Objective: Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR. Methods: We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction. Results: KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients. Conclusion miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.

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.

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.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.

Background: The oxygen reserve index (ORi) noninvasively measures oxygen levels within the mild hyperoxia range. To evaluate whether a degree of increase in the ORi during preoxygenation for general anesthesia is associated with the occurrence of postoperative pulmonary complications (PPCs). Methods: We enrolled 154 patients who underwent preoperative pulmonary function tests and were scheduled for elective surgery under general anesthesia. We aimed to measure the increase in ORi during preoxygenation before general anesthesia and analyze its association with PPCs. Results: PPCs occurred in 76 (49%) participants. Multivariate logistic regression analysis revealed that the three-minute preoxygenation ORi was significantly associated with PPCs (Odds ratio [OR]: 0.02, 95% CI [0.00–0.16], P < 0.001). The areas under the curve (AUC [95% CI]) in the receiver operating characteristic curve analysis for the three-minute preoxygenation ORi for PPCs were 0.64 (0.55–0.73). After a subgroup analysis, multivariate logistic regression showed that the three-minute preoxygenation ORi was significantly associated with PPCs among patients who underwent thoracic surgery (OR: 0.01, 95% CI [0.00–0.19], P = 0.006). The AUC of the three-minute preoxygenation ORi for PPCs was 0.72 (0.57–0.86) in patients who underwent thoracic surgery. Conclusions A low ORi measured after 3 min of preoxygenation for general anesthesia was associated with an increased risk of PPCs, including those undergoing thoracic surgery. This study demonstrated the potential of ORi, measured after oxygen administration, as a tool for evaluating lung function that complements traditional lung function tests and scoring systems.

Frailty is a condition marked by a progressive decline in physiological functioning due to aging, leading to increased disease morbidity and rising healthcare costs. Therefore, it is important to prevent frailty through proper management. Not only does a lack of physical activity contribute to frailty, but inadequate dietary intake, resulting from decreased appetite and malabsorption, is also a significant risk factor. This study aimed to develop a 16-week algorithm to assess the nutritional risks associated with frailty, provide personalized nutritional solutions, and manage frailty risk factors through continuous monitoring and periodic reassessment. A total of 20 indicators were selected to create a nutritional health score. The selected indicators encompassed nutritional risk factors for frailty, disease history, and hematological factors. Reassessments were designed to occur at four-week intervals to revise personalized management goals and adjust solutions. Metrics were prioritized to provide a personalized solution. A user-friendly monitoring system was developed that leveraged voice recognition technology to determine compliance. It is anticipated that the algorithm will serve several purposes. First, this outcome will allow us to help prevent and delay the onset of frailty by utilizing a mobile app. Second, it will reduce the time and economic costs associated with nutritional management. Finally, it will facilitate future professional counseling and monitoring.

Accessory breast tissue can appear along the mammary ridge, extending from the axilla to the groin, with the axilla being the most common site. Malignancies arising in accessory breast tissue are rare, representing approximately 0.3%–0.6% of all breast cancer cases.When evaluating accessory breasts, it is essential to apply the same management strategies used for conventionally positioned breasts. This report presents a case of ductal carcinoma in situ originating from accessory breast tissue in the axilla of a 55-year-old woman. The diagnosis was established through a comprehensive assessment involving mammography, ultrasound, and magnetic resonance imaging. Since the axillary accessory breast tissue wasn’t initially included in the routine mammography, we added an axillary tail view to evaluate the extent and morphology of malignant microcalcifications.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: Although excessive physical activity (PA) does not always confer additional health benefits, there is a paucity of studies that have quantitatively examined the doseresponse relationship between PA and type 2 diabetes. Therefore, this study investigated the relationship between the type 2 diabetes prevalence and intensity, frequency, and metabolic equivalent of task (MET) score of PA in a large population sample. Methods: We conducted a nationwide cross-sectional analysis examining sociodemographic variables, PA habits, and type 2 diabetes prevalence in 2,428,448 participants included in the Korea Community Health Survey. The non-linear association between MET score and odds ratios (ORs) for type 2 diabetes prevalence was plotted using a weighted generalized additive model. Categorical analysis was used to examine the joint association of moderate-intensity PA (MPA) and vigorous-intensity PA (VPA), and the influence of PA frequency. Results: MET score and diabetes prevalence revealed a non-linear association with the nadir at 1,028 MET-min/week, beyond which ORs increased with additional PA. Joint analysis of MPA and VPA showed the lowest OR of 0.79 (95% confidence interval, 0.75–0.84) for those engaging in 300–600 MET-min/week of MPA and > 600 MET-min/week of VPA concurrently, corresponding with World Health Organization recommendations. Additionally, both “weekend warriors” and “regularly active” individuals showed lower ORs compared to the inactive, although no significant difference was noted between the active groups. Conclusion In a large South Korean sample, higher PA is not always associated with a lower prevalence of type 2 diabetes, as the association follows a non-linear pattern; differences existed across sociodemographic variables. Considering the joint association, an adequate combination of MPA and VPA is recommended. The frequency of PA does not significantly influence the type 2 diabetes prevalence.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.