Search

Laparoscopic living donor hepatectomy for transplantation has been well established over the past decade. This study aimed to assess its safety and feasibility in pediatric living donor liver transplantation (LDLT) by comparing the surgical and long-term survival outcomes on both the donor and recipient sides between open and laparoscopic groups. The medical records of 100 patients (≤17 years old) who underwent ABO-compatible LDLT using a left lateral liver graft between May 2008 and June 2016 were analyzed. A total of 31 donors who underwent pure laparoscopic hepatectomy and their corresponding recipients were included in the study; 69 patients who underwent open living donor hepatectomy during the same period were included as a comparison group. To overcome bias from the different distributions of covariables among the patients in the 2 study groups, a 1:1 propensity score matching analysis was performed. The mean follow-up periods were 92.9 and 92.7 months in the open and laparoscopic groups, respectively. The mean postoperative hospital stay of the donors was significantly shorter in the laparoscopic group (8.1 days) than in the open group (10.6 days; P < 0.001). Overall, the surgical complications in the donors and overall survival rate of recipients did not differ between the groups. Our data suggest that the laparoscopic environment was not associated with long-term graft survival during pediatric LDLT. In addition, the laparoscopic approach for the donors did not adversely affect the corresponding recipient's outcome. Laparoscopic left lateral sectionectomy for living donors is a safe, feasible, and reproducible procedure for pediatric liver transplantation., (Copyright © 2020 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. Due to its rarity and protean behavior, the optimal treatment of hepatic EHE has not yet been standardized. This single-center study describes outcomes in patients with hepatic EHE who underwent living donor liver transplantation (LDLT)., Methods: The medical records of patients who underwent LDLT for hepatic EHE from 2007 to 2016 were reviewed., Results: During 10-year period, four patients, one man and three women, of mean age 41.3±11.1 years, underwent LDLT for hepatic EHE. Based on imaging modalities, these patients were preoperatively diagnosed with EHE or hepatocellular carcinoma, with percutaneous liver biopsy confirming that all four had hepatic EHE. The tumors were multiple and scattered over entire liver, precluding liver resection. Blood tumor markers were not elevated, except that CA19-9 and des-γ-carboxy prothrombin was slightly elevated in one patient. Mean model for end-stage liver disease score was 10.8±5.7. All patients underwent LDLT using modified right liver grafts, with graft-recipient weight ratio of 1.11±0.19, and all recovered uneventfully after LDLT. One patient died due to tumor recurrence at 9 months, whereas the other three have done well without tumor recurrence, resulting in 5-year disease-free and overall patient survival rates of 75% each. The patient with tumor recurrence was classified as a high-risk patient based on the original and modified hepatic EHE-LT scoring systems., Conclusions: LDLT can be an effective treatment for patients with unresectable hepatic EHEs that are confined within the liver and absence of macrovascular invasion and lymph node metastasis., (Copyright © 2021 The Korean Society for Transplantation.)

High crystalline ZnO nanorods (NRs) on Zn pre-deposited graphene/Cu sheet without graphene transfer process have been fabricated by self-catalyzed vapor-phase transport synthesis. Here, the pre-deposited Zn metal on graphene not only serves as a seed to grow the ZnO NRs, but also passivates the graphene underneath. The temperature-dependent photoluminescence spectra of the fabricated ZnO NRs reveal a dominant peak of 3.88 eV at 10 K associated with the neutral-donor bound exciton, while the redshifted peak by bandgap shrinkage with temperature and electron-lattice interactions leads a strong emission at 382 nm at room temperature. The optical absorption of the ZnO NRs/graphene hetero-nanostructure at this ultraviolet (UV) emission is then theoretically analyzed to quantify the absorption amount depending on the ZnO NR distribution. By simply covering the ZnO NR/graphene/Cu structure with the graphene/glass as a top electrode, it is observed that the current-voltage characteristic of the ZnO NR/graphene hetero-nanojunction device exhibits a photocurrent of 1.03 mA at 3 V under a light illumination of 100 μW/cm 2 . In particular, the suggested graphene/ZnO NRs/graphene hybrid-nanostructure-based devices reveal comparable photocurrents at a bidirectional bias, which can be a promising platform to integrate 1D and 2D nanomaterials without complex patterning process for UV device applications.

According to recent international consensus conferences, pure laparoscopic donor hepatectomy (PLDH), particularly right and left hepatectomies, is not yet considered a standard practice because studies remain limited. Thus, we present the outcomes of more than 500 PLDH patients, mostly receiving a right hepatectomy. To our knowledge, this is the largest study to date on PLDH. Data from all living liver donors who underwent PLDH at 5 centers in Korea until June 2018 were retrospectively analyzed. The outcomes of both donors and recipients were included. Pearson correlation analysis was used to explore the relationship between the duration of surgery and cumulative experience at each center, which reflects the learning curve. Overall, 545 PLDH cases were analyzed, including 481 right hepatectomies, 25 left hepatectomies, and 39 left lateral sectionectomies (LLS). The open conversion was necessary for 10 (1.8%) donors, and none of the donors died or experienced irreversible disability. Notably, there were 25 (4.6%) patients with major complications (higher than Clavien-Dindo grade 3). All centers except one showed a significant decrease in surgery duration as the number of cases accumulated. Regarding recipient outcomes, there were 110 cases (20.2%) of early major complications and 177 cases (32.5%) of late major complications. This study shows the early and late postoperative outcomes of 545 donors and corresponding recipients, including 481 right hepatectomies and 25 left hepatectomies, from 5 experienced centers. Although the results are comparable to those of previously reported open donor hepatectomy series, further studies are needed to consider PLDH a new standard practice., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Background: More than 400 liver transplants were performed at Asan Medical Center (AMC) in 2011, and over 500 liver transplants including 420 living-donor liver transplants (LDLTs) were performed in 2019. Herein, we report the methodology of these procedures., Methods: Since the first adult LDLTs at AMC using the left and right lobes were successfully performed, various innovative techniques and approaches have been developed: modified right lobe, dual graft, donor exchange for ABO incompatibility, expansion of indications and no-touch techniques for hepatocellular carcinoma, intraoperative cine-portogram and additional intervention for large collaterals, management of portal vein thrombosis (PVT) and stenosis, salvage LDLT after major hepatectomy, and timely LDLT for patients with acute-on-chronic liver failure., Results: Four hundred twenty LDLTs in 403 adult and 17 pediatric patients and 85 deceased-donor liver transplants in 74 adult and 11 pediatric patients were performed. The number of deceased-donor liver transplants remained constant since 2011, but the number of LDLTs increased steadily. One hundred thirty patients (25.7%) required urgent liver transplantations and 24 patients with acute-on-chronic liver failure underwent LDLT. PVT including grade 1,2,3, and 4 was reported in 91 patients (18.0%), and Yerdel's grade 2, 3, and 4 PVT was reported in 47 patients (51.6%); all patients with PVT were successfully treated. Adult LDLTs for hepatocellular carcinoma and ABO incompatibility accounted for 52.6% and 24.3% of the cases, respectively. In-hospital mortality in 2019 was 2.97%., Conclusion: Continual efforts to overcome challenging problems in LDLT with various innovations and dedication of the team members during the perioperative period to improve patient outcomes were crucial in increasing the number of liver transplantations at Asan Medical Center., (Copyright © 2020. Published by Elsevier Inc.)

The fruit of Prunus mume (PM) is widely cultivated in East Asia, and it has been used as a folk medication for gastrointestinal disorders, e.g., diarrhea, stomach ache and ulceration. In this study, the pectinase-treated PM juice (PJ) was fermented with Lactobacillus strains containing fundamental organic acids and free amino acids. The PJ fermented with Lactobacillus plantarum and L. casei (FP) was investigated for its protective effect in dextran sodium sulfate (DSS)-induced colitis mice model. The administration of FP reduced lipid peroxidation and histopathological colitis symptoms, e.g., shortening of the colon length, depletion of mucin, epithelial injury and ulceration, in colonic tissues. The FP-supplemented group showed the alleviation of pro-inflammatory cytokines. Compared with the DSS control group, the supplementation of FP significantly reduced the levels of serum interferon-γ (IFN-γ), interleukin (IL)-1β, IL-6, IL-12 and IL-17 as well as colonic tumor necrosis factor-α, IFN-γ, IL-12 and IL-17. Furthermore, the DSS-induced TUNEL-positive area was significantly reduced by the FP supplementation. These results show that the supplementation of FP fermented with mixed lactic acid bacteria, L. plantarum and L. casei , elucidated the protective effect in DSS-induced colitis mice. Hence, this study suggests that FP can be utilized as a natural therapeutic agent for colitis and intestinal inflammation.

