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.

Extensive column chromatography separation of the MeOH extract from the aerial parts of Phyllanthus urinaria afforded seventeen compounds (1 - 17). The structures of the compounds were elucidated by physicochemical and spectroscopic methods to be 5′-β-D-glucopyranosyloxyjasmonic butyl ester (1), (+)-cucurbic acid (2), dendranthemoside B (3), boscialin 4′-O-β-D-glucoside (4), 4,5-dihydroblumenol A (5), (6R,9R)-megastigman-4-ene-9,13-diol (6), (3S,5R,6S,9R)-3,6-dihydroxy-5,6-dihydro-β-ionol (7), (6S,9R)-roseoside (8), mallophenol B (9), icariside B 5 (10), corchoinoside B (11), canangaionoside (12), 5,6-epoxy-3-hydroxy-7-megastigmen-9-one (13), icariside B 2 (14), (7E)-2β,3β-dihydroxy-megastigm-7-en-9-one (15), betulalbuside A (16), and loliolide (17). The compounds 1, and 3 - 16 were isolated for the first time from this plant. The absolute stereochemistry of compound 1 was newly determined. The isolated compounds were tested for cytotoxic activity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay, but all the compounds showed weak cytotoxic activities.

Vacuolar protein sorting-associated protein 13B (VPS13B), also known as COH1, is one of the VPS13 family members which is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Mutations in the VPS13B gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the patho-physiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a Vps13b exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that Vps13b mutant mice showed reduced activity in open field test and significantly shorter latency to fall in the rotarod test, suggesting that the mutants have motor deficits. In addition, we found that Vps13b mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The Vps13b mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that Vps13b mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. Vps13b mutant mice may serve as a useful model to investigate the pathophysiology of VPS13B-associated disorders.
Animals ; Autism Spectrum Disorder ; Cognition Disorders ; Exons ; Humans ; Intellectual Disability ; Learning Disorders ; Memory, Short-Term ; Mice ; Models, Animal ; Muscle Hypotonia ; Phenotype ; Rotarod Performance Test ; Social Behavior ; Spatial Learning ; Water

BACKGROUND: For proper recovery from craniofacial fracture, it is necessary to establish guidelines based on trends. This study aimed to analyze the patterns and causes of craniofacial fractures. METHODS: This retrospective study analyzed patients who underwent surgery for craniofacial fractures between 2010 and 2017 at a single center. Several parameters, including time of injury, region and cause of fracture, alcohol intoxication, time from injury to surgery, hospitalization period, and postoperative complications, were evaluated. RESULTS: This study analyzed 2708 fracture lesions of 2076 patients, among whom males aged 10 to 39 years were the most numerous. The number of patients was significantly higher in the middle of a month. The most common fractures were a nasal bone fracture. The most common causes of fracture were ground accidents and personal assault, which tended to frequently cause more nasal bone fracture than other fractures. Traffic accidents and high falls tended to cause zygomatic arch and maxillary wall fractures more frequently. Postoperative complications—observed in 126 patients—had a significant relationship with the end of a month, mandible or panfacial fracture, and traffic accidents. CONCLUSIONS: The present findings on long-term craniofacial fracture trends should be considered by clinicians dealing with fractures and could be useful for policy decisions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40902-018-0168-y) contains supplementary material, which is available to authorized users.
Accidental Falls ; Accidents, Traffic ; Hospitalization ; Humans ; Incidence ; Male ; Mandible ; Nasal Bone ; Postoperative Complications ; Retrospective Studies ; Zygoma

PURPOSE: To evaluate the thickness and volume of the choroid in healthy Korean children using swept-source optical coherence tomography. METHODS: We examined 80 eyes of 40 healthy children and teenagers (<18 years) using swept-source optical coherence tomography with a tunable long-wavelength laser source. A volumetric macular scan protocol using the Early Treatment Diabetic Retinopathy Study grid was used to construct a choroidal thickness map. We also examined 44 eyes of 35 healthy adult volunteers (> or =18 years) and compared adult measurements with the findings in children. RESULTS: The mean age of the children and teenagers was 9.47 +/- 3.80 (4 to 17) vs. 55.04 +/- 12.63 years (36 to 70 years) in the adult group (p < 0.001, Student's t-test). Regarding the Early Treatment Diabetic Retinopathy Study subfields, the inner temporal subfield was the thickest (247.96 microm). The inner and outer nasal choroid were thinner (p = 0.004, p = 0.002, respectively) than the surrounding areas. The mean choroidal volumes of the inner and outer nasal areas were smaller (p = 0.004, p = 0.003, respectively) than those of all the other areas in each circle. Among the nine subfields, all areas in the children, except the outer nasal subfield, were thicker than those in adults (p < 0.05). Regression analysis showed that age, axial length, and refractive error correlated with subfoveal choroidal thickness (p < 0.05). CONCLUSIONS: Overall macular choroidal thickness and volume in children and teenagers were significantly greater than in adults. The nasal choroid was significantly thinner than the surrounding areas. The pediatric subfoveal choroid is prone to thinning with increasing age, axial length, and refractive error. These differences should be considered when choroidal thickness is evaluated in children with chorioretinal diseases.
Adolescent ; Adult ; Aged ; Aging/physiology ; Asian Continental Ancestry Group ; Axial Length, Eye/anatomy & histology ; Child ; Child, Preschool ; Choroid/*anatomy & histology ; Female ; Healthy Volunteers ; Humans ; Macula Lutea/anatomy & histology ; Male ; Middle Aged ; Republic of Korea ; *Tomography, Optical Coherence

