• BMB Reports
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• v.55 no.9
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• pp.453-458
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• 2022

Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy.

• BMB Reports
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• v.56 no.6
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• pp.359-364
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• 2023

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.

• The Korean Journal of Nuclear Medicine Technology
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• v.28 no.1
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• pp.81-87
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• 2024

Purpose: CA 19-9 is the most widely used tumor marker for the diagnosis of digestive system tumor, especially pancreatic and biliary tract cancer. This study was conducted to improve the result value near reference range by comparing the reagents of CA 19-9 one step method and two step method. In addition, it was intended to establish a standard for selecting reagents. Material and Methods: 120 patients who visited the National Cancer Center in 2023 were selected as subjects for this study. The reagents used in the study were CA 19-9 IRMA kits (Shinjin, Korea) and three types of reagents were compared. Two step method reagent that is currently being used (A), one step method reagent (B) and two step method reagent improved by request (C) were compared and regression analysis was performed on their data. And we also performed recovery test, linearity test and hook effect test for each reagent. Result: There were 46 cases of reagent B in which the concentration value was lower than the result measured in reagent A that was previously used, and 77 cases of reagent C. As a result of regression analysis of reagents A, B, and C, the coefficients of determination of reagents A and B, reagents A and C, and reagents B and C were 0.653, 0.577, and 0.875. In the recovery rate test and the linearity test, the results of all reagents were good, and in the hook effect test, reagent B showed a hook effect at a low value. Conclusion: The improved reagent C appears to have been improved based on the concentration value of reagent B, which the manufacturer judged to be more stable at low concentrations. The hook effect in reagent B can be a fatal reason for disqualification when selecting reagents in general patient samples which high-concentration samples appear frequently. The first improved reagent C will be able to be used once it is confirmed that it has more stability for various concentration values.

• Korean Journal of Radiology
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• v.23 no.2
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• pp.180-188
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• 2022

Objective: To validate the performance of 3T spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) for staging hepatic fibrosis in a large population, using surgical specimens as the reference standard. Materials and Methods: This retrospective study initially included 310 adults (155 undergoing hepatic resection and 155 undergoing donor hepatectomy) with histopathologic results from surgical liver specimens. They underwent 3T SE-EPI MRE ≤ 3 months prior to surgery. Demographic findings, underlying liver disease, and hepatic fibrosis pathologic stage according to METAVIR were recorded. Liver stiffness (LS) was measured by two radiologists, and inter-reader reproducibility was evaluated using the intraclass correlation coefficient (ICC). The mean LS of each fibrosis stage (F0-F4) was calculated in total and for each etiologic subgroup. Comparisons among subgroups were performed using the Kruskal-Wallis test and Conover post-hoc test. The cutoff values for fibrosis staging were estimated using receiver operating characteristic (ROC) curve analysis. Results: Inter-reader reproducibility was excellent (ICC, 0.98; 95% confidence interval, 0.97-0.99). The mean LS values were 1.91, 2.41, 3.24, and 5.41 kPa in F0-F1 (n = 171), F2 (n = 26), F3 (n = 38), and F4 (n = 72), respectively. The discriminating cutoff values for diagnosing ≥ F2, ≥ F3, and F4 were 2.18, 2.71, and 3.15 kPa, respectively, with the ROC curve areas of 0.97-0.98 (sensitivity 91.2%-95.9%, specificity 90.7%-99.0%). The mean LS was significantly higher in patients with cirrhosis (F4) of nonviral causes, such as primary biliary cirrhosis (9.56 kPa) and alcoholic liver disease (7.17 kPa) than in those with hepatitis B or C cirrhosis (4.28 and 4.92 kPa, respectively). There were no statistically significant differences in LS among the different etiologic subgroups in the F0-F3 stages. Conclusion: The 3T SE-EPI MRE demonstrated high interobserver reproducibility, and our criteria for staging hepatic fibrosis showed high diagnostic performance. LS was significantly higher in patients with non-viral cirrhosis than in those with viral cirrhosis.

