Dual oxidase 1 and NADPH oxidase 2 exert favorable effects in cervical cancer patients by activating immune response.

BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) not only can promote cancer progression, but also they have recently emerged as mediators of the mucosal immune system. However, the roles and clinical relevance of the collective or individual NADPH oxidase (NOX) family genes in cervical cancer have not been studied. METHODS: We investigated the clinical significance of the NOX family genes using data from 307 patients with cervical cancer obtained from The Cancer Genome Atlas. Bioinformatics and experimental analyses were performed to examine NOX family genes in cervical cancer patients. RESULTS: Dual Oxidase1 (DUOX1) and Dual Oxidase 2 (DUOX2) mRNA levels were upregulated 57.9- and 67.5-fold, respectively, in cervical cancer patients. The protein expression of DUOX1, DUOX2, and NOX2 also identified in cervical squamous cell carcinoma tissues. Especially, DUOX1 and DUOX2 mRNA levels were significantly increased in patients infected with human papillomavirus (HPV) 16. Moreover, high DUOX1 mRNA levels were significantly associated with both favorable overall survival and disease-free survival in cervical cancer patients. High NOX2 mRNA levels was significantly associated with favorable overall survival. Gene set enrichment analyses revealed that high DUOX1 and NOX2 expression was significantly correlated with the enrichment of immune pathways related to interferon (IFN)-alpha, IFN-gamma, and natural killer (NK) cell signaling. Cell-type identification by estimating relative subsets of known RNA transcript analyses indicated that the fraction of innate immune cells, including NK cells, monocytes, dendritic cells, and mast cells, was elevated in patients with high DUOX1 expression. CONCLUSIONS: DUOX1 and NOX2 expression are associated with mucosal immunity activated in cervical squamous cell carcinoma and predicts a favorable prognosis in cervical cancer patients.

Clinical Significance of the Thioredoxin System and Thioredoxin-Domain-Containing Protein Family in Hepatocellular Carcinoma.

BACKGROUND: Oxidative stress occurs due to the excessive generation of cellular reactive oxygen species and antioxidant system dysfunction. The thioredoxin (TXN) system and TXN-domain-containing protein (TXNDC) family form networks maintaining the cellular reducing environment. Recently, the importance of these genes in the tumor environment has been emphasized. AIM: To investigate the clinical significance of TXNs and TXNDC family members in HCC. METHODS: Genomic data from 367 hepatocellular carcinoma (HCC) patients who underwent hepatic resections were analyzed to determine genetic alterations in mRNA and protein levels between patients and healthy controls. In addition, functional enrichment and survival analyses were performed. RESULTS: HCC patients were shown to have enhanced expression of TXN, TXNRD1, and TXNDC7/9/14 mRNA and protein compared with controls. In accordance with the survival analyses, strong associations were found that patients with TXN, TXNRD1, and TXNDC1/7/9 alterations were proven to have poor prognosis in overall survival. Moreover, gene set enrichment analysis and network analyses revealed that positive correlations were found in mRNA expression of TXN, TXNRD1, and TXNDC7/9 genes with upregulation of the tumor-promoting genes, specifically mTORC1, E2F targets, and Myc targets. On the other hand, elevated expressions of TXNIP and TXNDC11 genes were correlated with suppression of the above tumor-promoting genes. CONCLUSIONS: TXN system and TXNDC family gene panel obtained from the resected tissue of the HCC patients could be used to predict survival prognosis of HCC, and these genes could be considered as potential therapeutic targets for improving HCC survival.

Treating nasal symptoms associated with rhinitis using the intranasal herbal ointment Biyeom-go: A prospective observational study.

