Graduate Institute of Medicine

Kaohsiung, Taiwan

Graduate Institute of Medicine

Kaohsiung, Taiwan
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Lin C.-S.,Graduate Institute of Medicine | Chiang S.-L.,Institute of Clinical Medicine | Ko Y.-C.,Institute of Clinical Medicine
Toxicological Sciences | Year: 2011

Previous investigations have shown that areca nut extracts (ANE) or arecoline (ARE) causes DNA damage, which in turn contributes to oral cell carcinogenesis. To understand the role of microRNA (miRNA) in ANE-associated carcinogenesis, miRNA expression profile was examined in ANE-treated normal human oral fibroblasts. Among the miRNAs changed by ANE exposure, we found that ANE-induced miR-23a overexpression was correlated with an increase of α-H2AX, a DNA damage marker. In addition, DNA double-strand breaks (DSB) repair that was determined by an in vivo plasmid-based assay was reduced in ANE-treated or miR-23a-overexpressed cells, suggesting the role of miR-23a in DSB repair. FANCG is one of Fanconi anemia susceptibility genes that participate in DSB repair pathway to prevent chromosomal aberrations. FANCG was predicted as a candidate target of miR-23a by TargetScan algorithm. This was confirmed by ectopic overexpression or knockdown of miR-23a. The correlation between miR-23a overexpression and areca nut-chewing habit could also be found in oral cancer patients. Finally, we showed that ANE-induced/ARE-induced miRNAs were significantly associated with the functional categories of "genetic disorders" and "cancer" using network-based analyses. In conclusion, our data showed for the first time that ANEinduced miR-23a was correlated with a reduced FANCG expression and DSB repair, which might contribute to ANEassociated human malignancies. © The Author 2011. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.

Juan Y.-S.,Graduate Institute of Medicine | Juan Y.-S.,Kaohsiung Medical University | Lee Y.-L.,Chi Shan Hospital | Long C.-Y.,Kaohsiung Municipal Hsia Kang Hospital | And 4 more authors.
BJU International | Year: 2012

Objective To evaluate whether green tea extract, epigallocatechin gallate (EGCG), could prevent ovariectomy-induced overactive bladder (OAB) and to investigate its antioxidant, anti-apoptotic and anti-fibrosis effects. Materials and Methods In all, 48 female Sprague-Dawley rats were divided into four groups. After bilateral ovariectomy, the first group served as the ovariectomy control, the second group received EGCG 1 ÂμM/kg daily i.p. injection after ovariectomy surgery, and the third group received EGCG 10 ÂμM/kg daily i.p. injection. The fourth group was taken as the sham without ovariectomy surgery. The rats were killed after 6 months after ovariectomy surgery. Cystometrograms were performed for the measure of bladder overactivity. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was used to evaluate apoptotic cells. Western immunoblots were performed to determine the expressions of inflammatory markers, apoptosis-associated proteins and oxidative stress markers. Results Long-term ovariectomy significantly increased non-voiding contractions and decreased bladder compliance. Treatment with EGCG significantly increased bladder compliance and diminished non-voiding contractions. Ovariectomy significantly increased apoptotic cells and enhanced interstitial fibrosis in bladders. The expression of caspase-3 significantly increased, while that of Bcl-2 notably decreased after ovariectomy. Inflammatory and fibrosis markers, TGF-β, fibronectin and type I collagen expressions were significantly increased after 6 months of ovariectomy surgery. Treatment with EGCG significantly decreased TGF-β and type I collagen expressions. Oxidative stress markers, nitrotyrosine and protein carbonylation levels were significantly increased in the ovariectomy group. EGCG could attenuate this oxidative damage in dose-dependent fashion. Conclusions Ovariectomy increased oxidative damage, enhanced voiding frequency and decreased bladder compliance. EGCG could restore ovariectomy-induced bladder dysfunction in a dose-dependent fashion through antioxidant, anti-fibrosis and anti-apoptosis effects. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

Huang C.-F.,Kaohsiung Medical University | Huang C.-F.,Graduate Institute of Medicine | Yang J.-F.,Kaohsiung Medical University | Dai C.-Y.,Kaohsiung Medical University | And 12 more authors.
Journal of Infectious Diseases | Year: 2010

