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Dian-Jeng Li,1– 3 Agata Chudzicka-Czupa&lstrok;a,4 Mateusz Paliga,5 Nadiya Hapon,6 Liudmyla Karamushka,7 Marta &Zdot;ywio&lstrok;ek-Szeja,4 Roger S McIntyre,8– 10 Soon-Kiat Chiang,11 Yi-Lung Chen,12,13 Cheng-Fang Yen,1,14,15 Roger Ho Chun Man16,17 1Graduate Institute of Medicine and School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 2Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, 80276, Taiwan; 3Department of Nursing, Meiho University, Pingtung, 91200, Taiwan; 4Faculty of Psychology, SWPS University of Social Sciences and Humanities, Katowice, Poland; 5Faculty of Social Sciences, Institute of Psychology, University of Silesia in Katowice, Katowice, Poland; 6Department of Psychology, Faculty of Philosophy, Ivan Franko National University in Lviv, Lviv, Ukraine; 7G. S. Kostiuk Institute of Psychology, National Academy of Educational Sciences of Ukraine, Kyiv, Ukraine; 8Department of Psychiatry University of Toronto, Toronto, Canada; 9Department of Pharmacology, University of Toronto, Toronto, Canada; 10Brain and Cognition Discovery Foundation, Toronto, Canada; 11Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 12Department of Psychology, Asia University, Taichung, Taiwan; 13Department of Healthcare Administration, Asia University, Taichung, Taiwan; 14Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 15College of Professional Studies, National Pingtung University of Science and Technology, Pingtung, Taiwan; 16Department of Psychological Medicine, National University of Singapore, Singapore, Singapore; 17Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, SingaporeCorrespondence: Cheng-Fang Yen, Department of Psychiatry, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung, 80708, Taiwan, Tel +886-7-3121101 ext. 6822, Fax +886-7-3134761, Email chfaye@cc.kmu.edu.tw Yi-Lung Chen, Department of Healthcare Administration, Asia University, No. 500, Lioufeng Road, Wufeng, Taichung, 41354, Taiwan, Tel +886-4-23323456&num;20106, Fax +886-4-23321206, Email elong@asia.edu.twBackground: The Russo-Ukrainian War has resulted in massive social, economic, and psychological burdens worldwide. This study aimed to investigate the associations between time spent on the war-related news and psychological distress, including depression, anxiety, and post-traumatic stress disorder (PTSD) and the mediating effects of rumination on the associations in people residing in Poland and Ukraine.Methods: This cross-sectional study recruited 1438 internet users in Poland and Ukraine, and collected data on levels of rumination, psychological distress, and the amount of time spent on and sources of the news of the Russo-Ukrainian War. Structural equation modeling with bootstrapping methods was used to evaluate the mediation effect. Multivariate linear regression was used to identify predictive effect of the source of the war-related news on psychological distress and rumination.Results: The results showed a mediating effect of rumination on the association between the amount of time spent on the war-related news and psychological distress among participants in Poland (β = 0.16, p < 0.001) and Ukraine (β = 0.15, p < 0.001). Approaching the news from television was associated with rumination (β = 0.607, p < 0.001) and PTSD symptoms in Poland (β = 2.475, p = 0.009), while approaching news from the internet was associated with rumination in Poland (β = 0.616, p = 0.001).Conclusion: The study identified the mediating effect of rumination and the associations of approaching the war-related news from television and the internet with mental health.Keywords: Russo-Ukrainian war, rumination, psychological distress, mediation, time spent on the news of war

Nian-Fang Lu,1 Hong-Xia Niu,2 An-Qi Liu,1 Ya-Lei Chen,1 Hu-Nan Liu,1 Pei-Hong Zhao,1 Jun Shao,3 Xiu-Ming Xi4 1Department of Critical Care Medicine, Capital Medical University Electric Teaching Hospital/Beijing Electric Power Hospital, Beijing, People’s Republic of China; 2Department of Emergency, Capital Medical University Electric Teaching Hospital/Beijing Electric Power Hospital, Beijing, People’s Republic of China; 3Department of Critical Care Medicine, Subei People’s Hospital of Jiangsu Province, Yangzhou, People’s Republic of China; 4Department of Critical Care Medicine, Capital Medical University Fuxing Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiu-Ming Xi, Department of Critical Care Medicine, Capital Medical University Fuxing Hospital, No. 20 Fuxingmenwai Street, Xicheng District, Beijing, 100038, People’s Republic of China, Tel +86 13801244610, Email xixuimingxxm@126.com Jun Shao, Department of Critical Care Medicine, Subei People’s Hospital of Jiangsu Province, No. 98 Nantong West Road, Guangling District, Jiangsu, Yangzhou, People’s Republic of China, Tel +86 18051061365, Email shaojunsj_08@126.comObjective: To explore the prognostic outcomes associated with different types of septic cardiomyopathy and analyze the factors that exert an influence on these outcomes.Methods: The data collected within 24 hours of ICU admission included cardiac troponin I (cTnI), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP); SOFA (sequential organ failure assessment) scores, and the proportion of vasopressor use. Based on echocardiographic outcomes, septic cardiomyopathy was categorized into left ventricular (LV) systolic dysfunction, LV diastolic dysfunction, and right ventricular (RV) systolic dysfunction. Differences between the mortality and survival groups, as well as between each cardiomyopathy subgroup and the non-cardiomyopathy group were compared, to explore the influencing factors of cardiomyopathy.Results: A cohort of 184 patients were included in this study, with LV diastolic dysfunction having the highest incidence rate (43.5%). The mortality group had significantly higher SOFA scores, vasopressor use, and cTnI levels compared to the survival group; the survival group had better LV diastolic function than the mortality group (p < 0.05 for all). In contrast to the non-cardiomyopathy group, each subgroup within the cardiomyopathy category exhibited elevated levels of cTnI. The subgroup with left ventricular diastolic dysfunction demonstrated a higher prevalence of advanced age, hypertension, diabetes mellitus, coronary artery disease, and an increased mortality rate; the RV systolic dysfunction subgroup had higher SOFA scores and NT-proBNP levels, and a higher mortality rate (P < 0.05 for all); the LV systolic dysfunction subgroup had a similar mortality rate (P > 0.05).Conclusion: Patients with advanced age, hypertension, diabetes mellitus, or coronary artery disease are more prone to develop LV diastolic dysfunction type of cardiomyopathy; cardiomyopathy subgroups had higher levels of cTnI. The RV systolic dysfunction cardiomyopathy subgroup had higher SOFA scores and NT-proBNP levels. The occurrence of RV systolic dysfunction in patients with sepsis significantly increased the mortality rate.Keywords: cardiac function, echocardiography, influencing factors, prognosis, sepsis, septic cardiomyopathy

Yu-Hsin Huang,1,2,&ast; Shu-I Wu,1,2 Min-Jing Lee,3– 5,&ast; Yi-Lung Chen,6,7,&ast; Yao-Hsu Yang,8,9 Ting-Yu Kuo,8 Tai-Hsin Hung,3,4 Michael E Dewey,10 Robert Stewart,11,12 Vincent Chin-Hung Chen3,4 1Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; 2Department of Psychiatry, MacKay Memorial Hospital, Taipei City, Taiwan; 3Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 4School of Medicine, Chang Gung University, Taoyuan, Taiwan; 5Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 6Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; 7Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; 8Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 9Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 10Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; 11Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; 12South London and Maudsley National Health Services Foundation Trust, London, UK&ast;These authors contributed equally to this workCorrespondence: Vincent Chin-Hung Chen, Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan, Tel +886-5-3621000 ext2303, Fax +886-5-3622188, Email cch1966@gmail.comPurpose: Autism spectrum disorder (ASD) may be associated with increased mortality, but relevant findings have been inconsistent. The modifying effects of gender and intellectual disability on excess mortality in individuals with ASD are underexplored.Patients and Methods: Using Taiwan’s National Health Insurance Research Database and the National Death Registry, this population-based cohort study selected the data of 75,946 patients with ASD (ASD cohort) and 75,946 age group-, gender-, and income-matched (1:1) patients without ASD (non-ASD cohort). Cox proportional hazards models were used to compare mortality rates between the cohorts, and stratified analyses were used to evaluate the influence of gender and intellectual disability on mortality risk.Results: The ASD cohort had higher mortality rates for all causes of death than did the non-ASD cohort (adjusted hazard ratio 1.64, 95% confidence interval 1.54– 1.75). Comorbid intellectual disability was associated with an increased risk of mortality, and this association was stronger in female patients than in male patients. Moreover, when focusing on deaths from natural causes, we found a significantly higher odds ratio for mortality in the ASD population with ID compared to those without ID.Conclusion: ASD is associated with increased mortality, especially among female individuals and those with intellectual disability.Keywords: mortality, autism, population-based cohort study

