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Rhus verniciflua Stokes (RVS) is a plant with a long history of medicinal use in Eastern Asia. RVS has been widely used to treat gastritis, stomach cancer and atherosclerosis. The cytotoxic effects of different solvent fractions from an RVS ethanol extract were measured in 11 human cancer cell lines. The study showed that the ethyl-acetate (EtOAC) fraction was the most cytotoxic. This fraction contains a number of phenolic compounds, and this phenolic-rich EtOAC fraction was particularly effective against gastric and breast cancer cells. A purified phenolic-rich EtOAC fraction (PPEF) had a stronger apoptotic effect on these cells. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that the PPEF contained gallic acid, protocatechuic acid, fisetin, sulfuretin, butein and 8 unknown compounds. There were only small amounts of flavonoids: fisetin, sulfuretin and butein. The results showed that PPEF induces apoptosis only in gastric and breast cancer cell lines, but not in lung, colon or liver cancer cell lines. Therefore, PPEF may have a significant potential as an organ-specific anti-cancer agent. [ABSTRACT FROM AUTHOR]

Abstract Background At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs) death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis. Apoptosis occurs in not only neuron but also in NPCs and neuroblast. When growth and survival signals such as EGF or LIF are removed, apoptosis is activated as well as the induction of differentiation. To investigate the regulation of cell death during developmental stage, it is essential to investigate the regulation of apoptosis of NPCs. Methods Neural progenitor cells were cultured from E14 embryonic brains of Sprague-Dawley rats. For in vivo VPA animal model, pregnant rats were treated with VPA (400 mg/kg S.C.) diluted with normal saline at E12. To analyze the cell death, we performed PI staining and PARP and caspase-3 cleavage assay. Expression level of proteins was investigated by Western blot and immunocytochemical assays. The level of mRNA expression was investigated by RT-PCR. Interaction of Bcl-XL gene promoter and NF-κB p65 was investigated by ChIP assay. Results In this study, FACS analysis, PI staining and PARP and caspase-3 cleavage assay showed that VPA protects cultured NPCs from cell death after growth factor withdrawal both in basal and staurosporine- or hydrogen peroxide-stimulated conditions. The protective effect of prenatally injected VPA was also observed in E16 embryonic brain. Treatment of VPA decreased the level of IκBα and increased the nuclear translocation of NF-κB, which subsequently enhanced expression of anti-apoptotic protein Bcl-XL. Conclusion To the best of our knowledge, this is the first report to indicate the reduced death of NPCs by VPA at developmentally critical periods through the degradation of IκBα and the activation of NF-κB signaling. The reduced NPCs death might underlie the neurodevelopmental defects collectively called fetal valproate syndrome, which shows symptoms such as mental retardation and autism-like behavior.

Abstract Background Prenatal ethanol exposure during pregnancy induces a spectrum of mental and physical disorders called fetal alcohol spectrum disorder (FASD). The central nervous system is the main organ influenced by FASD, and neurological symptoms include mental retardation, learning abnormalities, hyperactivity and seizure susceptibility in childhood along with the microcephaly. In this study, we examined whether ethanol exposure adversely affects the proliferation of NPC and de-regulates the normal ratio between glutamatergic and GABAergic neuronal differentiation using primary neural progenitor culture (NPC) and in vivo FASD models. Methods Neural progenitor cells were cultured from E14 embryo brain of Sprague-Dawley rat. Pregnant mice and rats were treated with ethanol (2 or 4 g/kg/day) diluted with normal saline from E7 to E16 for in vivo FASD animal models. Expression level of proteins was investigated by western blot analysis and immunocytochemical assays. MTT was used for cell viability. Proliferative activity of NPCs was identified by BrdU incorporation, immunocytochemistry and FACS analysis. Results Reduced proliferation of NPCs by ethanol was demonstrated using BrdU incorporation, immunocytochemistry and FACS analysis. In addition, ethanol induced the imbalance between glutamatergic and GABAergic neuronal differentiation via transient increase in the expression of Pax6, Ngn2 and NeuroD with concomitant decrease in the expression of Mash1. Similar pattern of expression of those transcription factors was observed using an in vivo model of FASD as well as the increased expression of PSD-95 and decreased expression of GAD67. Conclusions These results suggest that ethanol induces hyper-differentiation of glutamatergic neuron through Pax6 pathway, which may underlie the hyper-excitability phenotype such as hyperactivity or seizure susceptibility in FASD patients.

The effects of wet-aging using a commercial refrigerator (CR, 4°C) and a pulsed electric field refrigerator (PEFR, 0°C and -1°C) on the quality of sous vide pork loin were analyzed. The moisture and fat contents, pH, CIE L*, CIE b*, chroma, and shear force of the wet-aged samples were lower than those of the raw meat samples, whereas the water holding capacity (WHC) was higher. The PEFR group showed higher pH, CIE b*, chroma, and WHC and lower weight loss than the CR samples. Electronic nose analysis indicated that positive flavor compounds were induced whereas negative flavor compounds were inhibited in the PEFR group. Wet-aging increased the sourness, saltiness, and umami of sous vide pork loin; the PEFR 0°C samples showed the highest umami. Sensory evaluation indicated that wet-aging improved the color of sous vide pork loin. The PEFR 0°C samples were rated higher than the raw meat and CR samples for all sensory traits. In conclusion, sous vide after wet-aging using a PEFR improved the quality of pork loin., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

