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Background/aim 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. Materials and methods 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. Results 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. Conclusion Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

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

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.

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.

OBJECTIVE Temporary vascular access (TVA) is frequently used during the first dialysis in patients with chronic kidney disease (CKD), and it is associated with an increased risk of infection, central vein stenosis, and mortality. Here, factors associated with TVA in patients with CKD were explored. METHODS This study included patients in a single-center CKD care program who initiated long-term renal replacement therapy. The primary outcome was TVA use at first dialysis. Factors possibly associated with TVA use were analyzed using Cox regression. RESULTS Temporary vascular access was used in 53.2% of the patients at first dialysis. In total, 73.2% (n = 865) and 26.8% (n = 317) of the patients were on hemodialysis and peritoneal dialysis, respectively. Multivariate Cox regression analysis showed that TVA use in patients with CKD was associated with diabetes (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.28-1.81, p

Flexible manipulation of the carrier transport behaviors in two-dimensional materials determines their values of practical application in logic circuits. Here, we demonstrated the carrier-type mani...

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.

Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function. During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05–1.81) before surgery and 2.47 years (1.37–6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (− 1.67 versus − 2.73 mL/min/1.73 m2/year, p

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 Urothelial cancer (UC) includes carcinomas of the bladder, ureters, and renal pelvis. New treatments and biomarkers of UC emerged in this decade. To identify the key information in a vast amount of literature can be challenging. In this study, we use text mining to explore UC publications to identify important information that may lead to new research directions. Method We used topic modeling to analyze the titles and abstracts of 29,883 articles of UC from Pubmed, Web of Science, and Embase in Mar 2020. We applied latent Dirichlet allocation modeling to extract 15 topics and conducted trend analysis. Gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to identify UC related pathways. Results There was a growing trend regarding UC treatment especially immune checkpoint therapy but not the staging of UC. The risk factors of UC carried in different countries such as cigarette smoking in the United State and aristolochic acid in Taiwan and China. GMCSF, IL-5, Syndecan-1, ErbB receptor, integrin, c-Met, and TRAIL signaling pathways are the most relevant biological pathway associated with UC. Conclusions The risk factors of UC may be dependent on the countries and GMCSF, IL-5, Syndecan-1, ErbB receptor, integrin, c-Met, and TRAIL signaling pathways are the most relevant biological pathway associated with UC. These findings may provide further UC research directions.

Background/aim Interleukin-16 (IL-16) is reported to play an important role in inflammation, carcinogenesis and tumoricidal processes, however, the contribution of IL-16 genotype to oral carcinogenesis is still largely unrevealed. Thus, the study aimed to investigate the contribution of IL-16 genotypes to Taiwan oral cancer risk. Materials and methods The genotypes of IL-16 rs4778889, rs11556218, and rs4072111 were revealed among 958 oral cancer cases and 958 control subjects by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results First, the distributions of genotypic (p=0.0004) and allelic (p=0.0001) frequencies of IL-16 rs11556218 were significantly different between the case and control groups. In detail, the frequencies of IL-16 rs11556218 TG and GG were 28.1 and 5.8%, respectively, among oral cancer patients, significantly higher compared to those among controls (25.0% and 2.7%, respectively). Second, no difference was observed regarding IL-16 rs4778889 or IL-16 rs4072111. Last, there was a synergistic effect of betel quid chewing behavior and risky IL-16 rs11556218 genotype on oral cancer risk. Conclusion The study indicates that the IL-16 rs11556218 G allele synergistically interacts with betel quid chewing behavior, contributing to increased risk of oral cancer in Taiwanese.

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.

Background: Urothelial carcinoma is a common urological cancer in patients with chronic kidney disease in Taiwan. However, urinary cystoscopy is an invasive procedure and urine cytology showed low sensitivity for low-grade tumor. High accuracy with noninvasive diagnostic tools for UC is needed for patients with CKD. Methods: A total of 272 urine and 138 plasma samples to detect the miRNA expression levels for establishing UC signatures from patients with CKD. 17 candidate miRNAs of urine and plasma were selected by the PCR array, and a single qRT-PCR assay was used to confirm the results. The website of a smRNA-seq analysis of the clinical specimens was compared to survival status. The miRNA prediction models were produced for predicting UC by multiple logistic regression.Results: Urinary miR-1274a and miR-30a-5p expression levels were significantly lower but miR-19a-5p expression levels were higher in UC when compared with CKD. In plasma samples, miR-155-5p, miR-19b-1-5p, miR-378 and miR-636 showed significantly lower expression in UC compared to those with CKD. The Kaplan-Meier curve showed that lower expression of miR-19a, miR-19b, miR-636 and miR-378, and higher expression of miR-708-5p were associated with poor prognosis in patients with bladder cancer. In addition, we produced classifiers for predicting UC by multiple logistic regression. The urine signature was developed with four miRNAs, and the AUC was 0.8211. Eight miRNA expression levels from both urine and plasma samples were examined, and the AUC was 0.8595.Conclusion: Two miRNA classifiers could improve the drawbacks of current UC biomarker screenings for patients with CKD.