OBJECTIVES: The aim of the current study was to investigate the effectiveness and clinical feasibility of Biyeom-go for the treatment of nasal symptoms associated with rhinitis. DESIGN: Prospective observational study. SETTING: This study was conducted at the Woosuk Korean Medicine Medical Center in South Korea. PARTICIPANTS: Fifty-eight patients with rhinitis participated in this study. All patients received Biyeom-go treatment >3 times daily for a total of 4 weeks. MAIN OUTCOME MEASURES: The primary outcome was the total nasal symptom score. Mini-rhinoconjunctivitis quality of life questionnaire, nasal endoscopy index, total serum immunoglobulin E levels and immunologic factors in nasal lavage fluid were also measured. RESULTS: Biyeom-go administration was associated with significant improvements in total nasal symptoms scores (P < .0001) and mini-rhinoconjunctivitis quality of life questionnaire scores (P < .0001) in a time-dependent manner. The nasal endoscopy index also significantly improved at weeks 2 (P = .0049), 3 (P < .0001) and 4 (P = .0001) after Biyeom-go treatment. Significantly, increased interleukin-2 levels (P = .005) and decreased interleukin-8, chemokine (C-C motif) ligand (CCL) 5, chemokine (C-X-C motif) ligand (CXCL) 9, CCL2 and CXCL10 levels were observed in the nasal lavage fluid. CONCLUSIONS: The present findings suggest that Biyeom-go may be beneficial for the management of rhinitis symptoms and rhinitis-associated quality of life. Further well-designed randomised controlled trials are needed to evaluate the effectiveness of Biyeom-go for rhinitis.

Development of the Korean Medicine Core Outcome Set for Facial Palsy: herbal medicine treatment of patients with facial palsy in primary clinics.

Introduction: Facial palsy (FP) significantly affects the quality of life of patients and poses a treatment challenge in primary healthcare settings. This study aimed to develop a Korean medicine (KM) core outcome set (COS) for FP, with a focus on evaluating the effectiveness of herbal medicine (HM) treatments in KM primary clinics. Methods: Outcomes and effect modifiers related to FP treatments were initially identified through related review articles. Subsequently, experts in the field took part in three rounds of modified Delphi consensus exercises to refine and prioritize these outcomes and effect modifiers. Additionally, primary KM clinicians were involved in a Delphi consensus round to assess the suitability and feasibility of the proposed COS in real-world clinical settings. Results: The initial review of related literature identified 44 relevant studies, resulting in an initial selection of 23 outcomes and 10 effect modifiers. The expert consensus process refined these to 8 key outcomes and 6 effect modifiers, which established the foundation of the COS-FP-KM. Subsequently, primary KM clinicians confirmed the practicality and applicability of the COS, endorsing its suitability for use in KM primary clinics. Conclusion: The COS-FP-KM establishes a standardized approach for assessing HM treatment effectiveness in FP patients in KM primary clinics. The COS-FP-KM encourages consistent outcome reporting and enhances patient care quality. Future work should aim to integrate broader stakeholder perspectives to refine and validate the COS further.

Clinical effectiveness of decoction form of herbal medicine in primary care treatment of allergic rhinitis: A retrospective cohort study.

Background: The decoction form of herbal medicine (D-HM) is mainly prescribed to patients with allergic rhinitis (AR) in Korean Medicine (KM) clinics in the Republic of Korea; however, it is difficult to conduct clinical trials of D-HM due to regulatory issues. This study investigated the clinical safety and effectiveness of D-HM combination therapy for the treatment of AR by analyzing the AR outpatient data from 17 KM clinics. Methods: This retrospective cohort study included patients who visited KM clinics for AR treatment from January 1, 2021, to March 31, 2022. Cases were collated using structured case report forms and divided into the D-HM with KM usual care group (D-HM group) and the KM usual care group (UC group). Since D-HM therapy could not be randomly assigned to the study population, we used optimal propensity score (PS) matching to investigate the effectiveness and safety of D-HM combination therapy in the treatment of AR. Results: Data from 228 patients were collected. After PS matching, 144 patients were finally analyzed. The total nasal symptom score (TNSS) and mini-rhinoconjunctivitis quality of life questionnaire (mini-RQLQ) were significantly improved in the D-HM group compared with those in the UC group (TNSS: p=0.02; mini-RQLQ: p=0.04). Four patients in the D-HM group experienced minor adverse events that were mild and resolved within 15 days. Conclusions: D-HM combination therapy may be beneficial in the management of symptoms and rhinitis-associated quality of life and potentially useful in clinical practice. However, randomized placebo-controlled clinical trials are required to confirm their effectiveness. Study registration: This study has been registered at Clinical Research Information Service (KCT0007242).

Feeder cell-dependent primary culture of single blastula-derived embryonic cell lines from marine medaka (Oryzias dancena).

