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Chi-Chen Huang,1 Sheng-Feng Tsai,2,3 Shu-Cheng Liu,4 Mei-Chen Yeh,5 Hao-Chang Hung,5 Chu-Wan Lee,6 Ching-Li Cheng,6 Pei-Ling Hsu,7– 9 Yu-Min Kuo2,3 1Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70403, Taiwan; 2Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 3Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 4Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70403, Taiwan; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, 71004, Taiwan; 6Department of Nursing, National Tainan Junior College of Nursing, Tainan, 700007, Taiwan; 7Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 8Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan; 9Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 80708, TaiwanCorrespondence: Pei-Ling Hsu, Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan, 80708, Tel +886-7-3121101 ext. 2144#16, Fax +886-7-3119849, Email plhsu@kmu.edu.tw Yu-Min Kuo, Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, 1 Ta Hsueh Road, Tainan, 70101, Taiwan, Tel +886-6-2353535 ext. 5294, Fax +886-6-2093007, Email kuoym@mail.ncku.edu.twIntroduction: Insulin, the key hormone for glucose regulation, has garnered attention for its role as an immune modulator. Impaired insulin signaling in the central nervous system is linked to neuroinflammation and neurodegenerative diseases. Microglia, the resident macrophage-like immune cells in the brain, are key regulators of neuroinflammation. However, the mechanisms by which insulin influences microglial immune responses remain relatively unknown.Methods: This study aimed to assess the effects of post-treatment with insulin [30 minutes after lipopolysaccharide (LPS) exposure] on LPS-induced inflammatory responses in BV2 microglial cells.Results: Post-treatment with insulin potentiated LPS-induced production of nitric oxide and pro-inflammatory cytokines, such as TNF and IL-6, through activation of the Akt/NF-κB pathway. Insulin also enhanced the ability of BV2 cells to phagocytose bacteria particles and β-amyloid fibrils. Conversely, insulin inhibited activation of NADPH oxidase and reduced intracellular levels of reactive oxygen species in LPS-treated BV2 cells.Conclusion: Insulin enhances microglial immune competence when challenged by endotoxins but mitigates oxidative stress in these cells. Keywords: β-amyloid, p47phox, phagocytosis, superoxide dismutase

Yu-Chieh Ho,1,&ast; Chia-Ti Wang,1,&ast; Tzu-Chieh Weng,2 Chung-Han Ho,3,4 Kang-Ting Tsai,5,6 Chien-Chin Hsu,1,7 Hung-Jung Lin,1,7,8 Hsiu-Chin Chen,5,9 Chien-Cheng Huang1,7,10 1Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 4Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 5Department of Senior Welfare and Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 6Division of Geriatrics and Gerontology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 7School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; 8Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Nursing, Chi Mei Medical Center, Tainan, Taiwan; 10Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chien-Cheng Huang, Department of Emergency Medicine, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan City, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email jasonhuang0803@gmail.com Hsiu-Chin Chen, Department of Nursing, Chi Mei Medical Center, Tainan, Taiwan, 901 Zhonghua Road, Yongkang District, Tainan City, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email 300006@mail.chimei.org.twPurpose: The home-based medical integrated program (HMIP) is a novel model for home healthcare (HHC) in Taiwan, initiated in 2016 to enhance care quality. However, the outcomes of this program on health outcomes and medical resource utilization in HHC patients remain unclear. Thus, we conducted this study to clarify it.Patients and Methods: The authors utilized the Taiwan National Health Insurance Research Database to identify HHC patients who received HMIP and those who did not between January 2015 and December 2017. A retrospective cohort study design was used. Convenience sampling was employed to select patients who met the inclusion criteria: being part of the HHC program and having complete data for analysis.Results: A total of 4982 HHC patients in the HMIP group and 10,447 patients in the non-HMIP group were identified for this study. The mean age in the HMIP group and non-HMIP group was 77.6 years and 76.1 years, respectively. Compared with the non-HMIP group, the HMIP group had lower total medical costs for HHC, fewer outpatient department visits and lower medical costs, lower medical costs for emergency department visits, fewer hospitalizations, and a lower mortality rate (34.6% vs 41.2%, p< 0.001).Conclusion: The HMIP is a promising model for improving care quality and reducing medical resource utilization in HHC patients. While this suggests that the non-HMIP model should be replaced, it’s important to note that both non-HMIP and HMIP models currently coexist. The HMIP may serve as an important reference for other nations seeking to improve care quality and reduce medical resource utilization in their own HHC systems.Keywords: home-based medical integrated plan, health outcomes, medical resource utilization, Taiwan

