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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  PMID: 25678801
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.  Concise Review: Stem Cell Microenvironment on a Chip: Current Technologies for Tissue Engineering and Stem Cell Biology 
Stem Cells Translational Medicine  2015;4(11):1352-1368.
Stem cells are highly sensitive to a variety of physicochemical cues, and their fate can be easily altered by a slight change of environment. This review introduces diverse microplatforms to provide in vitro stem cell niches. Microplatforms could control microenvironments around cells and have recently attracted much attention in biology including stem cell research. These microplatforms and the future directions of stem cell microenvironment are described.
Stem cells have huge potential in many therapeutic areas. With conventional cell culture methods, however, it is difficult to achieve in vivo-like microenvironments in which a number of well-controlled stimuli are provided for growing highly sensitive stem cells. In contrast, microtechnology-based platforms offer advantages of high precision, controllability, scalability, and reproducibility, enabling imitation of the complex physiological context of in vivo. This capability may fill the gap between the present knowledge about stem cells and that required for clinical stem cell-based therapies. We reviewed the various types of microplatforms on which stem cell microenvironments are mimicked. We have assigned the various microplatforms to four categories based on their practical uses to assist stem cell biologists in using them for research. In particular, many examples are given of microplatforms used for the production of embryoid bodies and aggregates of stem cells in vitro. We also categorized microplatforms based on the types of factors controlling the behaviors of stem cells. Finally, we outline possible future directions for microplatform-based stem cell research, such as research leading to the production of well-defined environments for stem cells to be used in scaled-up systems or organs-on-a-chip, the regulation of induced pluripotent stem cells, and the study of the genetic states of stem cells on microplatforms.
Stem cells are highly sensitive to a variety of physicochemical cues, and their fate can be easily altered by a slight change of environment; therefore, systematic analysis and discrimination of the extracellular signals and intracellular pathways controlling the fate of cells and experimental realization of sensitive and controllable niche environments are critical. This review introduces diverse microplatforms to provide in vitro stem cell niches. Microplatforms could control microenvironments around cells and have recently attracted much attention in biology including stem cell research. These microplatforms and the future directions of stem cell microenvironment are described.
PMCID: PMC4622410  PMID: 26450425
Stem cell microenvironment; Microplatform; Embryoid body; Stem cell behaviors; Stem cell fate; Organ regeneration
4.  Anticancer activity of TTAC-0001, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR-2/KDR) monoclonal antibody, is associated with inhibition of tumor angiogenesis 
mAbs  2015;7(6):1195-1204.
Vascular endothelial growth factor (VEGF) and its receptors are considered the primary cause of tumor-induced angiogenesis. Specifically, VEGFR-2/kinase insert domain receptor (KDR) is part of the major signaling pathway that plays a significant role in tumor angiogenesis, which is associated with the development of various types of tumor and metastasis. In particular, KDR is involved in tumor angiogenesis as well as cancer cell growth and survival. In this study, we evaluated the therapeutic potential of TTAC-0001, a fully human antibody against VEGFR-2/KDR. To assess the efficacy of the antibody and pharmacokinetic (PK) relationship in vivo, we tested the potency of TTAC-0001 in glioblastoma and colorectal cancer xenograft models. Antitumor activity of TTAC-0001 in preclinical models correlated with tumor growth arrest, induction of tumor cell apoptosis, and inhibition of angiogenesis. We also evaluated the combination effect of TTAC-0001 with a chemotherapeutic agent in xenograft models. We were able to determine the relationship between PK and the efficacy of TTAC-0001 through in vivo single-dose PK study. Taken together, our data suggest that targeting VEGFR-2 with TTAC-0001 could be a promising approach for cancer treatment.
PMCID: PMC4966428  PMID: 26325365
TTAC-0001; VEGF signaling; fully human neutralizing antibody, angiogenesis inhibitor; tumor growth inhibition; pharmacokinetics; glioblastoma; colorectal cancer
5.  Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis 
BioMed Research International  2015;2015:789298.
Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n = 19] and septic shock [n = 98]) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p = 0.043, p = 0.020, p = 0.005, and p = 0.015, resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p = 0.018 and p = 0.008, resp.). Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.
PMCID: PMC4553311  PMID: 26351639
6.  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
7.  New Empirical Equation for the Atomic Form Factor Function in the Momentum Transfer Range, q = 0–50 Å−1 for the Elements in the Range 1≤ Z ≤30 
PLoS ONE  2013;8(8):e69608.