Tsai-Chun Lai,1– 3 Chiang-Wen Lee,4– 6 Mei-Hsiang Hsu,1 Yu-Chen Chen,1,7 Shu-Rung Lin,8,9 Shu-Wha Lin,10 Tzu-Lin Lee,1 Shin-Yu Lin,11,12 Shu-Hao Hsu,1 Jaw-Shiun Tsai,13,14 Yuh-Lien Chen1 1Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; 2Department of Life Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Republic of China; 3The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung, Taiwan, Republic of China; 4Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County, Taiwan, Republic of China; 5Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County, Taiwan, Republic of China; 6Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan City, Taiwan, Republic of China; 7Department of Medicine, Mackay Medical College, New Taipei City, Taiwan, Republic of China; 8Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Taoyuan, Taiwan, Republic of China; 9Center for Nanotechnology and Center for Biomedical Technology, Chung-Yuan Christian University, Taoyuan, Taiwan, Republic of China; 10Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; 11Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan; 12Department of Obstetrics and Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China; 13Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; 14Center for Complementary and Integrated Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of ChinaCorrespondence: Yuh-Lien Chen, Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen Ai Road, Taipei, 10051, Taiwan, Republic of China, Tel +886-2-23123456-288176, Fax +886-2-33931713, Email ylchenv@ntu.edu.tw Jaw-Shiun Tsai, Department of Family Medicine, National Taiwan University Hospital, No. 1, Changde Street, Taipei, 10048, Taiwan, Republic of China, Tel +886-2-23123456-265147, Fax +886-2-23118674, Email jawshiun@ntu.edu.twPurpose: Particulate matter (PM) 2.5, harmful air pollutants, and diabetes are associated with high morbidity and mortality from cardiovascular disease (CVD). However, the molecular mechanisms underlying the combined effects of PM and diabetes on CVD remain unclear.Methods: Endothelial cells (ECs) treated with high glucose (HG) and PM mimic hyperglycemia and air pollutant exposure in CVD. Endothelial inflammation was evaluated by Western blot and immunofluorescence of ICAM-1 expression and monocyte adhesion. The mechanisms underlying endothelial inflammation were elucidated through MitoSOX Red analysis, JC-1 staining, MitoTracker analysis, and Western blot analysis of mitochondrial fission-related, autophagy-related, and mitophagy-related proteins. Furthermore. nanocurcumin (NCur) pretreatment was used to test if it has a protective effect.Results: ECs under co-exposure to HG and PM increased ICAM-1 expression and monocyte adhesion, whereas NCur pretreatment attenuated these changes and improved endothelial inflammation. PM exposure increased mitochondrial ROS levels, worsened mitochondrial membrane potential, promoted mitochondrial fission, induced mitophagy, and aggravated inflammation in HG-treated ECs, while NCur reversed these changes. Also, HG and PM-induced endothelial inflammation is through the JNK signaling pathway and miR-221/222 specifically targeting ICAM-1 and BNIP3. PM exposure also aggravated mitochondrial ROS levels, mitochondrial fission, mitophagy, and endothelial inflammation in STZ-induced hyperglycemic mice, whereas NCur attenuated these changes.Conclusion: This study elucidated the mechanisms underlying HG and PM-induced endothelial inflammation in vitro and in vivo. HG and PM treatment increased mitochondrial ROS, mitochondrial fission, and mitophagy in ECs, whereas NCur reversed these conditions. In addition, miR-221/222 plays a role in the amelioration of endothelial inflammation through targeting Bnip3 and ICAM-1, and NCur pretreatment can modulate miR-221/222 levels. Therefore, NCur may be a promising approach to intervene in diabetes and air pollution-induced CVD.Keywords: particulate matter, high glucose, mitochondrial fission, endothelial inflammation, miR-221/222, nanocurcumin

Yi-Chun Liu,1– 4 Yin-To Liao,5,6 Vincent Chin-Hung Chen,7,8,&ast; Yi-Lung Chen3,9,&ast; 1Department of Psychiatry, Changhua Christian Children’s Hospital, Changhua, 500, Taiwan; 2Department of Psychiatry, Changhua Christian Hospital, Changhua, 500, Taiwan; 3Department of Healthcare Administration, Asia University, Taichung, 413, Taiwan; 4Department of Eldercare, Central Taiwan University of Science and Technology, Taichung, Taiwan; 5Department of Psychiatry, China Medical University Hospital, Taichung, 404, Taiwan; 6China Medical University, Taichung, 406, Taiwan; 7School of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 8Department of Psychiatry, Chiayi Chang Gung Memorial Hospital, Chiayi, 613, Taiwan; 9Department of Psychology, Asia University, Taichung, 413, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yi-Lung Chen, Department of Healthcare Administration, Asia University, No. 500, Lioufeng Road, Wufeng, Taichung, 41354, Taiwan, Tel +886-4-23323456 (ext. 20106), Fax +886-4-2331669, Email elong@asia.edu.twObjective: Our study aimed to determine whether mothers with bipolar disorder, major depressive disorder, schizophrenia, or schizoaffective disorder affected the risk of type 1 diabetes (T1D) in their offspring.Methods: We conducted a nationwide cohort study by using data from Taiwan’s National Health Insurance Research Database and the Maternal and Child Health Database from 2004 to 2018. A total of 2,556,640 mother-child pairs were identified. Cox proportional hazards models were used to compare the risk of T1D between children born to mothers with mood disorders and schizophrenia and those without.Results: No significant difference in risk of T1D was observed between the offspring of mothers with major psychiatric disorders and those without (adjusted hazard ratio (aHR) of 0.86 with a 95% confidence interval (CI) of 0.58– 1.24). In subgroup analysis, we found an aHR of 1.81 with a 95% CI of 0.83– 3.82 in the maternal bipolar disorder on the risk of T1D in offspring and an aHR of 0.87 (95% CI: 0.59– 1.25) in maternal major depressive disorder. In the schizophrenia/schizoaffective disorder group, aHR cannot be obtained due to lesser than three events in the analysis.Conclusion: The risk of T1D in offspring of mothers with mood disorders and schizophrenia was not significant. However, children born to mothers with bipolar disorder may have a tendency to develop T1D. The relationship between maternal psychiatric disorders and the risk of T1D in offspring warrants further investigation in studies with longer follow-up periods.Keywords: type 1 diabetes mellitus, schizophrenia, major depressive disorder, bipolar disorder

Han-Kun Chen,1 Yi-Ling Chen,2 Chih-Yang Wang,3,4 Wei-Pang Chung,5,6 Jung-Hua Fang,7 Ming-Derg Lai,8,9 Hui-Ping Hsu10 1Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 3PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; 4Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; 5Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 70403, Taiwan; 6Center of Applied Nanomedicine, National Cheng Kung University, Tainan, Taiwan; 7Laboratory Animal Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan; 9Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 10Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanCorrespondence: Hui-Ping Hsu, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan City, 704, Taiwan, Tel +886-6-2353535, ext 5272, Fax +886-6-2766676, Email hphsu@mail.ncku.edu.twBackground: Resistance to standard chemotherapy is a critical problem for breast cancer patients. The ATP-binding cassette (ABC) superfamily transporters actively pump out drugs and play an important role in chemoresistance. ABCB1 (ABC subfamily B, member 1, also named as multidrug resistance protein 1, MDR1) and suppressive myeloid-derived suppressor cells (MDSCs) potentially involve in chemoresistance of breast cancer. The relationship between ABCB1 and immune genes in breast cancer has not been widely studied.Methods: Microarray and RNA sequencing data were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma in Genomic Data Commons Data Portal and Gene Expression Omnibus database. A patient-derived xenograft (PDX) model of HER2+ breast cancer was established to investigate the association between ABCB1 and immune genes in breast cancer.Results: Expression of ABCB1 increased in doxorubicin-selected MCF-7/ADR cells. High expression of ABCB1 mRNA is correlated with lymph-node metastasis and worse overall survival in patients with breast cancer. ABCB1 is positively correlated with IL6, CSF1, CSF3, and PTGS2. In the HER2+ stage IIA breast cancer PDX model, both doxorubicin and paclitaxel suppressed growth of P2 tumors. IL6, CSF1, CSF3, and PTGS2 expression were suppressed by paclitaxel but not doxorubicin. Intrasplenic MDSCs, including CD11b+Ly6G+ and CD11b+Ly6C+ cells, were more abundant than intratumor MDSCs in PDX-carrying nude mice. Clinically, the patient developed cancer recurrence after adjuvant chemotherapy with doxorubicin-based regimen and was well controlled after paclitaxel-trastuzumab combined therapy.Conclusion: ABCB1 was a poor predictor of HER2+ LN– breast cancer. Regulation of immune genes by ABCB1 contributed to cancer recurrence and treatment effect. The PDX model was suitable for investigation the expression of target genes and expansion of immune cells.Keywords: breast cancer, ABC transporters, ABCB1, myeloid-derived suppressor cells, patient-derived xenograft

Yu-Syuan Wei,1 Yu-Liang Chen,2 Wei-Yun Li,1 Ya-Yi Yang,3 Sung-Jan Lin,4– 6 Ching-Ho Wu,7 Jiue-In Yang,8 Tse-En Wang,1 Jiashing Yu,2 Pei-Shiue Tsai1,3,4 1Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 2Department of Chemical Engineering, College of Engineering, National Taiwan University, Taipei, 106, Taiwan; 3Department of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 4Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 10617, Taiwan; 5Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, 10051, Taiwan; 6Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, 10002, Taiwan; 7Graduate Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 8Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, TaiwanCorrespondence: Jiashing Yu, Department of Chemical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Daan District, Taipei, 10617, Taiwan, Tel +886 2 33669477, Email jiayu@ntu.edu.tw Pei-Shiue Tsai, Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Daan District, Taipei, 10617, Taiwan, Tel +886 2 33661290, Fax +886 2 23661475, Email psjasontsai@ntu.edu.twIntroduction: Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology.Methods: We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks.Results: We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte.Discussion: Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.Keywords: nanomedicine, antioxidant, cisplatin, reproduction, DNA repair, polyphenol

