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1.  The usefulness of contrast-enhanced ultrasonography in the early detection of hepatocellular carcinoma viability after transarterial chemoembolization: pilot study 
Clinical and Molecular Hepatology  2015;21(2):165-174.
The therapeutic effect of transarterial chemoembolization (TACE) against hepatocellular carcinoma (HCC) is usually assessed using multidetector computed tomography (MDCT). However, dense lipiodol depositions can mask the enhancement of viable HCC tissue in MDCT. Contrast-enhanced ultrasonography (CEUS) could be effective in detecting small areas of viability and patency in vessels. We investigated whether arterial enhancement in CEUS after treatment with TACE can be used to detect HCC viability earlier than when using MDCT.
Twelve patients received CEUS, MDCT, and gadoxetic-acid-enhanced dynamic magnetic resonance imaging (MRI) at baseline and 4 and 12 weeks after TACE. The definition of viable HCC was defined as MRI positivity after 4 or 12 weeks.
Eight of the 12 patients showed MRI positivity at 4 or 12 weeks. All patients with positive CEUS findings at 4 weeks (n=8) showed MRI positivity and residual viable HCC at 4 or 12 weeks. Five of the eight patients with positive CEUS findings at 4 weeks had negative results on the 4-week MDCT scan. Four (50%) of these eight patients did not have MRI positivity at 4 weeks and were ultimately confirmed as having residual HCC tissue at the 12-week MRI. Kappa statistics revealed near-perfect agreement between CEUS and MRI (κ=1.00) and substantial agreement between MDCT and MRI (κ=0.67).
In the assessment of the response to TACE, CEUS at 4 weeks showed excellent results for detecting residual viable HCC, which suggests that CEUS can be used as an early additive diagnosis tool when deciding early additional treatment with TACE.
PMCID: PMC4493360  PMID: 26157754
Hepatocellular carcinoma; Transarterial chemoembolization; Contrast-enhanced ultrasonography; Computed tomography; Magnetic resonance imaging
2.  Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension 
Clinical and Molecular Hepatology  2014;20(4):376-383.
Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial.
Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders.
The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups.
The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.
PMCID: PMC4278069  PMID: 25548744
Portal hypertension; Angiotensin receptor blocker; Non-selective beta blocker; Cirrhosis; Hepatic venous pressure gradient
3.  Alcoholic liver disease: Treatment 
World Journal of Gastroenterology : WJG  2014;20(36):12934-12944.
The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation.
PMCID: PMC4177474  PMID: 25278689
Liver disease; Alcoholic; Treatment
4.  Clinical characteristics and outcomes of antenatal fetal intra-abdominal umbilical vein varix detection 
Obstetrics & Gynecology Science  2014;57(3):181-186.
This study reviewed clinical characteristics of fetal intra-abdominal umbilical vein (FIUV) varices that were detected during antenatal ultrasound examinations.
Between January 2006 and January 2012, 121 cases of FIUV varices were detected and 7 cases were lost to follow-up. We retrospectively reviewed the medical records of 114 patients and neonates.
From a total 96,553 ultrasound examinations in 43,995 pregnancies, 121 cases of FIUV varices were identified (2.8 per 1,000 pregnancies). Gestational age at diagnosis was 32.0 ± 2.9 weeks (range, 20.1-36.3 weeks), the mean diameter of the FIUV varix was 12.6 ± 2.1 mm (range, 8.0-21.0 mm) at initial diagnosis and the mean maximal diameter was 13.1 ± 2.3 mm (range, 8.0-21.0 mm) during follow-up. The most severe pregnancy complications included one case of intrauterine fetal death and another case of fetal hydrops. Associated fetal anomalies (n = 11, 9.6%) detected by ultrasonography included bilateral renal pelvis dilatation, ventriculomegaly, cryptorchidism, incomplete renal duplication and pulmonary sequestration. A total of 104 cases (91.2%) were delivered at term and 10 cases (8.8%) were preterm deliveries before 37 weeks of gestation.
FIUV varices that are not associated with fetal anomalies based on ultrasound examination during prenatal care have favorable pregnancy outcomes. Nevertheless, close fetal monitoring is recommended to decrease perinatal complications.