The importance of Atomic Form Factors (f) is well-known to the scientific community. Tabulated values for f are mostly used in calculating cross-sections and Monte Carlo sampling for the coherent scattering of photons. The uses of these values are subjected to different approximations and interpolation techniques because the available data points for f in the literature for specified momentum-transfer-grids are very limited. In order to make it easier to accurately use the tabulated data, a mathematical expression for f functions would be a great achievement. Therefore, the current study was designed to suggest an empirical expression for the f functions. In the results, an empirical equation for Hubbell's tabulated data for f is created in the momentum transfer range, q = 0–50 Å−1 for the elements in the range 1≤ Z ≤30. The number of applied parameters was seven. The fitting to f showed that the maximum deviation was within 3%, 4% and 5% for the element having, Z = 1–11, Z = 12–22 and Z = 23–30, respectively, while the average deviations were within 0.3–2.25% for all elements (i.e., Z = 1–30). The values generated by the analytical equation were used in the Monte Carlo code instead of Hubbell’s tabulated values. The statistical noise in the Probability Distribution Functions of coherently scattered photons was efficiently removed. Furthermore, it also reduced the dependence on different interpolation techniques and approximations, and on the use of large tabulated data for f with the specified elements.
PMCID: PMC3731328  PMID: 23936339
8.  Biophysical evaluation of aminoclay as an effective protectant for protein stabilization during freeze-drying and storage 
This study aimed to evaluate aminoclay (3-aminopropyl-functionalized magnesium phyllosilicate) as an effective protectant for the stabilization of protein formulation in freeze-drying. Bovine serum albumin (BSA), as a model protein, was freeze-dried with aminoclay at various concentrations, and the effects of aminoclay on the structural stability of proteins were compared with those of the conventional stabilizers. The structural characteristics of the protein were determined by size exclusion chromatography (SEC), circular dichroism (CD), and Fourier transform infrared (FTIR) spectroscopy. Furthermore, physicochemical and morphological characteristics were examined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). XRPD and DSC patterns indicated that the glass transition temperature (Tg) of the amorphous formulation of aminoclay mixed with proteins was gradually elevated as the concentration of aminoclay increased. FTIR and CD spectral analysis suggested that the protein structure was well maintained with aminoclay during the freeze-drying process and 3 months of storage at 4°C and 40°C. Furthermore, aminoclay conferred the greatest protection against aggregation and retained the monomer content of BSA even at a high temperature. The morphological characteristics of lyophilized proteins were also well conserved during the storage with aminoclay. These results suggested that aminoclay may be useful as an alternative stabilizer for maintaining the structural stability of protein formulations.
PMCID: PMC5161340  PMID: 28003745
aminoclay; cryoprotectant; lyoprotectant; freeze-drying; protein; stability
9.  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
10.  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
11.  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
12.  Interoperation of an UHF RFID Reader and a TCP/IP Device via Wired and Wireless Links 
Sensors (Basel, Switzerland)  2011;11(11):10664-10674.
A main application in radio frequency identification (RFID) sensor networks is the function that processes real-time tag information after gathering the required data from multiple RFID tags. The component technologies that contain an RFID reader, called the interrogator, which has a tag chip, processors, coupling antenna, and a power management system have advanced significantly over the last decade. This paper presents a system implementation for interoperation between an UHF RFID reader and a TCP/IP device that is used as a gateway. The proposed system consists of an UHF RFID tag, an UHF RFID reader, an RF end-device, an RF coordinator, and a TCP/IP I/F. The UHF RFID reader, operating at 915 MHz, is compatible with EPC Class-0/Gen1, Class-1/Gen1 and 2, and ISO18000-6B. In particular, the UHF RFID reader can be combined with the RF end-device/coordinator for a ZigBee (IEEE 802.15.4) interface, which is a low-power wireless standard. The TCP/IP device communicates with the RFID reader via wired links. On the other hand, it is connected to the ZigBee end-device via wireless links. The web based test results show that the developed system can remotely recognize information of multiple tags through the interoperation between the RFID reader and the TCP/IP device.
PMCID: PMC3274307  PMID: 22346665
UHF RFID; RFID reader; RFID tag; RF coordinator; ZigBee; interrogator; TCP/IP; UHF antenna
13.  Coronary Calcification Is Reversely Related with Bone and Hair Calcium: The Relationship among Different Calcium Pools in Body 
Journal of Bone Metabolism  2016;23(4):191-197.
With aging, calcium efflux from bone is increased with age-related bone loss, and it can reduce bone mineral density (BMD). On the contrary, age-related calcium adoption into arterial wall progressively stiffens blood vessels. Theses process insinuates shift of calcium among different pools in body. However, their relationships have not been elucidated yet. So we investigated the correlation among calcium contents in different body pools, such as hair, bone, and blood vessels in women.
