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Ying-Fei Yang,1 Yi-Jun Lin,2 Shu-Han You,3 Tien-Hsuan Lu,4 Chi-Yun Chen,5,6 Wei-Min Wang,1 Min-Pei Ling,7 Szu-Chieh Chen,8,9 Chung-Min Liao1 1Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, 10617, Taiwan; 2Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Taipei, 11230, Taiwan; 3Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung City, 20224, Taiwan; 4Department of Science Education and Application, National Taichung University of Education, Taichung, 403514, Taiwan; 5Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL, 32610, USA; 6Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32608, USA; 7Department of Food Science, National Taiwan Ocean University, Keelung City, 20224, Taiwan; 8Department of Public Health, Chung Shan Medical University, Taichung, 40201, Taiwan; 9Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, 40201, TaiwanCorrespondence: Chung-Min Liao, Department of Bioenvironmental Systems Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan, Email cmliao@ntu.edu.twBackground: The emergence and progression of highly divergent SARS-CoV-2 variants have posed increased risks to global public health, triggering the significant impacts on countermeasures since 2020. However, in addition to vaccination, the effectiveness of non-pharmaceutical interventions, such as social distancing, masking, or hand washing, on different variants of concern (VOC) remains largely unknown.Objective: This study provides a mechanistic approach by implementing a control measure model and a risk assessment framework to quantify the impacts of control measure combinations on the transmissions of five VOC (Alpha, Beta, Delta, Gamma, and Omicron), along with a different perspective of risk assessment application.Materials and Methods: We applied uncontrollable ratios as an indicator by adopting basic reproduction number (R0) data collected from a regional-scale survey. A risk assessment strategy was established by constructing VOC-specific dose-response profiles to implicate practical uses in risk characterization when exposure data are available.Results: We found that social distancing alone was ineffective without vaccination in almost all countries and VOC when the median R0 was greater than two. Our results indicated that Omicron could not be contained, even when all control measure combinations were applied, due to its low threshold of infectivity (~3× 10− 4 plague-forming unit (PFU) mL− 1).Conclusion: To facilitate better decision-making in future interventions, we provide a comprehensive evaluation of how combined control measures impact on different countries and various VOC. Our findings indicate the potential application of threshold estimates of infectivity in the context of risk communication and policymaking for controlling future emerging SARS-CoV-2 variant infections.Keywords: SARS-CoV-2, variants of concern, basic reproduction number, modeling, non-pharmaceutical interventions, infection risk

Qing-Lin Li,1,2,* Xue-Jiao Liu,1,2,* Shu-E Zhang,3 Chao-Yi Chen,1,2 Liang Zhang,4 Xiang Zhang1,2 1Department of Health Administration, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2The Key Research Institute of Humanities and Social Science of Hubei Province, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Health Management, School of Health Management, Harbin Medical University, Harbin, 150081, People’s Republic of China; 4School of Political Science and Public Administration, Wuhan University, Wuhan, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang Zhang, Department of Health Administration, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 18907145152, Email zhangchxiang@163.comPurpose: This study aimed to identify distinct trends among Chinese residents based on their health-related quality of life (HR-QoL) outcomes and to analyze the demographic characteristics that contribute to these trends.Materials and Methods: The study conducted latent class analysis using baseline data obtained from a survey of health service utilization behaviors (from July to December 2016) among residents of Hubei Province, China (N = 1517). Latent classes were used to implement the HR-QoL grouping of different trends among the respondents. Multinomial logistic regression analysis was used to identify demographic characteristic factors affecting HR-QoL in the trend groups.Results: A three-class model emerged as the most suitable grouping classification for HR-QoL among Chinese residents: the low HR-QoL class, exhibiting a downward trend (5.5%); the medium HR-QoL class, exhibiting an upward trend (12.1%); and the stable HR-QoL class, exhibiting high HR-QoL (82.4%). Participants in the medium class were more likely to be without chronic diseases, aged 45– 64 years, and employed than those in the low class. Conversely, urban participants had a higher likelihood of belonging to the low class. Participants in the stable class were more likely to be without chronic diseases, aged 15– 44 years or 45– 64 years, and employed than those in the low class. Conversely, urban participants had a higher likelihood of belonging to the low class.Conclusion: Three latent trend classes of HR-QoL were observed, which exhibited distinct characteristics. Residents without chronic diseases, residents under 65 years of age, and employed residents had better HR-QoL than individuals in other classes, while urban residents had poorer HR-QoL than individuals in other classes.Plain Language Summary: Health-related quality of life (HR-QoL) is an essential predictor of healthcare utilization, mortality, morbidity, and poor health. The rapid pace of modernization has corresponded with changes in the HR-QoL of the population. However, more empirical research is needed on the changes in HR-QoL among the Chinese population. In this study, we identified different trends in HR-QoL among Chinese residents and the demographic factors influencing HR-QoL among these trends. This study highlighted variations in longitudinal HR-QoL trends among Chinese residents. HR-QoL for Chinese residents is divided into three classes: low, exhibiting a downward trend; medium, exhibiting an upward trend; and stable, exhibiting high HR-QoL. Residents without chronic diseases, residents under the age of 65, and employed residents had better HR-QoL than other classes of individuals, while urban residents had worse HR-QoL than other classes of individuals. Understanding these HR-QoL trends could aid the development of targeted interventions for Chinese residents and improve their health and quality of life.Keywords: Chinese resident, health-related quality of life, latent class analysis

Yi-Chun Liu,1 Shuh-Kuan Liau,1 Cheng-Chieh Hung,1 Chao-Yu Chen,1 Yueh-An Lu,1 Yu-Jr Lin,2 Ya-Chung Tian,1 Yung-Chang Chen,1 Fan-Gang Tseng,3,4 Hsiang-Hao Hsu1 1Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Research Services Center for Health Information, from Chang Gung University, Taoyuan, Taiwan; 3Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan; 4Institute of Nano Engineering and Microsystems, National Tsing Hua University, Hsinchu, TaiwanCorrespondence: Hsiang-Hao Hsu, Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, No. 5 Fu-Shin Street, Guishan, Taoyuan, 333, Taiwan, Tel +886-3-328-1200 ext. 8181, Fax +886-3-3282173, Email hsianghao@gmail.comBackground: Listeriosis is caused by the facultative anaerobic bacterium Listeria monocytogenes. Infection from Listeria-contaminated food or water is the main etiology. If Listeria travels outside the intestines, it can cause invasive listeriosis, such as sepsis, meningitis, and meningoencephalitis. Invasive illness is especially dangerous for pregnant women and their newborns, elderly people, and people with compromised immune systems or medical conditions such as end-stage kidney disease (ESKD) patients receiving long-term dialysis.Purpose: Describe the manifestations and hospital outcomes of invasive listeriosis and identify the risk factors for in-hospital and one-year mortality in ESKD patients receiving long-term dialysis.Patients and Methods: This retrospective observational study examined hospitalized patient records at a Taiwanese tertiary medical center from August 1, 2000, to August 31, 2021. ESKD patients on chronic dialysis were identified with invasive listeriosis by blood culture and discharge diagnosis. Over 21 years, we accurately recorded 26 cases.Results: ESKD patients on chronic dialysis with invasive listeriosis have a poor prognosis. Only 53.8% of chronic dialysis patients with invasive listeriosis survived their first hospital episode. 42.3% of hospitalized ESKD patients with invasive listeriosis survived one year later. In univariate analysis, shock, tachypnea (RR ≥ 22), respiratory failure, qSOFA score ≥ 2, and lower initial platelet count were linked to greater in-hospital mortality rates.Conclusion: ESKD patients with invasive listeriosis have a grave prognosis. Our research reveals that an early blood sample for a bacterial culture may identify invasive listeriosis in chronic dialysis patients with fever, nausea or vomiting, confusion, and respiratory distress. This study is the first to identify a lower platelet count and qSOFA score ≥ 2 as markers of high-risk invasive listeriosis in ESKD patients.Keywords: chronic dialysis, ESKD, invasive listeriosis, qSOFA, outcome

Chao-Ying Chen,1,2 Kuan-Ying Lee,3 Xavier CC Fung,4 Ji-Kang Chen,5 Yu-Chen Lai,6 Marc N Potenza,7– 12 Kun-Chia Chang,13,14 Chuan-Yin Fang,6 Amir H Pakpour,15 Chung-Ying Lin16– 20 1School of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2New Taipei City Tucheng Hospital (Chang Gung Medical Foundation), Department of Pediatric Internal Medicine, New Taipei City, Taiwan; 3Department of Child and Adolescent Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan; 4Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong; 5Department of Social Work, Chinese University of Hong Kong, New Territories, Hong Kong; 6Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 621, Taiwan; 7Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; 8Connecticut Mental Health Center, New Haven, CT, USA; 9Connecticut Council on Problem Gambling, Wethersfield, CT, USA; 10Child Study Center, Yale School of Medicine, New Haven, CT, USA; 11Department of Neuroscience, Yale University, New Haven, CT, USA; 12Wu Tsai Institute, Yale University, New Haven, CT, USA; 13Department of General Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan; 14Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 15Department of Nursing, School of Health and Welfare, Jönköping University, Jönköping, Sweden; 16Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 17Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 18Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 19Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 20INTI International University, Nilai, Negeri Sembilan, 71800, MalaysiaCorrespondence: Kun-Chia Chang, Department of General Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan, Tel +886-6-2795019 ext. 1532, Fax +886-6-2797659, Email kunchiachang0517@gmail.com Chuan-Yin Fang, Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 621, Taiwan, Email 04969@cych.org.twBackground: Problematic use of internet (PUI) may have negative impacts on psychological distress and quality of life (QoL). This situation might be more profound in people with attention-deficit/hyperactivity disorder (ADHD) due to poorer behavioral control and regulatory capacity. However, there is little evidence regarding mediated effects in the associations between PUI, psychological distress, and QoL in people with ADHD.Aims: To investigate mediating effects of psychological distress in the associations of problematic smartphone use (PSPU), problematic use of social media (PUSM), and problematic gaming (PG) with QoL in individuals with ADHD.Methods and Procedures: PUI behaviors of participants with ADHD (n = 99) were assessed using the Smartphone Application-Based Addiction Scale, Bergen Social Media Addiction Scale, and Internet Gaming Disorder-Short Form. Psychological distress was assessed using the Depression, Anxiety, Stress Scale and QoL using the Kid-KINDL.Outcomes and Results: Psychological distress mediated the associations between PUI and different domains of QoL, except for self-esteem QoL. There were also positively direct effects between PG and physical QoL, PUSM and friends’ QoL, and PSPU and physical QoL.Conclusions and Implications: PUI may associate with poor QoL in people with ADHD via psychological distress. Programs on reducing PUI for people with ADHD are needed.Keywords: attention-deficit/hyperactivity disorder, ADHD, impulsive behavior, addictive behavior, internet, psychological distress, quality of life

Chen-Yu Chen,1,2 Ying-Hao Wang,1 Chie-Pein Chen,1 Fang-Ju Sun,3 Yi-Yung Chen,1 Yu-Jun Huang,1 Nan-Fu Chiu4,5 1Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei, 10449, Taiwan; 2Department of Medicine, MacKay Medical College, New Taipei City, 252005, Taiwan; 3Department of Medical Research, MacKay Memorial Hospital, Taipei, 10449, Taiwan; 4Laboratory of Nano-Photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, Taipei, 11677, Taiwan; 5Department of Life Science, National Taiwan Normal University, Taipei, 11677, TaiwanCorrespondence: Chen-Yu Chen, Department of Obstetrics and Gynecology, MacKay Memorial Hospital, No. 92, Section 2, Zhong-Shan North Road, Taipei, 10449, Taiwan, Tel +886-2-25433535, Fax +886-2-25433642, Email f122481@mmh.org.tw Nan-Fu Chiu, Laboratory of Nano-Photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, No. 88, Section 4, Ting-Chou Road, Taipei, 11677, Taiwan, Tel +886-2-77496722, Fax +886-2-86631954, Email nfchiu@ntnu.edu.twBackground: Preeclampsia, a major cause of adverse pregnancy outcomes, involves metalloproteinases pregnancy-associated plasma protein (PAPP)-A and PAPP-A2 from placental trophoblasts. The graphene oxide (GO)-based surface plasmon resonance (SPR) biosensor has higher sensitivity, affinity, and selective ability than the traditional SPR biosensor. The aim of this study was to explore the feasibility of measuring first-trimester serum PAPP-A/PAPP-A2 ratio as a novel predictor of preeclampsia using the GO-SPR biosensor.Methods: This prospective case-control study of pregnant women was conducted at MacKay Memorial Hospital, Taipei, Taiwan between January 2018 and June 2020. The SPR angle shifts of first-trimester serum PAPP-A, PAPP-A2, and PAPP-A/PAPP-A2 ratio measured using the GO-SPR biosensor were compared between preeclampsia and control groups.Results: Serum samples from 185 pregnant women were collected, of whom 30 had preeclampsia (5 early-onset; 25 late-onset). The response time between the antibody-antigen association and dissociation only took about 200 seconds. The SPR angle shift of PAPP-A in the preeclampsia group was significantly smaller than that in the control group (median (interquartile range): 5.33 (4.55) versus 6.89 (4.10) millidegrees (mDeg), P = 0.008). Conversely, the SPR angle shift of PAPP-A2 in the preeclampsia group was significantly larger than that in the control group (5.70 (3.81) versus 3.63 (2.38) mDeg, P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict all preeclampsia of ≤ 0.76, with an area under the ROC curve (AUC) of 0.79 (95% CI 0.73– 0.85, P < 0.001). Sub-group analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict early-onset preeclampsia of ≤ 0.53 (AUC 0.99, 95% CI 0.96– 1.00, P < 0.001), and ≤ 0.73 to predict late-onset preeclampsia (AUC 0.75, 95% CI 0.68– 0.81, P < 0.001).Conclusion: Measuring first-trimester serum PAPP-A/PAPP-A2 ratio using the GO-SPR biosensor could be a valuable method for early prediction of preeclampsia. Keywords: graphene oxide, surface plasmon resonance, biosensor, preeclampsia, PAPP-A/PAPP-A2 ratio

