The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway.
Adenoma ; Age of Onset ; Carcinogenesis ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; CpG Islands* ; Cytoplasm ; Female ; Humans ; Microsatellite Instability ; Phenotype ; Prognosis

Purpose: : This study aimed to understand and describe the nurses’ experiences caring for severe COVID-19 patients at isolation room with negative pressure in South Korea. Methods: : Data were collected through individual in-depth interviews from February 16 to March 31, 2021 with 11 nurses who had been caring for severe COVID-19 patients at isolation room. Verbatim transcripts were analyzed according to Colaizzi’s phenomenological analysis. Results: : As a result, 5 theme clusters were extracted about nurses’ experiences. The 5 theme clusters, “Adapting to unexpected adversity”, “Accepting unresonable and heavy work”, “Dulness and disconnection from the outside world”, “Changing in perception of new infectious diseases”, and “Pathetic isolated patients” emerged. Conclusion : The results of this study provided a deeper understanding of nurses struggling to care for COVID-19 severe patients. This study is expected to be useful in providing basic evidence for improving intensive care practices and for preparing policies in other infection disease situations.

Schwannomas are slow-growing benign tumors originating from the Schwann cells of the peripheral nerve sheaths. Herein, we report the first documented case of a schwannoma presenting as a painful nipple mass in a 32-year-old woman. This mass initially developed six years ago following a period of breastfeeding. Breast magnetic resonance imaging (MRI) scans revealed an iso-intense mass, with an approximate size of 2.2 cm, on a T1-weighted image with internal cystic changes. The mass exhibited heterogeneously delayed enhancement and restricted diffusion.Surgical excision was performed, and the diagnosis of cutaneous plexiform nipple schwannoma was confirmed histopathologically. A literature review revealed that the MRI findings of the nipple mass in our case were consistent with the common features of a schwannoma.

Objective: This study investigated associations of life stressors and serum ghrelin levels with suicidal ideation (SI), and evaluated the potential mediating effect of ghrelin on associations between life stressors and SI in patients with acute coronary syndrome (ACS). Methods: In total, 969 ACS patients recruited from a tertiary university hospital in Korea within 2 weeks of disease onset were evaluated in terms of life stressors (using the List of Threatening Events Questionnaire), serum ghrelin levels, and SI (using the “suicidal thoughts” item of the Montgomery–Asberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI; logistic regression was performed with adjustment for covariates. Results: Life stressors were significantly associated with SI at baseline and follow-up. Serum ghrelin showed no such associations, but high levels thereof mediated associations of life stressors with SI; significant interaction terms were also observed after adjustment for covariates. Conclusion By evaluating life stressors and serum ghrelin levels, clinical prediction of SI in the acute and chronic phases of ACS could be improved.

Objective: We aimed to identify the individual and interactive effects of childhood abuse and suicidal ideation on antidepressant treatment response in 12 months. Methods: In this prospective research, 1,262 depressive patients were asked about their childhood abuse history, suicidal ideation, and other clinical characteristics and socio-demographic features at baseline, and 1,015 of them were followed during 1 year of stepwise pharmacotherapy. The individual and interactive relationships of the childhood abuse history and suicidal ideation on 12-month antidepressant non-remission were explored by logistic regression with relevant covariates. Results: Having a childhood abuse history and higher suicidal ideation significantly predicted a non-remission state in 12 months respectively. The interaction term of childhood abuse and suicidal ideation was also significantly related to a non-remission state at 12 months. To be specific, in the low suicidal ideation group, depressive patients with a childhood abuse history were more likely to be in a non-remission state after 12 months of medication. In the high suicidal ideation group, however, childhood abuse history was not significantly associated with the non-remission state at 12 months. Conclusion The childhood abuse history and the level of suicidal ideation are informative factors predicting the long-term results of antidepressant treatment, especially when they are combined. Clinicians may consider antidepressants with a higher affinity for patients with childhood abuse history even if they don’t have suicidal ideation. The cognitive intervention for suicidal ideation might be helpful in addition to pharmacological treatment.

BACKGROUND: Every practitioner, however skilled, will encounter patients who are unexpectedly difficult to intubation. The incidence of difficult laryngoscopy appears to be approximately 0.5% to 2%. So many methods are used to intubate the trachea, but endotraheal intubation by them is not always possible. The purpose of the this study is to evaluate the effectiveness of magnet on the endotracheal intubation. METHODS: Twenty patients(aged 30 to 59yr, ASA physical status 1) required general anesthesia with an endotracheal tube. Anesthesia was induced with thiopental sodium and succinylcholine, ventilation was controlled with 100% O2. The tip of the epiglottis was exposed wtih a No.3 MacIntosh laryngoscope. A catheter with ferrous stylet was placed behind epiglottis close to tracheal lumen and a magnet was placed over the cricoid cartilage allowing the stylet to be pulled. Endotraheal tube was guided into the trachea over the stylet. The time to intubation, the blood pressure and heart rate of pre- and postintubation, and the difficulty of intubation were recorded and the complications of the endotracheal intubation such as bronchial spasm, oral and tracheal mucosal trauma, and sore throat, were observed. RESULTS: The mean time to intubation was 31.2+/- 8(18 to 50)sec. There were statistically signigicant increase in blood pressure and heart rates following intubation. The incidence of excellent and good intubating condition were 14 and 6 respectively. Seventeen and three intubations were successful on the 1st and 2nd attempts respectively. There were no differences in incidence of complications of endotracheal intubation compared to other reports. CONCLUSIONS: Though magnet guided technique has some limitations to use in case of difficult laryngoscopy, it can be used with merits such as simplicity and cheapness when other methods are not available.
Anesthesia ; Anesthesia, General ; Blood Pressure ; Bronchial Spasm ; Catheters ; Cricoid Cartilage ; Epiglottis ; Heart Rate ; Humans ; Incidence ; Intubation* ; Intubation, Intratracheal ; Laryngoscopes ; Laryngoscopy ; Pharyngitis ; Succinylcholine ; Thiopental ; Trachea ; Ventilation

