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Androgen deprivation therapy (ADT) is the major treatment for metastatic prostate cancer (PCa), but few studies have investigated the effects of ADT on thyroid diseases.This population-based, nationwide cohort study utilized the Taiwan National Health Insurance Research Database (NHIRD) with 17,192 PCa patients between 1997 and 2013. We used the Cox proportional hazards models and propensity score-matched analysis to analyze the association between ADT and the development of thyroid diseases.A total of 17,192 newly diagnosed men with PCa were selected from the NHIRD. There were 6200 ADT users and 6200 non-ADT users after 1:1 propensity score matching. There was a significantly decreased risk of thyroid diseases among ADT users compared with non-ADT users (adjusted hazard ratio (aHR): 0.79, 95% confidence interval (CI): 0.65-0.95, p 0.001). Further analysis showed a significantly decreased risk of thyroid diseases with increasing ADT duration (p 0.001).The result showed that ADT use in men with PCa was associated with a decreased risk of thyroid disease development.

Ischemic cardiac or cerebrovascular disease (ICCD) survivors represent a subpopulation with a high cancer risk. Antiplatelet medications, such as aspirin, remain a fundamental therapy for the secondary prevention of ischemic attack in these patients. We conducted a population-based cohort study to investigate the association of long-term low-dose aspirin use with the risk of primary cancer in ICCD survivors. Patients aged ≥20 years with newly diagnosed ICCD (n = 98,519) between January 2000 and December 2013 were identified from the Taiwan National Health Insurance Research Database. The aspirin user and nonuser groups (each n = 24,030) were propensity-matched (1:1) for age, sex, comorbidities, prior medications, ICCD diagnosis year, and year of index dates. The incidence rate of primary cancer was significantly lower in the user group (6.49/1000 person-years) than in the nonuser group (14.04/1000 person-years). Multivariate Cox regression analysis indicated that aspirin use was an independent factor associated with a reduced risk of primary cancer (aHR (95% confidence interval) = 0.42 (0.38–0.45)) after adjustment. Kaplan–Meier curve analysis revealed that the cumulative incidence rate of primary cancer was significantly lower (p < 0.0001) in the user group than in the nonuser group over the 14-year follow-up period. Subgroup analyses demonstrated that this anticancer effect increased with duration of treatment and with similar estimates in women and men. In addition, aspirin use was associated with a reduced risk for seven out of the ten most common cancers in Taiwan. These findings suggest the anticancer effect of aspirin in ICCD survivors and provide information for assessing the benefit-to-risk profile of aspirin as an antiplatelet medication in these patients.

Chlorpyrifos (CPF) is one of the most abundant and widely used organophosphate pesticides for agricultural, industrial, and household purposes in the world. Epidemiological studies have reported that CPF can induce neurotoxic impairments in mammalian, which is linked to an important risk factor for development of neurodegenerative diseases (NDs). However, limited information is available on CPF-induced neurotoxicity, with the underlying exact mechanism remains unclear. In this study, CPF exposure (10-400 μM) significantly reduced Neuro-2a cell viability and induced apoptotic events, including the increase in caspase-3 activity, apoptotic cell population, and cleavage of caspase-3/-7 and PARP. Exposure of Neuro-2a cells to CPF also triggered CHOP activation. Transfection with CHOP-specific siRNA markedly suppressed the expression of CHOP, and attenuated cytotoxicity and apoptotic events in CPF-exposed Neuro-2a cells. Furthermore, CPF exposure obviously evoked the phosphorylation of Akt as well as ROS generation in a time-dependent manner. Pretreatment with LY294002 (an Akt inhibitor) effectively attenuated the CPF-induced Akt phosphorylation, CHOP activation, and apoptotic events, but not that ROS production. Of note, buffering the ROS generation with antioxidant N-acetylcysteine effectively prevented the CPF-induced ROS generation, CHOP activation, and apoptotic events, but not that the Akt phosphorylation. Collectively, these findings indicate that CPF exposure exerts neuronal cytotoxicity via the independent pathways of ROS generation and Akt activation downstream-regulated CHOP-triggered apoptosis, ultimately leading to neuronal cell death.

