Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values.CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression.The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300–CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

Background and Objectives: Early diastolic mitral annular tissue (e’) velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e’ velocity in patients with mitral regurgitation (MR). Methods: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively.According to the current guidelines, the cut-off value of e’ velocity was defined as 7 cm/s. Results: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e’ velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634–0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477–0.998;p=0.049). Abnormal e’ velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170–5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189–21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e’ velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308– 0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680–1.356; p<0.001). Conclusions In patients aged <65 years with primary MR, e’ velocity served as an independent predictor of all-cause and cardiovascular deaths.

Background: Mandibular split fractures, in which the fracture occurs exclusively in the posterior wall, are uncommon. This study aimed to enhance clinicians’ understanding of mandibular split fractures and offer insights for future research. Methods: This study included six patients who visited our hospital between January 2020 and June 2023 and were diagnosed with mandibular split fractures. We retrospectively collected data from patients’ medical records on their age, sex, symptoms, mechanism, impact site, associated injuries, and treatment method, as well as the location, pattern, and number of fractures observed on computed tomography (CT) and panoramic images. The frequency of split fractures among all mandibular fractures was calculated. Results: The six patients included three men (50%) and three women (50%), ranging in age from 20 to 71 years (mean age, 49.8 years). The split fractures were located in the symphysis in one patient (16.7%), symphysis to parasymphysis in two patients (33.3%), parasymphysis in one patient (16.7%), and parasymphysis to the body in two patients (33.3%). Four patients (66.7%) had condylar head fractures, while two patients (33.3%) had single split fractures. The mechanism of trauma was a slip-down incident in four cases (66.7%), while two cases (33.3%) were caused by motorcycle traffic accidents. Four patients (67%) underwent intermaxillary fixation, while two patients (33%) improved with conservative treatment. Split fractures were diagnosed in all six patients on CT, whereas the fracture line was not clearly visible on panoramic images. Mandibular split fractures accounted for 5.6% of all mandibular fractures. Conclusion This study provides insights into the clinical characteristics of rare mandibular split fractures and the diagnostic imaging findings. Furthermore, CT scans and three-dimensional image synthesis-instead of panoramic images-may be essential for accurately diagnosing mandibular fractures, including mandibular split fractures, in the future.

Metastasis of lung cancer to the skin is uncommon, presenting in 0.22% to 12% of lung cancer patients, and it is extremely rare for skin metastasis to be the first clinical manifestation of lung cancer. In the few cases where skin metastasis has been reported as the first sign of lung cancer, the patients were typically heavy smokers or had preexisting respiratory diseases and symptoms. This prompted clinicians to consider skin metastasis of a pulmonary malignancy. Large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer that accounts for approximately 3% of lung cancers. LCNEC mainly metastasizes to visceral organs, such as the liver, bone, and brain, and it only shows metastasis to the skin in very rare cases. Herein, we report an unusual case of a metastatic skin lesion as the first sign of primary pulmonary LCNEC, in a 63-year-old woman with no pulmonary symptoms or personal history of smoking or pulmonary disease.

Purpose: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. Results: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). Conclusion Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Purpose: There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). Materials and Methods: Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. Results: Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. Conclusion Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Objective: This study aims to investigate the prevalence and psychological impact of social isolation and loneliness in South Korea. Loneliness and social isolation have been regarded as a risk to both physical and mental health. However, most studies have focused on the elderly; hence, there are limited studies on the characteristics of socially isolated or lonely people considering age. Methods: A sample of 1,700 participants was selected from three major cities in South Korea. In-person interviews were conducted to evaluate loneliness, social isolation and mental health status. Results: Among the participants, the prevalence of social isolation and loneliness was 17.8% and 4.1%, respectively. Males decreased the odds of loneliness (AOR 0.49, 95% CI=0.28–0.87), while increasing the odds of social isolation (AOR 1.44, 95% CI=1.12–1.86) after adjusting for age and sex. Greater depressive and social phobic symptoms were associated with increased odds of loneliness and social isolation. Conclusion Social isolation and loneliness are prevalent among Koreans and associated with depression, social phobic symptoms, and suicidality. This study provides a foundation for further research to investigate nationwide prevalence and a more in-depth analysis of loneliness and social isolation.

Purpose: The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. Materials and Methods: A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core. Results: The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS. Conclusion The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Objective: This study aims to investigate the prevalence and psychological impact of social isolation and loneliness in South Korea. Loneliness and social isolation have been regarded as a risk to both physical and mental health. However, most studies have focused on the elderly; hence, there are limited studies on the characteristics of socially isolated or lonely people considering age. Methods: A sample of 1,700 participants was selected from three major cities in South Korea. In-person interviews were conducted to evaluate loneliness, social isolation and mental health status. Results: Among the participants, the prevalence of social isolation and loneliness was 17.8% and 4.1%, respectively. Males decreased the odds of loneliness (AOR 0.49, 95% CI=0.28–0.87), while increasing the odds of social isolation (AOR 1.44, 95% CI=1.12–1.86) after adjusting for age and sex. Greater depressive and social phobic symptoms were associated with increased odds of loneliness and social isolation. Conclusion Social isolation and loneliness are prevalent among Koreans and associated with depression, social phobic symptoms, and suicidality. This study provides a foundation for further research to investigate nationwide prevalence and a more in-depth analysis of loneliness and social isolation.

Objectives: To develop a Loneliness and Social Isolation scale (LSIS) that can measure both social isolation and loneliness in order to understand the degree of social isolation in Korea. Exploratory and confirmatory factor analysis was used to examine the factorial validity of the scale. Methods: The subjects of the study were 300 adults aged 19 or older who visited Samsung Medical Center and voluntarily expressed their willingness to participate in this research. Exploratory factor analysis (n=150) and confirmatory factor analysis (n=150) were conducted to construct the factorial structure model and to determine the model fit. Results: Exploratory factor analysis showed a three-factor structure with a total variance of 65.8%; factor 1 consisted of social support, factor 2 of social networks, and factor 3 of items representing loneliness. After conducting confirmatory factor analysis on the three-factor models, a three-factor model consisting of 8 items (LSIS-8) and a three-factor model consisting of 6 items (LSIS-6) showed significant goodness-of-fit. Internal consistency for all items was good (Cronbach’s α=0.774), and correlations with existing social isolation and loneliness measures were significant. Conclusion This study is meaningful as provides a tool that comprehensively measures social support, social networks, and loneliness. We believe that the application of such tools that are relatively easy to apply in communities will aid understanding of the current state of social isolation and loneliness in Korea.