The effects on the quality of loin ham from using wet-aging with a commercial refrigerator (CR) and with a pulsed electric field system refrigerator (PEFR, at 0 and - 1 °C) were compared. The CR sample recorded an increased cooking loss alongside a decrease in color stability and shear force. In contrast, the samples using PEFR observed improved color stability, water holding capacity, and weight loss. In electronic nose analysis, wet-aging samples were shown to be significantly different from raw meat samples, however, the use of PEFR did not significantly affect the flavor. In electronic tongue analysis, wet-aging was observed to increase the umami of the loin ham, whilst the PEFR - 1 °C sample showed the highest umami. In sensory evaluation, the PEFR 0 °C sample showed significantly higher overall acceptability than raw meat. Conclusively, the application of wet-aging with PEFR in the manufacturing of loin ham led to an improvement in quality., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Migraine is a relatively common disease that has a significant effect on the daily activities of affected individuals. The purpose of this study was to explore the effects of herbal medicine (Jodeungsan, JDS) on migraine., Methods: Sixty-four patients with migraine were recruited and randomized to either the JDS or placebo group at a 1:1 ratio. The subjects received JDS or placebo daily for four weeks. The primary outcome was a change in the number of headache attack days (HADs), and the secondary outcome measures were the headache impact test (HIT), migraine-specific quality of life (MSQoL), the deficiency and excess pattern identification questionnaire (DEPIQ), the cold and heat pattern identification questionnaire (CHPIQ), and the blood stasis pattern questionnaire (BSPQ)., Results: In all, 61 of the 64 patients took the investigational drugs for four weeks. The number of HADs did not significantly differ between the JDS and placebo groups at the end of the study. However, the HIT and MSQoL results showed significant improvement over the baseline in both groups., Conclusion: JDS did not have a significant effect on chronic migraine. Larger studies are needed to confirm this result., Trial Registration: Clinical Research Information Service (https://cris.nih.go.kr/): KCT0003121., Competing Interests: The authors declare no conflict of interests., (© 2022 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Background: In Korea, Gyejibongnyeong-Hwan (GBH), a herbal decoction used to treat blood stasis (BS), is widely used to treat shoulder pain in clinics. Nevertheless, the therapeutic mechanism of GBH in alleviating shoulder pain has not yet been elucidated., Purpose: In this study, we applied mass spectrometry-based metabolomics to explore the therapeutic mechanism of GBH in BS-induced shoulder pain., Study Design: We conducted a two-center, randomized, wait-list controlled pilot trial to explore the therapeutic effect of GBH on shoulder discomfort related to BS., Methods: A total of 40 participants with shoulder pain were randomly assigned to either the immediate treatment (GBH-Treat; n = 20) or waiting treatment (Wait-List; n = 20) group. A non-targeted metabolomics approach was then applied to investigate the therapeutic mechanism of GBH., Results: After 8 weeks of treatment, the visual analog scale (VAS) scores for shoulder pain decreased significantly in the GBH-Treat and Wait-List groups compared with baseline VAS scores (p = 0.004 and p = 0.013, respectively). However, the VAS and BS scores were significantly more reduced in the GBH-Treat group than in the Wait-List group. The plasma metabolic pattern between GBH-Treat and Wait-List groups also differed significantly, which was shown by the score plot of a partial least-squared-discriminant analysis (R 2  = 0.806 and Q 2  = 0.229, p = 0.016). Arginine, bilirubin, carnitine, glutamine, maltol, mystic acid, N,N dimethylarginine, trimethylamine N-oxide, valine, kynurenine, and linoleic acid significantly contributed to the different metabolic patterns between the GBH-Treat and Wait-List groups (all p < 0.05). Pathway analysis revealed that these metabolites were involved in arginine biosynthesis and tryptophan metabolism, which are related to pain generation and transmission. We also confirmed that the ratio of kynurenine to tryptophan, one of the indicators for chronic pain and neuro-inflammation, was significantly lower in the GBH-Treat group than in the Wait-List group (p = 0.02)., Conclusion: These results demonstrated that GBH may be a potential treatment option for shoulder pain, and it acts by regulating metabolic patterns. In particular, our study provides evidence for the use of GBH treatment for patients with should pain caused by BS, and we believe that our findings can provide evidence for precision medicine based on traditional Chinese medicine (TCM) or traditional Korean medicine (TKM). We also verified that metabolomics studies provide comprehensive understanding of herbal decoctions in TCM or TKM., (Copyright © 2022. Published by Elsevier GmbH.)

The effect of hot-air dried Lentinula edodes pileus (DLE) on the quality and organoleptic properties of rolled-dumplings was evaluated. DLE was prepared by drying at 60°C for 24 h and added (Non, 7%, and 9%) to rolled-dumplings. The proximate composition, pH, color (CIE L*, a*, b*), and cooking yield were analyzed. Texture profile analysis, electronic-nose (e-nose), electronic-tongue (e-tongue), and organoleptic evaluation were also conducted. The cooking yield of dumplings with 9% DLE was significantly lower than that of the congeners without DLE, whereas 7% DLE did not lead to significant differences compared without DLE. With increasing DLE addition, the pH and lightness of the dumplings decreased significantly, whereas the redness tended to increase. The texture profile was significantly higher for the dumplings with DLE compared to those without DLE. E-nose analysis confirmed that DLE addition led to the positive odors (methanethiol: meaty, sulfurous; 3-methylbutanal: malty, toasted) and the negative odors (trimethylamine: ammoniacal; acetic acid: acidic, sour). E-tongue analysis showed that DLE addition decreased the intensity of the sourness and increased the intensity of the saltiness and umami of rolled-dumplings. DLE addition improved the overall organoleptic properties, but 9% DLE can be recognized as a foreign substance in organoleptic acceptance. Consequently, DLE has the potential to serve as a flavor and odor enhancer for rolled-dumplings, and the addition of DLE can positively improve consumer acceptance by improving the quality and organoleptic properties., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Background and Objectives : Migraine headaches are chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as facial flushing, nasal stuffiness, and sweating. Their major treatment methods include medication and cognitive behavioral therapy (CBT). CBT has been used for pain treatment and various psychogenic neurological diseases by reducing pain, disability, and emotional disorders caused by symptoms of mental illness and improving the understanding of mental health. This study aimed to evaluate the effectiveness and safety of CBT in treating migraines. Materials and Methods : Seven electronic databases were searched from the date of inception to December 2020. Randomized controlled studies (RCTs) using CBT as an intervention for migraine were included. The primary outcome of this study was to determine the frequency of migraines and the intensity of migraines on Visual Analog Scale (VAS), the frequency of drug use, Migraine Disability Assessment (MIDAS), and Headache Impact Test (HIT-6) index. The two authors independently conducted the data extraction and quality assessment of the included RCTs, and conducted meta-analysis with RevMan V.5.4. Results : Among the 373 studies, 11 RCTs were included in this systematic review. Seven out of the 11 RCTs were conducted in the USA, and four were conducted in the UK, Germany, Iran, and Italy, respectively. Headache frequency and MIDAS scores were statistically significant reduced. In the subgroup analysis, headache strength was significantly reduced. Two of the included studies reported adverse effects, including worsening of migraine intensity and frequency, respiratory symptoms, and vivid memory of a traumatic event. Conclusions : CBT for migraine effectively reduced headache frequency and MIDAS score in meta-analysis and headache intensity subgroup analysis, with few adverse events. Additional RCTs with CBT for migraine headaches are needed for a more accurate analysis.