Ketamine-associated cystitis is characterized by suburothelial inflammation and urothelial cell death. Norketamine (NK), the main metabolite of ketamine, is abundant in urine following ketamine exposure. NK has been speculated to exert toxic effects in urothelial cells, similarly to ketamine. However, the molecular mechanisms contributing to NK-induced urothelial cytotoxicity are almost unclear. Here, we aimed to investigate the toxic effects of NK and the potential mechanisms underlying NK-induced urothelial cell injury. In this study, NK exposure significantly reduced cell viability and induced apoptosis in human urinary bladder epithelial-derived RT4 cells that NK (0.01–0.5 mM) exhibited greater cytotoxicity than ketamine (0.1–3 mM). Signals of mitochondrial dysfunction, including mitochondrial membrane potential (MMP) loss and cytosolic cytochrome c release, were found to be involved in NK-induced cell apoptosis and death. NK exposure of cells also triggered the expression of endoplasmic reticulum (ER) stress-related proteins including GRP78, CHOP, XBP-1, ATF-4 and -6, caspase-12, PERK, eIF-2α, and IRE-1. Pretreatment with 4-phenylbutyric acid (an ER stress inhibitor) markedly prevented the expression of ER stress-related proteins and apoptotic events in NK-exposed cells. Additionally, NK exposure significantly activated JNK, ERK1/2, and p38 signaling and increased intracellular calcium concentrations ([Ca2+]i). Pretreatment of cells with both PD98059 (an ERK1/2 inhibitor) and BAPTA/AM (a cell-permeable Ca2+ chelator), but not SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), effectively suppressed NK-induced mitochondrial dysfunction, ER stress-related signals, and apoptotic events. The elevation of [Ca2+]i in NK-exposed cells could be obviously inhibited by BAPTA/AM, but not PD98059. Taken together, these findings suggest that NK exposure exerts urothelial cytotoxicity via a [Ca2+]i-regulated ERK1/2 activation, which is involved in downstream mediation of the mitochondria-dependent and ER stress-triggered apoptotic pathway, consequently resulting in urothelial cell death. Our findings suggest that regulating [Ca2+]i/ERK signaling pathways may be a promising strategy for treatment of NK-induced urothelial cystitis.

Breast-conserving surgery (BCS) followed by whole breast radiation therapy (BCS-WBRT) or total mastectomy without WBRT (TM-no-WBRT) is the primary treatment for early stage breast cancer patients. Our study aimed to identify which early stage breast cancer treatment strategies had a subsequent lower incidence rate of mood disorder over a period of 10 years after the primary treatment.This retrospective cohort study consisted of newly diagnosed early stage breast cancer patients in Taiwan from 2000 to 2013 using the National Health Insurance Research Database in Taiwan. We used a 1:1 propensity score matching by age to enrol patients into the BCS-WBRT and TM-no-WBRT groups. Statistical analyses were performed to calculate the hazard ratio and cumulative incidence rate.Our study consisted of 876 BCS-WBRT patients and 1949 TM-no-WBRT patients. After propensity score matching, each study group included 876 patients. The results showed that the mood disorder incidence rate was lower in the BCS-WBRT group than in the TM-no-WBRT group. Multivariate Cox regression analysis revealed that the BCS-WBRT group had a decreased risk of developing mood disorder (adjusted hazard ratio 0.69, 95% CI 0.53-0.90, p 0.01). Furthermore, the Kaplan-Meier analysis showed that the BCS-WBRT group had a lower cumulative incidence rate of mood disorder, especially depression, after undergoing 10 years of primary treatment (p = 0.004).Our results indicated that BCS-WBRT was associated with a lower risk of development of mood disorder over a 10-year period compared to TM-no-WBRT in early stage breast cancer patients. Our findings may provide helpful information, along with other clinical data, for breast cancer patients as they choose the type of appropriate surgery for treatment.

(1) Background: In Taiwan, prostate cancer is a major malignancy with an increasing incidence among men. This study explores the medical utilization of emergency departments among patients with prostate cancer in Taiwan. (2) Methods: This nationwide, population-based study was conducted via a cross-sectional method based on the Registry for Catastrophic Illness Patient Database from Taiwan’s National Health Insurance Research Database. Patients with newly diagnosed prostate cancer between 1997 and 2013 were enrolled in the study and divided into four treatment-related groups. The rate of emergency department presentation, disease categorization of emergency department visits, emergency department-related medical expenditures, and temporal trends were investigated. (3) Results: A total of 18,728 patients with prostate cancer were identified between 1997 and 2013, for whom 13,098 emergency department visits were recorded. The number of emergency department visits increased during the study period. The incidence rate for the medical utilization of emergency department visits was 822 per 1000 people during the study period. The incidence rates for patients with prostate cancer in the radical prostatectomy, radiotherapy, androgen deprivation therapy, and chemotherapy groups were 549, 1611, 1101, and 372, respectively. The average medical expenditure per emergency department visit was TWD 3779.8 ± 5116.2, and the expenditure was recorded for the chemotherapy group at TWD 4690.8 ± 7043.3. The most common disease diagnoses among patients with prostate cancer who presented to the emergency department were injury/poisoning (16.79%), genitourinary disorders (10.66%), and digestive disorders (10.48%). (4) Conclusions: This nationwide population-based study examined the emergency department visits of patients with prostate cancer in Taiwan, providing useful information for improving the quality of medical care.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence in 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is caused by uncontrolled inflammation, aberrant immune response, cytokine storm, and an imbalanced hyperactive immune system. The cytokine storm further results in multiple organ failure and lung immunopathology. Therefore, any potential treatments should focus on the direct elimination of viral particles, prevention strategies, and mitigation of the imbalanced (hyperactive) immune system. This review focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines. In addition to the review focus, we discuss potential immunotherapeutic approaches based on relevant pathophysiological features, the systemic immune response against SARS-CoV-2, and data from recent clinical trials and experiments on the COVID-19-associated cytokine storm. Prompt use of these cytokines as diagnostic markers and aggressive prevention and management of the cytokine storm can help determine COVID-19-associated morbidity and mortality. The prophylaxis and rapid management of the cytokine storm appear to significantly improve disease outcomes. For these reasons, this study aims to provide advanced information to facilitate innovative strategies to survive in the COVID-19 pandemic.