Background: The present study evaluated the efficacy and safety of pegylated interferon (PegIFN)/ribavirin treatment in elderly patients with hepatitis C virus (HCV) infection. Methods: Seventy elderly patients with hepatitis C virus (HCV) infection (group A; age, ≥65 years) and 140 sex- and HCV genotype-matched controls (group B; age, 50-64 years) were allocated to receive a PegIFN-α-2a/ribavirin standard-of-care regimen. Results: Group A had a significantly higher rate of treatment discontinuation (21.4% vs 6.4%; Pp.001) and grade 3 or 4 adverse events (34.3% vs 20%; Pp.002) than group B. In intention-to-treat analysis, the sustained virologic response (SVR) rate was substantially lower in group A than in group B (67.1% vs 78.6%; Pp.07). The inferiority of the SVR rate in group A was observed among patients with HCV genotype 1 (HCV-1) (51.9% vs 75.9%; Pp.03) but not among patients with HCV genotype 2 or 3 (HCV-2/3) (76.7% vs 80.2%; Pp.65). Among patients in group A who had a rapid virologic response, those infected with HCV-1 and those infected with HCV- 2/3 had similar SVR rates (80% and 87.9%, respectively). For patients receiving treatment for >80% of its expected duration, SVR rates were similar between the 2 groups (80.4% vs 82.6%, respectively), regardless of viral genotype. Conclusions: Older patients with HCV infection, especially those in the subgroup infected with HCV-1, had a greater frequency of adverse events and poorer adherence to the standard-of-care regimen, which may be the major reason for treatment inferiority. Trial registration: identifier NCT00629824. © 2010 by the Infectious Diseases Society of America.

Chu K.-S.,Graduate Institute of Medicine | Chen T.-I.,Graduate Institute of Medicine | Wang H.-M.,Kaohsiung Medical University | Lu I.-C.,Graduate Institute of Medicine
Anaesthesia | Year: 2010

Fibreoptic intubation is a valuable modality for airway management. This study aimed to compare the effectiveness of dexmedetomidine vs target controlled propofol infusion in providing sedation during fibreoptic intubation. Forty patients with anticipated difficult airways and due to undergo tracheal intubation for elective surgery were enrolled and randomly allocated into the dexmedetomidine group (1.0 μ over 10 min) (n = 20) or the propofol target controlled infusion group (n = 20). Intubating conditions and patient tolerance as graded by a scoring system were evaluated as primary outcomes. Intubation was successful in all patients. Satisfactory intubating conditions were found in both groups (19 ? 20 in each group). The median (IOR [range]) comfort score was 2 (1-2 [1-4]) in the dexmedetomidine group and 3 (2-4 [2-5]) in the propofol group (p = 0.027), favouring the former. The dexmedetomidine group experienced fewer airway events and less heart rate response to intubation than the propofol group (p < 0.003 and p = 0.007, respectively). Both dexmedetomidine and propofol target-controlled infusion are effective for fibreoptic intubation. Dexmedetomidine allows better tolerance, more stable haemodynamic status and preserves a patent airway. © 2010 The Authors.

Yu M.-L.,Kaohsiung Municipal Ta Tung Hospital | Huang C.-F.,Kaohsiung Municipal Ta Tung Hospital | Huang J.-F.,Graduate Institute of Medicine | Huang J.-F.,Kaohsiung Municipal Hsiao Kang Hospital | And 7 more authors.
Hepatology | Year: 2011

Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r2 = 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P = 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) = 4.27, 95% confidence interval (CI) = 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR = 0.28, 95% CI = 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR = 3.10, 95% CI = 1.34-7.21, P = 0.008), and the pretreatment level of aspartate aminotransferase (OR = 0.996, 95% CI = 0.99-1.00, P = 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI = 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. © 2010 American Association for the Study of Liver Diseases.

