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Background The prevalence of obesity among women is increasing. Obesity is associated with various metabolic syndromes; conventional treatments are limited and may induce serious adverse events due to polytherapy regimens. Currently, demands for complementary and alternative medicine that has a proven safety profile for the treatment of obesity with or without metabolic risk factors are increasing.Our team of preclinical experts reported a significant anti-obesity effect of the Korean herbal medicine, Galgeun-tang (GGT). Thus, we designed this trial to explore the effects of GGT among obese women to accumulate optimal clinical evidence.Obesity is not only a component of metabolic syndrome and a factor associated with an increased risk of cardiovascular disease but is also related to insulin resistance. Previous research has confirmed that an increasing body mass index is highly related with increased risk of metabolic syndrome among overweight and obese individuals. The effectiveness of the Korean medicine herbal formula, GGT on obesity has been previously reported. The objective of this study is to assess the efficacy and safety of GGT for weight loss among obese Korean women with or without high risk for metabolic syndrome. Methods/design This study is a randomized, double-blinded, placebo-controlled, multi-center clinical trial. A total of 160 participants will be randomly distributed in 2 groups, the GGT group or the placebo group in a 1:1 ratio using a web-based randomization system. Each group will be administered GGT or placebo 3 times a day for 12 weeks. The primary endpoint is to assess the change in weight from baseline. The secondary endpoints are the following: the changes in body composition measurements, anthropomorphic measurements, obesity screening Laboratory tests, patient self-reported questionnaires, and economic evaluation outcomes. Adverse events will also be reported. Discussion The findings of this study will confirm methodologies regarding the efficacy and safety of GGT for weight loss among obese Korean women with or without metabolic risk factors.

Background Cold hypersensitivity in the hands and feet (CHHF) is a common complaint in Asian female population especially in Korea. Due to the symptoms of CHHF the quality of individual's daily life can be degraded. Ucha-Shinki-Hwan (UCHA) is widely used in the treatment of various diseases including CHHF by harmonizing Yin and Yang, and improving the vitality of whole body. However, the efficacy of UCHA as a treatment option of CHHF has not been assessed in trials. Thus, we aimed to investigate the efficacy and safety of UCHA in Korean women with CHHF through this trial. Methods This study will be an exploratory, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Korean women aged 19 to 59 years who complaint with CHHF will be enrolled from 5 university affiliated Korean medicine hospitals. A total of 164 subjects will be randomly assigned to a treatment group (UCHA) or a placebo group at a 1:1 ratio. The subjects will receive 2.5 g of either UCHA or placebo three times a day for 8 weeks. The primary outcome will be evaluated with the visual analog scale score of CHHF. The secondary outcome measures will be changes in skin temperature in extremities as measured by using a thermometer and the Korean version of the World Health Organization Quality of Life Scale Abbreviated Version. Discussion This study will be the first trial to explore the efficacy and safety of UCHA for CHHF patient. This will provide meaningful clinical information on herbal medicine treatment of CHHF and a clinical evidence for planning a full randomized clinical trial. Disclosures and acknowledgments The authors report no competing interests. Trial registration This study is registered at ClinicalTrials.gov, ID: NCT03790033. Registered on (31 December 2018) PROTOCOL VERSION:: The final approved version of the trial protocol is V1.3. (25 January 2019).

Background Obesity is associated with metabolic syndrome, a condition that increases one's risk for heart disease and other conditions. The prevalence of obesity and associated diseases have steadily increased among Korean adults. The effect of the herbal medicines Daesiho-tang (DSHT) and Chowiseungcheng-tang (CST) on obesity have been reported. The purpose of this study is to evaluate the efficacy and safety of Daesiho-tang and Chowiseungcheng-tang on obese Korean women with high risk for metabolic syndrome. Methods/design This study is a randomized, double-blinded, placebo-controlled, multi-center, 3-arm, parallel group clinical trial. A total of 120 participants will be enrolled and randomly assigned to the Daesiho-tang group, the Chowiseungcheng-tang group, or the placebo group in a 1:1:1 ratio using an internet-based randomization system at visit 2. Each group will be administered DSHT, CST, or placebo 3 times per day for 12 weeks. The primary outcome is to evaluate the changes in mean body weight of participants in the DSHT and CST groups and compare with those in the placebo group, and determine their statistical significance, if any, after 12 weeks. The secondary outcomes are the following: changes in body fat percentage and body fat mass, changes in waist circumference, waist-to-hip ratio, and body mass index, changes in serum lipids, fasting blood sugar, blood pressure, and C-reactive proteins (CRP) levels between visit 1 and visit 5 measurements. Changes in visceral fat volume determined through abdominal computed tomography, patient-reported health outcomes surveys-the Korean version of the Obesity-related Quality of Life and the Korean version of Eating Attitudes Test. Discussion This study will provide research methodologies for evaluating the efficacy and safety of Daesiho-tang and Chowiseungcheng-tang on obese Korean women with high risk for metabolic syndrome. Trial registration ClinicalTrials.gov, NCT02651454. Registered on 11 January 2016.Protocol version: The final approved version of the trial protocol is V1.3.(2017.11.10).

Alzheimer's disease is a common neurodegenerative disease characterized by progressive degeneration and neuronal cell death, resulting in neural network dysfunction. As the underlying mechanisms, oxidative damage and neuroinflammation have been reported to contribute to the onset and deterioration of Alzheimer's disease. The nuclear factor E2-related factor 2-antioxidant responsive element signaling pathway is a pivotal cellular defense mechanism against oxidative stress. Nrf2, a transcription factor, regulates the cellular redox balance and is primarily involved in anti-inflammatory responses. In this study, we synthesized novel chalcone derivatives and found a highly potent Nrf2 activator, compound 20a. Compound 20a confirmed to activate Nrf2 and induce expression of the Nrf2-dependent enzymes HO-1 and GCLC at both mRNA and protein levels. It also suppressed the production of nitric oxide and downregulated inflammatory mediators in BV-2 microglial cells. We found that compound 20a effectively increased the expression level and the activity of superoxide dismutase in both BV-2 microglial cells and brain hippocampus region of the scopolamine-induced mouse model. In addition, compound 20a effectively recovered the learning and memory impairment in a scopolamine-induced mouse model.