The objective of the study was to explore the status of usage of complementary and alternative medicine (CAM) among Korean elite athletes. A survey was emailed to all Korean national sports federations recognized by the International Olympic Committee and the Olympic Council of Asia. A total of 705 Korean elite athletes participated in this study. The athletes had to be any of the following to participate in this survey: elite intercollegiate athletes, professional athletes, and national team athletes. 83.3% of the participants stated that they have previously experienced Korean medicine (KM). Compared to the general population in Korea, athletes had more experience (general population = 73.8%). The participants without experience mentioned that they either did not need any KM treatments (39.8%) or lacked information (39.8%) regarding KM treatments. The primary reason for the utilization of KM was the effectiveness of treatments. Therefore, 70.8% of the participants have mentioned recommending KM to others. Generally, athletes are worrisome that the consumption of herbal medicine may not be doping-free; however, it is vital to note that 62% of the participants expressed that prescribed herbal medicine is safe. Overall, this research demonstrates a high prevalence of KM usage by intercollegiate, professional, and national team athletes in Korea. Hence, this study's results may serve as the foundation in future research directions for promoting KM among Korean elite athletes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Bo-Young Youn et al.)

Background: Cold hypersensitivity in the hands and feet (CHHF) commonly affects Asian women, especially Korean women, and it negatively impacts the quality of life of the affected individuals. One commonly used herbal prescription for treating CHHF is Onkyeong-tang (OKT). Although OKT is widely used clinically in treating CHHF, no randomized clinical trial has been performed to evaluate the efficacy and safety of OKT in the treatment of cold hypersensitivity in the feet (CHF). This clinical trial aims to provide objective evidence for the basis of using OKT in the treatment of CHF in Korean women., Methods: This trial will be a double-blind, randomized, placebo-controlled, parallel-group, multicenter pilot study. A total of 112 participants will be randomly divided into an OKT treatment group or a placebo group with a 1:1 ratio via a web-based randomization system. The OKT and placebo groups will receive prescribed medications orally three times per day (3 g each time) before or between meals for 8 weeks. The primary outcome studied will be the changes in Visual Analog Scale (VAS) scores of CHF from baseline. Secondary outcomes studied will be the VAS score changes of cold hypersensitivity in the hands, changes in the skin temperature of the hands and feet, total scores of the Korean version of the World Health Organization Quality of Life Scale-abbreviated version, and the results of the cold stress test., Discussion: This trial will be the first clinical trial to assess the efficacy and safety of OKT in the treatment of CHF. We anticipate that the findings of the study will provide evidence for the basis of using OKT in treating CHF symptoms and generate basic data for designing a further large-scale randomized clinical trial., Trial Registration: Clinical Research Information Service (CRIS): KCT0003723. Retrospectively registered on 8 April 2019.

After publication of our article [1] the authors have notified us that one of the names has been incorrectly spelled.

Background: Shoulder pain is an uncomfortable feeling in the muscle around the shoulder. The cause of myalgia is the accumulation of lactic acid in muscles and impaired blood circulation, which is called blood stasis in traditional East Asian medicine. This study aimed to explore the therapeutic effect of Gyejibongnyeong-Hwan (GBH) for shoulder discomfort related to blood stasis before and after treatment., Methods/design: This study will be a double-centre, randomised, wait-list controlled pilot trial. Participants with shoulder pain and with a visual analogue scale score of 4 or higher out of 10, blood stasis score of 9 or higher, and triglyceride level of ≥150 mg/dl or total cholesterol level of ≥200 mg/dl will be recruited from two university hospitals. A total of 40 participants will be assigned to the immediate and waiting treatment groups. The immediate treatment group will receive GBH for 8 weeks on enrolment while the waiting treatment group will receive GBH for 8-16 weeks after 8 weeks of controlled waiting. The primary outcome is shoulder pain, and the secondary outcomes are the blood stasis score, blood pressure, ankle-brachial pressure index, brachial-ankle pulse wave velocity, body mass index, waist circumference, indexes of oximetry, and levels of blood lipid, blood sugar, resistin, C-reactive protein, serum amyloid P, and D-dimer., Discussion: The results of this pilot trial will be the bases for a full-scale clinical trial of GBH., Trial Registration: Clinical Research Information Service, KCT0003837. Registered on 23 April 2019. https://cris.nih.go.kr/cris/en/search/search&#95;result&#95;st01.jsp?seq=14258.

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: The aim of this study was to investigate the clinical practice of Korean medicine doctors (KMDs) for managing menopausal disorders., Methods: We conducted a web-based questionnaire for KMDs to respond to recommendations across the three main KM domains: major symptoms of menopausal disorders, herbal prescriptions, and pattern identification., Results: We received responses from 227 doctors who have treated menopausal disorders. The major pattern identifications recommended by the doctors for the pre-, peri-, and postmenopausal phases, respectively, were depression of liver energy (59.5%), kidney yin deficiency (49.8%), and kidney yin deficiency (50.7%). The most frequent herbal remedies prescribed for the pre-, peri-, and postmenopausal phases were Jiawei shaoyao-san (58.1%), Jiawei shaoyao-san (48.5%), and Jiawei guipi-decoction (37.9%), respectively., Conclusion: The results of our clinical practice survey provide information on KMDs' clinical experiences of using herbal medicines and their use of pattern identification to manage menopausal disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Most women experiencing menopause have sought out traditional treatment options to relieve their symptoms. The aim of this study, which used a web-based survey, was to investigate perceptions of Korean medicine doctors (KMDs) on managing menopausal symptoms with herbal medicines., Methods: We developed and then sent a questionnaire via email to a total 497 KMDs in obstetrics and gynecology affiliated with the Society of Korean Medicine. The questionnaire consisted of three categories and a total of 26 items focusing on major menopausal symptoms, prescriptions, pattern identification, and background characteristics., Results: Out of the 497 KMDs, we received responses from 48 doctors, a response rate of 9.7%. The most common symptoms of menopausal disorder perceived by responded KMDs were hot flashes (22.9%), sleep disorders (18.2%), systemic fatigue (12.5%), and sweating (12.0%). The herbal medicines reported to be the most effective when treating patients with menopausal disorders were Jiawei shaoyao-san (12.5%), Jiawei guipi-decoction (11.8%). The responding KMDs recommended one to two months of treatment for female menopausal disorder, using two to three doses of herbal medicine per day in combination with traditional Korean medicine (KM) therapies such as acupuncture, moxibustion, cupping, and pharmacopuncture., Conclusion: The results of this survey may provide information about doctor's perceptions on using herbal medicines to manage patient's menopausal symptoms. Future studies should be done with a larger sample size to overcome the limitation of this study and to examine how KM is used for treating menopausal symptoms in clinical practice., (© 2019 Korea Institute of Oriental Medicine. Published by Elsevier.)

