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Abstract This study assessed survival for lung cancer patients meeting criteria for the National Lung Cancer Screening Program in Korea launched in 2019 and updated guideline reported by the US Preventive Service Task Force (USPSTF). We assessed all-cause mortality based on the Korean Lung Cancer Registry (KLCR), including lung cancer patients diagnosed in 2014–2016. We compared survival among lung cancer patients eligible for extended USPSTF criteria (age 50–80 years and ≥ 20 pack-years) and those meeting current criteria (age 54–74 years and ≥ 30 pack-years, current or within the past 15 years). The nearest neighbour propensity-score matching was performed to generate a matched set. Kaplan–Meier curves were generated to compare survival among groups; differences in survival were analyzed using the stratified log-rank test. The mortality risk was estimated based on a Cox proportional hazards regression model and the robust standard error was calculated. Of 8110 patients, 37.4% and 24.3% met the extended USPSTF eligibility criteria and National Lung Cancer Screening Program (NLCSP) criteria, respectively. Overall mortality risk was not significantly different between the extended younger age group and the NLCSP group (hazard ratio [HR] [95% confidence interval (CI)]: 0.78 [0.59–1.02]). The extended older age group had a significantly higher mortality risk (HR [95% CI]: 1.41 [1.26–1.58]). Mortality risk was not significantly different between patients who smoked 20–29 pack-years and those who smoked ≥ 30 pack-years (HR [95% CI]: 0.90 [0.79–1.03]). Lung cancer patients aged 50–53 years and those with a 20–29 pack-years smoking history exhibited similar mortality risk to individuals meeting current criteria, while patients aged 75–80 years were at a higher risk of death. Although we verified similar or higher mortality risks in extended subgroups, a careful assessment of the benefits and harms of the screening tests is necessary when contemplating the extension of criteria.

Objectives: This study analyzed the Korea Health Panel Annual Data 2019 to investigate factors related to the use of non-insured Korean medicine (KM) treatment in individuals with chronic diseases. The non-insured KM treatments of interest were herbal decoction (HD) and pharmacopuncture (PA). Methods: Among adults aged 19 or older, 6,159 individuals with chronic diseases who received outpatient KM treatment at least once in 2019 were included. They were divided into three groups according to the KM treatment used: (1) basic insured KM non-pharmacological treatment (BT) group (n = 629); (2) HD group (n = 256); (3) PA group (n = 184). Logistic regression analysis was used to explore factors associated with favoring HD or PA use over BT. Potentially relevant candidate factors were classified using the Andersen Behavior Model. Results: Compared to BT, the 1st to 3rd quartiles of income compared to the 4th quartile (odds ratio: 1.50 to 2.06 for HD; 2.03 to 2.83 for PA), health insurance subscribers compared to medical aid (odds ratio: 2.51; 13.43), and presence of musculoskeletal diseases (odds ratio: 1.66; 1.91) were significantly positively associated with HD and PA use. Moreover, the presence of cardiovascular disease (odds ratio: 1.46) and neuropsychiatric disease (odds ratio: 1.97) were also significantly positively associated with HD use. Conclusion: The presence of some chronic diseases, especially musculoskeletal diseases, was significantly positively associated with HD and PA use, while low economic status was significantly negatively associated with HD and PA use, indicating the potential existence of unmet medical needs in this population. Since chronic diseases impose a considerable health burden, the results of this study can be used for reference for future health insurance coverage policies in South Korea.