We analyzed 50 females retrospectively who measured Agatston coronary artery calcium score (CACS), BMD, and hair calcium concentration at a regular health check-up in a university hospital. CACS was achieved by coronary multidetector computed tomography, BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femur, and hair calcium level was checked by hair tissue mineral analysis.
CACS inversely correlated with BMD (r=-0.280, P=0.049 with lumbar vertebrae 1-4, r=-0.310, P=0.028 with femur neck, r=-0.333, P=0.018 with femur total) and hair calcium concentration (r=-0.352, P=0.012).
CACS has negative correlation with BMD and hair calcium level in women. Different body calcium pools such as bone, hair and blood vessel significantly correlated each other.
PMCID: PMC5153375  PMID: 27965940
Bone density; Calcium; Hair; Homeostasis; Minerals; Vascular calcification
14.  Clinical Outcomes of Vasospastic Angina Patients Presenting With Acute Coronary Syndrome 
Coronary vasospasm is an important pathogenesis of acute coronary syndrome (ACS). However, the clinical features and prognosis of vasospastic angina (VA) patients presenting with ACS (VAACS) are still unclear. We aimed to evaluate the clinical characteristics and long‐term outcomes of VAACS patients without significant coronary artery stenosis.
Methods and Results
A total of 986 VA patients confirmed by ergonovine provocation test were analyzed. VAACS was defined as VA patients visiting the emergency room with documented electrocardiographic changes, significant arrhythmias, or elevated cardiac biomarkers. VA patients with elevated cardiac biomarkers were further considered to have myocardial infarction (MI; VAMI). During 4.4 years of median follow‐up, we investigated major adverse cardiac events including cardiac death, MI, revascularization, and rehospitalization because of recurrent angina. The VAACS group consisted of 149 patients (15.1%), and VAMI occurred in 81 patients (8.2%). VAACS patients were younger and had a higher prevalence of diabetes mellitus, MI history, and higher levels of inflammatory markers compared with non‐VAACS patients. In multivariable Cox regression analyses, VAACS patients were associated with an increased risk of major adverse cardiac events (hazard ratio, 1.65; 95% CI 1.14–2.37; P=0.007) and recurrent MI hazard ratio, 2.57; 95% CI, 1.35–4.87; P=0.004). In addition, VAMI patients had an increased risk of major adverse cardiac events (hazard ratio, 1.75; 95% CI, 1.11–2.76; P=0.016) and recurrent MI (hazard ratio, 2.43; 95% CI, 1.09–5.40; P=0.03).
VAACS patients showed worse clinical outcomes, driven mainly by recurrent MI. Therefore, intensive medical treatment might be required in VAACS patients.
PMCID: PMC5210370  PMID: 27852592
acute coronary syndrome; myocardial infarction; variant angina; vasospasm; Coronary Artery Disease
15.  Effects of Morphological Characteristics of Muscle Fibers on Porcine Growth Performance and Pork Quality 
The aim of this study was to investigate the effects of morphological characteristics of porcine muscle fibers on growth performance, muscle fiber characteristics, and pork quality taken from the longissimus dorsi muscle. A total of 239 crossbred pigs (164 castrated males and 75 females) were used in this study. Experimental pigs were categorized by the total number of muscle fiber (TNF: High and Low) and cross sectional area of muscle fiber (CSAF: Large, Middle, and Small). Their combinations were classified into six groups (High-Large, HL; High-Middle, HM; High-Small, HS; Low-Large, LL; Low-Middle, LM; Low-Small, LS). The TNF and CSAF were significantly (p<0.05) correlated with growth rate and carcass productivity, while the only of the type I number had no meaningful relationships excluding the correlation with loin area (p<0.001). The proportion of type I area was positively correlated with pH45 min while the proportion of type IIB area was negatively correlated with pH45 min and pH24 h (p<0.05). Drip loss and protein denaturation had strong relationships with the proportion of type IIB number or area. The HL group exhibited the greatest growth performance. In addition, the HL group had significantly greater values in protein solubility than the other groups. In conclusion, this study suggest that high TNF combined to large CSAF improve the ultimate lean meat productivity and assure normal meat quality simultaneously with increased both proportion of number and area of type I, type IIA muscle fibers and lowered proportion of number and area of type IIB.