Introduction: Many infertile patients have used Korean medicines (KMs) as a primary or adjuvant therapeutic method to improve in vitro fertilization success rates. The aim of this multicenter observational study is to investigate the effects of KMs on poor ovarian reserve (POR) in infertile patients., Methods and Analysis: We will perform a prospective multicenter observational study. This study will recruit 50 women between 25 and 44 years of age with infertility caused by POR from among patients who visit the KM clinic. All participants will visit the KM clinic on the 2nd or 3rd day of menstruation to receive the KMs. KM treatment will be delivered for 3 menstrual cycles (3 months) and will include herbal decoction, acupuncture, or moxibustion on demand. Every participant will be assessed based on KM clinical symptoms, a quality of life questionnaire, and ovarian reserve test results., Ethics and Dissemination: The study was approved by Institutional Review Board of Semyung University (SMU-IM-190501). The results will be published in a peer-reviewed journal and will be disseminated electronically and in print., Trial Registration Number: Clinical Research Information Service: KCT0004209.

Aim: We investigated the distribution of cold hypersensitivity in the hands and feet (CHHF) and examined the association between CHHF and health-related quality of life (HRQOL) among Koreans., Methods: Stratified multistage sampling was used for random selection of 2,201 adults. HRQOL was assessed using the Short-Form 12-Item Health Survey (SF-12). Cold hypersensitivity was measured using a new self-report questionnaire to score the extent of cold sensation in their hands, feet, and abdomen using a 7-point scale. The correlation between CHHF and HRQOL was analysed using multiple regression analysis., Results: Cold hypersensitivity was present in the hands of 21.6%, the feet of 23.0%, and the abdomen in 22.5% of participants. Cold hypersensitivity in the hands and feet was observed in 17.9%, at least one body part (hands, feet, or abdomen) in 34.2%, and all three body regions in 12.3% of participants. The prevalence of cold hypersensitivity was significantly higher among women than among men, irrespective of the involved body part. Cold hypersensitivity scores in the hands and feet correlated negatively with body mass index, but not with age. The physical component summary (PCS) and mental component summary (MCS) of the SF-12 were both significantly lower in women with than in those without CHHF. Among men, only the PCS was significantly lower in the CHHF group. Multiple regression analysis, adjusted for sociodemographic variables, age, sex, and body mass index (BMI), confirmed that CHHF had negative effects on PCS and MCS., Conclusions: CHHF is more common in women and in individuals with a lower BMI. CHHF has an independent negative effect on HRQOL.

Background: Cold hypersensitivity in the hands and feet (CHHF) is frequent in Asian countries including Korea. The quality of life can be degraded by the symptoms of CHHF. In particular, gynecological disorders such as menstrual pain, infertility, leucorrhea, and irregular bleeding may be related to CHHF. Sipjeondaebo-tang (SDT) is widely used in the treatment of various diseases including CHHF by balancing Yin and Yang, restoring the deterioration of physiological function, and improving immunity. However, the efficacy of SDT in the treatment of CHHF has not been assessed in clinical trials. Therefore, we aimed to investigate the feasibility of a full randomized clinical trial of SDT for the treatment of CHHF in Korean women through this trial., Methods: This study will be a pilot, randomized, double-blind, two-arm, placebo-controlled, parallel-group, multicenter clinical trial. Women aged 19-59 years who present with CHHF will be recruited from five university hospitals. A total of 60 subjects will be randomly assigned to a treatment group (SDT) or a placebo group at a 1:1 ratio. The subjects will receive 3 g of either SDT or placebo three times daily for 8 weeks. The primary outcome measures will be the Visual Analogue Scale scores of CHHF. The secondary outcome measures will be changes in body temperature in both the hands and the feet as measured using a thermometer and the Korean version of the World Health Organization Quality of Life Scale Abbreviated Version., Discussion: This will be the first trial to investigate the efficacy and safety of SDT in the treatment of CHHF. This study will provide basic clinical information regarding Korean herbal medicine treatment of CHHF and a clinical basis for designing a full randomized clinical trial., Trial Registration: ClinicalTrials.gov, NCT03374345 . Registered on 15 February 2018.

Background: This study aims to evaluate the safety, efficacy, and feasibility of a full randomized clinical trial of Ojeok-san in Korean female patients with cold hypersensitivity in the hands and feet., Methods: This study is a multicenter, double-blinded, randomized, placebo-controlled, two-arm, parallel-group pilot clinical trial. A total of 60 participants will be enrolled and randomly assigned to the Ojeok-san treatment group or the placebo control group, in a 1:1 ratio using an Internet-based randomization system. Each group will be administered Ojeok-san or placebo three times per day for 8 weeks. The primary outcome will be the mean change in the Visual Analog Scale scores of cold hypersensitivity in the hands from baseline to week 8. Secondary outcomes will include the mean changes in the skin temperature of the extremities, recovery rate of the skin temperature of hands after cold stress test, and the score of Korean version of the WHO Quality of Life Scale abbreviated version., Discussion: The findings of this study should provide meaningful information for a further large-scale, randomized controlled trial to confirm the safety and efficacy of Ojeok-san on cold hypersensitivity in the hands and feet in female patients., Trial Registration: ClinicalTrials.gov, ID: NCT03083522 . Registered on 20 March 2017.

Objectives: The study was to survey use of electronic medical records in subjects of Korean medicine doctors working for Korean medicine organizations and to contemplate ways to develop utilization of electronic medical records., Methods: On August 2017, it conducted online self-reported survey on subjects of Korean medicine doctors at Korean hospitals and clinics who agreed to participate in the study. A total 40 doctors in hospital and 279 doctors in clinic were included. The surveyed contents include kinds of electronic chart, reason for not using electronic medical records and problems with creation of medical records., Results: It finds that 100% of those working at Korean medicine hospitals and 86.4% of those at Korean medicine clinics have used electronic medical records. Subjects answered the biggest reason for not using electronic medical records was inconvenience. The most serious problems with creation of electronic medical records at Korean medicine organizations found in the study include there was no method of creation of medical records and no standardized terminology for use in electronic medical records., Conclusion: For utilization of electronic medical records at Korean medicine organizations, standardization of terminology, development of EMR in favour of its users and development of strategy that motivates use of EMR are required., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest.

