• YAKHAK HOEJI
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• v.42 no.1
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• pp.25-30
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• 1998

This study was designed to compare the absorption fraction and extent of ketoprofen gels and a matrix typed ketoprofen plaster patch. 3g (90mg as ketoprofen) of the two gels whi ch has oleohydrogel or hydrogel as a base, respectively, and 3 pieces of plaster patches (90mg as ketoprofen) were, applied in the area of 210$cm^2$ on forearm in 12 volunteers by cross over design. Blood samples were collected serially up to 24 hours and the plasma concentrations of ketoprofen were analyzed by HPLC using flurbiprofen as an internal standard. The detection limit of the assay was 1ng/ml of ketoprofen in plasma. The pharmacokinetic parameters (e.g. $AUC_{24hr}$, $AUMC_{24hr}$, MRT, Fraction Absorbed) were calculated from the plasma concentrations time data of each volunteer. The oleo-hydrogel showed significantly higher absorption fraction and extent of ketoprofen than the current hydrogel. The mean plasma concentrations of the oleo-hydrogel were increased to 98.46${\pm}$23.15ng/ml by 6 hour after application, and increased futher to 100.61${\pm}$18.65ng/ml at 24 hour. On the other hand, those of the hydrogel were increased 17.61${\pm}$18.65ng/ml at 5 hour to 34.68${\pm}$9.65ng/ml at 24 hour gradually. Therefore the plasma concentrations of oleo-hydrogel at each measured time were 3~7 times greater than those of the hydrogel with statistical significance. The $AUC_{24hr}$ (1797.26${\pm}$52.09ng.h/ml) of the oleo-hydrogel was 3.5 times greater (P<0.05) than that (516.17${\pm}$104.52ng.h/ml) of the hydrogel. The plaster patches showed higher bioavailability ($AUC_{24hr}$ 2877.37${\pm}$578.27ng.h/ml) than the olea-hydrogel ($AUC_{24hr}$ 1797.26${\pm}$52.09ng.h/ml) without statistical significance. But the absorption fraction of the oleo-hydrogel was rather higher than that of the plaster patches during the first 6 hours after administration. These results suggest that newly developed ketoprofen gel which is used oleo-hydrogel as a base would show excellent skin permeation on topical application for the corresponding clinical indications and could be absorbed as well as plaster patches.

• Journal of Gastric Cancer
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• v.21 no.3
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• pp.268-278
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• 2021

Purpose: While several prognostic models for the stratification of death risk have been developed for patients with advanced gastric cancer receiving first-line chemotherapy, they have seldom been tested in the Chinese population. This study investigated the performance of these models and identified the optimal tools for Chinese patients. Materials and Methods: Patients diagnosed with metastatic or recurrent gastric adenocarcinoma who received first-line chemotherapy were eligible for inclusion in the validation cohort. Their clinical data and survival outcomes were retrieved and documented. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the predictive ability of the models. Kaplan-Meier curves were plotted for patients in different risk groups divided by 7 published stratification tools. Log-rank tests with pairwise comparisons were used to compare survival differences. Results: The analysis included a total of 346 patients with metastatic or recurrent disease. The median overall survival time was 11.9 months. The patients were different into different risk groups according to the prognostic stratification models, which showed variability in distinguishing mortality risk in these patients. The model proposed by Kim et al. showed relative higher predicting abilities compared to the other models, with the highest χ² (25.8) value in log-rank tests across subgroups, and areas under the curve values at 6, 12, and 24 months of 0.65 (95% confidence interval [CI]: 0.59-0.72), 0.60 (0.54-0.65), and 0.63 (0.56-0.69), respectively. Conclusions: Among existing prognostic tools, the models constructed by Kim et al., which incorporated performance status score, neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, and tumor differentiation, were more effective in stratifying Chinese patients with gastric cancer receiving first-line chemotherapy.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.398-406
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• 2018

Objective: Hospitalization of patients with delirium after visiting the emergency department (ED) is often required. However, the readmission risk after discharge from the ED should also be considered. This study aimed to explore whether (i) immediate hospitalization influences the readmission risk of patients with delirium; (ii) the readmission risk is affected by various risk factors; and (iii) the healthcare cost differs between groups within 28 days of the first ED visit. Methods: Using the National Health Insurance Research Database, the data of 2,780 subjects presenting with delirium at an ED visit from 2000 to 2008 were examined. The readmission risks of the groups of patients (i.e., patients who were and were not admitted within 24 hours of an ED visit) within 28 days were compared, and the effects of the severities of different comorbidities (using Charlson's comorbidity index, CCI), age, gender, diagnosis and differences in medical healthcare cost were analyzed. Results: Patients without immediate hospitalization had a higher risk of readmission within 3, 7, 14, or 28 days of discharge from the ED, especially subjects with more severe comorbidities ($CCI{\geq}3$) or older patients (${\geq}65years$). Subjects with more severe comorbidities or older subjects who were not admitted immediately also incurred a greater healthcare cost for re-hospitalization within the 28-day follow-up period. Conclusion: Patients with delirium with a higher CCI or of a greater age should be carefully considered for immediate hospitalization from ED for further examination in order to reduce the risk of re-hospitalization and cost of healthcare.

