Objectives: . Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats. Methods: . Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: . In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1β significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01). Conclusion . The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.

Purpose: The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC). Materials and Methods: Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity. Results: Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin. Conclusion The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.

Proximal junctional problems are among the potential complications of surgery for adult spinal deformity (ASD) and are associated with higher morbidity and increased rates of revision surgery. The diverse manifestations of proximal junctional problems range from proximal junctional kyphosis (PJK) to proximal junctional failure (PJF). Although there is no universally accepted definition for PJK, the most common is a proximal junctional angle greater than 10° that is at least 10° greater than the preoperative measurement. PJF represents a progression from PJK and is characterized by pain, gait disturbances, and neurological deficits. The risk factors for PJK can be classified according to patient-related, radiological, and surgical factors. Based on an understanding of the modifiable factors that contribute to reducing the risk of PJK, prevention strategies are critical for patients with ASD.

Owing to rapidly changing global demographics, adult spinal deformity (ASD) now accounts for a significant proportion of the Global Burden of Disease. Sagittal imbalance caused by age-related degenerative changes leads to back pain, neurological deficits, and deformity, which negatively affect the health-related quality of life (HRQoL) of patients. Along with the recognized regional, global, and sagittal spinopelvic parameters, poor paraspinal muscle quality has recently been acknowledged as a key determinant of the clinical outcomes of ASD. Although the Scoliosis Research Society-Schwab ASD classification system incorporates the radiological factors related to HRQoL, it cannot accurately predict the mechanical complications. With the rapid advances in surgical techniques, many surgical options for ASD have been developed, ranging from minimally invasive surgery to osteotomies. Therefore, structured patient-specific management is important in surgical decision-making, selecting the proper surgical technique, and to prevent serious complications in patients with ASD. Moreover, utilizing the latest technologies such as robotic-assisted surgery and machine learning, should help in minimizing the surgical risks and complications in the future.

Purpose: Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to treat desmoid tumor. However, the molecular mechanism of why imatinib works remains unclear. Here, we describe potential roles of NOTCH2 and HES1 in clinical response to imatinib at genome and transcriptome levels. Materials and Methods: We identified somatic mutations in coding and noncoding regions via whole-genome sequencing. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale whole-genome sequencing and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response. Results: Among 20 patients, four (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥ 1 year. With gene-wise functional analyses, we detected a significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on Pan-Cancer Analysis of Whole Genomes data analyses, NOTCH2 mutations affect expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate between responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders. Conclusion Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, and an important therapeutic consideration for desmoid tumor.

In this study, we investigated the chemical profile and effects of RW0117 (Artemisia argyi 65 .5 % ethanol extract) on gastric lesions in rats. We optimized and validated a method to obtain the chemical profile of RW0117. We then investigated the antioxidant and anti-inflammatory effects in vivo, and the protective effects on gastric lesions in vivo. The IC50 of 2,2-diphenyl-1-picrylhydrazyl free radical scavenging considering the antioxidant effects of RW0117 was 166.55 μg/mL, and the IC50 of nitric oxide scavenging considering the antiinflammatory effects was 41.16 μg/mL. Oral administration of RW0117 at lower concentrations (25, 50, 100 mg/ kg) had similar or greater effects than the daily intake conversion concentration (115mg/kg) of a health functional food (Avexol® ) in the acetic acid-induced ulcer and the ethanol-induced gastric injury rat models. In addition, oral administration of RW0117 increased the expression of prostaglandin E2 , which enhances the protective effect in the gastric mucosa in the ethanol-induced gastric injury rat model. These results suggest that RW0117 may have potential therapeutic uses in the protection of the gastric mucosa.