PMCID: PMC4038683  PMID: 24883288
Antenatal ultrasound; Umbilical veins; Varicose veins
5.  Invasive and non-invasive diagnosis of cirrhosis and portal hypertension 
With advances in the management and treatment of advanced liver disease, including the use of antiviral therapy, a simple, one stage description for advanced fibrotic liver disease has become inadequate. Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential, current diagnostic tests have not kept pace with the progression of this new paradigm. Liver biopsy and hepatic venous pressure gradient measurement are the gold standards for the estimation of hepatic fibrosis and portal hypertension (PHT), respectively, and they have diagnostic and prognostic value. However, they are invasive and, as such, cannot be used repeatedly in clinical practice. The ideal noninvasive test should be safe, easy to perform, inexpensive, reproducible as well as to give numerical and accurate results in real time. It should be predictive of long term outcomes related with fibrosis and PHT to allow prognostic stratification. Recently, many types of noninvasive alternative tests have been developed and are under investigation. In particular, imaging and ultrasound based tests, such as transient elastography, have shown promising results. Although most of these noninvasive tests effectively identify severe fibrosis and PHT, the methods available for diagnosing moderate disease status are still insufficient, and further investigation is essential to predict outcomes and individualize therapy in this field.
PMCID: PMC3989965  PMID: 24764667
Hepatic fibrosis; Portal hypertension; Liver biopsy; Hepatic venous pressure gradient; Non-invasive test; Transient elastography
6.  The usefulness of non-invasive liver stiffness measurements in predicting clinically significant portal hypertension in cirrhotic patients: Korean data 
Clinical and molecular hepatology  2013;19(4):370-375.
Liver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis.
LSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG ≥10 and ≥12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves.
A strong positive correlation between LSM and HVPG was observed in the overall population (r2=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG ≥10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG ≥12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively.
LSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.
PMCID: PMC3894436  PMID: 24459641
Portal hypertension; Liver stiffness measurement; Cirrhosis
7.  Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus 
Clinical and molecular hepatology  2013;19(4):421-425.
Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are nonspecific, and include abdominal discomfort, mild hepatomegaly, and transaminase elevation. In this report we describe three cases of patients presenting serum transaminase elevation and hepatomegaly with a history of poorly controlled type I DM. All of the cases showed sudden elevation of transaminase to more than 30 times the upper normal range (like in acute hepatitis) followed by sustained fluctuation (like in relapsing hepatitis). However, the patients did not show any symptom or sign of acute hepatitis. We therefore performed a liver biopsy to confirm the cause of liver enzyme elevation, which revealed GH. Clinicians should be aware of GH so as to prevent diagnostic delay and misdiagnosis, and have sufficient insight into GH; this will be aided by the present report of three cases along with a literature review.
PMCID: PMC3894443  PMID: 24459648
Glycogen hepatopathy; Transaminase; Type I diabetes mellitus
8.  Therapeutic Effects of Mesenchymal Stem Cells for Patients with Chronic Liver Diseases: Systematic Review and Meta-analysis 
Journal of Korean Medical Science  2015;30(10):1405-1415.
Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.
PMCID: PMC4575928  PMID: 26425036
Mesenchymal Stem Cells; Chronic Liver Diseases; Systematic Review; Meta-analysis
9.  Maternal and Neonatal Outcomes in Korean Women with Type 1 and Type 2 Diabetes 
Diabetes & Metabolism Journal  2015;39(4):316-320.
The purpose of this study was to evaluate maternal and neonatal outcomes in Korean women with type 1 diabetes and type 2 diabetes.
We performed a retrospective survey of 163 pregnancies in women with type 1 diabetes (n=13) and type 2 diabetes (n=150) treated from 2003 to 2010 at Cheil General Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics as well as maternal and neonatal outcomes between groups.
Differences in glycosylated hemoglobin between type 1 and type 2 diabetes were not significant. Birth weight (3,501±689.6 g vs. 3,366±531.4 g) and rate of major congenital malformations (7.7% vs. 5.6%) were not significantly different. However, women with type 1 diabetes had higher rates of preeclampsia (38.5% vs. 8.2%, P=0.006), large for gestational age (LGA; 46.2% vs. 20.4%, P=0.004), macrosomia (38.5% vs. 13.4%, P=0.032), and admission for neonatal care (41.7% vs. 14.8%, P=0.03) than women with type 2 diabetes.
