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1.  Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma 
OncoTargets and therapy  2015;8:347-356.
Liver stiffness (LS) measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC). We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA).
This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence.
This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months), 47 (42.3%) patients experienced HCC de novo recurrence, and 18 (16.2%) died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P<0.05). On multivariate analysis, together with previous anti-HCC treatment history, patients with LS values >13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR) of 3.115 (95% confidence interval [CI], 1.238–7.842, P<0.05). Moreover, LS values independently predicted the mortality after RFA, with a HR of 9.834 (95% CI, 1.148–84.211, P<0.05), together with total bilirubin.
Our data suggest that LS measurement is a useful predictor of HCC de novo recurrence and overall survival after RFA.
PMCID: PMC4322870
hepatocellular carcinoma; radiofrequency ablation; recurrence; liver stiffness; fibroscan
2.  Factors Affecting the Accuracy of Controlled Attenuation Parameter (CAP) in Assessing Hepatic Steatosis in Patients with Chronic Liver Disease 
PLoS ONE  2014;9(6):e98689.
Background & Aims
Controlled attenuation parameter (CAP) can measure hepatic steatosis. However, factors affecting its accuracy have not been described yet. This study investigated predictors of discordance between liver biopsy (LB) and CAP.
A total of 161 consecutive patients with chronic liver disease who underwent LB and CAP were enrolled prospectively. Histological steatosis was graded as S0 (<5%), S1 (5–33%), S2 (34–66%), and S3 (>66% of hepatocytes). Cutoff CAP values were calculated from our cohort (250, 301, and 325 dB/m for ≥S1, ≥S2, and S3). Discordance was defined as a discrepancy of at least two steatosis stages between LB and CAP.
The median age (102 males and 59 females) was 49 years. Repartition of histological steatosis was as follows; S0 26.1% (n = 42), S1 49.7% (n = 80), S2 20.5% (n = 33), and S3 3.7% (n = 6). In multivariate linear regression analysis, CAP value was independently associated with steatosis grade along with body mass index (BMI) and interquartile range/median of CAP value (IQR/MCAP) (all P<0.05). Discordance was identified in 13 (8.1%) patients. In multivariate analysis, histological S3 (odd ratio [OR], 9.573; 95% confidence interval [CI], 1.207–75.931; P = 0.033) and CAP value (OR, 1.020; 95% CI, 1.006–1.034; P = 0.006) were significantly associated with discordance, when adjusting for BMI, IQR/MCAP, and necroinflammation, reflected by histological activity or ALT level.
Patients with high grade steatosis or high CAP values have a higher risk of discordance between LB and CAP. Further studies are needed to improve the accuracy of CAP interpretation, especially in patients with higher CAP values.
PMCID: PMC4046989  PMID: 24901649
3.  Box-Shape Cervical Expansive Laminoplasty: Clinical and Radiological Outcomes 
Korean Journal of Spine  2014;11(3):152-156.
Box-shape cervical expansive laminoplasty is a procedure that utilizes a Miniplate® or Maxpacer® to achieve maximal canal expansion. This method is expected to show much larger canal expansion and good clinical outcome. So we investigated the clinical and radiological outcome of Box-shape cervical expansive laminoplasty.
Between June 2008 and July 2013, we performed cervical expansive laminoplasty in 87 and 48 patients using the Box-shape cervical expansive laminoplasty, respectively. We analyzed the clinical results of these operations using the Japanese Orthopedic Association (JOA) scoring system and by assessing the position of intralaminar screws with postoperative computed tomography (CT) at POD-6 months.
A total of 48 patients with ossification of the posterior longitudinal ligament (OPLL) (36 pts), cervical spondylotic myelopathy (CSM) (12 pts) were enrolled. Overall JOA scores improved from 11.49 to 14.22 at POD-6 months (OPLL: 11.32 -->14.3; CSM: 12-->14). Postoperative CT scans were performed in 39 patients at 177 levels for a total of 354 screws. The malpositioning rate of intralaminar screws was 3.4% and hardware-related neurologic complications did not occur.
Box-shape cervical expansive laminoplasty creates maximal spinal canal expansion and leads to improved cervical myelopathy. The use of intralaminar screws to fix the remodeled lamina-facet does not represent a significant difficulty.
