Systematic review and meta-analysis of cardiac neurosis for development of clinical practice guidelines of Korean medicine.

Background: The development of clinical practice guidelines in traditional medicine requires evidence that sufficiently reflects the medical field. Cardiac neurosis is a disease that occurs because of problems in the autonomic nervous system and is characterized by symptoms of the circulatory system that are representative of autonomic dysfunction. In traditional medicine, the heart is considered to be involved in mental health problems, and cardiac neurosis is accompanied by a variety of mental symptoms. Furthermore, there is a categorized diagnosis for cardiac neurosis, and active empirical research is being conducted in China. Objective: This study aimed to systematically review and quantitatively synthesize the effects of Korean medicine treatments in patients with cardiac neurosis to develop evidence-based clinical practice guidelines for the treatment of autonomic dysfunction. Methods: Nine databases were searched for articles published before September 13, 2022. The methodological quality of the studies was assessed using the RoB tool. The primary outcomes were somatization, depression, anxiety, and effectiveness rate. The secondary outcome was the rate of adverse effects. Results: Based on a systematic literature review, 151 randomized controlled trials were selected and analyzed. For patients with cardiac neurosis, herbal medicine, combined treatment of herbal medicine and Western medicine, combined treatment of herbal medicine and acupuncture, acupuncture, and combined treatment of acupuncture and Western medicine showed better overall effects than Western medicine alone. Furthermore, the combined treatment of herbal medicine and psychotherapy and that of herbal medicine, psychotherapy, and Western medicine showed an overall better effect than the combined treatment of Western medicine and psychotherapy. Conclusion: A meta-analysis of articles revealed the effectiveness of Korean medicine treatments and verified the effectiveness of a Korean medicine treatment alone, Korean medicine combined treatment, and combined treatment of Korean medicine and Western medicine on cardiac neurosis. Limitations included the inability to verify the cause of high heterogeneity between studies and the poor quality of the included studies. Nevertheless, this systematic review and meta-analysis of cardiac neurosis showed that the disease concept of traditional medicine can also be organized based on the latest research. Future research related to traditional diseases such as these should be conducted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022347992, identifier CRD42022347992.

Long-Term Impact of COVID-19 on Heart Rate Variability: A Systematic Review of Observational Studies.

Coronavirus disease 2019 (COVID-19) sequelae (or long COVID) has become a clinically significant concern. Several studies have reported the relationship between heart rate variability (HRV) parameters and COVID-19. This review investigates the long-term association between COVID-19 and HRV parameters. Four electronic databases were searched up to 29 July 2022. We included observational studies comparing HRV parameters (measurement durations: 1 min or more) in participants with and without a history of COVID-19. We used assessment tools developed by the National Heart, Lung, and Blood Institute group to evaluate the methodological quality of included studies. Eleven cross-sectional studies compared HRV parameters in individuals who recovered from acute COVID-19 infection to controls (n = 2197). Most studies reported standard deviation of normal-to-normal intervals (SDNN) and root mean square of the successive differences. The methodological quality of the included studies was not optimal. The included studies generally found decreased SDNN and parasympathetic activity in post-COVID-19 individuals. Compared to controls, decreases in SDNN were observed in individuals who recovered from COVID-19 or had long COVID. Most of the included studies emphasized parasympathetic inhibition in post-COVID-19 conditions. Due to the methodological limitations of measuring HRV parameters, the findings should be further validated by robust prospective longitudinal studies.

Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis.