Nian-Fang Lu,1 Jun Shao,2 Hong-Xia Niu,3 Wen-Yong Han,4 Ya-Lei Chen,1 An-Qi Liu,1 Hu-Nan Liu,1 Xiu-Ming Xi5 1Department of Critical Care Medicine, Capital Medical University Electric Teaching Hospital/Beijing Electric Power Hospital, Beijing, 100073, People’s Republic of China; 2Department of Critical Care Medicine, Subei People’s Hospital of Jiangsu Province, Yangzhou, Jiangsu, 225001, People’s Republic of China; 3Department of Emergency, Capital medical university electric teaching hospital/Beijing Electric Power Hospital, Beijing, 100073, People’s Republic of China; 4Department of Anesthesiology, Capital Medical University Electric Teaching Hospital/Beijing Electric Power Hospital, Beijing, 100073, People’s Republic of China; 5Department of Critical Care Medicine, Capital Medical University Fuxing Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiu-Ming Xi, Department of Critical Care Medicine, Capital Medical University Fuxing Hospital, A 20, Fuxingmenwai Street, Xicheng District, Beijing, People’s Republic of China, Tel +86 010 13801244610, Email xixuimingxxm@126.comObjective: To analyze the epidemiological data of patients with septic cardiomyopathy and investigate the relationship between ultrasonic parameters and prognosis of patients with sepsis.Methods: In this study, we enrolled patients with sepsis who were treated at the Department of Critical Care Medicine in the Beijing Electric Power Hospital (No.1 Taipingqiao Xili, Fengtai District, Beijing) from January 2020 to June 2022. All patients received standardized treatment. Their general medical status and 28-day prognosis were recorded. Transthoracic echocardiography was performed within 24 hours after admission. We compared the ultrasound indexes between the mortality group and the survival group at the end of 28 days. We included parameters with significant difference in the logistic regression model to identify the independent risk factors for prognosis and evaluated their predictive value using receiver operating characteristic (ROC) curve.Results: We included 100 patients with sepsis in this study; the mortality rate was 33% and the prevalence rate of septic cardiomyopathy was 49%. The peak e’ velocity and right ventricular systolic tricuspid annulus velocity (RV-Sm) of the survival group were significantly higher than those of the mortality group (P < 0.05). Results of logistic regression analysis showed that the peak e’ velocity and RV-Sm were independent risk factors for prognosis. The area under curve of the peak e’ velocity and the RV-Sm was 0.657 and 0.668, respectively (P < 0.05).Conclusion: The prevalence rate of septic cardiomyopathy in septic patients is high. In this study, we found that the peak e’ velocity and right ventricular systolic tricuspid annulus velocity were important predictors of short-term prognosis.Keywords: peak e’ velocity by tissue Doppler imaging, prognosis, right ventricular systolic tricuspid annulus velocity, septic cardiomyopathy

Wen-Zhao Luo,1,2 Xian Li,2 Xiu-Xia Wu,2 Yi-Wan Shang,1,3 Dan-Hua Meng,1,3 Yu-Long Chen,1,3 Qin-Sheng Zhang2 1School of Basic Medicine (Zhongjing School), Henan University of Chinese Medicine, Zhengzhou, Henan Province, 45000, People’s Republic of China; 2Department of Hepatobiliary and Spleen Stomach, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province, 450000, People’s Republic of China; 3Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan Province, 45000, People’s Republic of ChinaCorrespondence: Yu-Long Chen, School of Basic Medicine (Zhongjing School), Henan University of Chinese Medicine, No. 156 East Jinshui Road, Jinshui District, Zhengzhou, Henan Province, 45000, People’s Republic of China, Email chenyulong1977@163.com Qin-Sheng Zhang, Henan Province Hospital of Traditional Chinese Medicine, Department of Hepatobiliary and Spleen Stomach, No. 6 Dongfeng Road, Jinshui District, Zhengzhou, Henan Province, 450000, People’s Republic of China, Email zhangqinsheng0319@163.comBackground: Gastric cancer is the second most common cause of cancer death worldwide with poor overall prognosis. It is important to study the molecular mechanism of stomach adenocarcinoma (STAD). MAGED4B, a member of the melanoma antigen gene (MAGE) family, is highly expressed in many tumor cells and is associated with tumor progression. Its prognostic value in and the function of the encoded protein are still unclear.Methods: The data of 415 STAD tissues was retrieved from TCGA database, and the expression level of MAGED4B mRNA was evaluated. The correlation between the expression of MAGED4B mRNA and the progression free survival (PFS) time of STAD patients was evaluated by Kaplan Meier analysis. The STAD cell lines with overexpressed and silent MAGED4B were constructed, and the effects of MAGED4B on the viability, migration and proliferation were evaluated by the CCK-8, scratch test and EDU test. The flow cytometry was used to detect apoptosis with overexpressed and silent MAGED4B under the cisplatin treatment, and WB was used to detect the expressions of related proteins, such as TNF-α.Results: The expression level of MAGED4B mRNA in the STAD tissues was higher than that in the normal tissues, and its high expression was related to poor PFS. The overexpression of MAGED4B in the STAD cell lines can promote the vitality, motility and proliferation of the STAD cells, while the silencing of MAGED4B can inhibit the above three cell functions of the STAD cells. The overexpression of MAGED4B can reduce the cisplatin induced apoptosis and increase the cisplatin IC50; the silencing of MAGED4B can promote the cisplatin induced apoptosis and reduce the cisplatin IC50. The overexpression of MAGED4B reduced the protein levels of TRIM27 and TNF- α.Conclusion: MAGED4B could be a valuable prognostic biomarker and a therapeutic target for gastric adenocarcinoma of great interest.Keywords: stomach adenocarcinoma, MAGED4B, prognosis, biomarkers

Yu-Ling Chen,1– 3,&ast; Yu-Dan Liang,4,&ast; Kai-Feng Guo,2 Zhen Huang,2 Wen-Qi Feng3 1Rehabilitation Department of the Panyu Central Hospital, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Rehabilitation Department of the Panyu Central Hospital, Guangzhou, People’s Republic of China; 3Department of Acupuncture and Moxibustion of the YiBin Hospital of Traditional Chinese Medicine, YiBin, People’s Republic of China; 4Department of Acupuncture and Rehabilitation, the Affiliated Jiangmen Traditional Chinese Medicine Hospital of Jinan University, Jiangmen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen Huang, Rehabilitation Department of the Panyu Central Hospital, No. 8 Fuyu Road, Qiaonan District, Guangzhou, 511400, People’s Republic of China, Tel +86 18922238059, Email Mishz@126.com Wen-Qi Feng, Department of Acupuncture and Moxibustion of the YiBin Hospital of Traditional Chinese Medicine, No. 2 Dawan Road, Nanan District, YiBin, 644000, People’s Republic of China, Tel +86 13629031868, Email Moonly1981@163.comPurpose: Acupuncture is widely used to relieve shoulder pain. A survey was conducted in order to recognize hotspots and frontiers of acupuncture for shoulder pain from the year 2000– 2022.Methods: The Web of Science Core Collection was used to collect literature related to acupuncture therapy for shoulder pain, which spanned January 2000 to August 2022. The number of publications yearly, countries/institutions, journals, and keywords was analyzed and visualized in shoulder pain with acupuncture therapy by CiteSpace v.5.7.R5.Results: We totally analyzed 214 articles that met the inclusion criteria. The overall trend of publication volume continues to increase. The most productive authors in the field were César Fernández las Peñas and José L Arias-Buría, and the most influential author was Green S. Kyung Hee University and the People’s Republic of China had the highest volume of publications, respectively. The most influential journal is Pain with high citation and impact factor. The hot keywords were “acupuncture”, “shoulder pain”, “dry needling”, “randomized trial”, and “injection”. The research frontier in acupuncture for treating chronic shoulder pain was mainly “mechanism”.Conclusion: Over the last 22 years, the findings of this bibliometric analysis have provided research trends and frontiers in clinical research on acupuncture therapy for patients with shoulder pain, which identifying hot topics and exploring new directions for the future may be helpful to researchers. Studying mechanisms underlying acupuncture therapy for shoulder pain remains a focus of future research.Keywords: acupuncture, shoulder pain, bibliometric analysis, CiteSpace

