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.Outcomes of Hip Arthroplasty in Patients with Preoperative Thrombocytopenia
Jong Jin GO ; Minji HAN ; Tae Woo KIM ; Byung Kyu PARK ; Jung-Wee PARK ; Young-Kyun LEE
Clinics in Orthopedic Surgery 2024;16(5):711-717
Background:
Thrombocytopenia is a condition where platelet counts are below the normal range (< 150 ×103 /µL), resulting in a higher risk of bleeding and affecting the results of hip arthroplasty. We assessed the impact of preoperative platelet counts on the clinical results of patients who underwent hip arthroplasty.
Methods:
Between April 2003 and March 2023, 437 patients (451 hips), who had preoperative thrombocytopenia of less than 150 ×103 /µL platelets, underwent hip arthroplasty. Preoperative platelet levels were categorized into severe thrombocytopenia (< 50 ×103 /µL) and non-severe thrombocytopenia (50–149 ×103 /µL). Total blood loss, operation time, requirement of transfusion, amount of transfusion, duration of surgical wound oozing, length of hospital stay, mortality rate at 1 year after surgery, and any complication were compared between the 2 groups.
Results:
No notable differences were observed in the surgery time or the total amount of blood loss between the groups. The requirement of transfusion and the amount of transfused blood were higher in the severe thrombocytopenia group. Prolonged oozing was found in around 18% in both groups, while periprosthetic joint infections occurred in 3 of the non-severe thrombocytopenia group. No significant difference was noted in the duration of hospital stay (25.6 ± 18.3 days vs. 19.4 ± 16.6 days, p = 0.067) and 1-year mortality (22.2% vs. 11.8%, p = 0.110).
Conclusions
Hip arthroplasties are safe for patients with low platelet counts and do not lead to prolonged hospital stays. On the other hand, patients with severe thrombocytopenia tend to need blood transfusions more frequently than those with less severe thrombocytopenia.
3.Reliability of the 2018 Revised Version of AO/OTA Classification for Femoral Shaft Fractures
Jung-Wee PARK ; Woo-Lam JO ; Byung Kyu PARK ; Jong Jin GO ; Minji HAN ; Sungha CHUN ; Young-Kyun LEE
Clinics in Orthopedic Surgery 2024;16(5):688-693
Background:
The Arbeitsgemeinschaft für Osteosynthesefragen (AO) and the Orthopaedic Trauma Association (OTA) classification system for diaphyseal fracture has been recently revised to refine and enhance the accuracy of fracture categorization. This study aimed to investigate the interobserver reliability of the new AO/OTA classification and to compare it with the older version in femoral shaft fractures.
Methods:
We retrospectively analyzed 139 patients (mean age, 43.8 ± 19.5 years; 92 men and 47 women) with femoral shaft fractures who were treated from 2003 to 2017. Four well-trained observers independently classified each fracture following the previous and revised AO/OTA classification system. We calculated the Fleiss kappa for the interobserver reliability.
Results:
The previous classification showed the kappa value of 0.580 (95% confidence interval [CI], 0.547–0.613), and the revised version showed 0.528 (95% CI, 0.504–0.552). Both the old and the revised versions showed moderate reliability.
Conclusions
Our study highlights the moderate interobserver reliability of both the previous and new AO/OTA classification systems for diaphyseal femur fractures. These findings emphasize the importance of standardized systems in clinical decision-making and underscore the need for ongoing education and collaboration to enhance fracture classification.