Decreased thyroid hormone (TH) has been considered as one of the potential predictors of mortality in sepsis. This study aimed to evaluate the prognostic impact of decreased TH on mortality in septic patients during intensive care unit (ICU) admission. We included studies that assessed thyroid function by measuring the serum thyroid hormone level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, commentaries, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 1,578 patients from eight studies were included. Triiodothyronine levels in non-survivors were relatively lower than that of survivors (6 studies; standardized mean difference [SMD] 2.31; 95% confidence interval (CI), 0.52–4.10; I2 = 97%; P = 0.01). Thyroxine levels in non-survivors were also lower than that of survivors (5 studies; SMD 2.40; 95% CI, 0.91–3.89). There were no statistically significant differences in thyroid-stimulating hormone levels between non-survivors and survivors. The present meta-analysis suggested that the decreased TH during ICU admission might be associated with the increase in mortality in adult septic patients. Hence, the measurement of TH could provide prognostic information on mortality in adult septic patients.

IntroductionCancer-related fatigue is a frequent symptom in patients with cancer and one of the most distressing symptoms in patients with breast cancer. Sipjeondaebo-tang (Juzen-taiho-to in Japanese or Shi-Quan-Da-Bu-Tang in Chinese) is a widely used herbal medicine for the treatment of fatigue in Korea, China and Japan. The purpose of the present study is to evaluate the feasibility of Sipjeondaebo-tang for cancer-related fatigue.Methods and analysisThe present study is a randomised, double-blind, placebo-controlled, cross-over study. Forty-eight patients with breast cancer who are indicated for doxorubicin and cyclophosphamide will be recruited. The participants will receive 3 g of Sipjeondaebo-tang or a placebo three times a day for 56 days. The primary outcome measurement is the change in the Brief Fatigue Inventory scores. The secondary outcome measurements include the changes in the Visual Analogue Scale (VAS) of fatigue, and quality of life measured by the European Organization for Research and Treatment of Cancer—QLQ-C30 and QLQ-BR23. VAS of fatigue will be measured on every visit, and other outcomes will be measured on visits 2, 4, 6 and 7. The total study period is 14 weeks.Ethics and disseminationThis study has been approved by the Institutional Review Board of the Catholic Kwandong University International St Mary’s Hospital (reference IS16MNSI0011). The results of this study will be published in a peer-reviewed journal and presented at a scientific conference.Trial registration numberNCT02858856; Pre-results.

Aims This study aimed to evaluate the prognostic accuracy of the gray matter to white matter ratio (GWR) in predicting neurological outcomes in post-cardiac arrest patients treated with target temperature management. Data sources We systematically searched MEDLINE and EMBASE (Search date: 09/13/2017). Included studies were those evaluating neurological outcomes using the cerebral performance categories scale. We performed a subgroup analysis based on the location of the measurement. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Results In total, 1150 patients from 10 observational studies were included. GWR of the basal ganglia (BG) average showed the highest value (area under the curve [AUC] 0.96, SE 0.02, Q 0.90) compared with the putamen/posterior limb of internal capsule (AUC 0.93, SE 0.05, Q 0.87), overall average (AUC 0.91, SE 0.02, Q 0.85), and cerebrum (AUC 0.89, SE 0.05, Q 0.82) for prognostic accuracy. Furthermore, the highest pooled diagnostic odd ratio of GWR for predicting poor neurological outcomes was shown for the BG average (21.00, 95% CI 6.85–64.40) followed by the overall average (20.71, 95% CI 9.53–44.98), putamen/posterior limb of internal capsule (16.08, 95% CI 4.36–59.23), and cerebrum (13.96, 95% CI 4.26–45.76). Conclusions GWR in the early cranial computed tomography scan had high prognostic value in predicting poor neurological outcomes in post-cardiac arrest patients. The BG GWR had the highest prognostic accuracy when compared to other locations of the brain.

BACKGROUND A receptor tyrosine kinase for ephrin ligands, EPHB2, is expressed in normal colorectal tissues and colorectal cancers (CRCs). The aim of this study was to investigate EPHB2 expression over CRC progression and determine its prognostic significance in CRC. METHODS To measure EPHB2 mRNA and protein expression, real-time polymerase chain reaction and immunohistochemistry were performed in 32 fresh-frozen and 567 formalin-fixed paraffin-embedded CRC samples, respectively. We further investigated clinicopathological features and overall and recurrence-free survival according to EPHB2 protein expression. RESULTS The EPHB2 level was upregulated in CRC samples compared to non-cancerous tissue in most samples and showed a strong positive correlation with AXIN2. Notably, CD44 had a positive association with both mRNA and protein levels of EPHB2. Immunohistochemical analysis revealed no difference in EPHB2 expression between adenoma and carcinoma areas. Although EPHB2 expression was slightly lower in invasive fronts compared to surface area (p < .05), there was no difference between superficial and metastatic areas. EPHB2 positivity was associated with lymphatic (p < .001) and venous (p = .001) invasion, TNM stage (p < .001), and microsatellite instability (p = .036). Kaplan-Meier analysis demonstrated that CRC patients with EPHB2 positivity showed better clinical outcomes in both overall (p = .049) and recurrence-free survival (p = .015). However, multivariate analysis failed to show that EPHB2 is an independent prognostic marker in CRCs (hazard ratio, 0.692; p = .692). CONCLUSIONS Our results suggest that EPHB2 is overexpressed in a subset of CRCs and is a significant prognostic marker.

Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST in Korean, Danggui-Sini-Jia-Wuzhuyu-Shengian-Tang in Chinese, and Tokishigyakukagoshuyushokyoto (TJ-38) in Japanese), a well-known traditional Korean/Chinese/Japanese medicine, has long been used to treat vascular diseases such as Raynaud’s phenomenon (RP). However, anticancer effect of DSGOST remains elusive. In this study, we checked if DSGOST has an anticancer effect against gastric cancer cells, and investigated the mechanisms underlying DSGOST resistance. Moreover, DSGOST regulates chemoresistance in cisplatin-treated gastric cancer cells. Interestingly, DSGOST treatment induced the accumulation of GFP-LC3 puncta and increased the level of autophagy markers, such as LC3-II, ATG5, and Beclin-1, indicating activated autophagy. Furthermore, DSGOST could activate epithelial-to-mesenchymal transition (EMT) and exosomes via induction of autophagy. DSGOST in combination with TGFβ also induced autophagy and EMT. However, autophagy inhibition induces DSGOST-mediated cell death in gastric cancer cells. In addition, autophagy inhibition blocks the activation of DSGOST-mediated EMT markers including N-cadherin, Snail, Slug, vimentin, β-catenin, p-Smad2, and p-Smad3. Taken together, these findings indicated that prosurvival autophagy was one of the mechanisms involved in the resistance of gastric cancer to DSGOST. Targeting the inhibition of autophagy could be an effective therapeutic approach to overcome resistance to DSGOST in gastric cancer.

