Purpose: Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases caused by heterozygous mutation in the NF1 gene. Mutation detection is complex owing to the large size of the NF1 gene, the presence of a high number of partial pseudogenes, and the great variety of mutations. We aimed to study the mutation spectrum of NF1 gene in Korean patients with NF1. Materials and Methods: We have analyzed total 69 unrelated patients who were clinically diagnosed with NF1. PCR and sequencing of the NF1 gene was performed in all unrelated index patients. Additionally, multiplex ligation-dependent probe amplification (MLPA) test of the NF1 and SPRED1 gene analysis (sequencing and MLPA test) were performed in patients with negative results from NF1 gene sequencing analysis. Results: Fifty-five different variants were identified in 60 individuals, including six novel variants. The mutations included 36 single base substitutions (15 missense and 21 nonsense), eight splicing mutations, 13 small insertion or deletions, and three gross deletions. Most pathogenic variants were unique. The mutations were evenly distributed across exon one through 58 of NF1, and no mutational hot spots were found. When fulfilling the National Institutes of Health criterion for the clinical diagnosis of NF1, the detection rate was 84.1%. Cafe-au-lait macules were observed in all patients with NF1 mutations. There is no clear relationship between specific mutations and clinical features. Conclusion This study revealed a wide spectrum and genetic basis of patients with NF1 in Korea. Our results aim to contribute genetic management and counseling.

Objective: To investigate the effects of dietary habits on general and abdominal obesity in community-dwelling patients with schizophrenia spectrum disorder according to sex. Methods: A total of 270 patients with schizophrenia spectrum disorder registered at mental health welfare centers and rehabilitation facilities were recruited. General obesity was defined as a body mass index ≥ 30 kg/m 2 , and abdominal obesity was defined as a waist circumstance ≥ 90 cm in men and ≥ 85 cm in women. Dietary habits were evaluated using dietary guidelines published by the Korean Ministry of Health and Welfare. Demographic and clinical characteristics along with dietary habits and information related to obesity were collected. Factors related to obesity were evaluated separately by sex. Results: Dietary habits differed according to sex, in that scores for healthy eating habits were lower in men than in women. In men, the prevalences of general and abdominal obesity were 17.0% and 37.3%, respectively. In women, the prevalences of general and abdominal obesity were 23.1% and 38.5%, respectively. Regression analysis showed that the scores of regular eating habits were negatively associated with general and abdominal obesity in men, and the scores of healthy eating habits were negatively associated with general and abdominal obesity in women. Conclusion Among patients with schizophrenia, regular eating habits might reduce the risk of obesity in men, and healthy eating habits might reduce the risk of obesity in women. Nutrition education should be provided to community-dwelling patients with schizophrenia to prevent obesity in this population.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies

Purpose: The ginger rhizome (Zingiber officinale) is widely cultivated as a spice for its aromatic and pungent components. One of its constituents, 6-hydroxydopamine (6-OHDA) is usually thought to cross the cell membrane through dopamine uptake transporters, and induce inhibition of mitochondrial respiration and the generation of intracellular reactive oxygen species (ROS). This study examines the neuroprotective effect and acetylcholinesterase (AChE) inhibitory activity of fermented ginger extracts (FGEs) on 6-OHDA induced toxicity in SH-SY5Y human neuroblastoma cells. Methods: Ginger was fermented using 2 species of Bacillus subtilis, with or without enzyme pretreatment. Each sample was extracted with 70% ethanol. Neurotoxicity was assessed by applying the EZ-Cytox cell viability assay and by measuring lactic dehydrogenase (LDH) release. Morphological changes of apoptotic cell nuclei were observed by Hoechst staining. Cell growth and apoptosis of SH-SY5Y cells were determined by Western blotting and enzyme activity analysis of caspase-3, and AChE enzymatic activity was determined by the assay. Results: In terms of cell viability and LDH release, exposure to FGE showed neuroprotective activities against 6-OHDA stimulated stress in SH-SY5Y cells. Furthermore, FGE reduced the 6-OHDA-induced apoptosis, as determined by Hoechst staining. The occurrence of apoptosis in 6-OHDA treated cells was confirmed by determining the caspase-3 activity. Exposure to 6-OHDA resulted in increased caspase-3 activity of SH-SY5Y cells, as compared to the unexposed group. However, pre-treatment with FGE inhibited the activity of caspase-3. The neuroprotective effects of FGE were also found to be caspase-dependent, based on reduction of caspase-3 activity. Exposure to FGE also inhibited the activity of AChE induced by 6-OHDA, in a dose-dependent manner. Conclusion Taken together, our results show that FGE exhibits a neuroprotective effect in 6-OHDA treated SH-SY5Y cells, thereby making it a potential novel agent for the prevention or treatment of neurodegenerative disease.

