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Ya-Chi Cheng,1,&ast; Yi-Chun Kuo,2,&ast; Pei-Chi Chang,2 Ya-Ching Li,2 Wan-Ting Huang,3 Wei Chen,4 Che-Yi Chou5– 7 1Division of Family Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan; 2Community Nursing Room, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan; 3Clinical Medicine Research Center, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan; 4Division of Pulmonary and Critical Care Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan; 5Division of Nephrology, Asia University Hospital, Wufeng, Taichung, Taiwan; 6Department of Post-baccalaureate Veterinary Medicine, Asia University, Wufeng, Taichung, Taiwan; 7Division of Nephrology, China Medical University Hospital, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Che-Yi Chou No. 222, Fuxin Road, Wufeng Dist, Taichung, 413, TaiwanTel +886-4-37061668-1878Fax +886-4-37061668-1337Email cychou.chou@gmail.comBackground: The World Health Organization (WHO) proposed the integrated care for older people (ICOPE) screening tool to identify functional impairment. We explore the association of geriatric functional impairment and hypertension, diabetes, dyslipidemia in the community-dwelling elderly.Methods: We enrolled individuals aged at least 65 with hypertension, diabetes, or dyslipidemia; or those aged at least 75 from May to July 2019. We applied ICOPE tools to evaluate six function assessments: cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms. Factors were analyzed using stepwise multivariable linear regression for ICOPE scores and logistic regression for geriatric functional impairment. All analyses were adjusted for age and glomerular filtration rate.Results: We enrolled 457 participants including 303 (66.3%) participants with hypertension, 296 (64.8%) diabetes, and 221 (48.4%) dyslipidemia. Seventy-eight (17.1%) participants have at least one geriatric functional impairment, including 41 (25.9%) participants aged ≥ 75 and 37 (12.4%) aged 65– 74. The ICOPE score (0.4 ± 0.6) of participants aged at least 75 was higher than that (0.1 ± 0.4) of the participants aged 65– 74 (p < 0.001). Dyslipidemia (p = 0.002) was positively associated with ICOPE score. Dyslipidemia (odds ratio: 2.15, 95% confidence interval: 1.27– 3.70, p = 0.005), not hypertension (p = 0.3) and diabetes (p = 0.9), was associated with geriatric functional impairment. Visual impairment was the most common function impairment. Female was linked to limited mobility, renal function was associated with mobility (p < 0.001) and nutrition (p = 0.02).Conclusion: Dyslipidemia but not hypertension, diabetes is linked to geriatric functional impairment in community-dwelling elderly. Lower renal function is associated with decreased mobility and nutrition. More studies are needed to determine if treatment of dyslipidemia reduces geriatric functional impairment.Keywords: aging, elderly, function impairment, geriatric functional impairment, ICOPE, renal function

Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). So far, there is no biomarker-based prediction tool available for EPS. Matrix metalloproteinase-2 (MMP-2) is a protein involved in the breakdown of the extracellular matrix, and the effluent MMP-2 can be a potential biomarker of EPS. This study is aimed at developing a nomogram for EPS based on effluent MMP-2 levels. Patients and Methods. We enrolled 18 EPS patients and 90 gender-matched PD patients without EPS in this cross-sectional case-controlled study. The effluent MMP-2 levels and possible risk factors for EPS were analyzed using multivariable logistic regression, and a nomogram was developed. The nomogram was validated using 200 bootstrap resamples to reduce overfit bias. Results. The effluent MMP-2 levels in EPS patients were significantly higher than those in normal PD patients (p<0.001, Manny-WhitneyUtest). Effluent MMP-2 levels and PD duration were independently associated with EPS risks (p<0.001andp=0.001) in multivariate logistic regression. A nomogram based on MMP-2 levels and PD duration was proposed. The AUC of MMP-2 was 0.824, and the AUC of the nomogram was 0.907 (p=0.05). Conclusion. A nomogram based on effluent MMP-2 levels and PD duration may predict EPS with high accuracy.

Background We previously showed the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) regions with extracephalic reference placement in improving negative symptoms in schizophrenia. In this ancillary investigation, the effects of this intervention on insight levels, other clinical outcomes, and cardio-respiratory and autonomic functions were examined and the potential of biomarkers for treatment response was explored. Methods Schizophrenia patients were randomly allocated to receive 10 sessions of bi-anodal tDCS over the PFC regions with extracephalic reference placement (2 mA, 20 minutes, twice daily for 5 weeks) or sham stimulation. We examined, in 60 patients at baseline, immediately after stimulation and at follow-up visits, the insight levels, other clinical outcomes, blood pressure, respiratory rate, heart rate, and heart rate variability. Results Insight levels as assessed by the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia awareness of the disease, positive and negative symptoms dimensions, and beliefs about medication compliance as assessed by Medication Adherence Rating Scale were significantly enhanced by active stimulation relative to sham. No effects were observed on cognitive insight, other clinical outcomes, or cardio-respiratory and autonomic functions. Heart rate variability indices as biomarkers were not associated with the clinical response to the intervention. Conclusions Our results provide evidence for bi-anodal tDCS over the PFC regions with extracephalic reference placement in heightening the levels of insight into the disease and symptoms, as well as beliefs about medication compliance in schizophrenia, without impacting other clinical outcomes and cardio-respiratory/autonomic functions.

Little is known about the impact of fronto-temporal transcranial direct current stimulation (tDCS) on attitudes toward mental illness, psychosocial and autonomic functioning, life quality, and medication adherence among schizophrenia patients.Sixty schizophrenia patients were randomly allocated to receive 10 sessions of active (2 mA, 20 min, 2 sessions/day for five weekdays) or sham fronto-temporal tDCS. Self-Appraisal of Illness Questionnaire (SAIQ), Medication Adherence Rating Scale (MARS), World Health Organization Quality of Life-BREF (WHOQOL-BREF) and indices of heart rate variability (HRV) were measured at baseline, immediately after tDCS and at one-month follow-up visit.There were significant group-by-time interactions for scores of SAIQ presence/outcome subscale, total MARS and its subscale of subjective response to taking medication, WHOQOL-BREF psychological domain. Relative to sham, tDCS significantly improved self-awareness of presence/outcome of schizophrenia (Cohen's d = 0.465, p = 0.0011), subjective response to taking medication (Cohen's d = 0.639, p 0.001) and psychological domain of life quality (Cohen's d = 0.459, p = 0.00114). These effects lasted for less than one month. The group-by-time interactions were non-significant for clinician-rated psychosocial functioning, mean RR intervals, and all HRV indices.Fronto-temporal tDCS briefly optimizes self-reported insight levels, beliefs about treatment adherence, and psychological domain of life quality in patients with schizophrenia. Further studies are required to confirm whether patients treated with 5-day, 10-session tDCS in combination with multisession "maintenance" stimulation every month would attain favourable outcomes.We provide novel evidence for the potential utility of tDCS in schizophrenia.

Background/aim The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. Materials and methods This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. Results The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. Conclusion The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.

