Effects of physical fitness training on metabolic syndrome among military personnel in Taiwan.

INTRODUCTION: Metabolic syndrome (MS) is strongly associated with cardiovascular diseases and diabetes but can be prevented with regular physical activity. This study aimed to assess the impact of a physical fitness training programme on MS among military personnel. METHODS: This retrospective observational study included volunteer army soldiers who underwent annual health examinations between 2011 and 2014. In 2011, the reformed physical fitness training programme and physical fitness test were introduced to the participants. MS evaluation and physical fitness performances were evaluated before and after implementing the training programme using a mixed-effects model and generalised estimating equation, adjusted for sex, age and smoking. RESULTS: From 2011 to 2014, 1720 soldiers underwent the annual health examination. In 2011, before the fitness programme, 246 soldiers (14.3%) had MS. After implementation, decreases in blood pressure and fasting glucose levels were observed and maintained for 3 years. Running performance was negatively correlated to triglycerides (ß=-11.37; p<0.001) and waist circumference (ß=-0.42; p<0.001) and positively correlated to high-density lipoprotein cholesterol levels (ß=2.14; p<0.001). The severity of MS was reduced following introduction of the physical fitness programme. CONCLUSIONS: MS and its components improved after introducing the reformed fitness programme, with running performance proving to be most relevant to MS. Clinicians should encourage increased physical activity to prevent MS among military personnel.

Management of colorectal anastomotic stricture with multidiameter balloon dilation: long-term results.

BACKGROUND: Postoperative colorectal anastomotic strictures are quite common. As such, many techniques have been available to address such a problem, one of which is endoscopic dilation. The aim of the present study was to evaluate the long-term outcomes following endoscopic dilation using a multidiameter balloon. METHODS: A retrospective study was conducted on patients with postoperative anastomotic stenosis treated with endoscopic dilation using a multidiameter balloon at our institution, in January 2005-December 2019 were retrospectively reviewed, excluding those with tumor recurrence. Perioperative factors, complications, and recurrence rates were analyzed. RESULTS: There were 40 patients, (22 males and 18 females, mean age 64.6 ± 10.7 years, range 33-84 years). The median follow-up period was 56 months (interquartile range 22.5-99 months). Only 1 complication occurred, micro-perforation due to guided wire injury, which was managed conservatively. Five (12.5%) patients developed restenosis and underwent repeat balloon dilation. None of the five recurrences required more aggressive management, such as redo anastomosis. CONCLUSIONS: Endoscopic multidiameter balloon dilation is a safe and effective method for treating benign colorectal anastomotic strictures.

Determination of Green's function for three-dimensional traction force reconstruction based on geometry and boundary conditions of cell culture matrices.

Cell migration plays a particular important role in the initiation and progression of many physical processes and pathological conditions such as tumor invasion and metastasis. Three-dimensional traction force microscopy (TFM) of high resolution and high accuracy is being developed in an effort to unveil the underlying mechanical process of cell migration in a vivo-like environment. Linear elasticity-based TFM (LETM) as a mainstream approach relies on the Green's function (that relates traction forces to matrix deformation), of which the inherent boundary conditions and geometry of the matrix could remarkably affect the result as suggested by previous 2D studies. In this study, we investigated this close linkage in 3D environment, via modeling of a cell sensing a close-by fixed boundary of a 3D matrix surrounding it, and comparing the reconstructed traction forces from three different solutions of the Green's function, including a fully matching solution derived using the adapted Mindlin's approach. To increase fidelity in the estimate of traction forces for extreme conditions such as a sparse sampling of deformation field or targeting small focal adhesions, we numerically solved the singularity problem of the Green's function in a non-conventional way to avoid exclusion of singular point regions that could contain representative deformation indicators for such extreme conditions. A single case experimental study was conducted for a multi-cellular structure of endothelial cells that just penetrated into the gel at the early stage of angiogenesis. STATEMENT OF SIGNIFICANCE: This study focused on the fundamental issue regarding extension of linear elasticity-based TFM to deal with physically realistic matrices (where cells are encapsulated), which concerns determination of the Green's function matching their geometry and boundary conditions. To increase fidelity in the estimate of traction forces for extreme conditions such as a sparse sampling of deformation field or targeting small focal adhesions, we numerically solved the singularity problem of the Green's function to avoid exclusion of singular point regions that could contain representative deformation indicators for such extreme conditions. The proposed approach to adapting the Green's function for the specific 3D cell culture situation was examined in a single case experimental study of endothelial cells in sprouting angiogenesis.