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INTRODUCTION AND OBJECTIVE:Androgen deprivation therapy (ADT) has been a mainstay treatment for advanced prostate cancer. However, the association between ADT and dementia remained controversial.ME...

Background Ginkgo biloba leaf extract contains many active ingredients that are beneficial for health. However, ginkgolic acid, one of the major components found in G. biloba extract, may cause serious allergic and toxic side effects. The purpose of this study is to immobilize the laccase system on the electrospun nylon fiber mat (NFM) to hydrolyze the ginkgolic acid in G. biloba leaf extract efficiently. Results Novel electrospinning technology successfully produced high-quality nanoscopic fiber mats made of a mixture of multi-walled carbon nanotube and nylon 6,6. Laccase that was immobilized onto the NFM exhibited much higher efficiency in the catalyzation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) than nylon 6,6 pellets. After being immobilized onto the NFM, the pH and temperature stability of laccase were significantly improved. The NFM-immobilized laccase could maintain more than 50% of its original activity even after 40 days of storage or 10 operational cycles. The kinetic parameters, including rate constant (K), the time (τ50) in which 50% of ginkgolic acid hydrolysis was reached, the time (τcomplete) required to achieve complete ginkgolic acid hydrolysis, Km and Vmax were determined, and were 0.07 ± 0.01 min-1 , 8.97 ± 0.55 min, 45.45 ± 2.79 min, 0.51 ± 0.09 mM and 0.49 ± 0.03 mM min-1 mg-1 , respectively. Conclusion The result successfully demonstrated the strong potential of using novel electrospun nanofiber mats as enzyme immobilization platforms, which could significantly enhance enzyme activity and stability. © 2020 Society of Chemical Industry.

Background: Pneumothorax is a rare complication of acupuncture and the risk factors are unclear. Objective: This study analysed the incidence of post-acupuncture pneumothorax requiring hospitalisation in a one-million-sample cohort derived from Taiwan’s National Health Insurance Research Database. Methods: We tracked this cohort between 1997 and 2012 and recorded all medical insurance information. Subjects were categorised according to gender, insurance amount, comorbidities, residential area, and number of acupuncture treatments. Pneumothorax risk was evaluated according to different demographic and medical variables by logistic regression analysis using an adjusted odds ratio (aOR) with a 95% confidence interval (95% CI). Results: Overall, 411 734 patients undergoing 5 407 378 acupuncture treatments were identified with data collected over the first 7 days after acupuncture. The incidence rates of iatrogenic pneumothorax were 0.87 per 1 000 000 acupuncture treatments overall and 1.75 per 1 000 000 acupuncture treatments in “at-risk” anatomical areas. Multivariate logistic regression demonstrated that a history of thoracic surgery (aOR 7.85, 95% CI 3.49 to 9.25), chronic bronchitis (aOR 2.61, 95% CI 1.03 to 6.87), emphysema (aOR 4.87, 95% CI 1.03 to 7.96), pneumonia (aOR 2.09, 95% CI 1.44 to 2.72), tuberculosis (aOR 3.65, 95% CI 1.39 to 9.56), and lung cancer (aOR 3.85, 95% CI 1.53 to 9.73) may increase the post-acupuncture risk of iatrogenic pneumothorax. Men had a higher risk of pneumothorax than women (aOR 3.41, 95% CI 1.36 to 8.57). The number of treatments was not associated with risk of pneumothorax. Conclusions: Patients with a history of lung disease including chronic bronchitis, emphysema, tuberculosis, lung cancer and pneumonia, and a history of thoracic surgery, might have an increased post-acupuncture risk of pneumothorax. This information may possibly help physicians avoid post-acupuncture pneumothorax.

