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.Clinical Relevance of Enlarged Perivascular Spaces in Neurodegenerative Disease
Yu-Ri JE ; Hong-Gi HAM ; Yu-Hyun PARK ; Tae-Yun KIM ; Min-su GO ; Hye-In LEE ; Da Eun KIM ; Na-Yeon JUNG ; Myung Jun LEE ; Sang-Won SEO ; Eun-Joo KIM
Journal of the Korean Neurological Association 2023;41(4):281-292
Background:
Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology.
Methods:
We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured.
Results:
There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336).
Conclusions
Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.
3.Improvements in Intractable Lumbar and LowerExtremity Symptoms after Systemic Administration of Tocilizumab, an Anti-interleukin-6 Receptor Antibody
Takeshi SAINOH ; Takeshi SAINOH ; Sumihisa ORITA ; Sumihisa ORITA ; Masayuki MIYAGI ; Masayuki MIYAGI ; Miyako SUZUKI-NARITA ; Miyako SUZUKI-NARITA ; Yoshihiro SAKUMA ; Yoshihiro SAKUMA ; Yasuhiro OIKAWA ; Yasuhiro OIKAWA ; Go KUBOTA ; Go KUBOTA ; Jun SATO ; Jun SATO ; Yasuhiro SHIGA ; Yasuhiro SHIGA ; Kazuki FUJIMOTO ; Kazuki FUJIMOTO ; Yawara EGUCHI ; Yawara EGUCHI ; Masao KODA ; Masao KODA ; Yasuchika AOKI ; Yasuchika AOKI ; Tsutomu AKAZAWA ; Tsutomu AKAZAWA ; Takeo FURUYA ; Takeo FURUYA ; Junichi NAKAMURA ; Junichi NAKAMURA ; Hiroshi TAKAHASHI ; Hiroshi TAKAHASHI ; Satoshi MAKI ; Satoshi MAKI ; Masahiro INOUE ; Masahiro INOUE ; Hideyuki KINOSHITA ; Hideyuki KINOSHITA ; Masaki NORIMOTO ; Masaki NORIMOTO ; Takashi SATO ; Takashi SATO ; Masashi SATO ; Masashi SATO ; Masahiro SUZUKI ; Masahiro SUZUKI ; Keigo ENOMOTO ; Keigo ENOMOTO ; Hiromitsu TAKAOKA ; Hiromitsu TAKAOKA ; Norichika MIZUKI ; Norichika MIZUKI ; Takashi HOZUMI ; Takashi HOZUMI ; Ryuto TSUCHIYA ; Ryuto TSUCHIYA ; Geundong KIM ; Geundong KIM ; Takuma OTAGIRI ; Takuma OTAGIRI ; Tomohito MUKAIHATA ; Tomohito MUKAIHATA ; Takahisa HISHIYA ; Takahisa HISHIYA ; Seiji OHTORI ; Seiji OHTORI ; Kazuhide INAGE ; Kazuhide INAGE
Asian Spine Journal 2022;16(1):99-106
Methods:
This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events.
Results:
Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events.
Conclusions
Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.
4.Improvements in Health-Related Quality of Life in Patients with Psoriatic Arthritis and Moderate-to-Severe Psoriasis Receiving Secukinumab: A Retrospective Study
Yong Jun HONG ; Gang Min GO ; Miri KIM
Korean Journal of Dermatology 2022;60(4):220-227
Background:
Psoriasis is a relapsing inflammatory skin disorder that can affect the nails and joints. Psoriatic arthritis (PsA) occurs in up to 30% of patients with psoriasis, leading to chronic articular pain, and impairing quality of life. Secukinumab is a human monoclonal antibody targeting interleukin-17A that has been shown to effectively improve the clinical signs and symptoms of PsA.
Objective:
To evaluate the effect of secukinumab on health-related quality of life (HRQOL) in Korean PsA patients.
Methods:
We retrospectively investigated the medical records and psoriasis area and severity index (PASI) scores of 13 patients with PsA who completed the psoriatic arthritis impact of disease 12-item questionnaire (PsAID-12) before and 3 months after receiving secukinumab treatment between October 2019 and August 2021 in Yeouido St.Mary’s Hospital.
Results:
At week 12, significant reductions in the total and each item PsAID-12 and mean PASI score were observed (p<0.01). The mean decrease of total PsAID-12 score was 4.8 (95% confidence interval [CI], 3.74∼5.86), with the greatest improvement observed in the item of ‘embarrassment’ (7.15; 95% CI, 5.59∼8.72). Of the 13 patients, 11 (84.6%) and 5 (38.5%) achieved PASI75 and PASI90 response, respectively.
Conclusion
This study showed that secukinumab improves the HRQOL of patients with PsA, implying a positive influence of secukinumab on patients’ physical and mental status in a real-world clinical setting.