Background Hypokalemia is a common clinical problem. The association between urinary tract infection (UTI) and hypokalemia is not clear. Hypokalemia is common in patients with UTI in clinical observation. The aim of the study is to determine if UTI is associated with hypokalemia. Methods Patients hospitalized with UTI and the control group were retrieved from the Longitudinal Health Insurance Database 2005. The control group was patients hospitalized with other reasons and were matched for the confoundings of UTI and hypokalemia. We analyze the risk of hypokalemia using logistic regression and calculate the odds ratio (OR) and 95% confidence interval (CI) of OR. Results We analyzed 43,719 UTI patients and control patients. Hypokalemia was found in 4540 (10.4%) patients with UTI and 1842 (4.2%) control patients. The percentage of patients with hypokalemia was higher in UTI patients (chi-square, p p Conclusions Urinary tract infection is associated with hypokalemia among inpatients. The association is independent of patients’ comorbidities and medications. Recurrent UTI is associated with increased hypokalemia in UTI patients.

Background/aim Solitary extramedullary plasmacytoma (SEP) is a rare, malignant plasma-cell tumor, which mainly occurs in the head and neck regions. Globally the disease has been rarely happening up to 2019, with only about ten papers focused on SEP cases reported in English. Thus, a literature collectively reviewing the characteristics of the patients would be valuable. Patients and methods We enrolled 10 SEP patients, and recorded their primary sites and the treatment modality, and analyzed their survival rates and outcomes. We also reviewed previous studies and compared their findings with ours. Results No gender or age disparity has been observed, and younger patients had a better local control with RT compared to surgery among our patients. Conclusion Further investigations with more patients and long-time follow-up may provide more information for treatment determination and the recurrence and progression from SEP to MM.

Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk.MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples.MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index.Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

Background/aim Rs3824129 is a functional six-nucleotide insertion(I)/deletion(D) polymorphism in the promoter region of caspase 8, an essential apoptosis gene. We aimed to examine the association of this polymorphism with the risk of bladder cancer in the Taiwanese population. Materials and methods Caspase-8 rs3834129 genotypes were determined and their associations with bladder cancer risk were evaluated among 375 patients and 375 controls by the PCR-RFLP methodology. In addition, the interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were examined. Results The frequencies of II, ID and DD genotypes for caspase-8 rs3834129 were non-differentially distributed between the two groups (p for trend=0.7187). Analysis of allelic frequency distribution also indicated that the D variant allele was not associated with a risk of bladder cancer. There was no obvious joint interaction between caspase-8 rs3834129 genotypes and smoking, alcohol consumption, and clinical stage and grade. Conclusion Caspase-8 rs3834129 genotypes play a minor role in the personal susceptibility to bladder cancer in Taiwan.

No studies have examined the effects of fronto-temporal transcranial direct current stimulation (tDCS) on cognitive insight and neurocognitive function in schizophrenia patients and the dynamic interplay between tDCS-induced changes in these two outcomes. In this double-blind, randomized, sham-controlled study, we investigated the effects of fronto-temporal tDCS [anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5 days] on illness severity, psychosocial functioning, cognitive insight and neurocognitive function in schizophrenia patients (N = 60). The authors observed significant trends that tDCS ameliorated the severity of total and general psychopathology as measured by the Positive and Negative Syndrome Scale. No significant effects were observed for other psychopathological symptoms and psychosocial functioning. Cognitive insight as measured by the Beck Cognitive Insight Scale (BCIS) was rapidly enhanced by 10-session tDCS (F = 10.80, Cohen's d = 0.44, p = 0.002) but the beneficial effect became borderline significant 1 month after stimulation. A trend-level improvement with tDCS of planning ability (F = 6.40, Cohen's d = 0.339, p = 0.014) as measured by the accuracy in Tower of London task was also observed. In the active tDCS group, the change in cognitive insight from baseline to immediately after tDCS assessment was positively correlated with that in planning ability (r = 0.46, p = 0.015), which was independent of the corresponding change in illness severity. The promising results regarding the fast-acting beneficial effects of tDCS on cognitive insight and planning ability in schizophrenia require confirmation in future replication studies.

Background: Glomerular filtrate rate (GFR) decline is associated with increased risk of dialysis in patients with chronic kidney disease (CKD). It is unclear whether the maximum, the minimum, or the average of GFR decline rate is associated with the risk of mortality and the initiation of renal replacement therapy (RRT). We investigated prognostic role of the maximum, the minimum, and the average of GFR decline rate in patients with CKD not yet on dialysis. Methods: Patients, enrolled in the CKD program of China Medical University Hospital between July 2004 and Aug 2013, with CKD stages 3–5 (estimated GFR [eGFR] < 60 mL/min/1.73 m2) not yet on dialysis were analyzed. Primary outcome was a composite of mortality and RRT. The association between 3 readings of GFR decline rate and primary outcome was analyzed using Cox proportional hazard regression. Results: We analyzed 815 patients aged 75 (interquartile range [IQR] 65–82) years with a median follow-up of 5.2 years (IQR 3.9–6.9). The maximum of eGFR decline rate was associated with the primary outcome (hazard ratio 2.19, 95% CI 1.16–4.12, p = 0.015), independent of age, gender, diabetes, cerebrovascular accident, smoking, baseline eGFR, serum albumin, calcium, urine protein/creatinine ratio, usage of renin-angiotensin system blockade. The minimum and the average of eGFR decline rate were not associated with the primary outcome. Conclusions: The maximum of GFR decline rate was associated with mortality and poor renal outcome in CKD patients, independent of other contributive confounders.

Objectives: Systemic inflammation has been reported to be associated with uremic pruritus (UP). Although a vegetarian diet can reduce systemic inflammation in hemodialysis patients, the effect of vegetarian diet on UP is not clear. The purpose of the study was to know the possible effects of vegetarian diet on UP. Methods: A cross-sectional study was done to compare the severity of UP and blood levels of systemic inflammatory markers between vegetarian and non-vegetarian hemodialysis patients. Six non-vegetarian patients with uremic pruritus changed their non-vegetarian diet to vegetarian diet for 2 months. Visual Analogue Scale (VAS) and pruritus score (PS) were used to measure the UP severity. The serum high-sensitivity C-reactive protein (hs-CRP), and interleukin-2 (IL-2) were used as markers of inflammation. Results: Both the median VAS scores (p = .043) and the median PS scores (p

OBJECTIVE Tracheostomy in children is a surgical procedure with considerable morbidity and mortality. However, there is still a lack of population-based survey in pediatric tracheostomy. This study analyses population-based data in pediatric tracheostomy among different ages in Taiwan. METHODS This study used National Health Insurance Research Database in Taiwan. All children (aged