Chen-Wei Lin,1,2,&ast; Jin-Jhe Wang,2,&ast; Chien-Hsiung Lai,2– 5 Chau-Yin Chen,2,3 Ing-Chou Lai2,3,6 1Department of Medical Education, Chang Gung Memorial Hospital, Chiayi, 61363, Taiwan; 2Department of Ophthalmology, Chang Gung Memorial Hospital, Chiayi, 61363, Taiwan; 3Department of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; 4Department of Nursing, Chang Gung University of Science and Technology, Chiayi, 61363, Taiwan; 5School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; 6Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan&ast;These authors contributed equally to this workCorrespondence: Jin-Jhe Wang, Department of Ophthalmology, Chiayi Chang Gung Memorial Hospital, No. 8, Sec. W., Jiapu Road, Puzi City, Chiayi County, 613, Taiwan, Tel +886 5 3621000, Fax +886 5 3623002, Email leo81819@gmail.comPurpose: Intraocular pressure (IOP) measurement is critical in diagnosing and managing eye conditions. This study aims to assess the comparability of three alternative devices for measuring IOP: Noncontact tonometer, Icare rebound tonometer, and Tono-Pen.Patients and Methods: A cross-sectional study included 172 adult participants (87 males and 85 females) who underwent IOP and central corneal thickness (CCT) assessments. IOP was measured using Noncontact (Canon TX-20), Icare (Icare TA01i), and Tono-Pen (Tonopen XL). CCT was measured with the built-in pachymetry of the Noncontact tonometer. Correlation coefficients and Bland-Altman analyses were conducted to assess the relationships and agreements between these tonometers. Participants were grouped based on IOP and CCT levels. The mean of the standard deviation of the three tonometer results was calculated to evaluate measurement result variability. One-way analysis of variance was conducted for comparing between the groups.Results: IOP measurements among the three devices were not significantly different, indicating their comparability. Correlation analysis revealed strong correlations between the tonometers. Bland-Altman analysis showed good agreement, with the Icare rebound tonometer and Tono-Pen exhibiting narrower limits of agreement. Furthermore, IOP levels influenced measurement result variability, with higher IOP levels associated with greater variance.Conclusion: This study demonstrates that the alternative devices examined can provide reliable IOP measurements. It highlights the potential of these alternative devices for IOP measurement. These findings have implications for clinical practice, offering practitioners additional tools for accurate IOP assessment.Keywords: intraocular pressure, tonometer, noncontact, icare, Tono-Pen

Yi-Jan Wu,1,2 Shu-Sen Chang,3 Hsien-Yi Chen,4 Kai-Fan Tsai,2,5 Wen-Chin Lee,2,5 I-Kuan Wang,6,7 Chern-Horng Lee,8 Chao-Yu Chen,1,2 Shou-Hsuan Liu,1,2 Cheng-Hao Weng,1,2 Wen-Hung Huang,1,2 Ching-Wei Hsu,1,2 Tzung-Hai Yen1,2 1Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 3Institute of Health Behaviors and Community Sciences, Department of Public Health, College of Public Health, National Taiwan University, Taipei City, Taiwan; 4Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan; 5Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Branch, Kaohsiung City, Taiwan; 6Department of Nephrology, China Medical University Hospital, Taichung City, Taiwan; 7College of Medicine, China Medical University, Taichung City, Taiwan; 8Division of General Internal Medicine and Geriatrics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, TaiwanCorrespondence: Tzung-Hai Yen, Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou Branch, 5 Fu-Hsing Street, Kweishan, Taoyuan City, Taiwan, Tel +886 3 3281200 ext 8181, Fax +886 3 3282173, Email m19570@cgmh.org.twBackground and Purpose: There is an overall paucity of data regarding the human toxicity of chlorpyrifos and cypermethrin pesticide mixture. Both organophosphate and pyrethroid insecticides are metabolized by carboxylesterases. Thus, its pesticide combination, organophosphates may boost the toxicity of pyrethroids via inhibited its detoxification by carboxylesterases. This study examined the clinical course, laboratory tests, and outcomes of patients with chlorpyrifos, cypermethrin or their pesticide mixture poisoning, and to determine what association, if any, might exist between these findings.Patients and Methods: Between 2000 and 2021, 121 patients poisoned with chlorpyrifos, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. Patients were categorized as chlorpyrifos (n=82), cypermethrin (n=27) or chlorpyrifos and cypermethrin (n=12) groups. Demographic, clinical, laboratory and mortality data were collected for analysis.Results: The patients experienced a broad range of clinical symptoms, including aspiration pneumonia (44.6%), salivation (42.5%), acute respiratory failure (41.3%), acute kidney injury (13.9%), seizures (7.5%), hypotension (2.6%), etc. Leukocytosis (12,700± 6600 /uL) and elevated serum C-reactive protein level (36.8± 50.4 mg/L) were common. The acute respiratory failure rate was 41.3%, comprising 48.8% in chlorpyrifos, 11.1% in cypermethrin as well as 58.3% in chlorpyrifos and cypermethrin poisoning. Patients with chlorpyrifos and cypermethrin pesticide mixture poisoning suffered higher rates of acute respiratory failure (P=0.001) and salivation (P=0.001), but lower Glasgow Coma Scale score (P=0.011) and serum cholinesterase level (P< 0.001) than other groups. A total of 17 (14.0%) patients expired. The mortality rate was 14.0%, including 17.1% in chlorpyrifos, 3.7% in cypermethrin as well as 16.7% in chlorpyrifos and cypermethrin poisoning. No significant differences in mortality rate were noted (P=0.214).Conclusion: Chlorpyrifos pesticide accounted for the major toxicity of the pesticide mixture. While the data show a higher rate of respiratory failure in the chlorpyrifos and cypermethrin pesticide mixture group than others, other measures of toxicity such as mortality and length of stay were not increased.Keywords: chlorpyrifos, cypermethrin, pesticide mixture, poisoning, acute respiratory failure, mortality

Pei-An Liao,1 Sheng-Wei Pan,2,3 Chun-Yu Chen,4,5 Chung-Yeh Deng,1,4 Yaa-Hui Dong1,4,5 1Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 2Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 3Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 4Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Yaa-Hui Dong, Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, 155, Sec 2, Linong Street, Taipei, 112, Taiwan, Tel +886-2-28267986, Fax +886-2-28237929, Email yaahuidong@gmail.comBackground: The clinical guideline recommends use of long-acting β 2 agonists/long-acting muscarinic antagonists (LABA/LAMA) or long-acting β 2 agonists/inhaled corticosteroids (LABA/ICS) combination therapies for patients with severe chronic obstructive pulmonary disease (COPD). The fixed-dose combination (FDC) inhalers of LABA/LAMA and LABA/ICS were reimbursed in Taiwan in 2015 and in 2002, respectively. This study aimed to examine prescription patterns of new use of either FDC therapy in real-world practice.Methods: We identified COPD patients who initiated LABA/LAMA FDC or LABA/ICS FDC between 2015 and 2018 from a population-based Taiwanese database with 2 million, randomly sampled beneficiaries enrolled in a single-payer health insurance system. We compared number of LABA/LAMA FDC and LABA/ICS FDC initiators in each calendar year, from different hospital accreditation levels, and cared for by different physician specialties. We also compared baseline patient characteristics between LABA/LAMA FDC and LABA/ICS FDC initiators.Results: A total of 12,455 COPD patients who initiated LABA/LAMA FDC (n=4019) or LABA/ICS FDC (n=8436) were included. Number of LABA/LAMA FDC initiators increased apparently (n=336 in 2015 versus n=1436 in 2018), but number of LABA/ICS FDC initiators decreased obviously (n=2416 in 2015 versus n=1793 in 2018) over time. The preference of use of LABA/LAMA FDC varied across clinical environments. The proportions of LABA/LAMA FDC initiators were more than 30% in the setting of non-primary care clinics (eg, medical centers) and in the services of chest physicians; but were only less than 10% in primary care clinics and non-chest physicians’ services (eg, family medicine physicians). LABA/LAMA FDC initiators appeared to be older, male, to have more comorbidities, and to utilize resources more frequently compared to LABA/ICS FDC initiators.Conclusion: This real-world study found evident temporal trends, variations in healthcare provider, and differences in patient characteristics among COPD patients who initiated LABA/LAMA FDC or LABA/ICS FDC.Keywords: chronic obstructive pulmonary disease, new users, long-acting β 2 agonists/long-acting muscarinic antagonists fixed-dose combination, LABA/LAMA FDC, long-acting β 2 agonists/inhaled corticosteroids fixed-dose combination, LABA/ICS FDC, temporal trends, healthcare provider characteristics, patient characteristics

Chao-Yang Chen,1 Ming-Ta Hsieh,1,2 Chen-Ting Wei,1 Chi-Wei Lin1,3 1Department of Family Medicine and Community Medicine, E-Da Hospital, Kaohsiung City, Taiwan; 2Department of Nursing, College of Medicine, I-Shou University, Kaohsiung City, Taiwan; 3School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City, TaiwanCorrespondence: Ming-Ta Hsieh, Department of Family Medicine and Community Medicine, E-Da Hospital, Kaohsiung City, Taiwan; Department of Nursing, College of Medicine, I-Shou University, No. 1, Yida Road, Jiao-Su Village, Yan-Chao District, Kaohsiung City, 824005, Taiwan, Email kaplan210@yahoo.com.twImportance: COVID-19 vaccination has been associated with various adverse outcomes. Although studies have reported cases of arrhythmia after COVID-19 vaccination, the precise underlying mechanism remains to be elucidated.Objective: Here, we report the case of a patient who developed atrial fibrillation after receiving the mRNA-1273 vaccine and describe our findings in light of relevant cases in the literature.Design, Setting, and Participants: This is a case report and a review of the relevant literature. A 55-year-old woman presented to our clinic with a history of paroxysmal atrial fibrillation, hypertension, and mild mitral valve prolapse. The patient developed atrial fibrillation 3 days after receiving a COVID-19 vaccine. She was diagnosed with moderate-to-severe tricuspid regurgitation and severe mitral regurgitation, and underwent valve repair surgery. To obtain relevant articles (December 2020 through August 2022), we searched the following key words on PubMed: atrial fibrillation and COVID-19 vaccination.Results: A total of 5 relevant case reports were identified. COVID-19 vaccination led to arrhythmia, including atrial fibrillation, within 14 days.Conclusions and Relevance: Cases of patients developing arrhythmia after COVID-19 vaccination have been increasingly reported. Although the underlying mechanism remains unclear, we hypothesize that mRNA vaccination may lead to arrhythmia and associated valve diseases. Thus, before administering mRNA-1273 vaccines to patients with a history of valvular heart disease or atrial fibrillation, the patients’ cardiologists must be consulted.Keywords: atrial fibrillation, valvular heart disease, COVID-19 vaccination, case report

Xiao-Xing Liu,1– 3 Chun-Yu Chen,1– 3 Li Li,1– 3 Miao-Miao Guo,1– 3 Yi-Fan He,1– 3 Hong Meng,1– 3 Yin-Mao Dong,1– 3 Pei-Gen Xiao,4 Fan Yi1– 3 1Beijing Key Laboratory of Plant Resources Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, People’s Republic of China; 2Key Laboratory of Cosmetic, China National Light Industry, Beijing Technology and Business University, Beijing, People’s Republic of China; 3Institute of Cosmetic Regulatory Science, Beijing Technology and Business University, Beijing, People’s Republic of China; 4Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Fan Yi, Email fantasyee@btbu.edu.cnBackground: Adaptogens are a class of medicinal plants that can nonspecifically enhance human resistance. Most of the plant adaptogens have relevant applications in dermatology, but there are still few studies related to their particular action and co-operative mechanisms in topical skin application.Methods: Plant adaptogens related articles and reviews that published between 1999 and 2022 were obtained from the Web of Science Core Collection database. Various bibliographic elements were collected, including the annual number of publications, countries/regions, and keywords. CiteSpace, a scientometric software, was used to conduct bibliometric analyses. Also, the patsnap global patent database was used to analyze the patent situation of plant adaptogens in the field of cosmetics up to 2021.Results: We found that the effects of plant adaptogens on skin diseases mainly involve atopic dermatitis, acne, allergic contact dermatitis, psoriasis, eczema, and androgenetic alopecia, etc. And the effects on skin health mainly involve anti-aging and anti-photoaging, anti-bacterial and anti-fungal, anti-inflammatory, whitening, and anti-hair loss, etc. Also, based on the results of patent analysis, it is found that the effects of plant adaptogens on skin mainly focus on aging retardation. The dermatological effects of plant adaptogens are mainly from Fabaceae Lindl., Araliaceae Juss. and Lamiaceae Martinov., and their mainly efficacy phytochemical components are terpenoids, phenolic compounds and flavonoids.Conclusion: The plant adaptogens can repair the skin barrier and maintain skin homeostasis by regulating the skin HPA-like axis, influencing the oxidative stress pathway to inhibit inflammation, and regulating the extracellular matrix (ECM) components to maintain a dynamic equilibrium, ultimately achieving the treatment of skin diseases and the maintenance of a healthy state.Graphical Abstract: Keywords: plant adaptogens, dermatology, skin HPA-like axis, ECMs, skin homeostasis, pharmacophylogeny