Background: Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of chronic peritoneal dialysis (PD). Late diagnosis is associated with high mortality. With the advancement of new diagnostic technologies, such as microRNA (miRNA), we attempted to develop a noninvasive test to assist in the diagnosis of EPS. Methods: MiRNA expression profiles of PD effluents from patients with or without EPS were examined by a high-throughput real-time PCR array to first screen candidate miRNAs. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression. Finding: We collected eight-hour PD effluents from 71 non-EPS and 56 EPS patients. The screening set included 28 samples (20 of non-EPS vs. 8 of EPS). After analyzing the ratio values of two miRNA expression levels from the PCR-array of 377 miRNAs, eight candidate miRNAs were selected. The prediction model was conducted using 127 samples (71 of non-EPS vs 56 of EPS) to produce an area under the curve (AUC) value of the miRNA classifier. The ratios of the five miRNAs with the top five ROC values were selected to calculate the combined AUC by logistic regression. The AUC value to detect EPS with the five miRNA ratios was 0.8929 with an accuracy of 78.7%. The accuracy of the EPS diagnosis was further improved to 94.1% after considering clinical characteristics (AUC value 0.9931, sensitivity: 100%, specificity: 94.1%). Interpretation: A signature-based model of clinical characteristics and miRNA expression in PD effluents can efficiently detect EPS, thus preventing the catastrophic prognosis. Funding: This work was supported by the following programs: Academia Sinica, Taiwan (BM103010089 and BM104010113 to CC Huang), the Taiwan Department of Health Cancer Research Center of Excellence (DOH101-TD-C-111-005), Ministry of Science and Technology, Taiwan (MOST 109-2628-B-008-001 and MOST 110-2823-8-008- 002), the National Central University-Landseed Hospital United Research Center (NCU-LSH-109-A-004), and Taoyuan Armed Forces General Hospital (TYAFGH-D- 109024). Declaration of Interest: All authors declare no conflict of interest. Ethical Approval: The study protocol was approved by the medical ethics committee of three medical centers in Taiwan (the China Medical University Hospital, CMUH103-REC2-070; the National Chen Kung University Hospital, B-ER-104-069; and the Kaohsiung Chang Gung Memorial Hospital, 100-2661B)

Recently, researchers have focused on optoelectronics based on two-dimensional van der Waals materials to realize multifunctional memory and neuron applications. Layered indium selenide (InSe) semiconductors satisfy various requirements as photosensitive channel materials, and enable the realization of intriguing optoelectronic applications. Herein, we demonstrate InSe photonic devices with different trends of output currents rooted in the carrier capture/release events under various gate voltages. Furthermore, we reported an increasing/flattening/decreasing synaptic weight change index (∆Wn) via a modulated gate electric field, which we use to imitate medicine-acting metaplasticity with effective/stable/ineffective features analogous to the synaptic weight change in the nervous system of the human brain. Finally, we take advantage of the low-frequency noise (LFN) measurements and the energy-band explanation to verify the rationality of carrier capture-assisted optoelectronics applied to neural simulation at the device level. Utilizing optoelectronics to simulate essential biomedical neurobehaviors, we experimentally demonstrate the feasibility and meaningfulness of combining electronic engineering with biomedical neurology.

