1.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
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.
2.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
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.
3.Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization
Jung Hoon KIM ; Hye-Ok KIM ; Su-Yeon LEE ; Eun-A PARK ; Kyoung Hee CHOI ; Kiye KANG ; Eun Jeong YU ; Mi Kyoung KOONG ; Kyung-Ah LEE
Clinical and Experimental Reproductive Medicine 2025;52(1):44-55
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.
4.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
5.UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer
Chi Young KIM ; Eun Hye LEE ; Se Hyun KWAK ; Sang Hoon LEE ; Eun Young KIM ; Min Kyoung PARK ; Yoon Jin CHA ; Yoon Soo CHANG
Tuberculosis and Respiratory Diseases 2024;87(4):494-504
Background:
Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer.
Methods:
Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated.
Results:
We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC.
Conclusion
UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.
6.Robotic Single-Site Plus One-Port Myomectomy versus Robotic Single-Site Plus Two-Port Myomectomy: A Propensity Score Matching Analysis
Su Hyeon CHOI ; Seyeon WON ; Nara LEE ; So Hyun SHIM ; Mi Kyoung KIM ; Mi-La KIM ; Yong Wook JUNG ; Bo Seong YUN ; Hye Sun JUN ; Seok Ju SEONG
Yonsei Medical Journal 2024;65(7):406-412
Purpose:
Robotic single-site plus one-port myomectomy (RSOM) was designed to reduce the number of incision sites for greater cosmetic satisfaction of patients while retaining the benefits of conventional robotic multi-site myomectomy (CRM). Robotic single-site plus two-port myomectomy (RSTM) eliminated one port relative to conventional CRM, and RSOM achieved the same advantage with respect to RSTM. This study aimed to compare RSOM with RSTM in terms of their respective methodologies and surgical outcomes.
Materials and Methods:
The medical records of 230 patients who had undergone RSOM and 146 patients who had undergone RSTM were reviewed. The groups’ surgical outcomes were compared using propensity score matching (PSM) analysis.
Results:
In the total data, RSOM had a shorter operative time (135.1±57.4 min vs. 149.9±46.2 min, p=0.009) and a shorter hospital stay (5.2±0.5 days vs. 5.4±0.7 days, p=0.033) relative to RSTM. The PSM analysis showed that there were no statistically significant intergroup differences in the patients’ baseline characteristics. Regarding the surgical outcomes, the RSOM group showed shorter operative time (129.2±49.3 min vs. 148.7±46.3 min, p=0.001) compared to the RSTM group.
Conclusion
Compared with RSTM, RSOM was associated with shorter operative time. Additionally, more detailed comparative and prospective studies are needed to evaluate RSOM relative to RSTM.
7.Treatment Outcomes of Percutaneous Radiofrequency Ablation for Hepatocellular Carcinomas:Effects of the Electrode Type and Placement Method
Jiyeon PARK ; Min Woo LEE ; Soo Hyun AHN ; Seungchul HAN ; Ji Hye MIN ; Dong Ik CHA ; Kyoung Doo SONG ; Tae Wook KANG ; Hyunchul RHIM
Korean Journal of Radiology 2023;24(8):761-771
Objective:
To investigate the association among the electrode placement method, electrode type, and local tumor progression (LTP) following percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) and to assess the risk factors for LTP.
Materials and Methods:
In this retrospective study, we enrolled 211 patients, including 150 males and 61 females, who had undergone ultrasound-guided RFA for a single HCC < 3 cm. Patients were divided into four combination groups of the electrode type and placement method: 1) tumor-puncturing with an internally cooled tip (ICT), 2) tumor-puncturing with an internally cooled wet tip (ICWT), 3) no-touch with ICT, and 4) no-touch with ICWT. Univariable and multivariable Cox proportional-hazards regression analyses were performed to evaluate the risk factors for LTP. The major RFA-related complications were assessed.
Results:
Overall, 83, 34, 80, and 14 patients were included in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. The cumulative LTP rates differed significantly among the four groups. Compared to tumor puncturing with ICT, tumor puncturing with ICWT was associated with a lower LTP risk (adjusted hazard ratio [aHR] = 0.11, 95% confidence interval [CI] = 0–0.88, P = 0.034). However, the cumulative LTP rate did not differ significantly between tumorpuncturing with ICT and no-touch RFA with ICT (aHR = 0.34, 95% CI = 0.03–1.62, P = 0.188) or ICWT (aHR = 0.28, 95% CI = 0–2.28, P = 0.294). An insufficient ablative margin was a risk factor for LTP (aHR = 6.13, 95% CI = 1.41–22.49, P = 0.019). The major complication rates were 1.2%, 0%, 2.5%, and 21.4% in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively.
Conclusion
ICWT was associated with a lower LTP rate compared to ICT when performing tumor-puncturing RFA. An insufficient ablation margin was a risk factor for LTP.
8.Percutaneous radiofrequency ablation of hepatocellular carcinoma in a recent cohort at a tertiary cancer center: incidence and factors associated with major complications and unexpected hospitalization events
Min Geun JO ; Min Woo LEE ; Soohyun AHN ; Tae Wook KANG ; Kyoung Doo SONG ; Dong Ik CHA ; Ji Hye MIN ; Hyunchul RHIM
Ultrasonography 2023;42(1):41-53
Purpose:
This study aimed to assess the incidence of and factors associated with major complications, delayed discharge, and emergency room (ER) visits or readmission after percutaneous radiofrequency ablation (RFA) for single hepatocellular carcinoma (HCC) <3 cm in a recent cohort at a tertiary cancer center.
