Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.

BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

Background: This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management. Methods: Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline. Results: Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%). Conclusion Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.

Purpose: Although some medications trigger the worsening of myasthenia gravis (MG), their clinical influence on patients with MG has not been significantly evaluated. We aimed to investigate whether the risk of clinical worsening of MG increases after administering cautionary drugs in patients with MG. Materials and Methods: This retrospective case-control study was based on the medical records of patients diagnosed with MG between 2007 and 2020. We analyzed the risk of MG worsening in patients exposed to cautionary drugs during the risk period, defined as 6 months from the first exposure to cautionary drugs. The risk of MG worsening in the exposed patients was compared to that in the non-exposed patients, who were individually matched in a 1:1 ratio with exposed cases for sex, age, thymoma, and autoantibodies. Results: Of the 2002 patients diagnosed with MG, 552 (27.6%) were exposed to cautionary drugs. Neuromuscular blocking agents (320 patients) and beta blockers (66123 person-days) were the most frequently prescribed medications. After exact matching, 220 exposed and 220 non-exposed patients were enrolled. The incidence rate of clinical worsening during the risk period was significantly higher in the exposed patients than in the non-exposed patients (odds ratio=4.09; 95% confidence interval, 1.88–8.90;p<0.001). Clinical worsening was observed in 31 (14.1%) of the exposed patients and in 8 (3.6%) of the non-exposed patients. Conclusion The administration of cautionary drugs increased the risk of clinical worsening in patients with MG. Clinicians should be aware of this risk when cautionary drugs need to be administered.

Background: s/Aims: In hepatocellular carcinoma (HCC), which exhibits high mortality and recurrence rates globally, the traits of cancer stem cells (CSCs) that significantly influence recurrence and metastasis are not well understood. CSCs are self-renewing cell types identified in most liquid and solid cancers, contributing to tumor initiation, growth, resistance, recurrence, and metastasis following chemo-radiotherapy or trans-arterial chemoembolization therapy. Methods: CSCs are classified based on the expression of cell surface markers such as CD133, which varies depending on the tumor type. Proteomic analysis of liver cancer cell lines with cancer stem cell potential and HCC cancer cell lines lacking stem cell propensity was conducted to compare and analyze specific expression patterns. Results: Proteomic profiling and enrichment analysis revealed higher expression of the calcium-binding protein S100 family in CD133+ Huh7 cells than in CD133- or wild-type cells. Furthermore, elevated expression of S100 family members was confirmed in an actual CD133+ liver cancer cell line via protein-protein network analysis and quantitative polymerase chain reaction (qPCR). Conclusion The S100 family members are not only new markers of cancer stem cells but will also assist in identifying new treatment strategies for CSC metastasis and tumor advancement.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Background/Aims: Post-infectious irritable bowel syndrome (PI-IBS) is characterized by chronic gastrointestinal symptoms that arise following an episode of infectious enteritis. The incidence rates vary, ranging from 5% to 32% and the risk factors are not well known. We aim to investigate the incidence and risk factors of PI-IBS in enteritis patients admitted to university hospitals in Korea. Methods: This multi-center prospective study was conducted in patients hospitalized for infectious enteritis. Each patient underwent 1 outpatient visit and 3 telephone surveys during the first year after discharge to determine if PI-IBS occurred within the follow-up period. Results: In the 3-month survey, 7 out of 354 patients (2%) were diagnosed with PI-IBS, and after 1 year, only 1 patient met the criteria for IBS.No statistically significant difference was found between the PI-IBS group and the non-PI-IBS group in terms of age, sex, underlying diseases, medication history, gastrointestinal symptoms, enteritis location, causative strain, hospitalization and treatment periods, and laboratory findings. Female sex (P = 0.003), enteropathogenic Escherichia coli (EPEC) infection (P = 0.044), and a longer total treatment period (P = 0.018) were independent risk factors for diarrhea lasting ≥ 3 months after enteritis. Conclusions The incidence of PI-IBS in Korea was relatively low, and most cases improved over time. No risk factors associated with the development of PI-IBS were found. However, persistent diarrhea after enteritis was associated with female sex, EPEC infection, and severe or long-lasting enteritis. IBS symptoms may persist after severe enteritis but usually improve with time.

Background: Residential smoking cessation therapy programs offer intensive treatment for heavy smokers who struggle to quit independently, particularly those with high nicotine dependence and health conditions that necessitate urgent cessation. While previous studies have established the effectiveness of such programs and identified various factors influencing smoking cessation success, it remains unclear how changes in smokers’ thoughts and attitudes following residential therapy correlate with their ability to quit smoking. We investigated the relationship between smoking cessation-related characteristics, smoking-related psychological status, and participants’ smoking cessation success after a residential smoking cessation therapy program. Methods: From January 2017 to December 2018, 291 participants completed the program. All participants completed questionnaires on smoking cessation-related characteristics and smoking-related psychological status before the program and on the 5th day. Six months later, smoking cessation success was assessed using a urine cotinine test. Results: After 6 months, 222 participants successfully quit smoking, while 69 failed. The success and failure groups exhibited statistically significant differences in age, marital status, total smoking duration, stress, and emotion regulation strategies. Participants who used ineffective emotion regulation strategies more frequently had a lower rate of smoking cessation success (odds ratio [OR], 0.969; 95% confidence interval [CI], 0.948–0.991). Moreover, an increase in the perception of the negative effects of smoking cessation (OR, 0.982; 95% CI, 0.967–0.997) and smoking temptation (OR, 0.960; 95% CI, 0.929–0.993) was associated with higher cessation success. Conclusion Emotion regulation strategies, perceptions of the effects of smoking cessation, and smoking temptation were associated with successful smoking cessation.

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.

Objective: As the demand for community mental health services continues to grow, the need for well-equipped and organized services has become apparent. This study aimed to optimize the roles and infrastructure of mental health services, by establishing, among other initiatives, standardized operating models. Methods: The study was conducted in multiple phases from May 12, 2021, to December 29, 2021. Stakeholders within South Korea and metropolitan mental health welfare centers were targeted, but addiction management support centers, including officials, patients, and their families, were integrated as well. A literature review and survey, focus group interviews, a Delphi survey, and expert consultation contributed to comprehensive revisions and improvements of the mental health service model. Results: The proposed model for community mental health welfare centers emphasizes the expansion of personnel and infrastructure, with a focus on severe mental illnesses and suicide prevention. The model for metropolitan mental health welfare centers delineates essential tasks in areas such as project planning and establishment, community research, and education about severe mental illnesses. The establishment of a 24-hour emergency intervention center was a crucial feature. In the integrated addiction support center model, the need to promote addiction management is defined as an essential task and the establishment of national governance for addiction policies is recommended. Conclusion This study proposed standard operating models for three types of mental health service centers. To meet the increasing need for community care, robust mental health service delivery systems are of primary importance.