Abstract Many patients in Korea use Korean Medicine (KM) after spine surgery, but related research is lacking. Therefore, this retrospective cohort study aimed to analyze factors affecting the use and costs of KM using nationally representative data from the National Health Insurance Service-National Sample Cohort, South Korea. Patients who underwent spinal surgery for spinal diseases from 2011 to 2014 were followed up for 5 years, and their medical care was described. The association between patient and spinal surgery characteristics and the use of KM was analyzed. A two-part model was used to analyze factors affecting the use of KM in patients undergoing spinal surgery. Of 11,802 patients who underwent spinal surgery, 11,367 who met the inclusion criteria were included. Overall, 55.5% were female, 32.3% were aged ≥ 70 years, and 50.2% received KM treatment during the follow-up period. Open discectomy was the most common surgical procedure performed (58.6%), and 40.2% of surgeries were performed because of lumbar disc disorder. Female sex, older age, high Charlson Comorbidity Index score, and use of KM before surgery were associated with increased KM use and expenditure after surgery. In conclusion, patient characteristics, rather than surgical characteristics, appeared to be more strongly associated with the use of KM after surgery, particularly prior experience with KM use. This study is significant in that it analyzed the entire spine surgery to provide a comprehensive view of the use of KM after spine surgery and analyzed the impact of various factors related patients and surgical characteristics on KM use. The results of this study may be useful to patients with spinal diseases, clinicians, and policymakers.

Abstract Cryopreservation is an important technique used in the conservation of various plant tissues. This study proposes a cryopreservation method for the long-term conservation of eastern bracken fern gametophytes (Pteridium aquilinum var. latiusculum). Encapsulation–dehydration of the gametophytes was performed, and the exogenous sucrose and abscisic acid (ABA) preculture conditions were investigated. Gametophytes are sensitive to dehydration and drying, and the following treatment conditions were applied: encapsulation by alginate containing 0.75 M sucrose, 18-h loading treatment with 0.75 M sucrose, and 6-h drying treatment. The survival rate following cryopreservation was determined. The water content of

This study aimed to investigate the changes in lymph node surgery types and prescription patterns of postoperative medications for pain management in patients with breast cancer using national health insurance claim data from South Korea. The study population comprised patients with at least one record of a principal diagnosis of breast cancer (ICD-10 code: C50) from the national health insurance claim database between 2010 and 2019. Patients who underwent mastectomy or lumpectomy only once were selected for the analysis. Patients who underwent axillary lymph node dissection (ALND) with mastectomy or lumpectomy on the day of surgery were included in the ALND group, whereas those who underwent sentinel lymph node biopsy (SLNB) were included in the SLNB group. Prescription records of opioids before, after and on the date of breast cancer surgery were collected and categorized according to the opioid type. Multivariate logistic regression modeling was used to compare postoperative opioid prescriptions. The proportion of those undergoing ALND among 3,080 patients decreased consistently after 2014, while the proportion undergoing SLNB increased. Although the rate of pain medication prescription on the day of surgery was similar between the two groups, the rate of prescription of postoperative pain medication and anticancer agents was lower in the SLNB group than in the ALND group. Logistic regression modeling showed that the SLNB group had lower odds of receiving opioids than did the ALND group (Odds ratio (OR) = 0.727, Confidence Interval (CI) = 0.546-0.970). A consistent trend was observed when the model was adjusted for neoadjuvant chemotherapy and the use of preoperative pain medications (OR = 0.718, CI = 0.538-0.959). To manage postoperative pain and prevent chronic pain with minimal side effects, sufficient discussion among clinicians, patients, and other healthcare professionals is imperative, along with adequate treatment planning.

The escalating prevalence of antibiotic-resistant bacteria poses an immediate and grave threat to public health. Antimicrobial peptides (AMPs) have gained significant attention as a promising alternative to conventional antibiotics. Animal venom comprises a diverse array of bioactive compounds, which can be a rich source for identifying new functional peptides. In this study, we identified a toxin peptide, Lycotoxin-Pa1a (Lytx-Pa1a), from the transcriptome of the Pardosa astrigera spider venom gland. To enhance its functional properties, we employed an in silico approach to design a novel hybrid peptide, KFH-Pa1a, by predicting antibacterial and cytotoxic functionalities and incorporating the amino-terminal Cu(II)- and Ni(II) (ATCUN)-binding motif. KFH-Pa1a demonstrated markedly superior antimicrobial efficacy against pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa, compared to Lytx-Pa1a. Notably, KFH-Pa1a exerted several distinct mechanisms, including the disruption of the bacterial cytoplasmic membrane, the generation of intracellular ROS, and the cleavage and inhibition of bacterial DNA. Additionally, the hybrid peptide showed synergistic activity when combined with conventional antibiotics. Our research not only identified a novel toxin peptide from spider venom but demonstrated in silico-based design of hybrid AMP with strong antimicrobial activity that can contribute to combating MDR pathogens, broadening the utilization of biological resources by incorporating computational approaches.