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

Yu-Chan Yang,1 Ke Zeng,2 Wei Wang,2 Zhi-Gang Gong,1 Yi-Lei Chen,1 Jian-Ming Cheng,1 Min Zhang,1 Yan-Wen Huang,1 Xin-Bo Men,2 Jian-Wei Wang,2 Songhua Zhan,1 Wen-Li Tan1 1Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Massage, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Songhua Zhan; Wen-Li TanDepartment of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, People’s Republic of China, Email zhansonghua@sina.com; 13764935974@163.comObjective: To investigate the changes of regional homogeneity (Reho) values before and after spinal manipulative therapy (SMT) in patients with chronic low back pain (CLBP) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI).Methods: Patients with CLBP (Group 1, n = 20) and healthy control subjects (Group 2, n = 20) were recruited. The fMRI was performed three times in Group 1 before SMT (time point 1, TP1), after the first SMT (time point 2, TP2), after the sixth SMT (time point 3, TP3), and for one time in Group 2, which received no intervention. The clinical scales were finished in Group 1 every time before fMRI was performed. The Reho values were compared among Group 1 at different time points, and between Group 1 and Group 2. The correlation between Reho values with the statistical differences and the clinical scale scores were calculated.Results: The bilateral precuneus and right mid-frontal gyrus in Group 1 had different Reho values compared with Group 2 at TP1. The Reho values were increased in the left precuneus and decreased in the left superior frontal gyrus in Group 1 at TP2 compared with TP1. The Reho values were increased in the left postcentral gyrus and decreased in the left posterior cingulate cortex and the superior frontal gyrus in Group 1 at TP3 compared with TP1. The ReHo values of the left precuneus in Group 1 at TP1 were negatively correlated with the pain degree at TP1 and TP2 (r = − 0.549, − 0.453; p = 0.012, 0.045). The Reho values of the middle temporal gyrus in Group 1 at TP3 were negatively correlated with the changes of clinical scale scores between TP3 and TP1 (r = 0.454, 0.559; p = 0.044, 0.01).Conclusion: Patients with CLBP showed abnormal brain function activity, which was altered after SMT. The Reho values of the left precuneus could predict the immediate analgesic effect of SMT.Keywords: blood-oxygen-level-dependent functional magnetic resonance imaging, spinal manipulation therapy, chronic low back pain, regional homogeneity

Yi-Lung Chen,1,2 Vincent Chin-Hung Chen,3,4 Michael Gossop5 1Department of Healthcare Administration, Asia University, Taichung, Taiwan; 2Department of Psychology, Asia University, Taichung, Taiwan; 3Department of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 4School of Medicine, Chang Gung University, Taoyuan, Taiwan; 5National Addiction Centre, Institute of Psychiatry, King’s College London, London, UKCorrespondence: Vincent Chin-Hung ChenDepartment of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, Puzi, Chiayi, TaiwanEmail cch1966@gmail.comPurpose: This study aimed to establish the Chen ADHD Scale and to examine its reliability and validity.Patients and Methods: We recruited 114 individuals diagnosed with attention-deficit/hyperactivity disorder (ADHD) and 39 non-ADHD controls aged between 5 and 18 years. Their parents completed the Chen ADHD Scale, Chinese versions of the SNAP-IV, and Strengths and Difficulties Questionnaire (SDQ). We examined the psychometric properties of Chen ADHD Scale, including test–retest reliability, internal consistency, construct validity, convergent and divergent validity.Results: Receiver operating characteristic analysis was performed to calculate the area under the curve (AUC), sensitivity, and specificity of the Chen ADHD Scale for predicting ADHD. The Chen ADHD Scale demonstrated satisfactory test–retest reliability (intraclass correlation = 0.916), internal consistency (alpha = 0.966 to 0.978), a good model fit for a two-factor structure (inattention and hyperactivity-impulsivity) and good convergent and divergent validity with SNAP-IV and SDQ. The AUC of Chen ADHD Scale for predicting ADHD was 0.944. The optimal cut-off value of Chen ADHD Scale with impairment requirement for predicting ADHD was 37 with a sensitivity of 0.87 and a specificity of 0.97.Conclusion: The Chen ADHD Scale is a reliable and valid instrument for screening ADHD symptoms in clinical settings in Taiwan.Keywords: ADHD, scale, reliability, validity, psychometric

Yi-Ju Tsai,1,2 Yueh-Chu Huang,3 Yi-Ling Chen,1 Ya-Wen Hsu,4 Yi-Liang Kuo1 1Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Acupressure Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan; 4School of Community Health Sciences, University of Nevada, Reno, NV, USACorrespondence: Yi-Liang KuoDepartment of Physical Therapy, College of Medicine, National Cheng Kung University, No. 1 Ta-Hsueh Road, Tainan 701, TaiwanTel +886-6-2757575 Ext. 6251Fax +886-6-2370411Email yiliangkuo@mail.ncku.edu.twPurpose: This pilot study aimed to determine the feasibility of hip corrective taping to improve self-reported knee pain and lower extremity joint kinematics in basketball players with patellofemoral pain.Patients and Methods: A single group pre-test and post-test design. Collegiate basketball players with patellofemoral pain were recruited. Three-dimensional hip and knee joint kinematics were measured during two tasks, single-leg squat (SLS) and lay-up jump (LUJ), and each task was conducted under no-taping and taping conditions. Subjective report of pain was compared between no-taping and taping conditions only during SLS.Results: Twelve collegiate basketball players with patellofemoral pain (median age, 22.7 [2.5] years; mean height, 173.8 ± 7.4 cm; mean weight, 72.5 ± 12.8 kg) participated in this study. Compared with no-taping, the use of hip corrective taping significantly increased the hip abduction angle at the instant of the maximal vertical ground reaction force during LUJ (no-taping vs taping: 0.6° ± 6.3° vs 3.3° ± 5.1°, p = 0.029), and also caused a trend of decreased maximal hip internal rotation angle during SLS (no-taping vs taping: 8.0° ± 6.6° vs 4.7° ± 6.9°, p = 0.050). Hip corrective taping also improved self-reported knee pain during SLS (no-taping vs taping: 3.4 ± 1.7 vs 2.6 ± 1.0, p = 0.046).Conclusion: Hip corrective taping may be used as an effective intervention for athletes with patellofemoral pain during basketball-related tasks.Keywords: anterior knee pain, kinesio taping, biomechanics, hip joint

Jia-Yin Yeh,1 Tsai-Yu Hou,1 Wei-Ting Tseng,1 Vincent Chin-Hung Chen,2,3 Yao-Hsu Yang,4,5 Ting-Yu Kuo,4 Jun-Cheng Weng,6,7 Charles Tzu-Chi Lee,8 Yi-Lung Chen,9,10 Min-Jing Lee2,3 1Department of Psychiatry, Chang Gung Memorial Hospital, Kaohsiung Branch, Kaohsiung, Taiwan; 2Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 3School of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 5Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 6Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan; 7Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 8Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan; 9Department of Healthcare Administration, Asia University, Taichung, Taiwan; 10Department of Psychology, Asia University, Taichung, TaiwanCorrespondence: Min-Jing LeeDepartment of Psychiatry, Chang Gung Memorial Hospital, Chiayi, Taiwan, No. 6, W. Sec., Jiapu Road, Puzi City, Chiayi County 613, TaiwanTel +886-5-3621000 ext2303Fax +886-5-3622188Email 8035c@cgmh.org.twPurpose: Literature suggests that attention deficit hyperactivity disorder (ADHD) is associated with a high risk of unintentional injury. However, few studies have focused on whether risk of burn injury is relatively high among patients with ADHD. The aim of this study was to investigate whether ADHD affects the risk of burn injury.Materials and Methods: Individuals aged < 18 years with a current diagnosis of ADHD (N = 52,705) and age-, sex-, and other comorbidity-matched controls were selected from Taiwan’s National Health Insurance Research Database for the period of January 1996 to December 2013. Burn injury was identified in both groups, and risk was evaluated using Cox proportional hazards models. We also explored the effects of age and sex on the association.Results: We determined that patients with ADHD had an increased probability of burn injury compared with the control group (ADHD vs controls, 4.6% vs 2.6%; adjusted hazard ratio [aHR] = 1.78; 95% confidence interval [CI] = 1.66– 1.90). The effect of ADHD on burn injury was more prominent among those aged < 6 years (aHR = 1.96; 95% CI = 1.75– 2.20) relative to those aged ≥ 6 years (aHR = 1.69; 95% CI = 1.56– 1.83). Both sexes had similar risk profiles.Conclusion: The study findings contribute to the increasing body of evidence that ADHD is associated with proneness to burn injury, particularly in children aged < 6 years.Keywords: ADHD, burn injury, propensity-matched, cohort

Hong-Ming Chen,1,2,* Vincent Chin-Hung Chen,1,2,* Han-Pin Hsiao,1 Yi-Ping Weng,1 Ya-Ting Hsu,1 Jun-Cheng Weng,1,3 Jian-An Su,1,2,4 Yi-Lung Chen5,6 1Department of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan; 4Department of Nursing, Chang Gung Institute of Technology, Taoyuan, Taiwan; 5Department of Healthcare Administration, Asia University, Taichung, Taiwan; 6Department of Psychology, Asia University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Yi-Lung ChenDepartment of Healthcare Administration, Asia University, 500, Lioufeng Road, Wufeng, Taichung 413, TaiwanTel +886 4 2332 3456 Ext 20106Fax +886 4 2331 6699Email elong@asia.edu.twJian-An SuDepartment of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, No. 6 West Sec., Chia-Pu Road, Puzi City, Chiayi 613, TaiwanTel +886 5 362 1000 Ext 2855Fax +886 5 362 3002Email jian.7715@gmail.comPurpose: Although post-traumatic growth (PTG) and post-traumatic stress symptoms (PTSS) might develop and coexist after a major trauma, few studies have simultaneously examined them in patients with breast cancer. This study investigated the correlation between PTG and PTSS and their differential correlates in patients with breast cancer.Patients and methods: Overall, 145 patients with breast cancer were recruited. PTG and PTSS were assessed using the PTG inventory and the Chinese version of startle, physiological arousal, anger, and numbness, respectively. We investigated the effects of demographics, chemotherapy, depression, family support, alexithymia, and anxiety symptoms on PTG and PTSS. Multivariate linear regression analyses were performed to select the independent correlates of PTSS and PTG.Result: An association was observed between PTG and PTSS (r = 0.21). Based on multiple regression models, the common correlate of PTG (β = 0.271) and PTSS (β = 0.212) was anxiety symptoms. Differential independent correlates were years of education (β = 0.272), receiving chemotherapy (β = 0.248), and family support (β = 0.259) for PTG, and chronic pain (β = 0.316) and poor cognition (β = −0.350) for PTSS.Conclusion: Differential correlates were observed for PTG and PTSS in patients with breast cancer. Possible mechanisms and relationships between PTG and PTSS were discussed.Keywords: post-traumatic stress symptoms, post-traumatic growth, breast cancer, chemotherapy, family support