Objectives: In this study, the clinical characteristics of OSA patients and the quality of life before and after CPAP use were compared to determine the degree of improvement in quality of life according to CPAP use. Methods: Age, sex, height, weight, body mass index, Epworth Sleepiness Scale, Modified Mallampatti Score, Montreal Cognitive Assessment-Korean, and Pittsburgh Sleep Quality Index were compared between men and women through medical records. To understand the degree of improvement in quality of life resulting from use of CPAP, a personal telephone call was made to compare the VAS scores for quality of life before and after CPAP use. Results: In height (HT) (Z = -4.525, p< 0.001), weight (BW) (Z = -2.844, p < 0.05), sleep quality (PSQI) (Z = -2.671, p < 0.05), and arousal index (AI) (Z = -2.105, p < 0.05), there was a difference between men and women (p < 0.05). There was no difference in the remaining variables. Cross-analysis (Chi-square test) confirmed a difference between severity and sex of OSA. It has been found that there is no statistically significant order in size according to level-specific severity of OSA for PreCPAP QOL, PostCPAP QOL, CPAPUse Months, and CPAP4Hr/d (%) (p > 0.05). The difference between AHI before and after CPAP was 36.48 ± 21.54 (t = 11.609, p < 0.001) and the difference between QOL before and after CPAP was –25.43 ± 22.06 (t = -7.901,p < 0.001), both of which were significant (p < 0.001). Conclusion Among OSA patients, there were differences in height (HT), weight (BW), sleep quality (PSQI), arousal index (AI), and severity of OSA between men and women, but the quality of life before and after CPAP was different. However, there was no difference between men and women in quality of life before and after CPAP. In addition, quality of life in OSA patients improved after using CPAP

Purpose: Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data. Materials and Methods: This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated. Results: Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007). Conclusion Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.

In this study, we investigated the chemical profile and effects of RW0117 (Artemisia argyi 65 .5 % ethanol extract) on gastric lesions in rats. We optimized and validated a method to obtain the chemical profile of RW0117. We then investigated the antioxidant and anti-inflammatory effects in vivo, and the protective effects on gastric lesions in vivo. The IC50 of 2,2-diphenyl-1-picrylhydrazyl free radical scavenging considering the antioxidant effects of RW0117 was 166.55 μg/mL, and the IC50 of nitric oxide scavenging considering the antiinflammatory effects was 41.16 μg/mL. Oral administration of RW0117 at lower concentrations (25, 50, 100 mg/ kg) had similar or greater effects than the daily intake conversion concentration (115mg/kg) of a health functional food (Avexol® ) in the acetic acid-induced ulcer and the ethanol-induced gastric injury rat models. In addition, oral administration of RW0117 increased the expression of prostaglandin E2 , which enhances the protective effect in the gastric mucosa in the ethanol-induced gastric injury rat model. These results suggest that RW0117 may have potential therapeutic uses in the protection of the gastric mucosa.

Objectives: In this study, the clinical characteristics of OSA patients and the quality of life before and after CPAP use were compared to determine the degree of improvement in quality of life according to CPAP use. Methods: Age, sex, height, weight, body mass index, Epworth Sleepiness Scale, Modified Mallampatti Score, Montreal Cognitive Assessment-Korean, and Pittsburgh Sleep Quality Index were compared between men and women through medical records. To understand the degree of improvement in quality of life resulting from use of CPAP, a personal telephone call was made to compare the VAS scores for quality of life before and after CPAP use. Results: In height (HT) (Z = -4.525, p< 0.001), weight (BW) (Z = -2.844, p < 0.05), sleep quality (PSQI) (Z = -2.671, p < 0.05), and arousal index (AI) (Z = -2.105, p < 0.05), there was a difference between men and women (p < 0.05). There was no difference in the remaining variables. Cross-analysis (Chi-square test) confirmed a difference between severity and sex of OSA. It has been found that there is no statistically significant order in size according to level-specific severity of OSA for PreCPAP QOL, PostCPAP QOL, CPAPUse Months, and CPAP4Hr/d (%) (p > 0.05). The difference between AHI before and after CPAP was 36.48 ± 21.54 (t = 11.609, p < 0.001) and the difference between QOL before and after CPAP was –25.43 ± 22.06 (t = -7.901,p < 0.001), both of which were significant (p < 0.001). Conclusion Among OSA patients, there were differences in height (HT), weight (BW), sleep quality (PSQI), arousal index (AI), and severity of OSA between men and women, but the quality of life before and after CPAP was different. However, there was no difference between men and women in quality of life before and after CPAP. In addition, quality of life in OSA patients improved after using CPAP