Background: Patients with chronic kidney disease (CKD) receiving maintenance renal replacement therapy are at higher risk of tuberculosis (TB) infection. The risk of TB infection in CKD patients not receiving dialysis is unknown.Aim: We conduct this study to test the hypothesis that TB infection is negatively correlated to renal function.Design: Non-dialysis CKD stage 1–5 patients, admitted in China Medical University Hospital from January of 2003 to May of 2014, were enrolled in this study and were prospectively followed up to the diagnosis of TB, death, loss to follow-up, or December 2014. The risk factors of TB infection were analyzed using competing-risks regression analysis with time-varying covariates. The initiation of dialysis and patients' death were considered as competing events. Patients' estimated glomerular filtration rate (eGFR) and body mass index (BMI) were recorded at enrollment.Results: They were followed-up for a median duration of 1.4 years. Of the 7221 patients, TB infection was identified in 114 patients. Higher eGFR was associated with lower risk of TB infection (P < 0.01). The adjusted subdistribution hazard ratio (aSHR) was 0.82 [95% confidence interval (CI), 0.72 to 0.94] for every 5 ml/min/1.73 m2 increase in eGFR. In addition, higher BMI (p = 0.01) was associated with a lower risk of TB infection and the aSHR was 0.91 (95% CI, 0.85 to 0.98) for every 1 kg/m2 increase in BMI.Conclusion: Renal function and body mass index are independently associated with the risk of tuberculosis infection in patients with chronic kidney disease not receiving dialysis.

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.

To promote the development of the solid state lighting and display industry, exploring excellent inorganic phosphors has always been a hot scientific and applied issue. Herein, we have constructed ...

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.

Matrix metalloproteinases-2 (MMP2) has been reported to be overexpressed in various types of cancer. However, the contribution of various genotypes of MMP2 to lung cancer is controversial and not yet been examined in Taiwan. Therefore, in the current study, we investigated the association of MMP2 genotypes with lung cancer risk among Taiwanese. In this hospital-based, case-control study, 358 lung cancer patients and 716 age- and gender-matched healthy controls were recruited, and the genotypic distributions of MMP2-1306 and MMP2- 735 were determined. Then, their association with lung cancer was evaluated, and their interaction with personal smoking status was also examined via stratification analysis. The results showed that the percentages of variant CT and TT at MMP2-1306 were 17.3% and 1.7% among the lung cancer patients, respectively, much lower than those of 28.7% and 2.4%, respectively, among the healthy controls (P for trend = 0.0001). The allelic frequency distribution analysis showed that the variant T allele at MMP2-1306 conferred a statistically significantly lower lung cancer risk than the wild-type C allele (adjusted odds ratio = 0.54, 95% confidence interval = 0.41-0.72, P = 0.0001). There was an obvious effect of MMP2-1306 genotype on lung cancer risk among the subpopulations of ever smokers but not nonsmokers. As for the genotypes of MMP2-735, there was no such differential distribution in the aspects of genotypic or allelic frequencies, or combinative effects with smoking status. The genotypes of MMP2-1306 may act as a biomarker in determining personal susceptibility to lung cancer in Taiwan. The contribution of MMP2 genotypes alone and its joint effects with personal cigarette smoking habit on lung cancer susceptibility should be taken into consideration of the clinical practices for early detection and prediction of lung cancer in Taiwan.

Adenostemma lavenia is a perennial herb belonging to the Compositae family and is widely distributed in the tropical parts of Asia. It has been widely used as medicine in Taiwan with the whole plant used to treat pulmonary congestion, pneumonia, bacterial infections of the respiratory tract, edema, and inflammation. This study sought to investigate the anti-inflammatory effects of A. lavenia in vitro and in animal models. The anti-inflammatory effects of ethyl acetate fractions of A. lavenia (EAAL) were stimulated with lipopolysaccharide (LPS) murine macrophages (RAW 264.7) and lung injury in mice. EAAL reduced proinflammatory cytokine responses. Preoral EAAL alleviated LPS-induced histological alterations in lung tissue and inhibited the infiltration of inflammatory cells and protein concentrations in bronchoalveolar lavage fluid (BALF). EAAL prevented protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2); phosphorylation of I[Formula: see text]B-[Formula: see text], MAPKs, and AMP-activated protein kinase (AMPK); and activated anti-oxidant enzymes (catalase, SOD, and GPx), heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) in LPS-stimulated cells and lung tissues. Fingerprinting of EAAL was performed with HPLC to control its quality, and [Formula: see text]-coumaric acid was found to be a major constituent. This study suggests that EAAL is a potential therapeutic agent to treat inflammatory disorders.