FLASH radiotherapy (FLASH RT) is a technique to deliver ultra-high dose rate in a fraction of a second. Evidence from experimental animal models suggest that FLASH RT spares various normal tissues including the lung, gastrointestinal track, and brain from radiation-induced toxicity (a phenomenon known as FLASH effect), which is otherwise commonly observed with conventional dose rate RT. However, it is not simply the ultra-high dose rate alone that brings the FLASH effect. Multiple parameters such as instantaneous dose rate, pulse size, pulse repetition frequency, and the total duration of exposure all need to be carefully optimized simultaneously. Furthermore it is critical to validate FLASH effects in an in vivo experimental model system. The exact molecular mechanism responsible for this FLASH effect is not yet understood although a number of hypotheses have been proposed including oxygen depletion and less reactive oxygen species (ROS) production by FLASH RT, and enhanced ability of normal tissues to handle ROS and labile iron pool compared to tumors. In this review, we briefly overview the process of ionization event and history of radiotherapy and fractionation of ionizing radiation. We also highlight some of the latest FLASH RT reviews and results with a special interest to neurocognitive protection in rodent model with whole brain irradiation. Lastly we discuss some of the issues remain to be answered with FLASH RT including undefined molecular mechanism, lack of standardized parameters, low penetration depth for electron beam, and tumor hypoxia still being a major hurdle for local control. Nevertheless, researchers are close to having all answers to the issues that we have raised, hence we believe that advancement of FLASH RT will be made more quickly than one can anticipate.

OBJECTIVETo extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.

METHODSAn MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups.

RESULTSThere were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups.

CONCLUSIONSTIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".

Animals ; Cadherins ; genetics ; metabolism ; Cell Line, Tumor ; Cyclooxygenase 2 ; genetics ; metabolism ; Extracellular Fluid ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Stomach Neoplasms ; metabolism ; secondary ; Telomerase ; genetics ; metabolism ; Tumor Microenvironment ; physiology ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

OBJECTIVETo observe the role of activation of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion (I/ R) injury in diabetic rats.

METHODSDiabetic rat model was simulated by intraperitoneal injection 55 mg/kg streptozotocin (STZ) and divided into diabetes and ethanol + diabetes groups (n = 8). After 8 weeks, myocardial ischemia/reperfusion model was mimicked in vitro. The ventricular dynamical parameters and lactate dehydrogenase (LDH) content in coronary flow were determined. The fasting blood glucose and glycosylated hemoglobin (HbA1c) level were determined by automatic biochemistry analyzer. The ALDH2 mRNA and protein expressions of left anterior myocardium were evaluated by RT-PCR and Western blot.

RESULTSIn contrast to I/R in normal rat, in diabetic rat, left ventricular development pressure (LVDP), maximal rise/fall rate of left ventricular pressure (+/- dp/dtmax) and left ventricular work (RPP) were decreased, left ventricular end diastolic pressure (LVEDP) and LDH release were increased, and ALDH2 mRNA and protein expressions were decreased; compared with I/R in diabetic rat, ALDH2 agonist ethanol significantly promoted the recovery of LVDP, +/- dp/dtmax, RPP, reduced HbA1c level, LVEDP and LDH released, ALDH2 mRNA and protein expressions were increased.

CONCLUSIONIn diabetic rat, the expression of ALDH2 was decreased when heart was subjected to I/R. Enhanced mitochondrial ALDH2 expression in diabetic rat could play cardiac protective role.

Aldehyde Dehydrogenase ; metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Male ; Mitochondrial Proteins ; metabolism ; Myocardial Reperfusion Injury ; etiology ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-beta1 initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain. METHODS: We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009. RESULTS: In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018). CONCLUSION: According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.
Adenocarcinoma* ; Biomarkers ; Carcinoma, Non-Small-Cell Lung ; Genotype ; Humans ; Medical Records ; Membranes ; Multivariate Analysis ; Phosphotransferases ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators* ; Plasminogen* ; Polymorphism, Single Nucleotide ; Prognosis* ; Receptor, Epidermal Growth Factor ; Retrospective Studies