We performed a meta-analysis to seek evidence for the usefulness of the delta neutrophil index (DNI) as a prognostic blood biomarker for mortality in the early stage of sepsis in adults. A literature search was performed using criteria set forth in a predefined protocol. Studies of adults with sepsis that provided a DNI measurement and that had mortality as the outcome, were included. Review articles, editorials, and non-human studies were excluded. The methodological quality of identified studies was assessed independently by two authors using the Quality in Prognosis Studies (QUIPS) tool. A total of 1,822 patients from eleven studies were ultimately included. Standardized mean differences between non-survivors and survivors were compared. An elevated DNI was associated with mortality in patients with sepsis (standardized mean difference [SMD] 1.22; 95% confidence interval 0.73–1.71; I2 = 91%). After excluding two studies—one that included paediatric patients and one with a disproportionately low mortality rate—heterogeneity was minimized (SMD 0.74, 95% confidence interval 0.53–0.94; I2 = 43%). Overall, the findings suggest that high DNI values are associated with mortality in septic patients.

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

We investigated the expression profile of leucine-rich, repeat-containing, G-protein-coupled receptor 5 (LGR5) during colorectal cancer (CRC) progression and determined the prognostic impact of LGR5 in a large cohort of CRC samples. LGR5 expression was higher in CRCs than in normal mucosa, and was not associated with other cancer stem cell markers. LGR5 positivity was observed in 68% of 788 CRCs and was positively correlated with older age, moderately to well-differentiated cells, and nuclear β-catenin expression. Enhanced LGR5 expression remained persistent during the adenoma-carcinoma transition, but markedly declined in the budding cancer cells at the invasive fronts, which was not due to altered wingless-type mouse mammary tumor virus integration site family (Wnt) or epithelial-mesenchymal transition signaling. LGR5 showed negative correlations with microsatellite instability and CpG island methylator phenotype, and was not associated with KRAS or BRAF mutation. Notably, LGR5 positivity was an independent prognostic marker for better clinical outcomes in CRC patients. LGR5 overexpression attenuated tumor growth by decreasing ERK phosphorylation along with decreased colony formation and migration abilities in DLD1 cells. Likewise, knockdown of LGR5 expression resulted in a decline in the colony-forming and migration capacities in LoVo cells. Taken together, our data suggest a suppressive role of LGR5 in CRC progression.

This study aims to examine the long-term effect of adjuvant treatment in Korean Medicine (KM) clinics in ischemic stroke patients, using a national sample cohort from the National Health Insurance Service in Korea between 2010 and 2013. The National Health Insurance Service – National Sample Cohort database from 2002 to 2013 was used in this study. Ischemic stroke patients were defined and covariates were included to account for socioeconomic variables, comorbidities and disease severity. Propensity score matching was applied. Cox proportional hazards modeling and Kaplan-Meier analysis were applied to determine the differences between KM and non-KM treated groups. The results shows that KM-treated group had a higher probability of survival than non-KM group patients. No significant difference was observed between the risk of readmission between the treated and non-treated patients. Kaplan-Meier analysis showed a weak effect of KM treatments in the patients with 8 to 28 days of hospital stay for a lower risk of recurrence than in non-treated patients. In conclusion, KM treatment of mild to moderate ischemic stroke patients has a mild effect on the survival probability of stroke. Its effect for improving long-term recurrence need to be explored in the future studies.

Overcoming drug resistance is an important task for investigators and clinician to achieve successful chemotherapy in cancer patients. Drug resistance is caused by various factors, including the overexpression of P-glycoprotein (P-gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. SH003 is extracted from the mixture of three different herbs, and its anticancer effect has been revealed in different cancer cell types. In the present study, we investigated whether SH003 is able to reverse drug resistance using paclitaxel-resistant breast cancer cells (MCF-7/PAC). In our experiments, SH003 significantly decreased cell growth and colony formation in MCF-7/PAC cells and parental MCF-7 cells. This growth inhibition was related to the accumulation of cells in the sub-G0/G1 apoptotic population and an increase in the number of apoptotic cells. SH003 reduced the mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated proteins (MRPs) in MCF-7/PAC cells. SH003 also down-regulated the expression of P-gp. SH003 reversed drug efflux from MCF-7/PAC cells, resulting in rhodamine123 (Rho123) accumulation. Inhibition of drug resistance by SH003 is related to the suppression of the signal transducer and activator of transcription 3 (STAT3) signaling pathway. SH003 decreased STAT3 activation (p-STAT3) and its nuclear translocation and inhibited the secretion of VEGF and MMP-2, which are STAT3 target genes. An STAT3 inhibitor, JAK inhibitor I and an HIF-1α inhibitor decreased cell growth in MCF-7 and MCF-7/PAC cells. Taken together, these results demonstrate that SH003 can overcome drug resistance, and SH003 might be helpful for chemotherapy in cancer patients.

Background: The biological significance of FOXO1, a member of the forkhead box O transcription factor family, in gastric cancer (GC) remains unclear. The present study provides direct evidence of the role of FOXO1 in tumour growth and metastasis of GC in relation to human epidermal growth factor receptor 2 (HER2). Methods: The expressions of FOXO1 and HER2 were modulated in GC cell lines (SNU-638, MKN45, SNU-216 and NCI-N87) by stable transfections. The effects of transfection on GC phenotypes were evaluated in vitro and in animal models. In addition, the relationship between FOXO1 and HER2 was analysed using GC clinical specimens, cell lines and xenografts. Results: FOXO1 silencing in GC cells increased colony formation and mesenchymal transition in vitro, as well as tumour growth and metastasis in nude mice, whereas HER2 silencing induced the opposite results.. Furthermore, an inverse relationship between FOXO1 and HER2 was found in clinical specimens of GC, GC cells and GC xenograft tumours. Although a negative crosstalk between these two molecules was shown, double knockdown of both FOXO1 and HER2 in GC cells revealed that HER2 silencing reversed the FOXO1 shRNA-induced migration and invasion even without the FOXO1 restoration. Conclusions: Our results indicate that loss of FOXO1 promotes GC growth and metastasis by upregulating HER2 expression and that the HER2 expression is more critical to the induction of GC cell metastasis. The present study provides evidence that the FOXO1/HER2 pathway may regulate GC progression in a subgroup of GC patients.