4.Relapsed Leprosy with Multiple Ulcerative Skin Lesions: A Case Report
Han Him JEONG ; Seung Gi HONG ; Jin Mo PARK ; Jong Pill KIM ; Eun Phil HEO ; Jae Wan GO
Korean Leprosy Bulletin 2019;52(1):55-61
Leprosy is a chronic infectious and granulomatous disease caused by Mycobacterium leprae. It is treated with a multidrug therapy (MDT), which is consisted of dapsone, rifampicin, and clofazimine. However, there were relapsed leprosy associated with various predisposing factors; persisting organism, multiple involved skin lesions and nerves, HIV infection, monotherapy, inadequate and irregular therapy. Early or late relapses were observed in leprosy. Early onset relapses may occur due to insufficient treatment, and late relapses are probably with persistent bacilli and drug resistant organisms. Herein, we report on an interesting case of a 78-year-old man presented with relapsed leprosy associated with ulcerative skin lesions. The patient was diagnosed with lepromatous leprosy about 40 years ago, and he was treated with dapsone monotherapy and MDT. Our case is thought to have occurred due to persistent bacilli related to irregular therapy.
5.Green urine after general anesthesia with propofol: different responses in the same patient: A case report.
Go Eun KIM ; Dae Yoon KIM ; Doek Kyu YOO ; Jong Hwan LEE ; Sangmin Maria LEE ; Jeong Jin MIN
Anesthesia and Pain Medicine 2017;12(1):32-36
Green discoloration of the urine after propofol administration is a rare clinical phenomenon. Although the exact incidence of propofol-induced green urine is not known, the reported incidence is thought to be less than 1%. In most reported cases of propofol-induced green urine, the clinical effects were benign and reversible. However, many clinicians are unfamiliar with this rare side effect of propofol. Here, we present the case of a patient who showed green urine following two-staged repair of a thoracoabdominal aortic aneurysm with propofol infusion. His urine had a normal yellowish color after the first operation, but appeared green immediately after the second surgery. Because propofol is a commonly used sedative agent, knowing that green urine can be attributed to propofol administration and that its clinical effect is mostly benign will help clinicians with patient management, as such knowledge will also reduce unnecessary concerns and laboratory tests.
Anesthesia, General*
;
Aortic Aneurysm, Thoracic
;
Humans
;
Incidence
;
Propofol*
6.Heme Oxygenase-1 Induction and Anti-inflammatory Actions of Atractylodes macrocephala and Taraxacum herba Extracts Prevented Colitis and Was More Effective than Sulfasalazine in Preventing Relapse.
Kyu Hyun HAN ; Jong Min PARK ; Migyeong JEONG ; Young Min HAN ; Eun Jin GO ; Juyeon PARK ; Hocheol KIM ; Jae Gab HAN ; Oran KWON ; Ki Baik HAHM
Gut and Liver 2017;11(5):655-666
BACKGROUND/AIMS: In inflammatory bowel disease (IBD), repeated bouts of remission and relapse occur in patients and can impose a risk of colitis-associated cancer. We hypothesized that plant extracts of Atractylodes macrocephala (AM) or Taraxacum herba (TH) may be better than sulfasalazine for treating this disease because these extracts can promote additional regeneration. METHODS: Murine intestinal epithelial IEC-6 cells were pretreated with AM or TH before a lipopolysaccharide (LPS)-induced challenge. Acute colitis was induced with 7 days of dextran sulfate sodium (DSS) in male C57BL/6 mice, and extracts of AM and TH were administered for 2 weeks before DSS administration. RESULTS: In vitro studies demonstrated that AM or TH treatment reduced LPS-induced COX-2 and tumor necrosis factor-α mRNA levels but increased heme oxygenase-1 (HO-1). Oral preadministration of AM and TH rescued mice from DSS-induced colitis by inhibiting inflammatory mediators via inactivated extracellular signal regulated kinase and repressed nuclear factor κB and signal transducer and activator of transcription 3, but the effect was weaker for sulfasalazine than that for the extracts. Anti-inflammatory activities occurred via the inhibition of macrophage and T lymphocyte infiltrations. Unlike sulfasalazine, which did not induce HO-1, TH extracts afforded significant HO-1 induction. CONCLUSIONS: Because the AM or TH extracts were far superior in preventing DSS-induced colitis than sulfasalazine, AM or TH extracts can be considered natural agents that can prevent IBD relapse.