Shih-Ching Chin,1,&ast; Yun-Hsuan Chang,2– 6,&ast; Chih-Chun Huang,6,7 Ting-Hsi Chou,1 Chieh-Liang Huang,8 Hsiu-Man Lin,9 Marc N Potenza10 1Department of Psychology, Asia University, Taichung, Taiwan; 2Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Psychology, National Cheng Kung University, Tainan, Taiwan; 5Institute of Genomics and Bioinformatics, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 6Department of Psychiatry, National Cheng Kung University Hospital, Douliou Branch, Yunlin, Taiwan; 7Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Psychiatry, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan; 9Department of Child and Adolescent Development and Mental Health, China Medical University Children’s Hospital, Taichung, Taiwan; 10Psychiatry, Child Study and Neuroscience, Center of Excellence in Gambling Research, Yale School of Medicine, New Haven, CT, USA&ast;These authors contributed equally to this workCorrespondence: Yun-Hsuan Chang, Licensed Clinical Psychologist, Institute of Gerontology, College of Medicine; Department of Psychology, National Cheng Kung University, No. 1., University Road, Tainan, Taiwan, Email z11108051@ncku.edu.tw; yh.chang.snoopy@gmail.comIntroduction: The surge in mobile gaming, fueled by smartphone and internet accessibility, lacks a comprehensive understanding of physiological changes during gameplay.Methods: This study, involving 93 participants (average age 21.75 years), categorized them into Problematic Mobile Gaming (PMG) and non-problematic Mobile Gaming (nPMG) groups based on Problematic Mobile Gaming Questionnaire (PMGQ) scores. The PMGQ is a 12-item scale developed in Taiwan to assess symptoms of problematic mobile gaming. The research delved into heart rate variability (HRV) alterations during real-time mobile gaming and self-gaming video viewing.Results: Results showed that the PMG group significantly presents a lower root mean square of successive differences (RMSSD), and High Frequency (lnHF) than does the nPMG group (F=4.73, p=0.03; F=10.65, p=0.002, respectively) at the baseline. In addition, the PMG group significantly displayed elevated HF and low-frequency to high-frequency (LF/HF) in the mobile-gaming (F=7.59, p=0.007; F=9.31, p=0.003) condition as well as in the watching self-gaming videos (F=9.75, p=0.002; F=9.02, p=0.003) than did the nPMG.Conclusion: The study suggests targeted interventions to mitigate autonomic arousal, offering a potential avenue to address adverse effects associated with problematic mobile gaming behavior. The PMG group displayed increased craving scores after real-time mobile gaming and watching self-gaming video excerpts, unlike the nPMG group. Elevated LF/HF ratios in frequent gaming cases heightened autonomic arousal, presenting challenges in relaxation after mobile gaming. These findings contribute to a nuanced understanding of the complex interplay between mobile gaming activities, physiological responses, and potential intervention strategies.Keywords: addictive behaviors, video games, internet addiction, autonomic nervous system, craving, heart rate variability, self-regulation

Chien-Chia Huang,1,2 Po-Hung Chang,1,&ast; Yen-Lin Huang,3– 5 Ta-Jen Lee,1,2,6 Chi-Che Huang,1,2 Pei-Wen Wu1,2,&ast; 1Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Anatomic Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4School of Medicine, National Tsing-Hua University, Hsinchu, Taiwan; 5Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Department of Otolaryngology, Xiamen Chang Gung Hospital, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pei-Wen Wu, Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, No. 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan, Tel +886-3-3281200 ext. 8466, Fax +886-3-3979361, Email a9665@cgmh.org.twIntroduction: Eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with greater inflammation, poorer prognosis, and a high recurrence rate after sinus surgery.Objective: This study evaluated the clinical and imaging characteristics of eosinophilic CRSwNP in patients aged 12– 17.Methods: We retrospectively enrolled 139 patients aged 12– 17 with bilateral CRSwNP. Clinical characteristics, computed tomography (CT) features, tissue eosinophil counts, and eosinophil activity were evaluated.Results: Twenty-three (16.5%) patients had recurrent nasal polyps that required revision surgery. Patients requiring revision surgery had higher tissue eosinophil infiltration in the sinus mucosa than those not requiring revision surgery. The optimal cut-off value to distinguish the need for revision surgery was a tissue eosinophil count > 21.5/high-power field determined by the receiver operating characteristic curve. The Lund-Mackay and olfactory cleft opacification scores on CT images were significant predictors of tissue eosinophil count in the univariate analysis, and only olfactory opacification scores remained statistically significant in the multivariate analysis.Conclusion: This study revealed that the CT feature of the olfactory cleft opacification score could be a significant characteristic of eosinophilic CRSwNP in adolescents.Plain Language Summary: Chronic rhinosinusitis (CRS) is an inflammation of the nasal and sinus mucosa characterized by nasal obstruction, mucopurulent rhinorrhea, facial pain/pressure, and decreased or loss of smell for over 12 weeks.CRS is classified as CRS without nasal polyps or CRS with nasal polyps (CRSwNP), depending on the presence of nasal polyps. Based on the predominance of tissue inflammatory cell infiltration by eosinophils or neutrophils, CRS can be categorized into eosinophilic and neutrophilic entities. Eosinophilic CRSwNP is clinically characterized by a greater extent of inflammation, more severe clinical symptoms and high recurrence rate after sinus surgery. Thus, early identification of the endotypes in patients with CRS is important for determining prognosis and treatment strategies.This study retrospectively enrolled 139 patients aged 12– 17 with bilateral CRSwNP. Clinical characteristics, CT features, tissue eosinophil counts, and eosinophil activity were evaluated. The results showed that patients requiring revision surgery had higher tissue eosinophil infiltration in the sinus mucosa than those not requiring revision surgery. The optimal cut-off value to distinguish the need for revision surgery was a tissue eosinophil count > 21.5/high-power field. The Lund-Mackay and olfactory cleft opacification scores on CT images were significant predictors of tissue eosinophil count in the regression analysis.Keywords: adolescent, chronic rhinosinusitis, computed tomography, eosinophil, nasal polyp

