1.DNA methylome analysis reveals epigenetic alteration of complement genes in advanced metabolic dysfunction-associated steatotic liver disease
Amal MAGDY ; Hee-Jin KIM ; Hanyong GO ; Jun Min LEE ; Hyun Ahm SOHN ; Keeok HAAM ; Hyo-Jung JUNG ; Jong-Lyul PARK ; Taekyeong YOO ; Eun-Soo KWON ; Dong Hyeon LEE ; Murim CHOI ; Keon Wook KANG ; Won KIM ; Mirang KIM ;
Clinical and Molecular Hepatology 2024;30(4):824-844
Background/Aims:
Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD.
Methods:
Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing.
Results:
Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data.
Conclusions
Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.
2.Does Rapid Eye Movement Sleep Aggravate Obstructive Sleep Apnea?
Sung Hee KIM ; Chan Joo YANG ; Jong Tae BAEK ; Sang Min HYUN ; Cheon Sik KIM ; Sang Ahm LEE ; Yoo Sam CHUNG
Clinical and Experimental Otorhinolaryngology 2019;12(2):190-195
OBJECTIVES.: To investigate the apnea-hypopnea index (AHI) according to the sleep stage in more detail after control of posture. METHODS.: Patients who underwent nocturnal polysomnography between December 2007 and July 2018 were retrospectively evaluated. Inclusion criteria were as follows: age >18 years, sleep efficacy >80%, and patients who underwent polysomnography only in the supine position (100% of the time). Patients were classified into different groups according to the methods: the first, rapid eye movement (REM)-dominant group (AHIREM/AHINREM >2), non-rapid eye movement (NREM)-dominant group (AHINREM/AHIREM >2), and non-dominant group; and the second, light sleep group (AHIN1N2>AHISWS) and slow wave sleep (SWS) group (AHISWS>AHIN1N2). RESULTS.: A total of 234 patients (mean age, 47.4±13.9 years) were included in the study. There were 108 patients (46.2%) in the REM-dominant group, 88 (37.6%) in the non-dominant group, and 38 (16.2%) in the NREM-dominant group. The AHI was significantly higher in the NREM-dominant group than in the REM-dominant group (32.9±22.9 events/hr vs. 18.3±9.5 events/hr, respectively). There were improvements in the AHI from stage 1 to SWS in NREM sleep with the highest level in REM sleep. A higher AHISWS than AHIN1N2 was found in 16 of 234 patients (6.8%); however, there were no significant predictors of these unexpected results except AHI. CONCLUSION.: Our results demonstrated the highest AHI during REM sleep stage in total participants after control of posture. However, there were 16.2% of patients showed NREM-dominant pattern (AHINREM/AHIREM >2) and 6.8% of patients showed higher AHISWS than AHIN1N2. Therefore, each group might have a different pathophysiology of obstructive sleep apnea (OSA), and we need to consider this point when we treat the patients with OSA.
Eye Movements
;
Humans
;
Polysomnography
;
Posture
;
Retrospective Studies
;
Sleep Apnea, Obstructive
;
Sleep Stages
;
Sleep, REM
;
Supine Position
3.Neonatal Characteristic of Congenital Cystic Adenomatoid Malformation of the Lung Requiring Early Operation and Preoperative Intervention.