Objectives: Chronic cough is a frequent condition worldwide that significantly impairs quality of life. Herbal medicine (HM) has been used to treat chronic cough due to the limited effectiveness of conventional medications. This study aimed to summarize and determine the effects of HM on patients with chronic cough. Methods: A comprehensive search of 11 databases was conducted to find randomized controlled clinical trials (RCTs) that reported the effects of HM for patients with chronic cough on 16 March 2023. The primary outcome was cough severity, and the secondary outcomes included cough-related quality of life, cough frequency, total effective rate (TER), and cough recurrence rate. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and the certainty of the evidence for effect estimates was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations tool. Results: A total of 80 RCTs comprising 7,573 patients were included. When HM was used as an alternative therapy to conventional medication, there were inconsistent results in improving cough severity. However, HM significantly improved cough-related quality of life and TER and significantly lowered the cough recurrence rate compared with conventional medication. When used as an add-on therapy to conventional medication, HM significantly improved cough severity, cough-related quality of life, and TER and significantly lowered the recurrence rate. In addition, HM had a significantly lower incidence of adverse events when used as an add-on or alternative therapy to conventional medication. The subgroup analysis according to age and cause of cough also showed a statistically consistent correlation with the overall results. The certainty of the evidence for the effect of HM was generally moderate to low due to the risk of bias in the included studies. Conclusion: HM may improve cough severity and cough-related quality of life, and lower the cough recurrence rate and incidence of adverse events in patients with chronic cough. However, due to the high risk of bias and clinical heterogeneity of the included studies, further high-quality placebo-controlled clinical trials should be conducted using a validated and objective assessment tool. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418736, CRD42023418736.

Anti-anger Effects of Herbal Medicine: A Mini-Review of Rat Studies.

OBJECTIVE: To analyze the available data on the anti-anger effects of herbal medicines (HMs) as well as their underlying mechanisms in rat models. METHODS: From 6 electronic databases [PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang, Oriental Medicine Advanced Searching Integrated System (OASIS), and Research Information Sharing Service (RISS)], relevant animal experiments were searched by using "anger," "rats," and "animal" as search keywords. The last search was conducted on November 22, 2019, and all experiments involving rat models of anger and treatment using HMs published until the date of the search were considered. RESULTS: A total of 24 studies with 16 kinds of HMs were included. Most studies have used the "tail irritating method" and "social isolation and resident intruder" method to establish anger models. According to the included studies, the therapeutic mechanisms of HMs for anger regulation and important herbs by their frequency and/or preclinical evidence mainly incladed regulation of hemorheology (Bupleuri Radix, Paeoniae Radix Alba, and Glycyrrhizae Radix), regulation of sex hormones (Bupleuri Radix, Cyperi Rhizoma, and Paeoniae Radix Alba), regulation of neurotransmitters (Cyperi Rhizoma), regulation of anger-related genes (Bupleuri Radix, Glycyrrhizae Radix, and Paeoniae Radix Alba), and other effects. Overall, Liver (Gan) qi-smoothing herbs including Bupleuri Radix and Cyperi Rhizoma were the most frequently used. CONCLUSIONS: This review found the frequent methods to establish an anger model, and major mechanisms of anti-anger effects of HMs. Interestingly, some Liver qi-smoothing herbs have been frequently used to investigate the anti-anger effects of HM. These findings provide insight into the role and relevance of HMs in the field of anger management.

Mothers' Experiences of Childbirth and Perspectives on Korean Medicine-Based Postpartum Care in Korea: A Qualitative Study.

This study aimed to record the experiences of childbirth and postpartum care of postpartum women and gain an in-depth understanding of their experiences of Korean medicine-based postpartum healthcare. The investigator conducted a 60-90-min interview with the 8 participants (mean age 34 years), and the comments were analyzed using the thematic analysis method. The two major themes emerging from the participants' comments were: "experience and awareness of childbirth and postpartum care" and "experiences of the Korean medicine-based postpartum program". The first theme was analyzed in four primary categories: (1) experiences of breakdown of the body and mind; (2) impossibility of postpartum care without help; (3) experiences of relentless effort for recovery; and (4) experiences of body and mind recovery. The second theme was analyzed in four primary categories: (1) participation with vague expectations; (2) experiences of the effects of managing postpartum symptoms; (3) the need for a comprehensive Korean medicine management for postpartum women; and (4) suggested improvements for the Korean medicine-based postpartum program. Mothers recognized the importance of Korean medicine treatment during the postpartum period for the management of Sanhupung symptoms and postpartum care and reported the benefits of body warming, Sanhupung prevention, pain reduction, and sense of psychological stability.