PMCID: PMC4206966  PMID: 25346761
Open door laminoplasty; Double door laminoplasty; Intralaminar screw; Spinal canal area; Box-shape laminoplasty
4.  Therapeutic Effects of Acupuncture through Enhancement of Functional Angiogenesis and Granulogenesis in Rat Wound Healing 
Acupuncture regulates inflammation process and growth factors by increasing blood circulation in affected areas. In this study, we examined whether acupuncture has an effect on wound healing in injured rat. Rats were assigned randomly into two groups: control group and acupuncture group. Acupuncture treatment was carried out at 8 sites around the wounded area. We analyzed the wound area, inflammatory cytokines, proliferation of resident cells, and angiogenesis and induction of extracelluar matrix remodeling. At 7 days after-wounding the wound size in acupuncture-treat group was decreased more significantly compared to control group. In addition, the protein levels of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly decreased compared to the control at 2 and 7 days post-wounding. Also, we analyzed newly generated cells by performing immunostaining for PCNA and using several phenotype markers such as CD-31, α-SMA, and collagen type I. In acupuncture-treated group, PCNA-positive cell was increased and PCNA labeled CD-31-positive vessels, α-SMA- and collagen type I-positive fibroblastic cells, were increased compared to the control group at 7 days post-wounding. These results suggest that acupuncture may improve wound healing through decreasing pro-inflammatory response, increasing cell proliferation and angiogenesis, and inducing extracellular matrix remodeling.
PMCID: PMC3529882  PMID: 23304201
5.  Assessment of Collagen-Induced Arthritis Using Cyanine 5.5 Conjugated with Hydrophobically Modified Glycol Chitosan Nanoparticles: Correlation with 18F-Fluorodeoxyglucose Positron Emission Tomography Data 
Korean Journal of Radiology  2012;13(4):450-457.
To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging of collagen-induced arthritis (CIA).
Materials and Methods
We used 10 CIA and 3 normal mice. Nine days after the injecting collagen twice, microPET imaging was performed 40 minutes after the intravenous injection of 9.3 MBq 18F-FDG in 200 µL PBS. One day later, NIRF imaging was performed two hours after the intravenous injection of HGC-cy5.5 (5 mg/kg). We assessed the correlation between these two modalities in the knees and ankles of CIA mice.
The mean standardized uptake values of 18F-FDG for knees and ankles were 1.68 ± 0.76 and 0.79 ± 0.71, respectively, for CIA mice; and 0.57 ± 0.17 and 0.54 ± 0.20 respectively for control mice. From the NIRF images, the total photon counts per 30 mm2 for knees and ankles were 2.32 ± 1.54 × 105 and 2.75 ± 1.51 × 105, respectively, for CIA mice, and 1.22 ± 0.27 × 105 and 0.88 ± 0.24 × 105, respectively, for control mice. These two modalities showed a moderate correlation for knees (r = 0.604, p = 0.005) and ankles (r = 0.464, p = 0.039). Moreover, both HGC-Cy5.5 (p = 0.002) and 18F-FDG-PET (p = 0.005) imaging also showed statistically significant differences between CIA and normal mice.
NIRF imaging using HGC-Cy5.5 was moderately correlated with 18F-FDG-PET imaging in the CIA model. As such, HGC-Cy5.5 imaging can be used for the early detection of rheumatoid arthritis.
PMCID: PMC3384827  PMID: 22778567
HGC-Cy5.5; 18F-FDG PET; Near-infrared fluorescence imaging; Rheumatoid arthritis
6.  Evaluation of the Chondromalacia Patella Using a Microscopy Coil: Comparison of the Two-Dimensional Fast Spin Echo Techniques and the Three-Dimensional Fast Field Echo Techniques 
Korean Journal of Radiology  2011;12(1):78-88.
We wanted to compare the two-dimensional (2D) fast spin echo (FSE) techniques and the three-dimensional (3D) fast field echo techniques for the evaluation of the chondromalacia patella using a microscopy coil.
Materials and Methods
Twenty five patients who underwent total knee arthroplasty were included in this study. Preoperative MRI evaluation of the patella was performed using a microscopy coil (47 mm). The proton density-weighted fast spin echo images (PD), the fat-suppressed PD images (FS-PD), the intermediate weighted-fat suppressed fast spin echo images (iw-FS-FSE), the 3D balanced-fast field echo images (B-FFE), the 3D water selective cartilage scan (WATS-c) and the 3D water selective fluid scan (WATS-f) were obtained on a 1.5T MRI scanner. The patellar cartilage was evaluated in nine areas: the superior, middle and the inferior portions that were subdivided into the medial, central and lateral facets in a total of 215 areas. Employing the Noyes grading system, the MRI grade 0-I, II and III lesions were compared using the gross and microscopic findings. The sensitivity, specificity and accuracy were evaluated for each sequence. The significance of the differences for the individual sequences was calculated using the McNemar test.