The impact of hepatitis B virus infection and vaccination on the development of non-Hodgkin lymphoma.

Hepatitis B virus (HBV) infection has been documented as a risk factor for non-Hodgkin lymphoma (NHL). However, there are few large cohort studies, and there is no report about the impact of HBV vaccination. We conducted this study to evaluate these issues. We used the nationwide cohort of the Taiwan National Health Insurance Research Database for 1997-2013. We compared the incidence and the risk of developing NHL and CD20+ aggressive lymphoma between HBV and non-HBV cohorts. The hazard ratios (HRs) were computed using Cox proportional hazards models. We matched these two large cohorts to reconfirm the data. We also compared the incidence of NHL between cohorts born before and after the inception of universal HBV vaccination. We found that HBV infection increased the risk for developing NHL and CD20+ aggressive lymphoma, with HRs of 4.14 and 5.52, with a higher incidence of 17.07 and 13.9 per 100 000 person-years, respectively, compared to the non-HBV cohort. The incidence of NHL in the cohort born in the era before universal HBV vaccination was higher with 1.85 per 100 000 person-years compared to 0.74 in the cohort born later aged younger than 20. Our study confirms that HBV confers a greater risk for developing NHL, especially CD20+ aggressive lymphoma. The impact of HBV vaccination is protective against lymphoma development in the teenagers in an endemic area, but longer follow-up is needed for older age.

Negative association between acrylamide exposure and body composition in adults: NHANES, 2003-2004.

BACKGROUND/OBJECTIVES: Acrylamide is present in mainstream cigarette smoke and in some food prepared at high temperature. Animal studies have shown that acrylamide exposure reduces body weight. Prenatal exposure to acrylamide also has been linked to reduced birth weight in human. Whether acrylamide exposure is associated with altered body compositions in adults is not clear. SUBJECTS/METHODS: We selected 3623 subjects (aged ⩾20 years) from a National Health and Nutrition Examination Survey (NHANES) in 2003-2004 to determine the relationship among hemoglobin adducts of acrylamide (HbAA), hemoglobin adducts of glycidamide (HbGA) and body composition (body measures, bioelectrical impedance analysis (BIA), dual energy x-ray absorptiometry (DXA)). Data were adjusted for potential confounding variables. RESULTS: The geometric means and 95% CI concentrations of HbAA and HbGA were 60.48 (59.32-61.65) pmol/g Hb and 55.64 (54.40-56.92) pmol/g Hb, respectively. After weighting for sampling strategy, we identified that one-unit increase in natural log-HbAA, but not HbGA, was associated with reduction in body measures (body weight, body mass index (BMI), subscapular/triceps skinfold), parameters of BIA (fat-free mass, fat mass, percent body fat, total body water) and parameters of DXA (android fat mass, android percent fat, gynoid fat/lean mass, gynoid percent mass, android to gynoid ratio). Subgroup analysis showed that these associations were more evident in subjects at younger age, male gender, whites, lower education level, active smokers and those with lower BMI. CONCLUSIONS: Higher concentrations of HbAA are associated with a decrease in body composition in the US general population. Further studies are warranted to clarify this association.

Incorporation of log odds of positive lymph nodes into the AJCC TNM classification improves prediction of survival in oral cancer.

OBJECTIVES: To assess the prognostic performance of a new N classification that incorporates the log odds of positive lymph nodes (LODDS) into the routinely used pathological N classification for oral squamous cell carcinoma (OSCC) patients. DESIGN: Retrospective cohort study utilising LODDS into pN category was performed, and the AJCC TNM stage and T-New N-M stage were compared with respect to 5-year disease-specific survival (DSS) rates. The discriminability was evaluated from the linear trend chi-square test, Akaike information criterion (AIC) and Harrell's c-statistic. SETTING: Medical centrer in Taiwan. PARTICIPANTS: A total of 463 patients received primary surgery and neck dissection between 2004 and 2013 for OSCC. MAIN OUTCOME MEASURES: The discriminability for 5-year DSS rates. RESULTS: The median follow-up period was 54 months, the mean patient age was 54 ± 11 years and 428 patients (92.4%) were male. The patients with higher LODDS had worse 5-year DSS rates. Incorporation of LODDS into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for 5-year DSS with a lower AIC (1883 versus 1897), and higher prediction accuracy (Harrell's c-statistic: 0.768 versus 0.764). CONCLUSIONS: By utilising a merger of the LODDS and pN classifications to create a new N classification has better discriminatory and predictive ability than pathological TNM staging and could help identify high-risk patients for intense adjuvant therapy.