Cells expressing LGR5, an intestinal stem cell marker, have been suggested as cancer stem cells in human colon cancers. Previously, we discovered that LGR5-expressing cells exist in the gastric antrum and remarkably increase in number in intestinal metaplasia. In addition, most gastric adenomas contain abundant LGR5-expressing cells coexpressing intestinal stem cell signatures. However, LGR5 expression in gastric cancers (GCs) and its prognostic significance remain unknown. We examined the LGR5 expression in GC tissues by real time-PCR and RNA in situ hybridization, and analyzed its clinicopathological relevance and prognostic value. The effects of LGR5 on cancer cell proliferation and migration were assessed with an in vitro transfection technique. LGR5 expression was significantly lower in GCs than in matched nontumorous gastric mucosa. RNA in situ hybridization on tissue microarrays showed that 7 % of GCs were positive for LGR5. LGR5 positivity was associated with old age, well to moderate differentiation, and nuclear β-catenin positivity. Although LGR5 did not show any prognostic significance for all GC cases, it was associated with poor survival in GCs with nuclear β-catenin expression. LGR5 expression was induced by transfection in GC cell lines with abnormal Wnt activation, which, however, showed no influence on the growth and migration of GC cells. A small portion of GCs expressed LGR5. Although LGR5 was associated with poor survival in GCs with nuclear β-catenin, LGR5 expression in GC cells had no effects on the growth and migration, requiring a further study exploring a biological role of LGR5 in GCs.

Purpose: Although a Do-Not-Resuscitate (DNR) order is widely in use, it is one of the challenging issues in end-of-life care. This study was conducted to investigate attit udes toward DNR according to education and clinical experience. Methods: Data were collected using a structured questionnaire comprisin g 30 items in a tertiary hospital in Seoul, Korea. Results: Participants were 238 nurses and 72 physicians. Most participants (99%) agreed to the necessity of DNR for reasons such as dignified death (52%), irreversible medical condition (23%) and patients' autonomy in decision making (19%). Among all, 33% participants had received education about DNR and 87% had DNR experience. According to participants' clinical DNR experience, their attitudes toward DNR significantly differed in terms of the necessity of DNR, timing of the DNR consent and post-DNR treatments including anti- biotics. However, when participants were grouped by the level of DNR education, no significant difference was observed except in the timing of the DNR consent. Conclusion: This study suggests that the attitudes toward DNR were more affected by clinical experience of DNR rather than education. Therefore, DNR education programs should involve clinical settings.

Ectopic pancreas is a well-known developmental anomaly found in approximately 2% of all autopsies, frequently in the gastrointestinal tract. Mediastinal pancreatic ectopia is very rare; only a few cases have been described in the English-language literature. According to previous reports, the pancreatic tissue is detected in the cyst wall or appears as small solid components of cystic masses within the anterior mediastinum. In this report, we present a case of ectopic pancreas appearing as a large solid mass in the anterior mediastinum of a 17-year-old male patient.

Background and Purpose Neuroinflammation through microglial activation is involved in the pathogenesis of neurodegenerative diseases including Parkinson's disease (PD), a major neurodegenerative disorder characterized by dopaminergic neuronal death in the substantia nigra. We examined our novel synthetic compound VSC2 for its anti-inflammatory properties towards development of a PD therapy. Experimental Approach We tested the effects of VSC2 on production of various NF-κB-dependent proinflammatory molecules and Nrf2-dependent antioxidant enzymes in BV-2 microglia and in vivo. Key Results The vinyl sulfone compound, VSC2, most effectively suppressed the production of NO in LPS-activated microglia. It also down-regulated expression of inducible NOS (iNOS), COX-2, IL-1β and TNF-α and inhibited nuclear translocalization and transcriptional activity of NF-κB. VSC2 increased total and nuclear Nrf2 levels, induced Nrf2 transcriptional activity and was bound to Keap1 with high affinity. Expression of the Nrf2-regulated antioxidant enzyme genes NAD(P)H quinone oxidoreducase-1 (NQO-1), haem oxygenase-1 (HO-1) and glutamylcysteine ligase (GCL) were up-regulated by VSC2. In the MPTP mouse model of PD, oral administration of VSC2 decreased the number of activated microglia in the substantia nigra, lowered the levels of iNOS, COX-2 and IL-1β, and protected the dopaminergic neurons. VSC2 also elevated the levels of NQO1, HO-1, GCL and Nrf2 in the nigrostriatal area. Conclusions and Implications VSC2 has both anti-inflammatory and antioxidant properties and prevented neuroinflammation in microglia and in an animal model of PD. This suggests VSC2 as a potential candidate for PD therapy.

Background Nodal , an embryonic morphogen, plays a role in tumorigenesis of melanoma, breast, and prostate cancer; however, its role in thyroid carcinoma is unknown. We examined Nodal expression in thyroid tumors by immunohistochemistry assay and The Cancer Genome Atlas (TCGA) analysis. Methods An immunohistochemistry assay was performed in a tissue microarray comprising 128 classic papillary thyroid carcinomas (PTC), 58 follicular thyroid carcinomas (FTC), 19 follicular variants of PTC (FVPTC), 57 follicular adenomas (FA), 54 adenomatous goiters (AG), and 5 normal thyroid tissues. The TCGA database was examined to evaluate the expression of Nodal mRNA in normal thyroid and PTC. Results The proportion of tumors showing negative Nodal expression in PTC, FTC, FVPTC, FA, and AG was 0%, 1.7%, 0%, 14%, and 41%, respectively. For the diagnosis of malignant tumors, the sensitivity, specificity, positive predictive value, and negative predictive value of positive Nodal staining was 99%, 27%, 72%, and 97%, respectively. High Nodal expression was associated with older age and BRAF mutation in PTC. TCGA analysis revealed PTC had greater Nodal mRNA expression than normal thyroid ( P = .012). Conclusion Nodal staining might be useful “rule-out test” for the diagnosis of malignant thyroid tumor. Nodal may be associated with the tumorigenesis of thyroid malignancy.