Purpose Chronic obstructive pulmonary disease (COPD) is a major pulmonary disease. However, few studies have investigated the relationship between COPD and prostate cancer (PCa). This study aimed to investigate the association between COPD severity and PCa risk. Patients and methods We conducted a nationwide population-based cohort study utilizing data from 2001 to 2013 from the National Health Insurance Research Database of Taiwan. Cox proportional hazards models with 1:1 propensity score-matched analysis were used to investigate the association between COPD and PCa risk. We further divided the COPD group according to severe complications (including acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation) to test for the relationship between COPD severity and PCa risk. Results This study included 47,634 patients (23,817 COPD patients and 23,817 matched non-COPD controls). Among them, 756 (1.59%) were diagnosed with PCa during a mean follow-up period of 7.05±4.13 years; 387 (1.62%) were from the COPD group and 369 (1.55%) were from the control group. Compared with the patients without COPD, the adjusted hazard ratio (HR) for PCa in the COPD patients was 1.10 (95% confidence interval [CI] 0.95-1.27), while that in the COPD patients with complications was 2.46 (95% CI 1.96-3.61). Conclusions An increased risk for PCa was found among the COPD patients with complications. COPD complications included acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation. These findings may help physicians in treating COPD with complications and in remaining alert to the potential development of PCa.

Androgen deprivation therapy (ADT) use in prostate cancer (PCa) patients has been reported to have an association with rheumatoid arthritis. We aimed to assess the impact of ADT on the subsequent risk of tenosynovitis. Using data from the National Health Insurance Research Database of Taiwan between 2001 and 2013, 3309 patients with PCa were identified. Among them, 729 ADT patients comprised the study group with 729 matched non-ADT controls. We used a 1:1 propensity score matched analysis. The demographic characteristics and comorbidities of the patients were analyzed; Cox proportional hazards regression was used to calculate the hazard ratios (HR) for the risk of tenosynovitis. There were 224 (15.3%) patients with newly diagnosed tenosynovitis. Compared with non-ADT patients, ADT patients had a lower risk of subsequent tenosynovitis with an adjusted HR of 0.38 [95% confidence interval (CI) 0.28–0.51; P

Postpartum depression (PPD) is associated with negative physical and mental health outcomes for the mother and infant. Women often experience elevated symptoms of PPD, and the incidence of PPD has increased in recent years. There were lack of studies to investigate the effects of medications during pregnancy. Herein, we focused on the most common obstetric medical therapies used in labor and determined whether the medical therapies cause mental stress in pregnant women. This 14-year retrospective population-based nationwide study was based on the National Health Insurance Research Database. Univariate and multivariate logistic regression analyses were used to evaluate unadjusted and adjusted odds ratios and 95% confidence intervals for each tocolytic and uterotonic treatments during pregnancy and common medical illnesses. In comparing the effects of tocolytic and uterotonic medications on maternal PPD, tocolysis with the injection form of ritodrine resulted in a significantly higher risk of PPD based on multivariate analysis. This study supports existing research demonstrating an association between tocolysis with ritodrine and PPD. Ritodrine treatment for preterm labor was a significant risk factor for PPD, especially the injection form. This information provides obstetricians and health policy providers to pay attention to maternal mental health outcomes among high-risk pregnant women.

Inorganic arsenic (As3+), a well-known worldwide industrial and environmental pollutant, has been linked to neurodegenerative disorders (NDs). Autophagy plays an important role in controlling neuronal cell survival/death. However, limited information is available regarding the toxicological mechanism at the interplay between autophagy and As3+-induced neurotoxicity. The present study found that As3+ exposure induced a concomitant activation of apoptosis and autophagy in Neuro-2a cells, which was accompanied with the increase of phosphatidylserine exposure on outer membrane leaflets and apoptotic cell population, and the activation of caspase-3, -7, and PARP as well as the elevation of protein expressions of LC3-II, Atg-5, and Beclin-1, and the accumulation of autophagosome. Pretreatment of cells with autophagy inhibitor 3-MA, but not that of Z-VAD-FMK (a pan-caspase inhibitor), effectively prevented the As3+-induced autophagic and apoptotic responses, indicating that As3+-triggered autophagy was contributing to neuronal cell apoptosis. Furthermore, As3+ exposure evoked the dephosphorylation of Akt. Pretreatment with SC79, an Akt activator, could significantly attenuated As3+-induced Akt inactivation as well as autophagic and apoptotic events. Expectedly, inhibition of Akt signaling with LY294002 obviously enhanced As3+-triggered autophagy and apoptosis. Exposure to As3+ also dramatically increased the phosphorylation level of AMPKα. Pretreatment of AMPK inhibitor (Compound C) could markedly abrogate the As3+-induced phosphorylated AMPKα expression, and autophagy and apoptosis activation. Taken together, these results indicated that As3+ exerted its cytotoxicity in neuronal cells via the Akt inactivation/AMPK activation downstream-regulated autophagy-dependent apoptosis pathways, which ultimately lead to cell death. Our findings suggest that the regulation of Akt/AMPK signals may be a promising intervention to against As3+-induced neurotoxicity and NDs.

