8-Methoxypsoralen Induces Apoptosis by Upregulating p53 and Inhibits Metastasis by Downregulating MMP-2 and MMP-9 in Human Gastric Cancer Cells

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

Transfer anxiety in parents of children transferred from pediatric intensive care units to general wards in South Korea: a hybrid concept analysis

Purpose@#This study aimed to analyze the concept of transfer anxiety in parents of children transferred from pediatric intensive care units to general wards. @*Methods@#The hybrid model by Schwarz-Barcott and Kim was used to analyze the characteristics of transfer anxiety in parents of children transferred from pediatric intensive care units to general wards. @*Results@#Transfer anxiety was defined by the following attributes: 1) stress concerning the adaptation process, 2) concern about the child’s condition worsening due to the parent’s caregiving, and 3) involuntary changes in daily life due to the treatment. Transfer anxiety has the following antecedents: 1) uncertainty; 2) a lack of knowledge about the illness, medical devices, and caregiving; and 3) a lack of social support. It resulted in 1) caregiver burden, 2) a decrease in the capacity for coping with caregiving, 3) delays in the child’s physical and psychological recovery, and 4) decreased quality of life. @*Conclusion@#It is necessary to develop an assessment scale that considers the attributes of transfer anxiety in parents of children transferred from pediatric intensive care units to general wards. Furthermore, an effective nursing intervention should be developed to reduce transfer anxiety.

Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis

Background@#Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). @*Methods@#BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. @*Results@#Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. @*Conclusion@#These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis

Background@#Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). @*Methods@#BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. @*Results@#Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. @*Conclusion@#These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

Imaging Characteristics of Brain SPECT, PET, and MRI in Neurosyphilis / 대한핵의학회잡지

The incidence of neurosyphilis has declined since effective penicillin therapy against Treponema pallidum was introduced. However, the diagnosis of neurosyphilis early in the disease course is very important in order to select appropriate antibiotic therapy. We report brain MRI, SPECT with Tc-99m ECD, and PET with F-18 FDG findings before antibiotic therapy in a neurosyphilis patient with neurological symptoms. The cerebral cortices showed hypoperfusion with a patchy distribution on SPECT and foci with high signal intensity on MRI, suggesting ischemia. Brain PET showed areas with hypometabolism in the temporoparietal lobes bilaterally.

Econazole Induces p53-Dependent Apoptosis and Decreases Metastasis Ability in Gastric Cancer Cells

Econazole, a potent broad-spectrum antifungal agent and a Ca2+ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

Factors Influencing Physical Activity in Adolescents with Complex Congenital Heart Disease

PURPOSE: We aimed to identify factors influencing physical activity in adolescents with complex congenital heart disease. METHODS: We recruited 92 adolescents with complex congenital heart disease from a tertiary medical center in Seoul, measured their levels of physical activity, and identified factors that influenced their physical activity levels using the Global Physical Activity Questionnaire, the New York Heart Association classification, congenital heart disease complexity, the Self-Efficacy Scale, and the Parental Bonding Instrument scale. Stepwise multiple linear regression was used to determine factors influencing physical activity. RESULTS: Total physical activity was higher in males than in females (t=4.46, p<.001). Adolescents who participated in school physical education classes engaged in more physical activity than those who did not (t=6.77, p<.001). Higher self-efficacy (β=.41, p<.001), male gender (β=.37, p<.001) and participation in school physical education classes (β=.19, p=.042) were associated with a higher likelihood of engagement in physical activity. CONCLUSION: It is necessary to develop nursing interventions that enhance self-efficacy in order to promote physical activity in adolescents with complex congenital heart disease. Physical activity should also be promoted in an individualized manner, taking into account gender, disease severity, and parental attitude.

Factors Affecting the Self-Management of Adolescents with Type 1 Diabetes Mellitus based on the Information-Motivation-Behavioral Skills Model

PURPOSE: The purpose of this study was to investigate associations between self-management and diabetes knowledge, diabetesrelated attitudes, family support, and self-efficacy in adolescents with type 1 diabetes mellitus based on the information-motivation- behavior skills model. METHODS: Data collection was conducted between March 18 and September 30, 2018. Patients (N=87) aged 12 to 19 years were recruited from the outpatient clinic of S children's hospital and an online community for patient with type 1 diabetes mellitus. Data were analyzed using descriptive statistics, the independent t-test, one-way ANOVA, Pearsons correlation, and hierarchical multiple linear regression with SPSS IBM 23.0, with the two-tailed level of significance set at 0.05. RESULTS: The mean score of self-management in adolescents with type 1 diabetes mellitus was 61.23±10.00 out of 80. The regression analysis showed that self-efficacy and family support significantly explained 56.9% of the variance in self-management (F=21.38, p<.001). Self-efficacy (β=.504, p<.001) and family support (β=.188, p<.001) were significant predictors of self-management. CONCLUSION: It is necessary to develop individual interventions to improve self-efficacy and family support for adolescents with type 1 diabetes mellitus to help them enhance their self-management.