Yang I.-P.,Kaohsiung Medical University | Tsai H.-L.,Graduate Institute of Medicine | Tsai H.-L.,Kaohsiung Medical University | Hou M.-F.,Kaohsiung Medical University | And 8 more authors.
Carcinogenesis | Year: 2012

Purpose: Colorectal cancer (CRC) is associated with high recurrence and mortality. Because deregulation of microRNAs is associated with CRC development and recurrence, the expression levels of microRNAs can be a simple and reliable biomarker to detect postoperative early relapse, thereby helping physicians to treat high-risk patients more efficiently. Experimental design: We used microRNA arrays and observed that microRNA-93 had substantially different expression levels in early (recurrence within 12 months after surgery) and non-early relapse CRC patients. The replication study, which included 35 early relapse and 42 non-early relapse subjects, further confirmed overexpression of microRNA-93 in non-early relapse samples. The in vitro and in vivo effects of microRNA-93 were investigated by examining cell proliferation, migration and invasion, as well as cell cycles, target-gene expression and xenograft in null mice. Results: Cellular studies showed that the overexpression of microRNA-93 inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that microRNA-93 caused an accumulation of the G2 population. However, microRNA-93 could not induce cell apoptosis or necrosis. Functional studies showed that microRNA-93 could suppress CCNB1 protein expression leading to cell cycle arrest in the G2 phase. Moreover, microRNA-93 repressed expression of ERBB2, p21 and VEGF, all of which are involved in cell proliferation. MicroRNA-93 also suppressed tumor growth in null mice. Conclusions: This study showed that microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these findings may have potential clinical applications for predicting the recurrence of CRC. © The Author 2012. Published by Oxford University Press. All rights reserved.

Huang M.-Y.,Kaohsiung Medical University | Wang J.-Y.,Kaohsiung Medical University | Wang J.-Y.,Graduate Institute of Medicine | Huang M.-L.,ZuoYing Armed Forces General Hospital | And 2 more authors.
International Journal of Molecular Sciences | Year: 2013

Using the comprehensive approach to selecting polymorphisms to date, we sought to examine whether recurrence in colorectal cancer was associated with inherited variation in three genes involved in DNA repair and cell proliferation. Three polymorphisms, which are excision repair cross-complementation 1 (ERCC1), xeroderma pigmentosum group D (XPD) and epidermal growth factor receptor (EGFR), were assessed in 257 postoperative stage II/III CRC patients with 5-fluorouracial chemotherapy in Taiwan. In addition, the correlations between genetic polymorphisms and patients' clinicopathological features were investigated. Genotypes of XPD codon751 A/A and ERCC1 codon118 T/T were associated with regional recurrence in a statistically significant way (p = 0.018). Patients who carried XPD AA and ERCC1 TT genotypes demonstrated a significantly greater regional recurrence risk (OR = 5.625, 95% CI, 1.557-20.32). Inherited variation in XPD and ERCC1 was associated with outcome in patients with colorectal cancer in Taiwan. As the significant association of single-nucleotide polymorphisms has not been studied previously in colorectal cancer, these findings suggest novel sites of variation, in part explaining the range of treatment responses seen in this disease. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Huang Y.-H.,Chang Gung University | Huang Y.-H.,Graduate Institute of Medicine | Lee T.-C.,Chang Gung University | Lee T.-H.,Chang Gung University | And 5 more authors.
Journal of Neurosurgery | Year: 2013

Object. Decompressive craniectomy is a life-saving measure for patients who have sustained traumatic brain injury (TBI), but patients undergoing this procedure may still die during an early phase of head injury. The aim of this study was to investigate the incidence, causes, and risk factors of 30-day mortality in traumatically brain-injured patients undergoing decompressive craniectomy. Methods. The authors included 201 head-injured patients undergoing decompressive craniectomy in this 3-year retrospective study. The main outcome evaluated was 30-day mortality in patients who had undergone craniectomy after TBI. Demographic and clinical data, including information on death, were obtained for subsequent analysis. The authors identified differences between survivors and nonsurvivors in terms of clinical parameters; multivariate logistic regression was used to adjust for independent risk factors of short-term death. Results. The 30-day mortality rate was 26.4% in traumatically brain-injured patients undergoing decompressive craniectomy. The majority of deaths following decompression resulted from uncontrollable brain swelling and extensive brain infarction, which accounted for 79.2% of mortality. In the multivariate logistic regression mode, the 2 independent risk factors for 30-day mortality were age (OR 1.035 [95% CI 1.006-1.064]; p = 0.018) and Glasgow Coma Scale (GCS) score before decompressive craniectomy (OR 0.769 [95% CI 0.597-0.990]; p = 0.041). Conclusions. There is a high 30-day mortality rate in traumatically brain-injured patients undergoing decompressive craniectomy. Most of the deaths are attributed to ongoing brain damage, even after decompression. Risk factors of short-term death, including age and preoperative GCS score, are important in patient selection for decompressive craniectomy, and these factors should be considered together to ensure the highest chance of surviving TBI. © AANS, 2013.