PMCID: PMC5112420  PMID: 27857533
muscle fiber morphology; total number of muscle fiber; cross sectional area of muscle fiber; growth performance; pork quality
16.  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
17.  Predicting survival of patients with idiopathic pulmonary fibrosis using GAP score: a nationwide cohort study 
Respiratory Research  2016;17:131.
The clinical course of idiopathic pulmonary fibrosis (IPF) varies widely. Although the GAP model is useful for predicting mortality, survivals have not yet been validated for each GAP score. We aimed to elucidate how prognosis is related to GAP score and GAP stage in IPF patients.
The Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate various characteristics in IPF patients from 2003 to 2007. Patients were diagnosed according to the 2002 criteria of the ATS/ERS. We enrolled 1,685 patients with IPF; 1,262 had undergone DLCO measurement. Patients were stratified based on GAP score (0–7): GAP score Group 0 (n = 26), Group 1 (n = 150), Group 2 (n = 208), Group 3 (n = 376), Group 4 (n = 317), Group 5 (n = 138), Group 6 (n = 39), and Group 7 (n = 8).
Higher GAP score and GAP stage were associated with a poorer prognosis (p < 0.001, respectively). Survival time in Group 3 was lower than those in Groups 1 and 2 (p = 0.043 and p = 0.039, respectively), and higher than those in groups 4, 5, and 6 (p = 0.043, p = 0.032, and p = 0.003, respectively). Gender, age, and DLCO (%) differed significantly between Groups 2 and 3. All four variables in the GAP model differed significantly between Groups 3 and 4.
The GAP system showed significant predictive ability for mortality in IPF patients. However, prognosis in IPF patients with a GAP score of 3 were significantly different from those in the other stage I groups and stage II groups of Asian patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12931-016-0454-0) contains supplementary material, which is available to authorized users.
PMCID: PMC5069824  PMID: 27756398
Idiopathic pulmonary fibrosis; GAP stage; Prognosis
18.  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
19.  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
20.  Electroceuticals: Mapping of Small Nerve Trunks and Branches Using Adaptive Flexible Electrodes (Adv. Sci. 9/2016) 
Advanced Science  2016;3(9):n/a.
There has been a lot of recent interest in using electrical impulses to interface with the nervous system to regulate organ functions in the body. In article 1500386, Shih‐Cheng Yen, Chengkuo Lee, and co‐workers demonstrate the ability to selectively stimulate the nerve trunk and, for the first time, record simultaneously the effect on different nerve branches with a range of very small diameters from 200 to 500 μm. This allows the nerve trunk to be mapped with high precision, potentially greatly increasing the efficacy of the stimulation and reducing the incidence of unintended side effects.
PMCID: PMC5039972
electroceuticals; flexible electronics; nerve mapping; peripheral neural interface; small diameter nerves
21.  DAMGO modulates two-pore domain K+ channels in the substantia gelatinosa neurons of rat spinal cord 
The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying K+ current. In this study, we examined whether a µ-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain K+ channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region. DAMGO caused a robust hyperpolarization and outward current in the SG neurons, which developed almost instantaneously and did not show any time-dependent inactivation. Half of the SG neurons exhibited a linear I~V relationship of the DAMGO-induced current, whereas rest of the neurons displayed inward rectification. In SG neurons with a linear I~V relationship of DAMGO-induced current, the reversal potential was close to the K+ equilibrium potentials. The mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying K+ channel) related acid-sensitive K+ channel (TASK) 1 and 3 was found in the SG region and a low pH (6.4) significantly blocked the DAMGO-induced K+ current. Taken together, the DAMGO-induced hyperpolarization at resting membrane potential and subsequent decrease in excitability of SG neurons can be carried by the two-pore domain K+ channel (TASK1 and 3) in addition to inwardly rectifying K+ channel.
PMCID: PMC5014999  PMID: 27610039
DAMGO; K+ current; Opioid; SG neuron; TASK
22.  Relationship between pulmonary function and bone mineral density in the Korean National Health and Nutrition Examination Survey 
Osteoporosis is common in chronic obstructive pulmonary disease (COPD) patients. The relationship between osteoporosis and COPD has been primarily reported in patients with moderate to severe COPD, but there is no report in the general population. The aim of this study is to investigate the relationship between bone mineral density (BMD) and lung function in the general Korean population.
This study was based on data acquired from the Fourth and Fifth Korea National Health and Nutrition Examination Surveys (KNHANES IV and V), conducted from 2008 to 2010. The study population included 4,501 subjects (aged ≥ 50 years) who underwent both spirometry and BMD. The study populations were divided into two groups by sex to correct for the effects of gender on BMD. All female participants were postmenopausal women.