Background: In Korea, there are two types of medical doctors: one practises conventional medicine (hereafter called a physician), and the other practises traditional medicine (hereafter called a Korean medical doctor). This study aimed to compare the provision of complementary and alternative medicine (CAM) by these providers to CAM use per self-judgement in Korea., Methods: We analysed 1668 Korean people via an internet survey with the Korean adopted version of the I-CAM-Q, namely, the International Questionnaire to measure use of CAM, to understand whether respondents used CAM based either on a prescription or advice from a physician or a Korean medical doctor or on self-judgement., Results: In the previous 12 months, the proportions of respondents who were treated by a physician, who were treated by a Korean medical doctor and who were not treated by anyone were 67.9, 20.7 and 14.2%, respectively. Among the respondents who received CAM based on a prescription or advice from a physician, traditional Korean medicine practices and dietary supplements were commonly used; only a small percentage used other CAM therapies. Respondents who received CAM based on a prescription or advice from a Korean medical doctor showed similar results. Acupuncture and moxibustion, traditional Korean medicines (decoction), or cupping were more commonly used. Korean traditional medicines as over-the-counter (OTC) drugs were more commonly used by respondents who received CAM therapy based on a prescription or advice from a physician than by those who received CAM therapy based on a prescription or advice from a Korean medical doctor. A total of 74% of the responders used any CAM by self-judgement in the previous 12 months., Conclusions: For the use of CAM in Korea, in addition to the Korean traditional medical care provided by Korean medical doctors, general physicians advised people regarding Korean traditional medical care and dietary supplements.

Introduction: Infertility has long been recognized as a treatable disease, and complementary and alternative medicine treatments, such as acupuncture and moxibustion, have been used in Korea and China. This study describes female infertility treatment programs that used traditional Korean medicine (TKM) and were conducted by local governments in Korea and evaluates its effectiveness and safety., Methods: The authors officially requested related information from the report of the infertility treatment programs and related sources from 2006 to 2016 from the Health & Welfare Ministry of Korea and the Association of Korean Medicine (AKOM). Additional information was obtained from six Korean databases. Data including basic information about the programs, participant information, interventions, and outcomes were abstracted., Results: A total of 9 reports, including multiple years of data from 6 programs (total 13 programs), were identified. In these 13 programs, a total of 1023 female subjects participated, and 205 of the 887 subjects who completed the program reported a successful pregnancy, indicating a 23.1% pregnancy rate. The programs lasted 3-9 months, and interventional elements, such as herbal medicine, acupuncture, fumigation, and massage, were identified. Significant adverse effects were not reported., Conclusions: This study suggests that infertility treatment programs with TKM interventions exhibited a positive effect on pregnancy in females with infertility. Thus, the infertility treatment programs with TKM interventions are expected to be useful and might serve as the primary treatment before assisted reproduction techniques.

Background: Cold hypersensitivity in the hands and feet (CHHF) is a symptom patients usually feel cold in their hands and feet, but not dealt with a disease in western medicine. However, it is often appealed by patients at a clinic of Korean medicine (KM), considered to be a sort of key diagnostic indicator, and actively treated by physicians. Nevertheless, there is no standardized diagnostic definition for CHHF. Therefore, we surveyed KM experts' opinions to address the clinical definition, diagnostic criteria, and other relevant things on CHHF., Methods: We developed a survey to assess the definition, diagnosis, causes, and accompanying symptoms on CHHF. 31 experts who work at specialized university hospitals affiliated with KM hospitals consented to participation. Experts responded to survey questions by selecting multiple-choice answers or stating their opinions., Results: Vast majority of experts (83.8%) agreed with our definition on CHHF ("a feeling of cold as a symptom; that one's hands or feet become colder than those of average people in temperatures that are not normally perceived as cold"). 77.4% of experts considered subjective symptoms on CHHF were more important than medical instrument results. Constitution or genetic factors (87.1%) and stress (64.5%) were the most common causes reported for CHHF., Conclusions: This study offers an expert consensus regarding the themes, opinions, and experiences of practitioners with CHHF. Our results underscore the need for standardized definitions and diagnostic criteria for CHHF.

Background: Cold hypersensitivity in the hands and feet (CHHF) is a common symptom in Korea and patients with CHHF complain of coldness in the hands and feet in an environment that is not considered cold by unaffected people. In traditional East Asian medicine, CHHF is believed to be accompanied by various diseases and symptoms, and is considered a symptom that needs active treatment. CHHF is used for pattern identification in the cold pattern, yang deficiency, and constitution. This study aimed to examine the differences in frequencies of chronic diseases with respect to the presence of CHHF., Methods: Disease history, CHHF, body measurements, and blood test survey data from 6149 patients collected by 25 medical institutes in Korea were obtained from the Korean Medicine Data Center. The participants were divided into CHHF (n = 1909) and non-CHHF groups (n = 3017) according to the CHHF survey. The differences in frequencies of 18 diseases were analysed using chi-square tests, and the odds ratios (ORs) for each disease according to CHHF status were examined via logistic regression with adjustment for age, sex, and body mass index (BMI)., Results: Based on chi-square test results, the CHHF group showed a higher frequency of the following diseases: anaemia, hypotension, chronic gastritis, reflux oesophagitis, chronic rhinitis, dysmenorrhoea, and gastroduodenal ulcer. Diseases found in lower frequencies were as follows: hypertension, diabetes mellitus, impaired fasting glucose, dyslipidaemia, stroke, fatty liver, and angina pectoris. In addition, from the logistic regression with adjustment for age, sex, and BMI, the CHHF group showed a lower OR in diabetes mellitus and dyslipidaemia than the non-CHHF group, but a higher OR in degenerative arthritis, chronic gastritis, gastroduodenal ulcer, reflux oesophagitis, and chronic rhinitis., Conclusions: This study showed that CHHF is associated with chronic disease. Further large-scale prospective studies are needed to validate these associations.

Background: In recent years, cold hypersensitivity in the hands (CHH) has become a common ailment of women in Korea. It can lead to gynecological problems such as irregular menstruation, miscarriage, and infertility. Traditionally, Korean herbal medicine has been the primary treatment method used to balance thermoregulation in the human body; however, its effectiveness has not been confirmed through systematic study. Thus, in this trial, we will investigate the feasibility of a full randomized clinical trial, Danggui-Sayuk-Ga-Osuyu-Saenggang-tang (DSGOST) in Korean women with CHH., Methods: This study will be a pilot, multicenter, double-blind, randomized, parallel-group, two-arm, placebo-controlled clinical trial. A total of 66 participants will be randomly divided into two groups, a DSGOST treatment group and a placebo control group, in a 1:1 ratio using a web-based randomization system. Each group will take DSGOST or placebo three times daily for 6 weeks. The primary outcome will be measured using Visual Analogue Scale (VAS) scores of CHH. Secondary outcomes will include changes in skin temperature of the hands, Clinical Global Impressions (CGI) scale scores, recovery rate of skin temperature of the hands after the cold stress test, and the Korean version of the WHO Quality of Life Scale, abbreviated version (WHOQOL-BREF)., Discussion: This trial will be the first trial to reflect the newly defined disease range of CHH which was compiled by Korean medicine expert consensus. This study will provide considerable evidence for further large-scale trials and general clinical guidelines for CHH in the Korean medical field., Trial Registration: This study is registered at ClinicalTrials.gov, ID: NCT02645916 . Registered on 30 December 2015.

