Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease

Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4

Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

The association of ambient air pollution with airway inflammation in schoolchildren.

Chen, Bing-Yu,Chan, Chang-Chuan,Lee, Chung-Te,Cheng, Tsun-Jen,Huang, Wen-Chuan,Jhou, Ji-Ci,Han, Yueh-Ying,Chen, Chu-Chih,Guo, Yue Leon School of Hygiene and Public Health of the Johns H 2012 American Journal of Epidemiology Vol.175 No.8

<P>The biologic mechanisms involved in airway inflammatory response to air pollution are not clearly understood. The authors conducted a longitudinal study to investigate whether exposure to ambient air pollutants affected inflammatory cells and mediators from nasal lavage in schoolchildren. Study participants were 100 elementary and middle-school students in New Taipei City, Taiwan. A structured respiratory health questionnaire was administered in September 2007, followed by monthly measurement of nasal inflammation from October 2007 to November 2009. During the study period, daily concentrations of air pollutants were obtained from the Environmental Protection Administration monitoring station and the Aerosol Supersite. Mixed-effects models were applied to examine the association between air pollution and nasal inflammatory cells and mediators, including percentages of neutrophils, eosinophils, and monocytes in lavaged cells and interleukin-8. A total of 824 measurements were obtained from 100 participants over a period of 10 months. The level of particulate matter with an aerodynamic diameter of 2.5 μm or less (PM(2.5)) was found to be associated with percentage of neutrophils (β = 3.45%, 95% confidence interval: 0.89, 6.01) and interleukin-8 level (β = 29.98 pg/mL, 95% confidence interval: 3.26, 56.69) in the nasal lavage on the day of exposure. In this longitudinal cohort study of schoolchildren, results indicated that exposure to PM(2.5) might induce nasal inflammation.</P>

Equal Z standard-setting method to estimate the minimum number of panelists for a medical school’s objective structured clinical examination in Taiwan: a simulation study

Ying-Ying Yang,Pin-Hsiang Huang,Ling-Yu Yang,Chia-Chang Huang,Chih-Wei Liu,Shiau-Shian Huang,Chen-Huan Chen,Fa-Yauh Lee,Shou-Yen Kao,Boaz Shulruf 한국보건의료인국가시험원 2022 보건의료교육평가 Vol.19 No.-

Purpose Undertaking a standard-setting exercise is a common method for setting pass/fail cut scores for high-stakes examinations. The recently introduced equal Z standard-setting method (EZ method) has been found to be a valid and effective alternative for the commonly used Angoff and Hofstee methods and their variants. The current study aims to estimate the minimum number of panelists required for obtaining acceptable and reliable cut scores using the EZ method. Methods The primary data were extracted from 31 panelists who used the EZ method for setting cut scores for a 12-station of medical school’s final objective structured clinical examination (OSCE) in Taiwan. For this study, a new data set composed of 1,000 random samples of different panel sizes, ranging from 5 to 25 panelists, was established and analyzed. Analysis of variance was performed to measure the differences in the cut scores set by the sampled groups, across all sizes within each station. Results On average, a panel of 10 experts or more yielded cut scores with confidence more than or equal to 90% and 15 experts yielded cut scores with confidence more than or equal to 95%. No significant differences in cut scores associated with panel size were identified for panels of 5 or more experts. Conclusion The EZ method was found to be valid and feasible. Less than an hour was required for 12 panelists to assess 12 OSCE stations. Calculating the cut scores required only basic statistical skills.

An integrate information technology model during earthquake dynamics

Chen-Yuan Chen,Ying-Hsiu Chen,Shang-En Yu,Yi-Wen Chen,Chien-Chung Li 국제구조공학회 2012 Structural Engineering and Mechanics, An Int'l Jou Vol.44 No.5

Applying Information Technology (IT) in practical engineering has become one of the most important issues in the past few decades, especially on internal solitary wave, intelligent robot interaction, artificial intelligence, fuzzy Lyapunov, tension leg platform (TLP), consumer and service quality. Other than affecting the traditional teaching mode or increasing the inter-relation with users, IT can also be connected with the current society by collecting the latest information from the internet. It is apparently a fashion-catching-up technology. Therefore, the learning of how to use IT facilities is becoming one of engineers’ skills nowadays. In addition to studying how well engineers learn to operate IT facilities and apply them into teaching, how engineers’ general capacity of information effects the results of learning IT are also discussed. This research introduces the “Combined TAM and TPB mode,” to understand the situation of engineers using IT facilities.

Ginsenoside Rg3 in combination with artesunate overcomes sorafenib resistance in hepatoma cell and mouse models

Ying-Jie Chen,Jia-Ying Wu,Yu-Yi Deng,Ying Wu,Xiao-Qi Wang,Amy Sze-man Li,Lut Yi Wong,Xiuqiong Fu,Zhi-Ling Yu,Chun Liang 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.3

Sorafenib is effective in treating hepatoma, but most patients develop resistance to it. STAT3signaling has been implicated in sorafenib resistance. Artesunate (ART) and 20(R)-ginsenoside Rg3 (Rg3)have anti-hepatoma effects and can inhibit STAT3 signaling in cancer cells. This study aimed to evaluatethe effects of Rg3 in combination with ART (Rg3-plus-ART) in overcoming sorafenib resistance, and toexamine the involvement of STAT3 signaling in these effects. Methods: Sorafenib-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro anti-hepatomaeffects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assessthe in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assays and Annexin V-FITC/PI double stainingwere used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed toexamine protein levels. ROS generation was examined by measuring DCF-DA fluorescence. Results: Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, andsuppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibitedactivation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination alsodecreased the STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Furthermore, overactivation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, andremoval of ROS diminished Rg3-plus-ART's inhibitory effects on STAT3 activation in HepG2-SR cells. Conclusions: Rg3-plus-ART overcomes sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. Thisstudy provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treatingsorafenib-resistant hepatoma.