The BMD values of the femur neck, total femur, and L-spine tended to decrease with degree of airflow limitation in both genders. To correct confounding factors, data were analyzed and adjusted for age, body mass index, fat free mass index, body fat percentage, smoking amount, parathyroid hormone levels, daily calcium and phosphorus intake, and alkaline phosphatase (ALP) levels. While the BMD of the femur neck, total femur, and L-spine was reduced significantly as age and ALP increased, the correlation between airway obstruction and BMD of all regions disappeared in both genders.
In the general population aged 50 years and older, diminution of BMD is not associated with airway obstruction. Further investigation along other factors is needed to determine the possible role of pulmonary function and BMD.
PMCID: PMC5016283  PMID: 27604798
Respiratory function tests; Bone density; Osteoporosis
23.  D-Dimer Levels Predict Myocardial Injury in ST-Segment Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study 
PLoS ONE  2016;11(8):e0160955.
Elevated D-dimer levels on admission predict prognosis in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), but the association of D-dimer levels with structural markers of myocardial injury in these patients is unknown.
We performed cardiac magnetic resonance (CMR) imaging in 208 patients treated with primary PCI for STEMI. CMR was performed a median of 3 days after the index procedure. Of the 208 patients studied, 75 patients had D-dimer levels above the normal range on admission (>0.5 μg/mL; high D-dimer group) while 133 had normal levels (≤0.5 μg/mL; low D-dimer group). The primary outcome was myocardial infarct size assessed by CMR. Secondary outcomes included area at risk (AAR), microvascular obstruction (MVO) area, and myocardial salvage index (MSI).
In CMR analysis, myocardial infarct size was larger in the high D-dimer group than in the low D-dimer group (22.3% [16.2–30.5] versus 18.8% [10.7–26.7]; p = 0.02). Compared to the low D-dimer group, the high D-dimer group also had a larger AAR (38.1% [31.7–46.9] versus 35.8% [24.2–45.3]; p = 0.04) and a smaller MSI (37.7 [28.2–46.9] versus 47.1 [33.2–57.0]; p = 0.01). In multivariate analysis, high D-dimer levels were significantly associated with larger myocardial infarct (OR 2.59; 95% CI 1.37–4.87; p<0.01) and lower MSI (OR 2.62; 95% CI 1.44–4.78; p<0.01).
In STEMI patients undergoing primary PCI, high D-dimer levels on admission were associated with a larger myocardial infarct size, a greater extent of AAR, and lower MSI, as assessed by CMR data. Elevated initial D-dimer level may be a marker of advanced myocardial injury in patients treated with primary PCI for STEMI.
PMCID: PMC4981325  PMID: 27513758
24.  Gene expression profile comparison in the penile tissue of diabetes and cavernous nerve injury-induced erectile dysfunction rat model 
To investigate the effects of cavernous nerve injury (CNI) on gene expression profiles in the cavernosal tissue of a CNI-induced erectile dysfunction (ED) model and to provide a basis for future investigations to discover potential target genes for ED treatment.
Materials and Methods
Young adult rats were divided randomly into 2 groups: sham operation and bilateral CN resection. At 12 weeks after CNI we measured erectile responses and performed microarray experiments and gene set enrichment analysis to reveal gene signatures that were enriched in the CNI-induced ED model. Alterations in gene signatures were compared with those in the diabetes-induced ED model. The diabetic-induced ED data is taken from GSE2457.
The mean ratio of intracavernosal pressure/blood pressure for the CNI group (0.54±0.4 cmH2O) was significantly lower than that in the sham operation group (0.73±0.8 cmH2O, p<0.05). Supervised and unsupervised clustering analysis showed that the diabetes- and CNI-induced ED cavernous tissues had different gene expression profiles from normal cavernous tissues. We identified 46 genes that were upregulated and 77 genes that were downregulated in both the CNI- and diabetes-induced ED models.
Our genome-wide and computational studies provide the groundwork for understanding complex mechanisms and molecular signature changes in ED.
PMCID: PMC4949699  PMID: 27437539
Erectile dysfunction; Gene expression; Microarray analysis; Peripheral nerve injuries
25.  First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry 
PLoS ONE  2016;11(6):e0157549.
Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES) versus first-generation DES in patients with coronary chronic total occlusion (CTO) who undergo percutaneous coronary intervention (PCI). The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO.
Methods and Results
Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557) or second-generation DES (n = 449) were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72) or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99). After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86) and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71) were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE.
This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.
PMCID: PMC4912116  PMID: 27314589

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