Chao-Jen Li,1,&ast; Hung-Wen Tsai,2,&ast; Yi-Li Chen,3 Chun-I Wang,4 Yang-Hsiang Lin,5 Pei-Ming Chu,6,7 Hsiang-Cheng Chi,8,9 Yi-Ching Huang,3 Cheng-Yi Chen3 1Department of General & Gastroenterological Surgery, An Nan Hospital, China Medical University, Tainan, Taiwan; 2Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; 5Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Department of Anatomy, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 7Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan; 8Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 9Chinese Medicine Research Center, China Medical University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Cheng-Yi Chen, Tel/Fax +886-6-2353535&num;5329, Email cychen@gs.ncku.edu.twIntroduction: Hepatocellular carcinoma (HCC) accounts for 80% of all liver cancers and is the 2nd leading cause of cancer-related death in Taiwan. Various factors, including rapid cell growth, a high recurrence rate and drug resistance, make HCC difficult to cure. Moreover, the survival rate of advanced HCC patients treated with systemic chemotherapy remains unsatisfactory. Hence, the identification of novel molecular targets and the underlying mechanisms of chemoresistance in HCC and the development more effective therapeutic regimens are desperately needed.Methods: An MTT assay was used to determine the cell viability after cisplatin or doxorubicin treatment. Western blotting, qRT‒PCR and immunohistochemistry were utilized to examine the protein tyrosine phosphatase IVA3 (PTP4A3) level and associated signaling pathways. ELISA was utilized to analyze the levels of the inflammatory cytokine IL-6 influenced by cisplatin, doxorubicin and PTP4A3 silencing.Results: In this study, we found that PTP4A3 in the cisplatin/doxorubicin-resistant microarray was closely associated with the overall and recurrence-free survival rates of HCC patients. Cisplatin or doxorubicin significantly reduced cell viability and decreased PTP4A3 expression in hepatoma cells. IL-6 secretion increased with cisplatin or doxorubicin treatment and after PTP4A3 silencing. Furthermore, PTP4A3 was highly expressed in tumor tissues versus adjacent normal tissues from HCC patients. In addition, we evaluated the IL-6-associated signaling pathway involving STAT3 and JAK2, and the levels of p-STAT3, p-JAK2, STAT3 and JAK2 were obviously reduced with cisplatin or doxorubicin treatment in HCC cells using Western blotting and were also decreased after silencing PTP4A3. Collectively, we suggest that cisplatin or doxorubicin decreases HCC cell viability via downregulation of PTP4A3 expression through the IL-6R-JAK2-STAT3 cascade.Discussion: Therefore, emerging evidence provides a deep understanding of the roles of PTP4A3 in HCC cisplatin/doxorubicin chemoresistance, which can be applied to develop early diagnosis strategies and reveal prognostic factors to establish novel targeted therapeutics to specifically treat HCC.Keywords: hepatocellular carcinoma, chemoresistance, cisplatin, doxorubicin, PTP4A3, IL-6

Kuang-Ming Liao,1 Yi-Ju Chen,2 Chuan-Wei Shen,2 Shao-Kai Ou,2 Chung-Yu Chen2– 4 1Department of Internal Medicine, Chi Mei Medical Center, Chiali, Taiwan; 2School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanCorrespondence: Chung-Yu Chen, School of Pharmacy, Kaohsiung Medical University, No. 100, Shihcyuan 1st Road, Sanmin District, Kaohsiung City, 80708, Taiwan, Tel +886-7-3121101 ext 2375, Fax +886-7-3210683, Email jk2975525@hotmail.comIntroduction: Chronic obstructive pulmonary disease (COPD) is a common disease and is preventable and treatable. A previous study showed that influenza virus infections were also associated with the risk of acute exacerbation in patients with COPD, and other studies showed that the influenza virus might increase the risk of stroke. However, studies on the influence of influenza infection among COPD patients are limited. In this study, we review the role of influenza infection in contributing to mortality, pneumonia, respiratory failure, COPD acute exacerbation, and ischemic stroke among COPD patients.Materials and Methods: We performed a population-based cohort study of COPD patients using data from Taiwan between January 1, 2011, and December 31, 2019. We excluded patients with lung cancer, lung transplantation and asthma. We also excluded patients who lacked COPD medication prescriptions and those treated with anti-influenza drugs without flu diagnosis records. Patients with missing or incomplete data were also excluded from the study cohort.Results: After 1:1 matching by age, sex, COPD duration, diagnosed years and comorbidities, we enrolled 10,855 cases and controls for further analysis. The risks of pneumonia, respiratory failure, COPD acute exacerbation, and ischemic stroke were 1.770 (95% CI=1.638– 1.860; P< 0.0001), 1.097 (95% CI=1.008– 1.194; P=0.0319), 1.338 (95% CI=1.248– 1.435; P< 0.0001), and 1.134 (95% CI=1.039– 1.239, P=0.0051), respectively, in the influenza infection group compared with COPD patients without influenza infection.Conclusion: Influenza infections are linked to an increased risk of ischemic stroke, pneumonia, respiratory failure, and COPD acute exacerbation among COPD patients. In conclusion, patients with COPD need to be closely monitored after having an influenza infection.Keywords: acute exacerbation, chronic obstructive pulmonary disease, influenza virus, pneumonia, stroke, respiratory failure

Pik-Qi Chin,1,&ast; Chau-Chyun Sheu,2,3 Jong-Rung Tsai,4,5 Hsu-Liang Chang,6 Li-Yao Lee,7,&ast; Chung-Yu Chen1,7,8 1Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Division of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Internal Medicine, Kaohsiung Municipal Cijin Hospital, Kaohsiung, Taiwan; 6Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital; Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 8Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chung-Yu Chen, Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, No. 100, Shihcyuan 1st Road, Sanmin District, Kaohsiung, 80708, Taiwan, Tel +886-7-3121101 ext 2375, Fax +886-7-3210683, Email jk2975525@hotmail.comBackground: To assess the health-related quality of life (HRQoL) of Taiwan patients with different stages of chronic obstructive pulmonary disease (COPD) and using different combination therapies and to explore the factors affecting HRQoL in these patients.Methods: This cross-sectional study included outpatient participants aged 35 years old and older who were receiving long-acting bronchodilator treatment in one of two hospitals in Southern Taiwan. Participants were categorized according to their Global Initiative for Obstructive Lung Disease (GOLD) classification as either their COPD group, based on symptoms and exacerbation risk, or their COPD stage, based on spirometry results. Patients’ HRQoL was assessed using the St. George’s Respiratory Questionnaire score (SGRQ), World Health Organization Quality of Life Quality of Life-BREF (WHOQOL-BREF), and EQ-5D-5L. The total scores of the SGRQ, WHOQOL-BREF, EQ-5D utility index, and EQ-VAS were presented as mean ± standard deviation (SD) among different combination treatments. Univariate and multivariate analyses were used to explore the association of patients’ baseline characteristics and environmental factors with HRQoL.Results: A total of 218 patients were enrolled in the study. The distribution of patients using GOLD group classification were as follows: 73.39% in group A, 20.19% group B, 1.83% group C and 4.59% group D. Triple therapy patients mostly showed a lower quality of life than other combination therapies, regardless of the GOLD classification system. However, only the SGRQ scores of GOLD groups A and B were significantly different when using different drug combinations (p-value = 0.0072 and 0.0430, respectively). The COPD assessment test (CAT) score, a questionnaire to assess impact of COPD on health status, was found to be associated with all the questionnaires.Conclusion: The HRQoL is impaired in patients with COPD, and it deteriorates with an increase of severity. The CAT was the strongest predictor of HRQoL.Keywords: chronic obstructive pulmonary disease, long-acting bronchodilators, health-related quality of life, risk factors, Taiwan

Yueh-An Lu, Chao-Yu Chen, George Kuo, Chieh-Li Yen, Ya-Chung Tian, Hsiang-Hao Hsu Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, TaiwanCorrespondence: Hsiang-Hao Hsu, Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, No. 5 Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan, Tel +886-3-328-1200 ext. 8181, Fax +886-3-3282173, Email hsianghao@gmail.comPurpose: The incidence of bloodstream infection among end-stage kidney disease (ESKD) patients on chronic hemodialysis (HD) was 26-fold higher than population controls, causing higher morbidity and costs. The aim of this investigation was to clarify the prognostic factors, in-hospital outcomes and recurrence of infectious spondylitis of patients with and without chronic HD.Patients and Methods: This nationwide study analyzed 2592 patients who admitted for first-time infectious spondylitis between January 1, 2003, and December 31, 2015. Patients were classified into the chronic HD or the non-HD group. The logistic regression model and the general linear model were utilized to determine the impact of chronic HD on in-hospital mortality and recurrence. The Cox proportional hazard model was used to estimate the predictive factors of in-hospital mortality and recurrence.Results: Compared to the non-HD group, patients in the chronic HD group had a higher risk of respiratory failure, sepsis, in-hospital mortality, longer hospital stay, and higher medical spending. Chronic HD was an independent risk factor for in-hospital mortality (hazard ratio 2.21, 95% confidence interval 1.34– 3.65, p=0.0019), but not for recurrence. Intravascular device implantation or revision was a prognosticator for the mortality of both groups and a predictor for recurrence of the non-HD group. Surgical treatment was associated with a decreased risk of recurrence, whereas treatment with CT-guided abscess drainage was associated with an increased risk of recurrence in both groups.Conclusion: Patients with infectious spondylitis who were receiving chronic HD had a higher in-hospital mortality compared to those without HD. Intravascular device implantations or revision within 6 months was a significant predictor of in-hospital mortality and disease recurrence. Surgical treatment of infectious spondylitis had a lower risk of recurrence than those with CT-guided abscess drainage in both patient groups.Keywords: infectious spondylitis, chronic hemodialysis, chronic kidney disease, end-stage kidney disease, outcome, recurrence, risk factor

Sau Xiong Ang,1 Chie-Pein Chen,1 Fang-Ju Sun,2 Chen-Yu Chen1,3 1Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; 3Department of Medicine, Mackay Medical College, New Taipei City, TaiwanCorrespondence: Chen-Yu ChenDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, No. 92, Section 2, Zhong-Shan North Road, Taipei, 10449, TaiwanTel +886-2-2543-3535Fax +886-2-2543-3642Email f122481@mmh.org.twPurpose: Early-onset sepsis is a major cause of neonatal morbidity and mortality. C-reactive protein (CRP) and procalcitonin (PCT) are acute phase reactants related to infection. The aim of this study was to explore the feasibility of measuring CRP and PCT concentrations in cervicovaginal secretions of pregnant women with preterm prelabor rupture of membranes (PPROM) using an immunomagnetic reduction (IMR) assay to predict early-onset neonatal sepsis.Patients and Methods: This prospective study was performed at Mackay Memorial Hospital, Taipei, Taiwan from February 2015 to January 2018. Pregnant women with PPROM between 22 and 34 weeks of gestation were recruited. CRP and PCT concentrations in cervicovaginal secretions were measured using an IMR assay.Results: Thirty-five cervicovaginal secretion samples were obtained. After excluding two neonatal deaths, early-onset neonatal sepsis was diagnosed in 15 of the 33 surviving neonates. There was no significant relationship between cervicovaginal secretion CRP level and neonatal sepsis; however, cervicovaginal secretion PCT levels were significantly higher in the neonatal sepsis group than in the non-sepsis group (45.99 vs 9.54 ng/mL, P = 0.039). Receiver operating characteristic (ROC) curve analysis revealed a PCT cut-off level of 20.60 ng/mL to predict early-onset sepsis, and the area under the ROC curve was 0.71 (95% confidence interval 0.52 to 0.90, P = 0.039), with sensitivity and specificity of 73.3% and 77.8%, respectively.Conclusion: Measuring the concentration of PCT in cervicovaginal secretions with an IMR assay can predict early-onset sepsis in neonates born to mothers with PPROM.Keywords: C-reactive protein, procalcitonin, immunomagnetic reduction, magnetic nanoparticle, preterm prelabor rupture of membranes, early-onset neonatal sepsis

Cheng-Yu Chang,1,&ast; Chung-Yu Chen,2,3,&ast; Shih-Chieh Chang,4– 6,&ast; Yi-Chun Lai,4,5 Yu-Feng Wei7– 9 1Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan; 3College of Medicine, National Taiwan University, Taipei, Taiwan; 4Division of Chest Medicine, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yi-Lan, Taiwan; 5Faculty of Medicine, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 6Department of Critical Care Medicine, National Yang-Ming Chiao Tung University Hospital, Yi-Lan, Taiwan; 7School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 8Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan; 9Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yu-Feng WeiDepartment of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan, No. 21, Yida Road, Jiao-su Village, Yan-chao District, Kaohsiung, 824, TaiwanTel +886-7-6150011Fax +886-7-6150927Email yufeng528@gmail.comIntroduction: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutated non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR-TKIs in older patients including poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) is seldom investigated.Methods: We enrolled patients 65 years or older with EGFR-mutated Stage IIIB–IV NSCLC and evaluated the efficacy and prognosis of first-line EGFR-TKI treatment. Clinical and demographic characteristics were reviewed and analyzed, including age, sex, PS, smoking history, EGFR mutation type, treatment regimen, progression-free survival (PFS), and overall survival (OS).Results: From January 2015 to December 2019, a total of 237 patients were included, 205 of whom were eligible for efficacy and outcome analyses. Among them, 91 (44.4%) were categorized as poor PS (2– 4). Compared with patients categorized as good PS (0– 1), those with poor PS were older (79 versus 75 years), had a higher proportion of brain metastases (41.8% versus 25.4%), more comorbidities (74.7% versus 54.4%), and more likely to be treated with first-generation TKIs (74.7% versus 57.0%). The PFS and OS were 17.1 and 26.7 months respectively in patients with good PS and 12.7 and 18.2 months in those with poor PS (both p < 0.001). In the multivariate analysis, good PS, < 3 metastatic sites, and first-line treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS. A relatively younger age, good PS, < 3 metastatic sites, and no brain metastasis at diagnosis were associated with better OS.Conclusion: In older patients with EGFR-mutated NSCLC and receive EGFR-TKI treatment, a good PS and < 3 metastatic sites at diagnosis were associated with a longer PFS and OS. In addition, afatinib as first-line treatment was associated with a longer PFS whereas a relatively younger age and no brain metastasis at diagnosis were associated with better OS.Keywords: older adults, epidermal growth factor receptor tyrosine kinase inhibitor, non-small-cell lung cancer, performance status