Young Eun SUH ; Hyun Kyung KIM ; Yong Sung CHOI ; Byung Sop LEE ; Ki Soo KIM ; Hye Sung WON ; Pil Ryang LEE ; Jae Yoon SHIM ; Ahm KIM ; Jong Hyun YOON ; Dong Kwan KIM ; Ellen Ai Rhan KIM
Neonatal Medicine 2013;20(1):81-89
PURPOSE: To identify neonatal characteristics associated with congenital cystic adenomatoid malformation (CCAM) who required early operations and to introduce preoperative interventions to delay definitive operations until stabilized. METHODS: A retrospective review of dataset was performed from January 2000 to December 2011 for neonates admitted to NICU at Asan Medical Center with prenatally diagnosed CCAM. Variable prenatal and postnatal factors were compared for those who required early operations to those asymptomatic neonates who required elective operations at later age. RESULTS: A total of 60 patients were enrolled and patients were divided into 2 groups according to time of operation. Median time of surgery for group 1 (n=12, 20%) and group 2 (n=48, 80%) was 5.5 days and 504 days, respectively. Maternal characteristics including age, parity, preterm labor, oligohydramnios were similar in between two groups. Factors associated with early operation included prenatal history of polyhydramnios (OR 23, P=0.001), who had undergone fetal interventions (OR 47, P=0.001), low 1 and 5 minute Apgar scores and increasing fetal fluid-filled cystic sizes (OR 26, P=0.013). Of those 3 neonates who required preoperative interventions to decrease air-filled cysts to relieve initial respiratory symptoms were successful and all underwent for definitive operations during NICU hospitalizations. All survived. CONCLUSION: Most neonates with CCAM undergo elective operations during infancy. However, about 20% neonates with polyhydramnios, fetal intervention, increasing fetal cystic mass and born with low Apgar scores required early operations for whom prenatal and postnatal interventions prior to definitive surgery can improve survival rate.
Cystic Adenomatoid Malformation of Lung, Congenital
;
Female
;
Hospitalization
;
Humans
;
Infant, Newborn
;
Lung
;
Obstetric Labor, Premature
;
Oligohydramnios
;
Parity
;
Polyhydramnios
;
Pregnancy
;
Retrospective Studies
;
Risk Factors
;
Survival Rate
4.A prospective multicenter randomized study on prophylactic antibiotics use in cesarean section performed at tertiary center.
Ji Kyung KO ; Yong Kyoon CHO ; Hye Jin YANG ; Chan Wook PARK ; Joong Shin PARK ; Jong Kwan JUN ; Min Gyun KIM ; Hye Sung WON ; Pil Ryang LEE ; Ahm KIM
Korean Journal of Obstetrics and Gynecology 2010;53(3):227-234
OBJECTIVE: To determine whether the duration and timing of prophylactic antibiotics influence maternal postoperative infectious morbidity in cesarean section performed at tertiary center. METHODS: This study was a prospective, randomized trial. Pregnant women who underwent cesarean section between December 2008 and September 2009 at tertiary center were enrolled and divided into two groups: Group A, antibiotic prophylaxis was applied for 24 hours and Group B, antibiotic prophylaxis was applied for 48 hours. First generation of cephalosporin was administrated within 30 minutes prior skin incision or after cord clamping. The occurrence of postoperative infectious morbidity such as febrile morbidity, wound infection, endometritis, urinary track infection, pneumonia, sepsis and pelvic abscess and hospital stays were compared. RESULTS: There were 413 pregnant women enrolled and then randomized into 220 for group A and 197 for group B. No demographic differences were observed between two groups. The infectious morbidity was 1.9% (8/413) and wound infection was the most common postoperative infections morbidity. No significant difference was found between the groups for infectious morbidity and hospital stays. Also timing of prophylactic antibiotics did not result in significant difference for infectious morbidity. CONCLUSION: Short course of prophylactic antibiotics has been shown to be as efficacious as multidose of prophylactic antibiotics for preventing infectious morbidity in cesarean section and timing did not influence on infections morbidity. Further studies focusing on duration and timing of prophylactic antibiotics for cesarean section are needed.
Abscess
;
Anti-Bacterial Agents
;
Antibiotic Prophylaxis
;
Cesarean Section
;
Constriction
;
Endometritis
;
Female
;
Humans
;
Length of Stay
;
Pneumonia
;
Pregnancy
;
Pregnant Women
;
Prospective Studies
;
Sepsis
;
Skin
;
Track and Field
;
Wound Infection
5.Clinical significance of fetal nuchal translucency during early pregnancy.
