BACKGROUND: Exogenous Cushing’s syndrome, which results from prolonged glucocorticoid treatment, is associated with metabolic abnormalities. Previously, we reported the inhibitory effect of tonsil-derived mesenchymal stem cell conditioned medium (T-MSC CM) on glucocorticoid signal transduction. In this study, we investigated the therapeutic efficacy of T-MSCs in a mouse model of exogenous Cushing’s syndrome. METHODS: Exogenous Cushing’s syndrome model mice was generated by corticosterone administration in the drinking water for 5 weeks, and T-MSCs were injected intraperitoneally twice during the third week. Serum lipid profiles were measured using a chemistry analyzer. HepG2 cells were treated with dexamethasone and co-cultured with T-MSCs.Expression levels of genes involved in cholesterol metabolism were examined using real-time PCR. Low-density lipoprotein receptor (LDLR) protein levels were determined using western blotting and immunohistochemistry. Liver RNA extracted from the CORT and CORT ? MSC mouse groups was used for transcriptome sequencing analysis and protein– protein interaction analysis. RESULTS: Weight reduction and improvements in dyslipidemia by T-MSC administration were observed only in female mice. T-MSCs reduce circulating LDL cholesterol levels by downregulating liver X receptor a (LXRa) and inducible degrader of LDLR (IDOL) expression, thereby stabilizing LDLRs in the liver. Transcriptome analysis of liver tissue revealed pathways that are regulated by T-MSCs administration. CONCLUSION Administration of MSCs to female mice receiving chronic corticosterone treatment reduced the circulating LDL cholesterol level by downregulating the LXRa–IDOL axis in hepatocytes. These results suggest that T-MSCs may offer a novel therapeutic strategy for managing exogenous Cushing’s syndrome by regulating cholesterol metabolism.

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: 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: Emphysematous pyelonephritis (EPN) is a life-threatening disease requiring immediate treatment. This multicenter retrospective cohort study aimed to analyze the mortality rate and risk factors associated with EPN. Materials and Methods: Between January 2011 and February 2021, 217 patients diagnosed with EPN via computed tomography who visited 14 teaching hospitals were retrospectively analyzed. Clinical data, including age, sex, comorbidities, Huang and Tseng classification, hydronephrosis, acute kidney injury, blood and urine tests, surgical interventions, percutaneous drainage, and conservative treatments, were compared between the survival and death groups. Risk factors for mortality due to EPN were analyzed using univariate and multivariate methods. Results: The mean age of survivors and deceased patients was 67.8 and 69.0 years, respectively (p=0.136). The sex distribution (male/female) was 48/146 and 8/15, respectively (p=0.298). Of the 217 patients, 23 died, resulting in a mortality rate of 10.6%. In univariate analysis, the Huang and Tseng classification (p=0.004), platelet count (p=0.005), and acute kidney injury (p=0.007) were significantly associated with mortality from EPN. In multivariate analysis, only the Huang and Tseng classification (p=0.029) was identified as a risk factor. Mortality rates according to the Huang and Tseng classification were as follows: class I (5.88%), class II (7.50%), class IIIa (14.28%), class IIIb (25.00%), and class IV (23.07%). Conclusions EPN is associated with a high mortality rate. Among various clinical factors, the Huang and Tseng classification was the most significant indicator for predicting mortality.

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.

