According to the American Association for the Study of Liver Diseases (AASLD) treatment guidelines for hepatocellular carcinoma (HCC), the role of surgery has been expanded beyond the Barcelona ...Clinic Liver Cancer (BCLC) algorithm. We compared primary hepatectomy (PH) with transarterial chemoembolization (TACE) in patients with intermediate‐ to advanced‐stage (BCLC stage B/C) HCC to determine the current evidence. Through a database search, we included 18 high‐quality studies (one randomized controlled trial RCT, five propensity‐score matching nonrandomized comparative trials NRCTs, and 12 NRCTs) that compared survival outcomes of 5,986 patients after PH and TACE. We found significant survival benefits for PH over TACE in BCLC stage B/C patients (hazard ratio HR, 0.59; 95% confidence interval CI, 0.51‐0.67; P < 0.00001; I2 = 84%). According to the BCLC, both stage B and stage C patients showed significantly better overall survival (OS) for PH compared to TACE (HR, 0.53; 95% CI, 0.43‐0.65; P < 0.00001; I2 = 77%; HR, 0.67; 95% CI, 0.59‐0.77; P < 0.00001; I2 = 79%, respectively). Five‐year survival rates for PH were significantly higher than those for TACE in BCLC stage B/C, stage B, and BCLC stage C patients (odds ratio OR, 2.71, 2.77, and 3.03, respectively; all P < 0.00001). Survival benefits persisted across subgroup, sensitivity, and metaregression analyses; interstudy heterogeneity remained constant. Conclusion: This meta‐analysis suggests that surgical resection provides survival benefits in patients with intermediate‐ to advanced‐stage HCC. The evidence found herein may assist in the choice of treatment modality based on diverse definitions of operability. (Hepatology 2018).
Metabolic syndrome (MetS) which is caused by obesity and insulin resistance, is well known for its predictive capability for the risk of type 2 diabetes mellitus and cardiovascular disease. The ...development of MetS is associated with multiple genetic factors, environmental factors and lifestyle. We performed a genome-wide association study to identify single-nucleotide polymorphism (SNP) related to MetS in large Korean population based samples of 1,362 subjects with MetS and 6,061 controls using the Axiom® Korean Biobank Array 1.0. We replicated the data in another sample including 502 subjects with MetS and 1,751 controls. After adjusting for age and sex, rs662799 located in the APOA5 gene were significantly associated with MetS. 15 SNPs in GCKR, C2orf16, APOA5, ZPR1, and BUD13 were associated with high triglyceride (TG). 14 SNPs in APOA5, ALDH1A2, LIPC, HERPUD1, and CETP, and 2 SNPs in MTNR1B were associated with low high density lipoprotein cholesterol (HDL-C) and high fasting blood glucose respectively. Among these SNPs, 6 TG SNPs: rs1260326, rs1260333, rs1919127, rs964184, rs2075295 and rs1558861 and 11 HDL-C SNPs: rs4775041, rs10468017, rs1800588, rs72786786, rs173539, rs247616, rs247617, rs3764261, rs4783961, rs708272, and rs7499892 were first discovered in Koreans. Additional research is needed to confirm these 17 novel SNPs in Korean population.
Printing orientation is an important decision in the initial steps of additive manufacturing, affecting printing accuracy and the mechanical properties of printed products. In addition, printing ...orientation determines the building direction of layers and the layer-by-layer configuration forming the surface geometry.
The purpose of this in vitro study was to evaluate the effect of printing orientation on the printing accuracy, flexural strength, surface characteristics, and microbial response of 3D-printed denture base resin.
Specimens were printed with denture base polymethyl methacrylate (PMMA) in 3 printing orientations (0, 45, and 90 degrees). The printing error rate, flexural strength, roughness, hydrophilicity, surface energy, and response to Candida albicans (C. albicans) were evaluated.
