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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

Summary Mechanoreceptors are essential components of the somatosensory system that convert received mechanical signals into electrical signals that can be sent to the brain. These receptors provide the ability to sense a variety of stimuli from the external environment, including touch, vibration, and heat. Mechanoreceptors do not convert signals monotonically; in addition, several fundamental characteristics are embedded in mechanoreceptors, including thresholds and adaptation properties. In this study, we proposed and experimentally demonstrated a van der Waals stacking field-effect transistor (VS-FET), which was inspired by an FET with a floating gate structure, to realize the important characteristics of mechanoreceptors. The VS-FET can not only demonstrate the fundamental biological functions but also produce other unique properties such as fatigue and accommodation. We also integrated an artificial touch receptor with an array of the proposed VS-FET to demonstrate the feasibility of these devices experimentally in artificial humanoid systems.

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

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)

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.

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

Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC.

Background Bacterial cultures allow the identification of infectious disease pathogens. However, obtaining the results of conventional culture methods is time-consuming, taking at least two days. A more efficient alternative is the use of concentrated bacterial samples to accelerate culture growth. Our study focuses on the development of a high-yield sample concentrating technique. Results A total of 71 paired samples were obtained from patients on peritoneal dialysis (PD). The peritoneal dialysates were repeat-centrifuged and then washed with saline, namely the centrifuging and washing method (C&W method). The concentrated samples were Gram-stained and inoculated into culture plates. The equivalent unprocessed dialysates were cultured as the reference method. The times until culture results for the two methods were compared. The reference method yielded no positive Gram stain results, but the C&W method immediately gave positive Gram stain results for 28 samples (p p = 0.044). The average time for bacterial identification achieved with the C&W method (22.0 h) was shorter compared to using the reference method (72.5 h) (p Conclusions The C&W method successfully concentrated bacterial samples and superseded blood culture bottles for developing adequate bacterial cultures. The C&W method may decrease the culture report time, thus improving the treatment of infectious diseases.

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.

Background: Nowadays, as technology and medical treatment improvements contribute to extending the lives of human beings, it also causes many diseases like noninfectious chronic and neurodegenerative with an aging population. Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases. It almost always occurs in older adults whose age is above 65 years old. AD is clinically characterized by a progressive loss of cognitive abilities. Pathologically, it is defined by the appearance of senile plaques-extracellular insoluble, congophilic protein aggregates composed of amyloid β (Aβ), resulting in oxidative stress, mitochondrial disorders, synaptic atrophy, leading to function degradation of the brain. The scientific name of adlay is Coix lacryma-jobi L., which is an annual botanical.Methods: This research uses the adlay hull, as a test sample in the experiment. The 95% ethanol extract of adlay hull (AHEE) was partitioned by ethyl acetate (AHEAE), n-butanol (AHBUE) and water (AHWE) subsequently, and the test of extracts by LPSinduce a RAW264.7 inflammatory response and Aβ25-35-induces dPC12 cells which cause neurotoxicity as an experimental model, respectively. Investigate the inflammatory and anti-apoptosis related protein expression.Results: The results shown that the AHEE, AHEAE and AHWE exert antiinflammatory effects, AHWE also have anti-apoptosis effects. Through mouse macrophages inflammatory protein expression experiments, as well as inhibition of iNOS expression, resulted in inhibited nitrite production. In this study, we investigated the protective effects of AHWE against the Aβ25-35-induced neurotoxicity in dPC12 cells and explored the underlying mechanism. The results showed that pretreatment with AHWE significantly attenuated cell death and the elevated Bax/Bcl-2 ratio evoked by Aβ25-35. Moreover, AHWE significantly inhibited Aβ25-35 and enhanced the protein levels of Akt in dPC12 cells. These observations unambiguously suggested that the protective effect of AHWE against Aβ25-35-induced apoptosis in dPC12 cells was associated with the enhancement of the PI3K/Akt signaling pathway.Conclusion: The results showed that adlay hull extracts have the anti-oxidant, antiinflammatory, anti-apoptotic and neuroprotective property. These results suggest that adlay hull extracts may have a preventive therapeutic potential in the management of AD.

A critical issue in executive control is how the nervous system exerts flexibility to inhibit a prepotent response and adapt to sudden changes in the environment. In this study, force measurement was used to capture “partial” unsuccessful trials that are highly relevant in extending the current understanding of motor inhibition processing. Moreover, a modified version of the stop-signal task was used to control and eliminate potential attentional capture effects from the motor inhibition index. The results illustrate that the non-canceled force and force rate increased as a function of stop-signal delay (SSD), offering new objective indices for gauging the dynamic inhibitory process. Motor response (time and force) was a function of delay in the presentation of novel/infrequent stimuli. A larger lateralized readiness potential (LRP) amplitude in go and novel stimuli indicated an influence of the novel stimuli on central motor processing. Moreover, an early N1 component reflects an index of motor inhibition in addition to the N2 component reported in previous studies. Source analysis revealed that the activation of N2 originated from inhibitory control associated areas: the right inferior frontal gyrus (rIFG), pre-motor cortex, and primary motor cortex. Regarding partial responses, LRP and error-related negativity (ERNs) were associated with error correction processes, whereas the N2 component may indicate the functional overlap between inhibition and error correction. In sum, the present study has developed reliable and objective indices of motor inhibition by introducing force, force-rate and electrophysiological measures, further elucidating our understandings of dynamic motor inhibition and error correction.

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

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.

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.

Bladder cancer is a common malignancy with mechanisms of pathogenesis and progression. This study aimed to identify the prognostic hub genes, which are the central modulators to regulate the progression and proliferation in the specific subtype of bladder cancer. The identification of the candidate hub gene was performed by weighted gene co-expression network analysis to construct a free-scale gene co-expression network. The gene expression profile of GSE97768 from the Gene Expression Omnibus database was used. The association between prognosis and hub gene was evaluated by The Cancer Genome Atlas database. Four gene-expression modules were significantly related to bladder cancer disease: the red module (human adenocarcinoma lymph node metastasis), the darkturquioise module (grade 2 carcinoma), the lightgreen module (grade 3 carcinoma), and the royalblue module (transitional cell carcinoma lymphatic metastasis). Based on betweenness centrality and survival analysis, we identified laminin subunit gamma-2 (LAMC2) in the grade 2 carcinoma, gelsolin (GSN) in the grade 3 carcinoma, and homeodomain-interacting protein kinase 2 (HIPK2) in the transitional cell carcinoma lymphatic metastasis. Subsequently, the protein levels of LAMC2 and GSN were respectively down-regulated and up-regulated in tumor tissue with the Human Protein Atlas (HPA) database. Our results suggested that LAMC2 and GSN are the central modulators to transfer information in the specific subtype of the disease.