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Chia-Yu Huang,1,2 Mei-Yao Wu,3– 5 Ming-Cheng Huang,2,3 Teng-Shun Yu,6,7 Peter Karl Mayer,3,8,&ast; Hung-Rong Yen2,3,5,8,9,&ast; 1Department of Family Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; 2Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 4School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 5Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 6Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 7College of Medicine, China Medical University, Taichung, Taiwan; 8International Master Program in Acupuncture, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 9Chinese Medicine Research Center, China Medical University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hung-Rong Yen, School of Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404, Taiwan, ext. 3001 Fax +886-4-22365141, Email hungrongyen@mail.cmu.edu.twPurpose: Disability is the comorbidity of dementia for which there is no available preventive measure. The aim of this study was to investigate the association between acupuncture treatment and the risk of disability development in dementia patients.Patients and Methods: A cohort study was performed using a nationwide health database in Taiwan. The included dementia patients were divided into acupuncture and non-acupuncture cohorts based on whether they received acupuncture treatment during the follow-up period. The variables in the two cohorts were controlled by 1:1 propensity-score matching. The difference in disability development in dementia patients between the acupuncture and non-acupuncture cohorts was also analyzed. Subgroup analyses were performed using socioeconomic variables, comorbidities and anti-dementia agents (donepezil, rivastigmine, galantamine and memantine) used for dementia treatment.Results: A total of 9,760 dementia patients met our inclusion criteria, and patients were divided into an equal number (n=2,422) of acupuncture and non-acupuncture groups, respectively, after 1:1 propensity-score matching. The dementia patients had a lower risk of disability development after acupuncture treatment than those who did not receive acupuncture treatment (adjusted hazard ratio 0.65, 95% confidence interval 0.60– 0.70, p < 0.001). The results were independent of basic variables or comorbidities in the two cohorts. Patients who did not use anti-dementia agents had a lower risk of developing disability after receiving acupuncture intervention than those who used anti-dementia agents.Conclusion: Our results revealed the relationship between acupuncture intervention and decreased risk of developing disability in dementia patients. The results are useful for dementia treatment, trial design and further planning of care programs.Keywords: acupuncture, disability, dementia, traditional Chinese medicine

Chun-Hao Chen,1 Ming-Chyi Huang,2 Yi-Hang Chiu,3 I-Ming Chen,1,4 Chun-Hsin Chen,3,5 Mong-Liang Lu,3,5 Tsung-Yang Wang,1 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 3Department of Psychiatry, Wan-Fang Hospital, Taipei, Taiwan; 4Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 5Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen, Department of Psychiatry, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, 10002, Taiwan, Tel +886-2-2312-3456 ext. 66787, Fax +886-2-2381-3208, Email hsichungchen@ntu.edu.twObjective: This study aimed to investigate the relationship between eveningness preference and poor sleep quality and eventually examine the moderation effect of stress susceptibility.Methods: Individuals with non-acute major depressive disorder or bipolar affective disorder and healthy participants were recruited. The Composite Scale of Morningness (CSM) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate chronotype and sleep quality, respectively. Eysenck Personality Questionnaire, Tridimensional Personality Questionnaire, Perceived Stress Scale, and Beck Anxiety Inventory were used to formulate stress susceptibility and as indicator variables for empirical clustering by latent class analysis (LCA). Linear regression models were used to examine the relationship between chronotype preference and sleep quality. The interaction terms of CSM and stress susceptibility were examined for the moderation effect.Results: A total of 887 individuals were enrolled in this study, with 68.2% female and 44.1% healthy participants. Three subgroups were derived from LCA and designated as low stresssusceptibility (40.2%), moderate stress susceptibility (40.9%), and high stress susceptibility (18.8%) groups. After controlling for covariates, the CSM scores inversely correlated with PSQI scores [b (se)=− 0.02 (0.01), p=0.01], suggesting that individuals with eveningness preferences tend to have poor sleep quality. Moreover, stress susceptibility moderated the relationship between CSM and PSQI scores (p for interaction term = 0.04). Specifically, the inverse association between CSM and PSQI was more robust in the high stress susceptibility group than that in the low stress susceptibility group.Conclusion: Eveningness preference was associated with poor sleep quality, and this relationship was moderated by stress susceptibility.Keywords: chronotype, empirical clustering, moderation effect, stress susceptibility, sleep quality