Jae Yoon SHIM ; Jong Yun HWANG ; Sun Kwon KIM ; Bon Sang KOO ; Hye Sung WON ; Pil Ryang LEE ; Ahm KIM
Korean Journal of Obstetrics and Gynecology 2005;48(4):875-883
OBJECTIVE: To examine the significance of fetal nuchal translucency during early pregnancy in detection of chromosomal abnormality and major cardiac defect METHODS: Between Jul 1998 and Jul 2002, ultrasound examination was performed in 1,253 unselected singleton pregnancies with a live fetus and fetal crown rump length of 24-88 mm. The fetal nuchal translucency thickness was measured successfully in all cases. We reviewed the pregnancy outcome about two parameters. Chromosomal abnormality was confirmed by antenatal karyotyping and newborn's feature suggestive of a chromosomal defect. Major cardiac defect was confirmed by newborn physical examination, targeted ultrasonography, neonatal echocardiography and autopsy. RESULTS: (1) Fetal nuchal translucency thickness increased significantly with crown-rump length. (2) Nuchal translucency was greater than 3 mm in 12 pregnancies with abnormal karyotypes, giving a detection rate of 75.0% with a false positive rate of 4.0%. With a cutoff of 2.5 mm, a detection rate of abnormal karyotype was 81.3% with a false positive rate of 8.3%. And with a gestational age specific cutoff, 95 percentile, a detection rate of abnormal karyotype was 75%, with a false positive rate of 6.4%. (3) With normal karyotype, the overall prevalence of major cardiac defects in this study population was 5/1,000 pregnancies (5/1,054). This prevalence increased from 48/1,000 (4/83) using 2.5 mm cutoff to 105/1,000 (4/38) using 3 mm cutoff. The detection rate for major cardiac defect of nuchal translucency above 3 mm is 80.0% with a false positive rate of 3.2%. CONCLUSION: Increased nuchal translucency is by far an important and efficient marker for screening of chromosomal defects and effective screening method for major cardiac defects.
Abnormal Karyotype
;
Autopsy
;
Chromosome Aberrations
;
Crown-Rump Length
;
Echocardiography
;
Female
;
Fetus
;
Gestational Age
;
Humans
;
Infant, Newborn
;
Karyotype
;
Karyotyping
;
Mass Screening
;
Nuchal Translucency Measurement*
;
Physical Examination
;
Pregnancy Outcome
;
Pregnancy*
;
Prevalence
;
Ultrasonography
6.Clinical evaluation of In-utero fetal shunt operation using basket-shaped catheter: 5-year experience at Asan Medical Center.
Hye Sung WON ; Jong Yun HWANG ; Sun Kwon KIM ; Eui JUNG ; Jee Young OH ; Jae Yoon SHIM ; Pyl Ryang LEE ; Ahm KIM
Korean Journal of Obstetrics and Gynecology 2005;48(11):2558-2569
OBJECTIVE: To evaluate the clinical outcomes of In-utero fetal shunt operations at Asan Medical Center. METHODS: We reviewed the medical records of 33 occasions in 28 pregnancies that underwent intrauterine shunt operations between December, 1998 and April, 2004. Fetal shunt operations were considered for cases of hydrothorax (N=10), congenital cystic adenomatoid malformation type I (CCAM Type I)(N=5), lower urinary tract obstruction (N=6), severe hydronephrosis (N=7) and severe fetal ascites (N=5). Selection criteria of fetus for the shunt operation required normal karyotype and negative infection. Basket-shaped catheter was used for the procedure. Kruskal-Wallis test, Mann-Whitney U test, and Chi-Square test were used for statistical analysis. P<0.05 was considered statistically significant. RESULTS: In CCAM Type I, the mean gestational age was 25.6+/-4.0 weeks at diagnosis, 26.0+/-4.4 weeks at shunt operation and 36.6+/-3.9 weeks at delivery. Perinatal survival rate was 66.7% (2/3). In hydrothorax, the mean gestational age was 26.7+/-3.3 weeks at diagnosis, 27.3+/-3.3 weeks at shunt operation and 34.9+/-3.0 weeks at delivery. Perinatal survival rate was 80.0% (4/5). In lower urinary tract obstruction, the mean gestational age was 18.5+/-3.7 weeks at diagnosis, 19.6+/-3.5 weeks at shunt operation and 34.5+/-2.9 weeks at delivery. Perinatal survival rate was 80.0% (2/3). In hydronephrosis, the mean gestational age was 25.3+/-5.3 weeks at diagnosis, 27.4+/-5.3 weeks at shunt operation and 36.9+/-2.2 weeks at delivery. Perinatal survival rate was 83.3% (5/6). In ascites, the mean gestational age was 29.6+/-3.9 weeks at diagnosis, 29.9+/-3.8 weeks at shunt operation and 34.1+/-3.0 weeks at delivery. Perinatal survival rate was 100.0% (5/5). Complications occurred in 48.5% (16/33) of the cases. The most common complication was shunt dislodgement (N=7). CONCLUSION: In-utero fetal shunt operation should be considered as a treatment option for hydrothorax, CCAM type I, lower urinary tract obstruction, severe hydronephrosis and severe ascites with a significant risk for pulmonary hypoplasia.