Noninvasive tracking of gene transcript and neuroprotection after gene therapy.

Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer's dementia, Parkinson's disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine.

Prevalence of post-operative morbidity risk factors following cardiac surgery in patients with chronic viral hepatitis: a retrospective study.

OBJECTIVE: Current cardiac risk assessments such as EuroSCORE II and the STS-Score do not take liver dysfunction into account. The purpose of this study was to evaluate the prevalence and post-operative morbidity risk factors following cardiac surgery of patients with chronic viral hepatitis. PATIENTS AND METHODS: The study group consisted of 105 patients with documented chronic viral hepatitis who were subject to elective cardiac surgery from 2001 to 2012. Subjects were evaluated for pre-operative liver dysfunction according to the MELD score. RESULTS: The average MELD score of the study group was 10.00 ± 6.00. The average EuroSCORE ii of the study group was 2.07% ± 1.62%. The primary post-operative complication was cardiac complications (n=57, 54.3%). Analysis showed significant differences in meld score, bilirubin and smoking. Multivariate logistic regression analysis showed that the variables entering into the model included such risk factors with a significant or near significant (p < 0.2) influence on hospital morbidity and consisted in valve vs. coronary artery disease, valve/cad, aortic valve replacement vs. Coronary artery bypass graft, and bilirubin (mg/dl). CONCLUSIONS: it is vital that liver dysfunction is added to the risk models which are currently utilized to predict the post-operative morbidity of cardiac surgery patients.

Androgen deprivation increases the risk of fracture in prostate cancer patients: a population-based study in Chinese patients.

UNLABELLED: Androgen deprivation therapy (ADT) or orchiectomy is associated with an increased risk of osteoporosis or fracture. In this nationwide database analysis, we found that ADT or orchiectomy increased the risk of fracture in Chinese patients with prostate cancer. However, the magnitude of increase is seemingly not as large as that in Western populations. INTRODUCTION: ADT using gonadotropin-releasing hormone (GnRH) agonists or orchiectomy is associated with an increased risk of osteoporosis or fracture. To investigate the effects of ADT duration or orchiectomy on any type of fracture in Asian patients with prostate cancer, we conducted this retrospective analysis using a nationwide database in Taiwan. METHODS: We included 17,359 subjects who were newly diagnosed with prostate cancer between January 1, 1998, and December 31, 2007. The risk of first fracture was our primary endpoint. RESULTS: The rates of fracture from 12 months after prostate cancer diagnosis until the last follow-up date were 8.7 % for all patients, 7.1 % for patients who did not receive ADT or orchiectomy, 9.8 % for patients who received ADT, and 14.4 % for patients who received orchiectomy with or without ADT (P < 0.0001). In a Cox proportional hazard analysis, the relative risk of fracture increased steadily with the number of doses of GnRH agonists received during the first year after cancer diagnosis and with dose density. A significant hazard ratio was observed in patients who received at least nine doses within 1 year after diagnosis and in those whose dose density exceeded two doses per year. Age greater than or equal to 65 years was associated with a significantly lower risk of fracture. CONCLUSION: ADT or orchiectomy increases the risk of fracture in Chinese patients with prostate cancer. However, the magnitude of this increase is seemingly not as large as that in Western populations.

Adult T-cell leukaemia/lymphoma can mimic other lymphomas in a non-endemic area: dilemmas in diagnosis and treatment.