Po-An Su,1 Mu-Chen Lo,2 Chiao-Ling Wang,2 Ping-Chen Yang,3 Chiao-I Chang,4 Meng-Chuan Huang,4,5 Ming-Kuo Huang,6 Kuang-I Cheng6 1Department of Operation Management, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Human Resource, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Nutrition and Dietetics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6Superintendent Office, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Meng-Chuan HuangDepartment of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin Dist., Kaohsiung, 80708, TaiwanTel +886 7-3121101 ext. 5341Fax +886 7-3121101 ext. 5345Email mechhu@kmu.edu.twPurpose: This study investigated the association between professional quality of life, working context, and mental health outcomes among hospital personnel in Taiwan during the worldwide upsurge in COVID-19 cases.Patients and Methods: We recruited 503 hospital personnel to whom we administered online questionnaires containing items from the Professional Quality of Life (ProQoL) scale, which covers compassion satisfaction (CS), burnout (BO) and compassion fatigue (CF), the Depression, Anxiety and Stress Scale (DASS-21) and questions on work-related variables. Data were collected from 13 July to 19 August 2020.Results: The participants generally reported moderate CS and BO and low CF. Overall prevalence of mild-to-extremely-severe stress, anxiety and depression was 24.5%, 39.6% and 31.2%, respectively. Multiple logistic regression revealed that moderate-to-high BO and CF correlated with increased risks of mild-to-extremely-severe stress (OR = 4.17 and 2.23, respectively), anxiety (OR = 4.86 and 2.81, respectively) and depression (OR = 5.83 and 3.01, respectively), while moderate-to-high CS correlated with reduced risks of stress (OR = 0.53) and depression (OR = 0.45) only. There were CS and BO differences in groups categorized by marital status and profession. Anxiety increased linearly by seniority < 10, 10– 19 and ≥ 20 years (p for trend < 0.05).Conclusion: In conclusion, the subscales of ProQOL, BO and CF appeared to be associated with increased risks of stress, anxiety and depression among hospital personnel during the COVID-19 epidemic. A long-term contingency program may be needed to adjust work context variables and support emotional well-being of these workers.Keywords: COVID-19, depression, Anxiety and Stress Scale, DASS-21, hospital personnel, professional quality of life, ProQoL

Kuan-Yu Chen,1 Ming-Cheng Huang,2,3 Cheng-Li Lin,4 Yu-Chen Lee,2,3,5 Mei-Yao Wu,2,6,&ast; Hung-Rong Yen2,3,7– 9,&ast; 1Department of Chinese Medicine, Taipei City Hospital, Yangming Branch, Taipei, Taiwan; 2Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 3Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 4Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 5Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 6School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 7Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 8Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; 9Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hung-Rong YenGraduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404328, TaiwanTel +886-4-22053366 ext. 3001Fax +886-4-22365141Email hungrongyen@mail.cmu.edu.twMei-Yao WuSchool of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404328, TaiwanTel +886-4-22052121 ext. 4561Fax +886-4-22037690Email meiyaowu0919@gmail.comBackground: Depression is one of the most disabling disorders, which causes long-term complications such as neurodegenerative disorder and cerebrovascular disease. Some patients with depression seek acupuncture treatment. We aimed to investigate the association between acupuncture treatment and the risk of dementia in patients with depression from the perspective of real-world evidence.Methods: Patients over 18 years old and newly diagnosed with depression between 1997 and 2010 were selected from the Taiwanese National Health Insurance Research Database and followed up until the end of 2013. Propensity score was used to match equal numbers of patients 1:1 (N = 16,609 per group) into acupuncture and non-acupuncture cohorts based on characteristics including sex, age, baseline comorbidity and drug use. The outcome measurement was the comparison of dementia incidence in the two cohorts.Results: Compared with the non-acupuncture cohort, patients who received acupuncture treatment had a decreased risk of dementia (adjusted hazard ratio (aHR) = 0.54; 95% confidence interval (CI) = 0.50– 0.58, P < 0.001) after adjustment for age, sex, comorbidities and drug use. Compared with depression patients who did not receive acupuncture, the aHR of vascular dementia and Alzheimer’s disease incidences for patients who had acupuncture therapy was 0.59 (95% CI 0.48– 0.71) and 0.51 (95% CI 0.39– 0.67), respectively. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (Log rank test, p < 0.001).Conclusion: The present study from real-world data revealed that acupuncture reduced the risk of dementia in depression patients, which supports healthcare decisions in clinical practice.Keywords: acupuncture, Alzheimer’s disease, depression, dementia, National Health Insurance Research Database, NHIRD, traditional Chinese medicine