Meditation-based intervention for obsessive-compulsive disorder: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to investigate the effects of the meditation-based intervention on obsessive-compulsive disorder (OCD). METHODS: The following databases were searched up to April 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline (via PubMed), PsycARTICLES, 4 Korean databases (Korean Medical Database [KMbase], Koreanstudies Information Service System [KISS], National Digital Science Library [NDSL], and Oriental Medicine Advanced Searching Integrated System [OASIS]), and China National Knowledge Infrastructure (CNKI). The search terms related to meditation-based intervention and OCD were used. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The selected articles were evaluated using the Cochrane risk of bias tool. The Review Manager (RevMan) 5.4 was used to perform the meta-analysis. RESULTS: In all, 16 randomized controlled trials were selected. The meta-analysis showed that the group receiving the treatment combining medication and meditation-based intervention for OCD showed a more significant post-treatment improvement in Yale-Brown obsessive compulsive scale than the group receiving medication only. Compared with other non-medication interventions that are known to be effective in treating OCD, the Yale-Brown obsessive compulsive scale showed a significant improvement immediately after the meditation-based intervention. However, no significant difference was found in the follow-up monitoring data across all examined cases. CONCLUSION: This study was conducted to verify the effects of meditation-based intervention on OCD. The results suggested that combined treatment with medication and meditation-based intervention was more effective in treating OCD than medication alone; the positive effects of meditation-based intervention may be greater than the effects of other non-medication interventions. However, the lack of significant difference in the follow-up indicates that long-term effect of meditation-based interventions is unclear. TRIAL REGISTRATION NUMBER: PROSPERO CRD42021244408.

Effects of mobile mindfulness training on mental health of employees: A CONSORT-compliant pilot randomized controlled trial.

BACKGROUND: Employee stress and well-being affect organizational efficiency and productivity, as well as physical and psychological health of employees. Mindfulness is believed to reduce stress, prevent diseases, and promote well-being. Mindfulness has been used as the main component of various smartphone-based healthcare applications. Previous studies have suggested that mindfulness applications have a positive effect on employee stress and mental health. However, relatively few randomized controlled trials have examined the effectiveness of mindfulness applications on employees. This study aims to evaluate whether mobile mindfulness training (MMT) as a stress self-management tool improves employees' perceived stress, subjective well-being, and Mibyeong, a condition that is not a disease but shows obvious health abnormalities. METHODS: Participants were recruited through advertisements displayed at 3 workplaces, including a patent attorney's office, a construction company, and a public relations firm. A total of 45 employees were randomly assigned to 1 of 2 groups: the MMT group (Group A) receiving smartphone application-based mindfulness training, and a wait-list control (WLC) group (Group B), who received no intervention. Group A employees conducted MMT following daily and event guidelines for 4 weeks. In contrast, Group B employees did not receive any intervention in that time. The outcome variables were perceived stress, subjective well-being, and Mibyeong. Surveys were conducted at baseline, post-intervention, and follow-up (fourth week post-intervention). RESULTS: Demographic characteristics and baseline assessments were not significantly different between the 2 groups. The results of this study revealed that subjective well-being and Mibyeong were significantly improved in the MMT group compared with the WLC group. Moreover, this improvement was maintained up to at least 4 weeks later. However, perceived stress was not significantly reduced in the MMT group compared to the WLC group. CONCLUSION: Four weeks of MMT improved the subjective well-being and Mibyeong of employees. However, further studies are required to investigate the effect of MMT on other areas of mental health.

How do children with Tourette's syndrome and their caregivers live with the disorder? A systematic review of qualitative evidence.

Background: Tourette's syndrome (TS) is a childhood neurodevelopmental disorder characterized by sudden, repetitive, involuntary, and irregular muscle movement and vocalization. Recently, non-pharmaceutical methods, such as behavioral therapy, psychotherapy, and deep brain stimulation, have been introduced as alternatives to pharmacological treatment for TS. This study aimed to systematically review and synthesize qualitative evidence on the experiences of children with TS and their caregivers. A meta-synthesis of qualitative evidence could help provide a comprehensive understanding of the challenges experienced by children with TS and their caregivers with the aim of providing more effective treatment and services for them. Materials and methods: A systematic search was conducted using MEDLINE/PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycARTICLES, and three Korean databases (Korean Medical Database, Research Information Sharing Service, and ScienceON) in July 2021. Studies were included if they collected and analyzed qualitative data from children with tic disorder or TS, or their caregivers. Qualitative research findings on the experiences and perspectives of children with TS and their caregivers were critically appraised and synthesized using the Joanna Briggs Institute methodology. Results: Eight eligible studies were included. The findings from these studies (i.e., themes or subthemes of qualitative research) were aggregated into categories (a group of similar findings) and synthesized findings (a group of categorized findings). Ultimately, the 60 findings were aggregated into 15 categories. Finally, four synthesized findings were derived from the 15 categories: (i) continuation of challenging daily life, (ii) denying that TS causes emotional distress, (iii) accepting and understanding TS as part of oneself, and (iv) looking to the future. Conclusion: Children with TS and their caregivers experience physical and psychological distress and social deprivation. Avoiding and suppressing TS causes secondary distress such as guilt. However, seeking social support and accepting the disorder reduce the distress caused by symptoms and lays the foundation for later growth. Even in the face of adversity, children with TS and their caregivers find personal value and acquire a more open and optimistic attitude toward life. This review shows that acceptance-based therapy and social support should be provided for the treatment and management of TS.