Yu-Min Yeh,1,2 Chun-Hui Lee,2 Shang-Hung Chen,2,3 Chung-Ta Lee,4 Yi-Lin Chen,4 Bo-Wen Lin,5 Shao-Chieh Lin,5 Ren-Hao Chan,5 Jenq-Chang Lee,5 Meng-Ru Shen,6,7 Peng-Chan Lin21Graduate Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 2Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 3National Institute of Cancer Research, National Health Research Institutes, Hsinchu, Taiwan; 4Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 5Division of Colorectal Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 6Department of Pharmacology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 7Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, TaiwanCorrespondence: Peng-Chan LinDepartment of Internal Medicine, National Cheng Kung University Hospital, No. 138, Sheng-Li Road, Tainan 704, TaiwanTel +886 6 235 3535, ext. 4620Email pengchanlin@gmail.comPurpose: Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic target in colorectal cancer (CRC). Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been used to determine HER2-positive CRCs; however, the clinical utility of next-generation sequencing (NGS)-based techniques for determining HER2 status in CRC has been limited. Here, we detail our experience regarding the assessment of HER2 alterations in a CRC cohort.Materials and methods: We prospectively enrolled 73 CRC patients who underwent surgery and received adjuvant oxaliplatin treatment. We then examined HER2 alterations using the Oncomine Comprehensive Assay version 1, as well as clinical outcomes, in this cohort.Results: Using the NGS-based assay, HER2 copy number gains in 12 of 73 CRCs were determined to range from 2.74 to 92.62. Of these 12 tumors, 6 had HER2 high-level copy number gain (92.6, 57.9, 57.0, 52.0, 35.2, and 8.42) and were all defined as HER2-positive CRC using HERACLES Diagnostic Criteria. Nevertheless, other 6 patients with low-level copy number gain (ranging from 2.74 to 3.04) and the remaining 61 patients without increase in HER2 copy number were all HER2-negative. Among the 6 HER2-positive CRCs, KRAS and PIK3CA mutations were detected in 1 (17%; G13D) and 2 (33.3%; 1 Q546R and 1 H1047R) patients, respectively. Moreover, 2 of the 6 (33.3%) HER2-positive patients had recurrent disease, while one patient had a partial response after anti-HER2 therapy.Conclusion: NGS-based tools could assist in the simultaneous detection of HER2 and other genomic alterations in patients with CRC. Only CRCs with HER2 high-level copy number gain were HER2-postive by current diagnostic criteria.Keywords: HER2, colorectal cancer, next generation sequencing, PIK3CA

Yan Lei Chen,1 Weirong Joshua Sng,2 De Yun Wang,2 Xue Yan Wang11Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Otolaryngology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeBackground: Several studies have shown that the use of antibiotics early in life significantly increases the risk of asthma in children. It is unclear whether antibiotics are more commonly used in patients with allergy-related diseases.Methods: A multistage, clustered and random sampling with a field-interviewer-administrated survey study was performed to investigate if there was multiple use of antibiotics (MUA) in patients with allergic rhinitis (AR), conjunctivitis, chronic urticaria (CU), and asthma in the grasslands of northern China. MUA was defined as antibiotic usage for at least 3 days and for more than 3 times a year in the past 2 years.Results: A total of 5,787 subjects completed the study, with 1,079 subjects (18.6%) identified as MUA. MUA was more common in patients with AR (23.7% vs 16.2%, P

Dong-Ping Li,1,* Ying-Ling Chen,1,* Hong-Yue Jiang,1,* Yun Chen,1 Xiao-Qing Zeng,1 Li-Li Xu,1 Yang Ye,2 Chang-Qiang Ke,2 Ge Lin,3 Ji-Yao Wang,1,4 Hong Gao1,41Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2State Key Laboratory of Drug Research & Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong, People’s Republic of China; 3School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR; 4Evidance-based Medicine Center of Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this work Purpose: To investigate the mitochondria-related mechanism of Gynura segetum (GS)-induced apoptosis and the protective effect of phosphocreatine (PCr), a mitochondrial respiration regulator.Methods: First, the mechanism was explored in human hepatocyte cell line. The mitochondrial oxidative stress was determined by fluorescence assay. The level of sirtuin 3 (SIRT3), acetylated superoxide dismutase 2 (Ac-SOD2), SOD2, and apoptosis were detected by Western blotting. Mito-TEMPO and cell lines of viral vector-mediated overexpression of SIRT3 and SIRT3H248Y, were used to further verify the mechanism of GS-induced apoptosis. GS-induced liver injury mice models were built by GS through intragastric administration and interfered by PCr through intraperitoneal injection. A total of 30 C57BL/6J mice were assigned to 5 groups and treated with either saline, PCr (100 mg/kg), GS (30 g/kg), or PCr (50 or 100 mg/kg)+GS (30 g/kg). Liver hematoxylin and eosin (HE) staining, immunohistochemical analysis, and blood biochemical evaluation were performed.Results: GS induced hepatocyte apoptosis and elevated levels of mitochondrial ROS in L-02 cells. The expression of SIRT3 was decreased. Downregulation of SIRT3 was associated with increased levels of Ac-SOD2, which is the inactivated enzymatic form of SOD2. Conversely, when overexpressing SIRT3 in GS-treated cells, SOD2 activity was restored, and mitochondrial ROS levels and hepatocyte apoptosis declined. Upon administration of PCr to GS-treated cells, they exhibited a significant upregulation of SIRT3 and were protected against apoptosis. In animal experiments, serum ALT level and mitochondrial ROS of the mice treated with GS and 50 mg/kg PCr were significantly attenuated compared with only GS treated. The changes in SIRT3 expression were also consistent with the in vitro results. In addition, immunohistochemical analysis of the mouse liver showed that Ac-SOD2 was decreased in the PCr and GS co-treated group compared with GS treated group.Conclusion: GS caused liver injury by dysregulating mitochondrial ROS generation via a SIRT3-SOD2 pathway. PCr is a potential agent to treat GS-induced liver injury by mitochondrial protection.Keywords: Gynura segetum, apoptosis, mitochondrial, ROS, SIRT3, phosphocreatine

Xi Lin,1 Cai Chang,2,3 Changjun Wu,4 Qin Chen,5 Yulan Peng,6 Baoming Luo,7 Lina Tang,8 Jing Li,9 Jihui Zheng,10 Ruhai Zhou,11 Guanghe Cui,12 Ao Li,13 Xuemei Wang,14 Linxue Qian,15 Jianxing Zhang,16 Chaoyang Wen,17 Joel Gay,18 Huili Zhang,18 Anhua Li,1 Yaling Chen2,3 1State Key Laboratory of Oncology in Southern China, Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China; 2Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China; 4Department of Ultrasound, First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China; 5Department of Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu 610072, P. R. China; 6Department of Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, P. R. China; 7Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510235, P. R. China; 8Department of Ultrasound, Fujian Provincial Cancer Hospital, Fuzhou 350014, P. R. China; 9Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, P. R. China; 10Department of Ultrasound, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, P. R. China; 11Department of Ultrasound, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, P. R. China; 12Department of Ultrasound, Binzhou Medical University Hospital, Binzhou 256603, P. R. China; 13Department of Ultrasound, Jiangsu Province Hospital, Nanjing 210029, P. R. China; 14Department of Ultrasound, The First Hospital of China Medical University, Shenyang 110001, P. R. China; 15Department of Ultrasound, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, P. R. China; 16Department of Ultrasound, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, P. R. China; 17Department of Ultrasound, First Affiliated Hospital of PLA General Hospital, Beijing 100037, P. R. China; 18Supersonic Imagine, Aix-en-Provence, France Purpose: This study aimed to investigate the value of shear wave elastography (SWE) for characterization of breast masses in a Chinese population. Patients and methods: Two thousand two hundred seventy-three women consented to be prospectively enrolled for the characterization of breast masses with ultrasound and SWE. Breast masses were known from symptoms, palpability, and/or previous imaging screening with mammography and/or ultrasound. Correlation of SWE qualitative and quantitative features with malignancy risk and impact on diagnostic performance of combining SWE features were assessed, and the Breast Imaging Reporting and Data System (BI-RADS) scoring was calculated using histopathology as reference. Results: Data of 2,262 masses (median size: 13 mm; range: 1.3–50) from 2,262 patients (median age: 43 years; range: 18–91) were investigated, of which 752 (33.3%) were malignant. Sensitivity and specificity of BI-RADS diagnosis were 97.5% (733/752) and 54.8% (827/1,510), respectively. By logistic regression, the combination of maximum elasticity (Emax) measurements with BI-RADS assessments increased the area under the receiver operating characteristic curve from 0.908 (95% CI: 0.896–0.920) to 0.954 (95% CI: 0.944–0.962). Using Emax of 30 kPa or lower to selectively downgrade BI-RADS 4a masses to follow-up, and Emax of 160 kPa or higher to selectively upgrade BI-RADS 3 lesions to biopsy, specificity significantly increased from 54.8% (827/1,510) to 66.1% (998/1,510) (P

