BACKGROUND/OBJECTIVES: The extract from Dendropanax morbifera exhibited diverse therapeutic potentials. We aimed to evaluate the efficacy and safety of D. morbifera leaf extract for improving metabolic parameters in human. SUBJECTS/METHODS: A 12-week, double blind, placebo-controlled and randomized trial included a total of 74 adults, and they were assigned to the placebo group (n = 38) or 700 mg/day of D. morbifera group (n = 36). The efficacy endpoints were changes in glycemic, lipid, obesity, and blood pressure (BP) parameters, in addition to the prevalence of metabolic syndrome (MetS) and the numbers of MetS components. Safety was assessed by monitoring adverse events (AEs). RESULTS: After 12 weeks of treatment, the hemoglobin A1c (HbA1c) level significantly decreased in the D. morbifera group compared to that of the placebo group (difference: −0.13 ± 0.20% vs. 0.00 ± 0.28%, P = 0.031; % of change: −2.27 ± 3.63% vs. 0.10 ± 5.10%, P = 0.025). The homeostatic model assessment for insulin resistance level also decreased significantly from its baseline in the D. morbifera group. The systolic BP of D. morbifera group decreased significantly than that of placebo group (difference: −3.9 ± 9.8 mmHg vs. 3.3 ± 11.7 mmHg, P = 0.005; % of change: −2.8 ± 7.7% vs. 3.3 ± 10.2%, P = 0.005). However, the lipid parameters and body composition including body weight did not differ between the groups. The prevalence of MetS (36.8% vs. 13.9%, P = 0.022) and the incidence of MetS (10.5% vs. 13.9%, P = 0.027) at 12 weeks was significantly lower in the D. morbifera group than it was in the placebo group. No serious AEs occurred in either group. CONCLUSIONS Supplementation with D. morbifera extracts over a 12-week period improved metabolic parameters such as HbA1c and BP and reduced the prevalence of MetS.

This study used data from the Korea National Health and Nutrition Examination Survey IV–VII from 2007 to identify the prevalence of obesity and its phenotypes (metabolically unhealthy obesity [MUO] and metabolically healthy obesity [MHO]) and their secular changes. The prevalence of obesity in Korea increased with significant secular changes observed (β=0.326, P trend <0.01) between 2007 and 2017, and especially in men (β=0.682, P trend <0.001) but not in women. The changes in the prevalence of obesity during the study period were different between men and women (P=0.001). The prevalence of MUO significantly increased only in men (β=0.565, P trend <0.01), while that of MHO increased only in women (β=0.179, P<0.05), especially in the younger age group (β=0.308, P<0.01).

Background: Fatty liver and/or increased liver enzyme values have been reported to be associated with incident diabetes. We sought to determine whether increased visit-to-visit liver enzyme variability is associated with incident diabetes. Methods: Study participants were recruited from the Korean Genome and Epidemiologic Study (KoGES). A total of 4,151 people aged 40 to 69 years was recruited and tested every 2 years for up to 12 years. Visit-to-visit aspartate aminotransferase (AST) and alanine aminotransferase (ALT) variability was evaluated in first the 6-year period through the use of various variability measurements: standard deviation (SD), average successive variability, coefficient of variation (CV), and variation independent of mean (VIM). Oral glucose tolerance test was performed at every visit. Results: During the 6-year follow‐up appointments, 13.0% (538/4,151) of people developed incident diabetes. Visit-to-visit AST variability was associated with an increased risk of diabetes independent of conventional risk factors for diabetes (hazard ratio per 1-SD increment [95% confidence interval]: 1.06 [1.00 to 1.11], 1.12 [1.04 to 1.21], and 1.13 [1.04 to 1.22] for SD, CV, and VIM, respectively; all P<0.05); however, no such associations were observed in the visit-to-visit ALT variability. According to alcohol consumption status, both AST and ALT variability were independent predictors for incident diabetes in subjects with heavy alcohol consumption; however, neither AST nor ALT variability was associated with diabetes risk in subjects who did not drink alcohol heavily. Conclusion Visit-to-visit liver enzyme variability is an independent predictor of incident diabetes. Such association was more evident in those who consumed significant amounts of alcohol.