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

BackgroundThe association between physical fitness performance tests and anthropometric indices is not clear. The study aims to explore the association between physical fitness performance and anthropometric indices in Taiwanese community-dwelling adults. This may help in monitoring anthropometric indices to improve physical fitness.MethodsWe recruited 2216 participants aged 23–64 years between 2014 and 2017. Physical fitness performance, including abdominal muscular endurance (60-s sit-up test), flexibility (sit-and-reach test), and cardiorespiratory endurance (3-min step test), was evaluated in all participants. The association of the physical fitness performance and anthropometric indices, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), was analyzed using linear regression, with adjustments for age and gender.ResultsBody mass index was negatively associated with abdominal muscular endurance (p < 0.001) and cardiorespiratory endurance (p < 0.001). Neither BMI, WC, WHR, nor WHtR were significantly associated with flexibility. Abdominal muscle endurance, flexibility, and cardiorespiratory endurance were significantly lower in obese participants when obesity was defined using a BMI of ≥27, 30, and 35 kg/m2. Participants with central obesity that was defined as WC ≥ 90 cm in men and 80 cm in women and WHtR ≥ 0.6 had lower abdominal muscular endurance than those without central obesity.ConclusionBody mass index is associated with abdominal muscular endurance and cardiorespiratory endurance in a reverse J-shaped manner. None of the anthropometric indices are significantly associated with flexibility. Obesity defined by BMI is linked to worse physical fitness performance and obesity defined using WHtR is linked to lower abdominal muscular endurance in Taiwanese community-dwelling adults.

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

Neuromorphic electronics with two-dimensional van der Waals materials meet the ever-increasing demands of both the semiconductor industry and biological engineering, such as miniaturization, structure flexibility, multifunctionality, and low power consumption. However, the majority of reported electronic devices achieve multifarious memory storage states or synaptic plasticity through regulation of an electrical or an optical signal. Herein, we propose an innovative touch-modulated device based on an indium selenide/hexagonal boron nitride/graphene van der Waals heterostructure coupled with a triboelectric nanogenerator. The device is prepared utilizing a simple copper grid shadow mask instead of the expensive and cumbersome electron beam lithography process, exhibits high mobility of 829 cm2 V−1 s−1, low voltage, and low power consumption. Nonvolatile memory with self-writing power, durability and multibit data storage is achieved through mechanical modulation without an additional gate-voltage supply. Moreover, by adjusting the distance between the two friction layers, essential synaptic plasticity, including short-term and long-term potentiation/depression and paired-pulse facilitation/depression, are successfully imitated in the device. Most importantly, we achieve ultralow power consumption of 165 aJ in tribotronic synapses owing to the ultra-high mobility of InSe. Our tribotronic synapse with self-writing power has great potential to simulate the low-power-consuming neuromorphic bioelectronic devices with multiple functions and lays the foundation for future advanced neuromorphic systems and artificial intelligence.

Background and Aims Introduction: Chronic kidney disease (CKD) patients are known to have greater risk of urothelial cancer (UC) than general population. Urine is the most non-invasive examination and is directly linked to UC. Urinalysis and urine cytology are the major screening tools; however, these tests have low sensitivity or specificity in early disease. In this study, we used both normal and Non-UC CKD patients as controls to discover novel and more specific protein biomarkers in urine for early UC diagnosis. Aims To discover novel and more specific urinary protein biomarkers for screening of urothelial cancer (UC) in CKD patients. Method This is a multicenter prospective cohort study, carried out at 10 nationwide hospitals covering different regions of Taiwan from 2013-2018. Subjects were Taiwanese healthy adults (healthy controls, n=210), patients with CKD but without UC (disease controls, n=273) and patients with ongoing UC (n=211). For non-UC patients, urine and blood specimens were collected at the time of the structured interview. For UC patients, urine and blood samples were collected before operation. iTRAQ-LC-MS/MS approach was applied to compare protein expression among normal, CKD and UC cohorts. Results A total of 3838 proteins in urine were identified and 2497 proteins of them can be quantified. By filtering with fold changes, published papers and Human ATLAS, 27 candidates were selected as potential biomarkers and were validated with ELISA assay in a large sample size of urine specimens. Among the 27 candidates, we found BRDT, CYBP, GARS and HDGF were highly-expressed in the UC cohort when compared to normal and CKD cohorts (Figure 1). To increase the diagnostic value of UC, we combined ROC of our newly discovered 4 protein biomarkers. The AUC values of our newly discovered 4-biomarker panel were higher than the AUC values of the published biomarker panel, including the FDA-approved protein biomarkers (Figure 2). Conclusion We discover and validate a highly specific urinary protein biomarker panel (BRDT, GARS, HDGF and CYBP) to distinguish UC from CKD and healthy controls. It may be used for high throughput screening of subjects, such as CKD patients, who are at high risk to develop UC.