Animals
;
Atractylodes*
;
Colitis*
;
Dextran Sulfate
;
Heme Oxygenase-1*
;
Heme*
;
Humans
;
In Vitro Techniques
;
Inflammation
;
Inflammatory Bowel Diseases
;
Lymphocytes
;
Macrophages
;
Male
;
Mice
;
Necrosis
;
Phosphotransferases
;
Plant Extracts
;
Recurrence*
;
Regeneration
;
RNA, Messenger
;
STAT3 Transcription Factor
;
Sulfasalazine*
;
Taraxacum*
7.Patient's Factors at Entering Hospice Affecting Length of Survival in a Hospice Center.
Guk Jin LEE ; Hye Shin AHN ; Se Eun GO ; Ji Hyun KIM ; Min Wu SEO ; Seung Hun KANG ; Yeo Ree YANG ; Mi Yeong LEE ; Ku Ock LEE ; Sang Hoon CHUN ; Jong Youl JIN
Cancer Research and Treatment 2015;47(1):1-8
PURPOSE: In order to provide effective hospice care, adequate length of survival (LOS) in hospice is necessary. However the reported average LOS is much shorter. Analysis of LOS in hospice has not been reported from Korea. We evaluated the duration of LOS and the factors associated with LOS at our hospice center. MATERIALS AND METHODS: We retrospectively examined 446 patients who were admitted to our hospice unit between January 2010 and December 2012. We performed univariate and multivariate analysis for analysis of factors associated with LOS. RESULTS: The median LOS was 9.5 days (range, 1 to 186 days). The LOS of 389 patients (86.8%) was< 1 month. At the time of admission to hospice, 112 patients (25.2%) were completely bedridden, 110 patients (24.8%) had mouth care only without intake, and 134 patients (30.1%) had decreased consciousness, from confusion to coma. The median time interval between the day of the last anticancer treatment and the day of hospice admission was 75 days. By analysis of the results of multivariate analysis, decreased intake and laboratory results showing increased total white blood cell (WBC), decreased platelet count, increased serum creatinine, increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) level were poor prognostic factors for survival in hospice. CONCLUSION: Before hospice admission, careful evaluation of the patient's performance, particularly the oral intake, and total WBC, platelet, creatinine, AST, ALT, and LDH level is essential, because these were strong predictors of shorter LOS. In the future, conduct of prospective controlled studies is warranted in order to confirm the relationship between potential prognostic factors and LOS in hospice.
Alanine Transaminase
;
Aspartate Aminotransferases
;
Blood Platelets
;
Coma
;
Consciousness
;
Creatinine
;
Hospice Care
;
Hospices*
;
Humans
;
Korea
;
L-Lactate Dehydrogenase
;
Leukocytes
;
Mouth
;
Multivariate Analysis
;
Platelet Count
;
Prognosis
;
Retrospective Studies
;
Survival Analysis
8.Analysis of Predictors of Results after Surgical Treatment of Acetabular Fractures.
Jong Ki SHIN ; Sung Jin AN ; Tae Sik GO ; Jung Sub LEE
Hip & Pelvis 2015;27(2):104-109
PURPOSE: The aim of this study was to analyze the factors affecting the outcomes after surgical treatment of acetabular fractures. MATERIALS AND METHODS: Between January 2000 and December 2012, 106 patients with acetabular fractures were treated with open reduction and internal fixation. We performed a retrospective cohort study to analyze the factors which may influence a patient's prognosis after surgical treatment of an acetabular fracture. The factors examined included age, femoral head injury, fracture type, dislocation, initial displacement, delay to injury-related surgery (in days), and quality of reduction. Additionally, we investigated clinical and radiological outcomes, as well as the development of osteoarthritis. RESULTS: Patients included 85 males (80.2%) and 21 females (18.8%) with a mean age of 50.4 (17-78) years. The mean follow-up period was 2.6 (1-10) years. In a univariable regression analysis, quality of reduction, age, and initial displacement were significantly associated with radiological and clinical outcomes. In a multivariable regression analysis, quality of reduction (P<0.001) and initial displacement (P=0.001) were found to be factors predictive of clinical and radiological outcomes. Additionally, the quality of reduction (P=0.005) was found to be predictive of osteoarthritis development. CONCLUSION: Study results indicated that the quality of reduction was the most important factor influencing the prognosis of patients with acetabular fractures.