The treatment of human colorectal cancer (CRC) cells through suppressing the abnormal survival signaling pathways has recently become a significant area of focus. In this study, our results demonstrated that decyl caffeic acid (DC), one of the novel caffeic acid derivatives, remarkedly suppressed the growth of CRC cells both in vitro and in vivo. The inhibitory effects of DC on CRC cells were investigated in an in vitro cell model and in vivo using a xenograft mouse model. CRC cells were treated with DC at various dosages (0, 10, 20 and 40 μM), and cell survival, the apoptotic index and the autophagy level were measured using an MTT assay and flow cytometry analysis, respectively. The signaling cascades in CRC were examined by Western blot assay. The anti-cancer effects of DC on tumor growth were examined by using CRC HCT-116 cells implanted in an animal model. Our results indicated that DC differentially suppressed the growth of CRC HT-29 and HCT-116 cells through an enhancement of cell-cycle arrest at the S phase. DC inhibited the expression of cell-cycle regulators, which include cyclin E and cyclin A proteins. The molecular mechanisms of action were correlated to the blockade of the STAT3 and Akt signaling cascades. Strikingly, a high dosage of DC prompted a self-protection action through inducing cell-dependent autophagy in HCT-116 cells. Suppression of autophagy induced cell death in the treatment of DC in HCT-116 cells. DC seemed to inhibit cell proliferation of CRC differentially, and the therapeutic advantage appeared to be autophagy dependent. Moreover, consumption of DC blocked the tumor growth of colorectal adenocarcinoma in an experimental animal model. In conclusion, our results suggested that DC could act as a therapeutic agent through the significant suppression of tumor growth of human CRC cells.

Background The efficacy of fronto-temporal transcranial direct current stimulation in treating auditory verbal hallucinations and other psychopathological symptoms of schizophrenia patients has been examined in a small number of clinical trials with limited sample sizes, but the results are mixed. Fronto-temporal transcranial direct current stimulation has also been demonstrated to enhance patients’ insight into their mental illness in an open-label pilot study. The current investigation aimed to investigate the therapeutic effects of fronto-temporal transcranial direct current stimulation on the severity of auditory verbal hallucinations, other schizophrenia symptoms, and insight in a large double blind, randomized, sham-controlled trial. Methods Sixty patients with medication-refractory auditory verbal hallucinations were randomized over 2 conditions: transcranial direct current stimulation with 2-mA, twice-daily sessions for 5 consecutive days, with anodal stimulation to the left prefrontal cortex and cathodal stimulation to the left temporo-parietal junction, and sham treatment. Results Fronto-temporal transcranial direct current stimulation failed to cause significant changes in the severity of auditory verbal hallucinations and other schizophrenia symptoms. The levels of insight into illness (effect size=0.511, P

Background/Purpose With an increasing geriatric population, the need for effective management of chronic conditions and medication use in the elderly is growing. Medication use in the elderly presents significant challenges due to changes in pharmacodynamic and pharmacokinetic profiles. We aimed to examine the impact of a collaborative physician-pharmacist medication therapy management (MTM) program for polypharmacy elderly patients. Methods Elderly patients with multiple chronic conditions on polypharmacy were enrolled in this prospective, randomized, and controlled study over 16 months of implementation. The intervention group consisted of patients randomized to a collaborative pharmacist-physician MTM program. They were monitored continuously by a clinical pharmacist, while patients in the control group received only usual care with follow-up assessment. Primary outcome was economic differences, measured in total medical expenditure. Secondary outcomes of clinical and humanistic effects were compared between the two groups. Results The total number of enrolled patients was 87 and 91 in the MTM and usual groups, respectively. The difference-in-difference estimate on medical expenditure during the 16-month implementation period was $3,758,373 New Taiwan Dollars ($127,015 US Dollars) less than the usually care group. Impact was also seen in humanistic outcomes while lipid profiles and mortality trended toward improvement. Conclusion The pharmacist-physician collaborative MTM program for polypharmacy elderly had significant cost savings and improvement in humanistic measures, demonstrating the importance of clinical pharmacists and MTM programs for elderly patients in Taiwan. The results suggest the possibility of clinical benefits, but the study was not substantially powered to find a statistical difference.

Patients with type 2 diabetes mellitus (T2DM) experience many cardiovascular complications. Several studies have demonstrated the cardioprotective effects of incretin-based therapies; however, there are few studies on the effects of long-term incretin-based therapies on cardiovascular events. Therefore, the present study conducted a systematic review and network meta-analysis to evaluate the effects of long-term incretin-based therapies on ischaemic diseases. We searched PubMed, CENTRAL, and Clinicaltrial.gov to retrieve randomised control trials reported until December 2016 and enrolled only RCTs with more than a 1-year follow-up. The network meta-analysis was performed using R Software with a GeMTC package. A total of 40 trials were included. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 agonists were associated with a lower risk of myocardial infarction (MI) than were sulfonylureas (odds ratio [95% credible interval] 0.41 [0.24–0.71] and 0.48 [0.27–0.91], respectively). These results suggested that patients with T2DM receiving long-term incretin-based therapies have a lower risk of MI than do those receiving sulfonylurea-based therapy. These findings highlight the risks of cardiovascular events in patients who receive long-term incretin-based therapies, and may provide evidence for the selection of antidiabetic therapy in the future.

To assess outcomes of pediatric tracheotomy and duration of associated hospital stay according to indications.In this retrospective study, subjects were 142 consecutive pediatric patients (18 years old) who underwent tracheotomy at a tertiary referral medical center, National Taiwan University Hospital, in 1997-2012. Age, sex, indications, pre-operative status (oxygen demand, number of repeated intubations), and post-operative status (duration of weaning, length of hospital stay, mortality) were analyzed.The indications included craniofacial anomalies (n = 19, 13.4%), upper airway obstruction (n = 41, 28.9%), neurological deficit (n = 58, 40.8%), prolonged ventilation (n = 15, 10.6%), and trauma (n = 9, 6.3%). Ninety-one patients (64.1%) were successfully weaned off ventilation after tracheotomy (40% in the prolonged ventilation group). Total hospital stay and duration of ventilation before tracheotomy were longest in patients with craniofacial anomalies (150.9 ± 98.8 days, p = 0.004; 108.8 ± 88.2, p 0.001). The early tracheotomy group had a shorter duration of post-tracheotomy mechanical ventilation support than the late tracheotomy group (14.4 ± 19.0, n = 49 vs. 34.9 ± 58.6, n = 80, p = 0.004). Decannulation was successful in 20 patients (14.1%), with the highest rate in the upper airway obstruction group (n = 14, 34.1%) and lowest in the prolonged ventilation group (none). Thirteen patients (9.2%) died during admission from causes unrelated to tracheotomy.Outcomes of pediatric tracheotomy and duration of hospitalization depend on indications. Children with craniofacial anomalies had earlier tracheotomy age and longer mechanical ventilation before tracheotomy resulted in longer hospitalization. Earlier tracheotomy can shorten the duration of post-tracheotomy mechanical ventilation in several conditions.