Ching-Huang Lin,1 Hsien-Chang Lin,2 Chien-Yu Chen,3 Chong-Chung Lih4 1Department of Electronic Engineering, National Yunlin University of Science & Technology, Yunlin, 640, Taiwan; 2Graduate School of Engineering Science and Technology, National Yunlin University of Science & Technology, Yunlin, 640, Taiwan; 3Graduate Institute of Color and Illumination Technology, National Taiwan University of Science and Technology, Taipei, 106, Taiwan; 4Department of Optometry, Central Taiwan University of Science and Technology, Taichung, 406, TaiwanCorrespondence: Chong-Chung LihDepartment of Optometry, Central Taiwan University of Science and Technology, Taichung, 406, TaiwanTel +866 4 22391647 6981Email cclih@phys.nthu.edu.twPurpose: This study used low-level laser irradiation on auricular points for the eyes of junior college teenagers with myopia to observe the changes in refractive errors and eye accommodation. According to the Sterner’s study, we used the relationship between the amplitude and subjective symptoms to assess the degree of improvement in visual fatigue caused by changes in accommodation.Methods: Participants were 49 healthy junior college teenagers, with an average age of 16.04± 0.80 years old, and the refractive errors of both eyes were between − 1.50 D and − 5.00 D. All participants underwent refractive error tests before and after class and after a 30-min break. In a 30-min break, all participants underwent two tests of with (experimental group) and without (control group) low-level laser irradiation on the auricular points. Then, refractive error tests were conducted to evaluate the participants’ eye accommodation.Results: The results revealed that with treatment of the auricular points with and without low-level laser irradiation, the refractive error of the participants’ binocular left and right eyes decreased by − 0.12 D (− 0.18 D) in the experimental grou and by − 0.05 D (− 0.02D) in the control group. For the amplitudes of accommodation (AA) examination, the AA of the participants’ binocular in the experimental group became 7.98 ± 1.35 D (7.65 ± 1.37 D). The AA of participants’ binocular can recover to the level before the class.Conclusion: The results indicated that low-level laser irradiation at auricular points restored the eye accommodation faster than did natural closing of the eyes.Keywords: low-level laser irradiation, myopia, teenager, accommodation, auricular point

Gilbert Aaron Lee,1,2 Wan-Li Lin,1 Duen-Pang Kuo,3 Yi-Tien Li,4,5 Yu-Wei Chang,1 Yung-Chieh Chen,4,6 Shiu-Wen Huang,1,7,8 Justin Bo-Kai Hsu,1 Cheng-Yu Chen3,4,6,9 1Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan; 2Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan; 4Translational Imaging Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 5Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan; 6Research Center of Translational Imaging, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanCorrespondence: Cheng-Yu ChenDepartment of Radiology, School of Medicine, College of Medicine, Taipei Medical University, No. 251 Wu Hsing Street, Taipei City 110, Taipei, TaiwanEmail sandy0932@gmail.comPurpose: Targeted superparamagnetic iron oxide (SPIO) nanoparticles are a promising tool for molecular magnetic resonance imaging (MRI) diagnosis. Lipid-coated SPIO nanoparticles have a nonfouling property that can reduce nonspecific binding to off-target cells and prevent agglomeration, making them suitable contrast agents for molecular MRI diagnosis. PD-L1 is a poor prognostic factor for patients with glioblastoma. Most recurrent glioblastomas are temozolomide resistant. Diagnostic probes targeting PD-L1 could facilitate early diagnosis and be used to predict responses to targeted PD-L1 immunotherapy in patients with primary or recurrent glioblastoma. We conjugated lipid-coated SPIO nanoparticles with PD-L1 antibodies to identify PD-L1 expression in glioblastoma or temozolomide-resistant glioblastoma by using MRI.Methods: The synthesized PD-L1 antibody-conjugated SPIO (PDL1-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, transmission electron microscopy images, Prussian blue assay, in vitro cell affinity assay, and animal MRI analysis.Results: PDL1-SPIO exhibited a specific binding capacity to PD-L1 of the mouse glioblastoma cell line (GL261). The presence and quantity of PDL1-SPIO in temozolomide-resistant glioblastoma cells and tumor tissue were confirmed through Prussian blue staining and in vivo T2&ast; map MRI, respectively.Conclusion: This is the first study to demonstrate that PDL1-SPIO can specifically target temozolomide-resistant glioblastoma with PD-L1 expression in the brain and can be quantified through MRI analysis, thus making it suitable for the diagnosis of PD-L1 expression in temozolomide-resistant glioblastoma in vivo.Keywords: PD-L1, superparamagnetic iron oxide, SPIO, magnetic resonance imaging, MRI, lipid-coated nanoparticle, glioblastoma

Wei-Chun Huang,1,2 Chih-Yu Chen,1 Wei-Chih Liao,1,2 Biing-Ru Wu,1,3,4 Wei-Chun Chen,1,3,4 Chih-Yen Tu,1,2 Chia-Hung Chen,1,2 Wen-Chien Cheng1– 4 1Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 3Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 4Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanCorrespondence: Wen-Chien Cheng; Chia-Hung ChenDivision of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, 40402, TaiwanEmail wcchengdr@gmail.com; hsnu758@gmail.comObjective: This real world study evaluated the effectiveness of switching to closed triple therapy from mono/dual combination or open triple therapy in patients with chronic obstructive pulmonary disease (COPD).Methods: We conducted this retrospective study at a single medical center from December 2014 to September 2020. Patients with COPD who were stepped up to triple therapy were enrolled. We analyzed the duration from initial COPD management to open or closed triple therapy and identified the clinical predictors of the patients who needed triple therapy early. We also evaluated the effectiveness of triple therapy after switching from initial management, and closed triple therapy after switching from open triple therapy.Results: A total 115 COPD patients who were stepped up to triple therapy from initial treatment were analyzed. The duration from initial treatment to triple therapy was 22.4 months. The baseline peripheral blood eosinophil counts of the patients who switched to triple therapy early (n=63, less than 22 months) and those who switched to triple therapy later (n=52, more than 22 months) were similar (489.6 vs 434.5 cells/uL; p=0.589). After univariate and multivariate analysis, the patients who were older had more acute exacerbations (AEs) in the previous year, asthma and COPD overlap (ACO), and initial dual bronchodilator therapy were stepped up to triple therapy early. The FEV1 of the patients was significantly increased after switching to open triple therapy from mono bronchodilator therapy. In addition, switching from initial or open triple therapy to closed triple therapy significantly reduced the incidence of AEs.Conclusion: COPD patients with high blood eosinophilia, older age, more AEs in the previous year, ACO, and initial dual bronchodilator therapy were stepped up to triple therapy early. Triple therapy showed improvements in lung function of most patients switching from mono bronchodilator therapy. After switching to closed triple therapy further reduced the incidence of AEs.Keywords: COPD, chronic obstructive pulmonary disease, closed triple therapy, open triple therapy, ACO, asthma COPD overlap

Chun-Yan Li,1 Chun-Ya Chen,1 Jian-Hong An,1 Jian-Bin Wu,2 Hong Shen1,3 1South China University of Technology School of Medicine, Guangzhou Higher Education Mega Center, Guangzhou, 510006, Guangdong, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510407, People’s Republic of China; 3Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaCorrespondence: Hong Shen Tel +86 20-61648227Email shenhong2010168@163.comAim: Basal epithelial cells are absent in distant prostate cancer. This study aimed to investigate whether basal epithelial cells could suppress migration and invasion of prostate cancer cells to become a new treatment strategy for prostate cancer.Main Methods: Basal epithelial cells were identified by immunofluorescence with anti-p63. Wound healing assays or transwell assays were used to explore the effects of basal epithelial cells, TGF-β 1, SB431542 (inhibitor of TGF-β type I receptor) or stattic (inhibitor of phosphorylated STAT3) on migration or invasion of mouse prostate cancer cell (RM-1). Concentration of TGF-β 1 was measured by ELISA assay. HE staining was used to investigate cell morphology. Immunocytochemistry with anti-p63 was used to identify basal epithelial cells. Levels of STAT3, p-STAT3 (Ser727) and proteins associated with EMT were measured with Western blot assay. Cell proliferation was measured with MTT or CCK8 assay.Results: Normal basal epithelial cells acquired from mouse prostate were specific to anti-p63 and more than 90%. Basal epithelial cells and RM-1 could both secrete TGF-β 1. Basal epithelial cells and TGF-β 1 promoted the migration and invasion of RM-1 through changing the cell morphology and up-regulating expression of ZEB1, N-cadherin, vimentin, snail and p-STAT3 (Ser727), at the same time down-regulating E-cadherin of RM-1. SB431542 strongly suppressed migration, invasion as well as the expressions of EMT relevant proteins and p-STAT3 (Ser727) of co-cultured RM-1. In addition, stattic suppressed proliferation, migration and invasion of non-treated RM-1 and co-cultured RM-1.Conclusion: Our study suggests that normal basal epithelial cells might stimulate the migration and invasion of RM-1 by TGF-β 1/STAT3 axis which could be suppressed by inhibitor of TGF-β receptor and inhibitor of p-STAT3. So, basal epithelial cells might not become a treatment strategy for prostate cancer, but our results could provide some researching references for other diseases which include basal epithelial cells such as prostatic intraepithelial neoplasia, prostatic hyperplasia, cervical cancer, or urinary bladder cancer.Keywords: normal basal epithelial cells, RM-1, migration, invasion, TGF-β 1, STAT3

Zhong-Wei Luo,1,2 Kun Xia,1,2 Yi-Wei Liu,1,2 Jiang-Hua Liu,1,2 Shan-Shan Rao,2,3 Xiong-Ke Hu,1,2 Chun-Yuan Chen,1,2 Ran Xu,4 Zhen-Xing Wang,1,2 Hui Xie1,2,5– 8 1Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Xiangya Nursing School, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 6Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan, People’s Republic of China; 7Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, Hunan, People’s Republic of China; 8National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Hui XieDepartment of Orthopedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of ChinaEmail huixie@csu.edu.cnRan XuDepartment of Urology, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of ChinaEmail xuran@csu.edu.cnPurpose: Prostate cancer (PCa) is one of the most common malignancies in males. Despite the success of immunotherapy in many malignant cancers, strategies are still needed to improve therapeutic efficacy in PCa. This study aimed to investigate the effects of Akkermansia muciniphila-derived extracellular vesicles (Akk-EVs) on PCa and elucidate the underlying immune-related mechanism.Methods: Akk-EVs were isolated by ultracentrifugation and intravenously injected to treat syngeneic PCa-bearing immune-competent mice. Immunophenotypic changes in immune cells, such as cytotoxic T lymphocytes and macrophages, were measured via flow cytometry analysis. Histological examination was used to detect morphological changes in major organs after Akk-EVs treatments. In vitro, flow cytometry was performed to confirm the effects of Akk-EVs on the activation of CD8+ T cells. Quantitative PCR and immunofluorescence staining were carried out to test the impact of Akk-EVs on macrophage polarization. Cell counting kit-8 (CCK-8) analysis, colony formation assays, and scratch wound healing assays were conducted to assess the effects of Akk-EVs-treated macrophages on the proliferation and invasion of PCa cells. CCK-8 assays also confirmed the impact of Akk-EVs on the viability of normal cells.Results: Intravenous injection of Akk-EVs in immune-competent mice reduced the tumor burden of PCa without inducing obvious toxicity in normal tissues. This treatment elevated the proportion of granzyme B-positive (GZMB+) and interferon γ-positive (IFN-γ+) lymphocytes in CD8+ T cells and caused macrophage recruitment, with increased tumor-killing M1 macrophages and decreased immunosuppressive M2 macrophages. In vitro, Akk-EVs increased the number of GZMB+CD8+ and IFN-γ+CD8+ T cells and M1-like macrophages. In addition, conditioned medium from Akk-EVs-treated macrophages suppressed the proliferation and invasion of prostate cells. Furthermore, the effective dose of Akk-EVs was well-tolerated in normal cells.Conclusion: Our study revealed the promising prospects of Akk-EVs as an efficient and biocompatible immunotherapeutic agent for PCa treatment.Keywords: Akkermansia muciniphila, extracellular vesicles, immunotherapy, prostate cancer, cytotoxic T lymphocytes, macrophages

Nan-Fu Chiu,1,2 Ming-Jung Tai,1 Devi Taufiq Nurrohman,1,3 Ting-Li Lin,1 Ying-Hao Wang,1 Chen-Yu Chen4,5 1Laboratory of Nano-Photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, Taipei City, Taiwan; 2Department of Life Science, National Taiwan Normal University, Taipei City, Taiwan; 3Department of Electronics Engineering, State Polytechnic of Cilacap, Cilacap, Indonesia; 4Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei City, Taiwan; 5Department of Medicine, Mackay Medical College, Taipei City, TaiwanCorrespondence: Nan-Fu ChiuLaboratory of Nano-Photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, No. 88, Sec. 4, Ting-Chou Road, Taipei City, 11677, TaiwanTel +886-2-77496722Fax +886-2-86631954Email nfchiu@ntnu.edu.twChen-Yu ChenDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei City, 10449, TaiwanTel +886-2-25433535Fax +886-2-25433642Email f122481@mmh.org.twBackground: Due to educational, social and economic reasons, more and more women are delaying childbirth. However, advanced maternal age is associated with several adverse pregnancy outcomes, and in particular a high risk of Down’s syndrome (DS). Hence, it is increasingly important to be able to detect fetal Down’s syndrome (FDS).Methods: We developed an effective, highly sensitive, surface plasmon resonance (SPR) biosensor with biochemically amplified responses using carboxyl-molybdenum disulfide (MoS2) film. The use of carboxylic acid as a surface modifier of MoS2 promoted dispersion and formed specific three-dimensional coordination sites. The carboxylic acid immobilized unmodified antibodies in a way that enhanced the bioaffinity of MoS2 and preserved biorecognition properties of the SPR sensor surface. Complete antigen pregnancy-associated plasma protein-A2 (PAPP-A2) conjugated with the carboxyl-MoS2-modified gold chip to amplify the signal and improve detection sensitivity. This heterostructure interface had a high work function, and thus improved the efficiency of the electric field energy of the surface plasmon. These results provide evidence that the interface electric field improved performance of the SPR biosensor.Results: The carboxyl-MoS2-based SPR biosensor was used successfully to evaluate PAPP-A2 level for fetal Down’s syndrome screening in maternal serum samples. The detection limit was 0.05 pg/mL, and the linear working range was 0.1 to 1100 pg/mL. The women with an SPR angle > 46.57 m° were more closely associated with fetal Down’s syndrome. Once optimized for serum Down’s syndrome screening, an average recovery of 95.2% and relative standard deviation of 8.5% were obtained. Our findings suggest that carboxyl-MoS2-based SPR technology may have advantages over conventional ELISA in certain situations.Conclusion: Carboxyl-MoS2-based SPR biosensors can be used as a new diagnostic technology to respond to the increasing need for fetal Down’s syndrome screening in maternal serum samples. Our results demonstrated that the carboxyl-MoS2-based SPR biosensor was capable of determining PAPP-A2 levels with acceptable accuracy and recovery. We hope that this technology will be investigated in diverse clinical trials and in real case applications for screening and early diagnosis in the future.Keywords: carboxyl-functionalized molybdenum disulfide, carboxyl-MoS2, surface plasmon resonance, SPR, pregnancy-associated plasma protein A2, PAPP-A2, Down’s syndrome, DS, fetal Down’s syndrome, FDS