The gross and microscopic findings demonstrated 167 grade 0-I lesions, 40 grade II lesions and eight grade III lesions. Iw-FS-FSE had the highest accuracy (sensitivity/specificity/accuracy = 88%/98%/96%), followed by FS-PD (78%/98%/93%, respectively), PD (76%/98%/93%, respectively), B-FFE (71%/100%/93%, respectively), WATS-c (67%/100%/92%, respectively) and WATS-f (58%/99%/89%, respectively). There were statistically significant differences for the iw-FS-FSE and WATS-f and for the PD-FS and WATS-f (p < 0.01).
The iw-FS-FSE images obtained with a microscopy coil show best diagnostic performance among the 2D and 3D GRE images for evaluating the chondromalacia patella.
PMCID: PMC3017887  PMID: 21228943
Cartilage; Magnetic resonance (MR); Knee; Histopathologic correlation
7.  Carcinoma of the middle bile duct: Is bile duct segmental resection appropriate? 
AIM: To compare survival between bile duct segmental resection (BDSR) and pancreaticoduodenectomy (PD) for treating distal bile duct cancers.
METHODS: Retrospective analysis was conducted for 45 patients in a BDSR group and for 149 patients in a PD group.
RESULTS: The T-stage (P < 0.001), lymph node invasion (P = 0.010) and tumor differentiation (P = 0.005) were significant prognostic factors in the BDSR group. The 3- and 5-year overall survival rates for the BDSR group and PD group were 51.7% and 36.6%, respectively and 46.0% and 38.1%, respectively (P = 0.099). The BDSR group and PD group did not show any significant difference in survival when this was adjusted for the TNM stage. The 3- and 5-year survival rates were: stage Ia [BDSR (100.0% and 100.0%) vs PD (76.9% and 68.4%) (P = 0.226)]; stage Ib [BDSR (55.8% and 32.6%) vs PD (59.3% and 59.3%) (P = 0.942)]; stage IIb [BDSR (19.2% and 19.2%) vs PD (31.9% and 14.2%) (P = 0.669)].
CONCLUSION: BDSR can be justified as an alternative radical operation for patients with middle bile duct in selected patients with no adjacent organ invasion and resection margin is negative.
PMCID: PMC2795184  PMID: 20014461
Bile duct cancer; Segmental resection; Pancreaticoduodenectomy
8.  Evaluation of Tumor Angiogenesis with a Second-Generation US Contrast Medium in a Rat Breast Tumor Model 
Korean Journal of Radiology  2008;9(3):243-249.
Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent.
Materials and Methods
The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis.
The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).
Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.
PMCID: PMC2627259  PMID: 18525227
Breast neoplasms; Breast, US; Contrast media; Experimental study
9.  Spinal Epidural Abscess with Pyogenic Arthritis of Facet Joint Treated with Antibiotic-Bone Cement Beads - A Case Report - 
Asian Spine Journal  2007;1(1):61-64.
Most epidural abscesses are a secondary lesion of pyogenic spondylodiscitis. An epidural abscess associated with pyogenic arthritis of the facet joint is quite rare. To the best of our knowledge, there is no report of the use of antibiotic-cement beads in the surgical treatment of an epidural abscess. This paper reports a 63-year-old male who sustained a 1-week history of radiating pain to both lower extremities combined with lower back pain. MRI revealed space-occupying lesions, which were located in both sides of the anterior epidural space of L4, and CT scans showed irregular widening and bony erosion of the facet joints of L4-5. A staphylococcal infection was identified after a posterior decompression and an open drainage. Antibiotic- bone cement beads were used as a local controller of the infection and as a spacer or an indicator for the second operation. An intravenous injection of anti-staphylococcal antibiotics resolved the back pain and radicular pain and normalized the laboratory findings. We point out not only the association of an epidural abscess with facet joint infection, but also the possible indication of antibiotic-bone cement beads in the treatment of epidural abscesses.
PMCID: PMC2857502  PMID: 20411156
Epidural abscess; Facet joint infection; Lumbar spine; Antibiotic-bone cement bead
10.  Eugenol Inhibits the GABAA Current in Trigeminal Ganglion Neurons 
PLoS ONE  2015;10(1):e0117316.
