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Vincent Chin-Hung Chen,1,2 Tsu-Nai Wang,3 Ming-Chia Hsieh,4 Shih-Yong Chou,1 Meng-Chih Lee,5,6 Roger S McIntyre,7 Mong-Liang Lu,8 Yin-To Liao,9,10 Chih-Jung Yeh11,12 1Department of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 4U Come Joint Clinic, Taichung, Taiwan; 5Department of Family Medicine, Taichung Hospital, Taichung, Taiwan; 6College of Management, Chaoyang University of Technology, Taichung, Taiwan; 7University of Toronto, Toronto, ON, Canada; 8Department of Psychiatry, Wan-Fang Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan; 10Department of Psychiatry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 11Institute of Population Health Sciences, National Health Research Institutes, Taipei, Taiwan; 12School of Public Health, Chung Shan Medical University, Taichung, TaiwanCorrespondence: Yin-To Liao, Email je2tezy@yahoo.com.tw Chih-Jung Yeh, School of Public Health, Chung Shan Medical University, No. 110, Section 1, Jianguo N. Road, Taichung, 402, Taiwan, Tel +886-4-24730022x12183, Fax +886-4-23248179, Email alexyeh@csmu.edu.twPurpose: Diabetes mellitus (DM) increases the risk of cardiovascular and all-cause mortality. The coexistence of depression and DM is associated with an increased risk of DM complications and functional morbidity. The independent effect of depression on mortality in patients with DM is unclear, and relevant Asian studies have provided inconsistent results. Accordingly, this study assessed the independent and additive effects of DM and depression on mortality in a nationally representative cohort of older adults in Taiwan over a 10-year observation period.Patients and Methods: A total of 5041 participants aged 50 years or older were observed between 1996 and 2007. We defined depression as a score of ≥ 8 on the 10-item Center for Epidemiologic Studies Depression (CES-D 10) scale. Additionally, we defined participants as having type 2 DM if they had received a diagnosis of type 2 DM from a health-care provider. Cox proportional hazard models were applied to analyze predictors of mortality in depression and DM comorbidity groups.Results: During the 10-year follow-up period, 1637 deaths were documented. After adjustment for potential confounders, the hazard ratios for mortality in participants with both depression and DM, DM only, and depression only were 2.47 (95% confidence interval [CI]: 2.02– 3.03), 1.95 (95% CI: 1.63– 2.32), and 1.23 (95% CI: 1.09– 1.39), respectively.Conclusion: The co-occurrence of depression with DM in Asian adults increased overall mortality rates. Our results indicate that the increased mortality hazard in individuals with DM and depression was independent of sex.Keywords: diabetes mellitus, depression, mortality, cohort

Yu-Hung Fang,1 Meng-Jer Hsieh,2,3 Ming-Szu Hung,1,4,5 Yu-Ching Lin,1,3– 5 Liang-Tseng Kuo,5,6 Mong-Liang Lu,7 Bor-Show Tzang,8– 10 Vincent Chin-Hung Chen5,11 1Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Respiratory Therapy, College of Medicine, Chang Gung University, Chiayi, Taiwan; 3Division of Pulmonary Infection and Critical Care Medicine, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 4Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan; 5Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 6Division of Sports Medicine, Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; 7Department of Psychiatry, Wan Fang Hospital, and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan; 9Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan; 10Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 11Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi, TaiwanCorrespondence: Vincent Chin-Hung ChenDepartment of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, No. 6, W. Sec., Jiapu Road, Puzi City, Chiayi County 61363, Taiwan, Republic of ChinaTel +886-5-3621000 ext. 2315Email cch1966@gmail.comBackground: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) concentrations were reported to decrease in patients with advanced cancer. However, the clinical significance of DHEA and DHEAS concentrations in patients with NSCLC receiving chemotherapy (CT) has not been sufficiently documented.Objective: To evaluate the correlation between mental health and hormone concentrations on patients with advanced non-small-cell lung cancer (NSCLC).Materials and Methods: The present study was a cross-sectional analysis based on a self-reported psychological investigation. Salivary samples were collected from 22 patients with advanced NSCLC after CT and 17 healthy controls. The concentrations of DHEA, DHEAS, and cortisol were analyzed to investigate their associations with the results of self-reported questionnaires on psychological health.Results: Patients with advanced NSCLC exhibited significantly higher Patient Health Questionnaire (PHQ-9) and Startle, Physiological arousal, Anger, and Numbness-Chinese version (SPAN-C) scores, poorer health conditions, lower sleep quality, and more severe fatigue after CT than did healthy controls, and salivary concentrations of DHEA and DHEAS were significantly lower among patients after CT than among controls. DHEAS concentrations were negatively associated with depression scores (PHQ-9, r = − 0.496, P = 0.019) and fatigue scores (Brief Fatigue Inventory-Taiwan, r = − 0.562, P = 0.006).Conclusion: Patients with advanced NSCLC after CT had lower DHEA and DHEAS concentrations than did controls. Lower DHEAS concentrations were associated with higher fatigue and depression scores.Keywords: cancer-related fatigue, chemotherapy, DHEA, DHEAS, lung cancer