A multicenter registry of neuropsychiatric outpatients in Korean medicine hospitals (KMental): Protocol of a prospective, multicenter, registry study.

INTRODUCTION: Mental health is an important global health concern. In Korea, many people visit Korean medicine clinics due to Stagnation syndrome and Hwabyung (cultural idioms of distress). METHODS AND ANALYSIS: We established a research collaboration comprising of professionals from 8 Korean medicine hospitals and planned a prospective, multicenter registry study. Demographic, socioeconomic, and clinical data will be collected from patients with mental disorders visiting the Korean medicine neuropsychiatric department of Korean medicine hospitals. We will include major psychiatric diagnoses related to neurosis and Korean traditional mental disorders such as Stagnation syndrome and Hwabyung.We expect to identify comprehensive characteristics of participants, measure the severity of their symptoms or distress, and investigate patterns of Korean medicine interventions and treatment responses for both the short-term and long-term (at least 4 years). Additionally, this study will include Health Insurance Review & Assessment Service data to analyze the medical use of registered patients before and after registration, in case the participant submits the consent form for personal information collection and use.To analyze the effectiveness of Korean medicine treatment for the participants, stratified or corrected analyses of age, sex, and diagnosis will be performed. The difference in the change in the psychometric measurements, quality of life measured by short form 36, and quality-adjusted life years will be calculated to evaluate the effectiveness of Korean medicine treatment.

How Suppressed Anger Can Become an Illness: A Qualitative Systematic Review of the Experiences and Perspectives of Hwabyung Patients in Korea.

Background: In the clinical field, anger has generally been studied in terms of aggressive behavior. However, in Asians, anger suppression is more common than anger expression. Hwabyung is a culture-related anger syndrome in Korea and is known to occur due to the continued repression of anger. Investigating Hwabyung should lead to a better understanding of the multiple dimensions of anger. To explore Hwabyung patients' experiences and perspectives, a meta-aggregation approach was used to conduct a systematic review and a qualitative synthesis. Methods: A systematic search was conducted in MEDLINE/PubMed, EMBASE, Allied and Complementary Medicine Database (AMED), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycARTICLES, and four Korean databases [Korean Medical Database (KMbase), Korean Studies Information Service System (KISS), National Digital Science Library (NDSL), and Oriental Medicine Advanced Searching Integrated System (OASIS)] in September 2020. Studies were included if they collected and analyzed qualitative data from Hwabyung patients. Qualitative research findings on the experiences and perspectives of Hwabyung patients in Korea were critically appraised and synthesized using the Joanna Briggs Institute methodology. Results: Seven eligible studies were included. The findings from those studies (i.e., theme or subtheme of qualitative research) were aggregated into categories (a group of similar findings) and synthesized findings (a group of categorized findings). Ultimately, 116 findings were aggregated into 15 categories. Finally, four synthesized findings were derived from the 15 categories: (i) anger arousal, (ii) blame, (iii) uncontrollable physical and emotional symptoms, and (iv) compromise and temporary coping. Conclusions: Patients with Hwabyung experience chronic anger through the complex cognitive processes involved in blame. Hwabyung negatively affects patients' physical, psychological, and social functions. Because Hwabyung patients feel as if they are losing control, due to emotional dysregulation and physical symptoms, professional support should be provided to facilitate their coping strategies. Further studies on Hwabyung can serve as a new model of pathological anger.