• Korean Journal of Radiology
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• v.23 no.4
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• pp.389-401
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• 2022

Objective: This study aimed to determine a factor for predicting suboptimal image quality of the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI in patients with extrahepatic bile duct (EHD) cancer before MRI examination. Materials and Methods: We retrospectively evaluated 259 patients (mean age ± standard deviation: 68.0 ± 8.3 years; 162 male and 97 female) with EHD cancer who underwent gadoxetic acid-enhanced MRI between 2011 and 2017. Patients were divided into a primary analysis set (n = 184) and a validation set (n = 75) based on the diagnosis date of January 2014. Two reviewers assigned the functional liver imaging score (FLIS) to reflect the HBP image quality. The FLIS consists of the sum of three HBP features, each scored on a 0-2 scale: liver parenchymal enhancement, biliary excretion, and signal intensity of the portal vein. Patients were classified into low-FLIS (0-3) or high-FLIS (4-6) groups. Multivariable analysis was performed to determine a predictor of low FLIS using serum biochemical and imaging parameters of cholestasis severity. The optimal cutoff value for predicting low FLIS was obtained using receiver operating characteristic analysis, and validation was performed. Results: Of the 259 patients, 140 (54.0%) and 119 (46.0%) were classified into the low-FLIS and high-FLIS groups, respectively. In the primary analysis set, total bilirubin was an independent factor associated with low FLIS (adjusted odds ratio per 1-mg/dL increase, 1.62; 95% confidence interval [CI], 1.32-1.98). The optimal cutoff value of total bilirubin for predicting low FLIS was 2.1 mg/dL with a sensitivity of 95.1% (95% CI: 88.9-98.4) and a specificity of 89.0% (95% CI: 80.2-94.9). In the validation set, the total bilirubin cutoff showed a sensitivity of 92.1% (95% CI: 78.6-98.3) and a specificity of 83.8% (95% CI: 68.0-93.8). Conclusion: Serum total bilirubin before acquisition of gadoxetic acid-enhanced MRI may help predict suboptimal HBP image quality in patients with EHD cancer.

• Clinical Endoscopy
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• v.56 no.1
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• pp.107-113
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• 2023

Background/Aims: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. Methods: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. Results: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. Conclusions: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

• Journal of the Korean Society of Radiology
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• v.85 no.3
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• pp.661-667
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• 2024

Afferent loop syndrome (ALS) is a rare complication of gastrectomies and gastrointestinal reconstruction. This can predispose patients to fatal conditions, such as cholangitis, pancreatitis, and duodenal perforation with peritonitis. Therefore, emergency decompression is necessary to prevent these complications. Herein, we report two cases in which transcholecystic duodenal drainage, an alternative decompression treatment, was performed in ALS patients without bile duct dilatation. Two patients who underwent distal gastrectomy with Billroth II anastomosis sought consultation in an emergency department for epigastric pain and vomiting. On CT, ALS with acute pancreatitis was diagnosed. However, biliary access could not be achieved because of the absence of bile duct dilatation. To overcome this problem, a duodenal drainage catheter was placed to decompress the afferent loop after traversing the cystic duct via a transcholecystic approach. The patients were discharged without additional surgical treatment 2 weeks and 1 month after drainage.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.17-20
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• 2010

Purpose: The hepatobiliary scan is the examination which is the possibility of knowing the function of liver, gall bladder and closing of the biliary tract. Also, after subtotal gastrectomy, the increased gastric-bile reflux is known as the primary reason of reflux gastritis. In this study, according to changing the acquisition method, we tried to prove the reflux time and reflux index in patients who underwent subtotal gastrectomy. Materials and Methods: From Oct 2008 to Jan 2009, 72 patients with subtotal gastrectomy who took the hepatobiliary scan (man: 52, woman: 20, age range: 31-77, mean age: $60.5{\pm}7$) in our department. We used the radiopharmaceutical $^{99m}Tc$-mebrofenin 185 MBq/0.5 cc. After 5 minutes, we acquired 300,000 counts anterior image on supine, and then we acquired right lateral and $45^{\circ}$ LAO position by using the time setting method. We acquired 30 min, 60 min, 90 min, 120 min and fatty meal by the same method. We painted the ROI of liver, GB and CBD on 30 min anterior image and LAO image in patients had occurred the bile juice reflux. And then we painted the ROI of stomach on others image. We calculated the reflux index from those values. Results: According to this study, we found out 40 patients (55.6%) who had occurred the gastric-bile juice reflux (1 person from 30 min, 7 persons from 60 min, 4 persons from 90 min, 28 persons from after fatty meal). Hourly, the bile reflux highest level is 6 persons from 60 min, 2 persons from 90 min, 32 persons from fatty meal among those people. The reflux index of anterior is 0.85-23.36% (mean 6.53%). The reflux index of LAO is 1-29.13% (mean 8.89%). By visual assessment, we can distinguish that there were 26 of the 40 patients (65%) had occurred the reflux on LAO image more than anterior image. Conclusion: We find out that the patients with subtotal gastrectomy had occurred gastric-bile juice reflux more than 50% from hepatobiliary scan. And after eating fatty meal, we can know that it's the most possible to occur the gastric-bile juice reflux. When it happened, we have to change the acquisition method to reduce the overlap between colon and stomach. This study will be more valuable in diagnosis.

