Background: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. Methods: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. Results: The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. Conclusion In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

Background: Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice. Methods: In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled. Results: Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42. Conclusion Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

BACKGROUND: This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS: In total, 168 participants (89 boys and 79 girls) aged 10–16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS: Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P<0.001, respectively). In the multiple logistic regression analysis, lower extremity muscle strength was inversely related to the clustered cardiometabolic risk of the children and adolescents with or without adjustment for confounders (OR, 4.32; 95% confidence interval [CI], 1.87–9.97; OR, 7.64; 95% CI, 1.55–37.74, respectively). CONCLUSION: Physical fitness, especially lower extremity muscle strength, is significantly inversely associated with individual and clustered cardiometabolic risks in Korean children and adolescents.
Adolescent ; Body Mass Index ; Child ; Depression ; Humans ; Korea ; Logistic Models ; Lower Extremity ; Muscle Strength ; Odds Ratio ; Pediatric Obesity ; Physical Fitness

BACKGROUND: This study examined the clinical effects of leuprolide acetate in sexual offenders with paraphilic disorders evaluated by means of objective psychiatric assessment. METHODS: The subjects of this study were seven sexual offenders who were being treated by means of an injection for sexual impulse control by a court order. They had been diagnosed with paraphilia by a psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and had been put on probation by the Ministry of Justice between January 2016 and December 2016. RESULTS: After twelve months, we observed significant improvement in symptoms, as decrease of abnormal sexual interest and activity, sexual fantasy, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Impulsivity (GCI-I). There were a mild feminization of the body shape, feelings of fatigue, and mild hot flushes. No other adverse effect was reported. CONCLUSION: These results suggested that the clinical effects of leuprolide acetate in sexual offenders might be an effective treatment and safety strategy.
Criminals* ; Diagnostic and Statistical Manual of Mental Disorders ; Fantasy ; Fatigue ; Feminization ; Humans ; Leuprolide* ; Paraphilic Disorders* ; Psychiatry ; Sexual Behavior ; Social Justice ; Therapeutic Uses*

PURPOSE: Peroxisome proliferator-activated receptor γ (PPARγ) is involved in the pathology of numerous diseases including atherosclerosis, diabetes, obesity, and cancer. Matrix metalloproteinases (MMPs) play a significant role in tissue remodeling related to various processes such as morphogenesis, angiogenesis, tissue repair, invasion, and metastasis. We investigated the effects of PPARγ on MMP expression and invasion in breast cancer cells. METHODS: MCF-7 cells were cultured and then cell viability was monitored in an MTT assay. Western blotting, gelatin zymography, real-time polymerase chain reaction, and luciferase assays were performed to investigate the effect of the synthetic PPARγ ligand troglitazone on MMP expression. Transcription factor DNA binding was analyzed by electrophoretic mobility shift assay. A Matrigel invasion assay was used to assess the effects of troglitazone on MCF-7 cells. RESULTS: Troglitazone did not affect MCF-7 cell viability. 12-O-tetradecanoylphorbol-13-acetate (TPA) induced MMP-9 expression and invasion in MCF-7 cell. However, these effects were decreased by troglitazone. TPA increased nuclear factor κB and activator protein-1 DNA binding, while troglitazone inhibited these effects. The selective PPARγ antagonist GW9662 reversed MMP-9 inhibition by troglitazone in TPA-treated MCF-7 cells. CONCLUSION: Troglitazone inhibited nuclear factor κB and activator protein-1-mediated MMP-9 expression and invasion of MCF-7 cells through a PPARγ-dependent mechanism.
Atherosclerosis ; Blotting, Western ; Breast Neoplasms* ; Breast* ; Cell Survival ; DNA ; Electrophoretic Mobility Shift Assay ; Gelatin ; Luciferases ; Matrix Metalloproteinase 9* ; Matrix Metalloproteinases ; MCF-7 Cells ; Morphogenesis ; Neoplasm Metastasis ; NF-kappa B ; Obesity ; Pathology ; Peroxisomes* ; PPAR gamma ; Real-Time Polymerase Chain Reaction ; Transcription Factor AP-1 ; Transcription Factors