Maternal and neonatal outcomes for women with type 1 diabetes were poorer than for women with type 2 diabetes, especially preeclampsia, LGA, macrosomia and admission to the neonatal intensive care unit.
PMCID: PMC4543195  PMID: 26301193
Pregnancy outcome; Type 1 diabetes; Type 2 diabetes
10.  Diagnostic and Prognostic Values of Noninvasive Predictors of Portal Hypertension in Patients with Alcoholic Cirrhosis 
PLoS ONE  2015;10(7):e0133935.
Portal hypertension is a direct consequence of hepatic fibrosis, and several hepatic fibrosis markers have been evaluated as a noninvasive alternative to the detection of portal hypertension and esophageal varices. In the present study, we compared the diagnostic and prognostic values of the noninvasive fibrosis markers in patients with alcoholic cirrhosis. A total of 219 consecutive alcoholic cirrhosis patients were included. Biochemical scores and liver stiffness (LS) were compared with hepatic venous pressure gradient (HVPG). For the detection of clinically significant portal hypertension (CSPH; HVPG≥10 mmHg) in compensated patients, LS and LS–spleen diameter to platelet ratio score (LSPS) showed significantly better performance with area under the curves (AUCs) of 0.85 and 0.82, respectively, than aspartate aminotransferase-to-platelet ratio index, FIB-4, Forns’ index, Lok index, (platelet count)2/[monocyte fraction (%) × segmented neutrophil fraction (%)], and platelet count-to-spleen diameter ratio (all P<0.001). However, for the detection of high-risk varices, none of the non-invasive tests showed reliable performance (AUCs of all investigated tests < 0.70). During a median follow-up period of 42.6 months, 46 patients with decompensated cirrhosis died. Lok index (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.05–1.22; P = 0.001) and FIB-4 (HR, 1.06; 95% CI, 1.01–1.10; P = 0.009) were independently associated with all-cause death in decompensated patients. Among the tested noninvasive markers, only Lok index significantly improved discrimination function of MELD score in predicting overall survival. In conclusion, LS and LSPS most accurately predict CSPH in patients with compensated alcoholic cirrhosis. In the prediction of overall survival in decompensated patients, however, Lok index is an independent prognostic factor and improves the predictive performance of MELD score.
PMCID: PMC4511411  PMID: 26196942
11.  Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis 
Clinical and Molecular Hepatology  2015;21(2):141-149.
Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs.
We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (α-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs.
The BM-MSCs in the direct co-culture system significantly decreased the production of α-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-β1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs.
These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.
PMCID: PMC4493357  PMID: 26157751
Bone-marrow-derived mesenchymal stem cell; Cirrhosis; Hepatic fibrosis
12.  The Accuracy of Ultrasonography for the Evaluation of Portal Hypertension in Patients with Cirrhosis: A Systematic Review 
Korean Journal of Radiology  2015;16(2):314-324.
Studies have presented conflicting results regarding the accuracy of ultrasonography (US) for diagnosing portal hypertension (PH). We sought to identify evidence in the literature regarding the accuracy of US for assessing PH in patients with liver cirrhosis.
Materials and Methods
We conducted a systematic review by searching databases, including MEDLINE, EMBASE, and the Cochrane Library, for relevant studies.
A total of 14 studies met our inclusion criteria. The US indices were obtained in the portal vein (n = 9), hepatic artery (n = 6), hepatic vein (HV) (n = 4) and other vessels. Using hepatic venous pressure gradient (HVPG) as the reference, the sensitivity (Se) and specificity (Sp) of the portal venous indices were 69-88% and 67-75%, respectively. The correlation coefficients between HVPG and the portal venous indices were approximately 0.296-0.8. No studies assess the Se and Sp of the hepatic arterial indices. The correlation between HVPG and the hepatic arterial indices ranged from 0.01 to 0.83. The Se and Sp of the hepatic venous indices were 75.9-77.8% and 81.8-100%, respectively. In particular, the Se and Sp of HV arrival time for clinically significant PH were 92.7% and 86.7%, respectively. A statistically significant correlation between HVPG and the hepatic venous indices was observed (0.545-0.649).
Some US indices, such as HV, exhibited an increased accuracy for diagnosing PH. These indices may be useful in clinical practice for the detection of significant PH.