Isoquercitrin (IQ), a major flavonol present in Prunus mume fruit, has gained much attention in recent studies because of its superior bioavailability and physiological effects. In this study, the anti-cancer mechanism of IQ against human melanoma, particularly its effect on the mitochondria-mediated apoptosis, was investigated. Treatment with IQ at 25 μM concentration effectively inhibited the proliferation of SK-MEL-2 skin cancer cells while the same concentration did not exhibit cytotoxicity against human keratinocytes HaCaT. Morphological analysis and clonogenic assay also showed that IQ can alter the growth and long-term survival of SK-MEL-2 cells. IQ also induced apoptosis in the melanoma cells as manifested in the nuclear morphology changes, DNA fragmentation, increase in the apoptosis rate (17.69% at 25 μM) and accumulation of sub-G1 cell cycle phase population (19.55% at 25 μM). Western blot analysis revealed the involvement of the mitochondrial apoptosis signaling pathway in the anti-cancer property of IQ. Treatment with IQ resulted in the decrease in the levels of procaspase-8 and -9, and Bcl-2 protein, and an increase in the expression of cleaved PARP and Bax. Moreover, AIF and Endo G protein expression increased, indicating a caspase-independent mitochondrial-mediated apoptosis. The anti-proliferative activity of IQ against SK-MEL-2 can also be attributed to the downregulation of the PI3K/AktmTOR signaling pathway. These findings showed that IQ can be developed into a chemopreventive therapeutic agent against the melanoma cells.

Purpose: A cryopreserved iliac artery homograft (IAH) has not been considered suitable for middle hepatic vein (MHV) reconstruction during living donor liver transplantation (LDLT), primarily due to the low patency from its small diameter. We revised our surgical techniques for MHV reconstruction using an IAH to improve its patency., Methods: This study analyzed the causes of early conduit occlusion and developed revised techniques to address this that had clinical application., Results: The potential risk factors for early conduit occlusion were the small IAH size, small graft in the segment V vein (V5) and segment VIII vein (V8) opening, and small recipient MHV-left hepatic vein stump. These factors were reflected to our revised surgical methods which included endarterectomy of the atherosclerotic plaque, unification of the internal and external iliac artery branches for large V5, and branch-patch arterioplasty for large V8. IAH endarterectomy, branch unification technique, and branch-patch arterioplasty were applied to 8, 5, and 5 patients, respectively and resulted in 1-month occlusion rates of 37.5%, 20.0%, and 40.0%, respectively. The overall patency rates of the IAH-MHV conduits in our 18 patients were 66.7% at 1 month, 38.9% at 3 months, and 33.3% at 1 year., Conclusion: Our refined MHV reconstruction using an IAH improved short-term MHV conduit patency, but did not effectively prevent early conduit occlusion, particularly with a small- or medium-sized IAH. Individualized reconstruction designs during LDLT operation are needed when an IAH is used for a modified right liver graft., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2020, the Korean Surgical Society.)

The immunohistochemical analysis of PD-L1 expression is still important in cancer immunotherapy. PD-L1 expression is affected by various tumor microenvironmental factors including tumor infiltrating lymphocytes (TILs) and DNA methylation biomarkers. Given the complex communication between tumor cells and immune cells, we analyzed the expression of PD-L1 and TET1 with TILs in human NSCLC and the correlation with various clinicopathological characteristics and patient prognosis. A total of 96 cases of NSCLC were enrolled in this study. Using tissue microarray, we performed immunohistochemical staining to analyze PD-L1 and TET1 expression. Image-Pro Plus was used as an automated imaging analysis software program to analyze the density of CD3+, CD4+ and CD8 + TILs. PD-L1 expression was positively correlated with the density of CD3+, CD4+ and CD8 + TILs (p = 0.038, p = 0.020, and p = 0.009, respectively); however, no significant relationship existed between TET1 expression and any TILs. The survival analysis revealed that a high PD-L1 expression was associated with favorable prognosis for OS (p = 0.049) and DFS (p = 0.029) in advanced-stage II-IV patients, but not in early stage I. Density of CD8+ TILs was an independent and favorable prognostic factor for DFS (p = 0.008) and OS (p = 0.002) in early-stage I patients. However, high TET-1 expression was associated with poor prognosis for OS (p = 0.029) in total NSCLC patients. These findings suggest the correlation and favorable prognostic impact of PD-L1 and TILs in NSCLC. In addition, DNA demethylase TET1 has oncogenic effects, showing association with poor prognosis., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Liver transplantation is a life-saving therapy for patients with end-stage liver disease. Living donation is a critical source of organs throughout the world. Reducing donor morbidity and mortality is of utmost importance while maintaining access to liver transplantation for recipients. While laparoscopy was more rapidly utilized in donor nephrectomy, laparoscopy has been slower to develop for living donor hepatectomies due to the concerns about hemostasis, safety of the donor and quality of the graft. Pure minimal invasive approach has become a standard of care for left lateral sectionectomy (LLS) for pediatric recipients. In the past few years, a number of centers with significant laparoscopic and living donor experience have reported fully minimally invasive approach to hemi-hepatectomies. In this manuscript we discuss the experiences, lessons learned and path forward for laparoscopic and minimal invasive surgery(MIS) in donor hepatectomies (DH)., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Split liver transplantation (SLT) has been occasionally performed in Korea. This study compared the incidence and prognosis of SLT with whole liver transplantation (WLT) in adult patients., Methods: Between June 2016 and November 2019, 242 adult patients underwent a total of 256 deceased donor liver transplantation operations. SLT was performed in 7 patients (2.9%)., Results: The mean age of SLT donors was 29.7 ± 7.4 years, and the mean age of recipients was 55.7 ± 10.6 years, with the latter having a mean model for end-stage liver disease score of 34.6 ± 3.1. Mean split right liver graft weight was 1,228.6 ± 149.7 g and mean graft-recipient weight ratio was 1.97 ± 0.39. Of the seven SLT recipients, Korean Network for Organ Sharing (KONOS) status was one in status 1, one in status 2 and five in status 3. The graft ( P = 0.72) and patient ( P = 0.84) survival rates were comparable in the SLT and WLT groups. Following propensity score matching, graft ( P = 0.61) and patient ( P = 0.91) survival rates remained comparable in the two groups. Univariate analysis showed that pretransplant ventilator support and renal replacement therapy were significantly associated with patient survival, whereas KONOS status category and primary liver diseases were not. Multivariate analysis showed that pretransplant ventilator support was an independent risk factor for patient survival., Conclusion: Survival outcomes were similar in adult SLT and WLT recipients, probably due to selection of high-quality grafts and low-risk recipients. Prudent selection of donors and adult recipients for SLT may expand the liver graft pool for pediatric patients without affecting outcomes in adults undergoing SLT., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: Lactic acid fermentation has been widely used to improve the nutritional and functional properties of food products. Cherry silverberry (Elaeagnus multiflora Thunb.) is considered as an invasive plant species with known medicinal and functional properties. In this study, improvement of the biological activity and health benefits of cherry silverberry fruit through lactic acid fermentation was investigated., Results: Extracts of cherry silverberry fruits fermented by pure cultures of Lactobacillus plantarum KCTC 33131 and L. casei KCTC 13086 exhibited favorable physicochemical properties and enhanced phytochemical content, antioxidant properties (DPPH radical scavenging activity, reducing power, superoxide dismutase-like property and hydrogen peroxide scavenging activity) and α-glucosidase and tyrosinase enzyme inhibitory activity as compared with unfermented fruits. Despite a decrease in the specific phenolic acid contents among the fermented samples, the cherry silverberry fruit fermented by mixed cultures of L. plantarum and L. casei contained superior total polyphenols (3.78 ± 0.22 mg GAE g -1 ) and total (0.66 ± 0.12 mg QE g -1 ) and individual flavonoid contents in comparison with fruits fermented by single cultures and unfermented ones. Multivariate analysis also showed strong association among total phytochemical contents and biological activities., Conclusions: This work has elucidated the effect of fermentation with L. plantarum KCTC 33131 and L. casei KCTC 13086 on the improvement of the physicochemical properties and biological activity of cherry silverberry fruit. It also revealed the potential application of fermented cherry silverberry in the production of food materials beneficial for health. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