Fish embryonic stem cells (ESCs) are derived from blastomeres that have been cultured from blastula embryos. The most widely used method for derivation of fish ESCs is the culture of blastomeres that have been isolated from approximately 10 blastula embryos under feeder-free conditions. However, this method leads to intercellular genetic heterogeneity among the cultured cells, which is a major obstacle to the development of stable ESC culture conditions. In this study, to establish ESC lines with intercellular genetic homogeneity at the early stage of culture, we attempted to derive embryonic cell lines from single blastula-derived blastomeres of marine medaka (Oryzias dancena) in a feeder cell culture system. Using basic fibroblast growth factor-expressing feeder cells during primary culture, we successfully established 22 single blastula-derived embryonic cell lines that could be subcultured more than 20 times. In contrast, we were unable to efficiently derive cell lines using wild-type feeder cells and under feeder-free conditions. The established cell lines exhibited ESC-like cell characteristics in terms of alkaline phosphatase activity, pluripotency-related gene expression, and embryoid body formation. The results of this study will contribute to the development of methods for derivation of fish ESCs.

Comparing acupoint catgut embedding and acupuncture therapies for simple obesity: A protocol for systematic review and meta-analysis.

BACKGROUND: This systematic review aimed to assess the effectiveness and safety of acupoint catgut embedding (ACE), which is widely used in simple obese patients. METHODS: Nine electronic databases and 2 trial registries were searched from inception to September 2021 without language limitations. All randomized controlled trials involving ACE therapies for simple obesity were included. Assessment of Cochrane's risk of bias and meta-analysis, as well as GRADE evaluation, were also performed. RESULTS: A total of 73 randomized clinical trials involving 5872 participants were included. The overall risk of bias was high or unclear. ACE showed higher efficacy in total effective rate, body mass index, and body weight than manual acupuncture. In addition, ACE is more beneficial in total effective rate than electroacupuncture (EA). Moreover, combination therapy of ACE with EA is more effective in total body mass index and body weight than EA alone. CONCLUSIONS: Despite some potential improvement, the evidence regarding the effectiveness and efficacy of ACE for simple obesity is inconclusive due to the poor quality of evidence. Further well-designed randomized controlled trials are needed to confirm the effectiveness of ACE for simple obesity.

A national survey on current clinical practice pattern of Korean Medicine doctors for treating obesity.

BACKGROUND AND AIMS: Given the multifactorial nature of obesity, there is current interest on Korean medicine (KM) for weight loss. This survey aimed to investigate current practice patterns of KM treatment for obesity among doctors. METHODS: A questionnaire on clinical practice patterns of KM treatment for obesity was constructed and distributed to 21,788 KM doctors (KMDs). The questionnaire was consisted of respondent characteristics, state of treated patient, diagnosis, treatment, and usage pattern of herbal medicine for obesity. RESULTS: A total of 4.9% of KMDs (n = 1,084/21,788) validly completed the survey. Patients with Obesity Class I (25 ≤ Body mass index (BMI) ≤ 29.9) are the most common in KM clinics. Bioelectric impedance and KM Obesity Pattern Identification Questionnaire were routinely used for diagnosis. The average treatment duration was 4.16 weeks, and patients visited on an average 4.25 times per month for treatment. Herbal medicine is the most commonly used for obesity treatment by KMDs, and Taeeumjowui-tang was the most frequently prescribed. Ephedrae Herba, which is identified as the most used herbs for weight loss, was prescribed 5.18 ± 2.7 g/day at minimum and 10.06 ± 4.23 g/day at maximum. A total of 62.9% of responded KMDs had ever a patient with uncomfortable symptoms due to Ephedrae Herba use, neuropsychiatric events were the most common symptoms, followed by gastrointestinal events. CONCLUSION: Taken together, this study provides information on real clinical practice patterns of KM including patients, diagnosis, treatments, and herbal medicine for obesity.

Korean medicine registry of herbal medicine for weight loss.