Difficulties in End-of-Life Care and Educational Needs of Intensive Care Unit Nurses: A Mixed Methods Study / 한국호스피스완화의료학회지

PURPOSE: This study aimed to identify the difficulties with end-of-life care (EOLC) experienced by intensive care unit (ICU) nurses and to investigate their educational needs for EOLC. METHODS: This study aimed to identify the difficulties with end-of-life care (EOLC) experienced by intensive care unit (ICU) nurses and to investigate their educational needs for EOLC. RESULTS: The mean score on the difficulty of EOLC was 3.41 out of 5. The education needs derived from the qualitative analysis was categorized into four themes: 1) guidelines on professional EOLC, 2) spiritual care, 3) a program to take care of feelings of patients, families and nurses, and 4) activities to think about death. CONCLUSION: This study confirmed that ICU nurses were experiencing an extreme difficulty in providing EOLC. In addition, a qualitative analysis confirmed that they needed an EOL nursing program. To mitigate the difficulties experienced by nurses involved in EOLC, there is an urgent need to develop an education program for EOLC tailored to nurses' needs.

Re-transmissibility of mouse-adapted ME7 scrapie strain to ovine PrP transgenic mice

Scrapie is a mammalian transmissible spongiform encephalopathy or prion disease that predominantly affects sheep and goats. Scrapie has been shown to overcome the species barrier via experimental infection of other rodents. To confirm the re-transmissibility of the mouse-adapted ME7 scrapie strain to ovine prion protein (PrP) transgenic mice, mice of an ovinized transgenic mouse line carrying the Suffolk sheep PrP gene that contained the A₁₃₆ R₁₅₄ Q₁₇₁/ARQ allele were intracerebrally inoculated with brain homogenates obtained from terminally ill ME7-infected C57BL/6J mice. Herein, we report that the mouse-adapted ME7 scrapie strain was successfully re-transmitted to the transgenic mice expressing ovine PrP. In addition, we observed changes in the incubation period, glycoform profile, and pattern of scrapie PrP (PrP(Sc)) deposition in the affected brains. PrP(Sc) deposition in the hippocampal region of the brain of 2nd-passaged ovine PrP transgenic mice was accompanied by plaque formation. These results reveal that the mouse-adapted ME7 scrapie strain has the capacity to act as a template for the conversion of ovine normal monomeric precursors into a pathogenic form in ovine PrP transgenic mice. The change in glycoform pattern and the deposition of plaques in the hippocampal region of the brain of the 2nd-passaged PrP transgenic mice are most likely cellular PrP species dependent rather than being ME7 scrapie strain encoded.

Correlations between a Flexible Parental Visiting Environment and Parental Stress in Neonatal Intensive Care Units

PURPOSE: The purpose of this study was to examine the correlation between a flexible parental visiting environment and parental stress in neonatal intensive care units (NICUs).METHODS: The study participants included 60 parents of premature infants in NICUs. Structured questionnaires and interviews, as well as observations by researchers using a caregiving behavior checklist, were used to measure the flexibility of the parental visiting environment and parents' stress levels. Quantitative and qualitative data were collected concurrently and were initially analyzed as separate data sets. Data collection extended from March 11, 2018 to June 30. 2018 and the data were analyzed using descriptive statistics, the independent t-test, one-way analysis of variance, and Pearson correlation coefficients.RESULTS: There was a negative correlation (r=−.30, p=.021) between parental stress and the total number of visits in 7 days. We also found that the average duration of each visit and the number of caregiving behaviors performed by parents were positively correlated (r=.73, p<.001).CONCLUSION: When designing a flexible visiting environment for parents, parents should be encouraged to visit their babies. By doing so, stress can be reduced both for babies and for parents. Therefore, it is suggested that the related polices and regulations in South Korea should be changed to provide more a flexible visiting environment to promote better parent-child attachment and family adjustment.

Estimating Nationwide Prevalence of Live Births with Down Syndrome and Their Medical Expenditures in Korea

BACKGROUND: This study aimed to estimate the nationwide prevalence of live births with Down syndrome (DS) and its trends and compare the observed and model-based predicted prevalence rates. Further, we compared the direct medical expenditures among DS and non-DS patients. METHODS: Using the health administrative data of Health Insurance Review and Assessment in Korea, we selected 2,301 children with DS who were born between 2007 and 2016 to estimate the prevalence of live births with DS, and 12,265 non-DS children who were born between 2010 and 2014 to compare the direct medical expenditures among patients. RESULTS: The prevalence of live births with DS was 5.03 per 10,000 births in 9 years, and 13% of children with DS were medical aid recipients during the study period. The medical expenditure of children with DS was about 10-fold higher than that of non-DS children and their out-of-pocket expenditure was about twice as high. CONCLUSION: The prevalence of live birth with DS is high in the low socioeconomic group and the healthcare costs for the children with DS are significantly higher than those for non-DS children. Therefore, health authorities should help mothers at lower socioeconomic levels to receive adequate antenatal care and consider the cost of medical care for children with DS.