Introduction: Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation., Methods and Analysis: The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3., Ethics and Dissemination: This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11-1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants, and the investigators will explain the study to the participants in detail. As an ethical clinical trial, the control group will also be given conventional cessation treatments, including NRT and counselling. Participants will be screened and provided with a registration number to protect their personal information. Informed consent will be obtained from the participants prior to enrolling them in the trial. Participants will be allowed to withdraw at anytime without penalty., Trial Registration Number: ClinicalTrials.gov (NCT02768025); pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The herbal extract Angelica gigas (AG) has been applied as a vasodilating agent for patients suffering from vascular diseases for many years; however, the underlying mechanism has not been fully elucidated. The present study hypothesized that the anti‑vasoconstrictive effect of AG may be effective in the treatment of abnormal cold‑mediated vasospasms that occur in Raynaud's phenomenon (RP). The effect of AG on the activity of ras homolog gene family member A (RhoA) was investigated in cold‑exposed vascular cells. Vascular cells were pretreated to AG, followed by a warm (37˚C) or cold (25˚C) incubation for 30 min and investigated with western blotting, ELISA and confocal microscopy. Cold treatment induced the activation of RhoA in pericytes and vascular endothelial cells, however this was reduced by treatment with AG. Furthermore, AG treatment reduced the endothelin‑1 (ET‑1)‑mediated RhoA activation in pericytes; however, cold‑induced ET‑1 production by vascular endothelial cells was not affected by treatment with AG. In addition, AG treatment suppressed the formation of stress fibers and focal adhesion complexes, and the cold‑induced phosphorylation of focal adhesion kinase, proto‑oncogene tyrosine‑protein kinase Src and extracellular signal‑related kinase. Therefore, AG treatment demonstrated an ability to reduce cold‑induced RhoA activation in pericytes and vascular endothelial cells, and attenuated ET‑1‑mediated RhoA activation in pericytes. In conclusion, the present study indicated that AG may be useful for the treatment of RP.

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: This study aimed to investigate medical records using traditional Korean medicine (TKM) in Sewol Ferry disaster in 2014 and further explore the possible role of traditional medicine in disaster situation., Methods: After Sewol Ferry accident, 3 on-site tents for TKM assistance by the Association of Korean Medicine (AKOM) in Jindo area were installed. The AKOM mobilized volunteer TKM doctors and assistants and dispatched each on-site tent in three shifts within 24 hours. Anyone could use on-site tent without restriction and TKM treatments including herb medicine were administered individually., Results: The total of 1,860 patients were treated during the periods except for medical assistance on the barge. Most patients were diagnosed in musculoskeletal diseases (66.4%) and respiratory diseases (7.4%) and circulatory diseases (8.4%) followed. The most frequently used herbal medicines were Shuanghe decoction (80 days), Su He Xiang Wan (288 pills), and Wuji powder (73 days)., Conclusions: TKM in medical assistance can be helpful to rescue worker or group life people in open shelter when national disasters occur. Therefore, it is important to construct a rapid respond system using TKM resources based on experience.

Danggui-Sayuk-Ga-Osuyu-Senggang-Tang (DSGOST), one of the traditional Chinese medicines, has long been prescribed for patients suffering from Raynaud phenomenon (RP) in Northeast Asian countries, including China, Japan and Korea. Although a previous in vitro study from our laboratory revealed that DSGOST prevents cold (25˚C)‑induced RhoA activation and endothelin‑1 (ET‑1) production in endothelial cells (ECs), the mechanisms by which DSGOST is able to alleviate the symptoms of RP have yet to be fully elucidated. The present study aimed to demonstrate that DSGOST regulates RhoA‑mediated pathways in cold‑exposed pericytes. In pericytes, DSGOST amplified cold‑induced RhoA activation, while markedly reducing ET‑1‑induced RhoA activation. Additionally, DSGOST‑mediated regulation of RhoA was closely associated with Rho‑associated, coiled‑coil‑containing protein kinase 1 (ROCK1)/testis‑specific kinase 1 (TESK1)/PDXP, but not with LIM domain kinase 1/2 (LIMK1/2), cofilin and myosin light chain (MLC). Thus, DSGOST activation of RhoA/ROCK1/TESK1/PDXP in cold‑exposed pericytes appeared to be crucial for treating vessel contraction. In addition, the DSGOST effect on the RhoA‑mediated pathway in cold‑induced human umbilical vein endothelial cells or human dermal microvascular endothelial cells was similar to that in ET‑1‑treated pericytes, but not in cold‑induced pericytes. The results of the present study further confirmed that DSGOST inhibits cold‑induced contraction of the mouse tail vein in vivo. Furthermore, DSGOST treatment reduced cold‑induced expression of the α2c‑adrenergic receptor in mouse tail vessels. Therefore, the data in the present study suggest that DSGOST may be useful for the treatment of RP‑like disease.

Objectives: The aim of this study was to evaluate the safety and the effect of dangguijagyag-san (DJS) on mild cognitive impairment (MCI)., Methods: This study examined the administration of DJS ([Formula: see text]; angelica and peony formula) and was conducted at Uijeongbu Health Center in Gyeonggi-do, Korea, in 2013. Ninety-five of 118 patients diagnosed with MCI were followed up for 1 year after the study ended, and their medical records were analyzed., Results: The patients included 36 men (37.9%) and 59 women (62.1%). When the results from before the study began were compared with the results 1 year after the study ended, the overall average score according to the Korean-Montreal Cognitive Assessment (K-MOCA) showed a statistically significant increase, from 15.46 ± 5.30 to 18.54 ± 5.11, respectively. Both male and female patients recorded a significant increase in K-MOCA scores for all sections, including the visuospatial/executive section, the naming section, the attention section, the language section, the abstraction section, the delayed recall section, and the orientation section. Scores assessed by the Mini-Mental State Examination for Dementia Screening (MMSE-DS) showed a statistically significant increase, from 21.84 ± 3.59 before the study to 24.43 ± 3.13 after the study, but decreased slightly to 23.04 ± 3.36 at the 1-year follow-up. However, MMSE-DS scores measured before the study began increased significantly when compared with scores measured 1 year after the study ended., Conclusions: DGJYS improved the cognitive skills of patients diagnosed with MCI, and no adverse effects were observed. In the future, the efficacy of DGJYS must be objectively verified by using a randomized controlled trial.