Androgen deprivation therapy (ADT) has been a mainstay of treatment for advanced prostate cancer (PCa), but limited studies have been performed to investigate the association between ADT and autoimmune diseases. We conducted a population-based nationwide cohort study of 17,168 patients newly diagnosed with PCa between 1996 and 2013 using the National Health Insurance Research Database (NHIRD) of Taiwan. Cox proportional hazards models with 1:1 propensity score-matched analysis were used to investigate the association between ADT use and the risk of autoimmune diseases. The autoimmune diseases included Graves’ disease, Crohn’s disease, psoriasis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, Guillain-Barre syndrome, Sjogren’s syndrome, myasthenia gravis, pernicious anemia, hereditary hemolytic anemia, polyarteritis nodosa, Celiac disease, uveitis, polymyalgia rheumatica, dermatomyositis, Hashimoto’s thyroiditis, hypersensitivity vasculitis, Behcet’s disease, polymyositis, alopecia areata, Wegener’s granulomatosis, ulcerative colitis, autoimmune hemolytic anemia, pemphigus, multiple sclerosis, systemic sclerosis, Goodpasture syndrome, giant cell arteritis, thromboangitis obliterans, arteritis obliterans, and Kawasaki disease. The duration of ADT use as a time-dependent variable was also examined for its association with autoimmune diseases. We also performed six secondary analyses. Of the 17,168 selected PCa patients, 14,444 patients met all the inclusion and exclusion criteria. After propensity score matching, 5590 ADT users and 5590 non-ADT users were included in the study cohort. A propensity score-matched analysis (adjusted hazard ratio (aHR), 0.619, 95% confidence interval (CI), 0.51–0.75, P

INTRODUCTION AND OBJECTIVE:Androgen deprivation therapy (ADT) has been a foundational treatment for advanced prostate cancer. However, the association between ADT and dementia remains in doubt.METH...

Renal calculi are common, with male predilection and androgen exposure potentially increasing the risk of renal calculi. Systemic effects of androgen deprivation therapy (ADT) have been observed but the influence of ADT on renal calculi in prostate cancer (PCa) patients is not fully understood. We conducted this population-based study to evaluate the impact of ADT on the subsequent risk of renal calculi. We used the National Health Insurance Research Database of Taiwan to analyze the incidences of renal calculi in ADT patients and non-ADT patients from 2001 to 2013. In total, 3309 patients with PCa were selected. After matching with 1:1 propensity-score analysis, 758 ADT patients with 758 matched non-ADT controls were enrolled in the final analysis. Demographic characteristics were analyzed and Cox regression analysis for calculating the hazard ratios (HR) was performed for the subsequent risk of renal calculi. Finally, 186 (186/1516, 12.3%) patients with diagnosed renal calculi were detected. ADT patients had a lower risk of subsequent renal calculi with an adjusted HR of 0.38 (7% vs. 17.5%, 95% confidence interval (CI) 0.28&ndash, 0.53, p &lt, 0.001) in comparison with the non-ADT group. The Kaplan&ndash, Meier curve showed significant differences of cumulative incidences of renal calculi. In conclusion, ADT patients had approximately one-third lower risk of subsequent renal calculi. Further studies are warranted to evaluate the clinical significance.

Jui-Ming Liu,1–3,* Chien-Yu Lin,4,* Heng-Chang Chuang,1 Ren-Jun Hsu3,5,6 1Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 2Department of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 4Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan; 5Biobank Management Center of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 6Department of Pathology and Graduate Institute of Pathology and Parasitology, the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan *These authors contributed equally to this work Objective: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) patients has been reported to exacerbate the course of psoriasis. We aimed to assess the impact of ADT on the subsequent risk of psoriasis. Methods: We utilized data from the National Health Insurance Research Database of Taiwan between 1996 and 2013. In total, 17,168 patients with PCa were identified; 5,141 ADT patients comprised the study group with 5,141 matched non-ADT controls. We used 1:1 propensity score-matched analysis. The demographic characteristics and comorbidities of the patients were analyzed; Cox proportional hazards regression was used to calculate the HRs for the risk of psoriasis. Results: Eighty-nine (0.87%) patients with newly diagnosed psoriasis were identified. Compared with non-ADT patients, ADT patients had similar risk of subsequent psoriasis with an HR of 0.95 (95% CI 0.63–1.45; P=0.816). However, a higher risk of psoriasis was observed in angiotensin-converting enzyme inhibitors patients (adjusted HR 2.14, 95% CI 1.09–4.20; P