BACKGROUND: The diagnosis of Adult T-cell leukaemia/lymphoma (ATL) in non-endemic regions is challenging. AIM: This study analyses the clinicopathologic features and diagnostic processes of ATL patients in Taiwan. METHODS: ATL patients diagnosed and treated at Taipei Veterans General Hospital from 1998 through 2010 were retrospectively identified. The diagnosis of ATL was confirmed by in situ detection of human T-cell leukaemia virus type 1 (HTLV-1) when necessary. Patients' data were reviewed and analysed. RESULTS: Fourteen ATL patients were identified, among whom six (42.9%) had an antecedent diagnosis of other malignant lymphomas before the ATL diagnosis, including two diagnosed with Hodgkin disease (HD), one with peripheral T-cell lymphoma, two with chronic lymphocytic leukaemia and one with angioimmunoblastic T-cell lymphoma. Of the 14 patients, eight (57%) were subclassified as the acute type, three (21.4%) as the lymphoma type, and three (21.4%) as the chronic type ATL. Five of six (83.3%) patients with initial non-ATL misdiagnosis were diagnosed with non-acute type ATL. In particular, a patient with an antecedent diagnosis of HD presented with typical Reed-Sternberg (RS)-like cells harbouring Epstein-Barr virus genomes in affected lymph nodes. The patient progressed to acute type ATL 3 years after the initial diagnosis, and HTLV-1 genomes were identified in the previous RS-like cells. CONCLUSION: In non-endemic areas, such as Taiwan, ATL, particularly the non-acute type, may mimic other lymphomas and easily be misdiagnosed. HTLV-1 serology should be routinely screened in all malignant lymphoma patients. In situ detection of HTLV-1 is helpful in cases with diagnostic dilemmas.

Hepatitis C viral infection and the risk of dementia.

BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) infection may cause cognitive impairment, but no studies have focused specifically on cognitive impairment stemming from HCV. The purpose of this study was to investigate the potential increased risk for dementia in HCV-infected patients. METHODS: A population-based cohort study based on the Taiwan National Health Insurance Research Database was conducted. From all potential participants aged 50 years or more, a total of 58,570 matched (1:1) pairs of HCV-infected patients and non-HCV-infected patients were included. Each subject was individually tracked from 1997 to 2009 to identify incident cases of dementia (onset in 1999 or later). Cox proportional hazards regressions were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HCV infection and dementia. RESULTS: There were 2989 dementia cases from the HCV-infected cohort during the follow-up period of 533,861.1 person-years; the overall incidence rates of dementia differed from the non-HCV cohort (56.0 vs. 47.7 cases per 10,000 person-years, P < 0.05). The adjusted HR for dementia was 1.36 (95% CI 1.27-1.42) for HCV-infected patients after adjusting for alcohol-related disease, liver cirrhosis, hepatic encephalopathy and hepatocellular carcinoma. CONCLUSIONS: HCV infection may increase the risk for dementia. Further mechanistic research is needed.

Blood trace minerals concentrations and oxidative stress in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased oxidative stress. Certain essential trace minerals have shown to play an important role in the maintenance of redox homeostasis. We determined the concentrations of trace minerals in OSA patients and assessed their relationships to OSA severity as indicated by the apnea/ hypopnea index (AHI). METHODS: We enrolled 44 patients with newly diagnosed mild to moderate OSA and 20 without OSA. The following parameters were measured: polysomnographic values of nocturnal sleep; plasma trace minerals zinc (Zn), copper (Cu), iron (Fe), and erythrocyte selenium (Se); oxidative stress status; and plasma high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α). RESULTS: Compared to controls matched for age, gender, and body mass index, OSA patients had lower concentrations of plasma Zn and erythrocyte Se and higher plasma concentrations of Cu and Fe. OSA patients had significantly higher plasma concentrations of hs-CRP, TNF-α, and malondialdehyde (MDA), and lower erythrocyte antioxidant enzyme glutathione peroxidase (GPx) and superoxide dismutase activities. Significant differences in all the above parameters were also found in patients with moderate OSA compared to those with mild OSA. Furthermore, AHI values correlated significantly with neck circumference, GPx activity, and MDA, hs-CRP, and TNF-α concentrations in OSA patients. AHI values were also negatively associated with concentrations of plasma Zn and erythrocyte Se, but were positively linked to plasma concentrations of Fe and Cu. CONCLUSIONS: Abnormal concentrations of these trace minerals may reflect oxidative damage and inflammatory response, thus increasing the severity of OSA.

Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk.

BACKGROUND: The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. METHODS: From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. RESULTS: Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8-33.0) than with prostatitis (10.5, 95% CI=3.36-32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7-69.9). CONCLUSION: Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions.

Prenatal smoke exposure, DNA methylation, and childhood atopic dermatitis.

