RESULTS: Resveratrol significantly reduced cardiac hypertrophy and remodeling in aging hearts. In addition, resveratrol significantly ameliorated aging-induced mitochondrial dysfunction (e.g., decreased oxygen respiration and increased hydrogen peroxide emission) and mitochondria-dependent apoptotic signaling (the Bax/Bcl-2 ratio, mitochondrial permeability transition pore opening sensitivity, and cleaved caspase-3 protein levels).Resveratrol also significantly attenuated aging-induced apoptosis (determined via cleaved caspase-3 staining and TUNEL-positive myonuclei) in cardiac muscles. CONCLUSION This study demonstrates that resveratrol treatment has a beneficial effect on aging-induced cardiac remodeling by ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptosis in the heart.

The prevalence of postpartum depression (PPD) in Asia is reported to range from 13.53% to 22.31%. However, there remains a gap in the identification of PPD, particularly regarding cultural cutoff points. Therefore, the purpose of this scoping review was to determine the prevalence and associated factors of PPD in Eastern, South-eastern, Western, and Southern Asian countries and analyze the cutoff points of the Edinburgh Postnatal Depression Scale (EPDS) used across these countries. Following Arksey and O'Malley’s five-step scoping review framework, the population was defined as mothers, the concept as the EPDS, and the context as the Asian region. A literature search was conducted using PubMed, Embase, CINAHL, PsycINFO, and Web of Science. The data analysis focused on demographic characteristics, EPDS cutoffs and features, PPD prevalence, and its associated factors. Nineteen studies were selected. Most countries used translated versions of the EPDS with demonstrated reliability and validity. The cutoff scores varied, with most using scores of 10 or higher. The prevalence of PPD ranged from 5.1% to 78.7%. Key associated factors for PPD included cultural factors such as relationships with in-laws and preferences for the newborn’s sex. To improve the accuracy of PPD screening in Asia, the EPDS should be used consistently, and appropriate cutoff criteria must be established. In addition, prevention strategies and programs that reflect the cultural characteristics and social context of Asia need to be developed for the early detection and prevention of PPD.

Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by hyperglycemia. While lifestyle modifications and oral medications are initial treatments, many patients require injectable therapies like insulin and incretin-based drugs. Insulin therapy, a cornerstone treatment for T2DM, can effectively control blood sugar but is associated with hypoglycemia and weight gain. Incretin-based therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists offer improved glycemic control, weight loss, and reduced cardiovascular risk. Recent studies have shown the superiority of incretin-based therapies over basal insulin. Among these, GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor dual agonists like tirzepatide have demonstrated significant weight loss and improved glycemic control. Selection of injectable therapy should be individualized based on factors like glycemic goals, cardiovascular risk, hypoglycemia risk, and patient preference. While insulin remains a useful option, incretin-based therapies, especially newer agents, offer promising therapeutic benefits for many patients with T2DM.

Background/Aims: This study aimed to investigate co-occurrence and clinical characteristics of sexually transmitted infections (STIs) and pelvic inflammatory disease (PID) in women hospitalized for acute pyelonephritis (APN). Methods: This single-center retrospective study reviewed medical records of inpatients with APN from January 2019 to February 2023 and identified records of 142 patients who were referred to a gynecologist to evaluate gynecological diseases including STIs. Results: Of the 142 patients, 47 were tested positive for sexually transmitted pathogens in nucleic acid amplification testing, confirming the presence of STIs. In patients with APN, those with STIs were more likely to have lower abdominal pain or cervical motion tenderness (CMT) on pelvic examination and leukocytosis (> 14.5 × 109/L) than those without STIs. Of the 93 patients who underwent pelvic examination, 34 had CMT with one or more of additional criteria for the clinical diagnosis of PID, such as abnormal vaginal discharge and leukorrhea confirmed by microscopic examination, which could be clinically diagnosed as PID. Conclusions In sexually active women with APN, it is important to evaluate the possibility of STIs and PID, considering several risk factors such as lower abdominal pain, abnormal vaginal discharge, CMT, and leukocytosis.

Fine particulate matter (FPM) is a major component of air pollution and has emerged as a significant global health concern owing to its adverse health effects. Previous studies have investigated the correlation between bone health and FPM through cohort or review studies. However, the effects of FPM exposure on bone health are poorly understood. This study aimed to investigate the effects of FPM on bone health and elucidate these effects in vitro and in vivo using mice. Micro-CT analysis in vivo revealed FPM exposure decreased bone mineral density, trabecular bone volume/total volume ratio, and trabecular number in the femurs of mice, while increasing trabecular separation. Histological analysis showed that the FPM-treated group had a reduced trabecular area and an increased number of osteoclasts in the bone tissue. Moreover, in vitro studies revealed that low concentrations of FPM significantly enhanced osteoclast differentiation. These findings further support the notion that short-term FPM exposure negatively impacts bone health, providing a foundation for further research on this topic.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Purpose: This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB). Methods: CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses. Results: Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P<0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P<0.001) and HFF (P<0.001) significantly affected CAP, whereas LSM and fibrosis stages did not. Conclusion CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.

Background: Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods. Methods: A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2. Results: All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%). Conclusions Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.