Eugenol has sedative, antioxidant, anti-inflammatory, and analgesic effects, but also serves as an irritant through the regulation of a different set of ion channels. Activation of gamma aminobutyric acid (GABA) receptors on sensory neurons leads to the stabilization of neuronal excitability but contributes to formalin-induced inflammatory pain. In this study, we examined the effect of eugenol on the GABA-induced current in rat trigeminal ganglia (TG) neurons and in human embryonic kidney (HEK) 293 cells expressing the GABAA receptor α1β2γ2 subtype using the whole-cell patch clamp technique. RT-PCR and Western blot analysis were used to confirm the expression of GABAA receptor γ2 subunit mRNA and protein in the TG and hippocampus. Eugenol decreased the amplitude ratio of the GABA-induced current to 27.5 ± 3.2% (p < 0.05) in TG neurons, which recovered after a 3-min washout. In HEK 293 cells expressing the α1β2γ2 subtype, eugenol inhibited GABA-induced currents in a dose-dependent manner. Application of eugenol also decreased the GABA response in the presence of a G-protein blocker. Eugenol pretreatment with different concentrations of GABA resulted in similar inhibition of the GABA-induced current in a non-competitive manner. In conclusion, eugenol inhibits the GABA-induced current in TG neurons and HEK 293 cells expressing the GABAA receptor in a reversible, dose-dependent, and non-competitive manner, but not via the G-protein pathway. We suggest that the GABAA receptor could be a molecular target for eugenol in the modulation of nociceptive information.
PMCID: PMC4311912  PMID: 25635877
11.  Association of COL2A1 Gene Polymorphism with Degenerative Lumbar Scoliosis 
Clinics in Orthopedic Surgery  2014;6(4):379-384.
Degenerative lumbar scoliosis (DLS) progresses with aging after 50-60 years, and the genetic association of DLS remains largely unclear. In this study, the genetic association between collagen type II alpha 1 (COL2A1) gene and DLS was investigated.
COL2A1 gene polymorphism was investigated in DLS subjects compared to healthy controls to investigate the possibility of its association with COL2A1 gene. Based on a single nucleotide polymorphism (SNP) database, SNP (rs2276454) in COL2A1 were selected and genotyped using direct sequencing in 51 patients with DLS and 235 healthy controls. The SNP effects were analyzed using three models of codominant, dominant, and recessive. Logistic regression models were calculated for odds ratios (ORs) with 95% confidence intervals (CIs) and corresponding p-values, controlling age and gender as co-variables.
SNP (rs2276454) in COL2A1 was significantly associated with the degenerative lumbar scoliosis in the codominant (OR, 1.90; 95% CI, 1.17 to 3.10; p = 0.008) and dominant models (OR, 3.58; 95% CI, 1.59 to 9.29; p = 0.001).
The results suggest that COL2A1 is associated with the risk of DLS in Korean population.
PMCID: PMC4233215  PMID: 25436060
Degenerative lumbar scoliosis; Single nucleotide polymorphism; COL2A1; Korean
12.  SUMO Proteins are not Involved in TGF-β1-induced, Smad3/4-mediated Germline α Transcription, but PIASy Suppresses it in CH12F3-2A B Cells 
Immune Network  2014;14(6):321-327.
TGF-β induces IgA class switching by B cells. We previously reported that Smad3 and Smad4, pivotal TGF-β signal-transducing transcription factors, mediate germline (GL) α transcription induced by TGF-β1, resulting in IgA switching by mouse B cells. Post-translational sumoylation of Smad3 and Smad4 regulates TGF-β-induced transcriptional activation in certain cell types. In the present study, we investigated the effect of sumoylation on TGF-β1-induced, Smad3/4-mediated GLα transcription and IgA switching by mouse B cell line, CH12F3-2A. Overexpression of small ubiquitin-like modifier (SUMO)-1, SUMO-2 or SUMO-3 did not affect TGF-β1-induced, Smad3/4-mediated GLα promoter activity, expression of endogenous GLα transcripts, surface IgA expression, and IgA production. Next, we tested the effect of the E3 ligase PIASy on TGF-β1-induced, Smad3/4-mediated GLα promoter activity. We found that PIASy overexpression suppresses the GLα promoter activity in cooperation with histone deacetylase 1. Taken together, these results suggest that SUMO itself does not affect regulation of GLα transcription and IgA switching induced by TGF-β1/Smad3/4, while PIASy acts as a repressor.