Objective: This study identified the distribution of lymphocele, as well as the factors associated with lymphocele formation, in patients undergoing pelvic and/or para-aortic lymph node dissection (PLND and/or PALND) for gynecologic malignancies. Methods: This study was retrospective, and data were collected from patients who underwent surgical procedures including lymphadenectomy due to gynecologic malignancies from March 2013 to May 2016. Lymphocele was defined by postoperative computer tomography within 2 weeks after surgery. Results: A total of 116 patients underwent lymphadenectomy, of whom, 47 (42.0%) developed lymphocele and 14 (12.1%) had symptomatic lymphocele formation. The affecting factors of lymphocele formation were PLND concomitant with PALND and a large amount of blood loss ≥600 mL (P=0.030 and P=0.006, respectively). All clinical factors were not significantly different between patients with symptomatic and asymptomatic lymphocele. Lymphocele developed more frequently in the left side (67.1%) of the body compared to the right side (48.7%), and in the pelvic area (75.9%) compared to the para-aortic area (24.1%, P<0.001, both). Conclusion Lymphocele formation is more prevalent in the left and pelvic area of the body compared to the right and paraaortic side. PLND concurrent with PALND and large amounts of blood loss were significant risk factors for lymphocele formation.

Objective:To preliminarily explore the treatment effect of nivolumab on Chinese non-small-cell lung cancer (NSCLC) patients with brain metastases, and further enrich the evidences of programmed death-ligand 1 (PD-1) monoclonal antibody in the treatment of NSCLC patients with brain metastases.Methods:The clinical and pathological data of 22 NSCLC patients with brain metastases treated with nivolumab were collected. The electronic imaging data were collected to confirm the treatment effect and time point of disease progression, and the survival data of the patients were obtained through follow-up.Results:Twenty-one patients were evaluated for the intracranial treatment effect. The intracerebral objective response rate (IORR) was 28.6%, the intracranial disease control rate (IDCR) was 47.6%. The median intracranial progression-free-survival (iPFS) of all the 22 patients was 5.2 months. Both the 1-year and 2-year survival rates were 56.7%.Conclusions:The treatment effect of PD-1 monoclonal antibody on NSCLC patients with brain metastases is similar as those without brain metastases.

Objectives: This study examined the dietary characteristics and needs for community kitchens among young adults of single-person households in Seoul according to the cooking attitude. Methods: During April 2018, an online survey was conducted on young adults of singleperson households in their 20s and 30s residing in Seoul. The respondents were classified into the more positive cooking attitude group (More Positive Group; n=152, mean=4.11) and the less positive cooking attitude group (Less Positive Group; n=190, mean=3.03) based on the mean score (3.51) of the 4-item 5-point Likert scales measuring the cooking attitude. The responses of the two groups were compared. Results: Approximately 90% of the More Positive Group had the cooking ability to prepare ordinary meals or more advanced cooking skills, whereas only 61% of the Less Positive Group had such skills. Approximately a half of the More Positive Group cooked at home three times a week or more; only 30% of the Less Positive Group did so, and more than 30% of the group seldom cooked. The More Positive Group had higher mean scores in the levels of satisfaction with dietary life and care for food safety and nutrition than the Less Positive Group. Approximately 30% of all the respondents expressed their needs for community kitchens. The most frequently answered reason for such needs was “being able to have a meal with others”. Conclusions The young adults of single-person households with a more positive cooking attitude possessed a higher cooking ability, cooked more often, and cared more about food safety and nutrition than those with a less positive cooking attitude. There were moderate needs for community kitchens among young adults of single-person households living in Seoul. Therefore, societal efforts to improve their cooking attitude would be meaningful for improving their quality of dietary life. Cooking lessons or social dining programs based on community kitchens could be an option.