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

Chia-Yu Huang,1– 3 Ming-Cheng Huang,3,4 Mao-Feng Sun,3,4 Cheng-Li Lin,5,6 Mei-Yao Wu,4,7 Wu-Chou Lin,3,8,&ast; Hung-Rong Yen3,4,9,10,&ast; 1Department of Family Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, 427, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, 970, Taiwan; 3Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan; 4Department of Chinese Medicine, China Medical University Hospital, Taichung, 404, Taiwan; 5Management Office for Health Data, China Medical University Hospital, Taichung, 404, Taiwan; 6College of Medicine, China Medical University, Taichung, 404, Taiwan; 7School of Post-baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan; 8Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, 404, Taiwan; 9Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan; 10Chinese Medicine Research Center, China Medical University, Taichung, 404, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hung-Rong Yen Tel +886-4-22053366 ext. 3313Email hungrongyen@mail.cmu.edu.twWu-Chou Lin Tel +886-4-22052121Email d0562@mail.cmuh.org.twBackground: Major depressive disorder is a significant public health concern, which often leads to loss of productivity, functional decline, and various complications. The aim of this study was to investigate the effectiveness of acupuncture in the risk reduction of coronary heart disease (CHD) in patients with depression.Methods: We enrolled patients diagnosed with depression between January 1, 1997, and December 31, 2010, through the Taiwanese National Health Insurance Research Database (NHIRD). Propensity score was used to match equal numbers (n=14,647) of acupuncture cohort and no-acupuncture cohort based on characteristics including sex, age, baseline comorbidity and medication. Patients were followed up until December 31, 2013, or withdrawn from the NHIRD. The Cox regression model was used to compare the hazard ratios (HRs) of CHD in the two cohorts.Results: The basic characteristics of the two groups were similar. A lower cumulative incidence of CHD was noted in the acupuncture cohort (Log rank test, p < 0.001). Over time, 1626 patients in the acupuncture cohort (21.05 per 1000 person-years) and 2412 patients in the no-acupuncture cohort (39.84 per 1000 person-years) developed CHD (adjusted HR=0.50, 95% CI 0.47– 0.53). The decreased CHD incidence was independent of age, sex, comorbidities, and medications used. The cumulative incidence of CHD was significantly lower in the acupuncture cohort than in the no-acupuncture cohort (Log rank test, p< 0.001).Conclusion: The results provided a real-world evidence that acupuncture may have beneficial effect on CHD risk reduction in patients with depression.Keywords: acupuncture, depression, coronary heart disease, National Health Insurance Research Database, real-world evidence

Sze-Yu Chen,1 Chun-Hao Chen,1 Chen Lo,1 Mong-Liang Lu,2 Cheng-Dien Hsu,3 Yi-Hang Chiu,2 Chun-Hsin Chen,2 Shih-Ku Lin,4,5 Ming-Chyi Huang,5 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Wan-Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Psychosomatic Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; 4Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen Email hsichungchen@ntu.edu.twPurpose: This study aimed to elucidate the various co-occurring patterns of depressive symptomatology and sleep-wake-related disturbances (SWRDs) in patients with mood disorders.Patients and Methods: Individuals in non-acute states of major depressive disorder or bipolar disorder were recruited. The Beck Depression Inventory II (BDI-II) was utilized to evaluate depressive symptoms. BDI-II items were classified into three domains: cognitive, affective, and somatic. Between-domain differences with various SWRDs were examined. Latent class analysis was used to empirically classify participants using BDI-II items as indicator variables. Co-occurring patterns between domains of BDI-II items and SWRDs were re-examined in each subgroup to elucidate inter-individual differences.Results: In total, 657 participants were enrolled. Of participants, 66.8% were female, and 52.4% were diagnosed with major depressive disorder. Each BDI-II domain exhibited different co-occurring patterns. The somatic domain was most likely to co-occur with various SWRDs. Three subgroups were derived from latent class analysis and were designated as poor sleep quality and high insomnia (n=150), poor sleep quality and moderate insomnia (n=248), and poor sleep quality and low insomnia (n=159). The group with more severe insomnia presented with more severe depressive and anxiety symptoms. The three subgroups further differed in co-occurring patterns. From the low insomnia to high insomnia group, the associations with various SWRDs appeared in the sequence of somatic, affective, and cognitive domains.Conclusion: Co-occurring patterns between domains of depressive symptomatology with various SWRDs differ and may vary among individuals.Keywords: co-occurring, latent class analysis, mood disorders, sleep-wake-related disturbance, depression