Acetabulum*
;
Cohort Studies
;
Craniocerebral Trauma
;
Dislocations
;
Female
;
Follow-Up Studies
;
Humans
;
Male
;
Methods
;
Osteoarthritis
;
Prognosis
;
Retrospective Studies
9.Genome-Wide Association Study of Liver Enzymes in Korean Children.
Tae Joon PARK ; Joo Yeon HWANG ; Min Jin GO ; Hye Ja LEE ; Han Byul JANG ; Youngshim CHOI ; Jae Heon KANG ; Kyung Hee PARK ; Min Gyu CHOI ; Jihyun SONG ; Bong Jo KIM ; Jong Young LEE
Genomics & Informatics 2013;11(3):149-154
Liver enzyme elevations, as an indicator of liver function, are widely associated with metabolic diseases. Genome-wide population-based association studies have identified a genetic susceptibility to liver enzyme elevations and their related traits; however, the genetic architecture in childhood remains largely unknown. We performed a genome-wide association study to identify new genetic loci for liver enzyme levels in a Korean childhood cohort (n = 484). We observed three novel loci (rs4949718, rs80311637, and rs596406) that were multiply associated with elevated levels of alanine transaminase and aspartate transaminase. Although there are some limitations, including genetic power, additional replication and functional characterization will support the clarity on the genetic contribution that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function.
Alanine Transaminase
;
Aspartate Aminotransferases
;
Child
;
Cohort Studies
;
Genetic Loci
;
Genetic Predisposition to Disease
;
Genome-Wide Association Study
;
Humans
;
Liver
;
Metabolic Diseases
10.Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight.
Mi Hyun PARK ; Soo Heon KWAK ; Kwang Joong KIM ; Min Jin GO ; Hye Ja LEE ; Kyung Seon KIM ; Joo Yeon HWANG ; Kuchan KIMM ; Young Min CHO ; Hong Kyu LEE ; Kyong Soo PARK ; Jong Young LEE
Experimental & Molecular Medicine 2013;45(2):e7-
The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes. Through fine-mapping analysis of chromosome 4q34-35, we detected a locus potentially linked (nonparametric linkage 2.81, logarithm of odds 2.27, P=6 x 10-4) to type 2 diabetes in overweight or obese individuals (body mass index, BMI> or =23 kg m-2). Multiple regression analysis with type 2 diabetes-related phenotypes revealed a significant association (false discovery rate (FDR) P=0.006 for rs13144140; FDR P=0.002 for rs6830266) between GPM6A (rs13144140) and BMI and waist-hip ratio, and between NEIL3 (rs6830266) and insulin level from 1314 normal individuals. Our systematic search of genome-wide linkage and association studies, demonstrate that a linkage peak for type 2 diabetes on chromosome 4q34-35 contains two type 2 diabetes-related genes, GPM6A and NEIL3.
Body Mass Index
;
Chromosomes, Human, Pair 4/*genetics
;
Diabetes Mellitus, Type 2/*complications/*genetics
;
Female
;
Genetic Linkage
;
*Genetic Loci
;
*Genetic Predisposition to Disease
;
Genome-Wide Association Study
;
Humans
;
Male
;
Middle Aged
;
Overweight/*complications/*genetics
;
Phenotype
;
Physical Chromosome Mapping
;
Statistics, Nonparametric

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