Yu-Ling Chen,1,2 Yu-Cheng Pei3–6 1Department of Music, Southwestern Oklahoma State University, Weatherford, OK, USA; 2Division of Music Education and Music Therapy, University of Kansas, Lawrence, KS, USA; 3Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Center of Vascularized Tissue Allograft, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5School of Medicine, Chang Gung University, Taoyuan, Taiwan; 6Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan Background/aims: Dual-task training may improve dual-task gait performance, balance, and cognition in older adults with and without cognitive impairment. Although music has been widely utilized in dementia management, there are no existing protocols for music-based dual-task training. This randomized controlled study developed a Musical Dual-Task Training (MDTT) protocol that patients with dementia can use to practice walking and making music simultaneously, to enhance attention control in patients during dual-tasking.Methods: Twenty-eight adults diagnosed with mild-to-moderate dementia were assigned to the MDTT (n=15) or control groups (n=13). The MDTT group received MDTT, while the control group participated in non-musical cognitive and walking activities. The effects of MDTT were evaluated through the primary outcome of attention control, and secondary outcomes of dual-task performance, balance, falls efficacy, and agitation.Results: The MDTT group showed a significant improvement in attention control, while the control group did not (P

Jianwei Duan,1,* Chao Liu,1,* Xiaoyu Liang,1 Xuanling Li,1 Youlu Chen,1 Zuoguan Chen,2 Xiaoli Wang,1 Deling Kong,1,3 Yongjun Li,2 Jing Yang1 1Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China; 2Department of Vascular Surgery, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; 3Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, China *These authors contributed equally to this work Background: To address the issue of delivery of proteins, a six-arm copolymer, six-arm poly(ε-caprolactone)–poly(ethylene glycol) (6S-PCL-PEG), was synthesized by a simple two-step reaction. Thereafter, the application of 6S-PCL-PEG as a protein carrier was evaluated. Materials and methods: A six-arm copolymer, six-arm poly(ε-caprolactone) (6S-PCL), was synthesized by ring-opening polymerization, with stannous octoate as a catalyst and inositol as an initiator. Then, poly(ethylene glycol) (PEG) was linked with 6S-PCL by oxalyl chloride to obtain 6S-PCL-PEG. Hydrogen-1 nuclear magnetic resonance spectrum, Fourier-transform infrared spectroscopy, and gel-permeation chromatography were conducted to identify the structure of 6S-PCL-PEG. The biocompatibility of the 6S-PCL-PEG was evaluated by a cell counting kit-8 assay. Polymeric nanoparticles (NPs) were prepared by a water-in-oil-in-water double emulsion (W1/O/W2) solvent evaporation method. The size distribution and zeta potential of NPs were determined by dynamic light scattering. Transmission electron microscopy was used to observe the morphology of NPs. Drug-loading capacity, encapsulation efficiency, and the release behavior of ovalbumin (OVA)-loading NPs were tested by the bicinchoninic acid assay kit. The stability and activity of OVA released from NPs were detected and the uptake of NPs was evaluated by NIH-3T3 cells. Results: All results indicated the successful synthesis of amphiphilic copolymer 6S-PCL-PEG, which possessed excellent biocompatibility and could formulate NPs easily. High drug-loading capacity and encapsulation efficiency of protein NPs were observed. In vitro, OVA was released slowly and the bioactivity of OVA was maintained for over 28 days. Conclusion: 6S-PCL-PEG NPs prepared in this study show promising potential for use as a protein carrier. Keywords: six-arm PCL-PEG, copolymer synthesis, protein carrier, sustained release

Zhongxue Yuan,1 Rui Xu,1 Jinquan Li,1 Yueli Chen,1 Binghui Wu,2 Jianghua Feng,1 Zhong Chen1 1Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian, China; 2State Key Laboratory for Physical Chemistry of Solid Surface, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, China Background: Core–shell-structured nanoparticles (NPs) have attracted much scientific attention due to their promising potential in biomedical fields in recent years. However, their underlying mechanisms of action and potential adverse effects following administration remain unknown. Methods: In the present study, a 1H nuclear magnetic resonance-based metabonomic strategy was applied to investigate the metabolic consequences in rats following the intravenous administration of parent NPs of core–shell-structured nanoparticles, Fe3O4@SiO2-NH2 (Fe@Si) NPs. Results: Alterations reflected in plasma and urinary metabonomes indicated that Fe@Si NPs induced metabolic perturbation in choline, ketone-body, and amino-acid metabolism besides the common metabolic disorders in tricarboxylic acid cycle, lipids, and glycogen metabolism often induced by the exogenous agents. Additionally, intestinal flora metabolism and the urea cycle were also influenced by Fe@Si NP exposure. Time-dependent biological effects revealed obvious metabolic regression, dose-dependent biological effects implied different biochemical mechanisms between low- and high-dose Fe@Si NPs, and size-dependent biological effects provided potential windows for size optimization. Conclusion: Nuclear magnetic resonance-based metabonomic analysis helps in understanding the biological mechanisms of Fe@Si NPs, provides an identifiable ground for the selection of view windows, and further serves the clinical translation of Fe@Si NP-derived and -modified bioprobes or bioagents. Keywords: core–shell structure, biomedical nanoparticles, metabonomics, NMR, biological effects

Geng Dou,1 Yu Zhang,1 Chunlin Zong,2 Yuanli Chen,2 Yuxuan Guo,2 Lei Tian2 1The First Brigade of Students, 2State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Cranio-facial Trauma and Orthognathic Surgery, School of Stomatology, The Fourth Military Medical University, Xi’an, People’s Republic of China Purpose: The present study aimed to evaluate the feasibility, accuracy, and clinical effect of intraoperative navigation for resection of elongated styloid process (ESP) in Eagle’s syndrome.Patients and methods: Twelve patients with Eagle’s syndrome with clinically and radiologically established diagnoses of ESP were included in this study. Preoperatively, all patients accepted three-dimensional computed tomography scan, and their skulls’ digital imaging and communications in medicine data were inputed into the navigation system workstation to make a virtual surgical plan in advance. During surgery, the intraoperative navigation was performed to excise the ESP accurately for both intraoral (without tonsillectomy) and extraoral approaches following the virtual plan. Postoperatively, the amount of bleeding, duration of operation and hospitalization, and the length of resected styloid process (SP) were measured and compared with those cases that had traditional styloidectomy without the help of surgical navigation (SN). A simple visual analog scale questionnaire was also used to assess patients’ satisfaction and the surgery effect after 3 months.Results: In total, 17 SPs from 12 patients were precisely resected by intraoral parapharyngeal approach and small cervical approach with the aid of SN. No severe complications occurred in any patients. The length of resected SPs was 21.93±14.26 mm. The average amount of bleeding and duration of operation were 22.50±8.54 mL and 40.35±11.81 minutes, respectively, which were all less than with traditional styloidectomy. The visual analog scale analysis showed that the discomfort in all patients was relieved, while ten patients’ symptoms were improved greatly, and two patients had some improvement.Conclusion: The higher accuracy of surgery, lesser amount of bleeding, decreased duration of surgery and hospitalization, absence of complications, and improved subjective symptoms indicated that SN is an effective and minimally invasive surgical procedure suitable for resection of ESP for treating Eagle’s syndrome. Keywords: elongation of styloid process, intraoperative navigation, oral and maxillofacial surgery, computer-aided surgery

Yi-Ping Fang,1 Chih-Hung Chuang,2 Pao-Chu Wu,1 Yaw-Bin Huang,1 Cherng-Chyi Tzeng,3 Yeh-Long Chen,3 Ya-Ting Liu,1 Yi-Hung Tsai,1 Ming-Jun Tsai4–6 1School of Pharmacy, College of Pharmacy, 2Department of Biomedical and Environment Biology, College of Life Science, 3School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, 4Department of Neurology, China Medical University Hospital, 5School of Medicine, Medical College, China Medical University, Taichung, 6Department of Neurology, China Medical University An-Nan Hospital, Tainan, Taiwan Abstract: Amsacrine analog is a novel chemotherapeutic agent that provides potentially broad antitumor activity when compared to traditional amsacrine. However, the major limitation of amsacrine analog is that it is highly lipophilic, making it nonconductive to intravenous administration. The aim of this study was to utilize solid lipid nanoparticles (SLN) to resolve the delivery problem and to investigate the biodistribution of amsacrine analog-loaded SLN. Physicochemical characterizations of SLN, including particle size, zeta potential, entrapment efficiency, and stability, were evaluated. In vitro release behavior was also measured by the dialysis method. In vivo pharmacokinetics and biodistribution behavior of amsacrine analog were investigated and incorporated with a non invasion in vivo imaging system to confirm the localization of SLN. The results showed that amsacrine analog-loaded SLN was 36.7 nm in particle size, 0.37 in polydispersity index, and 34.5±0.047 mV in zeta potential. More than 99% of amsacrine analog was successfully entrapped in the SLN. There were no significant differences in the physicochemical properties after storage at room temperature (25°C) for 1 month. Amsacrine analog-loaded SLN maintained good stability. An in vitro release study showed that amsacrine analog-loaded SLN sustained a release pattern and followed the zero equation. An in vivo pharmacokinetics study showed that amsacrine analog was rapidly distributed from the central compartment to the tissue compartments after intravenous delivery of amsacrine analog-loaded SLN. The biodistribution behavior demonstrated that amsacrine analog mainly accumulated in the lungs. Noninvasion in vivo imaging system images also confirmed that the drug distribution was predominantly localized in the lungs when IR-780-loaded SLN was used. Keywords: amsacrine analog, solid lipid nanoparticle, pharmacokinetics, biodistribution, water insolubility