Chien-Cheng Huang,1– 3 Tzu-Hao Chen,3,4 Chung-Han Ho,4,5 Yi-Chen Chen,4 Rong-Jane Chen,3,6 Ying-Jan Wang,3 Chien-Chin Hsu,1 Hung-Jung Lin,1,7 Jhi-Joung Wang,8,9 Ching-Ping Chang,4 How-Ran Guo3,10,11 1Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 5Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 6Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan; 8Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; 9Department of Anesthesiology, National Defense Medical Center, Taipei, Taiwan; 10Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 11Occupational Safety, Health and Medicine Research Center, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Chien-Cheng Huang, Department of Emergency Medicine, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email cmher11001@mail.chimei.org.tw How-Ran Guo, Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 1 Daxue Road, Tainan, 701, Taiwan, Tel +886-6-235-3535, Fax +886-6-275-2484, Email hrguo@mail.ncku.edu.twPurpose: Carbon monoxide (CO) poisoning may damage the pancreas, but the effects of CO poisoning on the development of diabetes and on existing diabetes remain unclear. We conducted a study incorporating data from epidemiologic analyses and animal experiments to clarify these issues.Methods: Using the National Health Insurance Database of Taiwan, we identified CO poisoning patients diagnosed between 2002 and 2016 (CO poisoning cohort) together with references without CO poisoning who were matched by age, sex, and index date at a 1:3 ratio. We followed participants until 2017 and compared the risks of diabetes and hyperglycemic crisis between two cohorts using Cox proportional hazards regressions. In addition, a rat model was used to assess glucose and insulin levels in blood as well as pathological changes in the pancreas and hypothalamus following CO poisoning.Results: Among participants without diabetes history, 29,141 in the CO poisoning cohort had a higher risk for developing diabetes than the 87,423 in the comparison cohort after adjusting for potential confounders (adjusted hazard ratio [AHR]=1.23; 95% confidence interval [CI]: 1.18– 1.28). Among participants with diabetes history, 2302 in the CO poisoning cohort had a higher risk for developing hyperglycemic crisis than the 6906 in participants without CO poisoning (AHR = 2.12; 95% CI: 1.52– 2.96). In the rat model, CO poisoning led to increased glucose and decreased insulin in blood and damages to pancreas and hypothalamus.Conclusion: Our epidemiological study revealed that CO poisoning increased the risks of diabetes and hyperglycemic crisis, which might be attributable to damages in the pancreas and hypothalamus as shown in the animal experiments.Keywords: animal, carbon monoxide poisoning, diabetes, epidemiology, hypothalamus, pancreas

Wen-Yin Chen,1,2 Hsing-Cheng Liu,1,3 Ying-Chih Cheng,2,4 Hua Li,2 Chi-Chieh Huang,2 Yu-Wei Ding,2 Ming-Chyi Huang,1,3 Chih-Chiang Chiu,1,3 Yu-Kang Tu,2,5 Po-Hsiu Kuo2,5,6 1Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; 2Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 3Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Psychiatry, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 5Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan; 6Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, TaiwanCorrespondence: Yu-Kang Tu; Po-Hsiu KuoDepartment of Public Health, College of Public Health, National Taiwan University, Room 521, No. 17, Xuzhou Road, Taipei City, 100, TaiwanEmail yukangtu@ntu.edu.tw; phkuo@ntu.edu.twIntroduction: The priority of interventions to alleviate cognitive deficits in patients with bipolar disorder (BD) is inconclusive. We systematically evaluate the efficacy of pharmacological or neurostimulation interventions for cognitive function in BD through a network meta-analysis.Methods: The PubMed, PsycINFO, Embase, and Cochrane Library databases were searched from database inception to September 30, 2021. Following PRISMA guidelines, all eligible studies were randomized controlled trials of adult bipolar patients that provided detailed cognitive outcomes. Studies were excluded if participants limited to comorbid substance use disorder or the intervention was a psychotherapy. Network meta-analysis comparing different interventions was conducted for 8 cognitive domains. Partially ordered set with Hasse diagram was used to resolve conflicting rankings between outcomes. The study was preregistered on PROSPERO database (CRD42020152044).Results: Total 21 RCTs including 42 tests for assessing intervention effects on cognition were retrieved. Adjunctive erythropoietin (SMD = 0.61, 95% CI = 0.00– 1.23), Withania somnifera (SMD = 0.58, 95% CI = 0.03– 1.13), and galantamine (SMD = 1.22, 95% CI = 0.10– 2.35) was more beneficial for attention, working memory, and verbal learning in euthymic BD patients than treatment as usual, respectively. Hasse diagram suggested ranking of choice when multiple domains were combined.Conclusion: Considerable variability in measurements of cognitive domains in BD was observed, and no intervention resulted in superior benefits across all domains. We suggested interventions priority can be tailored according to individual patients’ cognitive deficits. As current findings from relatively small and heterogeneous dataset, future trials with consensus should be applied for building further evidence.Keywords: cognitive function, systematic review, network meta-analysis, Hasse diagram, partially ordered set

Ching-Ju Chiu,1 Min-Chia Yang,2 Chi-Chang Huang,3 Chia-Ming Chang1,3 1Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 2Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 3Division of Geriatrics and Gerontology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Min-Chia YangDepartment of Medicine, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, TaiwanTel +886-6-2353535 ext. 5739Fax +886-6-3028175Email kh9531023@gmail.comBackground: In this study, factors associated with the duration of a disability before death in older adults who are moderately to severely disabled in Taiwan are investigated.Methods: A nationally representative sample of older adults (65+) in 1996 who died before 2016 (n = 1139) were analyzed to calculate their disability status and the length of time they were disabled before death.Results: The mean period during which the participants experienced moderate to severe disability before death for older adults in Taiwan was 5.53 years (SD = 3.15). Men who were overweight had an average of 1.17 more survival years (βoverweight = 1.17, p < 0.05) as compared to those who were normal weight, and in the case of those who were cognitively impaired (SPMSQ ≤ 7), years of survival were decreased by an average of 1.70 years as compared to those who were cognitively intact before death (βcognition = − 1.70, p < 0.01). The aforementioned effects were independent of age. In women, the number of diseases was the most dominant independent correlate for survival years (βdisease = − 0.34, p < 0.05).Conclusion: Disability distribution at various time points before death among the elderly in Taiwan was revealed in the study. At 10 years before death, 93% of the elderly were free from any ADL disabilities, and only 4% reported more than three ADL disabilities. At 6 years before death, an average of 10% of the participants had more than three ADL disabilities, and at one year before death, moderate to severe disability increased to 38%. Factors associated with the survival years among those who were moderately to severely disabled showed distinct gender differences.Keywords: disability, duration before death, elderly, risk factor