PMCID: PMC4347267  PMID: 25741193
Ultrasonography; Hepatic venous pressure gradient; Portal hypertension; Cirrhosis
13.  Probiotics (Lactobacillus rhamnosus R0011 and acidophilus R0052) Reduce the Expression of Toll-Like Receptor 4 in Mice with Alcoholic Liver Disease 
PLoS ONE  2015;10(2):e0117451.
The role of lipopolysaccharide (LPS) and toll-like receptor 4 (TLR 4) in the pathogenesis of alcoholic liver disease (ALD) has been widely established. We evaluated the biological effects of probiotics (Lactobacillus rhamnosus R0011 and acidophilus R0052), KRG (Korea red ginseng), and urushiol (Rhus verniciflua Stokes) on ALD, including their effects on normal and high-fat diet in mice.
One hundred C57BL/6 mice were classified into normal (N) and high-fat diet (H) groups. Each group was divided into 5 sub-groups: control, alcohol, alcohol+probiotics, alcohol+KRG, and alcohol+urushiol. A liver function test, histology, electron-microscopy, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-10, and TLR 4 were evaluated and compared.
In the N group, probiotics, KRG, and urushiol significantly reduced levels of TNF-α (12.3±5.1, 13.4±3.9, and 12.1±4.3 vs. 27.9±15.2 pg/mL) and IL-1β (108.4±39.4, 75.0±51.0, and 101.1±26.8 vs. 162.4±37.5 pg/mL), which were increased by alcohol. Alcohol-induced TLR 4 expression was reduced by probiotics and urushiol (0.7±0.2, and 0.8±0.1 vs. 1.0±0.3, p<0.001). In the H group, IL-10 was significantly increased by probiotics and KRG, compared with alcohol (25.3±15.6 and 20.4±6.2 vs. 7.6±5.6 pg/mL) and TLR 4 expression was reduced by probiotics (0.8±0.2 vs. 1.0±0.3, p = 0.007).
Alcohol-induced TLR 4 expression was down-regulated by probiotics in the normal and high-fat diet groups. Probiotics, KRG, and urushiol might be effective in the treatment of ALD by regulating the gut-liver axis.
PMCID: PMC4333821  PMID: 25692549
14.  2014 First-trimester ultrasound forum from the Korean Society of Ultrasound in Obstetrics and Gynecology 
A first-trimester ultrasound scan has become an essential part of antenatal care. The Korean Society of Ultrasound in Obstetrics and Gynecology held a first-trimester ultrasound forum on April 5, 2014. The forum aimed to present an updated review of the literature on the topic of first-trimester ultrasound in specific lectures and to host a panel discussion on several important issues regarding first-trimester scans. The forum provided evidence- and consensus-based best practice patterns for obstetricians in Korea. Here, we report the review and checklists presented from the forum.
PMCID: PMC4303746  PMID: 25629012
Korean Society of Ultrasound in Obstetrics and Gynecology; Nuchal translucency measurement; Pregnancy trimester, first; Ultrasonography
15.  Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model 
BMC Gastroenterology  2014;14:198.
Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis. No effective therapy is currently available for decompensated cirrhosis except liver transplantation. Hence, we investigated the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model.
The BM-MSCs were injected directly into the right liver lobe twice, at 6 and 8 weeks during the 12-week TAA administration, in thioacetamide (TAA)-induced cirrhotic rats model, and hepatic fibrosis was evaluated. At 12 weeks, the effect of BM-MSCs on hepatic fibrosis was analyzed histomorphologically using the Laennec fibrosis scoring system, and the collagen proportionate area was quantified. Cirrhosis-related factors, such as transforming growth factor β1 (TGF-β1), type 1 collagen (collagen-1), α-smooth muscle actin (α-SMA), and P-Smad3/Smad3 expression levels, were evaluated using real-time polymerase chain reaction and western blot assays.
According to the Laennec fibrosis scoring system, histological improvement was observed in hepatic fibrosis after BM-MSC treatment (P <0.01). The percentage of the collagen proportionate area decreased from 16.72 ± 5.51 to 5.06 ± 1.27 after BM-MSC treatment (P <0.01). The content of hepatic hydroxyproline was significantly lower in the BM-MSC treated group (46.25 ± 13.19) compared to the untreated cirrhotic group (85.81 ± 17.62; P <0.01). BM-MSC administration significantly decreased TGF-β1, collagen-1, and α-SMA expression in TAA-induced cirrhotic rats (P <0.01). We also confirmed P-Smad3/Smad3, downstream effectors of the TGF-β1 signaling pathway, and found that MSC transplantation inhibited Smad3 phosphorylation.