BACKGROUND/AIMS: The clinical outcomes of angiography and transcatheter arterial embolization (TAE) for acute gastrointestinal bleeding (GIB) have not been completely assessed, especially according to bleeding sites. This study aimed to assess the efficacy of angiography and safety of TAE in acute GIB. METHODS: This was a retrospective study evaluating the records of 321 patients with acute GIB who underwent angiography with or without TAE. Targeted TAE was conducted in 134 patients, in whom angiography showed bleeding sources. Prophylactic TAE was performed in 29 patients when the bleeding source was not detected but a specific vessel was strongly suspected by other examinations. The rate of technical success, clinical success, and complications were analyzed. RESULTS: The detection rate of bleeding source via angiography was 50.8% (163/321), which was not different according to the bleeding sites. The detection rate was higher if the probable bleeding source had already been found by another investigation (59.7% vs. 35.8%, p<0.001). TAE sites were upper GIB in 67, mid GIB in 74, and lower GIB in 22. The technical success rate was 99.3% (133/134), and the clinical success rate was 63.0% (104/163). The prophylactic embolization group showed lower clinical success rate than the targeted embolization group (44.8% vs. 67.9%, p=0.06). The TAE-related complication rate was 12.9% (21/163). Ischemia and/or infarction was more common after TAE for mid and lower GIB than for upper GIB (15.6% vs. 3.0%, p=0.007). CONCLUSIONS: Angiography with or without TAE was an effective method for acute GIB. Targeted embolization should be performed if possible given that it has a higher clinical success rate.
Angiography* ; Embolization, Therapeutic ; Gastrointestinal Hemorrhage ; Hemorrhage* ; Humans ; Infarction ; Ischemia ; Methods ; Retrospective Studies

BACKGROUND/AIMS: Helicobacter pylori infection is linked to the development of gastric cancer. H. pylori-associated gastric inflammation is considered to be the first important step in the histogenesis of such neoplasia. However, studies that compare proteome of gastric mucosa infected with or without H. pylori are lacking. METHODS: We employed proteomics analysis on the endoscopic biopsy specimens of gastric mucosa obtained from two groups (30 cases): healthy subjects without H. pylori infection (15 cases), and gastritis patients with H. pylori infection (15 cases). The pooled proteins obtained from gastric mucosa infected with or without H. pylori were separated by two-dimensional gel electrophoresis and analyzed by a computer-aided program. The altered protein expressions were then identified by mass spectrometry and validated by Western blotting and immunohistochemistry. RESULTS: On mass spectrometry using MALDI TOF(TM) Analyzer, the up-regulation of Keratin 1, ezrin, adenosine triphosphate (ATP) synthase subunit alpha mitochondrial isoform c, Keratin type I cytoskeletal 19, and Keratin type I cytoskeletal 9 were identified; in contrast, 71 kd heat shock cognate protein, ATP synthase subunit alpha mitochondrial precursor, and annexin IV were down-regulated. Among them, membrane cytoskeleton linker ezrin was validated using Western blot and immunohistochemistry. CONCLUSIONS: Expression of ezrin was significantly different between the gastric mucosa with and without H. pylori infection. Therefore, ezrin could be considered a promising potential molecular marker for detecting H. pylori infection in gastric mucosa.
Blotting, Western ; Cytoskeletal Proteins/metabolism ; Down-Regulation ; Electrophoresis, Gel, Two-Dimensional ; Female ; Gastric Mucosa/*metabolism/microbiology ; Gastritis/complications/metabolism/pathology ; Gastroscopy ; Helicobacter Infections/complications/metabolism/*pathology ; *Helicobacter pylori ; Humans ; Immunohistochemistry ; Male ; Proteome/*analysis ; *Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Up-Regulation