Pei-Lun Chung,1 Chien-Wei Huang,2 Min-Jing Lee,1,3 Yao-Hsu Yang,4,5 Ko-Jung Chen,4 Mong-Liang Lu,6 Jun-Cheng Weng,1,7 Vincent Chin-Hung Chen1,3 1Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 2Division of Nephrology, Department of Medicine, School of Medicine, Kaohsiung Veterans General Hospital, and National Yang-Ming University, 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 Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, TaiwanCorrespondence: Vincent Chin-Hung ChenDepartment of Psychiatry, Chang Gung Memorial Hospital, Chiayi, TaiwanEmail cch1966@gmail.comPurpose: This study explored and compared the effects of depression and antidepressants on sexual dysfunction in men with diabetes mellitus (DM).Patients and Methods: Patients older than 18 years who had been newly diagnosed with DM (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 250) between 1999 and 2010 were identified from Taiwan’s National Health Insurance Research Database and were followed up until 2013. Patients with preexisting depression or sexual dysfunction were excluded. A total of 636,210 patients with DM were enrolled. These patients were divided into two groups: DM with comorbid depression and a matched cohort without depression. The groups were followed up until the end of 2010 for the first diagnosis of sexual dysfunction (ICD-9-CM codes 302.70, 302.71, 302.72, 302.74, 302.75, 302.76, 302.79, 607.84, and V417). A Cox proportional hazard model and a Cox regression model with time-dependent covariates were applied.Results: Patients with DM and depression had a higher risk of sexual dysfunction than those with DM without depression (hazard ratio [HR] =  1.44; 95% confidence interval [CI], 1.33– 1.55). The risk of sexual dysfunction was lower in the subgroup who used antidepressants (per 28 cumulative defined daily doses [cDDDs]), HR = 0.96; 95% CI, 0.94– 0.97). A significantly lower incidence of sexual dysfunction was also associated with the use of selective serotonin reuptake inhibitors (SSRIs, per 28 cDDD). The adjusted HR was 0.95 (95% CI, 0.93– 0.97). Subgroup analysis indicated that SSRI use was significantly associated with an amelioration of erectile dysfunction (per 28 cDDD), with an HR of 0.95 (95% CI, 0.92– 0.97).Conclusion: Male patients with DM and depression are at increased risk of sexual dysfunction. Antidepressant use had a small inverse association with the risk of sexual dysfunction in men with DM and depression. Antidepressants, in particular SSRIs, did not increase the risk of sexual dysfunction in this population.Keywords: selective serotonin reuptake inhibitor, SSRI, sexual functioning, diabetes mellitus, depression

Ana Isabel Wu Chou,1 Mong-Liang Lu,1,2 Winston W Shen1,2 1Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, 2Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan Abstract: Clozapine is an effective antipsychotic drug but is associated with serious side effects. Most treatment guidelines give no clear recommendations on regular monitoring of liver function tests, even though up to 60% of patients experience elevations in hepatic transaminases, with 15% to 30% experiencing an elevation two to three times greater than normal. Though elevations in liver function tests are often transient and asymptomatic, there are many reported cases of clozapine-induced hepatotoxicity, with damage to the liver, involvement of multiple organs, and even fulminant liver failure arising with moderate clozapine doses. This case report describes a Chinese woman who developed hepatotoxicity on a low dose of clozapine, and reviews the relevant literature. Keywords: hepatitis, antipsychotic adverse effects, drug-induced liver injury