Benzyloxyphenyl moiety is a common structure of highly potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B), safinamide and sembragiline. We synthesized 4-(benzyloxy)phenyl and biphenyl-4-yl derivatives including halogen substituents on the terminal aryl unit. In addition, we modified the carbon linker between amine group and the biaryl linked unit. Among synthesized compounds, 12c exhibited the most potent and selective MAO-B inhibitory effect (hMAO-B IC50: 8.9 nM; >10,000-fold selectivity over MAO-A) as a competitive inhibitor. In addition, 12c showed greater MAO-B inhibitory activity and selectivity compared to well-known MAO-B inhibitors such as selegiline, safinamide and sembragiline. In the MPTP-induced mouse model of Parkinson’s disease (PD), 12c significantly protected the tyrosine hydroxylase (TH)-immunopositive DAergic neurons and attenuated the PD-associated behavioral deficits. This study suggests characteristic structures as a MAO-B inhibitor that may provide a good insight for the development of therapeutic agents for PD.

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.

Background ‘Work related musculoskeletal disorders (WRMSDs)’ have been mostly reported in the manufacturing industry but recently the occurrence of industrial injuries has been constantly increasing in the service industry. This research is going to analyze the data about workers’ compensation for WRMSDs in five different service sectors and identify characteristics of occupations with the highest approved occupations. Methods According to the data released from the Korea Worker’s Compensation & Welfare Service, the overview of 12,730 cases of workers’ compensation for WRMSDs in five service sectors from 2004 to 2013 is going to be analyzed and the source data is going to be classified by the Korean Standard Classification of Occupations to select the top five occupations that have the highest number of approval. Results After selecting each five occupations from the service sector that have work related musculoskeletal disorders, the result showed that the occupation with the highest number of approval in the health and social care sector were the early childhood educators, cooks in the school canteens in education services sector, garbage collectors in the sanitation and similar services sector, deliverymen in wholesale and retail, consumer goods repair and building cleaners in general management businesses such as those in building maintenance. The major event observed in the top five occupations was the overexertion and reaction as a cause of WRMSDs. The day when the WRMSDs mostly occurred was on Monday and the most likely time was 10 am. The median days away from work and lost working days are 29–90 days and 0–50 days respectively. The difference in each occupation was observed in year of service, age, and gender. Conclusions 83.21% of the approved cases of workers’ compensation for WRMSDs occurred in the top 25 occupations in all of the five service sectors, which meant that the approval of workers’ compensation is concentrated in specific occupations. This research is going to suggest preventive measures for work related musculoskeletal disorders in the service industry and to help prioritize the preventive measures. Trial registration Not applicable.

Drug resistance in chemotherapy is a serious obstacle for the successful treatment of cancer. Drug resistance is caused by various factors, including the overexpression of P‑glycoprotein (P‑gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in vivo and in vitro. In the present study, we investigated whether apigenin is able to reverse drug resistance using adriamycin‑resistant breast cancer cells (MCF‑7/ADR). In our experiments, apigenin significantly decreased cell growth and colony formation in MCF‑7/ADR cells and parental MCF‑7 cells. This growth inhibition was related to the accumulation of cells in the sub‑G0/G1 apoptotic population and an increase in the number of apoptotic cells. Apigenin reduced the mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance‑associated proteins (MRPs) in MCF‑7/ADR cells. Apigenin also downregulated the expression of P‑gp. Apigenin reversed drug efflux from MCF‑7/ADR cells, resulting in rhodamine 123 (Rho123) accumulation. Inhibition of drug resistance by apigenin is related to the suppression of the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Apigenin decreased STAT3 activation (p‑STAT3) and its nuclear translocation and inhibited the secretion of VEGF and MMP‑9, which are STAT3 target genes. A STAT3 inhibitor, JAK inhibitor I and an HIF‑1α inhibitor decreased cell growth in MCF‑7 and MCF‑7/ADR cells. Taken together, these results demonstrate that apigenin can overcome drug resistance.

Background. This survey aimed to investigate the characteristics of users and nonusers of herbal medicine and the adverse events experienced due to herbal medicines in South Korea. Methods. The questionnaire consisted of safety, using experience, using type, usage and nonusage reason, purchase location, and adverse events of herbal medicine. The survey was administered by online. Results. Of the total 1,134 respondents, 726 (64.0%) considered herbal medicine safe, and 693 (61.1%) answered that they have taken herbal medicines within the past year. Most common place to purchase them was “TKM hospital or clinic” (63.6%), and most participants (72.2%) took a decoction from a TKM institution. The biggest reason for taking them was for “health improvement” (57.3%), and the reasons for not using them was “medication not necessary” (63.7%). Among those who took herbal medicines, 46 experienced adverse events, and the most frequently reported symptoms were digestive disorders (52.2%). Of the 46 participants who experienced adverse events, 20 (43.5%) were treated by TKM doctors. Conclusions. This study suggests that regulation of herbal medicines is needed in order to resolve problems related to the safety of herbal medicines.

Background Obesity is a public health concern in many countries due to its increasing prevalence. Euiiyin-tang is an herbal medicine formula often used as a clinical treatment for obesity. It acts to eliminate humidity and purify the blood, the causes of obesity identified by the theoretical framework of Korean medicine. The purpose of this study is to evaluate the efficacy and safety of Euiiyin-tang in treating obesity. Methods/design This study is a randomised, double-blinded and placebo-controlled, multicentre trial. It has two parallel arms: the Euiiyin-tang group and the placebo group. A total of 160 obese adult women will be enrolled in the trial. The participants will be randomly divided at a 1:1 ratio at visit 2 (baseline). The participants will be administered Euiiyin-tang or placebo for 12 weeks. The primary endpoint is the change in weight occurring between baseline and post-treatment. The secondary outcomes include average weight reduction, changes in body fat, waist and hip circumferences, body mass index, and lipid profile, and the results of questionnaires such as the Korean version of Obesity-related Quality of Life, the Korean version of Eating Attitudes Test, the Social Readjustment Rating Scale, and the Stress Reaction Inventory. Discussion The present study will provide research methodologies for evaluating the efficacy and safety of Euiiyin-tang in patients with obesity. In addition, it will provide evidence of correlation between obesity and Sasang constitutional medicine. Trial registration ClinicalTrials.gov, NCT01724099. Registered on 2 November 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2039-8) contains supplementary material, which is available to authorized users.

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.