PURPOSE: To report a case of choroidal neovascularization (CNV) secondary to candida chorioretinitis initially treated with an intravitreal bevacizumab injection. CASE SUMMARY: A 50-year-old female presented at our clinic with decreased vision and metamorphopsia in her left eye of 5 days duration. She received an anti-fungal treatment 2 months prior due to the presence of endogenous candida choroiditis in both eyes. Fluorescein angiography and optical coherence tomography (OCT) revealed juxtafoveal CNV in her left eye. Three monthly intravitreal injections of bevacizumab were administered as the initial loading dosage. Her visual symptoms improved and CNV regression was observed on OCT. No recurrence or complications were observed during the 6 month follow-up. CONCLUSIONS: Based on the present study results we suggest that intravitreal bevacizumab injection can be used to effectively treat CNV and improve visual symptoms during the treatment of juxtafoveal CNV associated with candida choroiditis.
Candida* ; Chorioretinitis* ; Choroid ; Choroidal Neovascularization* ; Choroiditis ; Female ; Fluorescein Angiography ; Follow-Up Studies ; Humans ; Intravitreal Injections ; Middle Aged ; Recurrence ; Tomography, Optical Coherence ; Vision Disorders ; Bevacizumab

PURPOSE: To report peripheral vascular retinal leakage findings of asymptomatic eyes based on fluorescein angiography, and investigate the associated factors. METHODS: Data were collected retrospectively from 47 subjects (94 eyes) and the peripheral leakage results based on fluorescein angiography were analyzed. The relationship between peripheral leakage findings and other factors including-arm-retinal circulation time (ARCT) and venous filling time (VFT), refractive error, age, hypertension, and diabetes- was evaluated. RESULTS: Ten eyes had peripheral leakage (21.3%). The mean age was 34.7 +/- 7.86 years in the non-leakage group and 44.3 +/- 9.63 years in the leakage group; the difference between the groups was statistically significant (p = 0.001). The mean spherical equivalent was -2.85 +/- 2.71 diopter in the non-leakage group and -3.46 +/- 3.62 diopter in the leakage group; the difference between the groups were not significant (p = 0.471). The mean ARCT was 10.50 +/- 2.06 seconds in the non-leakage group and 11.76 +/- 2.47 seconds in the leakage group; the difference between the groups was statistically significant (p = 0.041). The mean VFT was 9.70 +/- 1.91 seconds in the non-leakage group and 10.75 +/- 1.40 seconds in the leakage group; the difference between the groups was statistically significant (p = 0.048). CONCLUSIONS: Peripheral leakage can be found in asymptomatic eyes. Age, VFT, and ARCT were correlated to peripheral leakage findings based on angiography. These leakage findings were thought to be related with histological properties and physiological changes in peripheral retina.
Angiography ; Fluorescein Angiography* ; Hypertension ; Refractive Errors ; Retina ; Retinaldehyde ; Retrospective Studies