INTRODUCTION: In South Korea, the prevalence of obesity has continuously increased over the last decade, and the burden of social and economic costs has also increased immensely. The purpose of this study is to investigate the clinical characteristics and current status of patients receiving herbal medicine (HM) treatment for weight loss in Korean medicine (KM) by constructing a multi-institutional prospective registry. METHODS AND ANALYSIS: This is a prospective, observational, multi-center registry, including patients visiting the KM clinics in South Korea for weight loss. This study will collaborate with 15 KM clinics and recruit patients into the registry between October 2021 and October 2022. The study population will include patients visiting the KM clinics for weight loss. A total of 1000 eligible patients visiting the KM clinics for weight loss who decide to undergo HM treatment will be enrolled in the registry. After enrollment, we will collect the individual characteristics of each patient, such as body mass index, body composition test, liver and kidney function tests, and information on prescribed HM. We will also record the adverse events at each visit. DISCUSSION: This study is the first prospective, multicenter registry of HM for weight loss in KM clinics. The results of this registry may show the current status of patients who receive HM treatments for weight loss and provide evidence for reasonable decision-making on KM healthcare policy for obese patients in the future.

Safety and efficacy of an herbal formula, Gwakhyangjeonggi-san on atopic dermatitis with gastrointestinal symptoms: Protocol for a randomized controlled trial.

INTRODUCTION: Gwakhyangjeonggi-san (GJS) is an herbal formula with anti-inflammatory and anti-allergic properties that is broadly used to treat a wide range of diseases including gastrointestinal disorders and allergic diseases. There have been several clinical studies conducted on its effects on atopic dermatitis (AD). So far, no randomized controlled trials have been conducted. Here, we describe the protocol for a randomized controlled study designed to investigate the efficacy and safety of GJS for treating patients with AD that have gastrointestinal symptoms. METHODS AND ANALYSIS: A randomized, double-blind, placebo-controlled, parallel-group, clinical trial has been designed to investigate the clinical efficacy and safety of GJS on patients with AD that have gastrointestinal symptoms. A total of 58 participants with AD will be recruited and randomly allocated to the GJS or placebo group in a 1:1 ratio. The participants will be administered GJS or placebo granules 3 times a day for 8 weeks. Data will be collected from the participants at baseline and after 4 and 8 weeks. The primary outcome measure will be the mean change in the SCORing of Atopic Dermatitis (SCORAD) index from baseline to 8 weeks. The secondary outcomes will include the eczema area and severity index (EASI), dermatology life quality index (DLQI), EuroQoL 5 dimensions 5 levels (EQ-5D-5L), and immunological factors. The Korean Gastrointestinal Symptom Rating Scale (KGSRS), Nepean Dyspepsia Index will also be obtained for assessing the gastrointestinal status. DISCUSSION: The findings of this study are expected to provide evidence on the safety and effectiveness of GJS and for treating patients with AD that have gastrointestinal symptoms. Additionally, the study will explore the mechanism of GJS action via gut microbiome. This study will provide new perspectives on approaching treatment for AD. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of Kyung Hee University Korean Medicine Hospital at Gangdong (KHNMCOH2019-06-002-001). TRIAL REGISTRATION NUMBER: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0004299).

Efficacy and Safety of Socheongryong-Tang Among Atopic Dermatitis Patients With Respiratory Disorders: A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial.

Atopic dermatitis is a chronic inflammatory skin disease that affects the growth and development of children. The prevalence of atopic dermatitis has been continually increasing, and this has also been accompanied by rising socioeconomic costs. Interest has been growing in alternative medicine as a means of alleviating the burden of atopic dermatitis. This was a single-center, double-blinded, randomized, placebo-controlled investigator-led clinical trial including 60 atopic dermatitis patients. The participants were classified into an experimental group (30 persons) and a control group (30 persons), who were administered, respectively, socheongryong-tang or a placebo for 4 weeks. After 4 weeks of treatment, the participants visited the trial center again and assess their efficacy and safety. The researchers performed statistical comparisons of the changes in the SCORAD Index, amount and frequency of ointment use, and height and weight to assess the efficacy. To assess the safety, diagnostic tests and vital sign checks were performed at each visit, and the presence or absence of adverse events was observed. As a result, the frequency and the amount of steroid ointment application in both groups increased, but the experimental group showed less tendency (p = 0.081). Results of analyzing the children in the experimental group in relation to growth showed a significantly greater height growth than the control group (p < 0.05). In addition, all study participants did not show any remarkable abnormal signs in the safety evaluation. In conclusion, compared to the control group, the experimental group, who took socheongryong-tang showed a tendency to be less dependent on steroid ointment and statistically significant increase in height.

The herbal drug, Bu-Zhong-Yi-Qi-Tang, for the treatment of atopic dermatitis: Protocol for a systematic review.