Yi-Ping Fang,1 Pao-Chu Wu,2 Yaw-Bin Huang,3 Cherng-Chyi Tzeng,4 Yeh-Long Chen,4 Yu-Han Hung,2 Ming-Jun Tsai,5,6 Yi-Hung Tsai31Department of Biotechnology, Yuanpei University, Hsinchu, Taiwan; 2School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 6School of Medicine, Medical College, China Medical University, Taichung, TaiwanBackground: The synthetic potential chemotherapeutic agent 3-Chloro-4-[(4-methoxyphenyl)amino]furo[2,3-b]quinoline (PK-L4) is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection.Aims: To utilize solid lipid nanoparticles (SLNs) modified with polyethylene glycol (PEG) to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration.Results: The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE%) of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%–64% in the human lung carcinoma cell line (A549), 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7), and 95% in the human breast adenocarcinoma cell line (MDA-MB-231). The amount of PK-L4 released by SLNs with PEG was significantly higher than that from the PK-L4 solution (P < 0.05). After intravenous bolus of the PK-L4-loaded SLNs with PEG, there was a marked significant difference in half-life alpha (0.136 ± 0.046 hours) when compared with the PK-L4 solution (0.078 ± 0.023 hours); also the area under the curve from zero to infinity did not change in plasma when compared to the PK-L4 solution. This demonstrated that PK-L4-loaded SLNs were rapidly distributed from central areas to tissues and exhibited higher accumulation in specific organs. The highest deposition of PK-L4-loaded SLNs with PEG was found in the lung and spine.Conclusion: Sufficient amounts of PK-L4 were entrapped in the SLNs, and the pharmacokinetic behavior of PK-L4-loaded SLNs was established. This formulation successfully resolved the delivery problem, and the drug was localized in particular organs.Keywords: 3-chloro-4-[(4-methoxyphenyl)amino]furo[2,3-b]quinoline, SLNs, solubility, cytotoxicity, biodistribution

Wan-Ju Hsieh,1 Chan-Jung Liang,1 Jen-Jie Chieh,4 Shu-Huei Wang,1 I-Rue Lai,1 Jyh-Horng Chen,2 Fu-Hsiung Chang,3 Wei-Kung Tseng,4–6 Shieh-Yueh Yang,4 Chau-Chung Wu,7 Yuh-Lien Chen11Institute of Anatomy and Cell Biology, College of Medicine, 2Department of Electrical Engineering, 3Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei, Taiwan; 4Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei, Taiwan; 5Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Taipei, Taiwan; 6Department of Medical Imaging and Radiological Sciences, I-Shou University, Taipei, Taiwan; 7Department of Internal Medicine and Primary Care Medicine, National Taiwan University Hospital, Taipei, TaiwanBackground: Active targeting by specific antibodies combined with nanoparticles is a promising technology for cancer imaging and detection by magnetic resonance imaging (MRI). The aim of the present study is to investigate whether the systemic delivery of antivascular endothelial growth factor antibodies conjugating to the surface of functionalized supermagnetic iron oxide nanoparticles (anti-VEGF-NPs) led to target-specific accumulation in the tumor.Methods: The VEGF expression in human colon cancer and in Balb/c mice bearing colon cancers was examined by immunohistochemistry. The distribution of these anti-VEGF-NPs particles or NPs particles were evaluated by MRI at days 1, 2, or 9 after the injection into the jugular vein of Balb/c mice bearing colon cancers. Tumor and normal tissues (liver, spleen, lung, and kidney) were collected and were examined by Prussian blue staining to determine the presence and distribution of NPs in the tissue sections.Results: VEGF is highly expressed in human and mouse colon cancer tissues. MRI showed significant changes in the T*2 signal and T2 relaxation in the anti-VEGF-NP- injected-mice, but not in mice injected with NP alone. Examination of paraffin sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice.Conclusion: These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.Keywords: nanoparticles, vascular endothelial growth factor, colon tumor, magnetic resonance imaging, transmission electron microscopy

Meimei Hao, Yan Zhang, Shuangxing Hou, Yanling Chen, Ming Shi, Gang Zhao, Yanchun Deng Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China Abstract: Hyperhomocysteinemia (HHcy) has been recognized as an independent risk factor for atherosclerotic vascular disease. Here we report a patient who suffered from spinal cord demyelination combined with HHcy. The patient was admitted to our hospital with a diagnosis of acute myelitis. However, hormone therapy was ineffective. Further investigations revealed that he had HHcy and a homozygous mutation of the gene encoding methylenetetrahydrofolate reductase (MTHFR) c.677C>T, which is a key enzyme involved in homocysteine metabolism. In view of these findings, we treated the patient with B vitamins and his symptoms gradually improved. Spinal magnetic resonance imaging performed 3 months after onset showed near recovery of the lesion. To our knowledge, similar reports are rare. Keywords: demyelination, hyperhomocysteinemia, homocysteine, methylenetetrahydrofolate reductase, methylation

EuTe4 is a van der Waals material exhibiting a charge density wave (CDW) with a large thermal hysteresis in the resistivity and CDW gap. In this paper, we systematically study the electronic structure and transport properties of EuTe4 using high-resolution angle-resolved photoemission spectroscopy (ARPES), magnetoresistance (MR) measurements, and scanning tunneling microscopy (STM). We observe a CDW gap of ∼200meV at low temperatures that persists up to 400 K, suggesting that the CDW transition occurs at a much higher temperature. The ARPES intensity near the Fermi level shows large thermal hysteretic behavior, consistent with the resistivity measurement. The hysteresis in the resistivity measurement does not change under a magnetic field up to 7 T, excluding the thermal magnetic hysteretic effect. Instead, the surface topography measured with STM shows surface domains with different CDW trimerization directions, which may be important for the thermal hysteretic behavior. Interestingly, we reveal a large negative MR at low temperatures that can be associated with the canting of magnetically ordered Eu spins. Our results shed light on the understanding of magnetic, transport, and electronic properties of EuTe4.

Crystal geometry can greatly influence the emergent properties of quantum materials. As an example, the kagome lattice is an ideal platform to study the rich interplay between topology, magnetism, and electronic correlation. In this work, combining high-resolution angle-resolved photoemission spectroscopy and ab initio calculation, we systematically investigate the electronic structure of XMn6Sn6 (X=Dy,Tb,Gd,Y) family compounds. We observe the Dirac fermion and the flat band arising from the magnetic kagome lattice of Mn atoms. Interestingly, the flat band locates in the same energy region in all compounds studied, regardless of their different magnetic ground states and 4f electronic configurations. These observations suggest a robust Mn magnetic kagome lattice across the XMn6Sn6 family, thus providing an ideal platform for the search for, and investigation of, new emergent phenomena in magnetic topological materials.

Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS2 with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS2 as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure.

The interplay between topological electronic structure and superconductivity has attracted tremendous research interests recently as they could induce topological superconductivity (TSCs) which may be used to realize topological qubits for quantum computation. Among various TSC candidates, superconducting BaSn3 (Tc∼4.4K) has been predicted to be a topological Dirac semimetal (TDS) hosting two pairs of Dirac points along the Γ-A direction. Here, by combining the use of angle-resolved photoemission spectroscopy and ab initio calculations, we identified the predicted topological Dirac fermions and confirmed the TDS nature of the compound. In addition, we observed surface states connecting the Dirac points. Our observations demonstrate BaSn3 as a superconductor with nontrivial topological electronic structures.

Recently, layered copper chalcogenides Cu2X family (X=S, Se, Te) has attracted tremendous research interests due to their high thermoelectric performance, which is partly due to the superionic behavior of mobile Cu ions, making these compounds "phonon liquids."Here, we systematically investigate the electronic structure and its temperature evolution of the less studied single crystal Cu2-xTe by the combination of angle resolved photoemission spectroscopy (ARPES) and scanning tunneling microscope/spectroscopy (STM/STS) experiments. While the band structure of the Cu2-xTe shows agreement with the calculations, we clearly observe a 2×2 surface reconstruction from both our low temperature ARPES and STM/STS experiments which survives up to room temperature. Interestingly, our low temperature STM experiments further reveal multiple types of reconstruction patterns, which suggests the origin of the surface reconstruction being the distributed deficiency of liquidlike Cu ions. Our findings reveal the electronic structure and impurity level of Cu2Te, which provides knowledge about its thermoelectric properties from the electronic degree of freedom.