Nonpharmacological treatments for Tourette syndrome and tic disorders: A protocol for systematic review and network meta-analysis.

BACKGROUND: A tic is a sudden, rapid, recurrent, nonrhythmic motor movement, or vocalization. Tic disorders are diagnosed based on the presence of motor or vocal tics, duration of tic symptoms, and age at onset. Current clinical practice guidelines strongly recommend behavioral therapies because they are more effective and safer than medications. To determine the most effective nonpharmacological intervention for tic disorders and Tourette syndrome, we will conduct a systematic review and network meta-analysis. METHODS: We will search the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycARTICLES, AMED, 3 Chinese databases (China National Knowledge Infrastructure, Chongqing VIP, and Wanfang Data), 3 Korean databases (Korean Medical Database, Korean studies Information Service System, and ScienceON), and a Japanese database (CiNii). There will be no language or date restrictions. The primary outcome will be the tic severity scale, the Yale Global Tic Severity Scale. The secondary outcomes will include the effective rate defined by the trial authors, dropout rate, and adverse events. Methodological quality will be assessed using the Cochrane risk of bias tool. RESULTS: Results of this review and network meta-analysis will be published in a peer-reviewed journal. CONCLUSIONS: This systematic review will assess the effectiveness of nonpharmacological interventions for treating tic disorders. A systematic review or meta-analysis will provide an unbiased overview of the existing evidence.

The mindfulness-based stress reduction program for improving sleep quality in cancer survivors: A systematic review and meta-analysis.

INTRODUCTION: This study aims to evaluate the efficacy and effectiveness of a mindfulness-based stress reduction (MBSR) program in improving sleep in cancer survivors. METHODS: Four electronic databases (Cochrane Library, EMBASE, PubMed, and PsycARTICLES) were searched for randomized controlled trials evaluating the effects of MBSR on the sleep of cancer survivors from their inception to May 2020. The primary outcome was sleep quality measured by validated questionnaires such as the Insomnia Severity Index and Pittsburgh Sleep Quality Index. The secondary outcomes were sleep parameters obtained from a sleep diary, polysomnography, and actigraphy. The included studies were critically appraised by the Cochrane risk of bias tool and meta-analyzed. RESULTS: Ten studies were included, and nine studies were analyzed quantitatively. MBSR significantly improved sleep quality compared to usual care (standardized mean difference -0.29, 95 % confidence interval -0.55 to -0.04, I2 = 58 %). However, there were no favorable results with sleep parameters. Compared to active controls, MBSR presented mixed results with sleep quality according to the outcomes and negative results with sleep parameters. CONCLUSION: This review suggests that MBSR helps cancer survivors improve sleep quality. Our results support the possibility of using MBSR for cancer survivors. However, its efficacy and effectiveness in improving sleep quality and sleep parameters are inconclusive because the number of included studies was few with inconsistent results. Further studies with high methodological quality are required to establish conclusive evidence about the efficacy and effectiveness of MBSR in improving sleep quality and sleep parameters in cancer survivors.

Effectiveness and Safety of the Korean Medicine Senior Health Promotion Program Using Herbal Medicine and Acupuncture for Mild Cognitive Impairment: A Retrospective Study of 500 Patients in Seoul, Korea.

BACKGROUND: The management of mild cognitive impairment (MCI) is becoming increasingly important. The Korean Medicine Senior Health Promotion Program (KSHPP) was developed in 2016, and it has been in use to date. This study aimed to assess the effectiveness of KSHPP using herbal medicine and acupuncture for treating MCI and the safety of herbal medicine using liver and renal function tests. METHODS: We retrospectively reviewed the medical records of the participants with MCI. We assessed the Korean version of the Montreal Cognitive Assessment (MoCA-K), the Mini-Mental State Examination-Dementia Screening (MMSE-DS), and the Geriatric Depression Scale Short Form-Korea version (GDSSF-K) scores before and after KSHPP to determine its effectiveness. To evaluate its safety, the liver and renal function tests were conducted before and after herbal treatment. RESULTS: We enrolled 1002 participants, and 500 participants satisfied the inclusion criteria. Of 500 patients, 364 (72.8%) were depressed and 136 (27.2%) were not. The mean MoCA-K score significantly increased by 2.77 for the entire sample and 3.22 for the depressed sample (all P < 0.0001). The mean MMSE-DS score significantly increased by 2.19 for the entire sample and 2.51 for the depressed sample (all P < 0.0001); the mean GDSSF-K score significantly decreased by 1.73 for the entire sample and 2.68 for the depressed sample (all P < 0.0001). CONCLUSIONS: Our findings suggest that Korean medicine interventions can improve cognitive function and depression symptoms in patients with MCI. In addition, the results of the liver and renal function tests were analyzed as surrogate outcomes to assess the safety of herbal medicine. Based on these results, we expect that Korean medicine interventions can promote the cognitive and mental health of seniors. However, as there were several study limitations, particularly study design, practice effect, and short follow-up, these results must be interpreted with caution. We need a further long-term study with a rigorous design to retain confidence in the effectiveness and safety of KSHPP.