Low price or convenience? What is more important for online and offline bookings? For the sustainable development of the hospitality industry, it is necessary to know the opinions of customers about their online/offline hotel booking experiences. This study aimed to predict the customers&rsquo, online/offline booking behavior toward a resort hotel in Taiwan by adapting the marketing mix elements. We first designed and executed a detailed questionnaire involving approximately 300 respondents from a five-star hotel in Taiwan, used hypothesis testing to extract important factors from the data, and finally used logistic regression of these factors to predict the customer choices effectively. The study results show that the majority of the customers believe that booking hotel services online provides for a broader choice, offers more discounts and more privacy than available while booking offline, and is cheaper, faster, and more reliable and convenient. The outcomes of logistic regression confirm that &ldquo, broad choice,&rdquo, but not &ldquo, low price&rdquo, has the most significant impact on the customers booking a resort accommodation online or offline. Furthermore, the results of the analysis of variance (ANOVA) show that the younger customers (under the age of 45) and those with university degrees are significantly more likely to make the reservations online for a resort. The findings and the recommendations can provide valuable inputs to the resort industry practitioners in Taiwan for improving the online booking services.

Summary: We introduced a novel protocol based on an artificial intelligence (AI)-assisted analytic system for facial expressions, Customized Precision Facial Assessment (CPFA), to evaluate and quantify the microexpressions of aesthetic concern. With the help of CPFA, physicians may be able to conduct static and dynamic assessments for the microexpressions of the ir patients and perform quantitative measurements before and after the treatments. Through the detection of microexpressions and its active action units of facial muscles, physicians are more likely to optimize the treatment with minimal intervention by precise localization of the foci of aesthetic concern. We presented 3 cases who received neuromodulators and injectable fillers, and we showed the differences in the area of treatment and outcomes of procedures between the CPFA-oriented treatments and human-facilitated ones. We found negative facial expressions decreased in all 3 cases in the group of CPFA while they decreased in only case 1 and case 2 in the group of human facilitated treatment. The CPFA group has more significant decrease in negative facial expression scores than the human group. This pilot study demonstrates that CPFA can objectively recognize and quantify the facial action units associated with negative emotions, and the physician may be able to customize the treatment for individuals accordingly with promising results.

Background Acute Kidney Injury (AKI) is common among inpatients. Severe AKI increases all-cause mortality especially in critically ill patients. Older patients are more at risk of AKI because of the declined renal function, increased comorbidities, aggressive medical treatments, and nephrotoxic drugs. Early prediction of AKI for older inpatients is therefore crucial. Methods We use 80 different laboratory tests from the electronic health records and two types of representations for each laboratory test, that is, we consider 160 (laboratory test, type) pairs one by one to do the prediction. By proposing new similarity measures and employing the classification technique of the K nearest neighbors, we are able to identify the most effective (laboratory test, type) pairs for the prediction. Furthermore, in order to know how early and accurately can AKI be predicted to make our method clinically useful, we evaluate the prediction performance of up to 5 days prior to the AKI event. Results We compare our method with two existing works and it shows our method outperforms the others. In addition, we implemented an existing method using our dataset, which also shows our method has a better performance. The most effective (laboratory test, type) pairs found for different prediction times are slightly different. However, Blood Urea Nitrogen (BUN) is found the most effective (laboratory test, type) pair for most prediction times. Conclusion Our study is first to consider the last value and the trend of the sequence for each laboratory test. In addition, we define the exclusion criteria to identify the inpatients who develop AKI during hospitalization and we set the length of the data collection window to ensure the laboratory data we collect is close to the AKI time. Furthermore, we individually select the most effective (laboratory test, type) pairs to do the prediction for different days of early prediction. In the future, we will extend this approach and develop a system for early prediction of major diseases to help better disease management for inpatients.

In the present study, we aim to help improve the design of van der Waals stacking, i.e., vertical 2D electronics, by probing charge transport differences in both parallel and vertical conducting channels of layered molybdenum disulfide (MoS2), with thin graphite acting as source and drain electrodes. To avoid systematic errors and variable contact contributions to the MoS2 channel, parallel and vertical electronics are all fabricated and measured on the same conducting material. Large differences in the on/off current ratio, mobility, and charge fluctuations, between parallel and vertical electronics are evident in electrical performance as well as in charge transport mechanisms. Further insights are drawn from a well-constrained analysis of both temperature-dependent current-voltage characteristics and low-frequency (LF) current fluctuations. This work offers significant insight into the fundamental understanding of charge transport and the development of future layered-materials-based integration technology.