Chieh-Chen Huang, Haw-Yueh Thong Department of Dermatology, Shin Kong Wu Ho Su Memorial Hospital, Taipei, TaiwanCorrespondence: Haw-Yueh ThongDepartment of Dermatology, Shin Kong Wu Ho Su Memorial Hospital, No. 95, Wenchang Road, Shilin Dist., Taipei City, 111045, Taiwan (R.O.C.)Tel +886-926-612-880Email drkellytang@gmail.comObjective: There are several clinical cases on the application of PRP (platelet-rich plasma) therapies. To improve disadvantages such as the inability to be standardized and stored long term, we proposed a novel platelet-lyophilized treatment (PLT) to enhance the wound healing rate and improve acne scarring.Study Design: A single-blinded study at a single health care center was performed. All subjects were treated with a fractional carbon dioxide laser. On the right side of the face, 2 mL PLT solution (dissolved in normal saline) was applied, while on the left side of the face (control group), 2 mL normal saline was applied. The treatment described above was repeated every 3 to 4 weeks, and 4 treatments were performed in total. Assessments were performed prior to each treatment and at the one-month follow-up after the fourth treatment. Subjective assessments included questionnaires administered by the principal investigator and a self-assessment questionnaire completed by the subjects. Moreover, VISIA complexion analysis was used for objective data collection, and spots, wrinkles, texture, pores, UV spots, brown spots, red areas, and porphyrins were objectively analyzed.Results: Our data indicated that the PLT side showed a more rapid recovery than the saline side; on average, the sloughing off of the crusts was noted on day 5 and day 6. The improvement rate for skin spots, texture, and pores was significantly increased on the PLT side, with the pigment and pore size both having a statistically significant improvement of p< 0.001, while the texture had a significant improvement of p< 0.01.Conclusion: The results suggested that the application of PLT could be a novel method to enhance wound healing and improve acne scarring after laser skin rejuvenation.Keywords: platelet-lyophilized treatment, PLT, wound healing, acne scars, ablative fractional carbon dioxide laser

Yun-Chen Chang,1 Ta-Jen Lee,1 Chi-Che Huang,1,2 Po-Hung Chang,1,2 Yi-Wei Chen,1 Chia-Hsiang Fu1,2 1Department of Otolaryngology-Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan City, 333, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, 333, TaiwanCorrespondence: Chia-Hsiang FuDivision of Rhinology, Department of Otolaryngology-Head and Neck Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University, No. 5 Fu-Shin Street, Guishan District, Taoyuan City, 333, TaiwanTel +886-3-3281200, ext.: 8465Fax +886-3-3979361Email fufamily@adm.cgmh.org.twBackground: Screening for the existence of aeroallergens in patients with possible allergic rhinitis using venous blood samples has become more popular, with advantages of increased convenience and less consumption of time.Objective: The aim of this study was to investigate the sensitivities and specificities of Phadiatop tests and total immunoglobulin E (IgE) levels in both adults and children.Methods: This study was conducted prospectively in a tertiary center. The process of recruitment took place from Jan 2015 to Dec 2019, and patients with clinical symptoms that suggested persistent allergic rhinitis were recruited and their serum samples collected. The results of the total IgE and Phadiatop tests as well as the positive items in the ImmunoCAP assay were recorded and analyzed.Results: A total of 9174 cases with complete data were enrolled, including 576 children and 8598 adults. A positive result in the ImmunoCAP assay was considered a positive atopic status towards aeroallergens. While using the total IgE levels to predict positive aeroallergens, the sensitivities and specificities were 65.7% and 85.7%, respectively, for adults and 86.3% and 77.4%, respectively, for children. When we used Phadiatop tests for allergy screening, the sensitivities and specificities was 94.5% and 98.2%, respectively, for the adult group and 98.5% and 96.8%, respectively, for the pediatric group.Conclusion: The Phadiatop test had better diagnostic power for aeroallergen detection than the serum total IgE levels, or even the dual test, for both the adult and pediatric groups in this hospital-based study. We suggest that the Phadiatop test is more cost-effective in aeroallergen screening for patients with suspected atopic airway diseases.Keywords: Phadiatop test, ImmunoCAP, total immunoglobulin E, IgE, aeroallergens

Chen-Lin Kang,1– 3 Tsair-Fwu Lee,1,4,5 Shan-Ho Chan,2 Shyh-Chang Liu,3 Jui-Chu Wang,6 Cheng-Hsiang Tsai,1 Kuan-Cho Liao,1 Fu-Min Fang,1 Liyun Chang,7 Chun-Chieh Huang1,8 1Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; 3Department of Information Engineering, I-Shou University, Kaohsiung, Taiwan; 4Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan; 5Biomedical Engineering, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Department of Anatomical Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 7Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung, Taiwan; 8Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanCorrespondence: Chun-Chieh HuangDepartment of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, No 123, Dapi Road, Niaosong Dist., Kaohsiung 833, TaiwanTel +886 9 75056110Fax +886 7 7322813Email cgukinace@gmail.comPurpose: Maintaining immobilization to minimize spine motion is very important during salvage stereotactic ablative radiation therapy (SABR) for recurrent head and neck cancer. This study aimed to compare the intrafractional motion between two immobilization methods.Patients and Methods: With a spine tracking system for image guiding, 9094 records from 41 patients receiving SABR by CyberKnife were obtained for retrospective comparison. Twenty-one patients were immobilized with a thermoplastic mask and headrest (Group A), and another 20 patients used a thermoplastic mask and headrest together with a vacuum bag to support the head and neck area (Group B). The intrafractional motion in the X (superior-inferior), Y (right-left), Z (anterior-posterior) axes, 3D (three-dimensional) vector, Roll, Pitch and Yaw in the two groups was compared. The margins of the planning target volume (PTV) to cover 95% intrafractional motion were evaluated.Results: The translational movements in the X-axis, Y-axis, and 3D vector in Group A were significantly smaller than in Group B. The rotational errors in the Roll and Yaw in Group A were also significantly smaller than those in Group B; conversely, those in the Pitch in Group A were larger. To cover 95% intrafractional motion, margins of 0.96, 1.55, and 1.51 mm in the X, Y and Z axes, respectively were needed in Group A, and 1.06, 2.86, and 1.34 mm, respectively were required in Group B.Conclusion: The immobilization method of thermoplastic mask and head rest with vacuum bag did not provide better immobilization than that without vacuum bag in most axes. The clinical use of 2 mm as a margin of PTV to cover 95% intrafractional motion was adequate in Group A but not in Group B.Keywords: stereotactic ablative radiation therapy, CyberKnife, intrafractional motion, immobilization method, head and neck cancer