Ascites
;
Catheters*
;
Chungcheongnam-do*
;
Cystic Adenomatoid Malformation of Lung, Congenital
;
Diagnosis
;
Fetus
;
Gestational Age
;
Hydronephrosis
;
Hydrothorax
;
Karyotype
;
Medical Records
;
Patient Selection
;
Pregnancy
;
Survival Rate
;
Ultrasonography
;
Urinary Tract
7.Clinical efficacy of urgent cerclage in cervical incompetence predicted by transvaginal ultrasonography in second trimester.
Jong Yun HWANG ; Sook Hee KIM ; Jun Sik CHO ; Dong Heon LEE ; Sun Jung PARK ; Sun Kwon KIM ; Jae Yoon SHIM ; Hye Sung WON ; Pil Ryang LEE ; Ahm KIM
Korean Journal of Obstetrics and Gynecology 2004;47(10):1852-1859
OBJECTIVE: To investigate the clinical efficacy of urgent cerclage on perinatal outcome in cervical incompetence predicted by transvaginal ultrasonography in second trimester. METHODS: We reviewed the medical records of 27 pregnant women who received urgent cerclage at Asan Medical Center between January, 1998 and August, 2002. When the cervical length was less than 25 mm and abnormal cervical shape by transvaginal ultrasonography in second trimester, we performed urgent cerclage. Abnormal cervical shapes were categorized as U-shape, Y-shape and V-shape. These data were compared with those of 102 patients who received prophylactic cerclage and 25 patients who received emergent cerclage during the same period. Analysis of variance and chi-square test were used for statistical analysis. P<0.05 was considered statistically significant. RESULTS: In urgent cerclage, the mean gestational age at delivery was 35.1 +/- 4.4 weeks. The mean birth weight was 2524.2 +/- 860.8 gm and perinatal survival rate was 92.6% (25/27). We compared these data with the other two cerclages. In prophylactic cerclage, the mean gestational age at delivery was 36.2 +/- 4.6 weeks. The mean birth weight was 2711.5 +/- 860.8 gm and perinatal survival rate was 94.1% (96/102). There was no statistically significant difference between urgent cerclage and prophylactic cerclage. In emergent cerclage, the mean gestational age at delivery was 27.5 +/- 6.9 weeks. The mean birth weight was 1373.8 +/- 1196.7 gm and perinatal survival rate was 48.0% (12/25). There was statistically significant difference between urgent cerclage and emergent cerclage based on our finding, The gestational age, birth weight and perinatal survival rate in urgent cerclage were not different from prophylactic cerclage. However, in emergent cerclage, these data were different from the other two cerclages. CONCLUSION: These data suggest that perinatal outcomes after urgent cerclage were comparable to those of prophylactic cerclage. Urgent cerclage could be a valuable alternative to a policy of uniform prophylactic cerclage.