Kuang-Ming Liao,1 Kai-Lin Chiu,2,3 Chung-Yu Chen2– 5 1Department of Internal Medicine, Chi Mei Medical Center, Chiali, Taiwan, Republic of China; 2Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 3Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China; 4Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China; 5Center for Big Data Research, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Chung-Yu ChenKaohsiung Medical University, No. 100, Shiquan 1st Road, Sanmin District, Kaohsiung, 807, Taiwan, Republic of ChinaEmail jk2975525@kmu.edu.twObjective: Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of osteoporosis. Few studies have addressed the prescription patterns in osteoporosis patients with COPD. The purpose of this study was to conduct a retrospective study of the prescription patterns in patients with COPD and osteoporosis in Taiwan.Methods: The study was conducted with data from the Taiwan National Health Insurance Research Database from January 1, 2003, to December 31, 2016. We selected the COPD population in Taiwan older than 40 years with at least one prescription for a bronchodilator. We excluded patients who had osteoporosis, fracture, asthma, or cancer before the diagnosis of COPD. After the diagnosis of COPD, patients who did not have osteoporosis were also excluded. We followed this COPD and osteoporosis cohort until they had been prescribed medication for osteoporosis.Results: There were 13,407 patients with COPD and osteoporosis who received osteoporosis treatment. Among the patients who received treatment, the majority were female (n = 9136), accounting for 68.14% of all treated patients. A total of 53.4% of the patients had been prescribed steroids least once within the last year before receiving a diagnosis of osteoporosis. A total of 34.61% of the patients received systemic corticosteroids with a daily dose equivalent to 5 mg of prednisolone within the 3 months prior to the diagnosis of osteoporosis. The older the patient was, the higher the probability of the prescription of medication for osteoporosis. Patients with depression had a high probability of receiving medication for osteoporosis with adjusted hazard ratio of 1.141 (95% confidence interval, 1.072– 1.214).Conclusion: The rate of prescriptions for the treatment of osteoporosis in patients with COPD was low. Physicians need to be aware of this issue and treat osteoporosis more aggressively in patients with COPD.Keywords: chronic obstructive pulmonary disease, National Health Insurance Research Database, osteoporosis, prescription pattern

Chung-Yao Chen,1,2 Chia-Ling Chen3,4 1Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan; 2School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taiwan; 4Graduate Institute of Early Intervention, College of Medicine, Chang Gung University, Taoyuan, TaiwanCorrespondence: Chung-Yao ChenDepartment of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, No. 200, Ln. 208, Jijin 1st Road, Anle Dist., Keelung City, 204, TaiwanTel +886-2-2432-9355 Ext 2545Fax +886-2-24315931Email jongyau2002@gmail.comBackground and Purpose: Obstructive sleep apnea (OSA) increases risk of stroke recurrence and mortality in ischemic stroke patients. However, equivocal treatment effects warrant further categorization of post-stroke OSA for risk stratification and individualized treatment planning.Methods: The study recruited 232 ischemic stroke patients with moderate-to-severe OSA admitted for inpatient rehabilitation consecutively. Latent class analysis was performed based on sex, age, smoking, daytime sleepiness, depression, obesity, sedative use, atrial fibrillation, diabetes, dyslipidemia, hypertension, recurrent stroke and dysphagia. The augmentation index, a marker of arterial stiffness, was measured by applanation tonometry.Results: A three-cluster model provided the best fit. Cluster 1 (n=84, 36.2%) was older in age, predominantly female, with the highest hypopnea index and prevalence of atrial fibrillation. Moreover, patients in Cluster 1 had significantly higher augmentation index than those in Cluster 2. Cluster 2 patients (N=80, 34.5%) were of older age, predominantly male, with the highest prevalence of depression, the lowest prevalence of hypertension and had the most normal body mass index (BMI). Additionally, Cluster 2 had less nocturnal hypoxia as compared to Cluster 3. Cluster 3 (n=68, 29.3%) was the youngest in age, predominantly male, with the highest BMI, cumulative risk score, and prevalence of dyslipidemia of the three clusters.Conclusion: Post-stroke OSA can be categorized into three clinical phenotypes. Patients in Clusters 1 and 3 both had elevated cardiovascular risk and treatment can be based on their distinct characteristics. Patients in Cluster 2 had relatively lower risk of cardiovascular events and the benefits of OSA treatment requires further study.Keywords: obstructive sleep apnea, ischemic stroke, cluster analysis, latent class analysis

Shuh-Kuan Liau,1 George Kuo,1 Chao-Yu Chen,1 Yu-Cheng Chen,2 Yueh-An Lu,1 Yu-Jr Lin,3 Cheng-Chieh Hung,1 Ya-Chung Tian,1 Hsiang-Hao Hsu1 1Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; 3Research Services Center for Health Information from Chang Gung University, Taoyuan, TaiwanCorrespondence: Hsiang-Hao HsuDepartment of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, No. 5 Fu-Shin Street, Kweishan, Taoyuan, 333, TaiwanTel +886-3-328-1200 ext. 8181Fax +886-3-3282173Email hsianghao@gmail.comPurpose: To elucidate the in-hospital and long-term outcomes of infective endocarditis (IE) in end-stage kidney disease (ESKD) patients on chronic dialysis and to analyze the risk factors of mortality.Patients and Methods: The case files of 1,817 patients who were hospitalized for IE over a 14-year period were retrospectively reviewed. Of these, 116 ESKD patients on chronic dialysis were enrolled in this study. Cox’s proportional hazard model was used to evaluate the risk factors of mortality and long-term outcomes.Results: The in-hospital mortality rate of the 116 enrolled patients was as high as 43.1%. Patients who survived the index admission had a three-year mortality rate of 33%. Univariate analysis was used to compare survivors and non-survivors; poor in-hospital outcomes were associated with the use of a tunneled cuffed catheter for dialysis access, a shorter duration hospitalization, shock or respiratory failure during hospitalization, a higher white blood count, a higher percentage of polymorphonuclear leukocytes, a higher C-reactive protein level, a lower serum albumin level, and a higher total bilirubin level. Following multivariate adjustment, shock (odds ratio, 9.29, with a 95% confidence interval [CI] of 2.78 to 34.24; p< 0.001) or respiratory failure (odds ratio, 25.16, with a 95% CI of 5.63 to 153.54; p< 0.001) during hospitalization was strongly associated with increased in-hospital mortality. Patients who underwent cardiac operations (odds ratio, 0.22, with a 95% CI of 0.052 to 0.86; p=0.031) had better in-hospital outcomes. Heart failure reduced ejection fraction (HFrEF) at the time of initial hospitalization was an independent risk factor for 3-year mortality (hazard ratio, 3.48, with a 95% CI of 1.09 to 11.09; p=0.035).Conclusion: The outcomes of IE for ESKD patients on chronic dialysis were poor. Only 56.9% of these patients survived the index admission and their mortality rate over three years was 33%. Shock or respiratory failure during hospitalization was associated with increased in-hospital mortality. Patients who underwent cardiac operations had better in-hospital outcomes. HFrEF at the time of initial hospitalization was an independent risk factor for three-year mortality.Keywords: infective endocarditis, chronic dialysis, end-stage kidney disease, blood-stream infection, infectious disease, sepsis

Hsi-Chung Chen,1,2 Chia-Yi Wu,3– 5 Ming-Been Lee,1,5– 7 Shih-Cheng Liao,1,5,6 Chia-Ta Chan,5,7 Chun-Ying Chen5 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 3School of Nursing, National Taiwan University College of Medicine, Taipei, Taiwan; 4Department of Nursing, National Taiwan University Hospital, Taipei, Taiwan; 5Taiwan Suicide Prevention Center, Taipei, Taiwan; 6Department of Psychiatry, National Taiwan University College of Medicine, Taipei, Taiwan; 7Department of Psychiatry, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanCorrespondence: Chia-Yi WuSchool of Nursing, National Taiwan University College of Medicine, No.1, Sec. 1, Jen-A1 Road, Taipei 100, TaiwanTel +886-2-23123456 ext. 88430Email jennycyw@ntu.edu.tw Ming-Been LeeDepartment of Psychiatry, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei 100, TaiwanTel +886-2-23123456 Ext. 66784Email mingbeen@ntu.edu.twBackground: Insomnia is closely related to psychological distress. This study aims to examine the role of age and sex in the association between various psychological distresses and insomnia symptoms.Participants and Methods: This population-based study used data provided by cumulative respondents of the annual survey of the Taiwan Suicide Prevention Center between 2006 and 2019. Potential respondents were aged ≥ 15 years and were selected by a stratified proportional randomization method according to the distribution of population size, sex, and age in different geographic areas of Taiwan. The Five-Item Brief Symptom Rating Scale was used to measure insomnia symptoms and four psychological distresses: depression, anxiety, hostility, and inferiority. The independent relationship between insomnia symptoms with depression, anxiety, hostility, and inferiority was further examined according to age and sex.Results: A total of 28,649 participants were included (women, 50.2%). The four types of psychological distress correlated differentially with insomnia symptoms. Concerning interaction effects, sex moderated the interaction effects between age with depression, anxiety, and hostility. In men, and not in women, age moderated the relationship between insomnia symptoms and all four psychological distresses. Specifically, the effect sizes of the associations between insomnia symptoms and depression, anxiety, and hostility showed an age-dependent decreasing trend in men.Conclusion: The associations between psychological distresses and insomnia symptoms varied in strength and according to age in a sex-specific manner.Keywords: insomnia symptoms, moderation effect, psychological distress, sex-specific

Feng-Hsiang Chiu,1,2 Chih-Yu Chen,1,2 Jih-Chin Lee,1,2 Ying-Shuo Hsu3,4 1Department of Otolaryngology, Head and Neck Surgery, Tri-Service General Hospital, Taipei, Taiwan; 2National Defense Medical Center, Taipei City, Taiwan; 3Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 4School of Medicine, Fu Jen Catholic University, New Taipei City, TaiwanCorrespondence: Jih-Chin LeeDepartment of Otolaryngology, Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, TaiwanTel +886-2-87927192Fax +886-2-87927193Email doc30450@mail.ndmctsgh.edu.twYing-Shuo HsuDepartment of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, TaiwanTel +886-2-28332211 ext.2551Email sulisky@gmail.comObjective: Uvulopalatopharyngoplasty (UPPP) is a common procedure for the treatment of obstructive sleep apnea (OSA) and is usually initiated with the resection of palatine tonsils. Because tonsillectomy potentially contributes to complications, minimally invasive upper airway surgeries have been proposed for OSA therapy. Whether tonsillectomy is always essential for UPPP remains unclear, particularly for patients with small tonsils. The purpose of this study was to present the effect of modified UPPP without tonsillectomy (UPsT) on patients with OSA and attempt to select the candidates for this procedure.Methods: This is a retrospective cohort study of patients with OSA, with tonsil size of grade 0– 2, and with only retropalatal obstruction in drug-induced sleep endoscopy (DISE). The patients underwent UPsT at a tertiary center from November 2017 to December 2019. The sleep study was performed before and at least 3 months after surgery. The demographics, surgical outcomes, and staging patterns of preoperative DISE were recorded. The correlation between surgical outcome and DISE was also established.Results: A total of 22 adults with an average age of 46.5 years [interquartile range: 40 to 60 years] completed the follow-up study. Their apnea–hypopnea index (AHI) and Epworth sleepiness scale values improved significantly after surgery. Of the 17 patients with partial collapse and complete anteroposterior collapse (APC) at the velum, 16 presented good responses to UPsT. However, among the five patients with complete concentric collapse (CCC), only two (2/5, 40%) satisfied the criteria for surgical success. Furthermore, their follow-up AHI values were significantly higher than those of patients without CCC in DISE.Conclusion: UPsT was demonstrated to be an effective therapy for patients with OSA who had small tonsils and retropalatal obstruction in DISE. CCC in sleep endoscopy indicates a poorer surgical outcome than does complete APC and partial collapse at the velum.Keywords: tonsillectomy, uvulopalatopharyngoplasty, suspension palatoplasty, lateral pharyngoplasty, obstructive sleep apnea, drug-induced sleep endoscopy, complete concentric collapse