Pei-Wen Wu,1,2 Ta-Jen Lee,1 Chun-Hua Wang,3 Chi-Che Huang,1,4 Po-Hung Chang,1,4 Chia-Hsiang Fu,1,4 Chien-Chia Huang1,4 1Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 2Department of Otolaryngology–Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Keelung, Taiwan; 3Department of Thoracic Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 4Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanCorrespondence: Chien-Chia HuangDivision of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, No. 5, Fu-Shin Street, Kweishan, Taoyuan 333, TaiwanTel +886-3-3281200 Ext 8466Fax +886-3-3979361Email agar@cgmh.org.twIntroduction: Most patients with asthma, either allergic or non-allergic, usually exhibit some level of concurrent rhinitis. Treatments for rhinitis and asthma can affect both conditions.Objective: The present study aimed to examine asthma-specific outcomes in patients with chronic rhinitis (CR) and asthma after surgery for nasal obstruction, and to identify the patient group most likely to experience improved asthma control after surgery.Methods: Asthmatic patients with CR and nasal obstruction were prospectively recruited for evaluations of nasal and asthma-specific outcomes before and after surgery for nasal obstruction.Results: Twenty-eight participants were enrolled. There was a significant association between the Asthma Control Test (ACT) and the Sino-Nasal Outcome Test-22 scores, both at the preoperative and 3-month postoperative assessments. Patients demonstrating ACT improvement after nasal surgery had worse preoperative ACT scores and predicted forced expiratory volume in 1 s.Conclusion: Nasal symptom severity was closely associated with the extent of asthma control in asthmatic patients with CR and nasal obstruction. Assessment of CR and nasal obstruction in patients with poorly controlled asthma should be considered an essential approach to improve the response to treatment and patients’ quality of life.Keywords: rhinitis, asthma, SNOT-22, quality of life, patient-reported outcome measure

Chien-Cheng Huang,1– 3 Chung-Han Ho,4,5 Yi-Chen Chen,4 Chien-Chin Hsu,1,6 Hung-Jung Lin,1,7 Jhi-Joung Wang,4,8 How-Ran Guo2,9,10 1Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Senior Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 4Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 5Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 6Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 7Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan; 8Allied AI Biomed Center, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 9Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 10Occupational Safety, Health and Medicine Research Center, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: How-Ran GuoDepartment of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 1 Daxue Road, East District, Tainan City 701, TaiwanTel +886-6-235-3535Fax +886-6-275-2484Email hrguo@mail.ncku.edu.twBackground: In addition to hypoxia, oxidative stress and inflammation due to carbon monoxide (CO) poisoning cause adverse health effects. These mechanisms are related to the occurrence of autoimmune connective tissue disease, but studies on the association between CO poisoning and autoimmune connective tissue disease are limited. We conducted a study to evaluate the occurrence of autoimmune connective tissue disease following CO poisoning.Methods: We identified participants with CO poisoning diagnosed between 1999 and 2012 from the Nationwide Poisoning Database and selected participants without CO poisoning from the Taiwan National Health Insurance Research Database with matching age and index dates at a 1:3 ratio. Sex, underlying comorbidities, and monthly income were also included in the analyses. We followed up the participants until 2013 and made comparison of the risk of autoimmune connective tissue disease between participants with and without CO poisoning.Results: The 23,877 participants with CO poisoning had a higher risk for autoimmune connective tissue disease than the 71,631 participants without CO poisoning (adjusted hazard ratio [AHR], 3.5; 95% confidence interval [CI], 3.1– 3.9) after adjustment for sex, diabetes, Lyme disease, herpes zoster, infectious mononucleosis, hepatitis, HIV infection, liver disease, renal disease, non-CO poisoning or drug abuse, malignancy, hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and monthly income. An increased risk was observed even after 4 years of follow-up (AHR, 3.6; 95% CI, 3.0– 4.4).Conclusion: The risk of autoimmune connective tissue disease increased following CO poisoning. Close follow-up of the patients with CO poisoning for the development of connective tissue disease is recommended, and further investigation of the detailed mechanisms is warranted.Keywords: autoimmune, carbon monoxide poisoning, connective tissue disease, hypoxia, inflammation, oxidative stress

Ya-Wen Shih,1 Chin-Sheng Hung,2,3 Cheng-Chiao Huang,4 Kuei-Ru Chou,1,5– 7 Shu-Fen Niu,8,9 Sally Chan,10 Hsiu-Ting Tsai1,8 1School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan; 2Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 4Division of Breast Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan; 5Center for Nursing and Healthcare Research in Clinical Practice Application, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 6Department of Nursing, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; 7Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 8Post-Baccalaureate Program in Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan; 9Department of Nursing, Shin Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan; 10UON Singapore Campus, Univesrity of Newcastle, Newcastle, NSW, AustraliaCorrespondence: Hsiu-Ting Tsai Email hsiuting@tmu.edu.twIntroduction: Breast cancer is a common malignancy worldwide. Smartphones have gradually become indispensable to our modern lives and have already changed lifestyles of human beings. To our best knowledge, no study has investigated the relationship between smartphone use and breast cancer. This case-control study purposely investigated the relationship between smartphone use and breast cancer risk.Materials and Methods: This was a case-control study comprising 894 healthy controls and 211 patients with breast cancer. All participants were asked to respond to standard questionnaires to collect information on sleep quality, smartphone addiction, and smartphone use.Results: Participants with smartphone addiction had a significantly higher 1.43-fold risk of breast cancer. Individuals with the habitual behavior of smartphone use > 4.5 minutes before bedtime had a significantly increased 5.27-fold risk of breast cancer compared to those who used a smartphone for ≤ 4.5 minutes before bedtime. Additionally, a closer distance between the smartphone and the breasts when using the smartphone exhibited a significantly increased 1.59-fold risk. Participants who carried their smartphone near their chest or waist-abdomen area had significantly increased 5.03-fold and 4.06-fold risks of breast cancer, respectively, compared to those who carried the smartphone below the waist. Moreover, there was a synergistic effect of smartphone addiction and smartphone use of > 4.5 minutes before bedtime which increased the breast cancer risk.Conclusion: Excessive smartphone use significantly increased the risk of breast cancer, particularly for participants with smartphone addiction, a close distance between the breasts and smartphone, and the habit of smartphone use before bedtime.Keywords: smartphone addiction, breast cancer, women, sleep quality