Clinical Characteristics of False-Positive Lymph Node on Chest CT or PET-CT Confirmed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Lung Cancer / 결핵및호흡기질환

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure to evaluate suspicious lymph node involvement of lung cancer because computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT (PET-CT) have limitations in their sensitivity and specificity. There are a number of benign causes of false positive lymph node such as anthracosis or anthracofibrosis, pneumoconiosis, old or active tuberculosis, interstitial lung disease, and other infectious conditions including pneumonia. The purpose of this study was to evaluate possible causes of false positive lymph node detected in chest CT or PET-CT. METHODS: Two hundred forty-seven patients who were initially diagnosed with lung cancer between May 2009 and December 2012, and underwent EBUS-TBNA to confirm suspicious lymph node involvement by chest CT or PET-CT were analyzed for the study. RESULTS: Of 247 cases, EBUS-TBNA confirmed malignancy in at least one lymph node in 189. The remaining 58 patients whose EBUS-TBNA results were negative were analyzed. Age ≥65, squamous cell carcinoma as the histologic type, and pneumoconiosis were related with false-positive lymph node involvement on imaging studies such as chest CT and PET-CT. CONCLUSION: These findings suggest that lung cancer staging should be done more carefully when a patient has clinically benign lymph node characteristics including older age, squamous cell carcinoma, and benign lung conditions.

Needs for Pediatric Palliative Care among Parents of Children with Complex Chronic Conditions

PURPOSE: The purpose of this study was to investigate the needs for pediatric palliative care (PPC) among parents of children with complex chronic conditions (CCCs) and to investigate differences in the needs for PPC according to their general characteristics. METHODS: A cross-sectional survey was conducted between March 28 and May 18, 2018. Parents (N=96) who had a child under 18 years with a CCC were recruited. Data were analyzed using descriptive statistics, independent t-test, and one-way ANOVA. RESULTS: The overall average need for PPC was 3.58±0.33 out of 4.00. In terms of care for the subjects' children, the highest need was physical care, followed by psychosocial and spiritual care. In the sub-dimensions, preservation of physical function received the highest score. Of the items, the highest need was for seizure control. In terms of care for the subjects themselves, the highest need was for psychosocial care, followed by bereavement and spiritual care. In the sub-dimensions, communication received the highest score. Of the items, the highest need was for smooth communication with medical staff. Differences in needs for PPC according to participants' general characteristics were not statistically significant. CONCLUSION: Medical staff should provide PPC according to the priorities of parents' perceived needs.

The Current Status of SPECT or SPECT/CT in South Korea / 대한핵의학회잡지

The first step to nuclear medicine in Korea started with introduction of the gamma camera in 1969. Although planar images with the gamma camera give important functional information, they have the limitations that result from 2-dimensional images. Single-photon emission computed tomography (SPECT) due to its 3-dimensional image acquisition is superior to earlier planar gamma imaging in image resolution and diagnostic accuracy. As demand for a hybrid functional and anatomical imaging device has increased, integrated SPECT/CT systems have been used. In Korea, SPECT/CT was for the first time installed in 2003. SPECT/CT can eliminate many possible pitfalls on SPECT-alone images, making better attenuation correction and thereby improving image quality. Therefore, SPECT/CT is clinically preferred in many hospitals in various aspects.More recently, additional SPECT/CT images taken from the region with equivocal uptake on planar images have been helpful in making precise interpretation as part of their clinical workup in postoperative thyroid cancer patients. SPECT and SPECT/CT have various advantages, but its clinical application has gradually decreased in recent few years. While some researchers investigated the myocardial blood flow with cardiac PET using F-18 FDG or N-13 ammonia, myocardial perfusion SPECT is, at present, the radionuclide imaging study of choice for the risk stratification and guiding therapy in the coronary artery disease patients in Korea. New diagnostic radiopharmaceuticals for AD have received increasing attention; nevertheless, brain SPECT will remain the most reliable modality evaluating cerebral perfusion.

Visual and Quantitative Analysis of Cisternography for the Detection of Cerebrospinal Fluid Leakage / 대한핵의학회잡지

We herein present a case of a 29-year-old man with clear rhinorrhea, which persisted for 8 years following a myringotomy. After cotton pledgets were placed in several different regions of the nasal cavity, cisternography using Tc-99m DTPA was performed to measure the radioactivity of each pledget. Cisternography showed subtle uptake in the nasal cavity. However, intense uptake was detected in the pledget placed in the right eustachian tube orifice, where the pledget:serum count ratio was 10.3:1. The patient underwent duroplasty and cranioplasty, and the rhinorrhea resolved.