Ethnopharmacological Relevance: Orostachys japonicus A. Berger (O. japonicus), so-called Wa-song in Korea, a traditional food and medicine that grows on mountain rocks and roof tiles. Wa-song containing various phenolic compounds have been reported as a medicinal plant for prevention of fibrosis, cancer, inflammation, and oxidative damage., Aim of the Study: The present study was designed to examine the anti-angiogenic effects of cultivated Orostachys japonicus 70% ethanol extract (CE) in vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs)., Materials and Methods: CE was prepared with 70% ethanol. HUVECs, rat aortic rings, and matrigel plug in mice were treated with CE (10-20 μg/mL) and VEGF (20-50 ng/mL), and the anti-angiogenic activities of CE were analyzed by SRB, wound healing, trans-well invasion, capillary-like tubule formation, rat aortas, Western blot, and matrigel plug assay. Phenolic compounds in CE were analyzed using a high-performance liquid chromatography (HPLC)-PDA system., Results: Treatment of CE (10-20 μg/mL) markedly suppressed proliferation of HUVECs in the presence (from 136.5% to 112.2%) or absence of VEGF (from 100.0% to 92.1%). The proliferation inhibitory effect of CE was caused by G0/G1 cell cycle arrest, and the decrease of CDK-2, CDK-4, Cyclin D1 and Cyclin E1. Furthermore, CE treatment showed significant angiogenesis inhibitory effects on motility, invasion and micro-vessel formation of HUVECs, rat aortic rings and subcutaneous matrigels under VEGF-stimulation condition. In HUVECs, CE-induced anti-angiogenic effect was regulated by inhibition of the PI3K/AKT/mTOR, MAPK/p38, MAPK/ERK, FAK-Src, and VEGF-VEGFR2 signaling pathways., Conclusion: This study demonstrated that CE might be used as a potential natural substance, multi-targeted angiogenesis inhibitor, functional food material., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An accurate and reliable method based on ion trap-time of flight mass spectrometry (IT-TOF MS) was developed for screening phosphodiesterase-5 inhibitors, including sildenafil, vardenafil, and tadalafil, and their analogs in dietary supplements. Various parameters affecting liquid chromatographic separation and IT-TOF detection were investigated, and the optimal conditions were determined. The separation was achieved on a reversed-phase column under gradient elution using acetonitrile and water containing 0.2% acetic acid at a flow rate of 0.2 mL/min. The chromatographic eluents were directly ionized in the IT-TOF system equipped with an electrospray ion source operating in the positive ion mode. The proposed screening method was validated by assessing its linearity, precision, and accuracy. Sequential tandem MS was conducted to obtain structural information of the references, and the fragmentation mechanism of each reference was proposed for providing spectral insight for newly synthesized analogs. Structural information, including accurate masses of both parent and fragment ions, was incorporated into the MS n spectral library. The developed method was successfully applied for screening adulterated dietary supplement samples.

Nowadays, new types of vinegar have been developed using various raw materials and biotechnological processes. The fruit of Prunus mume has been extensively distributed in East Asia and used as a folk medication for fatigue. In this study, the Prunus mume vinegar (PV) was produced by a two-step fermentation and was evaluated for its anti-fatigue activity by C2C12 myoblasts and high-intensity exercised rats. The administration of PV significantly improved running endurance and glycogen accumulation in the liver and muscle of PV supplemented rats compared to sedentary and exercised control groups. In addition, PV supplementation elicited lower fatigue-related serum biomarkers, for instance, ammonia, inorganic phosphate, and lactate. PV administered rats exhibited higher lactate dehydrogenase activity and glutathione peroxidase activity, and lower creatine kinase activity and malondialdehyde levels. Furthermore, phenolic compounds in PV were identified using HPLC analysis. The phenolic acids analyzed in PV were protocatechuic acid, syringic acid, chlorogenic acid, and its derivates. These results indicate that the administration of PV with antioxidative property contributes to the improvement of fatigue recovery in exhausted rats. The findings of this study suggest that the PV containing various bioactive constituents can be used as a functional material against fatigue caused by high-intensity exercise.

Many studies have analyzed nicotine metabolites in blood and urine to determine the toxicity caused by smoking, and assess exposure to cigarettes. Recently, hair and nails have been used as alternative samples for the evaluation of smoking, as not only do they reflect long-term exposure but they are also stable and easy to collect. Liquid-liquid or solid-phase extraction has mainly been used to detect nicotine metabolites in biological samples; however, these have disadvantages, such as the use of toxic organic solvents and complex pretreatments. In this study, a modified QuEChERS method was proposed for the first time to prepare samples for the detection of nicotine metabolite cotinine (COT) and trans -3'-hydroxycotinine (3-HCOT) in hair and nails. High-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze traces of nicotine metabolites. The established method was validated for selectivity, linearity, lower limit of quantitation, accuracy, precision and recovery. In comparison with conventional liquid-liquid extraction (LLE), the proposed method was more robust, and resulted in higher recoveries with favorable analytical sensitivity. Using this method, clinical samples from 26 Korean infants were successfully analyzed. This method is expected to be applicable in the routine analysis of nicotine metabolites for environmental and biological exposure monitoring.

The application of dried blood spots in clinical research is becoming increasingly popular owing to its convenient collection, storage, and transportation compared to that of conventional biological samples. The potential of trimethylamine N-oxide and its related compounds as biomarkers for various cardiovascular diseases, such as atherosclerosis, stroke, thrombosis, and heart failure, was recently highlighted, which was the driving force behind the development of an analytical method to identify trimethylamine N-oxide and eight related compounds in dried blood spots. In the proposed method, a novel "on-spot reaction" approach was introduced to overcome the low loading efficiency of trimethylamine in dried blood spots. Upon the addition of 50 μL of blood onto the filter paper pretreated with dilute HCl, an acid-base neutralization reaction in the blood spots transformed the volatile trimethylamine to a salt. Next, a punched disc with a diameter of 6.0 mm was eluted by agitation with 20 mM ammonium formate for 10 min and derivatized with 1.0 M ethyl bromoacetate at 80 °C for 60 min. A surrogate analyte approach was employed for quantification of these endogenous compounds in the complex matrix. Analysis was carried out using zwitterionic hydrophilic interaction liquid chromatography-high-resolution mass spectrometry. The established method was validated and applied to monitor real samples from 30 clinical cases. The proposed new methodology based on dried blood spots could greatly improve the convenience, analytical sensitivity, and selectivity of cardiovascular disease testing., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Living donor liver transplantation (LDLT) causes bleeding in recipients during the careful preservation of most perihilar structures during this surgery. This case-control study aimed to analyze the effect of prolonged hepatic inflow occlusion (PHIO) when applied during recipient hepatectomy in LDLT., Methods: The study group comprised patients who underwent PHIO with Model for End-Stage Liver Disease (MELD) scores ranging from 26 to 35 (n=20). The following two control groups were selected according to their MELD scores: the low-MELD score group (MELD scores of 15-20, n=40) and the high-MELD score group (MELD scores of 26-35, n=40). Total dissection time for hepatic mobilization and dissection and blood loss during these procedures were compared between the two groups., Results: In the PHIO study group, mean total dissection time and mean PHIO duration were 226.3±59.4 and 68.2±19.1 minutes, respectively. Twelve patients underwent PHIO twice, and the other eight patients underwent PHIO once. The low-MELD score control group and the PHIO study group showed similar dissection duration (216.0±43.9 vs. 226.3±59.4 minutes, P=0.82) and similar blood loss volume during dissection (2,112.5±1,614.9 vs. 2,350.0±951.9 mL, P=0.17). The high-MELD score control group and the PHIO study group showed similar dissection duration (241.0±41.9 vs. 226.3±59.4 minutes, P=0.71), but the PHIO group showed a significantly lower blood loss during dissection than the high-MELD score group (2,350.0±951.9 vs. 2,815.0±1,813.9 mL, P=0.002). During and after PHIO, no adverse complication was observed, except for transient splanchnic congestion., Conclusions: Our findings suggest that PHIO is a simple effective method to reduce intraoperative bleeding during hepatic mobilization and dissection during LDLT operation requiring difficult dissection., (Copyright: © 2020 The Korean Society for Transplantation.)