Xian Hu Zhang,1 Bing Feng Li,1 Jie Ding,2 Lei Shi,1 Huo Ming Ren,1 Kui Liu,1 Chuan Cai Huang,1 Fu Xiao Ma,1 Xin Yao Wu1 1Department of General Surgery, Suzhou First People’s Hospital, Suzhou, Anhui 234000, People’s Republic of China; 2Physical Examination Department, Suzhou Central Blood Station, Suzhou, Anhui 234000, People’s Republic of ChinaCorrespondence: Xian Hu ZhangDepartment of General Surgery, Suzhou First People’s Hospital, No. 26 Yinhe Road, Suzhou, Anhui 234000, People’s Republic of ChinaTel +86 18134605661Email zhang64332277735@126.comObjective: This study set out to probe into the effects of long non-coding RNA (LncRNA) differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis and autophagy of breast cancer (BC) cells.Methods: The expression levels of DANCR, miR-758-3p and paired box 6 (PAX6) in BC tissues and cell lines were detected. The transcription and protein levels of PAX6, apoptosis-related factors (caspase-3, caspase-9, Bax/Bcl-2), and autophagy-related factors (LC3B, Atg5, Beclin-1) in BC cells were detected. The cell proliferation, apoptosis, autophagy and the regulatory relationship between genes and target genes were analyzed.Results: DANCR and PAX6 were up-regulated in BC tissues and cell lines, while miR-758-3p was opposite. Down-regulating DANCR inhibited the malignant proliferation of BC cells and also promoted apoptosis and autophagy, which showed that caspase-3, caspase-9, Bax/Bcl-2, LC3B, Atg5 transcription and protein levels increased, while Beclin-1 transcription and protein levels decreased. DANCR regulated miR-758-3p in a targeted manner, and its over-expression could weaken the anti-cancer effect of miR-758-3p on BC cells. In addition, miR-758-3p also directly targeted PAX6, and knocking down its expression could weaken the inhibitory effect of down-regulating PAK6 on BC cell apoptosis and autophagy. We also found that DANCR acted as a competitive endogenous RNA sponge miR-758-3p, thus regulating the PAX6 expression.Conclusion: DANCR-miR-758-3p-PAX6 molecular network plays a key regulatory role in BC cell apoptosis and autophagy, which may provide reference for treating patients.Keywords: DANCR, miR-758-3p, PAX6, breast cancer, BC, apoptosis and autophagy

Hui Hua Chang,1–4 Wei Hung Chang,5 Mei Hung Chi,5 Yi Chin Peng,1 Chih-Chun Huang,5 Yen Kuang Yang,5–7 Po See Chen5,6 1Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Pharmacy, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan; 5Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 6Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, TaiwanCorrespondence: Po See ChenDepartment of Psychiatry, National Cheng Kung University Hospital, 138 Sheng Li Road, North District, Tainan 70403, TaiwanTel +886-6-2353535 ext. 5189Fax +886-6-2759259Email chenps@mail.ncku.edu.twObjective: Previous animal studies have shown that the oxytocin system might affect glucose homeostasis through the hypothalamus–pituitary–adrenal (HPA) axis and peripheral organs. Moreover, whether the effect is stratified by the polymorphism of oxytocin receptor gene (OXTR) remains unclear.Methods: In this study, we recruited 89 non-diabetic participants. Their plasma oxytocin and serum insulin profiles were obtained, and the polymorphism of OXTR rs53576 was genotyped.Results: There were significant correlations between the oxytocin level and fasting glucose level (r = –0.29, P

Chin-Chou Huang,1–5 Min-Ji Charng2,3 1Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan; 2Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 3Faculty of Medicine, School of Medicine, National Yang–Ming University, Taipei, Taiwan; 4Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; 5Institute of Pharmacology, National Yang-Ming University, Taipei, TaiwanCorrespondence: Min-Ji CharngDivision of Cardiology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11217, Taiwan, R. O. C.Tel +886 2 28757507Fax +886 2 28756849Email mjcharng@vghtpe.gov.twChin-Chou HuangDepartment of Medical Education, Taipei Veterans General hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11217, Taiwan, R. O. C.Tel +886 2 28757725Fax +886 2 28757726Email cchuang4@vghtpe.gov.ytwAbstract: Evolocumab, which can lower low-density lipoprotein (LDL) cholesterol levels by approximately 60% and prevent cardiovascular events in patients with cardiovascular disease, is a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Some studies have investigated its efficacy and safety in the treatment of the homozygous form of familial hypercholesterolemia (HoFH), and others have focused on its efficacy and safety in Asians with high cardiovascular risk. Although no direct evolocumab clinical trials have been conducted in Chinese HoFH patients, its efficacy and safety in the Chinese population should be similar to those in other ethnic groups.Keywords: Chinese, evolocumab, homozygous familial hypercholesterolemia, low-density lipoprotein, proprotein convertase subtilisin/kexin type 9