Background/Aims: Several treatment options are currently available for patients with hepatocellular carcinoma (HCC) failing previous sorafenib treatment. We aimed to compare the effectiveness of regorafenib and nivolumab in these patients. Methods: Consecutive HCC patients who received regorafenib or nivolumab after failure of sorafenib treatment were included. Primary endpoint was overall survival (OS) and secondary endpoints were time to progression, tumor response rate, and adverse events. Inverse probability of treatment weighting (IPTW) using the propensity score was conducted to reduce treatment selection bias. Results: Among 150 study patients, 102 patients received regorafenib and 48 patients received nivolumab. Median OS was 6.9 (95% confidence interval [CI], 3.0–10.8) months for regorafenib and 5.9 (95% CI, 3.7–8.1) months for nivolumab (P=0.77 by log-rank test). In multivariable analysis, nivolumab was associated with prolonged OS (vs. regorafenib: adjusted hazard ratio [aHR], 0.54; 95% CI, 0.30–0.96; P=0.04). Time to progression was not significantly different between groups (nivolumab vs. regorafenib: aHR, 0.82; 95% CI, 0.51–1.30; P=0.48). HRs were maintained after IPTW. Objective response rates were 5.9% and 16.7% in patients treated with regorafenib and nivolumab, respectively (P=0.04). Conclusions After sorafenib failure, the use of nivolumab may be associated with improved OS and better objective response rate as compared to using regorafenib.

This study provides a statistical analysis of 1,226 cases of death occurring in Area 8, Seoul Metropolitan Police Agency (Gangseo, Yangcheon, and Guro Police Stations) from January 1 to December 31, 2017. There were 427 postmortem inspection cases in Gangseo, 393 in Yangcheon, 377 in Guro, and 29 in other areas. The number of autopsy cases was 69 in Gangseo, 70 in Yangcheon, 86 in Guro, and seven in other areas. According to the postmortem inspection reports, there were 593 cases of natural death and 336 cases of unnatural death, while in 297 cases the cause of death was unknown. Of the 297 unknown cases, autopsy rates from each police station were as follows: 54 of 99 cases (54.5%) in Gangseo, 60 of 101 cases (59.4%) in Yangcheon, 67 of 93 cases (72.0%) in Guro, and in all four cases (100%) from other areas. Unnatural deaths included 215 cases of suicide, nine cases of homicide, and 64 accidental death, while 48 cases were undetermined. Among the unnatural deaths, the cause of death included 138 cases of hanging, 72 cases of falls from a height, and 32 cases of poisoning. Since this statistical study is based on actual postmortem inspection data for 1,226 cases of death in the eight areas of Seoul (excluding deaths from traffic accidents), it raises issues relating to the current postmortem inspection system, and can be used as reference material for a comprehensive overview of causes of death.

This study provides a statistical analysis of 1,226 cases of death occurring in Area 8, Seoul Metropolitan Police Agency (Gangseo, Yangcheon, and Guro Police Stations) from January 1 to December 31, 2017. There were 427 postmortem inspection cases in Gangseo, 393 in Yangcheon, 377 in Guro, and 29 in other areas. The number of autopsy cases was 69 in Gangseo, 70 in Yangcheon, 86 in Guro, and seven in other areas. According to the postmortem inspection reports, there were 593 cases of natural death and 336 cases of unnatural death, while in 297 cases the cause of death was unknown. Of the 297 unknown cases, autopsy rates from each police station were as follows: 54 of 99 cases (54.5%) in Gangseo, 60 of 101 cases (59.4%) in Yangcheon, 67 of 93 cases (72.0%) in Guro, and in all four cases (100%) from other areas. Unnatural deaths included 215 cases of suicide, nine cases of homicide, and 64 accidental death, while 48 cases were undetermined. Among the unnatural deaths, the cause of death included 138 cases of hanging, 72 cases of falls from a height, and 32 cases of poisoning. Since this statistical study is based on actual postmortem inspection data for 1,226 cases of death in the eight areas of Seoul (excluding deaths from traffic accidents), it raises issues relating to the current postmortem inspection system, and can be used as reference material for a comprehensive overview of causes of death.
Accidental Falls ; Autopsy ; Cause of Death ; Homicide ; Humans ; Poisoning ; Police ; Seoul ; Statistics as Topic ; Suicide