Birth Weight
;
Chungcheongnam-do
;
Female
;
Gestational Age
;
Humans
;
Medical Records
;
Pregnancy
;
Pregnancy Trimester, Second*
;
Pregnant Women
;
Survival Rate
;
Ultrasonography*
8.Benefits of Antenatal Corticosteroid in Infants Delivered before 33 weeks of Gestation after Premature Rupture of Membranes.
Bon Sang KOO ; Ji Youn CHUNG ; Jong Soo KIM ; So Ra KIM ; Sang Su LEE ; Hye Sung WON ; Dae Shik SUH ; Pil Ryang LEE ; Ahm KIM
Korean Journal of Obstetrics and Gynecology 2004;47(1):166-172
OBJECTIVE: To evaluate the benefits of maternal corticosteroid therapy in infants delivered before 33 weeks of gestation after premature rupture of membranes (PROM). METHODS: This retrospective study included the pregnant women complicated by preterm delivery within 32 weeks of gestation after PROM at the Asan Medical Center between 1997 to 1999. Patients were divided into 2 groups according to the gestational age at delivery, i.e., one group who delivered within 28 weeks of gestation and the other group who delivered between 29 and 32 weeks of gestation. Within each group, we evaluated the effect of maternal dexamethasone therapy on the perinatal and neonatal outcomes based on the medical records. Data were analyzed with pearson's chi-square test, Fisher's exact test, and two sample t-test. p<0.05 was considered statistically significant. RESULTS: One hundred and fifteen pregnancies complicated by preterm delivery within 32 weeks of gestation after premature rupture of membranes were included. Preterm deliveries occurred within 28 weeks of gestation in 48 cases (41.7%) and between 28 and 32 weeks of gestations in 67 cases (58.3%). Antenatal dexamethasone therapy was done in 27 out of 48 mothers (56.3%) who delivered within 28 weeks of gestation and in 47 out of 67 mothers (70.1%) who delivered between 29 and 32 weeks of gestation. Antenatal dexamethasone therapy did not affect the selected perinatal outcome variables (gestational age at delivery, birth weight, Apgar scores, cesarean section rate, and maternal and neonatal WBC counts and serum C-reactive protein concentrations). Incidences of neonatal complications (respiratory distress syndrome, intraventricular hemorrhage, retinopathy of prematurity, and periventricular leukomalacia) between the groups who did and did not received antenatal dexamethasone were not significantly different in pregnancies who delivered within 28 weeks of gestation. However, incidences of respiratory distress syndrome and intraventricular hemorrhage were significantly lower in a group who received antenatal dexamethasone than in a group who did not in pregnancies who delivered between 29 and 32 weeks of gestation (p<0.05). CONCLUSION: Antenatal corticosteroid therapy may be beneficial to the infants delivered between 29 and 32 weeks of gestation after PROM. However, it may have no therapeutic advantage to the group who delivered within 28 weeks of gestation after PROM.
Birth Weight
;
C-Reactive Protein
;
Cesarean Section
;
Chungcheongnam-do
;
Dexamethasone
;
Female
;
Gestational Age
;
Hemorrhage
;
Humans
;
Incidence
;
Infant*
;
Medical Records
;
Membranes*
;
Mothers
;
Pregnancy*
;
Pregnant Women
;
Premature Birth
;
Retinopathy of Prematurity
;
Retrospective Studies
;
Rupture*
9.Applicable Indications and Effectiveness of the Selective Arterial Embolization in the Management of Obstetrical Hemorrhage.