Background: To understand the changing demands and recent trends in the indications for living donor liver transplantation (LDLT), the present study aimed to analyze the indications for LDLT performed in a high-volume transplantation center over 10 years., Methods: The liver transplantation database at our institution was searched to identify patients who underwent LDLT during a 10-year period from January 2008 to December 2017. The study subjects (n=3,145) were divided into two groups: adult patients (n=3,019, 92.7%) and pediatric patients (n=126, 3.9%)., Results: In the adult recipients, the primary diagnoses were hepatitis B virus (HBV)-associated liver cirrhosis (n=1,898, 62.9%), alcoholic liver disease (n=482, 16.0%), hepatitis C virus-associated cirrhosis (n=203, 6.7%), acute liver failure (n=127, n=4.2%), and other diseases (n=157, 5.2%). The mean Model for End-Stage Liver Disease score was 15.6±8.8 (range, 6-40). The proportion of patients with HBV-associated liver disease gradually decreased, but the proportion of those with alcoholic liver disease increased. Hepatocellular carcinoma (HCC) was diagnosed in 1,467 patients (48.6%). The mean proportion of patients with HCC was 63.1% among those with HBV-associated liver disease. In pediatric recipients, the primary diagnoses were biliary atresia (n=51, 40.5%), liver failure of various causes (n=37, 29.4%), metabolic disease (n=22, 17.5%), hepatoblastoma (n=12, 9.5%), and infectious diseases (n=4, 3.2%)., Conclusions: Our results showed that there were some significant changes in the indications of LDLT. We believe that our results may reflect the real changes in the indications of LDLT and they will be useful for predicting further changes in the future., (Copyright: © 2020 The Korean Society for Transplantation.)

Background: Homologous vein allografts are adequate for reconstruction of the middle hepatic vein (MHV) in living-donor liver transplantation (LDLT). However, supply is a matter of concern. To replace homologous vein allografts, polytetrafluoroethylene (PTFE) grafts were used. This study aimed to assess the long-term patency rates and complications of PTFE grafts used for MHV reconstruction of LDLT in a high-volume liver transplantation center., Methods: We analyzed the patency rates of PTFE-interposed MHV in 100 LDLT recipients and reviewed complications including PTFE graft migration., Results: The mean age was 53.5±5.4 years and male to female ratio was 73:27. Primary diagnoses were hepatitis B virus infection (n=71) and other (n=28). Mean model for end-stage liver disease score was 16.2±8.3. V5 reconstruction was performed as either single anastomosis (n=85) or double anastomoses (n=14). No V5 reconstruction was required in one patient. V8 reconstruction was performed as single anastomosis, double anastomoses, and no reconstruction in 75, 0, and 25 patients, respectively. During a mean follow-up of 6 years, three recipients required early MHV stenting within 2 weeks. After 3 months, there were no episodes of congestion-associated infarct, regardless of MHV patency. Patency rates of PTFE-interposed MHV were 54.0%, 37.0%, and 37.0% at 1, 3, and 5 years, respectively. Unwanted PTFE graft migration occurred in two recipients, and the actual incidence was 2% at 5 years., Conclusions: PTFE grafts combined with small-artery patches demonstrated acceptably high short- and long-term patency rates. Since the risk of unwanted migration of PTFE graft is not negligibly low, lifelong surveillance is necessary to detect unexpected rare complications., (© The Korean Society for Transplantation.)

Background: Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death., Methods: We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016., Results: The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively ( P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively ( P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM., Conclusion: Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Phthalates are commonly used as plasticizers and are known as risk factors toward several conditions such as cancer, birth defects, and endocrine disruption. Biomonitoring of phthalates is necessary to assess the potentially harmful effects of long-term exposure. In this work, we have developed a novel QuEChERS method to determine eight phthalate metabolites-mono-(3-carboxypropyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-n-butyl phthalate, mono-benzyl phthalate, mono-(carboxyloctyl) phthalate, and mono-(carboxynonyl) phthalate-in human milk. The extraction process was optimized by comparing three different QuEChERS methods, and a further purification step was used to eliminate interferential lipid. In this process, several factors, such as the pH based on QuEChERS additive salts, acid dissociation constant, and distribution coefficient of the analyte, were found to have a significant effect on the extraction efficiency of the QuEChERS method. Target compounds were determined using liquid chromatography-tandem mass spectrometry equipped with electrospray ionization in the multiple-reaction monitoring mode. The developed method was verified by evaluating the selectivity, linearity, lower limit of quantification, accuracy, precision, and recovery, and applied to monitor real milk samples from 26 people. It is expected that the established method can be utilized not only to monitor phthalate metabolites in biological samples but also to identify the correlation between phthalate concentrations observed for the mother and the newborn., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Two-dimensional paper networks (2DPNs) have enabled the use of paper-based platforms to perform multistep immunoassays for detection of pathogenic diseases at the point-of-care. To date, however, detection has required the user to provide multiple signal enhancement solutions and been limited to protein targets. We solve these challenges by using mathematical equations to guide the device design of a novel 2DPN, which leverages multiple fluidic inputs to apply fully dried solutions of hydrogen peroxide, diaminobenzidine, and horseradish peroxidase signal enhancement reagents to enhance the limit-of-detection of numerous nucleic acid products. Upon rehydration in our unique 2DPN design, the dried signal enhancement solution reduces the limit-of-detection (LOD) of the device to 5 × 10 11 nucleic acid copies/mL without increasing false positive detection. Our easy-to-use device retains activity after 28 days of dry storage and produces reliable signal enhancement 40 min after sample application. The fully integrated device demonstrated versatility in its ability to detect double-stranded and single-stranded DNA samples, as well as peptide nucleic acids., Competing Interests: The authors declare the following competing financial interest(s): Dr. HyunDae D. Cho is CEO and President of CrossLife Technologies, which holds a patent for the TARA assay we used in this publication., (Copyright © 2020 American Chemical Society.)

Background: Laparoscopic treatment for hepatocellular carcinoma (HCC) has increased. We retrospectively compared the perioperative and long-term oncological outcomes of laparoscopic liver resection (LLR) with those of open liver resection (OLR) for hepatocellular carcinoma (HCC) in well-matched patient groups using propensity score matching (PSM)., Methods: We reviewed medical records of patients with HCC who underwent liver resection between July 2007 and April 2016 at our center. In total, 2335 patients were included in this study and divided into LLR (n = 264) and OLR (n = 2071) groups. For group comparisons, 1:2 PSM was used with covariates of baseline characteristics, including tumor characteristics and surgical liver resection procedures., Results: After PSM, there were 217 and 434 patients in the LLR and OLR groups, respectively. The LLR group had shorter hospital stays (8.9 vs. 14.8 days; P < 0.001) and lower postoperative morbidity (6.5% vs. 12.0%; P = 0.022). The 1-, 3-, and 5-year overall survival rates were 98.1%, 87.0%, and 78.6%, respectively, for the LLR group, and 98.3%, 90.8%, and 84.3%, respectively, for the OLR group (P = 0.570). The 1-, 3-, and 5-year disease-free survival rates were 81.0%, 62.0%, and 49.1%, respectively, for the LLR group, and 85.3%, 64.7%, and 56.2%, respectively, for the OLR group (P = 0.563)., Conclusions: Long-term oncological outcomes were comparable between LLR and OLR for selected patients. LLR was associated with multiple benefits, even for selected patients with cirrhosis who underwent major hepatectomy. LLR for HCC performed by an experienced surgeon could be considered a safe and feasible alternative to OLR for selected patients.