Angle-resolved photoemission spectroscopy (ARPES) and torque magnetometry (TM) measurements have been carried out to study the electronic structures of a correlated topological insulator (TI) candidate YbB6. We observed clear surface states on the [001] surface centered at the Γ and M points of the surface Brillouin zone. Interestingly, the fermiology revealed by the quantum oscillation of TM measurements agrees excellently with ARPES measurements. Moreover, the band structures we observed suggest that the band inversion in YbB6 happens between the Yb5d and B2p bands, instead of the Yb5d and Yb4f bands as suggested by previous theoretical investigation, which will help settle the heavy debate regarding the topological nature of samarium/ytterbium hexaborides.

Weyl semimetals are crystalline solids that host emergent relativistic Weyl fermions and have characteristic surface Fermi-arcs in their electronic structure. Weyl semimetals with broken time reversal symmetry are difficult to identify unambiguously. In this work, using angle-resolved photoemission spectroscopy, we visualized the electronic structure of the ferromagnetic crystal Co3Sn2S2 and discovered its characteristic surface Fermi-arcs and linear bulk band dispersions across the Weyl points. These results establish Co3Sn2S2 as a magnetic Weyl semimetal that may serve as a platform for realizing phenomena such as chiral magnetic effects, unusually large anomalous Hall effect and quantum anomalous Hall effect.

Using high-resolution angle-resolved photoemission spectroscopy and ab initio calculation, we have studied the bulk and surface electronic structure of metallic rutile 5d transition metal oxide IrO2 that harbors both edge and corner sharing Ir-O octahedrons. We observe strong modulation of the band structure by spin-orbit coupling (SOC). The measured band structure is well reproduced by our ab initio calculation without band renormalization, suggesting the absence of the SOC-enhanced correlation effect in IrO2. In accordance with the calculation, we visualize two types of Dirac nodal lines (DNLs) protected by mirror symmetry and nonsymmorphic crystal symmetry, respectively. SOC gaps the first type of DNLs, which may contribute largely to the strong spin Hall effect. The second type of DNLs at the edges of Brillouin zone, however, remain intact against SOC. Our results not only provide important insights into the exotic transport properties of IrO2, but also shed light on the understanding of the role of SOC in the iridate family.

The recent discovery of the extreme magnetoresistance (XMR) in the nonmagnetic rare-earth monopnictides LaX (X = P, As, Sb, Bi,), a recently proposed new topological semimetal family, has inspired intensive research effort in the exploration of the correlation between the XMR and their electronic structures. In this work, using angle-resolved photoemission spectroscopy to investigate the three-dimensional band structure of LaBi, we unraveled its topologically nontrivial nature with the observation of multiple topological surface Dirac fermions, as supported by our ab initio calculations. Furthermore, we observed substantial imbalance between the volume of electron and hole pockets, which rules out the electron-hole compensation as the primary cause of the XMR in LaBi.

Topological insulators represent unusual topological quantum states, typically with gapped bulk band structure but gapless surface Dirac fermions protected by time-reversal symmetry. Recently, a distinct kind of topological insulator resulting from nonsymmorphic crystalline symmetry was proposed in the KHgX (X=As, Sb, Bi) compounds. Unlike regular topological crystalline insulators, the nonsymmorphic glide-reflection symmetry in KHgX guarantees the appearance of an exotic surface fermion with hourglass shape dispersion (where two pairs of branches switch their partners) residing on its (010) side surface, contrasting to the usual two-dimensional Dirac fermion form. Here, by using high-resolution angle-resolved photoemission spectroscopy, we systematically investigate the electronic structures of KHgSb on both (001) and (010) surfaces and reveal the unique in-gap surface states on the (010) surface with delicate dispersion consistent with the "hourglass Fermion" recently proposed. Our experiment strongly supports that KHgSb is a nonsymmorphic topological crystalline insulator with hourglass fermions, which serves as an important step to the discovery of unique topological quantum materials and exotic fermions protected by nonsymmorphic crystalline symmetry.

Topological Weyl semimetal (TWS), a new state of quantum matter, has sparked enormous research interest recently. Possessing unique Weyl fermions in the bulk and Fermi arcs on the surface, TWSs offer a rare platform for realizing many exotic physical phenomena. TWSs can be classified into type-I that respect Lorentz symmetry and type-II that do not. Here, we directly visualize the electronic structure of MoTe2, a recently proposed type-II TWS. Using angle-resolved photoemission spectroscopy (ARPES), we unravel the unique surface Fermi arcs, in good agreement with our ab initio calculations that have nontrivial topological nature. Our work not only leads to new understandings of the unusual properties discovered in this family of compounds, but also allows for the further exploration of exotic properties and practical applications of type-II TWSs, as well as the interplay between superconductivity (MoTe2 was discovered to be superconducting recently) and their topological order.

An extreme magnetoresistance (XMR) has recently been observed in several nonmagnetic semimetals. Increasing experimental and theoretical evidence indicates that the XMR can be driven by either topological protection or electron-hole compensation. Here, by investigating the electronic structure of a XMR material, YSb, we present spectroscopic evidence for a special case which lacks topological protection and perfect electron-hole compensation. Further investigations reveal that a cooperative action of a substantial difference between electron and hole mobility and a moderate carrier compensation might contribute to the XMR in YSb.

Topological quantum materials represent a new class of matter with both exotic physical phenomena and novel application potentials. Many Heusler compounds, which exhibit rich emergent properties such as unusual magnetism, superconductivity and heavy fermion behaviour, have been predicted to host non-trivial topological electronic structures. The coexistence of topological order and other unusual properties makes Heusler materials ideal platform to search for new topological quantum phases (such as quantum anomalous Hall insulator and topological superconductor). By carrying out angle-resolved photoemission spectroscopy and ab initio calculations on rare-earth half-Heusler compounds LnPtBi (Ln=Lu, Y), we directly observe the unusual topological surface states on these materials, establishing them as first members with non-trivial topological electronic structure in this class of materials. Moreover, as LnPtBi compounds are non-centrosymmetric superconductors, our discovery further highlights them as promising candidates of topological superconductors.

Topological Weyl semimetals (TWSs) represent a novel state of topological quantum matter which not only possesses Weyl fermions (massless chiral particles that can be viewed as magnetic monopoles in momentum space) in the bulk and unique Fermi arcs generated by topological surface states, but also exhibits appealing physical properties such as extremely large magnetoresistance and ultra-high carrier mobility. Here, by performing angle-resolved photoemission spectroscopy (ARPES) on NbP and TaP, we directly observed their band structures with characteristic Fermi arcs of TWSs. Furthermore, by systematically investigating NbP, TaP and TaAs from the same transition metal monopnictide family, we discovered their Fermiology evolution with spin-orbit coupling (SOC) strength. Our experimental findings not only reveal the mechanism to realize and fine-tune the electronic structures of TWSs, but also provide a rich material base for exploring many exotic physical phenomena (for example, chiral magnetic effects, negative magnetoresistance, and the quantum anomalous Hall effect) and novel future applications.

The level of electronic correlation has been one of the key questions in understanding the nature of superconductivity. Among the iron-based superconductors, the iron chalcogenide family exhibits the strongest electron correlations. To gauge the correlation strength, we performed a systematic angle-resolved photoemission spectroscopy study on the iron chalcogenide series Fe1+ySexTe1-x (0

© 2015 Springer Science+Business Media New York Solid-state processes of bonding 1 mm copper (Cu) wires on Cu substrates and silicon (Si) chips, respectively, were developed. To overcome Cu oxidation issue, the bonding surface on the wire was plated a silver (Ag) layer. An annealing step followed to make the Ag layer much easier to deform and conform to the Cu or Si bonding surfaces. The bonding process was performed at 300 °C with 6.89 MPa. Wire-bond cross sections were studied using optical and electron microscopy, respectively. The images obtained exhibit nearly perfect Ag–Cu bonding interface. For wire-bonds made on Cu substrate, in-plane (shear) pull test measured a breaking of force 20.7–23.7 kg, comparable to the 22.5 kg breaking force of the Cu wire itself. Breaking forces on vertical (peel) pull test are about one-half of in-plane pull test results. For wire-bonds made on Si chip, breaking forces are about 80 % of those made on Cu substrate. Fracture modes were evaluated in details. 90 % of the wire-bonds broke with three modes mixed together: near Cu–Ag plating interface, inside Ag layer, and Ag–Cu bonding interface. Thus, the bonding interface is as strong as other regions of the wire-bond. This solid-state wire bonding process is expected to have valuable applications in high power and high temperature devices and modules where the wire-bonds have to stand alone without protection due to lack of high temperature molding compound and reinforcing materials.

We present ultrahigh resolution angle-resolved photoemission data of the prototypical Kondo lattice system YbRh 2Si 2, using a 7 eV laser photon source. Detailed temperature dependent measurements reveal the development of coherent states, in the form of sharp, weakly dispersing peaks at the lowest energy of single-electron spectra, below a characteristic temperature. The characteristic temperature, obtained from angle-resolved photoemission, is intriguingly of exactly the same scale as the energy and the lifetime of the coherent state. © 2012 American Physical Society.