Introduction: Efforts have been made in assessing efficacy and tolerability to various antidepressants, but understanding personalized chances of stability to medication switching sequence is still inconclusive. This study aimed to identify naturalistic switching patterns of medication in stratifying MDD patients., Methods: MDD patients were stratified based on treatment difficulty evaluated with the "Treatment Resistance to Antidepressants Evaluation Scale for Unipolar Depression" (TRADES). The duration of the time of diagnoses until the final switch to another class of antidepressants was used as prediction of unstable to drug therapy. ROC analysis was used to determine the cutoff values. A continuous temporal events function from the visual analytic tool was employed to perform patterns of switching between distinct pharmacological class such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)., Results: TRADES scores of 4.5 and not-switching times of 12.5 months were used as cutoff values to divide patients into four subgroups: stable/easy-to-treat (SE), unstable/easy-to-treat (UE), stable/difficult-to-treat (SD) and unstable/difficult-to-treat (UD). A total of 80% and 76.9% of patients initially treated with the SSRIs paroxetine or fluoxetine, respectively, were predicted to be stable to drug therapy. Approximately 70%, 44.8% and 41.4% of patients initially treated with the SNRIs fluvoxamine, sertraline and venlafaxine, respectively, were predicted to be UD, and 60% of patients using duloxetine were predicted to be stable to drug therapy. Analysis of the switching phenomenon showed that SSRIs were the first prescribed medications and mostly taken by the stable subgroups, and SNRIs were the preferentially chosen switching alternative. Medication switching patterns in unstable MDD patients are discussed., Conclusion: Paroxetine, fluoxetine and duloxetine users were mostly stable among MDD patients in Taiwan with various stability and difficulty to treatments. Although responsiveness to specific medication sequence is likely required for clinical application, the results provide a baseline for such studies., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Hung et al.)

Objective: To investigate the effect of recombinant adenovirus-mediated HIF-1 alpha (HIF-1α) on the expression of vascular endothelial growth factor (VEGFA) and HIF-1α in hypoxic brain microvascular endothelial cells (BMEC) in rats., Methods: Primary cultured rat BMEC in vitro were treated without or with either recombinant adenovirus-mediated hypoxia-inducible factor-1 alpha (AdHIF-1α) or recombinant adenovirus empty vector (Ad) in the presence of CoCl 2 (simulating hypoxia conditions), or were grown under normoxia conditions. The expression of VEGFA and HIF-1α was analyzed at 12h, 24h, 48h and 72h incubation time, respectively. We also accessed a GEO dataset of stroke to analyze in vivo the alteration of HIF-1α and VEGFA expression, and the correlations between HIF-1α, VEGFA and CD31 mRNA levels in vascular vessels after stroke., Results: VEGFA and HIF-1α expression were significantly higher in at each time point in the AdHIF-1α than other groups (p<0.05), whereas the Ad group and hypoxia group, showed no statistically significant difference (p>0.05). Moreover, VEGFA and HIF-1α levels were significantly higher in BMEC under hypoxia conditions than normoxia conditions (p <0.05). Both HIF-1α and VEGFA expression significantly increased after stroke in vivo with 1.30 and 1.57 fold-change in log2, respectively. There were significantly positive associations between HIF-1α, VEGFA and CD31 mRNA levels in vivo after stroke., Conclusion: Hypoxia-induced HIF-1α and VEGFA expression in vascular vessels, and recombinant AdHIF-1α could up-regulate VEGFA, and enhance HIF-1ααlevels in BMEC in vitro, which may play an important role in the recovery of stroke., Competing Interests: The authors report grants from Guizhou Province Outstanding Scholars and Talents Fund Project 2006-60, grants from Guizhou Science and Technology Fund Project 2007-2096, grants from Guizhou Province Department of Health Science and Technology Fund Project 2014-41, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2020 Jin et al.)