Purpose: Hepatorenal syndrome (HRS) is a fatal complication in patients with end-stage liver disease awaiting liver transplantation (LT). HRS often develops in patients with high model for end-stage liver disease (MELD) score. This study investigated the outcomes of peritransplant management of HRS in a high-volume LT center in Korea for 2 years., Methods: A total of 157 recipients that deceased donor liver transplantation (DDLT) from January 2017 to December 2018 were included. In-hospital mortality (IHM) was analyzed in relation to pre- and posttransplant application of renal replacement therapy (RRT)., Results: Primary diagnoses for DDLT were alcoholic liver disease (n = 61), HBV-associated liver cirrhosis (n = 48), retransplantation for chronic graft failure (n = 24), and others (n = 24). Mean MELD score was 34.6 ± 6.2 with 72 patients at Korean Network for Organ Sharing MELD status 2 (45.9%), 43 at status 3 (27.4%), 36 at status 4 (22.9%), and 6 at status 5 (3.8%). Pretransplant RRT was performed in 16 patients (10.2%) that did not show IHM. Posttransplant RRT was performed in 69 patients (44.0%), for whom IHM incidence was 15.9%. In 53 patients that had undergone de novo posttransplant RRT, IHM incidence increased to 20.8%. IHM in the 88 patients not requiring RRT was 2.3%., Conclusion: The majority of adult DDLT recipients in Korean MELD score-based allocation system have very high MELD scores, which is often associated with HRS. Pretransplant RRT appears to improve posttransplant survival outcomes. We thereby recommend that, if indicated, pretransplant RRT be performed while awaiting DDLT., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2020, the Korean Surgical Society.)

Background: The mammalian target of the rapamycin inhibitor has dual inhibitory effects on cell growth and angiogenesis. This study aimed to analyze the usage of everolimus on actual immunosuppression (IS) regimens through a cross-sectional study in a high-volume liver transplantation (LT) center., Methods: Our institutional LT database was searched for adult patients who underwent primary LT surgery between January 2010 and December 2016. We identified 2,093 LT recipients with observation periods of 1 to 8 years., Results: We divided the 2,093 recipients into three groups according to the posttransplant follow-up period as follows: group A (12-36 months; n=680), group B (37-60 months; n=560), and group C (>60 months; n=853). The individual IS agents were tacrolimus in 1,807 patients (86.3%), cyclosporine in 169 patients (8.1%), mycophenolate mofetil (MMF) in 1,310 patients (62.6%), and everolimus in 115 patients (5.5%). The most common IS regimens were tacrolimus-MMF combination and tacrolimus monotherapy, regardless of the posttransplant period. Patients with pretransplant malignancies were administered everolimus more frequently than those without pretransplant malignancies (P<0.001). In 102 patients with hepatocellular carcinoma recurrence or de novo malignancies, IS regimens included everolimus-tacrolimus in 41 patients (40.2%), tacrolimus-MMF in 27 patients (26.4%), tacrolimus in 20 patients (19.6%), MMF in 10 patients (9.8%), cyclosporine in three patients (2.9%), and cyclosporine-MMF in one patient (1.0%)., Conclusions: Administration of everolimus after LT has been gradually increasing with the expansion of indications in our institutional practice. Currently, the role of everolimus is minimal and not comparable to that of tacrolimus, but it has a unique position in the field of IS after LT., (Copyright: © 2019 The Korean Society for Transplantation.)

Background: Autologous portal vein Y-graft (PYG) interposition has been the standard procedure for reconstruction of double portal vein (PV) orifices of right liver grafts during living donor liver transplantations. However, it has the disadvantage of being vulnerable to anastomotic stenosis. A refined technique of conjoined unification venoplasty (CUV) was developed to secure PV reconstruction., Methods: We reviewed the surgical outcomes in PV reconstructions using CUVs in 21 cases which were followed up for >3 years., Results: The mean age of recipients was 51.7±4.9 years. The model for end-stage liver disease score was 15.3±6.4. The graft-recipient weight ratio was 1.12±0.21. Recipient PYGs were harvested in all cases. All living donors were blood relatives or relatives through marriage with type III PV anomalies. The number of right liver graft PV orifices was two in 19 cases and three in two cases. For the central intervening vein patch, a PV segment was used in six cases, and an autologous greater saphenous vein patch was used in the remaining 15 cases. The 21 patient cohort displayed a 100% 4-year patient survival rate. None of them underwent any PV interventions including interventional stenting. Serial follow-up computed tomography scans revealed that the reconstructed PV showed early reshaping with a stable streamlined configuration for over 3 years., Conclusions: PV reconstruction using the CUV technique appears to be significantly more effective in preventing PV complications. We believe that CUV is a useful technique to reconstruct right liver grafts with multiple PV orifices., (Copyright: © 2019 The Korean Society for Transplantation.)

BACKGROUND Because of the supply shortage for homologous vein allografts, we previously used ringed Gore-Tex vascular grafts for middle hepatic vein (MHV) reconstruction in living donor liver transplantation. However, owing to the subsequent unavailability of ringed Gore-Tex grafts, we replaced them with Hemashield vascular grafts. This study aimed to compare the patency of Hemashield grafts with that of ringed Gore-Tex grafts. MATERIAL AND METHODS This was a retrospective double-arm study between the study group that used Hemashield grafts (n=63) and the historical control group that used ringed Gore-Tex grafts (n=126). RESULTS In the Gore-Tex and Hemashield groups, mean age was 53.1±6.2 and 54.3±10.4 years; model for end-stage liver disease score was 16.5±8.3 and 17.5±9.9; and graft-recipient weight ratio was 1.11±0.23 and 1.12±0.25, respectively. In the Gore-Tex graft group, V5 reconstruction was done in single (n=107, 84.9%), double (n=17, 13.5%), and none (n=2, 1.6%). V8 reconstruction was done in single (n=95, 75.4%), double (n=1, 0.8%), and none (n=30, 23.8%). In the Hemashield group, V5 reconstruction was done in single (n=43, 68.3%), double (n=19, 30.2%), and triple (n=1, 1.6%). V8 reconstruction was done in single (n=45, 71.4%), double (n=9, 14.3%), and none (n=9, 14.3%). One-year conduit patency rates in the Gore-Tex and Hemashield groups were 54.8% and 71.6%, respectively (p=0.048). CONCLUSIONS MHV reconstruction using Hemashield vascular grafts demonstrated higher short-term patency rates than those associated with ringed Gore-Tex vascular grafts. We suggest that the Hemashield vascular graft is one of the best prosthetic materials for MHV reconstruction.

Context: Kochia scoparia (L.) Schrad (Amaranthaceae), known as a traditional medicine in China, Japan and Korea, is reported to have various biological activities. However, K. scoparia seed extract (KSE) functional roles on angiogenesis and prostate cancer inhibition have not been elucidated. Objective: This study elucidates the effects of KSE on vascular endothelial growth factor (VEGF)-induced angiogenesis in human umbilical vein endothelial cells (HUVECs) and inhibition of proliferation in prostate cancer cells. Materials and methods: HUVECs were treated with 10-20 µg/mL of KSE and 20-50 ng/mL of VEGF for 12-72 h. Anti-angiogenesis properties of KSE were determined by wound healing, trans-well, tube formation, rat aortic ring assay and western blotting. Prostate cancer and normal cells were incubated with 10-250 µg/mL of KSE for 24 h, and cell viability was measured by SRB assay. Phenolic compounds in KSE were analyzed using a HPLC-PDA system. Results: IC 50 for cell viability of HUVECs, LNCaP, PC-3, RC-58T and RWPE-1 by KSE were 30.64, 89.25, 123.41, 141.62 and >250 µg/mL, respectively. Treatment with KSE (20 µg/mL) significantly suppressed VEGF-induced migration, invasion and capillary-like structure formation of HUVECs and microvessel sprouting from rat aortic rings. In addition, KSE down-regulated PI3K/AKT/mTOR levels and phosphorylation of VEGF receptor 2 in HUVECs. 3-OH-tyrosol (1.63 mg/g) and morin hydrate (0.17 mg/g) were identified in KSE. Conclusions: KSE inhibits angiogenesis in HUVECs as well as proliferation in human prostate cancer cells, suggesting KSE may be useful herbal medicine for preventing progression of prostate cancer and angiogenesis.