Specimens printed at a 90-degree orientation showed the lowest error rates for length (P<.001), and those printed at a 45-degree orientation showed statistically higher error rates for thickness than those of other groups (P<.001). Flexural strength increased in order of the specimens printed at orientation degrees of 90<45<0 with statistical significance. The 45-degree oriented specimens showed higher roughness and surface energy than those of other groups (P<.001). A higher proportion of C. albicans was found in the specimens printed at orientation degrees of 90<45<0 with statistical significance.
Printing orientation significantly influenced the printing accuracy, flexural strength, roughness, and response to C. albicans. Therefore, the printing orientation should be carefully decided to fabricate products with appropriate properties.
Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains ...unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes. Compared with controls, PA-treated hepatocytes displayed significantly increased CD36 and exosome production. The microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and PA-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. In conclusion, PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile. Moreover, exosomes derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. Therefore, exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH.
To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. ...For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 x 10(-9)) and 6q22 (rs12110693, P = 1.6 x 10(-9)), with the latter approximately 400 kb from the coding sequence of GJA1. For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 x 10(-7)). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 x 10(-12)) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius (P = 1.0 x 10(-11)), tibia (P = 1.6 x 10(-6)) and heel (P = 1.9 x 10(-10)). On chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene) showed consistent associations at the same three sites (P = 2.2 x 10(-3), P = 1.4 x 10(-7) and P = 6.0 x 10(-4), respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.
Nonalcoholic fatty liver disease (NAFLD), together with metabolic syndrome and obesity, has shown a rapid increase in prevalence worldwide and is emerging as a major cause of chronic liver disease ...and liver transplantation. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to development of end-stage liver disease and cardiometabolic disease, resulting in liver-related and non-liver-related mortality. Nonetheless, there is no standardized pharmacotherapy against NASH and many drugs are under development in ongoing clinical trials. To develop a successful anti-NASH drug, it is necessary to select an appropriate target population and treatment outcomes depending on whether the mode of action is anti-metabolic, anti-inflammatory or anti-fibrotic. Recently, innovative surrogate markers have been investigated to replace hard outcomes such as liver histology and mortality and reduce the clinical trial duration. Currently, several drugs with fast track designation are being tested in phase III clinical trials, and many other drugs have moved into phase II clinical trials. Both lean NAFLD and typical obese NAFLD have been extensively studied and genetic variants such as PNPLA3 and TM6SF2 have been identified as significant risk factors for lean NAFLD. In the near future, noninvasive biomarkers and effective targeted therapies for NASH and associated fibrosis are required to develop precision medicine and tailored therapy according to various phenotypes of NAFLD.
Epidemiologic evidence indicates that the prevalence and severity of coronary artery disease vary depending on ethnicity. In this study, a genome-wide association study for coronary artery ...calcification (CAC) was performed in a Korean population-based sample of 400 subjects without prior coronary artery disease and replicated in another of 1,288 subjects. CAC score, as assessed by multi-detector computed tomography, was evaluated in volunteers for screening purposes as part of a routine health examination. CAC score greater than the 90th percentile across the age in each sex group was considered severe CAC. Single nucleotide polymorphisms (SNPs) associated with severe CAC after adjusting for age, sex, hypertension, and diabetes were investigated using the additive model of logistic regression. One SNP (rs10757272 in the intronic region of the CDKN2B-AS1 gene in chromosome 9p21.3) met Bonferroni correction in the discovery set (p = 7.55E-08) and was also significant in the validation set by TaqMan assay (p = 0.036). Subjects with rs10757272 were found to have an increased odds ratio (OR) of having severe CAC in multivariate logistic regression analysis after adjusting for age, sex, hypertension, and diabetes (adjusted OR 3.24 and 95% CI 2.11-4.97). In conclusion, SNP rs10757272 in chromosome 9p21.3 was associated with severe CAC based on age and sex in an asymptomatic community-based Korean population. Therefore, it was associated with promotion of coronary artery calcification in subclinical state.