Effect of the Emotional Freedom Techniques on anger symptoms in Hwabyung patients: A comparison with the progressive muscle relaxation technique in a pilot randomized controlled trial.

CONTEXT: Hwabyung is a psychosomatic disease resulting from the suppression of anger over an extended period. The Emotional Freedom Techniques (EFT) are meridian-based psychotherapy known to cure many psychosomatic diseases, and progressive muscle relaxation (PMR) is a therapeutic method that relieves physical and psychological tension by repeated tensing and relaxation of the muscles. OBJECT: In this study, we compared the effects of EFT and PMR in patients with Hwabyung. DESIGN: 40 patients were enrolled and randomized to receive 4 weeks of group sessions with either EFT (n = 20) or PMR (n = 20). Evaluations were conducted pre- and post-treatment and at 4-week and 24-week follow-ups after session end. MAIN OUTCOME MEASURES: The Hwabyung Scale, Visual Analogue Scale of Hwabyung Symptoms (VAS-HS), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and State-Trait Anger Expression Inventory (STAXI) were administered as self-report tools. The analysis excluded 8 patients who never attended treatment and 1 patient meeting the exclusion criteria. RESULT: EFT (n = 15) and PMR (n = 16) improved Hwabyung symptoms (-13.95% and -11.46%, respectively), state anxiety (-12.57% and -12.64%, respectively), and depression (-32.11% and -18.68%, respectively) (p < 0.05 for all). Trait anger improved in EFT group (-13.4%, p = 0.004). There were no significant differences between the groups (p > 0.05) except for trait anger at post-treatment (p = 0.022 for between group). No adverse events were reported during the study.

Neurocircuitry of acupuncture effect on cognitive improvement in patients with mild cognitive impairment using magnetic resonance imaging: a study protocol for a randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) is defined as a decline in cognitive state with preservation of activities of daily living. Medications such as donepezil and rivastigmine have been commonly prescribed for MCI, but their use is controversial. Acupuncture has been widely used in Korea and has been shown to improve cognitive function. The aim of this study is to evaluate the efficacy of acupuncture for MCI and investigate the effect of acupuncture on structural and functional brain changes in patients with MCI. METHODS: This study is a randomized, assessor-blinded, sham-controlled trial. Fifty participants with MCI will be randomly assigned to the acupuncture group (n = 25) or sham acupuncture group (n = 25). The acupuncture group will receive acupuncture treatment at nine acupuncture points (GV20, EX-HN1, bilateral LI4, and ST36) twice a week for 12 weeks. The sham acupuncture group will receive sham acupuncture treatment at the same points with non-penetrating sham needles. Both groups will be restricted from all other treatments for the improvement of cognitive function. The primary outcome measure is the Digit Span Test (DST). The secondary outcome measures are the Digit Symbol Substitution Test (DSST), Korean version of Montreal Cognitive Assessment (MoCA-K), Seoul Neuropsychological Screening Battery-II (SNSB-II), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI), working memory (WM) task performance score, and structural/functional brain changes. Outcomes will be assessed at screening, baseline, 4 and 8 weeks, and after the end of treatment. We will also observe adverse events. In the statistical analysis, a full analysis set and per-protocol analysis will be performed. DISCUSSION: This randomized clinical trial aims to examine the efficacy of acupuncture treatment for MCI. Neuropsychological tests, psychological inventories for measuring depression and anxiety, and magnetic resonance imaging will be performed to investigate the underlying neurological mechanisms and the association between cognition, emotion, and brain networks following acupuncture treatment. The results of the trial will provide evidence supporting the efficacy of acupuncture and also add to the neurobiological understanding of acupuncture treatment for MCI. TRIAL REGISTRATION: Clinical Research Information Service, KCT0002896 . Registered on 25 May 2018.