Hyperglycemia is associated with a reduced number of endothelial progenitor cells (EPCs) that impairs vascular function. Circulating EPCs play important roles in postnatal neovasculogenesis and the prevention of ischemic injury. Frequent consumption of fish oil (FO) that is abundant with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) is reportedly associated with an alleviation of diabetic complications and a lowered incidence of cardiovascular disease. The aim of this study was to examine whether N-3 polyunsaturated fatty acids such as EPA and DHA would reverse the high glucose-mediated dysfunction of EPCs in vitro and thereby prevent the ischemic injury that occurs under the hyperglycemic conditions in Type 2 diabetes (T2D) db-/- mice. The results demonstrate that EPA and DHA alleviate high glucose-mediated impairment of tubular formation in EPCs through a rescue of neovasculogenic capability. The molecular mechanisms underlying the effects of EPA and DHA include the activation of the extracellular signal-regulated kinase 1/2, Akt/endothelial nitric oxide synthase (eNOS) and AMP-activated kinase (AMPK) signaling cascades as well as the phosphorylation of the downstream FOXO3a protein in EPCs. Moreover, EPA and DHA up-regulate the expression of c-kit, erythroid 2-related factor and heme oxygenase-1 proteins. Daily consumption of FO at dosages of 4% and 6% (wt/wt) significantly increased the level of bone marrow-derived and circulating EPCs, induced a recovery of blood flow and prevented ischemic injuries in a T2D db-/- mouse model. The effects of FO consumption were exerted the activation of Akt/eNOS and AMPK signaling cascades without any effect on the plasma VEGF level in vivo.

The treatment of breast cancer cells obtained by blocking the aberrant activation of the proliferation signaling pathways PI3K/Akt/mTOR and MEK/ERK has received considerable attention in recent years. Previous studies showed that Taiwanin A inhibited the proliferation of several types of cancer cells. In this study, we report that 3,4-bis-3,4,5-trimethoxybenzylidene-dihydrofuran (BTMB), a novel derivative of Taiwanin A, significantly inhibited the proliferation of triple-negative breast cancer (TNBC) cells both in vitro and in vivo. The results show that BTMB inhibited the proliferation of human TNBC cells by the induction of cell-cycle arrest and apoptosis in a dose-dependent fashion. BTMB inhibited the expression of β-catenin, cdc2 and the cell-cycle regulatory proteins, cyclin A, cyclin D1, and cyclin E. The mechanism of action was associated with the suppression of cell survival signaling through inactivation of the Akt and ERK1/2 signaling pathways. Moreover, BTMB induced cell apoptosis through an increase in the expression of BAX, cleaved caspase-3, and cleaved PARP. Moreover, BTMB inhibited TNBC cell colony formation and sensitized TNBC cells to cisplatin, a chemotherapeutic drug. In a TNBC mouse xenograft model, BTMB significantly inhibited the growth of mammary carcinomas through decreased expression of cyclin D1. BTMB was shown to significantly suppress the growth of mammary carcinoma and therefore to have potential as an anticancer therapeutic agent. Mol Cancer Ther; 16(3); 480–93. ©2016 AACR.

Depression is a common bio-psycho-social problem in hemodialysis (HD) patients. Traditional Chinese medicine has been used for symptom management in patients with depression. Identification of the specific constitution in traditional Chinese medicine is critical for personalized care. However, the association between depression and specific constitution in HD patients is unknown.We conducted a cross-sectional study in all chronic HD patients (HD for more than 3 months) at China Medical University Hospital in Taiwan. The depression symptom severity was determined using the Beck Depression Inventory II (BDI-II). Clinical patterns in Chinese medicine were determined using the Constitution in Chinese Medicine Questionnaire. The association between constitution and depression was analyzed using logistic regression.We recruited 467 chronic hemodialysis patients, including 219 females and 248 males, with a mean age of 63±12years. The mean duration of HD was 5.8 years. The mean score for the BDI-II was 11 (interquartile range 8-14). The major constitution was Yang-deficiency (43.7%) among these chronic HD patients. Qi-deficiency was correlated with a duration of HD of more than 5.8 years (p=0.04). Qi-deficiency [odds ratio (OR): 4.05, 95% confidence interval (CI): 1.69-9.72, p0.01] was also associated with depression in logistic regression with adjustments for confounders, including calcium, phosphorus and hemoglobin levels.Qi-deficiency constitution in Chinese medicine is associated with depression in chronic HD patients. Further studies are needed to determine whether treating Qi-deficiency integrating Chinese medicine treatment can improve patients' depression symptoms.

QRS duration has been associated with the response to cardiac resynchronization therapy (CRT). However, the methods for defining QRS duration to predict the outcome of CRT have discrepancies in previous reports. The aim of this study was to determine an optimal measurement of QRS duration to predict the response to CRT.Sixty-one patients who received CRT were analyzed. All patients had class III-IV heart failure, left ventricular ejection fraction not more than 35%, and complete left bundle branch block. The shortest, longest, and average QRS durations from the 12 leads of each electrocardiogram (ECG) were measured. The responses to CRT were determined using the changes in echocardiography after 6 months. Thirty-five (57.4%) patients were responders and 26 (42.6%) patients were non-responders. The pre-procedure shortest, average, and longest QRS durations and the QRS shortening (ΔQRS) of the shortest QRS duration were significantly associated with the response to CRT in a univariate logistic regression analysis (P = 0.002, P = 0.03, P = 0.04 and P = 0.04, respectively). Based on the measurement of the area under curve of the receiver operating characteristic curve, only the pre-procedure shortest QRS duration and the ΔQRS of the shortest QRS duration showed significant discrimination for the response to CRT (P = 0.002 and P = 0.038, respectively). Multivariable logistic regression showed the pre-procedure shortest QRS duration is an independent predictor for the response to CRT.The shortest QRS duration from the 12 leads of the electrocardiogram might be an optimal measurement to predict the response to CRT.

The objective of the study was to determine whether chronic osteomyelitis (COM) is associated with increased risk of new-onset atrial fibrillation (AF).A national insurance claim data set of 23 million enrollees was used to identify 19,002 patients with newly-diagnosed COM and 76,008 randomly selected age- and sex-matched control subjects between January 1, 2000 and December 31, 2009 for comparing the risk and incidence of AF. The study end point was defined as the first diagnosis of AF, death, withdrawal from the insurance program, or the end of 2010.During a follow-up period of 91,927 person-years, the incidence of new-onset AF in COM cohort was 1.42-fold higher than for the non-COM cohort (4.54 vs 3.19 per 1000 person-years). After adjusting for age, sex, and classical AF risk factors such as hypertension, diabetes, heart failure, coronary artery disease, and valvular heart disease, the risk of new-onset AF remained significantly higher in the COM cohort (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.18-1.49; P0.0001). In age-stratified analysis, the younger population carried a higher risk for incident AF than the elderly population (from HR 2.05; 95% CI, 1.12-3.74 in age younger than 50 years to HR 1.19; 95% CI, 0.95-1.49 in age 80 years and older). The adjusted Kaplan-Meier analysis showed a lower AF-free survival rate in the COM group compared with the control group (log-rank P0.0001) during the follow-up period.This study showed that patients with COM carry an increased risk for developing new-onset AF, particularly in the younger population. Further studies are required to explore the underlying mechanisms that link COM and AF.