Pectinase is a well-known enzyme used in the food processing industry to produce fruit juice and concentrate. This study evaluated the anticancer and antiangiogenesis activities of pectinase-treated Prunus mume fruit concentrate (PC) and its phenolic components. PC treatment (250 to 1,000 µg/mL) resulted in decreased proliferation of SW480 human colorectal cancer cells through S-phase cell cycle arrest; however, equivalent concentrations of PC did not show toxicity toward CRL-1539 colon normal cells. Furthermore, PC-induced caspase-dependent apoptosis in SW480 cells, which was characterized by accumulation of apoptotic cell population, cell shrinkage, formation of apoptotic bodies, upregulation of proapoptotic Bax, cleaved PARP, caspase-3, caspase-8, and caspase-9, and downregulation of antiapoptotic Bcl-2. Antiangiogenesis effects of PC were assessed using human umbilical vein endothelial cells (HUVECs). We found that PC did not inhibit HUVECs proliferation at concentrations of 500 to 1,500 µg/mL. In addition, treatment with PC at nontoxic concentrations (500 to 1,000 µg/mL) blocked vascular endothelial growth factor induced cell migration, invasion, capillary-like tube formation, and angiogenesis from rat aortic rings. HPLC-PDA analysis showed that there were at least four different phenolics including 5-HMF, neochlorogenic acid, protocatechuic acid, and syringic acid. Taken together, these results indicated that PC could be used as a good source of phenolic compounds with selective anticancer and antiangiogenesis activities. PRACTICAL APPLICATION: Pectinases are one of the well-known enzyme used in the part of food processing. Treatment of pectinase is a useful strategy to reduce viscosity, turbidity, and pulp particles in the production of fruit juice, extract, and concentrate. In the present study, we found that pectinase-treated P. mume fruit concentrate significantly suppresses colorectal cancer proliferation and angiogenesis of human umbilical vein endothelial cells. The significance of our findings is that pectinase-treated P. mume concentrate may be used as a commercial functional food material to inhibit colorectal cancer and angiogenesis., (© 2019 Institute of Food Technologists®.)

MoS 2 2D nanosheets (NS) with intercalated 0D quantum dots (QDs) represent promising structures for creating low-dimensional (LD) resistive memory devices. Nonvolatile memristors based 2D materials demonstrate low power consumption and ultrahigh density. Here, the observation of a photoinduced phase transition in the 2D NS/0D QDs MoS 2 structure providing dynamic resistive memory is reported. The resistive switching of the MoS 2 NS/QD structure is observed in an electric field and can be controlled through local QD excitations. Photoexcitation of the LD structure at different laser power densities leads to a reversible MoS 2 2H-1T phase transition and demonstrates the potential of the LD structure for implementing a new dynamic ultrafast photoresistive memory. The dynamic LD photomemristive structure is attractive for real-time pattern recognition and photoconfiguration of artificial neural networks in a wide spectral range of sensitivity provided by QDs., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study established an individualized HBV prophylaxis protocol, through optimization of hepatitis B immunoglobulin (HBIG) administration, with application of simulative half-life (SHL)., Methods: This study involved five parts: Part 1 developed the SHL estimation method with 20 patients; Parts 2 and 3 assessed the SHL variability and developed a simulation model to apply SHL in 100 patients; Part 4 validated the simulation model in 114 patients, and Part 5 was a cross-sectional study on the current status of HBIG infusion intervals in 660 patients., Results: In Part 1, infusion of 10,000 IU HBIG induced add-on rise hepatitis B surface antibody (anti-HBs) titer of 5,252.5 ± 873.7 IU/L, which was 4.4% lower than actual measurement. Mean SHL of 20.0 ± 3.7 days was 2.2% longer than actual measurement. In Part 2, the medians of the intra- and inter-individual coefficient of variation in SHL were 13.5% and 18.5%, respectively. Pretransplant HBV DNA load and posttransplant antiviral therapy did not affect SHL. In Part 3, a simulation model was developed to determine the interval of HBIG infusion, by using SHL. In Part 4, all 114 patients were successfully managed with regular HBIG infusion intervals of ≥ 8 weeks, and the interval was prolonged to ≥ 12 weeks in 89.4%, with a target trough anti-HBs titer ≥ 200 IU/L. In Part 5, 47.4% of our patients received HBIG excessively, at a target trough titer of 500 IU/L., Conclusion: SHL estimation using only clinically available parameters seems to be reliably accurate when compared with actual measurements. We believe that SHL estimation is helpful to establish a personalized HBV prophylaxis protocol for optimizing HBIG administration., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Rationale: Smooth muscle tumors of the vulva are infrequent neoplasms with diverse histologic features and unclear biologic behavior. Herein, we report a very rare case of vulvar epithelioid leiomyoma and review of previous reported cases of these tumors. In addition, we have discussed the representative diagnostic criteria of vulvar smooth muscle tumors and prognostic significance of epithelioid morphology., Patient Concerns: We recently met a 45-year-old woman with complaint of painful vulvar mass., Interventions: Excisional biopsy was performed., Diagnoses: Pathologic examination revealed a vulvar epithelioid leiomyoma with multinodular growth pattern. Mitotic activity was rare and cellular atypia was not identified. Based on histology and immunohistochemical staining results, the case was diagnosed as vulvar epithelioid leiomyoma., Outcomes: After mass excision, the patient was discharged with no complication and there was no evidence recurrence for 6 months., Lessons: After reviewing previous papers and diagnostic criterion, we thought that vulvar smooth muscle tumors with predominant epithelioid morphology may be associated with unfavorable prognosis, Therefore, pathologists should examine the epithelioid component in vulvar smooth muscle tumors carefully.

Background: Mulberry silkworm larvae (Bombyx mori) are known as the oldest resource of food and traditional medicine. Although silkworm larvae have been reported to treat various chronic diseases, the effect of fermentation by microorganisms improving the biological activities of silkworm larvae was not reported. In the present study, fermented silkworm larvae was developed via solid-state fermentation with Aspergillus kawachii and investigated its anti-cancer activity in human hepatocellular carcinoma cells., Methods: We investigated the anti-cancer effects of unfermented (SEE) and fermented silkworm larva ethanol extract (FSEE) on HepG2 human hepatocellular carcinoma cells as well as compared changes in free amino acid, fatty acid, and mineral contents. Anti-cancer activities were evaluated by SRB staining, cell cycle analysis, Annexin V staining, Hoechst staining, DNA fragmentation analysis and western blot analysis. Fatty acid, free amino acid and mineral contents of SEE and FSEE were determined by gas chromatography, amino acid analyzer and flame atomic absorption spectrophotometer, respectively., Results: Compared with SEE, treatment with FSEE resulted in apoptotic cell death in HepG2 cells characterized by G0/G1 phase cell cycle arrest, DNA fragmentation, and formation of apoptotic bodies. Furthermore, FSEE significantly up-regulated pro-apoptotic as well as down-regulated anti-apoptotic proteins in HepG2 cells. However, an equivalent concentration of SEE did not induce cell cycle arrest or apoptosis in HepG2 cells. Moreover, fermentation process by Aspergillus kawachii resulted in enhancement of fatty acid contents in silkworm larvae, whereas amino acid and mineral contents were decreased., Conclusion: Collectively, this study demonstrates that silkworm larvae solid state-fermented by Aspergillus kawachii strongly potentiates caspase-dependent and -independent apoptosis pathways in human hepatocellular carcinoma cells by regulating secondary metabolites.