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: Emerging research findings suggest that long non-coding RNAs (lncRNAs) are key regulators to fibrosis formation. Nevertheless, the role of lncRNA GAS5-AS1 in the progression of precancerous oral submucous fibrosis (OSF) remains to be elucidated. Methods: Quantitative real-time PCR were used to examine the expression of GAS5-AS1 in OSF tissues. The activities of myofibroblasts, including collagen contractility and cell migration, as well as the marker α-smooth muscle actin (SMA) were assessed following overexpression of GAS5-AS1. Also, we analyzed the expression of Smad activity in order to gain insight into the downstream regulator. Results: The level of GAS5-AS1 was found significantly downregulated in the OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs). Ectopic expression of GAS5-AS1 significantly reduced the abilities of collagen gel contraction and migration in fBMFs or arecoline-treated BMFs. Moreover, we have shown that overexpression of GAS5-AS1 inhibited the expression of p-Smad and the marker of myofibroblasts. Conclusion: We showed the reduced expression of GAS5-AS1 in OSF tissues and demonstrated its effect on the myofibroblast activities and the level of p-Smad and α-SMA, indicating its potential contribution in OSF pathogenesis. Keywords: lncRNA GAS5-AS1, Myofibroblasts, Oral submucous fibrosis

Background The prevalence of hypothyroidism is high in hemodialysis (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. Method 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. Result 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

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.

Background Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalates and is associated with breast cancer. Ths association between DEHP and other types of cancer is not clear. DEHP may increase matrix metalloproteinase-9 that is critical for the development of urothelial cancer (UC). We examined the association between urinary phthalate metabolites and UC. CKD patients were selected as a control group because CKD patients are more at risk of UC than the general population. Methods In this cross-sectional study, we measured seven urinary phthalate metabolites that are abundant and can be measured using HPLC-MS/MS in Taiwan CKD patients between Jul 2013 and Dec 2015. MiBP (a urinary metabolite of Dibutyl phthalates[DBP]) and MEHHP (a urinary metabolite of DEHP) were described because they are the most abundant phthalate metabolites. The association of phthalate (log-transformed) and UC were analyzed using logistic regression with adjustments for age, gender, renal function, use of traditional Chinese medicine, toxins (dye, organic solvent), and non-steroidal anti-inflammatory drugs. Results We measured the urinary MEHHP and MiBP of 496 patients (224 UC and 272 CKD patients). The urinary MEHHP was associated with UC but MiBP was not. Medical history including the use of non-steroid anti-inflammatory drugs, exposure to environmental toxins (dye, paint, and organic solvent), and the use of traditional Chinese medicine was independently associated with UC. The adjusted odds ratio of MEHHP was 1.42 (95% confidence interval: 1.21–1.68). Conclusion Phthalate urinary metabolite(MEHHP) may be associated with UC in CKD patients and the association is independent of well-known risk factors of UC.

// Che-Yi Lin 1 , Pei-Ling Hsieh 2, * , Yi-Wen Liao 3, * , Chih-Yu Peng 3 , Ming-Yi Lu 3 , Ching-Hsuan Yang 2 , Cheng-Chia Yu 2, 3, 4 and Chia-Ming Liu 3, 4 1 Department of Oral and Maxillofacial Surgery, Chi Mei Hospital, Tainan, Taiwan 2 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 3 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 4 Department of Dentistry, Chung Shan Medical University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Cheng-Chia Yu, email: ccyu@csmu.edu.tw Chia-Ming Liu, email: y337@csmu.edu.tw Keywords: oral squamous cell carcinomas, miR-21, berberine Received: June 16, 2017 Accepted: August 04, 2017 Published: September 08, 2017 ABSTRACT Cancer recurrence and chemoresistance are two major obstacles to the treatment of oral squamous cell carcinomas (OSCC). And cancer stem cells (CSCs) have been found to possess tumor initiating, self-renewal and metastasis abilities, resulting in the relapse and chemoresistance of OSCC. In the present study, we investigated the anti-CSCs effect of berberine, a phenanthrene alkaloid isolated from the Berberis genus. Our results demonstrated that berberine dose dependently downregulated the oncogenicity in vitro , including ALDH1 activity, self-renewal property, and colony formation and invasion abilities as well as potentiated chemosensitivity of OSCC-CSCs. In addition, tumor growth in mice was attenuated after oral gavage treatment of berberine. We showed that the expression of miR-21 was suppressed following administration of berberine in OSCC-CSCs. And inhibition of endogenous miR-21 reduced the characteristics of CSCs, including self-renewal, migration, invasion capabilities and ALDH1 activity. Taken together, we demonstrated the anti-CSC effect of berberine in oral cancer and its potential to serve as adjuvant to traditional chemotherapy to improve treatment effect.