INTRODUCTION: Bu-Zhong-Yi-Qi-Tang (BZYQT) is an herbal drug that is widely used to treat various diseases, including gastrointestinal diseases, allergic rhinitis, and atopic dermatitis (AD) in East Asian countries. BZYQT has been shown to have anti-allergic, anti-inflammatory, and immunoregulatory properties in experimental studies, and there is substantial clinical evidence of its effect on AD. This review will systematically assess the evidence of BZYQT for the treatment of AD. METHODS/DESIGN: Eleven databases will be searched from their inception without language restriction. Randomized controlled trials that examined BZYQT or modified BZYQT for AD will be included. The selection of the studies, data abstraction, and validations will be performed independently by 2 researchers. The methodological qualities of the randomized controlled trials will be assessed using the Cochrane Collaboration tool for assessing the risk of bias. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal and will also be disseminated electronically or in print. It will be useful to inform and guide healthcare practitioners. TRIAL REGISTER NUMBER: CRD42018105173.

Association of atopic dermatitis with obesity via a multi-omics approach: A protocol for a case-control study.

INTRODUCTION: Several studies have found that obesity is associated with atopic dermatitis (AD); however, the mechanisms underlying the association are largely unknown. This study aims to assess the association of AD with obesity in the Korean population and verify its mechanism via a multi-omics analysis. METHODS AND ANALYSIS: A case-control study will be conducted in the Republic of Korea. A total of 80 subjects, aged 4 to 12 years, matched for age and sex, with body mass index at or above the 85th percentile or at or below the 25th percentile, will be included. Subjects will be assigned to the following 4 groups: obese/overweight with AD, normal/underweight with AD, obese/overweight control, and normal/underweight control. Serum metabolome and immune biomarkers, as well as fecal metabolome and microbiome biomarkers, will be analyzed. Serum eosinophil cationic protein, total serum Immunoglobulin E (IgE), and specific IgE will be analyzed to assess allergic tendency. The SCORing of AD index, the children's dermatology life quality index, body composition analysis, and the Korean gastrointestinal symptom rating scale will be obtained to assess the disease status and severity of the subjects. DISCUSSION: The findings of this study are expected to provide evidence of an association between AD and obesity via a gut microbiome-metabolome-immune mechanism. Therefore, it may improve future management strategies for AD. TRIAL REGISTRATION: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0003630).

Socheongryong-tang for improving nasal symptoms associated with allergic rhinitis: A study protocol for a randomized, open-label, cetirizine controlled, clinical trial.

INTRODUCTION: Socheongryong-tang (SCRT) is an herbal medicine with anti-inflammatory and anti-allergic properties, commonly used in East Asian countries to reduce rhinitis symptoms. There have been several clinical studies of its effects on allergic rhinitis (AR), but no trials comparing it with conventional treatment. We present the protocol for a feasibility trial to assess the safety and clinical effectiveness of SCRT in AR in comparison with cetirizine. METHODS AND ANALYSIS: This is a randomized, open-label, cetirizine-controlled clinical trial. A total of 30 AR patients who have signed informed consent forms will be recruited and randomly assigned to SCRT or cetirizine groups at a 1:1 ratio. The participants will visit the clinical research center every week and receive SCRT granules or cetirizine tablets. SCRT will be taken twice daily, cetirizine will be taken once daily, and treatment medication will be taken for 2 weeks. Data will be collected at baseline, at week 2, and at week 4 after random allocation. The primary outcome will be the mean change in the total nasal symptom score from baseline to week 2. Secondary outcome measures will include the mini Rhinoconjunctivitis Quality of Life Questionnaire and total serum immunoglobulin E. To assess the safety of SCRT, a liver and renal function test will be conducted before and after treatment, and the participants will be asked about any occurrence of adverse events at every visit. The recruitment rate, completion rate, and medication adherence will also be calculated to assess feasibility. DISCUSSION: The findings of this study are expected to provide the basis for a full-scale randomized controlled trial to confirm the safety and effectiveness of SCRT for the treatment of nasal symptoms in patients with AR patients not controlled by conventional therapy. TRIAL REGISTRATION: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0002380).

An Herbal Drug, Gongjin-dan, Ameliorates Acute Fatigue Caused by Short-Term Sleep-Deprivation: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Clinical Trial.