Cheun Sic KANG ; So Yean PARK ; Ji Young LEE ; Jee Young OH ; Won Deuk JU ; Sun Kwon KIM ; Jong Yun HWANG ; Mi Kyung KIM ; Jae Yoon SHIM ; Gi Young KO ; Hye Sung WON ; Dae Shik SUH ; Pil Ryang LEE ; Ahm KIM
Korean Journal of Obstetrics and Gynecology 2004;47(1):51-59
OBJECTIVE: To describe the angiographic embolization as a safe and an effective alternative treatment in the management of obstetrical hemorrhage and in preserving fertility. METHODS: Between March 1999 and May 2003, 43 patients at Asan Medical Center underwent angiographic embolization for the management of obstetrical hemorrhage. All cases received arterial embolization because of obstetrical hemorrhage unresponsive to conservative management or prophylaxis for massive obstetrical hemorrhage. Medical records were reviewed and detailed to collect adequate clinical data such as clinical status, underlying conditions, amount of transfusion, embolization sites, materials of embolization, duration of the procedure, complications associated with embolization, hospital stay, and the success rate. Patients were contacted by telephone to obtain long-term outcome for menstruation, desire for conception, and subsequent pregnancies. RESULTS: We have experienced the clinical successful embolization in 37 (86.0%) of 43 patients of obstetrical hemorrhage resulting from various causes. The main cause of hemorrhage was atony of uterus (n=17), followed by abnormal placentation (n=6), genital tract laceration (n=5). The average amount of blood transfusion was 7.0 units (range; 0-36 units). The average length of the time for the procedure was 68.2 minutes (range; 30-150 minutes). The average duration of hospitalization was 6.4 days (range; 3-20 days). The main complication after embolization was numbness and pain on right lower extremities in 5 cases and vessel dissection occurred in 1 case. But there was no major complication related to the procedure. We were able to follow up 28 patients. In all cases menses resumed spontaneously soon after the procedure. Seven cases of long-term follow-up became pregnant, and 3 cases of them completed gestations giving birth to healthy babies. CONCLUSION: The results suggest that angiographic embolization is a relatively noninvasive and highly effective method for the management of obstetrical hemorrhage and a useful technique for preserving fertility.
Blood Transfusion
;
Chungcheongnam-do
;
Female
;
Fertility
;
Fertilization
;
Follow-Up Studies
;
Hemorrhage*
;
Hospitalization
;
Humans
;
Hypesthesia
;
Lacerations
;
Length of Stay
;
Lower Extremity
;
Medical Records
;
Menstruation
;
Parturition
;
Placentation
;
Pregnancy
;
Telephone
;
Uterus
10.A Multi-center Study for Birth Defect Monitoring Systems in Korea.
Jae Hyug YANG ; Yon Ju KIM ; Jin Hoon CHUNG ; Moon Young KIM ; Hyun Mee RYU ; Hyun Kyong AHN ; Jung Yul HAN ; Soon Ha YANG ; Ahm KIM ; Hyun Se KIM ; Pyo Jong LEE ; Sung Soo KIM ; Young Ju KIM ; Kyung Sim KOH ; Jong Chul SHIN ; Yong Kun CHO ; Bo Hyun YOON
Journal of Korean Medical Science 2004;19(4):509-513
The aim of this study was to establish a multi-center birth defects monitoring system to evaluate the prevalence and the serial occurrence of birth defects in Korea. Ten medical centers participated in this program. A trained nurse collected relevant records from delivery units and pediatric clinics in participating hospitals on a monthly basis. We observed 1,537 cases of birth defects among 86,622 deliveries, which included live births and stillbirths. The prevalence of birth defects was 1.8%, and the sex distribution of the birth defect cases was 55.2% male and 41.6% female. The highest proportion of birth defects was in the cardiovascular system (17.5%), followed by birth defects involving in the genitourinary system (15.6%). Chromosomal anomalies were detected 30.0 per 10,000 births. Of these chromosomal anomalies, Down syndrome was most frequently observed. This study led to an establishment of a multi-center active monitoring system for birth defects. To better understand the serial occurrence of birth defects in Korea, it is necessary to increase the number of participating hospitals and to launch on a nation-wide multi-center study.
Abnormalities/*epidemiology
;
Child
;
*Chromosome Aberrations
;
Female
;
Humans
;
Korea/epidemiology
;
Male
;
*Population Surveillance
;
Pregnancy
;
Pregnancy Outcome
;
Research Support, Non-U.S. Gov't

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