The purpose of this study is to investigate the effect of new materials from the traditional herbal medicines which induce anti-aging and anti-melanogenesis process of skin in vitro. Among 22 traditional herbal medicines which were tested in this study, Rhus vernciflua stokes (RVS) showed prominent effects for anti-aging and whitening of skin compared to other herbal extracts. In our study, RVS showed the highest elastase inhibitory effect and a higher anti-tyrosinase activity. Pretreatment with RVS significantly inhibited the expressions of UVB-induced MMP-1 protein and mRNA in a dose-dependent manner, and also inhibited the UV-induced activation of extracellular signal regulated kinase (ERK). In whitening, it was found that RVS significantly inhibits melanin biosynthesis in a dose-dependent manner. Moreover, α-MSH-induced increases of microphthalmia-associated transcription factor (MITF) and tyrosinase were significantly inhibited in B16F1 melanoma cells treated with RVS. Therefore, these data suggest that RVS extracts could be a potential agent for the prevention and treatment of skin photoaging and hyperpigmentation.

Objective : This study aimed to assessment for concordance rate in pattern analysis between pattern diagnosis of KiFDA on allergic rhinitis in 2008 and doctor of Korean medi cine. Methods : Data were obtained from 35 patients with allergic rhinitis(AR). They were asked to perform the questionnaires and had been interviewed by specialist of Korean Medicine. For correlation analysis, we used Cohen's Kappa. Results : The pattern diagnosis was done only 15 patients(42.9%). Corr elation between pattern diagnosis of questionnaires and specialist showed 0.2105 in Kappa and 0.1993 in weighed Kappa. Conclusions : The result may provide the basis of modification in Pattern Diagnosis of KiFDA on allergic rhinitis in 2008.Key words ; Pattern diagnosis; Allergic rhinitis ⓒ 2014 the Society of Korean Medical Ophthalmology & Otolaryngo logy & DermatologyThis is an Open Access journal distributed under the terms of t he Creative Commons Attribution Non-Commercial License (http://creativecommons.org/license/by-nc/3.0/) which permits u nrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 is a prospective, assessor-blinded, parallel-group, randomized controlled pilot trial to explore the effectiveness of 12-week adjuvant moxibustion therapy for arthralgia in menopausal females at stage I to III breast cancer on aromatase inhibitor (AI) administration, compared with those receiving usual care.

Introduction In Korea, low back pain (LBP) which is occupation-related symptom is one of the major health issues owing to rapid industrialization. Even traditional Korean medicine has the long history in pain treatment, there still has been lack of supporting evidence on herbal prescription itself. Sogyeonghwalhyeol-tang, a Korean herbal medicine prescription, has been suggested as a medication for treating chronic LBP as well as work-related pains. Objective This study aims to evaluate the clinical efficacy and safety of herbal medicine, Sogyeonghwalhyeol-tang on work-related chronic LBP patients. Method This trial is designed as a multicenter, randomized, controlled, clinical trial. Seventy-two participants who have chief complaint of LBP in Korean medicine rehabilitation center will be randomly assigned to ether Sogyeonghwalhyeol-tang group or placebo group with a ratio of 1:1. They will receive assigned drugs in 4 weeks and follow-up for 2 weeks. Discussion The result of this study will provide the valuable information for efficacy and safety of Sogyeonghwalhyeol-tang for patients with work-related chronic LBP.

Introduction:This is a prospective, open-label, parallel-group, randomized controlled trial that evaluates the effectiveness and safety of adjuvant application of Jaungo (JUG) for radiation-induced dermatitis (RD) in breast cancer patients undergoing radiation therapy, in comparison with gen

Isolating the effects of a single nutrient or food in relation to health outcomes including increased skeletal muscle mass is a challenging task because dietary constituents are highly correlated and synergistic. Hence, diet pattern analysis may be used to investigate the role of certain diets in health outcomes. The present study investigated the dietary patterns and their relationship to skeletal muscle mass in Korean adults. Data were extracted from the 2008-2011 Korea National Health and Nutrition Examination Surveys. To explore the dietary patterns of the study subjects, factor analysis was performed using data obtained from a 24-hour recall. The skeletal muscle index according to dietary pattern scores was then investigated to estimate the changes in skeletal muscle mass. Three patterns were initially identified from the factor analysis. Of these vegetables and fish (VF) pattern was the primary factor with high reliability and was a common factor in sex-separated analyses. The VF pattern scores were positively associated with increased skeletal muscle mass in both men and women. Further analysis according to quartile levels of VF pattern scores showed a positive association between skeletal muscle mass and VF pattern in men but not in women. These results suggest that dietary patterns focused on vegetables and seafoods may contribute to increased skeletal muscle mass in Korean men but that sex difference should be considered in nutrition care for skeletal muscle health.

Inflammatory response is a major defense mechanism against pathogens and chemical or mechanical injury. Rhus verniciflua Stokes (RVS) has traditionally been used as an ingredient in East Asian medicine for the treatment of gastritis, stomach cancer and atherosclerosis. The aim of the current study was to analyze the effect of RVS on LPS‑induced inflammatory responses in the RAW264.7 mouse macrophage cell line. RAW264.7 cells were treated with various concentrations of RVS and LPS at specific time points. WST assay, trypan blue assay and quantification of activated cells revealed that RVS suppressed cell proliferation in a dose‑dependent manner. RVS induced G1 cell cycle arrest, suppressed iNOS and COX‑2 mRNA expression induced by LPS and decreased intracellular ROS levels induced by LPS. In addition, RVS induced PARP and caspase‑3 cleavage suggesting that RVS causes cell death. Results of the present study indicate that RVS may be advantageous in treating inflammatory disease.

P-wave velocity was measured by the low frequency flaw detector in order to analyze the weathered state of a halo stone Buddha, Unju temple, Hwasun, Korea. By the results of laboratory tests on a fresh acidic tuff with the same rock of a halo stone Buddha, average absorption, average P-wave velocity, and average uniaxial compressive strength were 5.38%, 4,008 m/s, and 70.1 MPa, respectively. The results correspond to moderately strong rock. Average P-wave velocity of a halo stone Buddha measured by the low frequency flaw detector was 2,257 m/s in the left zone, 3,437 m/s in the right zone, and 2,802 m/s overall. Weathering index of a halo stone Buddha was 0.45 in the left zone, 0.21 in the right zone, and 0.33 overall. Comparing the results of a halo stone Buddha with them of laboratory tests, weathered state of a halo stone Buddha was analyzed highly weathered state in the left zone and moderately weathered state in the right zone. Furthermore, it suggests that the left zone of a halo stone Buddha was affected weathering more than the right one. Overall a halo stone Buddha corresponds to moderately weathered state of weathering degrees. In conclusion, it is considered that low frequency flaw detector may be applicable as a valuable method on analyzing the P-wave velocity of the stone cultural heritage with an irregular surface.