Abstract Information technology advances may help in conducting epidemiological studies using web-based surveys. Questionnaire-based headache diagnosis should be validated against the doctor’s diagnosis. This study aimed to develop and validate a web-based diagnostic questionnaire for migraine, probable migraine (PM), and tension-type headache (TTH). We constructed a seven-item questionnaire for diagnosing migraine, PM, and TTH. A web-based survey was conducted among adults aged 20–59 years; migraine, PM, and TTH were diagnosed based on the responses. Validation interview was performed via telephone by a neurologist within 1 month after the web-based interview. Finally, 256 participants completed both web-based survey and validation interview. Of them, 121 (47.3%), 65 (25.4%), 61 (23.8%), and 9 (3.5%) were diagnosed with migraine, PM, TTH, and unclassified headache (UH), respectively in the web-based survey, whereas 119 (46.5%), 60 (23.4%), 74 (28.9%), 2 (0.8%), and 1 (0.4%) were diagnosed with migraine, PM, TTH, UH, and primary stabbing headache, respectively in the validation interview. The best agreement was found in migraine (sensitivity: 92.6%; specificity: 94.8%; kappa coefficient: 0.875), followed by TTH (sensitivity: 78.4%; specificity: 98.4%; kappa coefficient: 0.809). PM showed the least agreement (sensitivity: 85.0%; specificity: 92.9%; kappa coefficient: 0.757). In conclusion, our questionnaire is valid in identifying these headache disorders.

Abstract Background Peer-support programs are a useful social support strategy for populations trying to quit smoking who are willing to maintain smoking abstinence. This study is a protocol for a systematic review and meta-analysis to assess the effectiveness of peer support for smoking cessation. Methods This protocol will be conducted in accordance with the Cochrane Handbook of Systematic Reviews of Interventions 6.2. We will conduct a comprehensive search in the Cochrane Central Register of Controlled Trials, ovidEmbase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, ovidMEDLINE, Google Scholar, and Open Grey, as well as the Trials Register of Promoting Health Interventions in EPPI-Centre, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and reference lists of included papers. The review will include randomized controlled trials of peer support interventions aimed to stop smoking in any population. Two reviewers will independently screen and select relevant studies. Version 2 of the Cochrane tool that assesses risk of bias in randomized trials will be used to assess the risk of bias in the included studies. The primary outcomes will be defined as the tobacco abstinence rate and adverse events. If a quantitative synthesis is not appropriate, a synthesis without meta-analysis will be undertaken. Discussion This review will provide the best available evidence regarding the effects of peer support interventions to quit smoking. The results from this study will help to inform healthcare providers on the optimal peer support intervention modalities such as intensity, delivery methods, type of support provider, and duration of the intervention. Systematic review registration PROSPERO CRD42020196288