PMCID: PMC4275389  PMID: 25550698
IgA; germline α transcripts; SUMO; PIASy; HDAC1
13.  Long-Term Outcomes of Complete Versus Incomplete Revascularization for Patients with Multivessel Coronary Artery Disease and Left Ventricular Systolic Dysfunction in Drug-Eluting Stent Era 
Journal of Korean Medical Science  2014;29(11):1501-1506.
We aimed to investigate that complete revascularization (CR) would be associated with a decreased mortality in patients with multivessel disease (MVD) and reduced left ventricular ejection fraction (LVEF). We enrolled a total of 263 patients with MVD and LVEF <50% who had undergone percutaneous coronary intervention with drug-eluting stent between March 2003 and December 2010. We compared major adverse cardiac and cerebrovascular accident (MACCE) including all-cause death, myocardial infarction, any revascularization, and cerebrovascular accident between CR and incomplete revascularization (IR). CR was achieved in 150 patients. During median follow-up of 40 months, MACCE occurred in 52 (34.7%) patients in the CR group versus 51 (45.1%) patients in the IR group (P=0.06). After a Cox regression model with inverse-probability-of-treatment-weighting using propensity score, the incidence of MACCE of the CR group were lower than those of the IR group (34.7% vs. 45.1%; adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44-0.95, P=0.03). The rate of all-cause death was significantly lower in patients with CR than in those with IR (adjusted HR, 0.48; 95% CI, 0.29-0.80, P<0.01). In conclusion, the achievement of CR with drug-eluting stent reduces long-term MACCE in patients with MVD and reduced LVEF.
Graphical Abstract
PMCID: PMC4234917  PMID: 25408581
Drug-Eluting Stents; Left Ventricular Systolic Dysfunction; Revascularization
14.  Self-adhesive epidermal carbon nanotube electronics for tether-free long-term continuous recording of biosignals 
Scientific Reports  2014;4:6074.
The long-term, continuous, inconspicuous, and noiseless monitoring of bioelectrical signals is critical to the early diagnosis of disease and monitoring health and wellbeing. However, it is a major challenge to record the bioelectrical signals of patients going about their daily lives because of the difficulties of integrating skin-like conducting materials, the measuring system, and medical technologies in a single platform. In this study, we developed a thin epidermis-like electronics that is capable of repeated self-adhesion onto skin, integration with commercial electronic components through soldering, and conformal contact without serious motion artifacts. Using well-mixed carbon nanotubes and adhesive polydimethylsiloxane, we fabricated an epidermal carbon nanotube electronics which maintains excellent conformal contact even within wrinkles in skin, and can be used to record electrocardiogram signals robustly. The electrode is biocompatible and can even be operated in water, which means patients can live normal lives despite wearing a complicated recording system.
PMCID: PMC4133715  PMID: 25123356
15.  Clinical Outcomes of Patients with Acute Myocardial Infarction Complicated by Severe Refractory Cardiogenic Shock Assisted with Percutaneous Cardiopulmonary Support 
Yonsei Medical Journal  2014;55(4):920-927.
Limited data are available on the role of percutaneous cardiopulmonary support (PCPS) for the treatment of acute myocardial infarction (AMI) patients with cardiogenic shock. We investigated the clinical outcomes and predictors of in-hospital mortality after PCPS in patients with AMI complicated by severe refractory cardiogenic shock.
Materials and Methods
From January 2004 to December 2011, we analyzed data from 96 consecutive AMI patients with cardiogenic shock assisted by a PCPS system. The primary outcome was in-hospital mortality. The predictors of in-hospital mortality were determined by a Cox proportional-hazards model.
In-hospital mortality occurred in 51 (53.1%) patients and 58 (60.4%) patients were able to be weaned from PCPS. Cardiopulmonary resuscitation (CPR) was performed in 61 (63.5%) patients before PCPS initiation. On multivariate analysis, age ≥67 years [adjusted hazard ratio (HR), 4.74; 95% confidence interval (CI), 2.27-9.93; p<0.001], CPR (adjusted HR, 2.32; 95% CI, 1.11-4.85; p=0.03), lactate clearance for 48 hours <70% (adjusted HR, 2.50; 95% CI, 1.04-6.05; p=0.041), and unsuccessful revascularization (adjusted HR, 3.57; 95% CI, 1.85-6.90; p=0.002) were independent predictors of in-hospital mortality after PCPS in patients with AMI complicated by cardiogenic shock.