Objective: To evaluate the efficacy, safety, satisfaction, discomfort and patient preference of moxa cones of artemisia vulgaris and charcoal moxa., Methods: This comparative study of moxibustion treatment with Artemisia vulgaris and charcoal moxa cone stimulating Zhongwan (CV 12) is a cross-over single-blinded, randomized clinical trial. A total of 40 healthy subjects (24 males and 16 females) participated in this study. Two subjects dropped out of the trial. Thirty-eight subjects were treated with Artemisia vulgaris and charcoal moxa cones for 30 min in a cross-over design. After treatment, the patients underwent a 30 minute waiting period, and then the temperatures at Tanzhong (CV 17), Zhongwan (CV 12) and Guanyuan (CV 4) were measured using digital infrared thermal imaging., Results: After the use of Artemisia vulgaris moxa, the patients' body temperatures were slightly lowered at Tanzhong (CV 17), Zhongwan (CV 12) and Guanyuan (CV 4), but the changes were not statistically significant. After the use of charcoal moxa, the patients' body temperatures were somewhat increased at Zhongwan (CV 12) and Guanyuan (CV 4), but the changes were not statistically significant. After Artemisia vulgaris moxa use, the body temperature difference between Zhongwan (CV 12) and Guanyuan (CV 4) was significantly increased. After charcoal moxa use, the body temperature difference between Tanzhong (CV 17) and Zhongwan (CV 12) was significantly decreased in males and in the whole group. This change was caused by the difference in the moxibustion type and by gender differences., Conclusion: This pilot study found that moxibustion did not raise the body temperature, but temperature differences between acupoints were affected. Further large-scale randomized controlled trials are needed for the effect of moxibustion on body temperature.

Herbal prescription, Danggui-Sayuk-Ga-Osuyu-Saenggang-tang (DSGOST), has long been used to treat Raynaud's phenomenon (RP) in traditional Chinese medicine (TCM). However, a biological mechanism by which DSGOST ameliorates RP is yet deciphered. In this study, we demonstrate that DSGOST inhibits cold-induced activation of RhoA, in both vascular smooth muscle cells (VSMC) and endothelial cells (EC), and blocks endothelin-1-mediated paracrine path for cold response on vessels. While cold induced RhoA activity in both cell types, DSGOST pretreatment prevented cold-induced RhoA activation. DSGOST inhibition of cold-induced RhoA activation further blocked α 2c-adrenoreceptor translocation to the plasma membrane in VSMC. In addition, DSGOST inhibited endothelin-1-mediated RhoA activation and α 2c-adrenoreceptor translocation in VSMC. Meanwhile, DSGOST inhibited cold-induced or RhoA-dependent phosphorylation of FAK, SRC, and ERK. Consistently, DSGOST inhibited cold-induced endothelin-1 expression in EC. Therefore, DSGOST prevents cold-induced RhoA in EC and blocks endothelin-1-mediated paracrine path between EC and VSMC. In conclusion, our data suggest that DSGOST is beneficial for treating RP-like syndrome.

Background: Atopic dermatitis is a chronic inflammatory skin disease with a high prevalence rate and a large socioeconomic cost. There are many treatments for atopic dermatitis, such as antihistamine, tacrolimus and corticosteroids. However, due to concern about the adverse effects, many patients seek alternative treatments. In this context, natural products are gaining interest. KM110329 is a functional food consisting of four herbs that are beneficial to skin health. The purpose of this study is to assess the efficacy and safety of KM110329 for atopic dermatitis., Methods/design: This study is a randomised, double-blind, placebo-controlled and multicentre trial of KM110329. For this study, we will recruit 66 atopic dermatitis patients of both sexes, with ages ranging from 18 to 65, from three university hospitals. The participants will receive either KM110329 or a placebo twice a day for 8 weeks. The primary end point will be a change in the scoring atopic dermatitis (SCORAD) index. The secondary end points will include changes to the dermatology life quality index (DLQI) and transepidermal water loss (TEWL), among others. The outcomes will be measured at every visit. The study will be continued for 8 weeks and will include five visits with each subject (at screening and at 0, 1, 4 and 8 weeks)., Discussion: This trial will provide research methodologies for evaluate clinical efficacy and safety of KM110329 in adult patients with atopic dermatitis. In addition, we will evaluate the changes in the general skin health status and quality of life., Trial Registrations: ClinicalTrials.gov NCT01692093.

Atrial natriuretic peptide (ANP, also known as NPPA) and brain natriuretic peptide (BNP, also known as NPPB) have been determined as genetic factors for several diseases, including stroke and myocardial infarction, in human and rat models. To investigate the potential association between polymorphisms of the NPPA gene and stroke in a Korean population, nine single-nucleotide polymorphisms (SNPs) of NPPA and NPPB genes were genotyped in a total of 941 Korean subjects, including 674 stroke patients (109 hemorrhagic and 565 ischemic) and 267 unaffected controls. Genotype comparisons of the targeted alleles revealed that there were no significant associations between stroke patients and control subjects, or among hemorrhagic, ischemic, and control groups. However, in logistic analysis for Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of ischemic stroke, nonsynonymous rs5065 (STOP152Arg) and rs5067 in 3'UTR of NPPA, which were in complete linkage disequilibrium, showed significant associations with cardioembolic stroke. These two SNPs showed higher frequencies in cardioembolic stroke patients than those in controls and ischemic patients with small-vessel occlusion (p=0.002, adjusted p=0.02). It was also found that NPPA rs5065C allele in all of the Korean subjects existed as heterozygous compared with Caucasian and African populations. Although further replications in larger cardioembolic stroke subjects are required, our preliminary findings suggest that the nonsynonymous rs5065C of the NPPA gene, which could produce a new or dysfunctional transcript, is possibly associated with cardioembolism.

Background: Gyejibongnyeong-hwan (GJBNH) is one of the most popular Korean medicine formulas for menstrual pain of dysmenorrhea. The concept of blood stagnation in Korean medicine is considered the main factor of causing abdominal pain, or cramps, during menstrual periods. To treat the symptoms, GJBNH is used to fluidify the stagnated blood and induce the blood flow to be smooth, reducing pain as the result. The purpose of this trial is to identify the efficacy of GJBNH in dysmenorrhea caused by blood stagnation., Methods: This study is a multi-centre, randomised, double-blind, controlled trial with two parallel arms: the group taking GJBNH and the group taking placebo. 100 patients (women from age 18 to 35) will be enrolled to the trial. Through randomization 50 patients will be in experiment arm, and the other 50 patients will be in control arm. At the second visit (baseline), all participants who were already screened that they fulfil both the inclusion and the exclusion criteria will be randomised into two groups. Each group will take the intervention three times per day during two menstrual cycles. After the treatment for two cycles, each patient will be followed up during their 3rd, 4th and 5th menstrual cycles. From the screening (Visit 1) through the second follow-up (Visit 6) the entire process will take 25 weeks., Discussion: This trial will provide evidence for the effectiveness of GJBNH in treating periodical pain due to dysmenorrhea that is caused by blood stagnation. The primary outcome between the two groups will be measured by changes in the Visual Analogue Score (VAS) of pain. The secondary outcome will be measured by the Blood Stagnation Scale, the Short-form McGill questionnaire and the COX menstrual symptom scale. Analysis of covariance (ANCOVA) and repeated measured ANOVA will be used to analyze the data analysis., Trial Registration: Current Controlled Trials: ISRCTN30426947.