BM-MSC treatment attenuated hepatic fibrosis in rats with TAA-induced cirrhosis, raising the possibility of the clinical use of BM-MSCs in the treatment of cirrhosis.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-014-0198-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4251876  PMID: 25425284
Bone marrow-derived mesenchymal stem cell; Cirrhosis; Hepatic fibrosis; Liver function
16.  Genome sequence of mungbean and insights into evolution within Vigna species 
Nature Communications  2014;5:5443.
Mungbean (Vigna radiata) is a fast-growing, warm-season legume crop that is primarily cultivated in developing countries of Asia. Here we construct a draft genome sequence of mungbean to facilitate genome research into the subgenus Ceratotropis, which includes several important dietary legumes in Asia, and to enable a better understanding of the evolution of leguminous species. Based on the de novo assembly of additional wild mungbean species, the divergence of what was eventually domesticated and the sampled wild mungbean species appears to have predated domestication. Moreover, the de novo assembly of a tetraploid Vigna species (V. reflexo-pilosa var. glabra) provides genomic evidence of a recent allopolyploid event. The species tree is constructed using de novo RNA-seq assemblies of 22 accessions of 18 Vigna species and protein sets of Glycine max. The present assembly of V. radiata var. radiata will facilitate genome research and accelerate molecular breeding of the subgenus Ceratotropis.
Mungbean is a fast-growing and warm-season legume crop, cultivated mainly in Asia. Here, the authors sequence the genomes of both wild and domesticated mungbean varieties and, together with detailed transcriptome data, provide insight into mungbean domestication, polyploidization and speciation.
PMCID: PMC4241982  PMID: 25384727
17.  Gestational weight gain is an important risk factor for excessive fetal growth 
Obstetrics & Gynecology Science  2014;57(6):442-447.
To estimate the odds ratio of prepregnant body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) for excessive fetal growth, which we define as large for gestational age (LGA).
We included 16,297 women who delivered a live-born singleton baby at term. We fit logistic regressions to estimate the odds ratios of variables, including maternal age, parity, prepregnant BMI ≥23, GWG ≥15 kg, and GDM, for LGA. We classified GWG into four categories (<10, 10-14.9, 15-19.9, and ≥20 kg) and BMI into four categories (underweight, normal, overweight, and obese). After adjusting for age and parity, we analyzed the odds ratios of prepregnant BMI according to GWG between non-GDM and GDM women for LGA.
The odds ratios of GWG ≥15 kg and prepregnancy BMI ≥23 for LGA were 2.40 (95% confidence interval [CI], 2.16-2.67) and 2.24 (95% CI, 1.99-2.51), respectively. The odd ratio of GDM was 1.37 (95% CI, 1.09-1.71). The risk of GDM women with normal/-overweight BMI and GWG <15 kg for LGA was not significantly greater than those of the reference group. The odd ratios of GDM women with overweight/obese BMI and GWG 15 to 19.9 kg were 3.95 (95% CI, 1.26-12.38) and 9.70 (95% CI, 3.79-24.87), respectively.
GWG ≥15 kg might be a more important risk factor for LGA than either prepregnancy BMI ≥23 or GDM. Risk for LGA was highest in obese GDM women with GWG ≥15 kg.
PMCID: PMC4245336  PMID: 25469331
Birth weight; Body mass index; Diabetes; Gestational; Weight gain
18.  The clinical practice patterns of fetal ultrasonography in the first-trimester: A questionnaire survey of members of the Korean Society of Ultrasound in Obstetrics and Gynecology 
Obstetrics & Gynecology Science  2014;57(6):448-456.
This study aimed to survey the current clinical practice of first-trimester ultrasonography among members of the Korean Society of Ultrasound in Obstetrics and Gynecology (KSUOG) and to provide basic data for making practical recommendations about first-trimester ultrasonography scan in Korea.
This survey was conducted using a self-administered anonymous questionnaire. The first-trimester in this survey was divided into two parts: early and late first-trimester. The survey was focused on safety issue, nuchal translucency (NT) cutoff, the anatomic structures they check, and the need for practical recommendations or educational courses during the first-trimester.