Jui-Ming Liu,1–3,* Ren-Jun Hsu,3–5,* Fung-Wei Chang,6 Feng-Hsiang Chiu,7,8 Chia-Lun Yeh,1 Chun-Fa Huang,9,10 Shu-Ting Chang,11 Hung-Chang Lee,12 Hsin Chi,12,13 Chien-Yu Lin14,15 1Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 2Department of Medicine, National Yang-Ming University, 3Graduate Institute of Life Sciences, 4Department of Pathology and Graduate Institute of Pathology and Parasitology, the Tri-Service General Hospital, National Defense Medical Center, 5Biobank Management Center of the Tri-Service General Hospital, 6Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, 7Department of Emergency Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 8Superintendent office, Lihuili Eastern Hospital, Ningbo, Zhejiang province, People’s Republic of China; 9School of Chinese Medicine, College of Chinese Medicine, China Medical University, 10Department of Nursing, College of Medical and Health Science, Asia University, Taichung City, 11Department of Gastroenterology, BinKun Women’s and Children’s Hospital, Taoyuan City, 12Department of Infectious Disease, MacKay Children’s Hospital, Taipei, 13Department of Medicine, MacKay Medical College, New Taipei city, 14Department of Pediatrics and Infectious Disease, Hsinchu MacKay Memorial Hospital, Hsinchu City, Taiwan; 15Division of Infection and Pathway Medicine, College of Medicine and Veterinary Medicine, The University of Edinburgh, Scotland, UK *These authors contributed equally to this work Objectives: Scabies is a common and annoying disorder. Pernicious anemia (PA) is a serious disease which, when untreated, leads to death. Mounting evidence suggests that immune-mediated inflammatory processes play a role in the pathophysiology of both diseases. The relationship between these two diseases has not been investigated. We conducted this study to explore the potential relationship between scabies and PA.Materials and methods: This nationwide, population-based study was conducted using the National Health Insurance Research Database of Taiwan. In total, 5,407 patients with scabies were identified as a study group and 20,089 matched patients were randomly selected as a control group. We tracked patients in both groups for a 7-year period to identify the incidence of PA. The demographic characteristics and comorbidities of the patients were analyzed, and Cox proportional hazards regression was used to calculate the hazard ratios for PA.Results: Of the 25,496 patients in this study, 183 (0.7%) patients with newly diagnosed PA were identified during the 7-year follow-up period; 71 of 5,407 (1.3%) from the scabies group and 112 of 20,089 (0.6%) from the control group. Patients with scabies had a higher risk of subsequent PA, with a crude hazard ratio of 2.368. After adjusting for covariates, the adjusted hazard ratio was 1.51 (95% confidence interval: 1.09–2.08).Conclusion: This study demonstrated an increased risk of PA (adjusted hazard ratio 1.51) among patients with scabies. Immune-mediated inflammatory processes may contribute to this association. Further studies are warranted to investigate the entire pathological mechanisms between these two diseases. Physicians should pay attention to patients with history of scabies presented with anemia. Further confirmative tests of PA may contribute to correct diagnosis and initiation of vitamin B12 supplement. Keywords: scabies, pernicious anemia, National Health Insurance Research Database, autoimmune gastritis, vitamin B12 deficiency, cobalamin

Scabies is a commonly occurring infectious immune-mediated inflammatory skin disease. Immune-mediated inflammatory processes are also observed in autoimmune diseases. There have been very few previous studies; however, that have investigated the possible association between scabies and autoimmune diseases. To address this research gap, we conducted a nationwide population-based cohort study that included a total of 4481 scabies patients and 16,559 control subjects matched by gender, age, insured region, urbanization and income. We tracked both cohorts for a 7-year period to identify the incidence of autoimmune diseases in both groups during that follow-up period. Relatedly, a Cox regression analysis was performed to calculate and compare the hazard ratio (HR) for autoimmune diseases of both groups. An overall increased risk for 19 autoimmune diseases was observed in the scabies patients, with an adjusted HR (aHR) of 1.14 (95% CI 1.04-1.25). Compared with the control group, the scabies patients exhibited increased risks of hypersensitivity vasculitis (aHR 5.44, 95% CI 1.64-18.07), dermatomyositis (aHR 4.91, 95% CI 1.80-13.38), polyarteritis nodosa (aHR 2.89, 95% CI 1.46-5.73), systemic lupus erythematosus (aHR 2.73, 95% CI 1.33-5.64), psoriasis (aHR 2.31, 95% CI 1.85-2.88), myasthenia gravis (aHR 2.01, 95% CI 1.31-3.12), type 1 diabetes mellitus (aHR 1.93, 95% CI 1.53-2.44), pernicious anemia (aHR 1.92, 95% CI 1.42-2.61), and rheumatoid arthritis (aHR 1.43, 95% CI 1.12-1.83). In conclusion, the associations between scabies and a variety of autoimmune diseases may exist. Further studies are needed to clarify the shared etiologies and relationships between scabies and autoimmune diseases.