An integrate information technology model during earthquake dynamics

Chen, Chen-Yuan,Chen, Ying-Hsiu,Yu, Shang-En,Chen, Yi-Wen,Li, Chien-Chung Techno-Press 2012 Structural Engineering and Mechanics, An Int'l Jou Vol.44 No.5

Applying Information Technology (IT) in practical engineering has become one of the most important issues in the past few decades, especially on internal solitary wave, intelligent robot interaction, artificial intelligence, fuzzy Lyapunov, tension leg platform (TLP), consumer and service quality. Other than affecting the traditional teaching mode or increasing the inter-relation with users, IT can also be connected with the current society by collecting the latest information from the internet. It is apparently a fashion-catching-up technology. Therefore, the learning of how to use IT facilities is becoming one of engineers' skills nowadays. In addition to studying how well engineers learn to operate IT facilities and apply them into teaching, how engineers' general capacity of information effects the results of learning IT are also discussed. This research introduces the "Combined TAM and TPB mode," to understand the situation of engineers using IT facilities.

Association of Immune-Related Adverse Events and the Efficacy of Anti-PD-(L)1 Monotherapy in Non-Small Cell Lung Cancer: Adjusting for Immortal-Time Bias

Ying Yu,Ning Chen,Sizhe Yu,Wanji Shen,Wanchen Zhai,Hui Li,Yun Fan 대한암학회 2024 Cancer Research and Treatment Vol.56 No.3

Purpose The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB). Materials and Methods We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB. Results With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival. Conclusion After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

Diffusion Tensor-Derived Properties of Benign Oligemia, True “at Risk” Penumbra, and Infarct Core during the First Three Hours of Stroke Onset: A Rat Model

Fang-Ying Chiu,Duen-Pang Kuo,Yung-Chieh Chen,Yu-Chieh Kao,Hsiao-Wen Chung,Cheng-Yu Chen 대한영상의학회 2018 Korean Journal of Radiology Vol.19 No.6

Objective: The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true “at risk” penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset. Materials and Methods: The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain. Results: The mean volume of oligemia was 24.7 ± 14.1 mm3, that of TP was 81.3 ± 62.6 mm3, and that of IC was 123.0 ± 85.2 mm3 at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from -24% to -36%) as compared with TP (from -7% to -13%). Significant differences (p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was -33.90%. The metric values for oligemia and NT remained similar at all time points. Conclusion: Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

Anti-inflammatory effect of hispidin on LPS induced macrophage inflammation through MAPK and JAK1/STAT3 signaling pathways

Han Ying-Hao,Chen Dong-Qin,Jin Mei-Hua,Jin Ying-Hua,Li Jing,Shen Gui-Nan,Li Wei-Long,Gong Yi-Xi,Mao Ying-Ying,Xie Dan-Ping,Lee Dong-Seok,Yu Li-Yun,Kim Sun-Uk,김지수,권태호,Cui Yu-Dong,Sun Hu-Nan 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

Severe inflammatory reactions caused by macrophage activation can trigger a systemic immune response. In the present study, we observed the anti-inflammatory properties of hispidin on LPS induced RAW264.7 macrophage cells. Our results showed that hispidin treatment significantly reduced the production of cellular NO, IL-6 and reactive oxygen species (ROS) while has not inhibitory effect on TNF-α productions. Excitingly, hispidin treatment retains the phagocytosis ability of macrophages which enabling them to perform the function of removing foreign invaders. Signaling studies showed, hispidin treatment dramatic suppressed the LPS induced mitogen activated protein kinases (MAPK) and JAK/STAT activations. In conclusion, our findings suggest that hispidin may be a new therapeutic target for clinical treatment of macrophages-mediated inflammatory responses.

A Genetic Variant in MiR-146a Modifies Digestive System Cancer Risk: a Meta-analysis

Li, Ying-Jun,Zhang, Zhen-Yu,Mao, Ying-Ying,Jin, Ming-Juan,Jing, Fang-Yuan,Ye, Zhen-Hua,Chen, Kun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

MicroRNAs (miRNAs) negatively regulate gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to digestive system cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed to identify all relevant studies published before August 31, 2013. A total of 21 independent case-control studies were included in this updated meta-analysis with 9,558 cases and 10,614 controls. We found that the miR-146a rs2910164 polymorphism was significantly associated with decreased risk of digestive system cancers in an allele model (OR=0.90, 95%CI 0.87-0.94), homozygote model (OR=0.84, 95%CI 0.77-0.91), dominant model (OR=0.90, 95%CI 0.84-0.96), and recessive model (OR=0.85, 95%CI 0.79-0.91), while in a heterozygous model (OR = 0.99, 95% CI 0.89-1.11) the association showed marginal significance. Subgroup analysis by cancer site revealed decreased risk in colorectal cancer above allele model (OR=0.90, 95%CI 0.83-0.97) and homozygote model (OR=0.85, 95%CI 0.72-1.00). Similarly, decreased cancer risk was observed when compared with allele model (OR=0.87, 95%CI 0.81-0.93) and recessive model (OR=0.81, 95%CI 0.72-0.90) in gastric cancer. When stratified by ethnicity, genotyping methods and quality score, decreased cancer risks were also observed. This current meta-analysis indicated that miR-146a rs2910164 polymorphism may decrease the susceptibility to digestive system cancers, especially in Asian populations.