In spite of PCPS management, AMI patients complicated by severe refractory cardiogenic shock demonstrated high mortality. Older age, CPR, lower lactate clearance for 48 hours, and unsuccessful revascularization were independent predictors of in-hospital mortality.
PMCID: PMC4075395  PMID: 24954319
Myocardial infarction; cardiogenic shock; percutaneous cardiopulmonary support
16.  Microfluidic Fabrication of Cell Adhesive Chitosan Microtubes 
Biomedical microdevices  2013;15(3):10.1007/s10544-013-9746-z.
Chitosan has been used as a scaffolding material in tissue engineering due to its mechanical properties and biocompatibility. With increased appreciation of the effect of micro- and nanoscale environments on cellular behavior, there is increased emphasis on generating microfabricated chitosan structures. Here we employed a microfluidic coaxial flow-focusing system to generate cell adhesive chitosan microtubes of controlled sizes by modifying the flow rates of a chitosan pre-polymer solution and phosphate buffered saline (PBS). The microtubes were extruded from a glass capillary with a 300 μm inner diameter. After ionic crosslinking with sodium tripolyphosphate (TPP), fabricated microtubes had inner and outer diameter ranges of 70-150 μm and 120-185 μm. Computational simulation validated the controlled size of microtubes and cell attachment. To enhance cell adhesiveness on the microtubes, we mixed gelatin with the chitosan pre-polymer solution and adjusted the pH values of the chitosan pre-polymer solution with gelatin and TPP. During the fabrication of microtubes, fibroblasts suspended in core PBS flow adhered to the inner surface of chitosan-gelatin microtubes. To achieve physiological pH values, we adjusted pH values of chiotsan pre-polymer solution and TPP. In particular, we were able to improve cell viability to 92% with pH values of 5.8 and 7.4 for chitosan and TPP solution respectively. Cell culturing for three days showed that the addition of the gelatin enhanced cell spreading and proliferation inside the chitosan-gelatin microtubes. The microfluidic fabrication method for ionically crosslinked chitosan microtubes at physiological pH can be compatible with a variety of cells and used as a versatile platform for microengineered tissue engineering.
PMCID: PMC3651799  PMID: 23355068
Chitosan-Gelatin Hydrogel; Microfluidic Flow-Focusing; Microtube; Cell Viability
17.  Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents 
Bioorganic & medicinal chemistry  2008;17(4):1764-1771.
Akt has emerged as a critical target for the development of anti-cancer therapies. It has been found to be amplified, overexpressed, or constitutively activated in numerous human malignancies with oncogenesis derived from the simultaneous promotion of cell survival and suppression of apoptosis. A valuable alternative to the more common ATP-mimetic based chemotherapies is a substrate-mimetic approach, which has the potential advantage of inherent specificity of the substrate-binding pocket. In this paper we present the development of high affinity non-peptidic, substrate-mimetic inhibitors based on the minimum GSK3β substrate sequence. Optimization of initial peptidic leads resulted in the development of several classes of small molecule inhibitors, which have comparable potency to the initial peptidomimetics, while eliminating the remaining amino acid residues. We have identified the first non-peptidic substrate-mimetic lead inhibitors of Akt 29a–b, which have affinities of 17 and 12 μM, respectively. This strategy has potential to provide a useful set of molecular probes to assist in the validation of Akt as a potential target for anti-cancer drug design.
PMCID: PMC4037933  PMID: 19179081
Akt; Protein kinase B; Substrate-mimetic; Cancer; Inhibitor
18.  A coronary heart disease prediction model: the Korean Heart Study 
BMJ Open  2014;4(5):e005025.
The objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score.
A prospective cohort study within a national insurance system.
18 health promotion centres nationwide between 1996 and 2001 in Korea.
268 315 Koreans between the ages of 30 and 74 years without CHD at baseline.
Outcome measure
Non-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI).
The optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3–6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort.
The present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individual's risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.
PMCID: PMC4039825  PMID: 24848088
19.  Shear Stress Induced by an Interstitial Level of Slow Flow Increases the Osteogenic Differentiation of Mesenchymal Stem Cells through TAZ Activation 
PLoS ONE  2014;9(3):e92427.
Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC) differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif), a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.
PMCID: PMC3962409  PMID: 24658423
20.  Changes in ginsenoside compositions and antioxidant activities of hydroponic-cultured ginseng roots and leaves with heating temperature 
Journal of Ginseng Research  2014;38(3):180-186.
This study evaluated changes in ginsenoside compositions and antioxidant activities in hydroponic-cultured ginseng roots (HGR) and leaves (HGL) with heating temperature.