Limited information is currently available on 24-h ambulatory blood pressure (ABP) changes after adenotonsillectomy (TA) in children with obstructive sleep apnea (OSA). In this study, the trajectory of 24-h ABP changes after surgery in children with OSA was examined at three-month and six-month follow-up.Children aged 4-16 years with clinical symptoms of OSA and polysomnography (PSG)-diagnosed OSA (apnea-hypopnea index [AHI]1) were included. All the children received TA. PSG was conducted before and after surgery. Twenty four hour ABP was monitored using the linear mixed model before, three months after, and six months after surgery.In total, 122 children were examined (mean age: 7.9 years; 71% were boys). The AHI significantly decreased from 12.7 ± 16.7 to 2.4 ± 3.2 events/h after TA (P 0.001). Overall diastolic blood pressure (DBP; from 65.1 to 63.4 mmHg, P = 0.01) and night-time DBP (from 57.4 to 55.4 mmHg, P = 0.032) decreased nonsignificantly during the six-month postoperative period. The OSA children with presurgical hypertension exhibited significant reductions in overall systolic blood pressure (SBP), overall DBP, daytime DBP, night-time SBP, and night-time DBP at the three-month and six-month postoperative follow-up (all P 0.05). The three-month and six-month ABP data did not differ significantly in the entire cohort, even between children with presurgical hypertension and non-hypertensive children.The 24-h ABP decreased significantly in the OSA children with hypertension at three and six months after surgery. Moreover, ABP findings did not differ significantly between the three- and six-month follow-up.

No studies have examined the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over bilateral dorsolateral prefrontal cortex (DLPFC) coupled with bilateral extracephalic references in treating negative symptoms of non-acute schizophrenia patients. This study aimed to investigate the therapeutic effects of the new approach of tDCS on negative symptoms, other schizophrenia symptoms, cognitive deficits and psychosocial functioning in a double-blind, randomized, sham-controlled trial. Patients with non-acute schizophrenia (N = 60) in randomized order received sham treatment or bilaterally provided tDCS (2 mA, twice-daily sessions for five consecutive days) with the anode over the DLPFC and the reference (cathode) over the ipsilateral forearm. The negative symptoms as measured by a dimensional approach of Positive and Negative Syndrome Scale (PANSS) were rapidly reduced by bimodal tDCS relative to sham stimulation (F = 24.86, Cohen's d = 0.661, p = 6.11 × 10−6). The beneficial effect on negative symptoms lasted for up to 3 months. The authors also observed improvement with tDCS of psychosocial functioning as measured by the global score of Personal and Social Performance scale (PSP) and psychopathological symptoms especially for disorganization and cognitive symptoms as measured by the PANSS. No effects were observed on other schizophrenia symptom dimensions and the performance on a series of neurocognitive tests. Our results show promise for bi-anodal tDCS over bilateral DLPFC using bilateral extracephalic references in treating negative symptoms and other selected manifestations of schizophrenia. Further studies with electrophysiological or imaging evaluation help unravel the exact mechanism of action of this novel stimulation parameter of tDCS in schizophrenia patients. ( ClinicalTrials.gov ID: NCT03701100 ).

Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24–10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67–2.35). A nomogram based on patients’ age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86–0.92, p

To investigate 24-hour ambulatory blood pressure changes 6 months after surgery among children with obstructive sleep apnea.Prospective interventional study.Tertiary medical hospital.Children aged 4 to 16 years with symptoms of obstructive sleep apnea (apnea-hypopnea index1) were recruited. All children underwent adenotonsillectomy and postoperative polysomnography overnight. The 24-hour ambulatory blood pressure was measured before and 6 months after surgery.The study cohort enrolled 124 children: mean (SD) age, 7.3 (3.1) years; 73% boys. After surgery, the apnea-hypopnea index significantly decreased from 13.3 (18.1) to 3.3 (7.2) events per hour ( P.001). Overall systolic blood pressure and diastolic blood pressure were not significantly different following surgery, while daytime systolic blood pressure was slightly increased (114.3 to 117.3 mm Hg, P.01) postoperatively. The hypertensive group (n = 43) exhibited significantly decreased levels of overall diastolic, nighttime systolic, and nighttime diastolic blood pressure ( P.05), and 54% of hypertensive children became nonhypertensive after surgery. The nonhypertensive group (n = 81) showed slightly increased levels of nocturnal overall systolic, daytime systolic, and nighttime systolic blood pressure. A generalized linear mixed model revealed that children with hypertension had a greater decrease in systolic and diastolic ambulatory blood pressure during the daytime and nighttime (all P.05) than those without hypertension.Ambulatory blood pressure changes after adenotonsillectomy among children with obstructive sleep apnea are minimal. The decrease in ambulatory blood pressure after surgery is more prominent for hypertensive children than nonhypertensive children.

Background Abdominal aortic calcification (AAC) has been known to be associated with cardiovascular mortality in hemodialysis. However, the association between AAC and future coronary artery disease (CAD) occurrence is not clear. We aimed to clarify the association of AAC severity and the occurrence of future CAD events in hemodialysis patients. Methods Hemodialysis (HD) patients were recruited in this prospective cohort study. AAC severity was quantified by AAC score, which was measured by lateral lumbar radiography. We used receiver operation curve (ROC) analysis to find the cutoff AAC value for CAD prediction. CAD-free survival was analyzed by Kaplan-Meier study. Results There were 303 patients recruited for study with a median (interquartile range) follow-up of 95 (65–146) months. The AAC score in patients with occurrence of new CAD [9 (3–15.25), n = 114] was higher than in patients without new CAD occurrence [5 (1–9) n = 189], p

Importance Adenotonsillar hypertrophy is an important cause of obstructive sleep apnea (OSA) in children. However, residual OSA and abnormal polysomnographic findings have been reported in up to 75% of cases after adenotonsillectomy. Other anatomical and functional factors that influence upper airway structures, including the lateral pharyngeal wall, have rarely been studied in children with OSA. Objective To determine whether the upper airway structures can be evaluated using head and neck ultrasonography and if there is an association between the ultrasonographic measurements for these structures and severity of OSA seen on polysomnography in children. Design, Setting, and Participants Prospective, single-center, observational study of 82 children younger than 18 years with a diagnosis of sleep-disordered breathing (20 with primary snoring, 62 with OSA, as determined by the apnea-hypopnea index) and admitted to a tertiary teaching hospital for adenotonsillectomy. Exposures Ultrasonography and polysomnography. Main Outcomes and Measures Ultrasonographic measurements of upper airway structures. Results Of the 82 children studied, 62 (76%) were boys; mean (SD) age, 7.7 (6.2). There was no significant difference found in tonsillar dimensions or volume between the children with OSA and those with primary snoring. However, the mean (SD) total lateral pharyngeal wall and the total neck thicknesses at the retropalatal level were both greater in children with OSA than in those with primary snoring at rest (24.9 [4.4] mm vs 21.3 [2.6] mm; difference, 3.61 mm; 95% CI of difference, 1.48-5.74 mm for lateral pharyngeal wall; and 59.9 [14.4] mm vs 49.9 [11.2] mm; difference, 10.9 mm, 95% CI of difference, 3.8-17.9 mm for the total neck). Conclusions and Relevance Estimated tonsillar volume measured using ultrasonography had no relationship with the apnea-hypopnea index in childhood sleep-disordered breathing. However, the lateral pharyngeal wall was significantly thicker in children with OSA than in those with primary snoring at rest.