BACKGROUND: The biological mechanisms of how prenatal smoke exposure leading to atopic disorders remain to be addressed. Whether prenatal smoke exposure affects DNA methylation leading to atopic disorders is not clear. OBJECTIVE: As most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure induces cord blood DNA methylation. METHODS: Methylation differences associated with smoke exposure were screened by Illumina Infinium 27K methylation arrays for 14 children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors was collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen. RESULTS: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p = 0.018). TSLP gene was further investigated in a larger sample of 150 children from the cohort who completed the follow-up study. Methylation status of the TSLP 5'-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR = 3.17, 95% CI = 1.63-6.19) and with AD (OR = 2.32, 95% CI = 1.06-5.11). The degree of TSLP 5'CGI methylation inversely correlated with TSLP protein expression levels (r = -0.45, P = 0.001). CONCLUSIONS & CLINICAL RELEVANCE: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation.

Young nasopharyngeal cancer patients with radiotherapy and chemotherapy are most prone to ischaemic risk of stroke: a national database, controlled cohort study.

OBJECTIVES: This population-based cohort study investigated the ischaemic stroke risk of patients with nasopharyngeal carcinoma (NPC) by treatment. DESIGN: Controlled cohort study. SETTING: Based on claims data of National Health Research Insurance Database in years 1996-2010. PARTICIPANTS: A total of 4615 patients with nasopharyngeal carcinoma newly diagnosed in 2000-2003 were divided into three subgroups: patients received radiotherapy only, patients received both radiotherapy/chemotherapy and patients received neither radiotherapy nor chemotherapy (non-radio/chemotherapy). They were compared with 36 919 reference persons without stroke and cancer, frequency matched with demographic characteristics. MAIN OUTCOME MEASURES: Study subjects were followed up until 2010 to measure ischaemic stroke incidences. Risks associated with treatment and comorbidity were evaluated using Cox proportional hazards regression analysis incorporated with the competing risk of deaths. RESULTS: Ischaemic stroke incidence rates were ≈2-fold higher in nasopharyngeal carcinoma patients with radiotherapy, radiotherapy/chemotherapy and non-radio/chemotherapy than in references (13.8, 12.8 and 12.6 versus 6.07 per 1000 person-years, respectively). The risk was much higher for 20- to 39-year-old nasopharyngeal carcinoma patients with radiotherapy/chemotherapy [hazard ratio (HR) 14.7, 95% confidence interval 9.24-23.4]. Hypertension, diabetes, hyperlipidaemia and alcoholism also enhanced the risk with hazard ratios ranging from 2.4 to 9.3. The overall adjusted ischaemic stroke risk was higher in nasopharyngeal carcinoma patients with the two types of treatment than those without, but not significant. CONCLUSIONS: Patients with nasopharyngeal carcinoma are at an elevated risk of ischaemic stroke, without significant difference among treatment modalities. The relative risk is more prominent in younger patients. Comorbidity may enhance the risk.

PP-1α and PP-1γ display antagonism and differential roles in tumorigenicity of lung cancer cells.

Protein serine/threonine phosphatases are important cellular signaling molecules and play major roles in regulating many different functions including cell proliferation, senescence, programmed cell death, and oncogenic cell transformation. Among different serine/threonine phosphatases, PP-1 and PP-2A contribute to more than 90% phosphatase activities in eukaryotes. While the functions of PP-2A in cell transformation and tumorigenesis have been well established, the role of PP-1 in carcinogenesis remains to be further explored. Moreover, PP-1 exists in different isoforms, whether these isoforms have differential functions in tumorigenesis remains to be examined. In the present study, we demonstrated that in lung cancer 1299 cells, PP1α and PP- 1 & γ exist in an antagonizing balance. In the parent H1299 cells, PP-1γ is dominant, about 4-fold higher than that of PP-1α. Overexpression of PP-1α significantly down-regulates PP-1γ at both mRNA and protein levels. In contrast, knockdown of PP-1α leads to upregulation of PP-1γ. Moreover, overexpression of PP-1α significantly attenuates the ability of the H1299 cells in promoting tumorigenicity as tested in immuno-deficient nude mice. This attenuation is derived from the halted cell cycle progression, which is largely attributed by the changed RB-E2F activity. Together, our results demonstrate that PP-1α and PP-1γ not only antagonize each other in lung cancer cells, but also display differential functions in tumorigenicity.

A population-based cohort study in Taiwan--use of insulin sensitizers can decrease cancer risk in diabetic patients?