Introduction Although various treatments exist for depression in patients with spinal cord injury (SCI), the comparative effects and relationships between these treatments have not been clearly presented. This study aims to present comprehensive evidence for the treatment of major depressive disorder or dysthymic disorder in patients with SCI by comparing the therapeutic and adverse effects of pharmacological and non-pharmacological treatments through a systematic review and network meta-analysis.Methods and analysis We will search for studies in five databases (Medline, Central, Embase, PsycINFO and CHINAL) as well as clinical trial registries (US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov), WHO International Clinical Trials Registry Platform (www.who.int/trialsearch)) and grey literature (Google Scholar). The references of the included studies, previous systematic reviews and meta-analyses will be reviewed. Study selection, data extraction and quality and risk of bias assessments will be independently performed by two authors (JMH and WSC), and disagreements will be resolved by discussion with JHK. Moreover, a Bayesian network meta-analysis will be performed using R software.Ethics and dissemination Our systematic review and network meta-analysis will be performed based on existing studies; thus, we did not seek ethical approval. Our results will be published in a peer-reviewed journal and presented at both domestic and international conferences.

Abstract Magnetic anisotropy energy (MAE) is one of the most important properties in two-dimensional magnetism since the magnetization in two dimension is vulnerable to the spin rotational fluctuations. Using density functional theory calculation, we show that perpendicular electric field dramatically enhances the in-plane and out-of-plane magnetic anisotropies in Fe3GeTe2 and Fe4GeTe2 monolayers, respectively, allowing the change of easy axis in both systems. The changes of the MAE under the electric field are understood as the result of charge redistribution inside the layer, which is available due to the three-dimensional (3D) network of Fe atoms in the monolayers. As a result, we suggest that due to the unique structure of FenGeTe2 compounds composed by peculiar 3D networks of metal atoms, the MAE can be dramatically changed by the external perpendicular electric field.

Background Long-term usage of glucocorticoids results in a loss of bone mass and a higher risk of fracture, and the most common cause of secondary osteoporosis is glucocorticoid-induced osteoporosis (GIOP). For preventing GIOP, bisphosphonate (BP) is widely used. However, analysis on BP’s effect on the prevention of re-fracture is insufficient. The purpose of the present study is to evaluate the comparative treatment effect and prevention of re-fracture according to the type of BP in GIOP as the basis for a reliable clinical strategy for patients.Methods and analysis We will search electronic databases of the PubMed, Cochrane Library and EMBASE using a comprehensive search strategy in December 2021 with no language restriction. Randomised controlled trials (RCTs), quasi-RCTs, controlled trials and cohort studies evaluating the effectiveness of BP to the patients with GIOP will be included in this study. The primary outcome will be the incidence of hip, vertebral and other fractures. The secondary outcome will include percentage changes on the bone mineral density and incidence of re-fracture. Assessing risk of bias for included studies is done using the Cochrane Risk of Bias tool and Risk Of Bias In Non-randomized Studies–of Intervention tool. If quantitative synthesis is possible, a meta-analysis will be performed. A subgroup analysis will be conducted to compare re-fracture rate on the patients with GIOP who experience previous fractures. This study’s result will provide evidence for the effectiveness of BP in the prevention of re-fracture on patients with GIOP.Ethics and dissemination The results will be disseminated through publishing in a peer-reviewed journal or public presentations. Ethical approval is not required as this is a systematic review of publicly available data.PROSPERO registration number CRD42022343787.

Objective To investigate the clinical factors associated with successful gastrostomy tube weaning in patients with prolonged dysphagia after stroke. Methods This study involved a retrospective medical chart review of patients diagnosed with prolonged dysphagia after stroke who underwent gastrostomy tube insertion between May 2013 and January 2020. Forty-seven patients were enrolled and consequently divided into gastrostomy tube sustaining and weaning groups. The numbers of patients in the sustaining and weaning groups were 31 and 16, respectively. The patients’ demographic data, Korean version of Mini-Mental State Examination (K-MMSE) score, Korean version of the Modified Barthel Index (K-MBI), Functional Dysphagia Scale (FDS) score, and Penetration-Aspiration Scale (PAS) score were compared between the two groups. A videofluoroscopic swallowing study was performed before making the decision of gastrostomy tube weaning. The clinical factors associated with gastrostomy tube weaning were then investigated. Results There were significant differences in age; history of aspiration pneumonia; K-MMSE, FDS, and PAS scores; and K-MBI between the groups. In the multiple logistic regression analysis, the FDS (odds ratio [OR]=0.791; 95% confidence interval [CI], 0.634–0.987) and PAS scores (OR=0.205; 95% CI, 0.059–0.718) were associated with successful gastrostomy tube weaning. In the receiver operating characteristic curve analysis, the FDS and PAS were useful screening tools for successful weaning, with areas under the curve of 0.911 and 0.918, respectively. Conclusion In patients with prolonged dysphagia, the FDS and PAS scores are the only factors associated with successful gastrostomy tube weaning. An evaluation of the swallowing function is necessary before deciding to initiate gastrostomy tube weaning.