Background Silibinin is the major active molecule of silymarin, the mixture of flavonolignans extracted from Cirsium japonicum. It has been used for the treatment of hepatitis and inflammation-related diseases. In the present study, the effects of silibinin on allergic inflammation and its signaling were investigated in the induced human mast cells. Methods Cell growth inhibition induced by silibinin was measured by MTS assay. Histamine release was measured by enzyme immunoassay. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) secreted protein levels and mRNA levels were measured by the ELISA assay and RT-PCR, respectively. The NF-κB promoter activity was examined by a luciferase assay. Results Silibinin suppressed the growth of HMC-1 cells and also reduced the production and mRNA expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8. Moreover, silibinin inhibited the nuclear translocation of nuclear factor (NF)-κB through inhibition of the phosphorylation of IκBα and suppressed NF-κB transcriptional activity in stimulated HMC-1 cells. Conclusions Taken together, these results indicate that silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells, suggesting that silibinin could be used for the treatment of mast cell-derived allergic inflammatory diseases.

Objectives:The aim of this study was to systematically assess the long-term (≥ 6 months) benefits of epidural steroid injection therapies for patients with low back pain.Methods:We identified randomized controlled trials by database searches up to October 2011 and by additional hand searches without language restrictions. Randomized controlled trials on the effects of epidurals for low back pain with follow-up for at least 6 months were included. Outcomes considered were pain relief, functional improvement in 6 to 12 months after epidural steroid injection treatment and the number of patients who underwent subsequent surgery. Meta-analysis was performed using a random-effects model.Results:Twenty-nine articles were selected. The meta-analysis suggested that a significant treatment effect on pain was noted at 6 months of follow-up (weighted mean difference [WMD], −0.41; 95 percent confidence interval [CI], −0.66 to −0.16), but was no longer statistically significant after adjusting for the baseline pain score (WMD, −0.19; 95 percent CI, −0.61 to 0.24). Epidural steroid injection did not improve back-specific disability more than a placebo or other procedure. Epidural steroid injection did not significantly decrease the number of patients who underwent subsequent surgery compared with a placebo or other treatments (relative risk, 1.02; 95 percent CI, 0.83 to 1.24).Conclusions:A long-term benefit of epidural steroid injections for low back pain was not suggested at 6 months or longer. Introduction of selection bias in the majority of injection studies seems apparent. Baseline adjustment is essential when we evaluate pain as a main outcome of injection therapy.

Objectives : We performed a pilot study to investigate inter- and intra-r ater reliability of pattern identification using nasal endoscopy for allergic rhinitis(AR). Methods : Eight experts of ophthalmology, otolaryngology and dermatolo gy of Korean medicine evaluated 20 nasal endoscopy photograph cases of AR patients with pattern id entification index using nasal endoscopy for AR including the nasal membrane color(pale / hyperemia), nasal mem brane humidity(dryness / dampness), rhinorrhea(watery / yellow), and membrane edema (atrophic / ede matous) on nasal endoscopy. Results : Intra-rater agreement(%) and Kappa coefficient was generally from 'moderate' to 'good'(% agreement: 73.13-90% / Kappa coefficient: 0.547-0.748). Inter-rater agreement(%) and Kappa coefficient was also from 'moderate' to 'good' (% agreement: 65-85% / Kappa: 0.475-0.778) except 'humidity(dryness / dampness)' item (% agreement: 55.98% / Kappa: 0.340). In findings of subgroup anal ysis according to affiliation of raters, Inter-rater agreement(%) and Kappa coefficient of raters in same affiliatio n was higher than inter-rater agreement(%) and Kappa coefficient of raters in different affiliation except 'dr yness / dampness' item. Conclusions : It is necessary to improve objectivity and reproducibility o f pattern identification using nasal endoscopy for allergic rhinitis(AR) through the development of detail-oriented criteria and enhanced training of clinicians with development of standard operating procedures(SO Ps).Key words : Allergic Rhinitis; Nasal Endoscopy; Pattern Identification

Objective. This study was a multicenter, randomized, double-blind, and controlled trial with two parallel arms: the GJBNH group and the placebo group. This trial recruited 100 women aging 18 to 35 years with primary dysmenorrhea caused by blood stagnation. The investigational drugs, GJBNH or placebo, were administered for two menstrual periods (8 weeks) to the participants three times per day. The participants were followed up for two menstrual cycles after the administration.Results. The results were analyzed by the intention-to-treat (ITT) dataset and the per-protocol (PP) dataset. In the ITT dataset, the change of the average menstrual pain VAS score in the GJBNH group was statistically significantly lower than that in the control group. Significant difference was not observed in the SF-MPQ score change between the GJBNH group and the placebo group. No significant difference was observed in the PP analyses. In the follow-up phase, the VAS scores of the average menstrual pain and the maximum menstrual pain continually decreased in the placebo group, but they increased in the GJBNH group.Conclusion. GJBNH treatment for eight weeks improved the pain of the dysmenorrhea caused by blood stagnation, but it should be successively administered for more than two menstrual cycles.Trial Registration. This trial is registered with Current Controlled Trials no.ISRCTN30426947.

Cancer-associated fibroblasts are the dominant cell population in the cancer stroma. Gremlin 1 (GREM1), an antagonist of the bone morphogenetic protein pathway, is expressed by cancer-associated fibroblasts in a variety of human cancers. However, its biological significance for cancer patients is largely unknown. We applied RNA in situ hybridization to evaluate the prognostic value of stromal GREM1 expression in a large cohort of 670 colorectal cancers (CRCs). Overall, GREM1 expression in CRCs was lower than that of the matched normal mucosa, and GREM1 expression had a strong positive correlation with BMI1 and inverse correlations with EPHB2 and OLFM4. RNA in situ hybridization localized the GREM expression to smooth muscle cells of the muscularis mucosa and fibroblasts around crypt bases and in the submucosal space of a normal colon. In various colon polyps, epithelial GREM1 expression was exclusively observed in traditional serrated adenomas. In total, 44% of CRCs were positive for stromal GREM1, which was associated with decreased lymphovascular invasion, a lower cancer stage, and nuclear β-catenin staining. Stromal GREM1 was significantly associated with improved recurrence-free and overall survival, although it was not found to be an independent prognostic marker in multivariate analyses. In addition, for locally advanced stage II and III CRC, it was associated with better, stage-independent clinical outcomes. In summary, CRCs are frequently accompanied by GERM1-expressing fibroblasts, which are closely associated with low lymphovascular invasion and a better prognosis, suggesting stromal GREM1 as a potential biomarker and possible candidate for targeted therapy in the treatment of CRCs.