• Clinical and Molecular Hepatology
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• v.24 no.4
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• pp.384-391
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• 2018

Backgrounds/Aims: The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis. Methods: A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ${\geq}7.9kPa$. Results: A total of 214 patients were included in the analysis, and 62% of them had a BMI ${\geq}25kg/m^2$. During follow-up, 4% of patients showed transaminase elevation (<1.5 times normal). Most patients had a viral DNA level <2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P<0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ${\geq}25kg/m^2$ versus 56% of patients without SF (P<0.05). Conclusions: In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.

• Journal of Gastric Cancer
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• v.22 no.2
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• pp.107-119
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• 2022

Purpose: We aimed to explore whether the prognosis of patients treated with capecitabine and oxaliplatin (XELOX) or S-1 and oxaliplatin (SOX) regimens who received fewer cycles of chemotherapy after D2 radical resection for gastric cancer (GC) would be non-inferior to that of patients who received the standard number of cycles of chemotherapy. Materials and Methods: Data on patients who received XELOX or SOX chemotherapy after undergoing D2 radical resection at Harbin Medical University Cancer Hospital between January 2011 and May 2016 were collected. Results: In patients who received 4, 6, and 8 cycles of chemotherapy, the 5-year overall survival (OS) rates were 59.4%, 64.8%, and 62.7%, respectively. Compared to patients who received 4 cycles of chemotherapy, those who received 6 cycles (hazard ratio [HR], 0.882; 95% confidence interval [CI], 0.599-1.299; P=0.52) or 8 cycles (HR, 0.882; 95% CI, 0.533-1.458; P=0.62) of chemotherapy did not exhibit significantly prolonged OS. The 3-year disease-free survival (DFS) rate of patients who received 4, 6, and 8 cycles of chemotherapy was 62.1%, 67.2%, and 60.8%, respectively. Compared to patients who received 4 cycles of chemotherapy, those who received 6 cycles (HR, 0.835; 95% CI, 0.572-1.221; P=0.35) or 8 cycles (HR, 0.972; 95% CI, 0.606-1.558; P=0.91) of chemotherapy did not show significantly prolonged DFS. However, the 3-year DFS and 5-year OS rates of patients who received 6 cycles of chemotherapy appeared to be superior to those of patients who received 4 and 8 cycles of chemotherapy. Conclusions: For patients with stage III GC, 4 to 6 cycles of XELOX or SOX chemotherapy may be a favorable option. This study provides a rationale for further randomized clinical trials.

• Pediatric Infection and Vaccine
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• v.29 no.1
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• pp.37-45
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• 2022

Purpose: During the coronavirus disease 2019 (COVID-19) pandemic, we conducted a Delphi survey that included the experts from the field of COVID-19 immunization in children aged 5-11 years. The aim was to organize collective expert opinions on COVID-19 vaccination in young children in the Republic of Korea, and so thus assist the vaccination policy. Methods: The panels included pediatric infectious disease specialists, preventive medicine experts, infectious disease physicians, and COVID-19 vaccine experts consulting the Ministry of Health and Welfare. The Delphi survey was conducted online using a questionnaire from February 14 to February 27, 2022. Results: The Delphi panels agreed that children were vulnerable to COVID-19, and the severity of illness was modest. Furthermore the panels reported that children with chronic illness were more susceptible to a worsening clinical course. There were generally positive opinions on the effectiveness of COVID-19 vaccination in children aged 5-11 years, and experts gathered a slightly positive opinion that the adverse events of pediatric COVID-19 were not numerous. The benefits of COVID-19 vaccination were evaluated at a level similar to the potential risks in children. Currently, the only approved mRNA platform vaccine in children seemed to be sustainable; however, the recombinant protein platform COVID-19 vaccines were evaluated as better options. Conclusions: Due to the surge of the Omicron variant and an increase in pediatric cases, the COVID-19 vaccination in young children may have to be considered. Panels had neutral opinions regarding the COVID-19 vaccination in children aged 5-11 years. Thus monitoring of the epidemiology and the data about the safety of COVID-19 vaccination should be continued.