Wen-Chien Cheng,1– 6 Biing-Ru Wu,1,3,5,6 Wei-Chih Liao,1,2,4,7 Chih-Yu Chen,1 Wei-Chun Chen,1,3– 6 Te-Chun Hsia,1,4,8 Chih-Yen Tu,1– 3 Chia-Hung Chen,1,2,7 Wu-Huei Hsu1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, China Medical University, Taichung, Taiwan; 3Department of Life Science, National Chung Hsing University, Taichung, Taiwan; 4Department of Internal Medicine, Hyperbaric Oxygen Therapy Center, China Medical University Hospital, Taichung, Taiwan; 5Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 6Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 7Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 8Department of Respiratory Therapy, China Medical University, Taichung, TaiwanCorrespondence: Chia-Hung Chen; Chih-Yu ChenDepartment of Internal Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung, TaiwanEmail hsnu758@gmail.com; cychen0808@gmail.comPurpose: Triple therapy versus dual therapy for chronic pulmonary obstructive disease (COPD) can reduce symptoms, limit the risk of acute exacerbations (AEs) as well as improve lung function. Currently, studies that feature clinically important deterioration (CID) as a composite endpoint to assess the need for treatment intensification for patients maintained on dual therapy remained to be scarce.Patients and Methods: This study is a retrospective analysis (January 2014 to January 2018) of COPD patients that presented with moderate to severe AEs during the previous year with blood eosinophil counts ≥ 100 cells/μL. The first line of therapy included a combination of inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Composite CID was used in assessing the response to treatment after 24 weeks of therapy.Results: This study included 110 patients, of which 49 patients reportedly experienced CID. The most common events of CID include a decline in forced expiratory volume in 1 second (FEV1) ≥  100 mL from baseline (25/49, 51%) and an increase in COPD Assessment Test (CAT) scores ≥ 2 (13/49, 26.5%); many of these patients respond to the addition of a long-acting muscarinic antagonist (LAMA). Seven patients (7/110, 6.3%) experienced moderate to severe exacerbations while undergoing treatment with ICS/LABA. Univariate and multivariate analyses have identified low baseline FEV1 (OR = 0.81, p = 0.004), high CAT score (OR = 1.89, p = 0.004), and the frequency of AE (OR = 19.86, p = 0.021) as independent predictors of CID. A baseline FEV1 of ≤ 42%, an initial CAT score ≥ 18, and AE ≥ 2 last year were considered the optimal cut-off values, which were identified via receiver operating characteristics (ROC) curve analysis.Conclusion: Triple therapy (ICS/LABAs/LAMAs) may be considered as first-line treatment in patients experiencing more than 2 times moderate to severe AEs of COPD in the previous year and who have blood eosinophil counts ≥ 100 cells/μL, reduced lung function (FEV1 ≤ 42%), and more symptoms (CAT score ≥ 18).Keywords: inhaled corticosteroid, ICS, long-acting muscarinic antagonist, LAMA, long-acting β2 agonist, LABA, triple therapy, chronic pulmonary obstructive disease, COPD, clinically important deterioration, CID

Chung-Yao Chen,1,2 Wen-Chun Tseng,1 Yao-Hung Yang,1 Chia-Ling Chen,3,4 Lain-Li Lin,5 Fang-Ping Chen,2,6,7 Alice MK Wong2,3,8 1Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung 204, Taiwan; 2Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; 3Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou 333, Taiwan; 4Graduate Institute of Early Intervention, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; 5Department of Tourism Leisure and Health, Ching Kuo Institute of Management and Health, Keelung 204, Taiwan; 6Keelung Osteoporosis Prevention and Treatment Center, Chang Gung Memorial Hospital, Keelung 204, Taiwan; 7Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Keelung 204, Taiwan; 8Healthy Aging Research Center, Chang Gung University, Taoyuan 333, TaiwanCorrespondence: Chung-Yao ChenDepartment of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, No. 200, Ln. 208, Jijin 1st Road, Anle District, Keelung City 204, TaiwanTel +886-2-2432-9292 #2725Email jongyau2002@gmail.comIntroduction: Sarcopenia is highly prevalent among residents of assisted-living facilities. However, the optimal screening tools are not clear. Therefore, we compared the performance of four recommended screening tools for predicting sarcopenia.Methods: The study recruited 177 people over 65 years of age in assisted-living facilities. Appendicular muscle mass index was measured using bioelectrical impedance analysis. Calf circumference (CC), handgrip, six-meters walking speed, and screening questionnaires including SARC-CalF, SARC-F and 5-item Mini Sarcopenia Risk Assessment (MSRA-5) were evaluated. The diagnosis criteria for sarcopenia were based on the Asian Working Group for Sarcopenia 2019 consensus. The area under the receiver operating characteristic curves (AUC) was used to contrast the diagnostic accuracy of screening tools.Results: The prevalence of sarcopenia was 52.7% among men and 51.2% among women. After adjusting for age, sex, body mass index and SARC-CalF score, CC remained significantly associated with sarcopenia in logistic regression analysis. The prediction model for sarcopenia based on CC alone had the highest accuracy compared to SARC-CalF, MSRA-5 and SARC-F (AUC, 0.819 vs 0.734 vs 0.600 vs 0.576; sensitivity/specificity, 80.4%/71.8% vs 38.0%/80.0% vs 60.7%/54.2% vs 10.9%/91.8%). Differences in AUCs between the prediction models were statistically significant (CC vs. SARC-CalF, P = 0.0181; SARC-CalF vs. MSRA-5, P = 0.0042). Optimal cutoff values for predicting sarcopenia were CC < 34 cm in men and < 33 cm in women.Conclusion: To predict sarcopenia based on low CC alone is accurate, easy and inexpensive for use in assisted-living facility settings. Further validation studies in different populations are suggested.Keywords: sarcopenia, calf circumference, SARC-F, SARC-CalF, MSRA, assisted-living

Nan-Fu Chiu,1,2 Ying-Hao Wang,1,3 Chen-Yu Chen3,4 1Laboratory of Nano-Photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, Taipei City 11677, Taiwan; 2Department of Life Science, National Taiwan Normal University, Taipei City 11677, Taiwan; 3Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei City 10449, Taiwan; 4Department of Medicine, Mackay Medical College, Taipei City 25245, TaiwanCorrespondence: Nan-Fu ChiuLaboratory of Nano-photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, No. 88, Sec. 4, Ting-Chou Road, Taipei 11677, TaiwanTel +886-2-77496722Fax +886-2-86631954Email nfchiu@ntnu.edu.twChen-Yu ChenDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei City 10449, TaiwanTel +886-2-25433535Fax +886-2-25433642Email f122481@mmh.org.twBackground: Advanced medical detection technology requires high sensitivity and accuracy to increase the disease detection rate. We showed that carboxyl-functionalized graphene oxide (carboxyl-GO) biosensing materials are capable of accurate detection.Methods: We developed a carboxylated GO-based surface plasmon resonance (SPR) aptasensor suitable for screening Down’s syndrome in clinical serum. This biosensing material could rapidly and accurately detect hCG protein with a low concentration to identify fetal Down’s syndrome. The developed carboxyl-GO-based SPR aptasensor showed excellent sensitivity and limit of detection without the use of antibodies and without any specific preference.Results: hCG protein detection limits of 1 pM in buffer samples and 1.9 pM in clinical serum samples were achieved. The results showed that the carboxyl-GO-based chip could detect hCG well below the normal physiological level of serum protein (5.0 mIU/mL). High affinity, sensitivity, and better detection limit were obtained in the range of 1.9 pM to 135 pM. The results showed a 5k-fold dilution factor, and that an SPR angle shift of more than 20 millidegrees (mo) was associated with a significant risk of fetal Down’s syndrome compared to normal pregnant women. The results clearly showed that the detection of hCG protein in serum samples from pregnant women at 12– 19 weeks could be used to screen Down’s syndrome with high selectivity and sensitivity.Conclusion: Our findings suggest the potential application of carboxyl-GO film in proof-of-concept studies for serum assays as a new type of SPR material. In addition, peptide and carboxyl-GO films may be conducive to the development of future point of care testing and rapid diagnostic devices for other diseases such as cancer.Keywords: surface plasmon resonance, SPR, aptasensor, carboxyl-functionalized graphene oxide, GO-COOH, peptides, human chorionic gonadotropin, hCG, Down’s syndrome, DS

Shi-Yuan Fan,1 Nan-Fu Chiu,2 Chie-Pein Chen,1,3 Chia-Chen Chang,4 Chen-Yu Chen1,3 1Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; 2Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan; 3Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; 4Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan City, TaiwanCorrespondence: Chen-Yu ChenDepartment of Medicine, Mackay Medical College, No. 46, Section 3, Zhongzheng Road, Sanzhi District, New Taipei City 252, TaiwanTel +886 2 2636 0303Email f122481@mmh.org.twBackground: Pregnancy-associated plasma protein-A and -A2 (PAPP-A and -A2) are principally expressed in placental trophoblasts and play a critical role in the regulation of fetal and placental growth. PAPP-A2 shares 45% amino acid similarity with PAPP-A. This study aimed to investigate the efficacy of real-time detection of PAPP-A and PAPP-A2 using a novel surface plasmon resonance (SPR) biosensor based on graphene oxide (GO).Methods: Traditional SPR and GO-based SPR chips were fabricated to measure PAPP-A and PAPP-A2 concentrations. We compared SPR response curves of PAPP-A and PAPP-A2 between traditional SPR and GO-SPR biosensors. We also performed interference tests and specificity analyses among PAPP-A, PAPP-A2, and mixed interference proteins.Results: The time to detect PAPP-A and PAPP-A2 was about 150 seconds with both traditional SPR and GO-SPR biosensors. Approximately double SPR angle shifts were noted with the GO-SPR biosensor compared to the traditional SPR biosensor at a PAPP-A and PAPP-A2 concentration of 5 μg/mL. The limit of detection of the GO-SPR biosensor was as low as 0.5 ng/mL for both PAPP-A and PAPP-A2. Interference testing revealed that almost all of the protein bonded on the GO-SPR biosensor with anti-PAPP-A from the mixture of proteins was PAPP-A, and that almost no other proteins were captured except for PAPP-A2. However, the SPR signal of PAPP-A2 (5.75 mdeg) was much smaller than that of PAPP-A (13.76 mdeg). Similar results were noted with anti-PAPP-A2, where almost all of the protein bonded on the GO-SPR biosensor was PAPP-A2. The SPR signal of PAPP-A (5.17 mdeg) was much smaller than that of PAPP-A2 (13.94 mdeg).Conclusion: The GO-SPR biosensor could distinguish PAPP-A and PAPP-A2 from various mixed interference proteins with high sensitivity and specificity. It could potentially be used to measure PAPP-A and PAPP-A2 in clinical blood samples during pregnancy.Keywords: pregnancy-associated plasma protein-A, pregnancy-associated plasma protein-A2, graphene oxide, surface plasmon resonance, biosensor

Yi-Jun Lin,1 Hsing-Chieh Lin,2 Ying-Fei Yang,2 Chi-Yun Chen,2 Min-Pei Ling,3 Szu-Chieh Chen,4,5 Wei-Yu Chen,6,7 Shu-Han You,8 Tien-Hsuan Lu,2 Chung-Min Liao2 1Institute of Food Safety and Health Risk Assessment, National Yang-Ming University, Taipei, Taiwan; 2Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan; 3Department of Food Science, National Taiwan Ocean University, Keelung City, Taiwan; 4Department of Public Health, Chung Shan Medical University, Taichung, Taiwan; 5Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 6Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung City, TaiwanCorrespondence: Chung-Min LiaoDepartment of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan, ROCTel +886 2 3366 3475Email cmliao@ntu.edu.twBackground: Broad-scale evidence has shown the significant association between ambient air pollutants and the development of tuberculosis (TB). However, the impact of air quality on the risk of TB in Taiwan is still poorly understood.Objective: To develop a probabilistic integrated population-level risk assessment approach for evaluating the contribution of ambient air pollution exposure to the risk of TB development among different regions of Taiwan.Materials and methods: A Bayesian-based probabilistic risk assessment model was implemented to link exposure concentrations of various air pollutants quantified in a probabilistic manner with the population-based exposure-response models developed by using an epidemiological investigation.Results: The increment of the risk of TB occurred in a region with a higher level of air pollution, indicating a strong relationship between ambient air pollution exposures and TB incidences. Carbon monoxide (CO) exposure showed the highest population attributable fraction (PAF), followed by nitrogen oxides (NOX) and nitrogen dioxide (NO2) exposures. In a region with higher ambient air pollution, it is most likely (80% risk probability) that the contributions of CO exposure to development of TB were 1.6–12.2% (range of median PAFs), whereas NOX and NO2 exposures contributed 1.2–9.8% to developing TB.Conclusion: Our findings provide strong empirical support for the hypothesis and observations from the literature that poor air quality is highly likely to link aetiologically to the risk of TB. Therefore, substantial reductions in CO, NOX, and NO2 exposures are predicted to have health benefits to susceptible and latently infected individuals that provide complementary mitigation efforts in reducing the burden of TB. Considering that people continue to be exposed to both TB bacilli and ambient air pollutants, our approach can be applied for different countries/regions to identify which air pollutants contribute to a higher risk of TB in order to develop potential mitigation programs.Keywords: tuberculosis, ambient air pollution, exposure-response function, probabilistic risk assessment, population attributable fraction