• The Korean Journal of Nuclear Medicine Technology
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• v.22 no.1
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• pp.98-102
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• 2018

Purpose When examining patients with digestive system Leakage, it is not easy to distinguish between bile leakage and bleeding only with Planar images. I would like to evaluate the utility of leakage of bile, confirmation of gastrointestinal bleeding and location discrimination using SPECT-CT. Materials and Methods SPECT-CT was performed according to the request of the reading room after acquiring Planar image for a total of 13 patients, including 8 patients suspected of bile leakage and 5 patients suspected of gastrointestinal bleeding, among patients visiting this specification went. We used Symbia T16 from SIEMENS and Discovery 670 from GE. Planar and SPECT-CT images were evaluated with a score of 1 to 10 by 4 experienced nuclear medicine doctors. Using the sensitivity and the specificity, the evaluation of the inspection by the ROC curve was carried out. The final diagnosis was confirmed by follow-up observation as a result of reoperative surgery. Results The sensitivity, specificity and accuracy of SPECT-CT were 91.7%, 100% and 94.2%, respectively. Planar images were 83.3%, 68.8% and 78.8%, respectively. Planar images showed lower diagnostic accuracy compared to SPECT-CT (78.8%, 94.2%, p<0.05). Moreover, the reliability of the diagnosis of SPECT-CT by ROC curve analysis showed a more useful result than the Planar image (p<0.05). Conclusion SPECT-CT had high sensitivity and specificity for diagnosis of biliary leakage and gastrointestinal bleeding and location discrimination. When SPECT-CT is additionally performed together with Planar images, it may be considered to improve bile leakage and diagnosis of gastrointestinal bleeding patients and position discrimination evaluation. There is usefulness depending on the patient's age and position, but consideration of additional CT exposure may be done sufficiently.

• Journal of radiological science and technology
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• v.38 no.2
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• pp.127-134
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• 2015

This study was designed to determine the prevalence of gallstones in the last three years and evaluate the associated risk factors in the population who underwent health screening. Although there are many studies reporting the prevalence and risk factors of GB polyp, the results varied among each report. The aims of this study were to evaluate the prevalence rate and risk factors of GB polyp, colon polyp and fatty liver in the population who underwent health screening. The study population consisted of 4,877 visited the health promotion center in Dalseogu, Daegu in Korea from January 2011 to December 2013. Each participant in the study had their biliary system gallbladder examined using ultrasonography. The prevalence of GB polyp was evaluated along with age, gender, metabolic syndrom, body mass index (BMI), Fatty liver, Colon polyp. A showed of total 383 (7.9%) people were found to have GB polyps. The prevalence of sex among 256 (9.8%) patients men and 127 (5.6%) women which showed significantly higher in male than in female subjects(p=0.001). The mean size of the GB polyps 4.92 mm (1.6-17 mm). The sizes of most GB polyps (73.6%) were less than 10 mm in diameter. 122 subjects (31.28%) had multiple GB polyps which 2 or more polyps and 261 subjects (68.2%) had single polyp. Independent risk factors related with GB polyp were male gender (OR 0.551, p<0.001), overweight that BMI above $23kg/m^2$ (OR 0.713, p=0.002) triglyceride (OR 0.571, P<0.001), metabolic syndrome (OR 0.049, p=0.033) and colon polyp (OR 1.409, p=0.002). In spite of the conclusion, the prevalence GB polyp was higher than previous Korea and other country reports. The GB polyp in a healthy population was results as 7.9%. The risk factors of GB polyps were found to be male, being overweight, triglyceride, metabolic syndrome and colon polyp. Not only the subject of a health examination is needed but, a further study of the general public when possible.