The Significance and Limitations of Korean Diagnosis-Related Groups in Psychiatric Inpatients' Hospital Charges / 신경정신의학

OBJECTIVES: This study was conducted to investigate whether the charges associated with Korean Diagnosis-Related Groups for mental health inpatients adequately reflect the degree of medical resource consumption for inpatient treatment in the psychiatric ward. METHODS: This study was conducted with psychiatric inpatients data for 2014 from the National Health Insurance claim database. The main diagnoses required for admission, classification of the hospitals, and main treatment services were analyzed by examining descriptive statistics. Homogeneities of the major diagnostic criteria were assessed by calculating coefficient variances. Explanation power was determined by R2 values. RESULTS: The most frequent disorders for psychiatric inpatient treatment were alcohol-use disorder, depressive episodes, bipolar affective disorder, and dementia in Alzheimer's disease. Hospitalization and psychotherapy fees were the main medical expenses. Regardless of the homogeneity of the disease group, duration of hospital stay was the factor that most influenced medical expenses. In the psychiatric area, explanation power of Korean Diagnosis-Related Groups was 16.52% (p<0.05), which was significantly lower than that for other major diagnostic area. CONCLUSION: Most psychiatric illnesses are chronic, and the density of services can vary depending on illness severity or associated complications. The current Korean Diagnosis-Related Groups criteria did not adequately represent the amount of in-hospital medical expenditures. A novel Korean classification system that reflects the expenditures of medical resources in psychiatric hospitals should be developed in order to provide appropriate reimbursements.

Erratum: The Significance and Limitations of Korean Diagnosis-Related Groups in Psychiatric Inpatients' Hospital Charges / 신경정신의학

This correction is being published to correct the errors and to added missing contents.

Real-Time Quaking-Induced Conversion Analysis for the Diagnosis of Sporadic Creutzfeldt-Jakob Disease in Korea

BACKGROUND AND PURPOSE: The level of 14-3-3 protein in the cerebrospinal fluid (CSF) is increased in Creutzfeldt-Jakob disease (CJD) patients, which has led to it being used as a clinical biomarker for the ante-mortem diagnosis of human prion diseases. However, the specificity of the 14-3-3 protein is less reliable for CJD diagnosis. Newly developed assays including real-time quaking-induced conversion (RT-QuIC) have made it possible to detect the PrPSc-like abnormal prion isoform with a high sensitivity in animal and human specimens that might contain a minute amount of PrP(Sc) due to in vitro prion replication. METHODS: This study applied a highly sensitive RT-QuIC assay using recombinant human PrP to detect PrP(Sc) in the CSF of 81 patients with sporadic CJD (sCJD) in Korea. RESULTS: RT-QuIC analysis of the CSF samples based on the expression levels of 14-3-3 and total tau proteins revealed positivity in 62 of 81 sCJD patients (sensitivity of 76.5%) but no positive results in the 100 non-CJD patients. CONCLUSIONS: The sensitivity of the RT-QuIC in this study was similar to that in some previous reports, and the specificity of RT-QuIC was higher than that of 14-3-3 in CSF, suggesting that RT-QuIC analysis can complement the weakness of the specificity of 14-3-3 for the diagnosis of sCJD. These results indicate that RT-QuIC might be very useful for the rapid and specific diagnosis of sCJD and provide a practical novel method for the ante-mortem diagnosis of human prion diseases.

Review of the Registration in the Clinical Research Information Service

Clinical research registration is required in many countries to improve transparency of clinical research and to ensure subject safety. Developed in February 2010, the Clinical Research Information Service (CRIS) is an online registration system for clinical studies in Korea and one of the primary registries of the World Health Organization (WHO) International Clinical Trials Registry Platform. The present analysis investigated the characteristics of studies registered in the CRIS between February 2010 and December 2014. Data for the analysis were extracted from the CRIS database. As of December 31, 2014, 1,323 clinical studies were registered. Of these, 938 (70.9%) were interventional studies and 385 (29.1%) were observational studies. A total of 248 (18.7%) studies were funded by government sources, 1,051 (79.4%) by non-government sources, and 24 (1.8%) by both. The most frequently studied disease category based on the ICD-10 classification was the digestive system (13.1%), followed by the nervous system (9.4%) and musculoskeletal system (9.1%). Only 17.8% of the studies were registered prior to enrollment of the first subject. Comparing the number of registered or approved clinical studies between the CRIS, the Ministry of Food and Drug Safety, and ClinicalTrials.gov suggests that a considerable number of clinical studies are not registered with the CRIS; therefore, we would suggest that such registration should be the mandatory legal requirement.