Purpose: To analyze anterior, posterior, and total corneal refractive profiles and thickness using anterior segment (AS) sweptsource optical coherence tomography (SS-OCT) in Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) patients. Methods: This retrospective study compared 23 eyes from 14 patients with SJS/TEN with 23 eyes from 14 age- and sexmatched controls. AS SS-OCT measured corneal refractive profiles and pachymetry. Parameters included anterior, posterior, and total corneal power values, posterior to anterior curvature ratio, maximal corneal power, and thickness profiles. The SJS/TEN group was subdivided based on corneal opacity presence (subgroup A) or absence (subgroup B). Results: The SJS/TEN group showed significantly higher corneal astigmatism and maximal corneal power values for both anterior and posterior curvatures. Steep total corneal power and total corneal astigmatism were higher in the SJS/TEN group. The thinnest corneal thickness was lower, and its distance from the corneal vertex was greater in the SJS/TEN group. Subgroup analysis revealed that these differences were primarily attributed to the presence of corneal opacity. Additionally, automated keratometry of the anterior corneal surface showed significantly higher values, including steep, flat, and average keratometry and corneal astigmatism, in the SJS/TEN group. Conclusions AS SS-OCT shows significant alterations in both anterior and posterior corneal curvatures in patients with SJS/TEN. These findings emphasize the importance of considering posterior corneal curvature changes in pre-cataract surgery assessments and contact lens prescriptions for patients with SJS/TEN.

Purpose: This study evaluated the objective changes in the contralateral eye after unilateral cataract surgery. Methods: The study was designed as retrospective observational study. It included 44 patients who underwent unilateral cataract surgery. Collected data were uncorrected and corrected visual acuity, spherical equivalent, intraocular pressure, contrast sensitivity (CS), stereoacuity, and anterior segment optical coherence tomography parameters. Data were collected preoperatively, and 1 week and 1 month postoperatively for each eye. Results: Following unilateral cataract surgery, the pupil size of the fellow eye decreased from 3.46 mm to 3.17 mm (postoperative week 1, p = 0.003) and 3.08 mm (postoperative month 1, p < 0.001). Anterior chamber depth of the fellow eye increased significantly from 3.16 mm to 3.27 mm (postoperative week 1, p = 0.005) and 3.26 mm (postoperative month 1, p = 0.001). Uncorrected distance visual acuity (UDVA) of the fellow eye improved significantly at postoperative week 1 (p = 0.042) and postoperative month 1 (p = 0.044). Change of UDVA of the fellow eye at postoperative month 1 was significantly correlated with that of the treated eye (p = 0.039). Conclusions Anterior chamber structures changed and UDVA improved in the contralateral eye after unilateral cataract surgery in our cohort. Because fellow eyes were positively affected by monocular cataract surgery, it would be good information if planning for unilateral cataract surgery due to inevitable reasons.

It is difficult to determine a cause of bile duct stricture and dilatation. Eosinophilic cholangitis, a rare benign condition, may be one cause of bile duct stricture and dilatation. It can be evaluated using various methods of histopathology, radiographs, endoscopy, and hematologic findings. Treatment generally involves steroid therapy which can lead to improvement. This case report will discuss eosinophilic cholangitis, emphasizing that while it can easily be overlooked but should be considered in differential diagnoses.

Objectives: To assess the trends and disparities in the utilization of F-18 fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) in Korea between 2018 and 2022, with a focus on disease classification, patient demographics, and regional distribution. Methods: This national surveillance retrospective study uses data from the Health Insurance Review and Assessment Service (HIRA) database, which includes all FDG PET/CT examinations conducted in Korea from 2018 to 2022. Disease classifications, cancer types, age groups, gender, and geographic regions were analyzed using descriptive statistics. Utilization rates per 100,000 population were calculated for regional comparisons. Results: FDG PET/CT utilization increased by 25.4%, from 174,885 examinations in 2018 to 219,377 in 2022. Older age groups (60 years and above) accounted for the majority of examinations, with males undergoing more examinations than females. Oncology remained the primary indication, with lung, colorectal, and non-Hodgkin lymphoma leading in examination numbers. The number of examinations performed on patients aged 60 and above increased at a higher rate compared to those under 60. Significant geographic disparities were found, with Seoul reporting the highest utilization rate (1,114.3 examinations per 100,000 population), while Gyeongbuk exhibited much lower rate (26.2 examinations per 100,000 population). Conclusions This study highlights the growing utilization of FDG PET/CT in Korea, particularly among older adults, with significant gender differences in cancer types. The findings also reveal disparities in FDG PET/CT utilization across regions, indicating varying access to advanced imaging technology.