N-nitrosamines, which are classified as carcinogens by IARC and US EPA, can be easily found in various foods. They are reaction products between nitrogen oxide and secondary amines, but can also be ...generated during fermentation. Ever since the 1960s, when nitrite, used as a preservative in processed meats, was suspected to generate N-nitrosamines, the usage of the food additive has been debated. However, the benefit of nitrite in food supply could not be ignored and the risk-benefit analysis has become a key issue in the use of the additive. For a risk analysis, an accurate estimation of the hazardous material is necessary; therefore, analytical methods for nitrosamines have continuously evolved from the 1950s. Solid supported liquid-liquid extraction and solid phase extractions have replaced the distillation for the clean-up steps, and tandem mass spectrometry is employed for higher selectivity and sensitivity. In the present study, for a better estimation of N-nitrosamine intake, the total diet study samples were prepared for the N-nitrosamines analysis. In order to obtain the most sensitive results, a partial preparation procedure was developed and modified for different food matrices. Among seven N-nitrosamines (N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitrosomorpholine) analyzed in the present study, N-nitrosodiethylamine has shown the highest detection rate in agricultural foods, while N-nitrosodimethylamine has appeared most frequently in livestock and fishery food products. The concentration of N-nitrosodimethylamine was the highest in seasoning.
Although genetic features vary across ethnicities, few genome-wide association studies (GWAS) have reported the genetic determinants of liver enzyme expression. This study was aimed to evaluate the ...associations of genome-wide single nuclear polymorphisms (SNPs) with the liver enzymes in a Korean population.
We performed a GWAS to identify genetic loci influencing liver function, as measured by concentrations of alkaline phosphatase (ALP), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) in in Korean study participants.
A total of 6,488 subjects (4,457 in the discovery and 2,031 in the validation set) were included. The mean subject age was 50.0±10.6 years (male, 53.7%). Among a total of 546,738 SNPs tested, rs651007 and rs579459 located in the ABO gene showed strong associations with ALP (P = 1.63×10-8 and 5.61×10-8, respectively discovery set; P = 4.08×10-15 and 9.92×10-16, respectively validation set). Additionally, rs5751901 and rs2006092, which are located in the GGT1 gene, showed strong associations with GGT (P = 6.44×10-15 and 1.26×10-15, respectively discovery set; P = 4.13×10-10 and 5.15×10-11, respectively validation set). Among the 13 SNPs that showed genome-wide significance with total bilirubin levels, rs10929302 and rs6742078 showed the most significant association (P = 3.08×10-64 and 2.05×10-62, respectively discovery set; P = 1.33×10-116 and 2.24×10-118, respectively validation set). No genome-wide significant associations was found for ALT.
We demonstrated that ABO, GGT1 and UGT1A family were associated with ALP, GGT and BIL, respectively in Korean population. These findings differ from reported results in GWAS in European populations in terms of associated genes and locations, suggesting different genetic mechanisms of liver enzyme regulation according to ethnicity.
Nonalcoholic steatohepatitis (NASH) is considered as a progressive form of nonalcoholic fatty liver disease (NAFLD). To distinguish NASH from nonalcoholic fatty liver (NAFL), we evaluated the ...diagnostic value of circulating miRNAs. Small RNA sequencing was performed on 12 NAFL patients and 12 NASH patients, and the miRNA expression was compared. After selecting miRNAs for the diagnosis of NASH, we analyzed the diagnostic accuracy of each miRNA and the combination of miRNAs. External validation was performed using quantitative reverse transcription PCR. Among the 2,588 miRNAs, 26 miRNAs significantly increased in the NASH group than in the NAFL group. Among the 26 elevated miRNAs in the NASH group, 8 miRNAs were selected, and in silico analysis was performed. Only four miRNAs (miR-21-5p, miR-151a-3p, miR-192-5p, and miR-4449) showed significant area under the receiver operating characteristic curve (AUC) values for NASH diagnosis. The combination of the four miRNAs showed satisfactory diagnostic accuracy for NASH (AUC 0.875; 95% CI 0.676-0.973). External validation revealed similar diagnostic accuracy for NASH (AUC 0.874; 95% CI 0.724-0.960). NASH represents significantly distinct miRNA expression profile compared with NAFL. The combination of serum circulating miRNAs can be used as a novel biomarker for the NASH diagnosis in NAFLD.
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