5.A Novel One-Step Knife Approach Can Reduce the Submucosal Injection Time of Endoscopic Submucosal Dissection: A SingleBlinded Randomized Multicenter Clinical Trials
Hyunil KIM ; Jin Woo KIM ; Hong Jun PARK ; Su Young KIM ; Hyun-Soo KIM ; Gwang Ho BAIK ; Sung Chul PARK ; Sang Jin LEE ; Tae-Hwa GO
Gut and Liver 2022;16(1):44-52
Background/Aims:
Endoscopic submucosal dissection (ESD) is a curative treatment modality for early gastric neoplasms; however, ESD can be a time-consuming process. To overcome this pitfall, we developed the one-step knife (OSK) approach, which combines an endoscopic knife and injection needle on a single sheath. We aimed to evaluate whether this approach could reduce the ESD procedure time.
Methods:
This single-blinded randomized multicenter trial at four tertiary hospitals from June 2019 to June 2020 included patients aged 19 to 85 years undergoing ESD. Patients were randomly assigned to two groups (OSK or conventional knife [CK]). The injection time, total procedure time, resected specimen size, submucosal fluid amount, degree of device satisfaction, and adverse events were evaluated and compared between groups.
Results:
Fifty-one patients were analyzed (OSK: 25 patients and CK: 26 patients). No baseline differences were observed between groups, with the exception of a higher portion of males in the OSK group. The mean injection time was significantly reduced in the OSK group (39.0 seconds) compared to that in the CK group (87.5 seconds, p<0.001). A decrease of more than 10 minutes in the total procedure time (18.0 minutes vs 28.1 minutes, p=0.055) in the OSK group compared to the CK group was observed. Second-look esophagogastroduodenoscopy revealed two delayed bleeding cases in the OSK group that were easily controlled by endoscopic hemostasis.
Conclusions
OSK reduced the injection time and showed a decrease in total procedure time compared with the CK approach. OSK can be a feasible tool for ESD, especially in difficult cases.
6.Humulus japonicus attenuates LPS-and scopolamine-induced cognitive impairment in mice
Jun GO ; Hye-Yeon PARK ; Da Woon LEE ; So-Young MAENG ; In-Bok LEE ; Yun Jeong SEO ; Jin-Pyo AN ; Won Keun OH ; Chul-Ho LEE ; Kyoung-Shim KIM
Laboratory Animal Research 2022;38(3):159-168
Background:
Neuroinflammation plays an important role in cognitive decline and memory impairment in neurodegenerative disorders. Previously, we demonstrated that Humulus japonicus (HJ) has anti-inflammatory effects in rodent models of Alzheimer’s disease and Parkinson’s disease. The present study aimed to examine the protective potential of HJ extracts against lipopolysaccharide (LPS)-induced cognitive impairment and scopolamine-induced amnesia in mouse models. Cognitive improvement of mice was investigated by novel object recognition test. For analyzing effects on neuroinflammation, immunohistochemistry and quantitative real-time polymerase chain reaction (qRTPCR) assays were performed.
Results:
We found that the oral administration of HJ significantly improved cognitive dysfunction induced by LPS in a novel object recognition test. The LPS-induced activation of microglia was notably decreased by HJ treatment in the cortex and hippocampus. HJ administration with LPS also significantly increased the mRNA expression of interleukin (IL)-10 and decreased the mRNA expression of IL-12 in the parietal cortex of mice. The increased expression of LPS-induced complement C1q B chain (C1bq) and triggering receptor expressed on myeloid cells 2 (Trem2) genes was significantly suppressed by HJ treatment. In addition, HJ administration significantly improved novel object recognition in a scopolamine-induced amnesia mouse model.
Conclusions
These findings revealed that HJ has a beneficial effect on cognitive impairment and neuroinflammation induced by systemic inflammation and on amnesia induced by scopolamine in mice.
7.Reference diameter and characteristics of the distal radial artery based on ultrasonographic assessment
Jun-Won LEE ; Jung-Woo SON ; Tae-Hwa GO ; Dae Ryong KANG ; Sang Jun LEE ; Se Eun KIM ; Dong-Hyuk CHO ; Young Jun PARK ; Young Jin YOUN ; Min-Soo AHN ; Sung Gyun AHN ; Jang-Young KIM ; Byung-Su YOO ; Junghan YOON ; Seung-Hwan LEE
The Korean Journal of Internal Medicine 2022;37(1):109-118
Background/Aims:
While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm.
Methods:
The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath.
Results:
The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm.
Conclusions
We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.