Yuk-Wah Tsang,1,2 Kwan-Hwa Chi,3,4 Cheng-Chung Huang,3,5 Mau-Shin Chi,3,6 Hsin-Chien Chiang,7 Kai-Lin Yang,3,4,8 Wen-Tyng Li,2 Yu-Shan Wang3,6 1Department of Radiation Oncology, Chiayi Christian Hospital, Chiayi, Taiwan; 2Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan, Taiwan; 3Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 4Institute of Radiation Science and School of Medicine, National Yang-Ming University, Taipei, Taiwan; 5Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; 6Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan; 7Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; 8School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan Purpose: Modulated electro-hyperthermia (mEHT) stands to be a significant technological advancement in the hyperthermia field, utilizing autofocusing electromagnetic power on the cell membrane to create massive apoptosis. Since mEHT possesses the unique ability to excite cell membranes, we hypothesized that mEHT could enhance the uptake of liposomal drugs by enhancing phagocytic activity. Materials and methods: Water bath control and mEHT were used to compare the enhancement of liposome-encapsulated doxorubicin (Lipodox®) uptake by cancer cells. Cancer cells were made visible by doxorubicin fluorescence to investigate drug uptake. Viable cell yield was determined via the Trypan Blue exclusion method. Various substrates were used to investigate the mechanism of drug-uptake enhancement. The murine colon carcinoma model, CT26, was used to confirm the tissue infiltration of Lipodox® and its therapeutic effect. Results: mEHT treatment showed a significant enhancement of Lipodox® uptake of doxorubicin fluorescence compared with 37°C or 42°C water bath treatment. Tumor tissue sections also confirmed that mEHT treatment achieved the highest doxorubicin concentration in vivo (1.44±0.32 µg/g in mEHT group and 0.79±0.32 µg/g in 42°C water bath). Wortmannin was used to inhibit the macropinocytosis effect and 70 kDa dextran-FITC served as uptake substance. The uptake of dextran-FITC by cancer cells significantly increased after mEHT treatment whereas such enhancement was significantly inhibited by wortmannin. Conclusion: The result showed mEHT-induced particle-uptake through macropinocytosis. mEHT-enhanced uptake of Lipodox® may amplify the therapeutic effect of liposomal drugs. This novel finding warrants further clinical investigation. Keywords: hyperthermia, cancer treatment, liposome, doxorubicin, micropinocytosis

Chi-Chun Huang,1 Hsin-Yi Chen,1 Ruei-Hsin Chang,1 Pen-An Liao,2 Heng-Hui Lien,3,4 Chih-Sheng Hung,5 Sien-Sing Yang,1,3 Jui-Ting Hu1,3 1Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan; 2Department of Radiology, Cathay General Hospital Medical Center, Taipei, Taiwan; 3School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei, Taiwan; 4Department of Surgery, Cathay General Hospital Medical Center, Taipei, Taiwan; 5Department of Gastroenterology, Cathay General Hospital Medical Center, Taipei, Taiwan Background: Sorafenib is an oral tyrosine kinase inhibitor that is indicated for advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine the clinical outcomes of HCC patients receiving sorafenib in real-life clinical setting in comparison with formal clinical trials.Methods: Patients diagnosed with advanced HCC between 2007 and 2015 at single institute were retrospectively enrolled and evaluated for survival and tolerability following sorafenib treatment. Overall survival (OS) and duration of treatment (TTP) were examined by different stratifications including age, gender, etiology, liver functions, and severities.Results: A total of 67 advanced HCC patients were enrolled for analysis. Of the 67 eligible patients, 66 patients (99%) were diagnosed as Barcelona Clinic Liver Cancer stage C and 45 (67%) were Child-Pugh A. Chronic hepatitis B virus infection was the main etiology (67%), followed by hepatitis C virus infection (12%) and alcohol liver disease (8%). The median duration of treatment was 3.0 months (95% CI 2.6–3.4 months) and median OS was 8.0 months (95% CI 5.0–11.0 months). By multivariate analysis, female gender (HR =2.462, 95% CI 1.126–5.387, P=0.024), Child-Pugh C (HR =3.913, 95% CI 1.063–14.410, P=0.04), extrahepatic spread (HR =2.123, 95% CI 1.122–4.015, P=0.021), and combined other therapies (HR =0.410, 95% CI 0.117–0.949, P=0.037) were the independent predictors of OS.Conclusion: OS of advanced HCC patients treated with sorafenib was longer than that reported in the Asia-Pacific trial study. Impaired hepatic functions are associated with the shorter survival in real-life setting. Keywords: advanced hepatocellular carcinoma, sorafenib, liver function, tumor burden

L-selectin, a lectin-like receptor, mediates rolling of lymphocytes on high endothelial venules (HEVs) in secondary lymphoid organs by interacting with HEV ligands. These ligands consist of a complex of sialomucins, candidates for which are glycosylation- dependent cell adhesion molecule 1 (GlyCAM-1), CD34, and podocalyxin. The ligands must be sialylated, fucosylated, and sulfated for optimal recognition by L-selectin. Our previous structural characterization of GlyCAM-1 has demonstrated two sulfation modifications, Gal-6-sulfate and GlcNAc-6-sulfate in the context of sialyl Lewis x. We now report the cloning of a Gal-6-sulfotransferase and a GlcNAc-6-sulfotransferase, which can modify GlyCAM-1 and CD34. The Gal-6-sulfotransferase shows a wide tissue distribution. In contrast, the GlcNAc-6-sulfotransferase is highly restricted to HEVs, as revealed by Northern analysis and in situ hybridization. Expression of either enzyme in Chinese hamster ovary cells, along with CD34 and fucosyltransferase VII, results in ligand activity, as detected by binding of an L-selectin/IgM chimera. When coexpressed, the two sulfotransferases synergize to produce strongly enhanced chimera binding.