Heat treatment was performed at temperatures of 90°C, 110°C, 130°C, and 150°C for 2 hours.
The ginsenoside content varied significantly with heating temperature. The levels of ginsenosides Rg1 and Re in HGR decreased with increasing heating temperature. Ginsenosides F2, F4, Rk3, Rh4, Rg3 (S form), Rg3 (R form), Rk1, and Rg5, which were absent in the raw ginseng, were formed after heat treatment. The levels of ginsenosides Rg1, Re, Rf, and Rb1 in HGL decreased with increasing heating temperature. Conversely, ginsenosides Rk3, Rh4, Rg3 (R form), Rk1, and Rg5 increased with increasing heating temperature. In addition, ginsenoside contents of heated HGL were slightly higher than those of HGR. The highest extraction yield was 14.39% at 130°C, whereas the lowest value was 10.30% at 150°C. After heating, polyphenol contents of HGR and HGL increased from 0.43 mg gallic acid equivalent/g (mg GAE eq/g) and 0.74 mg GAE eq/g to 6.16 mg GAE eq/g and 2.86 mg GAE eq/g, respectively.
Antioxidant activities of HGR and HGL, measured by 1,1-diphenyl-2-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging ability, increased with increasing heating temperature. These results may aid in improving the biological activity and quality of ginseng subjected to heat treatments.
PMCID: PMC4213819  PMID: 25378992
antioxidant activity; ginsenoside; heating temperature; hydroponic-cultured ginseng; polyphenol
21.  The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: implications for arthritic joints 
This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or 10 μg ml−1) or IL-1β (0.1 ng ml−1) in the presence or absence of hypoxia for 24 h. The protein expression patterns were examined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantly stimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production induced by adiponectin was significantly greater than that induced by IL-1β. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1β-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1β. In addition, IL-8 production in endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced by adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1β in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.
PMCID: PMC3909890  PMID: 24434628
adiponectin; cytokines and inflammatory mediators; endothelium; osteoblast; rheumatoid arthritis
22.  A Nation-Wide, Outpatient-Based Survey on the Pain, Disability, and Satisfaction of Patients with Osteoporotic Vertebral Compression Fractures 
Asian Spine Journal  2013;7(4):301-307.
Study Design
A nation-wide, outpatient-based, cross-sectional survey with the use of questionnaires.
To evaluate the pain, disability and satisfaction of patients with osteoporotic vertebral compression fractures (OVCFs).
Overview of Literature
There are no nation-wide data in Korea on the degree of pain, disability and satisfaction with treatment in patients with OVCFs.
We performed a cross-sectional survey of 573 patients with OVCFs. After excluding incomplete questionnaires (missing more than 30% of the variables), 430 patient-physician-matched data sets were collected for this survey.
Patients with OVCFs were managed with conservative treatment in 63% and with a vertebroplasty in 37%. The means of the latest visual analogue scale (VAS, 5.2) and Oswestry Disability Index (ODI, 47.7) scores checked at the time of survey were significantly higher than those VAS and ODI scores prior to OVCFs (the prefracture VAS and ODI scores, 3.6 and 26.3, respectively; p<0.001 for both comparisons). However, the means of the latest VAS and ODI scores were insignificantly different between the conservative and vertebroplasty groups, irrespective of the duration from the fractures. Overall, 75% of patients were satisfied with their clinical outcomes. However, the percentages of patient's satisfaction were not significantly different between the conservative and vertebroplasty groups. Eighty-eight percent of patients felt some or marked deterioration of their general health condition following OVCFs.
These results indicate that although most patients with OVCFs were satisfied with their clinical outcomes, their subjective general health conditions, as well as their pain and disability, did not recover to the prefracture state.
PMCID: PMC3863656  PMID: 24353847
Osteoporotic vertebral compression fracture; Pain; Disability; Satisfaction
23.  Alloplastic total temporomandibular joint replacement using stock prosthesis: a one-year follow-up report of two cases 
Alloplastic total replacement of the temporomandibular joint (TMJ) was developed in recent decades. In some conditions, previous studies suggested the rationale behind alloplastic TMJ replacement rather than reconstruction with autogenous grafts. Currently, three prosthetic products are available and approved by the US Food and Drug Administration. Among these products, customized prostheses are manufactured, via computer aided design/computer aided manufacturing (CAD/CAM) system for customized design; stock-type prostheses are provided in various sizes and shapes. In this report, two patients (a 50-year-old female who had undergone condylectomy for the treatment of osteochondroma extending to the cranial base on the left condyle, and a 21-year-old male diagnosed with left temporomandibular ankylosis) were treated using the alloplastic total replacement of TMJ using stock prosthesis. The follow-up results of a favorable one-year, short-term therapeutic outcome were obtained for the alloplastic total TMJ replacement using a stock-type prosthesis.