Objectives: CVS, the largest US pharmacy chain, discontinued selling tobacco products in 2014; meanwhile, Family Dollar and Dollar General, the two largest dollar store chains, began selling tobacco in 2012 and 2013, respectively. The purpose of this study is to evaluate the differential change in tobacco retailer density (TRD) by rurality throughout 12 Southeastern US states., Methods: Tobacco retailer density was calculated for CVS and dollar store locations and combined to represent retailer density change before and after policy changes. Bivariate analyses were conducted to compare the corporate-initiated changes in county-level retailer density across rurality categories., Results: Findings suggest a statistically significant difference ( p  < 0.0001) between TRD effect and rurality. Urban counties together experienced a retailer density increase of 0.4 stores per 10 k adult population, while rural counties reported a TRD increase of 2.6-eight (8) times the increase in urban areas., Conclusions: Recent corporate policy changes on tobacco sales have increased access to tobacco retailers in rural counties considerably more than in urban counties, contributing to further disparities. CVS pharmacies discontinuing tobacco sales caused a decrease in retail density in urban areas, and the decision of the dollar stores locations initiating tobacco sales resulted in a greater burden to rural and small-metro counties., Competing Interests: None declared.

Orostachys japonicus has traditionally been used as a food product and a fork medicine in Asia to treat various diseases. Angiogenesis is a critical process that contributes to various chronic diseases via excessive delivery of oxygen and nutrients. Common anti-angiogenic drugs have serious problems related to high costs and side effects; thus, natural products with low costs and no cytotoxicity have garnered increasing interest. In this study, we evaluated and compared the anti-angiogenic effects and phenolic compound contents between wild (WOEs) and cultivated O. japonicus extracts (COEs) prepared under various extract conditions. WOEs and COEs suppressed cell proliferation of human umbilical vein endothelial cells (HUVECs) and inhibited vascular endothelial growth factor-induced chemotactic migration, invasion, and capillary-like tube formation in HUVECs. Among COEs, that prepared by 70% EtOH (70% CE) showed the most effective anti-angiogenic activity in HUVECs. When compared to WOEs, total polyphenol and total flavonoid contents were 1.28 to 4.38 times higher in COEs, and 70% CE contained the greatest flavonoid contents (28.28 ± 0.93 mg%), as well as the highest levels of major phenolic compounds including gallic acid (21.84 µg/mL), epicatechin-gallate (6.58 µg/mL), kaempferol (6.32 µg/mL), and quercetin (8.55 µg/mL). Although further studies are required to identify the molecular mechanisms behind these anti-angiogenic effects, 70% CE could be used as an herbal medicine, functional food ingredient, and potent angiogenesis inhibitor. PRACTICAL APPLICATION: Environmental factors such as altitude, nutrients, exposure to sunlight, and temperature can influence the type and quantity of bioactive components in plants. The advantage of cultivated plants is that the above-mentioned factors can be artificially adjusted compared to wild plants. Based on economic efficiency, productivity, and consistent quality, anti-angiogenesis activity of cultivated O. japonicus is of greater commercial value as a functional food than wild O. japonicus., (© 2019 Institute of Food Technologists®.)

Tin sulfides are promising materials in the fields of photoelectronics and photovoltaics because of their appropriate energy bands. However, doping in SnS 2 can improve the stability and robustness of this material in potential applications. Herein, we report the synthesis of SnS 2 nanoflakes with Zn doping via simple hydrothermal route. The effect of doping Zn was found to display a huge influence in the structural and crystalline order of as synthesized SnS 2 . Their optical properties attest Zn doping of SnS 2 results in reduction of the band gap which benefits strong visible-light absorption. Significantly, enhanced photoresponse was observed with respect to pristine SnS 2 . Such enhancement could result in improved electronic conductivity and sensitivity due to Zn doping at appropriate concentration. These excellent performances show that Sn 1- x Zn x S 2 nanoflakes could offer huge potential for nanoelectronics and optoelectronics device applications.

The antioxidant and anti-adipogenic activities of a mixture of Nelumbo nucifera L., Morus alba L., and Raphanus sativus were investigated and their anti-obesity activities were established in vitro and in vivo . Among the 26 different mixtures of extraction solvent and mixture ratios, ethanol extract mixture no. 1 (EM01) showed the highest antioxidant (α,α-Diphenyl-β-picrylhydrazyl, total phenolic contents) and anti-adipogenic (Oil-Red O staining) activities. EM01 inhibited lipid accumulation in 3T3-L1 adipocytes compared to quercetin-3-O-glucuronide. Furthermore, body, liver, and adipose tissue weights decreased in the high-fat diet (HFD)-EM01 group compared to in the high-fat diet control group (HFD-CTL). EM01 lowered blood glucose levels elevated by the HFD. Lipid profiles were improved following EM01 treatment. Serum adiponectin significantly increased, while leptin, insulin growth factor-1, non-esterified fatty acid, and glucose significantly decreased in the HFD-EM01 group. Adipogenesis and lipogenesis-related genes were suppressed, while fat oxidation-related genes increased following EM01 administration. Thus, EM01 may be a natural anti-obesity agent.

Simultaneous splenectomy (SSPX) in adult living donor liver transplantation (ALDLT) has definitely beneficial roles such as portal flow modulation in small-for-size graft and correction of hypersplenism-related pancytopenia, and so on, but disastrous complications after SSPX often occur. For the first time, we devised unique and innovative splenic devascularization (SDV) procedure to alleviated untoward effects of SSPX but to maintain its benefits for the indicated patients. From April 2013 to December 2014, 520 recipients underwent ALDLT, and the SSPX and SDV were simultaneously performed in 62 (11.9%) and 61 (11.7%) patients, respectively. The most common indication was hypersplenism-related pancytopenia (n = 101), small-for-size graft (n = 14), hepatitis C virus (HCV) (n = 7), and splenic artery aneurysm (n = 1). Postoperative small-for-size graft syndrome (SFSS) was absent in both SSPX and SDV, and preoperative pancytopenia was improved in both groups since postoperative 1 week, although SSPX was more substantial than SDV. Preoperative splenic volume (706.2 ± 282.9 ml) after SDV significantly decreased to 425.5 ± 204.4 ml on 1 month, respectively. In contrast to SDV, SSPX resulted in longer operation time and higher incidence of postoperative complications including mortality. In conclusion, SDV can replace SSPX during ALDLT without hampering its beneficial roles seriously, but get rid of splenectomy-related lethal complication., (© 2019 Steunstichting ESOT.)