PURPOSE: The purpose of this study was to investigate the efficacy of stereotactic body radiation therapy (SBRT) as a tumor-associated antigen (TAA) presentation method for dendritic cell (DC) sensitization and evaluate its effect in combination with immunotherapy using an intratumoral injection of immature DCs (iDCs). MATERIALS AND METHODS: CT-26 colon carcinoma cell was used as a cancer cell line. Annexin V staining and phagocytosis assays were performed to determine the appropriate radiation dose and incubation time to generate TAAs. BALB/c mice were used for in vivo experiments. Cancer cells were injected into the right legs and left flanks to generate primary and metastatic tumors, respectively. The mice were subjected to radiation therapy (RT) alone, intradermal injection of electroporated DCs alone, or RT in combination with iDC intratumoral injection (RT/iDC). Tumor growth measurement and survival rate analysis were performed. Enzyme-linked immunospot and cytotoxicity assays were performed to observe the effect of different treatments on the immune system. RESULTS: Annexin V staining and phagocytosis assays showed that 15 Gy radiation dose and 48 hours of incubation was appropriate for subsequent experiments. Maximum DC sensitization and T-cell stimulation was observed with RT as compared to other TAA preparation methods. In vivo assays revealed statistically significant delay in the growth of both primary and metastatic tumors in the RT/iDC group. The overall survival rate was the highest in the RT/iDC group. CONCLUSION: The combination of SBRT and iDC vaccination may enhance treatment effects. Clinical trials and further studies are warranted in the future.
Animals ; Annexin A5 ; Cell Line ; Colon ; Dendritic Cells ; Immune System ; Immunotherapy ; Injections, Intradermal ; Leg ; Methods ; Mice ; Phagocytosis ; Radiation Dosage ; Radiosurgery ; Survival Rate ; T-Lymphocytes ; Vaccination

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.
Classification ; Discrimination (Psychology) ; Disease-Free Survival ; Humans ; Joints ; Neoplasm Staging ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors ; Pancreas ; Survival Rate

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.
Apolipoprotein A-I ; Apolipoproteins ; Apolipoproteins B ; Cardiovascular Diseases ; Cholesterol, LDL ; Diabetes Mellitus, Type 2 ; Ezetimibe ; Fatty Acids, Nonesterified ; Hand ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea ; Liver ; Rosuvastatin Calcium ; Triglycerides

PURPOSE: Platycodon grandiflorum (PG) is known to have effective antimicrobial and anticancer activity. The main bioactive components of PG are saponins, and these could contribute to anti-inflammatory activity. However, little is known about the anti-inflammatory effect of PG. In this study, we aim to assess the anti-inflammatory response to Red PG Extract (RPGE) in splenocytes under ex vivo conditions. METHODS: The cell viability of isolated splenocytes taken from mice was analyzed by performing a Cell Counting Kit-8 assay. The productions of nitric oxide (NO) and cytokines (specifically interleukin-6 (IL-6) and interleukin-10 (IL-10)) were measured utilizing Griess reagent and ELISA, respectively. RESULTS: We found that co-treatment with RPGE and Lipopolysaccharide (LPS) decreased isolated splenocyte proliferation as compared with that of the LPS-stimulated control. We also observed that RPGE markedly suppressed NO synthesis and IL-6 production that was induced by LPS. There were no significant differences of IL-10 production between co-treatment with RPGE plus LPS and treatment with LPS alone. CONCLUSION: When taken together, our data has shown that RPGE mitigates LPS-induced inflammation in splenocytes isolated from mice. Further research is surely needed to confirm the anti-inflammation effects of RPGE in an in vivo model.
Animals ; Cell Count ; Cell Survival ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Inflammation ; Interleukin-10 ; Interleukin-6 ; Mice ; Nitric Oxide ; Platycodon ; Saponins