Aim: Accumulating evidence suggests that DNA damage and repair play a role in asthma etiology, however, little is known about the contribution of genotypes of DNA repair genes to asthma susceptibility. This study aimed to examine the contribution of genotypes of DNA double-strand break repair gene X-ray repair cross complementing protein 3 (XRCC3) and its polymorphisms to asthma risk in the Taiwanese. Materials and Methods: Associations of seven XRCC3 genotypes, namely rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539 and rs28903081, with the risk of asthma were investigated among 198 patients with asthma and 453 non-asthma controls by polymerase chain reaction-restriction fragment length polymorphism genotyping methodology. Results: Unlike Caucasian populations, no polymorphic genotypes at XRCC3 rs3212057 or rs28903081 were found among the Taiwanese. For the genotypes of XRCC3 rs1799794, rs45603942, rs861530, rs1799796 and rs861539, the percentages of hetero-and homo-variant genotypes were not differentially represented between the asthma patient and the non-asthma control groups. In addition, there was no differential distribution of allelic frequencies for these XRCC3 polymorphic sites between the two groups. No interaction of these genotypes with gender or age were found. Conclusion: Although XRCC3 plays a role in asthma etiology, the variant XRCC3 genotypes do not serve as practicable predictive markers for asthma risk in Taiwanese.

AIM Abdominal aortic calcification (AAC) score in dialysis patients was associated with coronary artery disease (CAD) in cross-sectional study, but the use of AAC score in the CAD prediction was not clear. We aimed to use AAC score in the estimation of CAD occurrence in middle-aged peritoneal dialysis (PD) patients. METHODS Middle-aged (45-65 years old) PD patients were recruited and followed up until CAD occurrence, patient mortality, or PD failure. We quantified AAC score by lateral lumbar radiography, and used receiver operation curve (ROC) analysis to find the cut-off value for CAD prediction. RESULTS There were 187 patients recruited for study with a mean follow-up of 1027 ± 427 days. AAC score in patients with CAD during follow-up period (9.7 ± 7.6, n = 41) was higher than in patients without CAD occurrence (5.5 ± 6.1, n = 146) (P

The purpose of this nationwide cohort study was to investigate the incidence and risk of coronary artery disease (CAD) in patients with acetaminophen (APAP) poisoning. We identified the patients with APAP poisoning and randomly selected comparison patients according to a 1:4 ratio, matching them by age, sex, and the index year using data from the National Health Insurance Research Database from 2000 to 2010. We traced both cohorts until a diagnosis of CAD, loss to follow-up, or the end of 2011. In total, 2723 patients with APAP poisoning and 10,892 comparison patients have followed. The incidence rate of CAD was higher in the APAP poisoning cohort than in the non-APAP poisoning cohort (1.53 vs 0.87 per 1000 patient-years). The APAP poisoning cohort exhibited a 1.85-fold higher risk of CAD than did the non-APAP poisoning cohort (adjusted hazard ratio [aHR] 1.85; 95% confidence interval [CI] 1.16-2.94). Male sex, advanced age, and hypertension were independently associated with CAD risk. The risk of CAD was considerably higher within 3 years following APAP poisoning (aHR 2.73; 95% CI 1.31-5.69). This study indicated that APAP poisoning may increase risk of CAD development.

To assess the effects of adenotonsillectomy (TA) on ambulatory blood pressure (ABP) in childhood obstructive sleep apnea (OSA).From 2012 to 2017, children aged 4-16 years with symptoms and polysomnography-diagnosed OSA (apnea-hypopnea index [AHI]1) underwent TA. PSG studies and 24-hour ABP monitoring were performed before and at 3 months after surgery.In total, 159 children were enrolled (mean age, 7.8 ± 3.3 years; 72% male). TA significantly reduced the AHI from 12.4 ± 15.9 events/hour to 2.7 ± 5.7 events/hour (P .001). A decrease was observed in the children's overall diastolic blood pressure (65.1 ± 6.1 mm Hg to 63.8 ± 7.4 mm Hg, P = .04) after surgery. In subgroup analysis, 100 (63%) patients were classified as nonhypertensive, and 59 (37%) were classified as hypertensive. Linear mixed model analysis revealed that compared with the children without hypertension, those with hypertension had superior improvement in systolic and diastolic blood pressure during daytime and nighttime (all P values .01). The ABP changes after surgery were not correlated with the AHI changes. Finally, preoperative hypertension was an independent risk factor of postoperative hypertension among these children (OR 3.66; 95% CI 1.70-7.86).Overall, in children with OSA, the 24-hour ABP change after TA is small. However, among children with preoperative hypertension, there is significant BP improvement after TA surgery.

BACKGROUND/AIM Up-regulation of metallo-proteinase (MMP) proteins has been shown in various types of solid cancers and the genotype of MMP1 has been associated with the risk of solid cancers. The contribution of MMP1 genotype to lung cancer has been investigated in various countries, though, to our knowledge, not in Taiwan. Therefore, in this study, we focused on the contribution of a polymorphism in the promoter region of MMP1 to lung cancer risk in Taiwan population. PATIENTS AND METHODS Genomic DNA was isolated from peripheral blood of 358 patients with lung cancer and 716 healthy individuals (non-cancer patients). MMP1 rs1799750 polymorphic genotypes of each sample were determined using the typical methodology of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS The percentages of 2G/2G, 1G/2G, and 1G/1G for MMP1 -1607 genotypes were 34.4%, 41.3% and 24.3% in the disease group and 33.9%, 44.0%, and 22.1% in the control group (p trend=0.6298), respectively. The results of carrier comparisons in dominant and recessive models also support the findings that 1G or 2G appears not to be a determinant allelic biomarker for Taiwan lung cancer. CONCLUSION The MMP1 -1607 1G allele is a non-significant protective biomarker for lung cancer in Taiwan.

Studies suggest that a low level of circulating human endothelial progenitor cells (EPCs) is a risk factor for ischemic injury and coronary artery disease (CAD). Consumption of S-allylcysteine (SAC) is known to prevent CAD. However, the protective effects of SAC on the ischemic injury are not yet clear. In this study, we examined whether SAC could improve blood flow recovery in ischemic tissues through EPC-mediated neovasculogenesis. The results demonstrate that SAC significantly enhances the neovasculogenesis of EPCs in vitro. The molecular mechanisms for SAC enhancement of neovasculogenesis include the activation of Akt/endothelial nitric oxide synthase signaling cascades. SAC increased the expression of c-kit, β-catenin, cyclin D1, and Cyclin-dependent kinase 4 (CDK4) proteins in EPCs. Daily intake of SAC at dosages of 0.2 and 2 mg/kg body weight significantly enhanced c-kit protein levels in vivo. We conclude that dietary consumption of SAC improves blood flow recovery and prevents ischemic injury by inducing neovasculogenesis in experimental models.