During the study period, 194 KSUOG members participated into this survey. The survey on early first-trimester scan reveal that 173 (89.2%) of respondents had used pulsed-wave Doppler or color Doppler imaging to monitor fetal heart beat. For the late first-trimester scan, 145 (74.7%) of respondents was found to check for fetal anatomical assessments during their NT screening performance; however, the clinical practice patterns were considerably varied among participants. More than half of the respondents used the criterion of NT ≥3.0 mm to define increased NT. Approximately 80% of respondents stated that the screening ultrasonography of fetal structures in the first-trimester was necessary. Furthermore, 187 (96.4%) of respondents were in favor of a recommendation for first-trimester ultrasonography in Korea.
This is the first survey of the current clinical practice of first-trimester ultrasonography in Korea. Our survey findings highlight the need for the practical recommendation or educational course for first-trimester ultrasonography.
PMCID: PMC4245337  PMID: 25469332
Clinical practical pattern; Data collection; Pregnancy trimester, first; Ultrasonography
19.  Elective tracheostomy scoring system for severe oral disease patients 
The purpose of this research was to create a scoring system that provides comprehensive assessment of patients with oromaxillofacial cancer or odontogenic infection, and to statistically reevaluate the results in order to provide specific criteria for elective tracheostomy.
Materials and Methods
All patients that had oral cancer surgery (group A) or odontogenic infection surgery (group B) during a period of 10 years (2003 to 2013) were subgrouped according to whether or not the patient received a tracheostomy. After a random sampling (group A: total of 56, group B: total of 60), evaulation procedures were observed based on the group classifications. For group A, four factors were evaluated: TNM stage, reconstruction methods, presence of pathologic findings on chest posterior-anterior (PA), and the number of systemic diseases. Scores were given to each item based on the scoring system suggested in this research and the scores were added together. Similarly, the sum score of group B was counted using 5 categories, including infection site, C-reactive protein level on first visit, age, presence of pathologic findings on chest PA, and number of systemic diseases.
The scoring system rendered from this research shows that there is a high correlation between the scores and TNM stage in oral cancer patients, or infection sites in odontogenic infection patients. However, no correlation between pathologic findings on chest PA could be found in either group. The results also indicated that for both groups, the hospital day increased with the tracheostomy score. The tracheostomy score cutoff value was 5 in oral cancer patients and 6 in odontogenic infection patients which was used for elective tracheostomy indication.
The elective tracheostomy score system suggested by this research is a method that considers both the surgical and general conditions of the patient, and can be very useful for managing patients with severe oral disease.
PMCID: PMC4217265  PMID: 25368833
Tracheostomy; Scoring system; Airway management; Mouth neoplasms; Odontogenic infection
20.  Pregnancy-associated pulmonary embolism during the peripartum period: An 8-year experience at a single center 
Obstetrics & Gynecology Science  2014;57(4):260-265.
The purpose of this study was to estimate the incidence, timing of onset, risk factors, and mortality rate of pregnancy-associated pulmonary embolism (PAPE).
We analyzed PAPE cases that occurred between January 2005 and December 2012 at Cheil General Hospital & Women's Healthcare Center. Those cases that were not confirmed by computed tomography scan or were confirmed as amniotic fuid embolisms were excluded. We analyzed various risk factors such as previous surgery, mode of delivery, maternal age, and obesity in PAPE.
There were 57,092 deliveries over 8 years. Of them, 13 cases (0.023%) were diagnosed with PAPE. All cases occurred in the postpartum period after cesarean delivery. There were no cases of PAPE after vaginal deliveries. Of the total cases, 10 cases (76.9%) were diagnosed in the early postpartum period within 48 hours. Eight cases (61.5%) had a history of previous surgery. There were 3 cases (23.1%) of multiple pregnancy and 3 cases (23.1%) of preterm delivery. No cases had a history of venous thromboembolism. Among 13 cases, 10 cases improved with only anticoagulation, 2 cases received surgical thrombectomy, and one case was maternal death.
Our results indicated that the incidence of PAPE was very low (0.023%) and occurred mainly in the postpartum period after cesarean section. However, its maternal mortality rate was significantly high (7.7%). Therefore, we suggest that immediate diagnosis and prompt treatment should be prioritized for improvement of PAPE patients' survival rate.