Uncoupling protein 2 (UCP2), a mitochondrial protein present in many organs and cell types, is known to dissipate the proton gradient formed by the electron transport chain. Its function is correlated with predictive parameters, such as obesity, diabetes, and metabolic syndromes. We analyzed the distribution of UCP2 polymorphisms in stroke patients diagnosed with one of the following four stroke subtypes based on the TKM standard pattern identification (PI): Qi-deficiency (QD), Dampness and Phlegm (D&P), Yin-deficiency (YD), and Fire and Heat (F&D). We studied a total of 1,786 stroke patients (397/QD, 645/D&P, 223/YD, and 522/F&D, 586/normal). Genotyping for the G-1957A, G-866A and A55V UCP2 polymorphisms was performed using the TaqMan. G-866A and A55V were significantly associated with the D&P and H&F subtypes. The frequency of subjects with the A allele of G-866A was significantly lower than the frequency of subjects with the GG type. The A55V polymorphism was also shown similar effect with G-866A in the dominant model. In contrast, no SNPs were shown to be associated with the QD or YD subtypes in this study. These results showed that the G-866A and A55V UCP2 polymorphisms may be genetic factors for specific PI types among Korean stroke patients.

Rhus verniciflua Stokes (RVS) is a traditional medicine used in Korea, Japan and China to treat various diseases including catharsis, diaphoretic gastritis and stomach cancer. However, the effects of RVS on allergic inflammatory diseases are unknown to date. This study showed the antiallergic inflammatory effects of RVS on human mast cells (HMC-1) which were stimulated by phorbol myristate acetate (PMA) and calcium ionophore A23187. RVS inhibited the expressions of TNF-alpha, IL-6 and IL-8 that were stimulated by treatment with both PMA and A23187. Among the mitogen-activated protein kinases (MAPKs), extracts of RVS suppressed the phosphorylation of ERK and p38, whereas RVS increased the phosphorylation of JNK in HMC-1. Consistent with the regulation of MAPKs, it was found that RVS inhibited the nuclear translocation of nuclear factor (NF)-kappaB via inhibition of the phosphorylation of IkappaB-alpha, which are important processes in controlling inflammatory responses. Taken together, these results suggest that RVS modulates the expressions of signal molecules related to allergic inflammatory responses mainly through the ERK signaling pathway, suggesting that RVS could be used as a treatment for mast cell-derived allergic inflammatory diseases., ((c) 2009 John Wiley & Sons, Ltd.)

Anthrax toxin detection before bacteremia, when toxin concentration is low, improves the chances of efficient treatment and cure. We present a novel technique for ultrasensitive detection of a protective antigen (PA(83)) of anthrax using an array of zinc oxide nanorods in conjunction with a FITC-labeled PA affinity peptide. The nanorods are composed of horizontally stacked hexagonal platelets which are uniformly spaced and grown unidirectionally upon a glass substrate via a new and simple technique. Images taken under UV emission demonstrate fluorescence sensitivity to PA as a function of antigen concentration, and a negative control using bovine serum albumin produced no fluorescence signal. The fluorescence signal of the PA-peptide complex is also significantly reduced in the absence of the nanorods, suggesting that the presence of ZnO nanorods inhibits the self-quenching properties of the fluorophore. A lower limit of detection for the assay system for PA is estimated at 150 aM, which demonstrates the possibility of using ZnO nanorods in biological sensor systems.

The dried roots of Sophora flavescens Aiton (SFA) has been used in traditional medicine for treatment of inflammation, gastrointestinal hemorrhage, diarrhea, and asthma. In the present study, we investigated the effect of SFA on the inflammatory allergic reaction using human mast cell-1 (HMC-1). SFA (200mg/kg) inhibited the mast cell-mediated passive cutaneous anaphylaxis reaction in vivo and the release of histamine from rat peritoneal mast cells by compound 48/80. In addition, the expression levels of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-alpha, IL-6, and IL-8 were also decreased by SFA treatment. In molecular mechanism level, this study showed that SFA inhibited the nuclear translocation of nuclear factor (NF) kappaB through inhibition of the phosphorylation and degradation of IkappaB-alpha, which is an inhibitor of NF kappaB. Moreover, SFA suppressed PMA plus A23187-induced phosphorylation of the mitogen-activated protein kinase p38 and c-jun N-terminal kinase. The inhibited induction of NF kappaB promoter by SFA was determined using luciferase activity. These results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.

Rhus verniciflua Stokes (RVS) has been used in traditional Eastern Asia medicine for the treatment of gastritis and stomach cancer, although the mechanism for its biological activity remains to be elucidated. We previously established that an ethanol extract of RVS-induced G(1)-cell cycle arrest via accumulation of p27(Kip1) controlled by Skp2 reduction and apoptosis in AGS human gastric cancer cells. Here, we showed that an ethanol extract of RVS-induced apoptosis via caspase-9 activation (mitochondrial death pathway) is mediated by the loss of mitochondrial membrane potential (MMP, Deltapsi(m)) and the release of cytochrome C from the mitochondrial intermembrane space. In addition, an ethanol extract of RVS inactivated PI3K-Akt/PKB kinase in a time-dependent manner. Moreover, combined treatment of an ethanol extract of RVS and LY294002 (a PI3K inhibitor) markedly increased apoptosis compared to treatment with an ethanol extract of RVS alone. The role of PI3K-Akt/PKB in this process was confirmed by constitutive expression of inactive mutants of this kinase in AGS cells. Finally, siRNA-mediated knockdown of Akt/PKB expression resulted in a significant reduction in AGS cell proliferation. Taken together, these results suggest that an ethanol extract of RVS induces apoptosis via a mitochondrial death pathway in human gastric cancer cells, but not in normal cells, and inhibition of the PI3K-Akt/PKB pathway enhanced the mitochondrial death pathway.