Yuan-Yun Tam,1,* Chia-Chen Wu,2,* Ta-Jen Lee,2 Yang-Yu Lin,3 Tai-Di Chen,4 Chi-Che Huang2 1Department of Otorhinolaryngology – Head and Neck Surgery, Lotung Poh-Ai Hospital, Yilan County, 2Department of Otorhinolaryngology – Head and Neck Surgery, 3Department of Medical Imaging and Intervention, 4Department of Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan County, Taiwan *These authors contributed equally to this work Background: Sinonasal angiomatous polyp (SAP) is a rare subtype of sinonasal polyp that might be misdiagnosed as a malignant lesion due to its clinical symptoms.Methods: We retrospectively enrolled the patients who were diagnosed with SAP in our hospital during 2008–2015. We analyzed the clinical symptoms, radiological findings, and pathological features of all patients diagnosed with SAP.Results: Unilateral nasal obstruction, rhinorrhea, and epistaxis were the common symptoms. SAPs all originated from maxillary sinus and extended to nasal cavity with or without involving the nasopharynx. Expansile mass with surrounding bony destruction is typical on computed tomography imaging but specific for SAPs. The magnetic resonance revealed high signal intensity on T1-weighted images and hypointense rim on T2-weighted images.Conclusion: Computed tomography and magnetic resonance together might give rise to more accurate diagnosis of SAP. Incisional biopsy does help if the clinician suspects a malignant lesion. To treat SAP, complete removal is the optimal choice. Keywords: sinonasal angiomatous polyp, angiomatous polyp, antrochoanal polyp, angiomatous nasal polyp, infarcted nasal polyp

Chih-Hao Chang,1 Kuo-Chien Tsao,2,3 Han-Chung Hu,1,4 Chung-Chi Huang,1,4 Kuo-Chin Kao,1,4 Ning-Hung Chen,1,4 Cheng-Ta Yang,1,4 Ying-Huang Tsai,4,5 Meng-Jer Hsieh4,51Department of Pulmonary and Critical Care Medicine, Linkou Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation, Chang-Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Laboratory Medicine, Linkou Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation; 3Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan; 4Department of Respiratory Therapy, Chang-Gung University, Taoyuan, Taiwan; 5Department of Pulmonary and Critical Care Medicine, Chiayi Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation, Puzi City, TaiwanBackground: Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations. Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial.Methods: Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations. The bacteria were identified by the semiquantitative culture of the expectorated sputum. The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections.Results: Viruses were isolated from 16 (22.2%) of the 72 patients enrolled. The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus. A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae. Five patients (6.9%) had both positive sputum cultures and virus identification. The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different. Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation.Conclusion: WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits. Those with increased sputum during a COPD exacerbation had higher risks for recurrent exacerbations.Keywords: chronic obstructive pulmonary disease, bacterial infection, virus, CRP

Huei-Ling Huang,1 Yea-Ing L Shyu,2,3 Min-Chi Chen,4 Chin-Chang Huang,5,6 Hung-Chou Kuo,5,6 Sien-Tsong Chen,5,6 Wen-Chuin Hsu6,71Department of Gerontological Care and Management, Chang Gung University of Science and Technology, Taoyuan, Taiwan; 2School of Nursing, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan; 4Department of Public Health and Biostatistics Consulting Center, Chang Gung University, Taoyuan, Taiwan; 5Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6School of Medicine, Chang Gung University, Taoyuan, Taiwan; 7Chang Gung Dementia Center, Taoyuan, TaiwanPurpose: The purpose of this study was to explore family caregivers’ role-implementation experiences at different stages of dementia.Patients and methods: For this cross-sectional, exploratory study, 176 dyads of family caregivers and their community-dwelling elderly relatives with dementia were recruited from the neurological clinics of a medical center in Taiwan. The Family Caregiving Inventory was used to assess family caregivers for caregiving activities, role strain, role preparation, and help from others at different stages of care receivers’ dementia.Results: Family caregivers’ caregiving activities were related to patients’ stages of dementia. For patients with mild dementia, caregivers provided more assistance in transportation and housekeeping. In addition to these two activities, family caregivers of patients with moderate dementia provided more assistance with mobility and protection. For patients with severe dementia, family caregivers provided more assistance with personal care, mobility and protection, transportation, and housekeeping. Overall, family caregivers reported having some preparation to provide care; the most difficult caregiving activity was identified as managing behavioral problems.Conclusion: This study’s results provide a knowledge base for designing dementia stage-specific interventions in clinical practice and developing community-based, long-term care systems for families of patients with dementia.Keywords: behavioral problem, illness trajectory, role strain, caregiving activity, prepar­edness

Hsieh-Chih Tsai,1,* Jeng-Yee Lin,2,* Faiza Maryani,1 Chun-Chiang Huang,1 Toyoko Imae1,31Graduate Institute of Applied Science and Technology, 2Division of Plastic Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, 3Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan *These authors contributed equally to this work Abstract: In this study, three types of hybrid nanotubes (NTs), ie, oxidized multiwalled carbon NTs (COOH MWCNTs), heparin (Hep)-conjugated MWCNTs (Hep MWCNTs), and diblock copolymer polyglycolic acid (PGA)-co-heparin conjugated to MWCNTs (PGA MWCNTs), were synthesized with improved biocompatibility and drug-loading capacity. Hydrophilic Hep substituents on MWCNTs improved biocompatibility and acted as nucleus-sensitive segments on the CNT carrier, whereas the addition of PGA enhanced drug-loading capacity. In the PGA MWCNT system, the amphiphilic copolymer (PGA-Hep) formed micelles on the side walls of CNTs, as confirmed by electron microscopy. The PGA system encapsulated the hydrophobic drug with high efficiency compared to the COOH MWCNT and Hep MWCNT systems. This is because the drug was loaded onto the PGA MWCNTs through hydrophobic forces and onto the CNTs by ∏–∏ stacking interactions. Additionally, most of the current drug-carrier designs that target cancer cells release the drug in the lysosome or cytoplasm. However, nuclear-targeted drug release is expected to kill cancer cells more directly and efficiently. In our study, PGA MWCNT carriers effectively delivered the active anticancer drug doxorubicin into targeted nuclei. This study may provide an effective strategy for the development of carbon-based drug carriers for nuclear-targeted drug delivery. Keywords: carbon nanotube, amphiphilic copolymer, drug loading, nucleus targeting, cancer therapy