Tu F.-Y.,Public Health Bureau | Lin G.-T.,Kaohsiung Medical University | Lin G.-T.,Kaohsiung Municipal United Hospital | Lin G.-T.,Graduate Institute of Medicine | And 5 more authors.
Joint Bone Spine | Year: 2015

Objective: Comorbidity is an important concern for chronic gout patients. We evaluated the relationship between comorbidity profiles and gout in Taiwan aborigines and Taiwanese Han. Methods: We used the claims data from the Taiwan national health insurance database for 2004 to 2006. Physician-diagnosed gout and comorbidities were coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Total sampling from Pingtung County of southern Taiwan included 37,482 aborigines (gout cases, n= 3906 and controls, n= 33,576) and 37,451 Han (gout cases, n= 1115 and controls, n= 36,336). Results: In 2006, the gout prevalences were 10.42% and 2.98% (prevalence ratio [PR]. = 3.50) in the aborigines and Han general populations, respectively. The prevalences of uric acid nephrolithiasis and tophi were higher in aborigines (0.42% and 0.30%, respectively) than in Han (0.09% and 0.04%, respectively). When stratified by comorbidity status, the prevalences of gout were 4.49% and 27.34% in aborigines and 1.52% and 9.44% in Han (approximate PR. = 3.00). Similarly, the prevalence ratios of gout in the comorbidity group, compared with the non-comorbidity group, were 6.09 in aborigines and 6.23 in Han. Multivariate odds ratios [ORs] showed that hypercholesterolemia, hyperglyceridemia, essential hypertension and renal insufficiency were the common comorbidities of gout (OR. = 1.63); heart failure exerted a significant effect only in aborigines (OR. = 1.55). For five comorbidity factors, patients with multiple comorbidities had higher gout prevalence (maximum OR. = 12.90). Conclusion: Gout prevalence was higher in aborigines, both with and without comorbidities, than in Han. The comorbid diseases and comorbidity aggregations showed a substantial association with gout occurrence in both ethnicities. © 2014 Société française de rhumatologie.

Su Y.-S.,Kaohsiung Medical University | Su Y.-S.,Graduate Institute of Medicine | Yu H.-S.,Kaohsiung Medical University | Li W.-C.,Kaohsiung Medical University | And 6 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2013

Background Psoriasis is a systemic disease associated with metabolic disorders and vascular complications. Both psoriasis and metabolic disorders are associated with systemic inflammation. We hypothesized that the sequence of events between the onset of psoriasis and metabolic disorder may affect the risk for subsequent development of vascular complications. Methods Nested case-control study was performed using the Taiwan National Health Insurance database. Accordingly, a total of 8180 psoriatic patients and 163 600 controls were included. Psoriasis was considered as the initiator of inflammatory march if metabolic disorder, including hypertension, diabetes mellitus and dyslipidemia, developed after onset of psoriasis. In patients with pre-existing metabolic disorder, psoriasis was considered as the amplifier of inflammatory march. Results In patients whose psoriasis served as the disease initiator, a lower risk for developing vascular disease (HR = 1.49; 95% CI = 1.11-2.00 and HR = 1.64; 95% CI = 1.31-2.05 for cerebrovascular and cardiovascular events, respectively) was found compared with patients whose psoriasis served as the disease amplifier (HR = 2.26; 95% CI = 1.72-2.97 and HR = 2.78; 95% CI = 2.26-3.42 for cerebrovascular and cardiovascular events, respectively) after adjusting for age and gender. In terms of treatment implications, methotrexate was associated with reduced risk for developing cerebrovascular event (HR = 0.22; 95% CI = 0.05-0.88) only in patients with psoriasis serving as the disease amplifier. Conclusions Our results suggested that two scenarios of systemic inflammatory marches are present among psoriatic patients with metabolic disorder and judicious use of methotrexate may reduce the risk of cerebrovascular event, especially when psoriasis served as the disease amplifier of the systemic inflammatory march. © 2012 European Academy of Dermatology and Venereology.

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