Efficacy and Safety of Auricular Acupuncture for Cognitive Impairment and Dementia: A Systematic Review.

OBJECTIVES: To analyze the efficacy and safety of auricular acupuncture (AA) in patients with cognitive impairment and dementia. METHODS: Twelve electronic databases were searched for randomized controlled trials evaluating effects of AA in patients with cognitive impairment and/or dementia, from their inception to August 2017. The primary outcome was cognitive function, and secondary outcomes were self-care ability, quality of life, clinical efficacy rate, and incidences of adverse events. RESULTS: Nine studies were included, and five involving 677 participants were analyzed quantitatively. Compared with Western medications (WM), AA had mixed effects on cognitive functions (Mini-Mental State Examination [MMSE], mean difference [MD] 0.73, 95% confidence interval [CI] -0.02 to 1.48; Hierarchic Dementia Scale [HDS], MD 2.21, 95% CI 1.09 to 3.33); there was no significant improvement in the activities of daily living (ADL) score (MD 0.20, 95% CI -3.51 to 3.91) in patients with vascular dementia (VD). Compared to WM, AA combined with WM showed better clinical efficacy rate (risk ratio [RR] 1.42, 95% CI 1.06 to 1.91) in patients with VD; there was no significant improvement in cognitive functions (MMSE, MD 0.97, 95% CI -0.44 to 2.38; Montreal Cognitive Assessment [MoCA], MD 0.22, 95% CI -1.83 to 2.27) in patients with mild cognitive impairment (MCI). Compared to herbal medicine (HM), AA plus HM showed significant improvements in cognitive function (MMSE, MD 1.31, 95% CI 0.13 to 2.49) in patients with MCI and patients with vascular cognitive impairment, no dementia (VCIND) and in ADL score (MD -6.70, 95% CI -8.78 to -4.62) in patients with MCI. No adverse event associated with AA was reported. CONCLUSION: The evidence reveals mixed efficacy of AA in patients with cognitive impairment and/or dementia. However, the results were inconclusive because of the small number and poor methodological quality of the included studies.

A bitter herbal medicine Gentiana scabra root extract stimulates glucagon-like peptide-1 secretion and regulates blood glucose in db/db mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana scabra root extract (GS) is frequently prescribed as an internal remedy in traditional Korean medicine for treatment of diabetes mellitus. GS contains bitter iridoid glycosides including loganic acid, gentiopicrin, trifloroside, and rindoside. We previously reported that the intestinal bitter taste sensation stimulates GLP-1 secretion, and thereupon hypothesized that the blood glucose regulatory effect of GS is due to its GLP-1 secreting effect in enteroendocrine L cells. MATERIALS AND METHOD: We studied GLP-1 secreting effect of GS treatment and its cellular downstream mechanism in human enteroendocrine NCI-H716 cells using the G protein-coupled receptor (GPCR) pathway inhibitors. Intracellular calcium assay also demonstrated the signal transduction pathway stimulated by the GS treatment. Using db/db mice, we performed oral glucose tolerance test (OGTT) to examine the blood glucose lowering effect of GS administration. We also collected the mouse plasma during the OGTT to measure the GLP-1 and insulin levels. RESULT: We demonstrated dose-dependent GLP-1 secreting effect of GS on the NCI-H716 cells. The GLP-1 secreting effect of GS is mediated by the G protein ßγ-subunit and inositol triphosphate. Using db/db mice, we found that the effect of GS on lowering blood glucose is due to its GLP-1 secretion, and consequential insulinotropic effect. The chemical fingerprint of GS was obtained through a direct analysis in realtime mass spectrometry (DART-MS) and high-performance liquid chromatography (HPLC)/MS. Through the GLP-1 secretion study, we found that loganic acid, an iridoid glycoside, contributes to the GLP-1 secreting effect of GS. CONCLUSION: The findings of this study highlight the potential of exploiting the antidiabetic effect of GS on type 2 diabetes mellitus patients.