.16 and 6.28 per 10,000 patient-years. Diabetic patients aged ≥ 45 years had significantly high HRs for developing colon cancer (1.20-1.45-fold). We also noted a significantly high HR of rectal cancer in diabetic men (1.18-fold) aged ≥ 45 years, but not in diabetic women. In conclusion, diabetes may significantly increase the risk of colorectal cancer, especially in patients aged 45-64 years. Diabetologists should keep this relationship in mind while treating middle-aged diabetic men and should also advise these patients to undergo regular screening tests for colorectal cancer.
Chen C.C.,Far Eastern Memorial Hospital
Journal of orthopaedic research : official publication of the Orthopaedic Research Society | Year: 2012
Extracellular matrix (ECM) is thought to participate significantly in guiding the differentiation process of mesenchymal stem cells (MSCs). In this study, we hypothesized that cartilage fragments from osteoarthritic knee could promote chondrogenesis of MSCs. Nonworn parts of cartilage tissues were obtained during total knee arthroplasty (TKA) surgery. Cartilage fragments and MSCs were wrapped into fibrin glue; and the constructs were implanted subcutaneously into nude mice. Histological analysis showed neocartilage-like structure with positive Alcian blue staining in the cartilage fragment-fibrin-MSC constructs. However, constructs with only MSCs in fibrin showed condensed appearance like MSCs in the pellet culture. Gene expression of type II collagen in the constructs with 60 mg cartilage fragments were significantly elevated after 4 weeks of implantation. Conversely, the constructs without cartilage fragments failed to express type II collagen, which indicated MSCs did not differentiate into a chondrogenic lineage. In conclusion, we demonstrated the effect of cartilage fragments from osteoarthritic knee in promoting chondrogenic differentiation of MSCs. This may be a favorable strategy for MSC chondrogenesis without exogenous growth factor induction. Copyright © 2011 Orthopaedic Research Society.
Wang S.Y.,Far Eastern Memorial Hospital
Clinical nuclear medicine | Year: 2011
A 14-year-old girl, who had been suffering from intermittent fevers for 2 months, developed painful erythematous plaques on the lower extremities. Laboratory data revealed elevated C-reactive protein, lactate dehydrogenase, and aspartate aminotransferase/alanine aminotransferase (AST/ALT). Blood and urine cultures were negative. CT showed hepatosplenomegaly. F-18 FDG PET revealed multiple patchy uptakes on the subcutaneous surfaces residing mainly at the lower trunk and extremities. The PET images and clinical manifestations appeared indistinguishable from those due to panniculitis while the pathology from skin biopsy demonstrated panniculitis-like T-cell lymphoma. She received chemotherapy and the follow-up PET showed significant resolution of previous abnormal uptakes from the subcutaneous lesions.