Methods:
A total of 188 patients with treatment-naïve single HCCs <3 cm who underwent RFA between January 2018 and April 2021 were included in the analysis. Univariable and multivariable logistic regression analyses were performed to identify the factors associated with major complications, delayed discharge, and ER visits or readmission. Local tumor progression (LTP) and overall survival were estimated using the Kaplan-Meier method and Cox proportional-hazards regression analysis.
Results:
Major complications occurred in 3.2% (6/188) of the patients. The longest diameter of the ablation zone was significantly larger in patients with major complications (P=0.023). Delayed discharge occurred in 5.8% (9/188) of the patients, for which albumin-bilirubin grade 3 was identified as an important determinant. No variables other than major complications were significantly associated with ER visits or readmission, which occurred in 7.0% (13/188) of the patients. Major complications, delayed discharge, and ER visits or readmission were not substantially related to the post-treatment outcomes of LTP and overall survival.
Conclusion
This study confirmed RFA as a highly safe procedure for single HCCs <3 cm, despite the rapidly changing RFA techniques in the most recent cohort. A large ablation zone and poor liver function were predictors of major complications and delayed discharge, respectively.
9.Laparoscopic Hepatic Resection Versus Laparoscopic Radiofrequency Ablation for Subcapsular Hepatocellular Carcinomas Smaller Than 3 cm: Analysis of Treatment Outcomes Using Propensity Score Matching
Seong Eun KO ; Min Woo LEE ; Soohyun AHN ; Hyunchul RHIM ; Tae Wook KANG ; Kyoung Doo SONG ; Jong Man KIM ; Gyu-Seong CHOI ; Dong Ik CHA ; Ji Hye MIN ; Dong Hyun SINN ; Moon Seok CHOI ; Hyo Keun LIM
Korean Journal of Radiology 2022;23(6):615-624
Objective:
To compare the therapeutic outcomes of laparoscopic hepatic resection (LHR) and laparoscopic radiofrequency ablation (LRFA) for single subcapsular hepatocellular carcinoma (HCC).
Materials and Methods:
We screened 244 consecutive patients who had received either LHR or LRFA between January 2014 and December 2016. The feasibility of LRFA in patients who underwent LHR was retrospectively assessed by two interventional radiologists. Finally, 60 LRFA-feasible patients who had received LHR and 29 patients who had received LRFA as the first treatment for a solitary subcapsular HCC between 1 cm and 3 cm were finally included. We compared the therapeutic outcomes, including local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) between the two groups before and after propensity score (PS) matching. Multivariable Cox proportional hazard regression was also used to evaluate the difference in OS and RFS between the two groups for all 89 patients.
Results:
PS matching yielded 23 patients in each group. The cumulative LTP and OS rates were not significantly different between the LHR and LRFA groups after PS matching (p = 0.900 and 0.003, respectively). The 5-year LTP rates were 4.6% and 4.4%, respectively, and OS rates were 100% and 90.7%, respectively. The RFS rate was higher in LHR group without statistical significance (p = 0.070), with 5-year rates of 78.3% and 45.3%, respectively. OS was not significantly different between the LHR (reference) and LRFA groups in multivariable analyses, with a hazard ratio (HR) of 1.33 (95% confidence interval, 0.12–1.54) (p = 0.818). RFS was higher in LHR (reference) than in LRFA without statistical significance in multivariable analysis, with an HR of 2.01 (0.87–4.66) (p = 0.102).
Conclusion
There was no significant difference in therapeutic outcomes between LHR and LRFA for single subcapsular HCCs measuring 1–3 cm. The difference in RFS should be further evaluated in a larger study.
10.Percutaneous radiofrequency ablation for hepatic metastasis of colorectal cancer: assessment of tumor visibility and the feasibility of the procedure with planning ultrasonography
Jeong Woo BAE ; Min Woo LEE ; Tae Wook KANG ; Kyoung Doo SONG ; Dong Ik CHA ; Ji Hye MIN ; Hyunchul RHIM
Ultrasonography 2022;41(1):189-197
Purpose:
The aim of this study was to assess the incidence and causes of percutaneous radiofrequency ablation (RFA) infeasibility in cases of metastatic colorectal cancer and to evaluate factors affecting the invisibility of the tumor on planning ultrasonography (US).
Methods:
This study screened 386 patients who underwent planning US using fusion imaging and/or contrast-enhanced US for percutaneous RFA for suspected metastatic colorectal cancer between January 2013 and December 2020, from whom 136 patients with a single hepatic metastasis from colorectal cancer measuring <3 cm were included. The factors related to the infeasibility of percutaneous RFA were investigated. Univariate and multivariate analyses were performed to assess the factors associated with tumor invisibility on planning US.
Results:
Among the 136 patients, percutaneous RFA was considered infeasible in 24.3% (33/136) due to a high risk of the heat-sink effect caused by the abutment of a large vessel (n=12), an inconspicuous tumor on planning US (n=11), a high risk of collateral thermal damage to an adjacent organ (n=8), and the absence of a safe electrode path (n=2). In univariate and multivariate analyses, tumor size was a statistically significant factor affecting invisibility on planning US (P=0.003 and P=0.018, respectively).
Conclusion
Percutaneous RFA was infeasible in approximately one-fourth of patients with metastatic colorectal cancer. The reason for the infeasibility was mainly an unfavorable tumor location and invisibility on planning US. Small tumor size was the sole significant factor affecting the invisibility of hepatic metastases on planning US.

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