Carolyn H Still,1 Seunghee Margevicius,2 Carla Harwell,3,4 Ming-Chun Huang,5 LaTonya Martin,6 Phuong B Dang,1 Jackson T Wright Jnr3,7 1Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 2Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; 3Department of Internal Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; 4University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 5Department of Electrical Engineering and Computer Science, Case School of Engineering, Case Western Reserve University, Cleveland, OH, USA; 6Community Partners, Cleveland Council of Black Nurses, Cleveland, OH, USA; 7Department of Nephrology and Hypertension, Clinical Hypertension Program, University Hospitals Cleveland Medical Center, Cleveland, OH, USACorrespondence: Carolyn H StillFrances Payne Bolton School of Nursing, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USATel +1 216 368 6338Fax +1 216 368 3452Email cwh11@case.eduPurpose: Adoption of technology has increased to support self-managing chronic diseases. However, behavioral interventions evaluating such technology have been understudied in African Americans with hypertension. The aim of this study was to explore a community and technology-based intervention for hypertension self-management (COACHMAN) intervention on blood pressure (BP) control and health-related quality of life (HRQoL) in African Americans with hypertension.Methods: Sixty African Americans (mean age 60; 75% females) who were prescribed antihypertensive medications and owning a smartphone were randomized to the COACHMAN (n = 30) or enhanced usual care (n = 30) group for 12 weeks. COACHMAN is comprised of four components: web-based education, home BP monitoring, medication management application, and nurse counseling. Hypertension knowledge, self-efficacy, technology adoption/use, medication adherence, BP, and HRQoL scores were assessed.Results: Mean systolic and diastolic BP at baseline was 150.49 (SD = 13.89) and 86.80 (SD = 13.39), respectively. After completing the 3-month intervention to improve hypertension self-management, the groups did not significantly differ in BP control and HRQoL. Clinically relevant BP reduction was observed in the intervention group. Paired t-test showed that mean medication-taking adherence scores significantly improved in the intervention group (P = 0.023) compared to the control group (P = 0.075).Conclusion: Using technology may have a positive impact on supporting hypertension self-management, particularly in medication-taking adherence. Further research is warranted in a larger sample and should include standardization of medication management to isolate the effects of behavioral interventions on changes in BP.Clinicaltrials.gov Identifier: NCT03722667.Keywords: African Americans, hypertension, minority health, technology, self-management

Edmund Cheung So,1,2 Yung-Chia Chen,3 Shu-Chun Wang,4 Chia-Ching Wu,4 Man-Chi Huang,4 Meng-Shao Lai,4 Bo-Syong Pan,4,5 Fu-Chi Kang,6 Bu-Miin Huang4 1Department of Anesthesia, An Nan Hospital, China Medical University, Tainan, Taiwan, Republic of China; 2Department of Anesthesia, School of Medicine, China Medical University, Taichung, Taiwan; Republic of China; 3Department of Anatomy, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 4Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; 5Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC, USA; 6Department of Anesthesia, Chi Mei Medical Center, Chiali, Tainan, Taiwan, Republic of China Purpose: Midazolam is widely used as a sedative and anesthetic induction agent by modulating the different GABA receptors in the central nervous system. Studies have also shown that midazolam has an anticancer effect on various tumors. In a previous study, we found that midazolam could induce MA-10 mouse Leydig tumor cell apoptosis by activating caspase cascade. However, the detailed mechanism related to the upstream and downstream pathways of the caspase cascade, such as endoplasmic reticulum (ER) stress, autophagy, and p53 pathways plus cell cycle regulation in MA-10 mouse Leydig tumor cells, remains elusive.Methods: Flow cytometry assay and Western blot analyses were exploited.Results: Midazolam significantly decreased cell viability but increased sub-G1 phase cell numbers in MA-10 cells (P