Background: Cellulitis is a complication of acupuncture, but the risk factors and annualized incidence remain unclear. Objective: This study analyzed the incidence and risk factors of cellulitis related to acupuncture in a cohort of one million participants derived from Taiwan&rsquo, s Longitudinal Health Insurance Database. Methods: We tracked this cohort between 1997 and 2012 and recorded all outpatient medical information including diagnosis and treatment. Patients were categorized according to age, gender, comorbidities, residential area, and number of acupuncture treatments. We compared the incidence and risk of cellulitis between different demographics and comorbidities by logistic regression analysis and adjusted odds ratio (aOR) with a 95% confidence interval (95% CI). Results: We included 407,802 patients and 6,207,378 acupuncture treatments. The incidence of cellulitis after acupuncture was 64.4 per 100,000 courses of acupuncture treatment. The most common sites of cellulitis after acupuncture were the legs, feet, and face. Comorbidity was associated with post-acupuncture cellulitis, a multivariate logistic regression analysis showed that chronic kidney disease (aOR, 1.71, 95% CI, 1.55&ndash, 1.88), rheumatoid arthritis (aOR, 1.86, 95% CI, 1.21&ndash, 3.60), liver cirrhosis (aOR, 1.23, 95% CI, 1.15&ndash, 1.32), diabetes mellitus (aOR, 1.69, 95% CI, 1.57&ndash, 1.82), stroke (aOR, 1.44, 95% CI, 1.31&ndash, 1.58), varicose veins (aOR, 2.38, 95% CI, 2.17&ndash, 2.84), or heart failure (aOR, 1.81, 95% CI, 1.65&ndash, 1.98) significantly increased cellulitis. Repeated exposure to acupuncture treatment was associated with an increased risk of cellulitis. Conclusions: A variety of chronic diseases may increase the risk of cellulitis after acupuncture. Physicians asked about past medical history before acupuncture might help to reduce cellulitis.

Xerostomia (dry mouth) is the cardinal symptom of Sj&ouml, gren&rsquo, s syndrome (SS), which is an autoimmune disease involving the exocrine glands and other organs. Xerostomia may predispose patients to periodontal disease (PD) and an association between SS and PD has been reported. This association may be bidirectional, therefore, we conducted this study to investigate the risk of SS in patients with PD using data from the National Health Insurance Research Database of Taiwan. A total of 135,190 patients were enrolled in our analysis. In all, 27,041 patients with PD were matched by gender, age, insured region, urbanization and income, with cases and controls in a 1:4 ratio. Both groups were followed and the risks of SS were calculated by Cox proportional hazards regression. Finally, 3292 (2.4%) patients had newly diagnosed SS. Patients with PD had a significantly higher risk of subsequent SS (903 (3.3%) vs. 2389 (2.2%), adjusted hazard 1.47, 95% confidence interval: 1.36&ndash, 1.59). In conclusion, patients with PD had an approximately 50% increased risk of subsequent SS. Physicians should be aware of the symptoms and signs of SS in patients with PD.

p-Cresyl sulfate (pCS), a uremic toxin, can cause renal damage and dysfunction. Studies suggest that renal dysfunction increases the prevalence of renal cancer. However, the effect of pCS on the proliferation and migration of renal cancer is unclear. Clear cell renal cell carcinoma (ccRCC) expresses mutant von Hippel-Lindau gene and is difficult to treat. Hypoxia-inducible factor-1α and 2-α (HIF-1α and HIF-2α) as well as microRNA-21 (miR-21) can regulate the proliferation and migration of ccRCC cells. However, the association between HIF-α and miR-21 in ccRCC remains unclear. Therefore, the effects of pCS on ccRCC cells were investigated for HIF-α and miR-21 signals. Our results showed that pCS induced overexpression of HIF-1α and promoted the proliferation and regulated epithelial-mesenchymal transition-related proteins, including E-cadherin, fibronectin, twist and vimentin in ccRCC cells. pCS treatment increased miR-21 expression. Specifically, inhibition of miR-21 blocked pCS-induced proliferation and migration. Taken together, the present results demonstrate that pCS directly induced the proliferation and migration of ccRCC cells through mechanisms involving miR-21/HIF-1α signaling pathways.