Primary prostate cancer cells frequently develop resistance toward chemotherapy as well as most chemotherapeutics have been reported to induce undesirable cytotoxicity in normal cells. In this study, we performed sensitizing activity analysis of auriculasin (AC) to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in RC-58T/h/SA#4 primary prostate cancer cells without significant cytotoxicity in RWPE-1 prostate epithelial cells. Combined treatment with AC and TRAIL at optimal concentrations resulted in tumor-specific apoptotic cell death in RC-58T/h/SA#4 cells, characterized by DNA fragmentation, accumulation of apoptotic cell population, and nuclear condensation. Compared to single treatment with AC or TRAIL, co-treatment with AC and TRAIL significantly increased expression of Bax, cleaved PARP, AIF, endo G, and cytochrome c but decreased expression of phosphorylation of AKT and mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K), Bcl-2 and caspases-9, -8, -3, and -10. The sensitizing effect of AC to TRAIL was well correlated with inhibition of death receptor 5 (DR5) CHOP, and p53 expression. Moreover, pre-treatment with a chimeric blocking antibody for DR5 effectively reduced AC-TRAIL-induced cell death and apoptosis-related protein expression. These results suggest that non-toxic concentrations of AC sensitize TRAIL-resistant primary prostate cancer cells to TRAIL-mediated apoptosis via up-regulation of DR5 and downstream signaling pathways., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Aims: EUS-guided fine-needle aspiration/biopsy (EUS-FNA/B) has a high diagnostic accuracy for pancreatic tumors. Most reports have focused on the diagnostic yield of cytology or histology; the ability of various FNA/B techniques to obtain an adequate mass of cells or tissue has rarely been investigated., Methods: Patients with suspected pancreatic malignancy underwent EUS-FNB using a 22-gauge ProCore needle by either the stylet slow-pull-back technique (group A), conventional negative suction after stylet removal (group B), or non-suction after stylet removal (group C) in the absence of an on-site cytopathologist. The adequacy of the 3 techniques based on the diagnostic yield, cellularity, blood contamination, and core-tissue acquisition was evaluated., Results: A total of 50 patients (27 males) were analyzed. The mean tumor size was 21 to 40 mm in 54%. The rate of a good or excellent proportion of cellularity was highest in group A compared with groups B and C (72% vs 60% vs 50%, P = .049). A >25% rate of blood contamination was more prevalent in group B (30% vs 42% vs 10%, P = .009). The rate of adequate core-tissue acquisition was not different (52% vs 34% vs 50%, P = .140). Based on the multivariate generalized estimation equation, the stylet slow-pull-back technique and a tumor size >40 mm were favorable factors for diagnostic adequacy., Conclusions: The stylet slow-pull-back technique might enable acquisition of tissue and assessment of cellularity for the diagnosis of pancreatic tumors suspected to be malignant. (Clinical trial registration number: KCT0002190.)., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Recently there has been immense interest in the exploration of richly available two-dimensional non-toxic layered material such as tin disulfide (SnS 2 ) for potential employment in energy and environmental needs. In this regard, we report on the synthesis of few-layered Sn 1-x Mg x S 2 nanosheets through a facile one-step hydrothermal route to address all such functions concerning photocatalysis and photoelectrochemical conversion. The crystalline order and structure of processed layered Sn 1-x Mg x S 2 were initially found to exhibit a strong influence on their physicochemical properties. Their optical properties attest the Mg doping in SnS 2 to benefit us with enhanced visible-light absorption via red-shift in their absorption edge. In the photoluminescence spectrum the emissions observed along visible and red region signifies the association of Mg related trap states in Sn 1-x Mg x S 2 . Next, the photocurrent and electrochemical impedance spectroscopic results revealed the Mg doping to promote the effective charge transfer process (which was beneficial to enhance their photocatalytic activity). Consequently, the layered Sn 0.98 Mg 0.02 S 2 made photoanodes displayed 1.7 fold higher photocurrent density under simulated solar radiation with respect to their undoped counterpart. Furthermore, the layered Sn 0.98 Mg 0.02 S 2 nanosheets exhibits enhanced visible light decomposition of organic dye while compared with pristine SnS 2 nanosheets. The value of rate constants obtained for the Sn 0.98 Mg 0.02 S 2 nanosheets was found to be 1.4 times higher than that of pristine SnS 2 . Finally, the results obtained through the present study projects the huge potential of layered Sn 0.98 Mg 0.02 S 2 nanosheets for future multifunctional applications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The factors associated with recurrence of colonic neoplasm after endoscopic resection with a positive lateral margin are not well known. Thus, we evaluate the relationship between recurrence and positive lateral margin after endoscopic en bloc resection of colorectal neoplasm., Methods: A retrospective review of 9302 patients who underwent colonic endoscopic resection from January 2008 to January 2015. Of these, a total of 76 patients with positive lateral margins with clear evidence of the its location on endoscopic picture after endoscopic en bloc resection of colorectal neoplasm (>10 mm) were included., Results: Ten of 76 (13.2%) patients experienced recurrence during the follow-up period (mean f/u month, 21.7 ± 15.6). In cases with positive lateral margins, the 3- and 5-year local recurrence rate of colorectal neoplasm was 28.1% and 40.1%, respectively. The histological features of the recurrence group were as follows: one case of adenocarcinoma [from low-grade adenoma (LGA)]; two cases of high-grade adenoma (HGA) (one from HGA and one from LGA); and seven cases of LGA (four from adenocarcinoma, two from LGA, and one from HGA). The mean age of patients, locations of the lesions, and histologic type were not significantly associated with local recurrence. In multivariate Poisson regression analyses, total length of lateral margin involvement ≥8 mm (relative risk 12.51; 95% CI 1.11-140.34, p = .040) was a significant predictor of local recurrence., Conclusions: Positive lateral margins ≥8 mm may be a reliable predictor of local recurrence after endoscopic en bloc resection of colorectal neoplasm.

BACKGROUND We assessed the prognostic impact of donor age on the outcome of adult living donor liver transplantation (LDLT). MATERIAL AND METHODS The study population comprised adult donor and recipients of right lobe grafts for LDLT performed from January 2005 to December 2016. There were 35 living donors aged ≥50 years (old-age donor group). As a control group, donors in their 20s (young-age donor group) were selected after one-to-one propensity score matching based on sex, model for end-stage liver disease (MELD) score, and primary diagnosis. RESULTS Donor age was 52.5±1.5 years versus 25.4±3.1 years in the old- and young-age donor groups, respectively. Remnant volumes of the 2 groups were 38.9±3.0% versus 38.1±2.9%, respectively (p=0.98). One-month regeneration rate of the remnant liver was 101.1±10.6% versus 104.5±11.8%, respectively (p=0.08), and there was no significant difference in the incidences of donor complications. Mean MELD score was 15 versus 14, respectively (p=0.82). Graft-to-recipient weight ratio was 1.02±0.43 versus 0.91±0.63, respectively (p=0.28). In the recipients, biliary complication occurred in 11.4% versus 8.6%, respectively (p=0.12), and there was no difference in 5-year survival rates of both groups (p=0.15). The 1-week and 1-month regeneration rates of the remnant left liver were 71.6±9.9% and 100.1±10.6% in the old-age group, respectively, whereas those were 80.2±12.1% and 104.5±11.8% in the young-age group, respectively (p=0.08). CONCLUSIONS Right lobe grafts from donors aged ≥50 years showed the usual recovery of graft function but rather delayed liver regeneration. Thus, old-aged donors should be selected prudently after consideration of hepatic resection rate, graft size, and hepatic steatosis.

Angiogenesis plays an important role in various pathological conditions such as cancer via excessive delivery of oxygen and nutrients. Recent studies have demonstrated that understanding the molecular basis of natural agents in angiogenesis is critical for the development of promising cancer therapeutics. In this study, auriculasin, an active component from Flemingia philippinensis, was found to exert strong anti-angiogenesis activity. Treatment with auriculasin suppressed proliferation of human umbilical vein endothelial cells (HUVECs) by modulating expression of Bcl-2, Bcl- XL , and vascular endothelial growth factor (VEGF). Further, auriculasin inhibited VEGF-induced chemotactic migration, invasion, and capillary-like structure formation of endothelial cells. In addition, auriculasin abrogated VEGF-induced vascular network formation around rat aortic rings as well as blocked accumulation of hemoglobin, endothelial cells and VEGF in the Matrigel plug of C57BL/6 mice. The inhibitory effect of auriculasin on angiogenesis was well correlated with inhibition of VEGF receptor 2 (VEGFR2) activation as well as phosphorylation of intracellular downstream protein kinases of VEGFR2 containing Akt, mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K), p-38, extracellular signal-related kinase (ERK), and Src. Taken together, this study reports that auriculasin potently inhibits angiogenesis by modulating VEGFR2-related signaling pathways, which further validates its great potential in clinical applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Liver resection is a potentially curative therapy for hepatocellular carcinoma (HCC). LLR is a newly developed and safe technique associated with shorter hospital stay, less pain, better cosmetic outcomes, and similar complication rates as open surgery; however, data on its long-term outcomes remain scarce., Methods: We retrospectively examined the clinical and follow-up data of 234 patients who underwent LLR (performed by a single surgeon in all cases) for the primary treatment of HCC between July 2007 and December 2015 at Asan Medical Center., Results: The mean patient age was 55.63 (range 31-76) years; 167 were men. The median follow-up duration was 38 (range 6-116) months. A total of 227 patients (97.0%) had Child-Turcotte-Pugh grade A disease. Of them, 167 (71.4%) underwent anatomical resections and 63 (28.6%) underwent non-anatomical partial hepatectomies. Overall survival rates were 98.3, 91.7, and 87.1%, and recurrence-free survival rates were 82.1, 67.5, and 55.3% at 1, 3, and 5 years, respectively. In Cox regression analysis, anatomical resection was a risk factor for recurrence (univariate analysis: hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.31-0.75; p = 0.001; multivariate analysis: HR 0.59; 95% CI 0.38-0.94; p = 0.025)., Conclusions: LLR is an acceptable primary treatment for patients with HCC with good hepatic function and with an appropriate anatomical structure, and is associated with improved prognosis. LLR can achieve lower recurrence rates through anatomical resection.