Background Recently, there have been some trials to use dexmedetomidine in the obstetric field but concerns regarding the drug include changes in uterine contractions after labor. We aimed to evaluate the effects of dexmedetomidine on the myometrial contractions of pregnant rats. Methods In a pilot study, the contraction of the myometrial strips of pregnant Sprague-Dawley rats in an organ bath with oxytocin at 1 mU/ml was assessed by adding dexmedetomidine from 10-6 to 10-2 M accumulatively every 20 min, and active tension and the number of contractions were evaluated. Then, changes in myometrial contractions were evaluated from high doses of dexmedetomidine (1.0 × 10-4 to 1.2 × 10-3 M). The effective concentrations (EC) for changes in uterine contractions were calculated using a probit model. Results Active tension and the number of contractions were significantly decreased at 10-3 M and 10-4 M dexmedetomidine, respectively (P < 0.05). A complete loss of contractions was seen at 10-2 M. Dexmedetomidine (1.0 × 10-4 to 1.2 × 10-3 M) decreased active tension and the number of contractions in a concentration-dependent manner. The EC95 of dexmedetomidine for inhibiting active tension and the number of contractions was 5.16 × 10-2 M and 2.55 × 10-5 M, respectively. Conclusions Active tension of the myometrium showed a significant decrease at concentrations of dexmedetomidine higher than 10-3 M. Thus, clinical concentrations of dexmedetomidine may inhibit uterine contractions. Further research is needed for the safe use of dexmedetomidine in the obstetrics field.

This study investigated the time-dependent characteristics of acupuncture and analyzed the association between acupuncture utilization and mortality rates, readmission rates, and complications among ischemic stroke patients. Data from the National Health Insurance Service-National Sample Cohort 2.0 from South Korea were used to track patients with subacute and chronic ischemic stroke, who had survived more than one month after onset, between 2010 and 2013. A total of 2299 patients were followed up until 2015. At baseline, the acupuncture group (n = 195) and the control group (n = 2104) had similar ages (acupuncture group: 69.0 ± 11.1 years; control group: 68.5 ± 11.8 years), but the acupuncture group had more comorbidities (Charlson comorbidity index; acupuncture group: 4.7 ± 2.1, control group: 4.3 ± 2.4). According to time-dependent Cox regression survival analysis, acupuncture treatment was associated with low hazard ratios (HR) for death (HR: 0.32; 95% confidence interval (CI): 0.18–0.60), fewer composite complications (HR: 0.34; 95% CI: 0.21–0.53), and reduced urinary tract infection (HR: 0.24; 95% CI: 0.11–0.54). Many acupuncture session sensitivity analyses were performed to assess the robustness using different criteria to define the acupuncture group, and the results were consistent with those of the main analysis. Therefore, acupuncture treatment might be associated with lower mortality rates and the prevention of complications after ischemic stroke.