Summary Aims Investigate if angiotensin II receptor blocker (ARB) decreases risk of upper gastrointestinal bleeding (UGIB) in hypertensive patients with chronic kidney disease (CKD) not on dialysis. Methods All hypertensive patients with CKD not on dialysis in outpatient department of China Medical University Hospital from 2003 to May 2013 were enrolled. The risk of UGIB was analysed using Cox proportional hazard regression. Results A total of 2744 hypertensive CKD patients including 1515 male and 1229 female, aged 64.9 ± 13.8 years old in a median of 1.9 (0.9–3.9) years were analysed. The incidence of UGIB was 4.5 per 100 patient-years. ARB was associated with a decreased risk of UGIB (p

Early detection of neck lymph node (LN) recurrence is paramount in improving the prognosis of treated head and neck cancer patients. Ultrasound (US) with US-guided fine needle aspiration (FNA) and core needle biopsy (CNB) have been shown to have great accuracy for LN diagnoses in the untreated neck. However, in the treated neck with fibrosis, their roles are not clarified. Here, we retrospectively review 153 treated head and neck cancer patients who had received US and US-guided FNA/CNB. In multivariate logistic regression analyses, size (short-axis diameter >0.8 cm) (odds ratio (OR) 4.19, P = 0.007), round shape (short/long axis ratio >0.5) (OR 3.44, P = 0.03), heterogeneous internal echo (OR 3.92, P = 0.009) and irregular margin (OR 7.32, P

Asthma is an inflammatory disease and interleukin 12 (IL-12) may play a regulatory role in allergen-induced inflammation. The aim of this study was to investigate the association of polymorphisms in IL-12A/IL-12B with asthma. The asthma group included 198 adult patients and the control group included 453 individuals without asthma that were frequency-matched by gender and age. The distribution of genotypic and allelic frequencies of IL-12A rs568408 demonstrated significant differences between case and control groups. Specifically, the percentages of AA genotype of IL-12A rs568408 was significantly higher among asthmatic patients in Taiwan than healthy controls, compared to GG genotype. No significant difference was observed among the IL-12A rs2243115 and IL-12B rs3212227 genotypes between case and control groups. In addition, the A allele at IL-12A rs568408 was associated with more severe symptoms (P = 0.0085) among asthmatic patients. These results suggest that IL-12A rs568408 may contribute to the etiology and symptoms severity of asthma, indicating its usefulness as a predictive and diagnostic biomarker of asthma.

Accumulated evidence has supported the hypothesis that the functional polymorphisms of matrix metalloproteinases (MMP) were associated with the risk of various types of cancer. However, few reports have studied the contribution of MMP-8 genotypes to either diagnostic or prognostic potential in lung cancer. In this study, we focused on the contribution of a polymorphism in the promoter region of MMP-8 (C-799T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to lung cancer risk.Genomic DNA was isolated from peripheral blood of 358 patients with lung cancer and 716 non-cancer healthy individuals. MMP-8 C-799T (rs11225395), Val436Ala (rs34009635) and Lys460Thr (rs35866072) polymorphic genotypes of each subject were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The results showed that the three polymorphisms were not significantly associated with increased risk of lung cancer in the overall investigated population. Furthermore, when the analyses were stratified according to age, sex, status of smoking and drinking, pack-years of smoking and family history of lung cancer, there was also no significant association between these genotypes and increased lung cancer risk.The polymorphisms MMP-8 C-799T, Val436Ala and Lys460Thr may not play a major role in mediating personal susceptibility to lung cancer in Taiwan.

Background Pruritus is a common and frustrating symptom in hemodialysis (HD) patients and 5-D itch scale is proposed as a reliable measurement of pruritus. However, information regarding 5-D itch scale categories is currently unavailable. We explored optimal cut-offs 5-D itching scale based on numerical rating scale (NRS) categories in HD patients. Methods Four hundred and nine HD patients in China Medical University Hospital in December 2014 were included and severity of pruritus was estimated using NRS and 5-D itch scale. The association of NRS and 5-D itch scale was analyzed by linear regression. The optimal cut-offs for 5-D itch scale based on NRS categories were generated. Results The average NRS was 3.4 ± 3.0 and the average 5-D itch scale was 10.9 ± 4.8. The 5-D score was strongly correlated with the NRS: r = 0.831 (p

Background: We hypothesize that autoantibodies are induced after the blood-brain barrier is damaged by stroke and the risk of bullous pemphigoid (BP) is increased after stroke. We assess the risk of BP after first-ever stroke in a nationwide population-based cohort of first-ever stroke patients. Methods: We extracted data from the Longitudinal Health Insurance Database 2005 and identified patients with first-ever stroke as well as control patients matched for age, gender, and year of enrollment. The risk of BP in first-ever stroke patients in comparison with that in control patients was analyzed using Cox regression. Results: Of 12,607 patients with first-ever stroke, 38 (0.3%) patients developed BP in a median of 3.5 years. In the control patients, 8 persons (0.06%) had BP in a median of 3.7 years. The crude hazard ratio (HR) of BP in first-ever stroke patients was 4.83 (95% CI 2.25-10.34, p < 0.001) compared to the control group. The adjusted HR was 4.20 (95% CI 1.94-9.08, p < 0.001) after adjustments for age, gender, hypertension, diabetes, dementia, epilepsy, Parkinson disease, furosemide, and neuroleptics for stroke patients. Conclusions: The risk of BP is increased in first-ever stroke patients in a nationwide population-based cohort and this association is independent of well-known confounders of BP.

Aim Frailty is a common syndrome in the elderly and is linked to poor outcomes. Walking performance is one of the indicators of frailty and can be associated with peripheral vascular disease (PVD). The association between frailty and PVD is unclear. The present study investigates the association between frailty and PVD in the elderly. Methods This cross-sectional study was carried out in a geriatric population of ≥65-year-old residents of Taichung, Taiwan, in June 2009. The association between frailty and subclinical PVD was analyzed using logistic regression with adjustments for PVD risk factors. Results The community-based study consisted of 1036 individuals (539 male and 497 female subjects) with a mean age of 74.2 ± 6.6 years. Frailty was found in 143 (13.8%), and subclinical PVD was identified in 74 (7.1%) individuals using the Ankle Brachial Index

Chronic inflammatory disease may trigger vascular atherosclerosis. This study aimed to determine whether chronic osteomyelitis (COM) is linked to an increased risk of coronary heart disease (CHD).A national insurance claim dataset of more than 23 million enrolees was used to identify 15 054 patients with newly diagnosed COM and 60 216 randomly selected age-matched and gender-matched controls between 2001 and 2009 for comparing the risk and incidence of CHD. The study period was from the entry date to the first date of the following events: the diagnosis of CHD, death, withdrawal from the Taiwan National Health Insurance programme or the end of 2010. The analysis of the CHD risk was performed using Cox proportional hazards regression model.During a follow-up period of 67 927 person-years, the overall incidence rate of CHD in COM cohort was 1.95 times higher than non-COM cohort (16.66 vs 8.52 per 1000 person-years). After controlling age, gender and four comorbidities (hypertension, diabetes, hyperlipidaemia and stroke), the risk remained significantly higher in the COM cohort than the control group (adjusted HR=1.65, 95% CI 1.54 to 1.78, p0.001). In age-stratified analysis, the younger population had a stronger association between COM and CHD risk than the elderly (from HR=3.42, 95% CI 1.60 to 7.32 in age35 to HR 1.39, 95% CI 1.15 to 1.68 in age ≥80).This study demonstrates that COM is an independent risk factor for CHD, particularly in the younger population. Further studies are necessary to explore the underlying mechanisms linking COM and CHD.