Objective: This study identified the distribution of lymphocele, as well as the factors associated with lymphocele formation, in patients undergoing pelvic and/or para-aortic lymph node dissection (PLND and/or PALND) for gynecologic malignancies. Methods: This study was retrospective, and data were collected from patients who underwent surgical procedures including lymphadenectomy due to gynecologic malignancies from March 2013 to May 2016. Lymphocele was defined by postoperative computer tomography within 2 weeks after surgery. Results: A total of 116 patients underwent lymphadenectomy, of whom, 47 (42.0%) developed lymphocele and 14 (12.1%) had symptomatic lymphocele formation. The affecting factors of lymphocele formation were PLND concomitant with PALND and a large amount of blood loss ≥600 mL (P=0.030 and P=0.006, respectively). All clinical factors were not significantly different between patients with symptomatic and asymptomatic lymphocele. Lymphocele developed more frequently in the left side (67.1%) of the body compared to the right side (48.7%), and in the pelvic area (75.9%) compared to the para-aortic area (24.1%, P<0.001, both). Conclusion Lymphocele formation is more prevalent in the left and pelvic area of the body compared to the right and paraaortic side. PLND concurrent with PALND and large amounts of blood loss were significant risk factors for lymphocele formation.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is a complex mixture of subclasses with heterogeneous atheroprotective activities. We analyzed HDL-C subclass in relation to cardiovascular risk and metabolic syndrome (MetS) in a population with high HDL-C levels. METHODS: A total of 300 Korean individuals with high HDL-C levels (≥2.331 mmol/L) were enrolled following a comprehensive general medical examination including body composition analysis. HDL3-C levels were measured using the HDL3-EX SEIKEN kit (Randox Ltd., Crumlin, UK) and non-HDL3-C levels were calculated by subtracting HDL3-C levels from total HDL-C levels. RESULTS: HDL3-C levels and HDL3-C proportion had a weak positive correlation with low-density lipoprotein cholesterol (LDL-C) and triglycerides (r=0.21, r=0.25; r=0.26, r=0.34, respectively, all P<0.001); in contrast, non-HDL3-C levels had a weak negative correlation with these parameters (r=−0.17 and r=−0.25, respectively, both P<0.005). HDL3-C levels and HDL3-C proportion were significantly higher in the MetS group (N=8) than in the non-MetS group (0.71 vs 0.63 mmol/L, P=0.001; 29.7 vs 25.8%, P=0.001, respectively); these were the only predictors of MetS among the lipid variables (areas under the curves [AUC]=0.84 and 0.83, respectively, both P=0.001). CONCLUSIONS In populations with high HDL-C levels, HDL-C subclass may provide a greater amount of information on cardiovascular risk and MetS than HDL-C levels alone.

BACKGROUND: Differences in the performance of suggested warfarin dosing algorithms among different ethnicities and genotypes have been reported; this necessitates the development of an algorithm with enhanced performance for specific population groups. Previous warfarin dosing algorithms underestimated warfarin doses in VKORC1 1173C carriers. We aimed to develop and validate a new warfarin dosing algorithm for Korean patients with VKORC1 1173C. METHODS: A total of 109 patients carrying VKORC1 1173CT (N=105) or 1173CC (N=4) were included in this study. Multiple regression analysis was performed to deduce a new dosing algorithm. Following literature searches for genotype-guided warfarin dosing algorithms, 21 algorithms were selected and evaluated using the correlation coefficient (ρ) of actual dose and estimated dose, mean error, and root mean square error. RESULTS: The developed algorithm is as follows: maintenance dose (mg/week)=exp [3.223−0.009×(age)+0.577×(body surface area [BSA])+0.178×(sex)−0.481×(CYP2C9 genotype)+0.227×(VKORC1 genotype)]. Integrated variables explained 44% of the variance in the maintenance dose. The predicted and actual doses showed moderate correlation (ρ=0.641) with the best performance with a mean error of −1.30 mg/week. The proportion of underestimated groups was 17%, which was lower than with the other algorithms. CONCLUSIONS This is the first study to develop and validate a warfarin dosing algorithm based on data from VKORC1 1173C carriers; it showed superior predictive performance compared with previously published algorithms.