Abstract The intestinal epithelium has two distinct two stem cell populations, namely, crypt base columnar (CBC) cells and +4 cells. Several specific markers have been identified for each stem cell population. In this study, we examined the expression profiles of these markers in colitis-associated carcinogenesis (CAC) to investigate whether they can be used as biomarkers for the early detection of dysplasia. The expression of intestinal stem cell (ISC) markers was measured by real-time polymerase chain reaction during CAC that was induced by azoxymethane and dextran sodium sulfate treatment. CBC stem cell markers increased continuously with tumor development, whereas a +4 cell expression profile was not present. CBC stem cell population was suppressed in the acute colitis and then expanded to repopulate the crypts during the regeneration period. Notably, RNA in situ hybridization revealed that all dysplasia and cancer samples showed increased expression of CBC stem cell markers in more than one-third of the tumor height, whereas regenerative glands had CBC stem cell markers confined to the lower one-third of the crypt. These results suggest that CBC stem cell markers could be a useful tool for the early detection of colitis-induced tumors.

Basal cell carcinoma (BCC) is the most common human cancer, characterized by aberrant activation of the hedgehog (HH) signaling pathway resulting from mutations in the patched 1 (PTCH1) or smoothened (SMO) genes. In the present study, to uncover the expression profile of HH signaling-related molecules, we thoroughly examined the mRNA and protein expression levels of six molecules including GLI1, GLI2, PTCH1, PTCH2, SHH, and SMO in BCC and various other cutaneous tumors. Real-time PCR analysis demonstrated that BCC showed remarkably enhanced mRNA expression of all HH molecules, except SMO compared to other skin tumors. However, immunohistochemical analysis revealed that only GLI1 protein was specifically upregulated in BCC, while the other HH-related proteins did not show any significant differences between the tumors. Notably, other skin malignancies such as squamous cell carcinoma, sebaceous carcinoma, and malignant melanoma showed no GLI1 expression and there was no difference in GLI1 expression between the BCC subtypes. In addition, GLI1 and GLI2 expression were strongly associated with the hair follicle stem cell markers, LGR4 and LGR5, which are known target genes of the Wnt pathway. Our results suggest that GLI1 has the potential to be a diagnostically useful marker for differentiating BCC from other skin malignancies and an interaction between the HH and Wnt signaling pathways may be involved in the development of BCCs.

BackgroundThe growing popularity of traditional medicine (TM) is reflected in the increasing trend for its use worldwide. Many people are turning to use TM as a complementary or integrative treatment. The aim of this study is to present the first nationwide report describing the use of TM in two countries (South Korea and Taiwan).Materials and methodsTo present the TM utilization patterns between South Korea and Taiwan, we analyzed data from the National Health Insurance cohorts in each country, each of which has approximately one million inhabitants.ResultsIn total, 261,478 (25.5%) of 1,025,340 people in South Korea and 260,529 (26.8%) of 970,866 people in Taiwan used TM services at least once under the National Health Insurance in 2011. Using multivariable logistic regression, TM users in South Korea were significantly more likely to be female, 61-80 years of age and individuals with a high income, and those in Taiwan were significantly more likely to be female, 21-40 years of age and individuals with a middle income. The two countries showed similar utilization patterns in visit seasons. People visited TM clinics more frequently than TM hospitals in both countries. The most common TM treatment in South Korea was acupuncture, whereas in Taiwan, various powdered Chinese herbal preparations were the most commonly used treatment. The most common diseases for people seeking TM services were musculoskeletal system and connective tissue diseases in South Korea and Symptoms, signs, and ill-defined conditions in Taiwan.ConclusionAccording to the National Health Insurance database, about one fourth of the NHI beneficiaries of South Korea and Taiwan had TM use in 2011. Different TM utilization patterns existed between South Korea and Taiwan, which might be due to the differences in insurance coverage between the two countries.