Nan-Fu Chiu,1 Ming-Jung Tai,1 Hwai-Ping Wu,1 Ting-Li Lin,1 Chen-Yu Chen2,31Laboratory of Nano-photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, Taipei 11677, Taiwan; 2Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei City 10449, Taiwan; 3Department of Medicine, Mackay Medical College, Taipei 25245, TaiwanCorrespondence: Nan-Fu ChiuLaboratory of Nano-photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, No. 88, Sec. 4, Ting-Chou Road, Taipei 11677, TaiwanTel +886 27 734 6722Fax +886 28 663 1954Email nfchiu@ntnu.edu.twBackground: Graphene-like material such as functionalized carboxyl-graphene oxide (carboxyl-GO) can be intelligently tuned to achieve particular properties for biological and chemical sensing applications.Methods: In this study, we propose a method to improve interference of non-specific proteins for use in human plasma assays. The highly specific interactions between molecules are an advantage of carboxyl-GO-based surface plasmon resonance (SPR) immunoassays, and this can be applied to spiked plasma samples with pregnancy-associated plasma protein A2 (PAPPA2).Results: The experiment results showed that carboxyl-GO could be used to modulate the plasmon resonance energy, work function and conductivity properties. In addition, carboxyl groups could be used to enhance the conduction of electrons between carboxyl-GO and Au electrodes due to the excellent conductivity and electron transfer rate. The carboxyl-GO-based SPR chip exhibited high sensitivity based on the electric field amplification effects of the composite dielectric material. Therefore, the surface electric field could be enhanced by electron transfer, thereby greatly improving the sensitivity of the sensing system. Enhanced electric field intensity was generated around the carboxyl-GO of 63.58 V/m, and the measured work function was 4.95 eV. The results showed that the carboxyl-GO-based SPR biosensor had high sensitivity, affinity and selective ability for PAPPA2 protein with a high association rate constant (ka) of 3.1 ×109, M-1, S-1, and a limit of detection of 0.01 pg/mL in spiked human plasma.Conclusion: The results showed a detection accuracy of protein in spiked plasma of >90% compared to PBS buffer, suggesting that the carboxyl-GO-based SPR biosensor could be used in assays of human plasma for early and late gynecological diseases. The future of this technology will be useful for the diagnosis and evaluation of the risk of early maternal preeclampsia and potentially in clinical applications for gestational diseases.Keywords: carboxyl, graphene oxide, carboxyl-GO, surface plasmon resonance, SPR, pregnancy, associated plasma protein A2, PAPPA2

Chun-Yu Chen,1,2 Ying-Hsuan Lee,1 Shih-Hsin Chang,1,3–5 Yung-Fong Tsai,1,2 Jia-You Fang,1–3,5 Tsong-Long Hwang1–3,5,61Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; 2Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; 3Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan; 4Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; 5Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; 6Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City 243, TaiwanAim: This paper reports on the incorporation of oleic acid (OA) within nanostructured lipid carriers (OA-NLC) to improve the anti-inflammatory effects in the presence of albumin.Materials and methods: NLCs produced via hot high-shear homogenization/ultrasonication were characterized in terms of particle size, zeta potential, and toxicity. We examined the effects of OA-NLC on neutrophil activities. Dermatologic therapeutic potential was also elucidated by using a murine model of leukotriene B4-induced skin inflammation.Results: In the presence of albumin, OA-NLC but not free OA inhibited superoxide generation and elastase release. Topical administration of OA-NLC alleviated neutrophil infiltration and severity of skin inflammation.Conclusion: OA incorporated within NLC can overcome the interference of albumin, which would undermine the anti-inflammatory effects of OA. OA-NLC has potential therapeutic effects in topical ointments.Keywords: oleic acid, nanostructured lipid carrier, neutrophil, reactive oxygen species, superoxide, elastase

Nan-Fu Chiu,1 Chia-Tzu Kuo,1 Chen-Yu Chen2,31Laboratory of Nano-Photonics and Biosensors, Institute of Electro-Optical Engineering, National Taiwan Normal University, Taipei 11677, Taiwan; 2Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei City 10449, Taiwan; 3Department of Medicine, Mackay Medical College, Taipei 252, TaiwanBackground: The use of functionalized graphene oxide (fGO) has led to a new trend in the sensor field, owing to its high sensitivity with regards to sensing characteristics and easy synthesis procedures.Methods: In this study, we developed an ultra-sensitive carboxyl-graphene oxide (carboxyl-GO)-based surface plasmon resonance (SPR) aptasensor using peptides to detect human chorionic gonadotropin (hCG) in clinical serum samples. The carboxyl-GO based SPR aptasensor provided high affinity and stronger binding of peptides, which are great importance to allow for a non-immunological label-free mechanism. Also, it allows the detection of low concentrations of hCG, which are in turn considered to be important clinical parameters to diagnose ectopic pregnancies and paraneoplastic syndromes.Results: The high selectivity of the carboxyl-GO-based SPR aptasensor for hCG recombinant protein was verified by the addition of the interfering proteins bovine serum albumin (BSA) and human serum albumin (HSA), which did not affect the sensitivity of the sensor. The carboxyl-GO-based chip can enhance the assay efficacy of interactions between peptides and had a high affinity binding for a ka of 17×106 M−1S−1. The limit of detection for hCG in clinical serum samples was 1.15 pg/mLConclusion: The results of this study demonstrated that the carboxyl-GO-based SPR aptasensor had excellent sensitivity, affinity and selectivity, and thus the potential to be used as disease-related biomarker assay to allow for an early diagnosis, and possibly a new area in the field of biochemical sensing technology.Keywords: carboxyl-graphene oxide (carboxyl-GO), surface plasmon resonance (SPR), human chorionic gonadotropin (hCG)

Ying-Fei Yang, Wei-Ming Wang, Chi-Yun Chen, Tien-Hsuan Lu, Chung-Min Liao Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan 10617, Republic of China Background: No systematic investigations have been conducted to assess the lung burden imposed by the chronic inhalation of silver nanoparticles (AgNPs) emitted by spray products.Objective: The objective of this study was to formulate a study framework that integrates a probabilistic risk assessment scheme with a mechanistic lung burden model for the estimation of health risks associated with the long-term inhalation of AgNP-containing spray products.Materials and methods: A compartmentalized physiologically based alveolar deposition (PBAD) model was used to estimate AgNP lung burden. Dose–response relationships were established using nanotoxicity data sets obtained from rats (as a model organism). Weibull model-based thresholds of AgNP lung burden based on neutrophil-elevated inflammation biomarkers were estimated from Hill-based exposure–response relationships. Finally, the risks of lung disease posed by various AgNP-containing spray products were assessed.Results: Conservative thresholds for the prevention of pulmonary disease were estimated as follows (mean ± SE): 34 nm AgNPs (0.32±0.22 mg) and 60 nm AgNPs (1.08±0.64 mg). Our results indicate that the risk probability was ~0.5 that the hazard quotient (HQ) estimates of deodorant with a count median diameter (CMD) ˜30 nm exceeded 1. The primary risk posed by AgNPs is transferred from the interstitial region to lymph nodes. Under the condition of 50% risk probability, the 97.5 percentile of HQ for the spray products were as follows: CMD ˜30 nm (~3.4) and CMD ˜60 nm (~1.1).Conclusion: Our application of the proposed risk assessment scheme to the results obtained in an in vivo animal model proved highly effective in elucidating the relationship between the characteristics of metallic NP-containing spray products and their corresponding toxicity. The integration of the proposed PBAD model with a risk assessment framework enables the rapid assessment of risk posed by spray products containing metallic NPs over various time scales. Keywords: silver nanoparticles, spray product, risk assessment, lung burdens, nanotoxicity

Chung-Chieh Yu,1–3 Chih-Yu Huang,1–3 Wei-Ke Kuo,1–3 Chung-Yao Chen2,4 1Division of Pulmonary Critical Care and Sleep Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; 2Department of Medicine, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 3Department of Respiratory Therapy, Chang Gung Memorial Hospital, Keelung, Taiwan; 4Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan Objectives: To assess the effect of continuous positive airway pressure (CPAP) on nocturia in ischemic stroke patients with obstructive sleep apnea (OSA).Methods: This was a prospective and non-randomized controlled study in which ischemic stroke patients with OSA being treated in a rehabilitation ward were enrolled. The participants who tolerated CPAP were classified as the CPAP group, while those who refused or could not tolerate CPAP were classified as the control group. The percentage change of nocturia before and after 2 weeks of CPAP therapy between the two groups were compared.Results: A total of 44 participants were enrolled in and 35 participants (mean age=59.8±11.7 years old; mean apnea hypopnea index=42.9±16.7/h) completed the study (control group: 14, CPAP group: 21). Overall, 69% of the participants had nocturnal polyuria and 69% of them had more than one nocturia episode per night. The baseline and initial nocturia characteristics did not differ significantly between the two groups. As compared to the control group, CPAP therapy significantly decreased the nocturnal polyuria index (mean percentage change: 9% vs -21% (P=0.005)) and nocturnal urine output (mean percentage change: 6% vs -26% (P=0.04)), but not the nocturia episodes or 24-hours total urine output.Conclusion: Nocturia due to nocturnal polyuria is very common in post-stroke patients with OSA. Treating OSA by CPAP significantly reduces nocturnal polyuria, but not nocturia frequency, in ischemic stroke patients. Keywords: nocturia, nocturnal polyuria index, nocturnal urine output, multiple comorbidities

Jian-Hong Chen,1,2,* Po-Hsin Tsai,1,2,* Yin-Chou Lin,2,3 Chih-Ken Chen,1,2 Ching-Yen Chen1,2 1Department of Psychiatry, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan, Republic of China; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; 3Department of Rehabilitation, Chang Gung Memorial Hospital at Taoyuan, Taoyuan, Taiwan, Republic of China *These authors contributed equally to this work Objective: To examine the effect of mindfulness-based training on performance and mental health among a group of elite athletes. Methods: This study aimed to evaluate the effect of mindful sport performance enhancement (MSPE) on mental health, flow state, and competitive state anxiety using a 4-week workshop. We recruited an amateur baseball team (N=21) in Taiwan, and collected information by self-reported questionnaires administered before, immediately after, and at a 4-week follow-up. The primary outcome was to evaluate sports performance by flow state and competitive state anxiety, which included self-confidence, somatic anxiety, and cognitive anxiety. The secondary outcome was to explore whether MSPE intervention can improve anxiety, depression, sleep disturbance, and eating disorders.Result: After the workshop and follow-up 1 month later, we found improvements in flow state (P=0.001; P=0.045), cognitive anxiety in competitive anxiety (P=0.056; P=0.008), global eating disorder (P=0.009; P

Chien-Yu Chen,1 Chih-Ching Wu,2,3 Yu-Chi Huang,1 Chi-Fa Hung,1 Liang-Jen Wang4 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan; 4Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan Background: Dehydroepiandrosterone (DHEA), its sulfate ester (DHEA-S), and pregnenolone are neurosteroids that can be synthesized in the brain. Previous studies have hypothesized that these neurosteroids have antiaging, mood-enhancing, and cognitive-preserving effects; however, these effects may be gender-specific. Therefore, the purpose of this study was to investigate the gender differences in the relationships among neurosteroids (DHEA, DHEA-S, and pregnenolone), cognitive function, and quality of life in healthy individuals. Method: In this cross-sectional study, we enrolled 47 men (mean age: 32.8 years) and 75 women (mean age: 35.4 years) who had no major physical or psychiatric illnesses and measured their serum DHEA, DHEA-S, and pregnenolone. Furthermore, we evaluated the subjects’ cognitive function and quality of life using the Brief Assessment of Cognition in Schizophrenia and the World Health Organization Quality of Life Scale, respectively. Results: The serum levels of DHEA and DHEA-S demonstrated significant gender differences, even after controlling for age effect. In the male subjects, the DHEA serum levels were positively correlated with three domains of the World Health Organization Quality of Life Scale, including physical health, social relations, and environmental dimensions. Meanwhile, the DHEA-S levels positively correlated with the performance of working memory, and pregnenolone levels had a positive correlation with working memory, verbal fluency, and Brief Assessment of Cognition in Schizophrenia composite score. However, in the female subjects, we observed a correlation only between the serum levels of DHEA-S and working memory. Conclusion: The findings of our study indicate that neurosteroids play a vital role in cognitive function and quality of life among men but less so among women. Nevertheless, the underlying mechanisms of the gender-specific effect of neurosteroids require further investigation. Keywords: endocrinology, DHEA, pregnenolone, cognition, quality of life

Chung-Yu Chen,1–3 Kuang-Ming Liao4 1Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan Background: Atrial fibrillation (AF) occurs frequently in patients with COPD. There are limited data about the impact of AF in hospitalized COPD patients on other serious health outcomes, such as acute organ dysfunction, severe sepsis, and respiratory failure. The aim of our study was to delineate the impact of AF in hospitalized COPD patients. Methods: We defined COPD populations with and without AF from the National Health Insurance database in Taiwan. The control subjects (patients with COPD without AF) were selected from the population of COPD patients who had no history of AF and were matched to the COPD patients with AF by age (±1 year), gender, and the year of COPD diagnosis (±1 year). The primary outcome was the time to any first event, which included acute organ dysfunction, severe sepsis, respiratory failure, and death during the hospitalization period. Secondary outcomes, which also included acute organ dysfunction, severe sepsis, respiratory failure, and death, were estimated separately over time. Results: The primary outcome probability was higher in COPD patients with AF than in COPD patients without AF, with an adjusted HR (aHR) of 1.169 (95% confidence interval [CI]: 1.034–1.320), and higher risks of acute organ dysfunction and respiratory failure were also observed in the former group, with aHRs of 1.179 (95% CI: 1.0370–1.339) and 1.176 (95% CI: 1.006–1.374), respectively. Conclusion: Compared with COPD patients without AF, those with AF had a higher risk of hepatic dysfunction and respiratory failure. Keywords: atrial fibrillation, acute organ dysfunction, COPD, respiratory failure, sepsis