BACKGROUND: The purpose of the study was to explore the possible association between the use of insulin sensitizers (thiazolidinediones, TZDs) and the risk of cancer in Taiwanese diabetic patients. PATIENTS AND METHODS: From the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 22 910 diabetic patients newly diagnosed from 2001 to 2009 and 91 636 non-diabetic comparisons frequency matched with age, sex, and calendar year, excluding those with cancer at the baseline. Among the diabetics, 4159 patients were treated with TZDs and the rest of 18 752 patients were on other anti-diabetic medications (non-TZDs). RESULTS: In comparison to the non-diabetes group, the non-TZDs group had an increased risk of developing cancer [the adjusted hazard ratio (HR): 1.20 and 95% confidence interval (CI) = 1.11-1.30]. The TZDs group had a HR of 1.18 (95% CI = 0.98-1.42). Analysis of site-specific cancer risks showed that both TZDs and non-TZDs groups with elevated risks of colorectal and pancreatic cancer. However, the non-TZDs group had an increased risk of liver cancer when comparing with TZD and non-diabetes groups. CONCLUSION: This study suggests that patients with diabetes are at an elevated risk of cancer (especially in colorectal and pancreatic cancers), and the use of TZDs might decrease the liver cancer risk in diabetic patients. Further investigation using large samples and rigorous methodology is warranted.

The PP2A-Aß gene is regulated by multiple transcriptional factors including Ets-1, SP1/SP3, and RXRα/ß.

Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65 kD scaffold A subunit, a 36 kD catalytic C subunit, and a regulatory B subunit of variable isoforms ranging from 54-130 kDs. The scaffold subunits, PP2A-Aα/ß, act as platforms for both the C and B subunits to bind, and thus are key structural components for PP-2A activity. Mutations in both genes encoding PP2A-Aα and PP2A-Aß lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-Aα is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2α but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-Aß gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXRα/ß, are present in the proximal promoter of the mouse PP2A-Aß gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXRα/ß all bind to PP2A-Aß gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXRα/ß positively regulate the promoter of the PP2A-Aß gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXRα/ß and the luciferase reporter gene driven by PP2A-Aß promoter further confirm their control over the PP2A-Aß promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXRα/ß can all bind to the PP2A-Aß gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aß gene. Moreover, our results provide important information explaining why PP2A-Aα and PP2A-Aß display distinct expression levels.

Magnetic resonance cholangiography in living donor liver transplantation: comparison of preenhanced and post-gadolinium-enhanced methods.

OBJECTIVE: The purpose of this study was to evaluate the image quality and diagnostic accuracy of postgadolinium complex of diethylenetriaminepentaacetic acid (GD-DTPA)-enhanced magnetic resonance cholangiography (MRC) in donor selection. MATERIALS AND METHODS: Donors (n=228) with both preoperative MRC and intraoperative cholangiography (IOC) were enrolled in this study. MRC pre- and post-GD-DTPA enhancement were performed using 1.5-T magnetic resonance imaging. The signal-to-noise ratio (SNR) of liver parenchyma and contrast-to-noise ratio of bile duct, as well as the contrast between bile duct and liver parenchyma, were calculated. The biliary anatomy correlation with the IOC during hepatectomy and patient prognosis were also evaluated. RESULTS: Quantitative results of the SNR of the liver parenchyma post-GD-DTPA were statistically significantly lower than preenhanced MRC (2.69 times reduced from the preenhanced MRC). The contrast of the bile duct and liver parenchyma in post-GD-DTPA were significantly higher than the preenhancement MRC. The anatomic diagnostic accuracy rate of post-GD-DTPA MRC was 92.9%. The sensitivity and specificity of GD-PTPA MRC were 85% and 96%, respectively. GD-DTPA-enhanced MRC has higher accuracy than the preenhanced MRC (92.9% vs 75%). The concurrence between GD-DTPA-enhanced MRC and IOC were commendable (kappa=0.9). The posttransplant biliary complication rate was 5.5%, and the 3-year survival rate was 91.2% in the recipients. CONCLUSION: GD-DTPA, a paramagnetic metal, can shorten the T1 and T2 relaxation values of surrounding protons. This decreases the signal of the liver parenchyma and brightens the biliary anatomy. It can improve the image quality of MRC and increase the diagnostic accuracy of the biliary tract classification. It is mandatory in the "donor and recipient surgery during the LDLT".