PMCID: PMC3912785  PMID: 24516821
Temporomandibular joint disorders; Replacement arthroplasty; Maxillofacial prosthesis; Temporomandibular ankylosis
24.  Verruciform xanthoma of the palatal gingiva: a report of two cases 
Verruciform xanthoma (VX) is a rare, benign lesion that presents in the oral cavity, skin, or genital organs as a verrucous, papillomatous, or flat papule with varying colors. VX has indistinct clinical features, making histopathological examination necessary for a definitive diagnosis. Histologically, VX is characterized by parakeratosis, rete ridges with uniform depth, and an accumulation of the foam cells, which are also known as the "xanthoma cells". These foam cells test positive for antibodies, such as CD-68 and vimentin; it is thought that VX foam cells are derived from the monocyte-macrophage lineage, and that VX's pathogenic mechanism is partly related to an immune mechanism. Nevertheless, the pathogenesis of VX remains unclear. VX can be treated by surgical excision; other medical, chemical, and radiological treatments are not required postoperatively. Recurrence and malignant transformation of VX are rare. Two patients, each with a mass of unknown origin on the palatal gingiva, were presented at our clinic. Excisional biopsies of the masses were performed for a histological diagnosis after clinical and radiological examinations. Histological examination confirmed a diagnosis of VX in both cases.
PMCID: PMC3912787  PMID: 24516820
Verruciform xanthoma; Mouth; Foam cells; Immune mechanism
25.  Current status of assisted reproductive technology in Korea, 2009 
Obstetrics & Gynecology Science  2013;56(6):353-361.
Great advances have been made in the field of assisted reproductive technology (ART) since the first in vitro fertilization (IVF) baby was born in Korea in the year of 1985. However, it deserve to say that the invaluable data from fertility centers may serve as a useful source to find out which factors affect successful IVF outcome and to offer applicable information to infertile patients and fertility clinics. This article intended to report the status of ART in 2009 Korean Society of Obstetrics and Gynecology surveyed. The current survey was performed to assess the status and success rate of ART performed in Korea, between January 1 and December 31, 2009. Reporting forms had been sent out to IVF centers via e-mail, and collected by e-mail as well in 2012. With International Committee Monitoring Assisted Reproductive Technologies recommendation, intracytoplasmic sperm injection (ICSI) and non-ICSI cases have been categorized and also IVF-ET cases involving frozen embryo replacement have been surveyed separately. Seventy-four centers have reported the treatment cycles initiated in the year of 2009, and had performed a total of 27,947 cycles of ART treatments. Among a total of 27,947 treatment cycles, IVF and ICSI cases added up to 22,049 (78.9%), with 45.3% IVF without ICSI and 54.7% IVF with ICSI, respectively. Among the IVF and ICSI patients, patients confirmed to have achieved clinical pregnancy was 28.8% per cycle with oocyte retrieval, and 30.9% per cycle with embryo transfer. The most common number of embryos transferred in 2009 is three embryos (40.4%), followed by 2 embryos (28.4%) and a single embryo transferred (13.6%). Among IVF and ICSI cycles that resulted in multiple live births, twin pregnancy rate was 45.3% and triple pregnancy rate was 1.1%. A total of 191 cases of oocyte donation had been performed to result in 25.0% of live birth rate. Meanwhile, a total of 5,619 cases of frozen embryo replacement had been performed with 33.7% of clinical pregnancy rate per cycle with embryo transfer. When comparing with international registry data, clinical pregnancy rate per transfer from fresh IVF cycles including ICSI (34.1%,) was comparable to clinical pregnancy rate per transfer in European Society for Human Reproduction and Embryology report was 32.5% though lower than 45.0% for USA data. There was no remarkable difference in status of assisted reproductive technology in Korea between the current report and the data reported in 2008. The age of women trying to get pregnant was reconfirmed to be the most important factor that may have impact on success of ART treatment.
PMCID: PMC3859020  PMID: 24396813
International Committee for Monitoring Assisted Reproductive Technologies; Korea; Reproductive techniques; Survey

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