Background This study was conducted to evaluate the risk of developing acute pancreatitis (AP) and the fatality from AP in hemodialysis (HD) and peritoneal dialysis (PD) patients, using the claims data of Taiwan National Health Insurance. Methods From patients with newly diagnosed end-stage renal disease (ESRD) in 2000–2010, we identified a PD cohort ( N = 9,766), a HD cohort ( N = 18,841), and a control cohort ( N = 114,386) matched by sex, age, and the diagnosis year of the PD cohort. We also established another 2 cohorts with 9,744 PD patients and 9,744 propensity score-matched HD patients. The incident AP and fatality from AP were evaluated for all cohorts by the end of 2011. Results The adjusted hazard ratios (HRs) of acute pancreatitis were 5.68 (95% confidence interval [CI] = 5.05 – 6.39), 4.91 (95% CI = 4.32 – 5.59), and 7.47 (95% CI = 6.48 – 8.62) in the all dialysis, HD, and PD patients, compared with the controls, respectively. Peritoneal dialysis patients had an adjusted HR of 1.41 (95% CI = 1.21 – 1.65) for AP, compared with propensity score-matched HD patients. Peritoneal dialysis patients under icodextrin treatment had a lower incidence of AP than those without the treatment, with an adjusted HR of 0.59 (95% CI = 0.47 – 0.73). There was no significant difference in the 30-day mortality from AP between HD and PD patients. Conclusions Peritoneal dialysis patients were at a higher risk of developing AP than HD patients. Icodextrin solution could reduce the risk of developing AP in PD patients.

The prevalence of hypothyroidism is high in haemodialysis (HD) patients and hypothyroidism increases all-cause mortality in HD patients. Comorbidities are common in HD patients and are associated with both mortality and hypothyroidism. The aim of the study is to explore the effect of the interactions of comorbidities and hypothyroidism on all-cause mortality in HD patients.Patients with hypothyroidism (ICD-9-CM 244.0, 244.1, and 244.9) and matched patients without hypothyroidism in the Registry for Catastrophic Illness Patient Database of Taiwan Health Insurance from 2000 to 2010 were analyzed. The association of hypothyroidism and risk of all-cause mortality was analyzed using Cox proportional hazard regression.Nine hundred and eight HD patients with hypothyroidism and 3632 sex-, age-, gender- matched HD patients without hypothyroidism were analyzed. Hypothyroidism was associated with increased all-cause mortality with an adjusted hazard ratio of 1.22 [95% confidence interval (CI): 1.10-1.36, P 0.001]. TRT may decrease mortality associated with hypothyroidism (P 0.001). There was a significant interaction (P = 0.04) between diabetes and hypothyroidism. There was no significant interaction found in hypothyroidism and the following comorbidities: hyperlipidaemia, hypertension, chronic obstructive pulmonary disease, coronary artery disease, stroke, peripheral arterial disease, asthma, congestive heart failure and cancer.Hypothyroidism is associated with increased all-cause mortality in chronic HD patients. The interaction of hypothyroidism and diabetes, but not other common comorbidities in HD patients, has an effect on mortality risks.

Matrix metalloproteinase-9 (MMP-9) plays a critical role in cancer metastasis. Andrographolide (AP) is a diterpene lactone in the leaves and stem of Andrographis paniculata (Burm. f) Ness that has been reported to possess anticancer activity. In this study, we investigated the effect of AP on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and invasion in MCF-7 breast cancer cells and the possible mechanisms involved. The results showed that AP dose-dependently inhibited TPA-induced MMP-9 protein expression, enzyme activity, migration and invasion. In addition, AP significantly induced heme oxygenase-1 (HO-1) messenger RNA (mRNA) and protein expression. Transfection with HO-1 small interfering RNA knocked down the HO-1 expression and reversed the inhibition of MMP-9 expression by AP. HO-1 end products, such as carbon monoxide, free iron and bilirubin, suppressed the TPA-induced MMP-9 mRNA and protein expression, enzyme activity, migration and invasion in MCF-7 cells. Furthermore, TPA-induced extracellular signal-regulated kinase (ERK) 1/2 and Akt phosphorylation and the DNA binding activity of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) were attenuated by pretreatment with AP and HO-1 end products. In conclusion, these results suggest that AP inhibits TPA-induced cell migration and invasion by reducing MMP-9 activation, which is mediated mainly by inhibition of the ERK1/2 and phosphatidylinositol 3-kinase/Akt signaling pathways and subsequent AP-1 and NF-κB transactivation. Additionally, induction of HO-1 expression is at least partially involved in the inhibition of TPA-induced MMP-9 activation and cell migration in MCF-7 cells by AP.

Matrix metalloproteinase-9 (MMP-9) plays a crucial role in tumor metastasis. Previous studies showed that polyunsaturated fatty acids exhibit an anti-cancer effect in various human carcinoma cells, but the effect of docosahexaenoic acid (DHA) and linoleic acid (LA) on metastasis of breast cancer cells is not fully clarified. We studied the anti-metastasis potential of DHA and LA in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. We found that TPA (100 ng/ml) induced MMP-9 enzyme activity both dose- and time-dependently, and 200 μM DHA and LA significantly inhibited MMP-9 mRNA and protein expression, enzyme activity, cell migration, and invasion. Treatment with PD98059 (10 μM), wortmannin (10 μM), and GF109203X (0.5 μM) decreased TPA-induced MMP-9 protein expression and enzyme activity. TPA-induced activation of ERK1, Akt, and PKCδ was attenuated by DHA, whereas LA attenuated only ERK1 activation. GF109203X also suppressed ERK1 activation. EMSA showed that DHA, LA, PD98059, and wortmannin decreased TPA-induced NF-κB and AP-1 DNA-binding activity. Furthermore, DHA rather than LA dose-dependently increased HO-1 expression. HO-1 siRNA alleviated the inhibition by DHA of TPA-induced MMP-9 protein expression and enzyme activity in MCF-7 cells, and HO-1 knockdown reversed the DHA inhibition of cell migration. These results suggest that DHA and LA have both similar and divergent signaling pathways in the suppression of TPA-induced MCF-7 metastasis.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.