PURPOSE: To study choroidal thickness and its topographic profile in normal eyes using 3D OCT-1000 spectral domain optical coherence tomography and the correlation with age and refractive error. METHODS: Fifty-seven eyes (45 individuals) with no visual complaints or ocular disease underwent horizontal and vertical line scanning using 3D OCT-1000. The definition of choroidal thickness was the vertical distance between the posterior edge of the hyper-reflective retinal pigment epithelium and the choroid/sclera junction. Choroidal thickness was measured in the subfoveal area at 500 microm intervals from the fovea to 2,500 microm in the nasal, temporal, superior, and inferior regions. The spherical equivalent refractive error was measured by autorefractometry. Statistical analysis was used to confirm the correlations of choroidal thickness with age and refraction error. RESULTS: The mean age of the 45 participants (57 eyes) was 45.28 years. Detailed visualization of the choroid for measuring its thickness was possible in 63.3% of eyes. The mean subfoveal choroidal thickness was found to be 270.8 microm (standard deviation [SD], +/-51 microm), in horizontal scanning and 275.0 microm (SD, +/-49 microm) in vertical scanning. The temporal choroidal thickness was greater than any 500 microm interval in corresponding locations, and there was no significant difference between the superior and inferior choroid as far as 2,000 microm from the fovea. Age and refractive error were associated with subfoveal choroidal thickness in terms of regression (p < 0.05). CONCLUSIONS: Choroidal thickness in normal Korean eyes can be measured using 3D OCT-1000 with high resolution line scanning. The topographical profile of choroidal thickness varies depending on its location. Age and refractive error are essential factors for interpretation of choroidal thickness.
Asian Continental Ancestry Group ; Choroid/*anatomy & histology ; Female ; Humans ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Organ Size ; Reference Values ; Refractive Errors ; Republic of Korea ; Tomography, Optical Coherence/*methods

PURPOSE: Using transmission electron microscopy (TEM), we studied the ultrastructures of rapidly proliferating preretinal membranes of young patients with very extensive ischemic proliferative diabetic retinopathy and diabetes with uncontrollable blood sugar level. METHODS: Nine cases of preretinal membranes were obtained from six eyes of five patients with rapidly progressed proliferative diabetic retinopathy (mean age, 35 years) during vitrectomy. We obtained each preretinal membrane bimanually as one single sheet membrane using intraocular scissors and forceps. Each tissue was fixed in 3% glutaraldehyde in the operating room. All specimens were prepared and studied using TEM. RESULTS: The preretinal membranes were composed of blood vessels and some interstitial cells. The blood vessels within the preretinal membranes varied in developmental stages, from the immature stage to the mature stage. The blood vessels were highly active, in that primitive cells showed a large nucleus and prominent chromatin clumping with abundant cytoplasm. Highly active fibroblast-like cells were also noted. CONCLUSIONS: We observed highly active angiogenesis in preretinal membranes, which rapidly proliferated in cases of severe retinal ischemia in young diabetes patients. This is the first report of such a finding, which may help to explain the poor prognosis of this disease modality.
Blood Glucose ; Blood Vessels ; Chromatin ; Cytoplasm ; Diabetic Retinopathy ; Eye ; Glutaral ; Humans ; Ischemia ; Membranes ; Microscopy, Electron, Transmission ; Operating Rooms ; Prognosis ; Retinaldehyde ; Surgical Instruments ; Vitrectomy

BACKGROUND AND OBJECTIVES: Aberrant activation of hepatocyte growth factor (HGF) and its receptor, c-Met, has been known to be involved in many human cancer development and progression. During the search for an effective molecule inhibitor of HGF/ c-Met signaling, we have found that Epigallocatechin-3-gallate (EGCG) in green tea might inhibit HGF/c-Met signaling. Studies were performed to address whether EGCG inhibited HGF-dependent tumor proliferation and invasion in HNSCC. MATERIALS AND METHOD: For EGCG inhibition of HGF/c-Met signaling, Western blot was performed. The proliferation of FaDu cells was assayed by counting the number of the cells after treatment by HGF 0, 10 ng/ml, EGCG 1 micrometer, EGCG 10 micrometer, HGF 10+EGCG 1 micrometer, HGF 10+EGCG 10 micrometer. The dispersion of cells was observed by measuring the separation and morphologic changes of the cells after treatment with HGF 0, 10 ng/ml HGF 10+EGCG 1 micrometer, HGF 10+EGCG 10 micrometer for 24 hours. Tumor cell migration was assessed by wound healing assay and tumor cell invasiveness was assessed by the membrane invasion assay. RESULTS: HGF treatment induced rapid activation of c-Met and EGCG inhibited HGF-induced c-Met signaling in FaDu cells. HGF significantly enhanced the growth of HNSCC cells and this phenomenon was inhibited by EGCG in a dose-dependant manner (p<0.05). EGCG inhibited HGF-induced scattering, migration, and invasion of HNSCC cells in a dose-dependent manner (p<0.05). CONCLUSION: Inhibition of HGF/Met by EGCG leads to decreased proliferation, scattering, migration and invasion in vitro, suggesting the possible use of EGCG in HNSCC associated with down-regulation of HGF/Met signaling.
Blotting, Western ; Catechin ; Cell Movement ; Down-Regulation ; Hepatocyte Growth Factor ; Humans ; Hypopharyngeal Neoplasms ; Membranes ; Tea ; Wound Healing