Introduction:Gongjin-dan (GJD) is an herbal drug commonly used in Korea and China to combat fatigue, but there are only few clinical studies on its effectiveness and experimental studies on its mechanism of action, and no randomized controlled trial of GJD on the efficacy and mechanism of action has been reported. Here, we performed an exploratory study to evaluate both questions regarding GJD use in humans. Methods: A randomized, double-blinded, placebo-controlled, crossover clinical trial was conducted in the Republic of Korea. Healthy male participants were recruited and randomly allocated to groups receiving GJD-placebo or placebo-GJD in sequence. Fatigue was artificially induced by sleep deprivation for 2 nights. The primary outcome was a change in serum cortisol level; levels of biomarkers for stress hormones as well as oxidative stress and immunologic factors were also assessed, and questionnaires on fatigue and sleep quality were conducted. Results: Twelve and 11 participants were assigned to the GJD-placebo and placebo-GJD groups, respectively. Of all 23 participants, depending on crossover design, we analyzed a total of 20 participants for GJD, and 21 for placebo. An increase in serum cortisol appeared to be attenuated by GJD administration (p = 0.25), but the effect was not statistically significant; a similar pattern was observed in salivary cortisol levels (p = 0.14). Overall, GJD showed a tendency to reduce fatigue according to the Brief Fatigue Inventory (BFI, p = 0.07) and the Fatigue Severity Scale (FSS, p = 0.13) questionnaires. BFI and FSS scores in the first stage (before the crossover), however, were significantly improved (BFI, p = 0.02; FSS, p = 0.05) after GJD treatment (relative to placebo). GJD also seemed to improve sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire (p = 0.06), with a significant improvement specifically in the condition "Getting To Sleep" (p = 0.02). Five participants experienced minor adverse events, but no adverse events were specific to the GJD administration period. Conclusions: This trial produced the first clinical evidence that GJD might have anti-fatigue properties, especially under sleep deprivation; however, the investigation of cortisol-mediated mechanisms requires further larger-scale studies in the future. TRIAL REGISTRATION: World Health Organization International Clinical Trials Registry Platform KCT0001681 (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0001681).

Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2-3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this study was to develop a protocol to determine the proper dosage of Mecasin. METHODS: This is a phase II-A, multi-center, randomized study with three arms. Thirty-six patients with ALS will be randomly assigned to one of three groups, each receiving the standard treatment with 100 mg of riluzole in addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes include results of the Short Form Health Survey-8, Medical Research Council Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function test, forced expiratory volume in 1 s and its ratio to forced vital capacity, creatine kinase, and body weight. The frequencies of total adverse events and serious adverse events will be described and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Gwangju and Sanbon Hospital (2016-5-4 and 2016-34-01, respectively). An Investigational New Drug status (30731) was granted by the Korea Food and Drug Administration. DISCUSSION: This trial will aim to identify the optimal dosage of Mecasin. Additionally, it will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS. TRIAL REGISTRATION: Korean National Clinical Trial Registry CRIS; KCT0001984 . Registered on 28 July 2016.

Safety and efficacy of Galgeun-tang-ga-cheongung-sinyi, a herbal formula, for the treatment of chronic rhinosinusitis: A study protocol for a randomized controlled trial.

INTRODUCTION: A herbal formula, Galgeun-tang-ga-cheongung-sinyi (GGTCS), is traditionally used for the treatment of rhinosinusitis in East Asian countries. However, there is a dearth of clinical evidence supporting the effects of this medication. Here, we describe the protocol for a randomized controlled study designed to investigate the efficacy and safety of GGTCS for the treatment of chronic rhinosinusitis (CRS). METHODS AND ANALYSIS: To investigate the clinical efficacy and safety of GGTCS for the treatment of CRS, a randomized, double-blind, placebo-controlled, parallel group, clinical trial has been designed. A total of 58 participants with CRS will be recruited and randomly allocated to a GGTCS or placebo group in a 1:1 ratio. The participants will be administered GGTCS or placebo granules 3 times a day for 8 weeks. Data will be collected from the participants at baseline and at 1, 2, 4, and 8 weeks after random allocation. The primary outcome measure will be the mean change in the Sino-Nasal Outcome Test-22 score from baseline to 8 weeks. The secondary outcomes will include the Total Nasal Symptom Score, EuroQoL 5 Dimensions 5 Levels score, Nasal Endoscopy Index, Lund-Mackay score, and total serum immunoglobulin E level. DISCUSSION: The key elements for conducting a high-quality randomized clinical trial have been addressed in this protocol. In summary, the findings of this study are expected to provide a base for large-scale randomized controlled trials to confirm the safety and efficacy of GGTCS for the treatment of CRS and may consequently serve to improve future treatment strategies for this condition. TRIAL REGISTRATION: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0002835).