• Journal of Gastric Cancer
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• v.22 no.3
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• pp.184-196
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• 2022

Purpose: Total or proximal gastrectomy of the upper-third early gastric cancer (u-EGC) often causes severe post-gastrectomy syndrome, suggesting that these procedures are extremely invasive for patients without pathologically positive lymph node (LN) metastasis. This study aimed to evaluate the clinical applicability of a stomach function-preserving surgery, local resection (LR), with prophylactic left gastric artery (LGA)-basin dissection (LGA-BD). Materials and Methods: The data of patients with u-EGC (pathologically diagnosed as T1) were retrospectively analyzed. Total gastrectomy was performed in 30 patients, proximal gastrectomy in 45, and subtotal gastrectomy in 6; the LN status was evaluated assuming that the patients had already underwent LR + LGA-BD. This procedure was considered feasible in patients without LN metastases or in patients with cancer in the LGA basin. The reproducibility of the results was also evaluated using an external validation dataset. Results: Of the 82 eligible patients, 79 (96.3%) were cured after undergoing LR + LGA-BD, 74 (90.2%) were pathologically negative for LN metastases, and 5 (6.1%) had LN metastases, but these findings were only observed in the LGA basin. Similarly, of the 406 eligible tumors in the validation dataset, 396 (97.5%) were potentially curative. Tumors in the lesser curvature, post-endoscopic resection status, and small tumors (<20 mm) were considered to be stronger indicators of LR + LGA-BD as all subpopulation cases met our feasibility criteria. Conclusions: More than 95% of the patients with u-EGC might be eligible for LR + LGA-BD. This function-preserving procedure may contribute to the development of u-EGC without pathological LN metastases, especially for tumors located at the lesser curvature.

• Archives of Craniofacial Surgery
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• v.23 no.4
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• pp.152-162
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• 2022

Background: The efficacy and safety of equine cartilage as a competent xenograft material for rhinoplasty were evaluated and compared to the outcomes of rhinoplasty using silicone implants. Methods: We performed a multicenter, double-blind, non-inferiority, and randomized confirmatory study. Fifty-six patients were randomized 1:1 to the study group (using MegaCartilage-E) and control group (using silicone implants). The Rhinoplasty Outcome Evaluation (ROE) score, photo documentation, Global Aesthetic Improvement Scale (GAIS), and adverse event data were obtained until 12 months after surgery. The primary efficacy, which is the change in ROE score 6 months after surgery, was assessed in the modified intention-to-treat set. The secondary efficacy was evaluated in the per-protocol set by assessing the change in ROE score 6 and 12 months after surgery and nasofrontal angle, the height of the nasion, and GAIS 1, 6, and 12 months after surgery. Results: The change in ROE score of the study group was non-inferior to that of the control group; it increased by 24.26±17.24 in the study group and 18.27±17.60 in the control group (p= 0.213). In both groups, all secondary outcome measures increased, but there was no statistical difference. In the safety set, treatment-emergent adverse events occurred in 10 patients (35.71%) in the study group and six patients (21.43%) in the control group (p= 0.237). There were 13 adverse device events in the study group and six adverse device events in the control group (p= 0.515). Conclusion: Processed equine cartilage can be used effectively and safely as xenograft material for rhinoplasty.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

• Journal of Animal Science and Technology
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• v.65 no.1
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• pp.244-257
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• 2023

The study aimed to investigate the effect of low-frequency oscillations on the cow udder, milk parameters, and animal welfare during the automated milking process. The study's objective was to investigate the impact of low-frequency oscillations on the udder and teats' blood circulation by creating a mathematical model of mammary glands, using milkers and vibrators to analyze the theoretical dynamics of oscillations. The mechanical vibration device developed and tested in the study was mounted on a DeLaval automatic milking machine, which excited the udder with low-frequency oscillations, allowing the analysis of input parameters (temperature, oscillation amplitude) and using feedback data, changing the device parameters such as vibration frequency and duration. The experimental study was performed using an artificial cow's udder model with and without milk and a DeLaval milking machine, exciting the model with low-frequency harmonic oscillations (frequency range 15-60 Hz, vibration amplitude 2-5 mm). The investigation in vitro applying low-frequency of the vibration system's first-order frequencies in lateral (X) direction showed the low-frequency values of 23.5-26.5 Hz (effective frequency of the simulation analysis was 25.0 Hz). The tested values of the first-order frequency of the vibration system in the vertical (Y) direction were 37.5-41.5 Hz (effective frequency of the simulation analysis was 41.0 Hz), with higher amplitude and lower vibration damping. During in vivo experiments, while milking, the vibrator was inducing mechanical milking-similar vibrations in the udder. The vibrations were spreading to the entire udder and caused physiotherapeutic effects such as activated physiological processes and increased udder base temperature by 0.57℃ (p < 0.001), thus increasing blood flow in the udder. Used low-frequency vibrations did not significantly affect milk yield, milk composition, milk quality indicators, and animal welfare. The investigation results showed that applying low-frequency vibration on a cow udder during automatic milking is a non-invasive, efficient method to stimulate blood circulation in the udder and improve teat and udder health without changing milk quality and production. Further studies will be carried out in the following research phase on clinical and subclinical mastitis cows.