We performed a meta-analysis to compare the impact of extracorporeal cardiopulmonary resuscitation (ECPR) to that of conventional cardiopulmonary resuscitation (CCPR) in adult patients who experience cardiac arrest of cardiac origin. A literature search was performed using criteria set forth in a predefined protocol. Report inclusion criteria were that ECPR was compared to CCPR in adult patients with cardiac arrest of cardiac origin, and that survival and neurological outcome data were available. Exclusion criteria were reports describing non-cardiac origin arrest, review articles, editorials, and nonhuman studies. The efficacies of ECPR and CCPR were compared in terms of survival and neurological outcome. A total of 38,160 patients from 7 studies were ultimately included. ECPR showed similar survival (odds ratio [OR] 2.26, 95% confidence interval [CI] 0.45–11.20) and neurologic outcomes (OR 3.14, 95% CI 0.66–14.85) to CCPR in out-of-hospital cardiac arrest patients. For in-hospital cardiac arrest (IHCA) patients, however, ECPR was associated with significantly better survival (OR 2.40, 95% CI 1.44–3.98) and neurologic outcomes (OR 2.63, 95% CI 1.38–5.02) than CCPR. Hence, ECPR may be more effective than CCPR as an adjuvant therapy for survival and neurologic outcome in cardiac-origin IHCA patients.

Although Korean Medicine (KM) is an important part of the Korean healthcare system and plays a significant role in chronic and incurable diseases, there is insufficient information about KM utilization. The aim of the study was to identify KM utilization patterns using a national representative sample data.KM users aged 0-80 years and older from the nationally representative sample in the National Health Insurance Service-National Sample Cohort of 778,506 KM users between 2002 and 2013 (were analyzed. Annual changes in utilization patterns were analyzed by sex, nine age groups, five income levels, and numbers of visits and hospitalizations. Utilization patterns by the type of healthcare institution and the top 10 major diseases were studied.Frequencies of KM use differed according to analyses of patients and claims. Women used KM 1.5 times more than did men. Patients in their 40s and 50s made up one third of KM users. In contrast to other studies, high-income groups used KM more than did low-income groups. More than 96% of ambulatory patients used mostly KM clinics, and more than 76% of inpatients used KM hospitals. Musculoskeletal disorders were the main disease treated, which conformed to the results of previous studies.The results suggest that women, people in their 40s and 50s, and people with a relatively high income use KM more often than other patients. Further comparison studies of both Western medicine in Korea and other countries should be conducted.

Background Since the biological function of c-Jun N-terminal kinase (JNK) in gastric cancer remains unclear, we investigated the clinical significance of JNK activation and its association with FOXO1 activation. Methods Immunohistochemical tissue array analysis of 483 human gastric cancer specimens was performed, and the results of the immunostaining were quantified. The correlation between JNK activation (nuclear staining for pJNK) and clinicopathological features, the proliferation index, prognosis or FOXO1 inactivation (cytoplasmic staining for pFOXO1) was analyzed. The SNU-638 gastric cancer cell line was used for in vitro analysis. Results Nuclear staining of pJNK was found in 38 % of the gastric carcinomas and was higher in the early stages of pTNM (P

The biomedical effects of natural products have been increasingly identified. Korean medicine originates from prehistoric times and shares its origin with Chinese medicine. However, Korean medicine, compared with the Chinese medicine, is not well known relatively. Though Korean medicine and Chinese medicine have a lot in common, Korean medicine has developed its own realm by developing unique approaches and research—“Four-Constitution (Sasang Constitutional) Medicine” as one of the diagnostic tools and Saam acupuncture as one of the treatments. In recent years, Korean medicine expanded its usages, thus, by integrating both traditional and modern approaches. Korean medicine covers many complementary and alternative approaches that are actively validated and developed. These efforts in the field of Korean medicine have been, and will be, an important contribution to the evidence-based complementary and alternative medicine. This special issue will introduce you to the history and current status of evidence-based Korean medicine with a focus on the recent developments. The following is a brief overview of the articles in this special issue. Biological activities of a compound or a mixture of herbal medicines in Korean medicine are explored on such conditions as nephrotoxicity, experimental colitis, vasoconstriction, cancer cell growth, multidrug resistant cancer cell growth, neutropenia, obesity and adipogenesis, adipocyte differentiation, cartilage degradation in arthritis, and inflammatory neuronal damage or on such an effect as stimulating osteogenic differentiation of bone marrow mesenchymal stem cells. For the sake of safe and effective use of herbal medicine in Korean medicine, potential interaction has to be cleared. Interaction between herb and herb or between herb and drug was investigated. Traditional rules on combining herbs for synergistic effect were validated. Effects on cytochrome P450 enzyme mediated drug metabolism were investigated in relation to herbal mixture. Randomized controlled trials were reported on the effect of Korean herbal medicine on dysmenorrhea and obesity. A new real-time measurement system using a wireless inertial measurement unit was developed and reported to be reliable and effective in measuring three-dimensional cervical spine movements. As an effort to explore the diagnostic concept of Korean medicine, conceptual perception on pattern identification was explored with regard to a phlegm pattern. Recent developments on voice-based approach to Four-Constitution Medicine were reviewed. Tinnitus patients treated in Korean medicine clinic were shown to be on sympathetic overactivity with chronic tinnitus more affecting the autonomic indices. In this special issue, several newly developed treatments are also introduced. The effect of cosmetic acupuncture was explored on facial elasticity in an open-label, single-arm pilot study. The effect of newly developed temporomandibular joint therapy targeting the postural Yin-Yang balance of the whole body was documented in a case series study. Detoxification program involving fasting, fluid administration, acupuncture, and herbal wet wrap dressing was reported to be positive for refractory cases of atopic dermatitis. As an exploration on varied application of herbal medicine, it was found to be safe and effective in hypertensive blood pressure when applied as enema agent. These therapies warrant further study with more rigid study design. Seong-Gyu Ko Bharat B. Aggarwal Mingyao Liu Chang Shik Yin Dong Hoon Jin Bo-Hyoung Jang