INTRODUCTION:This study aimed to determine the diagnostic accuracy of adding copeptin to cardiac troponin (cTn) on admission to the emergency department (ED) for non-ST elevation myocardial infarction (NSTEMI) compared to cTn alone. MATERIALS AND METHODS:A literature search of MEDLINE, EMBASE, and the Cochrane Library was performed (search date: April 13, 2018). Primary studies were included if they accurately reported on patients with symptoms suggestive of acute myocardial infarction and measured both cTn alone and cTn with copeptin upon admission to the ED. The patients with evidence of ST elevation myocardial infarction were excluded. To assess the risk of bias for the included studies, the QUADAS-2 tool was used. RESULTS:The study participants included a total of 7,998 patients from 14 observational studies. The addition of copeptin to cTn significantly improved the sensitivity (0.81 [0.74 to 0.87] vs. 0.92 [0.89 to 0.95], respectively, p

Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1. Real-time polymerase chain reaction analysis showed significantly higher GREM1 expression in skin cancers and pilomatricomas (PMCs) than in other benign skin tumors. Tissue microarrays analyzed by RNA ISH for GREM1 expression also demonstrated that 23% of BCCs, 42% of squamous cell carcinomas, 20% of melanomas, and 90% of PMCs were positive for GREM1 expression, whereas trichoepitheliomas, eccrine poromas, hidradenomas, and spiradenomas were negative for GREM1 expression. Most BCCs that were GREM1 expression positive were of desmoplastic or mixed subtypes, and GREM1 expression was localized to activated myofibroblasts at the tumoral-stromal interface. Interestingly, most PMCs harbored GREM1-expressing fibroblasts, probably because of the inflammatory responses caused by foreign body reactions to keratin. Additionally, in BCCs, stromal GREM1 expression had a strong correlation with CD10 expression. In conclusion, GREM1 is frequently expressed by myofibroblasts in scars or in the stroma of basal cell carcinomas, suggesting that GREM1 expression can be a marker for activated myofibroblasts in the cancer stroma or in scar tissue.

Gastric intestinal metaplasia (IM) is a highly prevalent preneoplastic lesion; however, the molecular mechanisms regulating its development remain unclear. We have previously shown that a population of cells expressing the intestinal stem cell (ISC) marker LGR5 increases remarkably in IM. In this study, we further investigated the molecular characteristics of these LGR5+ cells in IM by examining the expression profile of several ISC markers. Notably, we found that ISC markers-including OLFM4 and EPHB2-are positively associated with the CDX2 expression in non-tumorous gastric tissues. This finding was confirmed in stomach lesions with or without metaplasia, which demonstrated that OLFM4 and EPHB2 expression gradually increased with metaplastic progression. Moreover, RNA in situ hybridization revealed that LGR5+ cells coexpress several ISC markers and remained confined to the base of metaplastic glands, reminiscent to that of normal intestinal crypts, whereas those in normal antral glands expressed none of these markers. Furthermore, a large number of ISC marker-expressing cells were diffusely distributed in gastric adenomas, suggesting that these markers may facilitate gastric tumorigenesis. In addition, Barrett's esophagus (BE)-which is histologically similar to intestinal metaplasia-exhibited a similar distribution of ISC markers, indicating the presence of a stem cell population with intestinal differentiation potential. In conclusion, we identified that LGR5+ cells in gastric IM and BE coexpress ISC markers, and exhibit the same expression profile as those found in normal intestinal crypts. Taken together, these results implicate an intestinal-like stem cell population in the pathogenesis of IM, and provide an important basis for understanding the development and maintenance of this disease.

We investigated MET mRNA expression status using RNA in situ hybridization (ISH) technique in primary and metastatic lesions of 535 surgically resected gastric carcinoma (GC) cases. We compared the results with those of immunohistochemistry and silver in situ hybridization, and examined the association with clinicopathologic characteristics and prognosis. Among 535 primary GCs, 391 (73.1%) were scored 0, 87 (16.3%) were scored 1, 38 (7.1%) were scored 2, 12 (2.2%) were scored 3 and 7 (1.3%) were scored 4 by RNA ISH. High MET mRNA expression (score ≥3) was associated with lymph node metastasis (P = .014), distant metastasis (P = .001), and higher TNM stage (P