Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.

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 and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

Background: This study aimed to investigate the prevalence, management, and comorbidities of diabetes mellitus among Korean adults. Methods: Data from the Korea National Health and Nutrition Examination Survey (2019–2022) were analyzed to assess the prevalence, treatment, risk factors, and comorbidities of diabetes. Comparisons between young and older adults with diabetes were emphasized. Results: Among Korean adults aged ≥30 years, the prevalence of diabetes is 15.5% during 2021–2022. Of these, 74.7% were aware of their condition, 70.9% received antidiabetic treatment, and only 32.4% achieved glycosylated hemoglobin (HbA1c) <6.5%. Moreover, 15.9% met the integrated management targets, which included HbA1c <6.5%, blood pressure <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL. In young adults aged 19 to 39 years, the prevalence of diabetes was 2.2%. Among them, 43.3% were aware of their condition, 34.6% received treatment, and 29.6% achieved HbA1c <6.5%. Obesity affected 87.1%, and 26.9% had both hypertension and hypercholesterolemia. Among adults aged ≥65 years, the prevalence of diabetes was 29.3%, with awareness, treatment, and control rates of 78.8%, 75.7%, and 31.2%, respectively. Integrated management targets (HbA1c <7.5%, hypertension, and lipids) were achieved by 40.1%. Conclusion Diabetes mellitus remains highly prevalent among Korean adults, with significant gaps in integrated glycemic, blood pressure, and lipid control. Older adults with diabetes show higher awareness and treatment rates but limited integrated management outcomes. Young adults with diabetes bear a significant burden of obesity and comorbidities, alongside low awareness and treatment rates. Therefore, early intervention programs, education, and strategies tailored to younger populations are urgently required.

Background: This study aimed to examine trends in the prevalence, incidence, metabolic characteristics, and management of type 2 diabetes mellitus (T2DM) among young adults in South Korea. Methods: Young adults with T2DM were defined as individuals aged 19 to 39 years who met the diagnostic criteria for T2DM. Data from the Korean National Health Insurance Service-Customized Database (2010–2020, n=225,497–372,726) were analyzed to evaluate trends in T2DM prevalence, incidence, metabolic profiles, comorbidities, and antidiabetic drug prescription. Additional analyses were performed using the Korea National Health and Nutrition Examination Survey. Results: The prevalence of T2DM in young adults significantly increased from 1.02% in 2010 to 2.02% in 2020 (P<0.001), corresponding to 372,726 patients in 2020. Over the same period, the incidence rate remained stable within the range of 0.36% to 0.45%. Prediabetes prevalence steadily increased from 15.53% to 20.92%, affecting 3.87 million individuals in 2020. The proportion of young adults with T2DM who were obese also increased, with 67.8% having a body mass index (BMI) ≥25 kg/m² and 31.6% having a BMI ≥30 kg/m² in 2020. The prevalence of hypertension, dyslipidemia, and fatty liver disease also increased, reaching 34.2%, 79.8%, and 78.9%, respectively, in 2020. Although the overall pharmacological treatment rate remained low, the prescription of antidiabetic medications with weight-reducing properties increased over the study period. Conclusion The prevalence of T2DM among young adults in South Korea nearly doubled over the past decade. The strong association with obesity and metabolic comorbidities emphasizes the urgent need for targeted prevention and management strategies tailored to this population.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2022, with international comparisons. Materials and Methods: Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2022), with survival follow-up until December 31, 2023. Mortality data obtained from Statistics Korea, while international comparisons were based on GLOBOCAN data. Results: In 2022, 282,047 newly diagnosed cancer cases (age-standardized rate [ASR], 287.0 per 100,000) and 83,378 deaths from cancer (ASR, 65.7 per 100,000) were reported. The proportion of localized-stage cancers increased from 45.6% in 2005 to 50.9% in 2022. Stomach, colorectal, and breast cancer showed increased localized-stage diagnoses by 18.1, 18.5, and 9.9 percentage points, respectively. Compared to 2001-2005, the 5-year relative survival (2018-2022) increased by 20.4 percentage points for stomach cancer, 7.6 for colorectal cancer, and 5.6 for breast cancer. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence (M/I) ratios for these cancers. The 5-year relative survival (2018-2022) was 72.9%, contributing to over 2.59 million prevalent cases in 2022. Conclusion Since the launch of the National Cancer Screening Program in 2002, early detection has improved, increasing the diagnosis of localized-stage cancers and survival rates. Korea recorded the lowest M/I ratio among major comparison countries, demonstrating the effectiveness of its National Cancer Control Program.