Ching-Yen Chen,1–3 Nan-Wen Yu,2–4 Tien-Hao Huang,4 Wei-Shin Wang,4 Ji-Tseng Fang2,3,5 1Department of Psychiatry, Chang Gung Memorial Hospital, Keelung, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Medical Education Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Psychiatry, Chang Gung Memorial Hospital, Linkou, Taiwan; 5Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan Purpose: During medical school training, increased stress, depression, and anxiety are common. Certain personality traits, particularly harm avoidance (HA), may increase the risk of psychopathological disorders, insomnia, and migraine among medical students. This study evaluated the role HA may play on levels of stress, depression, anxiety, and insomnia among Taiwanese medical students starting their fifth and final year of medical school.Patients and methods: A series of self-report questionnaires were used to measure the severity of anxiety, depression, and insomnia, as well as somatic symptoms, particularly migraine headache, among 143 Taiwanese fifth-year medical students (94 males and 49 females). Most had normal or mild levels of anxiety, depression, insomnia, and migraine.Results: HA personality trait was significantly associated with depression (all P ≤ 0.001) after adjusting for other factors. HA was not significantly associated with anxiety, insomnia, or migraine headache days.Conclusion: HA personality trait was significantly associated with depression among fifth-year medical students in Taiwan. Keywords: anxiety, depression, harm avoidance, psychological stress, sleep initiation and maintenance disorders, migraine, students, medical

Chih-Hsun Tai,1 Chi-Hao Shao,2 Chen-You Chen,2 Shu-Wen Lin,1–3 Chien-Chih Wu1,2 1Department of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 2School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan Background: Treatment options are limited for infections due to multidrug-resistant Gram-positive pathogens. Daptomycin is a lipopeptide antibiotic with concentration-dependent killing characteristic and dose-dependent post-antibiotic effect. To achieve optimized pharmacodynamic effect, some experts advocated using a high dose of daptomycin (≥9 mg/kg) for severe infections. However, the safety of high-dose therapy in patients with renal impairment remains unknown. This study was aimed to evaluate the safety of daptomycin in patients with severe renal impairment. Methods: This was a retrospective study performed by reviewing electronic medical records. Patients with severe renal impairment who were treated with daptomycin in a tertiary teaching hospital between January 1, 2013, and June 30, 2016, were included for evaluation. The incidence rates of creatine kinase (CK) elevation between high-dose (≥9 mg/kg) and standard-dose (

Ching-Yen Chen,1,2 Tze-Chun Tang,3 Tzu-Ting Chen,4 Ya Mei Bai,5,6 Huei-Huang Tsai,7 Hou-Liang Chen,7 Chun-Jen Huang,8,9 Chih-Ken Chen,1,2 Chun-Chih Chen,10 Mei-Chun Hsiao,11 Chia-Yih Liu,2,12 Hong-Shiow Yeh,13 Nan-Ying Chiu,10 Cheng-Chen Hsiao,14 Cheng-Sheng Chen,8,9 Tung-Ping Su5,15,16 1Department of Psychiatry, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Dr Tang’s Psychiatric Clinic, Kaohsiung, Taiwan; 4Department of Psychiatry, National Taiwan University Hospital, Yunlin Branch Hospital, Yunlin, Taiwan; 5Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; 6Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Tsao Tun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan; 8Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 9Department of Psychiatry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Department of Psychiatry, Changhua Christian Hospital Lukang Branch Hospital, Changhua, Taiwan; 11Yong Mei Psychiatric Clinic, Taoyuan City, Taiwan; 12Department of Psychiatry, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 13Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan; 14Cheng Chen Hsiao Clinic, Chiayi, Taiwan; 15Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; 16Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan Purpose: Paliperidone extended release (ER) is an oral psychotropic treatment formulated to release paliperidone at a controlled, gradually ascending rate. We evaluated the efficacy and safety of switching to paliperidone ER in Taiwanese patients with schizophrenia who were unresponsive or intolerant to previous antipsychotic therapy.Patients and methods: This was a 24-week, open-label, single-arm, multicenter, Phase IV trial. Based on consulting psychiatrists’ judgment, patients were deemed eligible for the switch to paliperidone ER; the switch was achieved by cross-tapering, using a recommended starting dose of 6 mg. Eligibility considerations included lack of efficacy, tolerability, and/or adherence to previous oral antipsychotic medication. Results: Of the 297 enrolled patients, 178 (59.5%) completed the study. The main reasons for discontinuation included insufficient efficacy (8.7%), patient decision (8.4%), and adverse events (AEs; 6.4%). Improvements in the: Positive and Negative Syndrome Scale total score and Clinical Global Impression-Severity score were observed only in patients treated at medical centers and not in those treated at psychiatric hospitals. The most common AEs were insomnia, headache, constipation, and extrapyramidal syndrome. One or more serious AEs were reported in 11 (3.7%) patients; none resulted in death. No significant changes in body weight, plasma glucose, or lipid levels were observed.Conclusion: Switching to paliperidone ER was effective and well tolerated for up to 24 weeks in patients with schizophrenia who were unresponsive or intolerant to previous antipsychotic therapy. The observed differences in treatment between psychiatric hospitals and medical centers with regard to dosage and titration of paliperidone ER warrant further investigation. Keywords: prospective, switch study, open-label, paliperidone extended release, schizophrenia, settings

Chun-Hao Liu,1,2 Po-Hsin Tsai,2,3 Ching-Yen Chen2,3 1Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, 2College of Medicine, Chang Gung University, Taoyuan, 3Department of Psychiatry, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan Background: Although many studies have discussed psychiatrists’ attitudes toward long-acting injectable antipsychotics (LAIs), no previous study has focused on differences in preference based on the facilities in which the psychiatrists practiced.Materials and methods: A pilot survey was conducted in a medical center in northern Taiwan, and a questionnaire was then distributed at the annual conference of the Taiwanese Society of Psychiatry in 2013. The questionnaire included general demographic data and preferences for the use of LAIs in different situations.Results: A total of 142 psychiatrists were included in our study. Among them, 114 were male (80.3%), and most practiced in general hospitals (n=110, 77.5%). We found that general hospital psychiatrists were more likely to prescribe LAIs for patients in the acute stage and with positive symptoms than were psychiatric hospital psychiatrists. General hospital psychiatrists also tended to prescribe LAIs at every time point of the disease.Conclusion: General hospital psychiatrists were more likely to prescribe LAIs than those in psychiatric hospitals. Knowing the factors affecting psychiatrists’ preferences may help us to develop a further study to explore “why” psychiatrists consider or do not consider LAIs in different facilities. Keywords: antipsychotic agents, general hospital, injections, psychiatric hospital

George Kuo,1 Wei-Chiao Sun,1 Yueh-An Lu,1 Chao-Yu Chen,1 Huang-Kai Kao,2 YuJr Lin,3 Yung-Chang Chen,4 Cheng-Chieh Hung,1 Ya-Chung Tian,1 Hsiang-Hao Hsu1 1Department of Nephrology, Kidney Research Center, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 2Department of Plastic and Reconstructive Surgery, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 3Center for Big Data Analytics and Statistics, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 4Department of Internal Medicine, Division of Nephrology, College of Medicine, Keelung Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan Purpose: Infectious spondylodiscitis is a serious disease that can lead to permanent neurological deficit. Because there were only a few case reports or series featuring infectious spondylodiscitis in chronic dialysis patients, we investigated the epidemiology and outcome in the chronic dialysis patients versus general population.Materials and methods: We retrospectively identified chronic dialysis patients admitted for infectious spondylodiscitis between January 2002 and December 2015. A total of 105 chronic dialysis patients were included, and we performed a 1:2 case–control match on propensity score in non-dialysis patients with infectious spondylodiscitis. The demographic features, clinical manifestation, infection focus, and disease outcome were recorded.Results: A total of 302 patients entered the final analysis. Chronic dialysis patients less frequently had fever (34.3%), and in the majority, bacterial entry was through dialysis vascular access (30.5%). Methicillin-resistant Staphylococcus aureus (MRSA) comprised the majority of causative pathogen. The chronic dialysis group had longer hospital stay, higher in-hospital mortality, and higher 1-year mortality. The odds ratio of in-hospital mortality was 2.20 compared with the non-dialysis group.Conclusions: The study highlighted poorer outcome and high frequency of resistant Staphylococcus of infectious spondylodiscitis in chronic dialysis patients. Therefore, high vigilance, prompt recognition, and empiric coverage of MRSA will be important in the management of infectious spondylodiscitis in chronic dialysis patients. Keywords: end stage renal disease, pyogenic spondylodiscitis, infectious spondylodiscitis, methicillin-resistant Staphylococcus aureus, mortality

Shou-Hsuan Liu,1–3,* Chao-Yu Chen,1,* Yi-Jung Li,1,2 Hsin-Hsu Wu,1,2 Chan-Yu Lin,1 Yung-Chang Chen,1 Ming-Yang Chang,1 Hsiang-Hao Hsu,1 Cheng-Lung Ku,2,3 Ya-Chung Tian1 1Kidney Research Center, Department of Nephrology, Lin-Kou Chang Gung Memorial Hospital and Department of Medicine, 2Graduate Institute of Clinical Medical Sciences, 3Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan *These authors contributed equally to this work Purpose: C-reactive protein (CRP) is a useful biomarker for prediction of long-term outcomes in patients undergoing chronic dialysis. This observational cohort study evaluated whether the time-averaged serum high-sensitivity CRP (HS-CRP) level was a better predictor of clinical outcomes than a single HS-CRP level in patients undergoing peritoneal dialysis (PD). Patients and methods: We classified 335 patients into three tertiles according to the time-averaged serum HS-CRP level and followed up regularly from January 2010 to December 2014. Clinical outcomes such as cardiovascular events, infection episodes, newly developed malignancy, encapsulating peritoneal sclerosis (EPS), dropout (death plus conversion to hemodialysis), and mortality were assessed. Results: During a 5-year follow-up, 164 patients (49.0%) ceased PD; this included 52 patient deaths (15.5%), 100 patients (29.9%) who converted to hemodialysis, and 12 patients (3.6%) who received a kidney transplantation. The Kaplan–Meier survival analysis and log-rank test revealed a significantly worse survival accumulation in patients with high time-average HS-CRP levels. A multivariate Cox regression analysis revealed that a higher time-averaged serum HS-CRP level, older age, and the occurrence of cardiovascular events were independent mortality predictors. A higher time-averaged serum HS-CRP level, the occurrence of cardiovascular events, infection episodes, and EPS were important predictors of dropout. The receiver operating characteristic analysis verified that the value of the time-average HS-CRP level in predicting the 5-year mortality and dropout was superior to a single serum baseline HS-CRP level. Conclusion: This study shows that the time-averaged serum HS-CRP level is a better marker than a single baseline measurement in predicting the 5-year mortality and dropout in PD patients. Keywords: dropout, encapsulating peritoneal sclerosis, high sensitivity C-reactive protein, malignancy, mortality, peritoneal dialysis

Kuang-Ming Liao,1 Chung-Yu Chen2,3 1Department of Internal Medicine, Chi Mei Medical Center Chiali, Tainan, 2Master Program in Clinical Pharmacy, School of Pharmacy, Kaohsiung Medical University, 3Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China Objective: To investigate the incidence and risk factors of atrial fibrillation (AF) in Asian chronic obstructive pulmonary disease (COPD) patients. Patients and methods: We selected a study population older than 40 years with a COPD diagnosis and who had used at least one inhaled bronchodilator medication between 1998 and 2012. The date of the index COPD diagnosis was defined as the index date. We excluded patients with a history of AF, significant mitral valve disease, disorders of the thyroid gland, or ischemic heart disease before the index date. We followed all patients from the index date to the day of AF occurrence, the day of death, or the date of December 31, 2013. The baseline of comorbidities was identified before the index date. Comorbidities included hypertension, diabetes mellitus, end-stage renal disease, congenital heart failure, stroke, peripheral arterial occlusive disease, and malignancy. Results: We included 6,208 COPD patients and 12,409 patients without COPD. The incidence of AF was higher in COPD patients than in those without COPD. The adjusted hazard ratio (HR) for AF among those with COPD was 2.23 with a 95% confidence interval (CI) of 1.98–2.51 compared to those without COPD. After multiple analyses, patients with hypertension (HR 1.43 [95% CI =1.26–1.62]) or heart failure (HR 2.36 [95% CI =1.81–3.08]) were found to have a significantly higher incidence of AF than those without these conditions. Conclusion: It is important for physicians to monitor, prevent, and provide early intervention for AF in COPD patients with hypertension or heart failure. Keywords: atrial fibrillation, COPD, incidence

Hsien-Hao Huang,1,2 Liang-Yu Chen,3,4 Ming-Luen Doong,5 Shi-Chuan Chang,6,7 Chih-Yen Chen8–10 1Institute of Clinical Medicine, National Yang-Ming University of Medicine, 2Department of Emergency Medicine, Taipei Veterans General Hospital, 3Aging and Health Research Center, National Yang-Ming University, 4Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, 5Institute of Physiology, National Yang-Ming University School of Medicine, 6Institute of Emergency and Critical Medicine, National Yang-Ming University School of Medicine, 7Department of Chest Medicine, Taipei Veterans General Hospital, 8Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 9Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, 10Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan Background: Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect.Objective: This study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats.Methods and procedures: We examined the effects of α-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters.Results: ICV injection of O-n-octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h (P

Chuanyu Chen, Peijun You Department of Anesthesiology, Shandong Jining No 1 People’s Hospital, Jining, Shandong, People’s Republic of China Purpose: Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC) systems for the delivery of local anesthetic drug, ropivacaine (RVC). Methods: In this study, transcriptional transactivator peptide (TAT)-decorated RVC-loaded NCs (TAT-RVC/NCs) were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. Results: The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs) and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. Conclusion: These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia. Keywords: local anesthetic system, ropivacaine, transcriptional transactivator peptide, nanocarriers, skin delivery

Chao-Yu Chen,1,2,* Ming-Hui Liu,3,* Ching-Wei Hsu,1,2 Cheng-Hao Weng,1,2 Tzung-Hai Yen,1,2 Wen-Hung Huang1,2 1Department of Nephrology and Division of Clinical Toxicology and Toxicology Laboratory, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, Republic of China; 2Chang Gung University College of Medicine, Taoyuan, Taiwan, Republic of China; 3Department of Pediatric Dentistry, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Patients undergoing hemodialysis (HD) have significantly higher mean blood lead levels (BLLs) than those in healthy individuals. Because elementary lead can be found in particulate matter with a diameter of