8.A study on the predictive indicators for the recovery of spontaneous circulation in the early arterial blood gas analysis of cardiac arrest in the elderly
Hyun Joon LIM ; Jun Hwi CHO ; Joong Bum MOON ; Chan Woo PARK ; Myoung Cheol SHIN ; Ka Eul KIM ; Yoon Soo PARK ; Go Eun YANG ; Taek Geun OHK
Journal of the Korean Society of Emergency Medicine 2021;32(2):103-111
Objective:
The number of elderly patients in Korea has been on the rise recently, and hence the number of out-of-hospital cardiac arrest (OHCA) elderly patients is also rising. The causes of cardiac arrest for the elderly vary, and, it is difficult to predict the recovery of spontaneous circulation (ROSC) in OHCA patients. Therefore, the purpose of this study was to ascertain the predictive value of arterial blood gas analysis (ABGA) results in achieving ROSC in the elderly.
Methods:
A retrospective analysis of emergency department patients with OHCA was performed at the Kangwon National University Hospital, Korea from 1 January 2016 to 31 December 2019. The initial ABGA results were compared between two patient groups, those who had achieved a return of spontaneous circulation and those who had not. Univariate and multivariable analyses were performed to elucidate the factors associated with ROSC.
Results:
Overall, 229 OHCA patients were included in the final analysis. The lactate level was independently related to ROSC. A receiver operating characteristics (ROC) curve was plotted to obtain the best cutoff value. The lactate level <9.85 mmol/L showed the largest area under the ROC curve (AUC) to predict ROSC (AUC, 0.666; 95% confidence interval, 0.588-0.743). Multiple regression analysis was performed using the cutoff value, which was a lactate level of 9.85 (odds ratio, 2.907; 95% confidence interval, 1.432-5.902; P=0.003).
Conclusion
The ABGA results during the cardiopulmonary resuscitation of OHCA patients, showed that the lactate level was an independent factor associated with ROSC. The lactate cutoff value was 9.85 mmol/L.
9.Effect of estimating equations for glomerular filtration rate on novel surrogate markers for renal outcome
Kipyo KIM ; Eunji BAEK ; Suryeong GO ; Hyung-Eun SON ; Ji-Young RYU ; Yongjin YI ; Jong Cheol JEONG ; Sejoong KIM ; Ho Jun CHIN
Kidney Research and Clinical Practice 2021;40(2):220-230
Background:
s: Recently, alternative surrogate endpoints such as a 30% or 40% decline in estimated glomerular filtration rate (eGFR) or eGFR slope over 2 to 3 years have been proposed for predicting renal outcomes. However, the impact of GFR estimation methods on the accuracy and effectiveness of surrogate markers is unknown.
Methods:
We retrospectively enrolled participants in health screening programs at three hospitals from 1995 to 2009. We defined two different participant groups as YR1 and YR3, which had available 1-year or 3-year eGFR values along with their baseline eGFR levels. We compared the effectiveness of eGFR percentage change or slope to estimate end-stage renal disease (ESRD) risk according to two estimating equations (modified Modification of Diet in Renal Disease equation [eGFRm] and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation [eGFRc]) for GFR.
Results:
In the YR1 and YR3 groups, 9,971 and 10,171 candidates were enrolled and ESRD incidence during follow-up was 0.26% and 0.19%, respectively. The eGFR percentage change was more effective than eGFR slope in estimating ESRD risk, regardless of the method of estimation. A 40% of decline in eGFR was better than 30%, and a 3-year baseline period was better than a 1-year period for prediction accuracy. Although some diagnostic indices from the CKD-EPI equation were better, we found no significant differences in the discriminative ability and hazard ratios for incident ESRD between eGFRc and eGFRm in either eGFR percentage change or eGFR slope.
Conclusion
There were no significant differences in the prediction accuracy of GFR percentage change or eGFR slope between eGFRc and eGFRm in the general population.
10.Epidural hematoma treated by aspiration after transforaminal epidural steroid injection - A case report -
Go Eun KIM ; Sung Jun HONG ; Sang Soo KANG ; Ho Joon KI ; Jae Hyun PARK
Anesthesia and Pain Medicine 2021;16(2):184-190
Background:
Spinal epidural hematoma is rare condition that can rapidly develop into severe neurologic deficits. The pathophysiology of this development remains unclear. There are several case reports of emergency hematoma evacuations after epidural steroid injection. Case: We report on two patients who developed acute, large amounts of epidural hematoma without neurological deficits after transforaminal epidural steroid injection. After fluoroscopy guided aspiration for epidural hematoma was performed, neurological defects did not progress and the hematoma was shown to be absorbed on magnetic resonance imaging.
Conclusions
These reports are believed to be the first of treating epidural hematoma occurring after transforaminal epidural steroid injection through non-surgical hematoma aspiration. If large amounts of epidural hematoma are not causing neurological issues, it can be aspirated until it is absorbed.

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