PMCID: PMC4124086  PMID: 25105098
Peripartum period; Pregnancy; Pulmonary; Thromboembolism
21.  Effects of Korean Red Ginseng (Panax ginseng), urushiol (Rhus vernicifera Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) on the gut–liver axis of alcoholic liver disease 
Journal of Ginseng Research  2014;38(3):167-172.
Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD).
We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a Lieber–DeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared.
No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group (0.37 ± 0.06 ng/mL, 0.39 ± 0.12 ng/mL, and 0.33 ± 0.07 ng/mL, respectively, vs. 0.88 ± 0.31 ng/mL; p < 0.05). Interleukin-1β levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-α level of liver tissue was decreased in the KRG group.
The pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments.
PMCID: PMC4213850  PMID: 25378990
alcoholic liver disease; Lactobacillus; Panax ginseng; urushiol
22.  Metastatic testicular tumor presenting as a scrotal hydrocele: An initial manifestation of pancreatic adenocarcinoma 
Oncology Letters  2014;7(6):1793-1795.
Metastatic pancreatic adenocarcinoma involving the testis is a rare condition with a poor prognosis. The current study describes the case of a 69-year-old male who presented with a painful swelling of the left scrotum. Scrotal ultrasonography revealed hydroceles in the scrotal sacs, with the left one being larger in size. The patient underwent left hydrocelectomy and was eventually diagnosed with metastatic adenocarcinoma. Abdominal computed tomography, which was performed to detect the primary cancer, showed a pancreatic tail carcinoma with liver and multiple lymph node metastases, and peritoneal carcinomatosis. The patient received gemcitabine-based chemotherapy but resulted in progressive disease. This case shows that in a patient in whom a primary testicular tumor is unusual due to their age, a testicular mass or hydrocele should be a suspect for possible metastatic disease.
PMCID: PMC4049672  PMID: 24932235
adenocarcinoma; neoplasm metastasis; pancreatic neoplasms; testicular hydrocele; testicular neoplasms
23.  Relationship between Tetrahydrobiopterin and Portal Hypertension in Patients with Chronic Liver Disease 
Journal of Korean Medical Science  2014;29(3):392-399.
Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.
Graphical Abstract
PMCID: PMC3945135  PMID: 24616589
Hypertension, Portal; Nitric Oxide; Liver Cirrhosis
24.  Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data 
This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.
Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals.
Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality.
A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.
PMCID: PMC3992326  PMID: 24757655
Liver cirrhosis; Transjugular intrahepatic portosystemic shunt; Portal hypertension
25.  Disease specific characteristics of fetal epigenetic markers for non-invasive prenatal testing of trisomy 21 
Non-invasive prenatal testing of trisomy 21 (T21) is being actively investigated using fetal-specific epigenetic markers (EPs) that are present in maternal plasma. Recently, 12 EPs on chromosome 21 were identified based on tissue-specific epigenetic characteristics between placenta and blood, and demonstrated excellent clinical performance in the non-invasive detection of fetal T21. However, the disease-specific epigenetic characteristics of the EPs have not been established. Therefore, we validated the disease-specific epigenetic characteristics of these EPs for use in non-invasive detection of fetal T21.
We performed a high-resolution tiling array analysis of human chromosome 21 using a methyl-CpG binding domain-based protein (MBD) method with whole blood samples from non-pregnant normal women, whole blood samples from pregnant normal women, placenta samples of normal fetuses, and placenta samples of T21 fetuses. Tiling array results were validated by bisulfite direct sequencing and qPCR.
Among 12 EPs, only four EPs were confirmed to be hypermethylated in normal placenta and hypomethylated in blood. One of these four showed a severe discrepancy in the methylation patterns of T21 placenta samples, and another was located within a region of copy number variations. Thus, two EPs were confirmed to be potential fetal-specific markers based on their disease-specific epigenetic characteristics. The array results of these EPs were consisted with the results obtained by bisulfite direct sequencing and qPCR. Moreover, the two EPs were detected in maternal plasma.
We validated that two EPs have the potential to be fetal-specific EPs which is consistent with their disease-specific epigenetic characteristics. The findings of this study suggest that disease-specific epigenetic characteristics should be considered in the development of fetal-specific EPs for non-invasive prenatal testing of T21.
PMCID: PMC3892082  PMID: 24397966
Trisomy 21; Non-invasive prenatal testing; Epigenetic markers

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