// Shih-Yi Lin 1, 2, 3 , Cheng-Li Lin 4, 5 , Chao-Hsiang Chang 6 , His-Chin Wu 6 , I-Kuan Wang 1, 2, 3 , Che-Yi Chou 1, 2, 3 and Ji-An Liang 1, 7 1 Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan 2 Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 3 Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan 4 Managment Office for Health Data, China Medical University Hospital, Taichung, Taiwan 5 College of Medicine, China Medical University, Taichung, Taiwan 6 Department of Urology, China Medical University Hospital, Taichung, Taiwan 7 Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan Correspondence to: Ji-An Liang, email: d4615@mail.cmuh.org.tw Keywords: upper tract urothelial carcinoma, acute myocardial infarction, mortality, radical nephroureterectomy, multivariable Cox proportional hazard regression analysis Received: April 07, 2017 Accepted: May 29, 2017 Published: June 15, 2017 ABSTRACT Background: The outcomes of upper tract urothelial carcinoma (UTUC) receiving radical nephroureterectomy were usually limited to small sample size, case-control studies, and often focused on cancer progression. Risk of acute myocardial infarction (AMI) in these patients was never investigated. Results: The overall incidences of AMI were 3.39, 1.44, and 1.70 per 10,000 person-years in the radical nephroureterectomy, nonnephroureterectomy, and non-UTUC cohorts, respectively. Multivariable Cox proportional hazard regression analysis revealed a significantly higher AMI risk in the radical nephroureterectomy cohort [adjusted HR (aHR) = 1.83, 95% confidence interval (CI) = 1.08–3.11], compared with non-UTUC cohorts. The risk of mortality were the highest in patients with UTUC who had undergone radical nephroureterectomy [adjusted HR (aHR) = 5.37, 95% confidence interval (CI) = 4.80–6.02]. Materials and Methods: From the Taiwan National Health Insurance claims data, 1,359 patients with UTUC who had undergone radical nephroureterectomy and 3,154 patients with UTUC who had undergone nephron sparing surgery and were newly diagnosed between 2000 and 2010 were identified. For each patient, 4 individuals without UTUC were randomly selected and frequency matched by age, sex, and diagnosis year. Conclusions: Patients with UTUC who have undergone radical nephroureterectomy are at a higher risk of developing AMI, compared with those receiving nephron sparing surgery.

AIM Prolonged QT interval is related to changes of electrolytes in haemodialysis (HD) and is associated with all-cause mortality in HD patients. It is unknown if prolonged QT interval is associated with all-cause mortality in peritoneal dialysis (PD) patients as the electrolytes were relatively stable in PD. We therefore investigated the association of prolonged QT interval and all-cause mortality in chronic PD patients. METHODS The QT intervals were measured in 2003 and all patients were followed to December 2012. A prolonged QT interval was defined as a QT interval > 450 ms. The association of prolonged QT interval with all-cause and cardiac-specific mortality was analyzed using Cox regression and Kaplan-Meier analysis. RESULTS Of 306 patients, 196 (64%) patients had prolonged QT interval. The incidence density rate was 9.7 per 100 persons-years for all-cause mortality and 5.6 for cardiac specific mortality in patients with prolonged QT interval. Prolonged QT interval was associated with all-cause mortality with a hazard ratio (HR) of 1.59 (95% confidence interval (CI): 1.06-2.39, P = 0.03] and cardiac mortality (HR: 1.66, 95% CI: 1.00-2.78, P = 0.05) with adjustments for age, gender, diabetes, and vintage of dialysis. Longer QT interval (>500 ms, 450-500 ms, and

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.

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11, 0.76, p-Value = 0.32, OS: 0.80, p-Value = 0.16, 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.