As the duration of diabetes mellitus (DM) increases, the risk of complications increases and the prevalence of depression becomes higher. Most studies on depression in Korean patients with DM have focused on a point 5-10 years after diagnosis, and there has not been much data reported regarding the early stages of DM, including newly developed DM. In this study, we examined whether blood glucose levels could be associated with emotional symptoms such as depression (DS) and anxiety (AS) in patients newly diagnosed with DM. Serum glucose and HbA1c were measured in 89 patients with DM. The Impact of Event Scale (IES) was used to investigate the extent of the psychological impact of a diagnosis of DM. The IES comprises four elements: hyperarousal, intrusiveness, avoidance, and sleep problems. DS and AS were investigated using the Hospital Anxiety and Depression Scales. DS was observed in 32 patients (36%) and AS was observed in 21 patients (23.6%), indicating a higher prevalence of DS and AS than in the general population. There was an inverse correlation between HbA1c and DS (Pearson's correlation coefficient: R = -0.227; P = 0.035), but no correlation was found for AS. The four elements of the IES had significant correlations with DS and AS. Logistic regression analysis showed that sleep problems (OR = 1.437) and HbA1c (OR = 0.51) were associated with DS, but only intrusiveness (OR = 0.629) showed a correlation with AS. In patients newly diagnosed with DM, DS is associated with sleep problems and low HbA1c levels. Emotional symptoms should be considered as part of glucose control, and efforts to mitigate psychological stress during the initial period of diabetes management should be made.
Anxiety ; Blood Glucose ; Depression ; Diabetes Mellitus ; Glucose ; Humans ; Logistic Models ; Prevalence ; Stress, Psychological ; Weights and Measures

QT prolongation is a serious adverse drug effect, which is associated with an increased risk of Torsade de pointes and sudden death. Many drugs, including both cardiac and non-cardiac drugs, have been reported to cause prolongation of QT interval. Although meperidine has not been considered proarrhythmic, we present a unique case of a 16-year-old boy without an underlying cardiac disease, who developed polymorphic ventricular tachycardia, ventricular fibrillation and QT prolongation after an intravenous meperidine injection. He had no mutation in long QT syndrome genes (KCNQ1, KCNH2, and SCN5A), but single nucleotide polymorphisms were reported, including H558R in SCNA5A and K897T in KCNH2.
Adolescent ; Death, Sudden ; Heart Diseases ; Humans ; Long QT Syndrome ; Meperidine ; Polymorphism, Single Nucleotide ; Tachycardia, Ventricular ; Torsades de Pointes ; Ventricular Fibrillation

We present the first case of enthesitis in the lumbar spine in a woman with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Enthesopathy is defined as pathological alterations at the site of insertion of a tendon, ligament, joint capsule, or fascia to bone. In particular, enthesitis is the universal hallmark of seronegative spondyloarthropathies (SpA), including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and spondyloarthropathies associated with inflammatory bowel diseases. A 36-year-old female SLE patient with a history of lupus nephritis and thrombosis from APS presented with low back pain that had been gradually worsening for several months. She reported no previous episodes of trauma. Plain radiography indicated sclerosis at the anterior superior bodies of L3 and L5. Magnetic resonance imaging (MRI) showed low-intensity lesions on T1-weighted images and high-intensity lesions on T2-weighted images at the anterior superior bodies of L3, L4, and L5, consistent with osteitis or enthesitis. A nonsteroidal antiinflammatory drug (NSAID) was used as the first-line therapy in this patient, which improved her symptoms. This is the first report of enthesitis in the context of SLE. Although the possibility of coincidental occurrence of SpA and SLE cannot be excluded, the observations in this case suggest that enthesitis may be one of the manifestations of SLE.
Adult ; Antiphospholipid Syndrome ; Arthritis, Psoriatic ; Arthritis, Reactive ; Collodion ; Fascia ; Female ; Humans ; Inflammatory Bowel Diseases ; Joint Capsule ; Ligaments ; Low Back Pain ; Lupus Erythematosus, Systemic ; Lupus Nephritis ; Magnetic Resonance Imaging ; Osteitis ; Rheumatic Diseases ; Sclerosis ; Spine ; Spondylarthropathies ; Spondylitis, Ankylosing ; Tendons ; Thrombosis