Shun-Ku Lin,1,2,* Jui-Ming Liu,3,* Ying-Hsu Chang,4 Yuan-Tien Ting,5 See-Tong Pang,4 Ren-Jun Hsu,6–8 Po-Hung Lin4,9 1Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 2Department of Chinese Medicine, Taipei City Hospital, Ren-Ai Branch, Taipei, 3Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, 4Division of Urology, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, 5Division of Urology, Department of Surgery, Chang Bing Show Chwan Memorial Hospital, Changhua, 6Biobank Management Center of the Tri-Service General Hospital, 7Department of Pathology and Graduate Institute of Pathology and Parasitology, the Tri-Service General Hospital, 8Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 9Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China *These authors contributed equally to this work Background: Urolithiasis is a common urinary tract disease worldwide. It has been connected to systemic diseases, including hypertension, diabetes mellitus, metabolic syndrome, and cardiovascular disease. In the current study, we aimed to evaluate the relationship between urolithiasis and the complications of acute myocardial infarction (AMI). Materials and methods: Data were obtained from the Longitudinal Health Insurance Database 2005 of the National Health Insurance Research Database. All AMI cases, both those who were hospitalized and those who were treated in the emergency department, were identified using the International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) code. Results: A total of 37,052 patients with urinary calculi and 148,209 control subjects were enrolled in this study. The average follow-up period was 9.51years. The risk of AMI was higher among patients with urolithiasis (adjusted hazard ratio [aHR] 1.07, 95% confidence interval [95% CI] 1.03–1.13). We detected a significant association between urolithiasis and intubation (aHR 1.53, 95% CI 1.36–1.73), intensive care unit treatment (aHR 1.22, 95% CI 1.13–1.32), heart failure (aHR 1.59, 95% CI 1.42–1.78), shock (aHR 1.53, 95% CI 1.32–1.77), and arrhythmias (aHR 1.18, 95% CI 1.06–1.33). Furthermore, certain medical treatments for urolithiasis were found to be related to myocardial infarction (MI). Nonsteroidal anti-inflammatory drugs (NSAIDs) were significantly associated with a high risk of AMI. In contrast, allopurinol, thiazide diuretic, potassium-sparing diuretics, and a-blockers have negative association with AMI. Conclusion: Urolithiasis had a significantly increased risk of endotracheal intubation and heart failure following AMI. In addition, urolithiasis was also associated with a high risk of intensive care unit treatment, shock, and arrhythmias after AMI. Medical treatments for urolithiasis may decrease the risk of MI, except the use of NSAIDs. Keywords: urolithiasis, renal calculi, acute myocardial infarction, National Health Insurance Research Database, endotracheal intubation, heart failure

// Jar-Yi Ho 1, * , Ren-Jun Hsu 1, 2, 3, * , Jui-Ming Liu 4 , Szu-Chi Chen 1 , Guo-Shiou Liao 5 , Hong-Wei Gao 1 , Cheng-Ping Yu 1, 2, 3 1 Department of Pathology, and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 2 Biobank Management Center of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 3 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan 4 Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan 5 Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Cheng-Ping Yu, email: cpyupath@yahoo.com.tw Keywords: miR-382-5p, RERG, Ras/ERK pathway, breast cancer Received: March 29, 2016 Accepted: September 20, 2016 Published: September 29, 2016 ABSTRACT Aberrant activation of the Ras/ERK pathway mediates breast cancer initiation and aggressiveness. Therefore, it is important to identify miRNAs that modulate the Ras/ERK pathway during breast carcinogenesis and progression. The Ras GTPase superfamily member RERG (Ras-related and estrogen-regulated growth inhibitor) acts as a tumor suppressor to reduce breast cancer cell proliferation and tumor formation and has been suggested to have a regulatory role in the Ras/ERK pathway. In this study, we found that RERG exerted its tumor suppressor role by attenuating the activation of Ras/ERK signaling effectors. Furthermore, we found that miR-382-5p directly targets and represses RERG to attenuate the inhibitory effects of RERG on the oncogenic Ras/ERK pathway. Thereby, miR-382-5p promoted breast cancer cell viability, clonogenicity, survival, migration, invasion and in vivo tumorigenesis/metastasis. In clinical interpretation, miR-382-5p expression was negatively correlated with RERG expression, and it also significantly functioned as an independent oncomiR for the higher incidence and poorer prognosis of breast cancer. This novel connection highlights new diagnostic and prognostic roles for miR-382-5p and RERG in breast cancer.