Herbal medicines for treating acute otitis media: A systematic review of randomised controlled trials.

INTRODUCTION: This systematic review aimed to assess the clinical evidence for the widespread use of herbal medicines in treating acute otitis media. METHODS: Eleven electronic databases, including MEDLINE, EMBASE, and the CENTRAL were searched, without language limitations. All randomised controlled trials involving the use of herbal medicines, alone or in combination with conventional therapies, for acute otitis media were included. RESULTS: We identified 4956 studies, of which seven randomised clinical trials met the inclusion criteria. The overall risk of bias of the included trials was relatively high or unclear. Treatment with Longdan-xiegan decoction or Shenling-baizhu powder, combined with antibiotics, appeared to be more effective than treatment with antibiotics alone in terms of the proportion of patients with total symptom recovery. Moreover, combination treatment of Sinupret® and antibiotics facilitated the recovery of middle ear conditions and hearing acuity. CONCLUSIONS: Despite some indications of potential symptom improvement, the evidence regarding the effectiveness and efficacy of herbal medicine for acute otitis media is inconclusive due to the poor quality of trials included. Moreover, we only analysed seven trials in this review. Therefore, to properly evaluate the effectiveness of herbal medicine for acute otitis media, systematic reviews based on more rigorously designed randomized trials are warranted in the future.

Development of an ultrasound-imaging procedure and acquisition of ultrasound images of acupuncture points for safety and accuracy of needle insertion.

BACKGROUND: Acupuncture is a relatively safe, commonly used "alternative" medical treatment for various symptoms. However, adverse effects can occur, including trauma, pneumothorax, and central-nervous-system injury. Our objective was to develop a reliable and practical procedure for ultrasound imaging of acupuncture points to improve safety during needling, and to acquire ultrasound images of several (44) acupuncture points, especially those in high-risk areas, according to an in-house standard operating procedure. METHODS: We created the standard operating procedure for ultrasound imaging for acupuncture, and collected ultrasound images of acupuncture points in clinical trials. RESULTS: Ultrasound images for 44 acupuncture points considered as high-risk points were collected from 85 healthy people who were classified by body-mass index, and high-quality, clear representative images of all 44 points were obtained. CONCLUSION: These baseline images could be helpful for understanding the anatomy under the skin at acupuncture points, which would allow for an enhanced safety and more accurate needling.

Herbal medicines for the treatment of otitis media with effusion: a systematic review of randomised controlled trials.

OBJECTIVES: This systematic review aimed to assess the clinical evidence supporting the use of herbal medicines (HMs) for the treatment of otitis media with effusion (OME). DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, AMED, CINAHL and three trial registries were searched up to January 2015. We also searched five Korean medical databases (KoreaMed, RISS, OASIS, DBPIA and KISS) and three Chinese databases (CNKI, Wanfang and VIP). STUDY ELIGIBILITY CRITERIA: This study included randomised clinical trials that reported the effects of HM for OME. The primary outcome was the complete resolution of OME at 2 or 3 months post randomisation. Secondary outcomes included the partial or complete resolution at all possible time points and hearing test. Three authors independently screened the titles and abstracts, selected studies and extracted the data relating to trial quality, characteristics and results. RESULTS: A total of 2141 potentially relevant studies were identified, of which 17 randomised clinical trials met our inclusion criteria. Most were evaluated as having a high or unclear risk of bias. Tongqiao tablets, Tongqiao huoxue decoctions and Tsumura-Saireito were associated with a lower complete or partial resolution rate when compared with conventional medicines (CMs) (p=0.02, p=0.0001, and p=0.04, respectively), and similar outcomes were observed with Huanglong tonger pills, Erzhang decoctions and Shenling baizhu powder when combined with CM versus CM alone (p<0.00001, p=0.02, and p=0.05, respectively). Tongqiao huoxue decoction plus CM appeared to be more effective than CM in terms of improving the pure tone threshold levels (p=0.0007). Tsumura-Saireito was found to affect the proportion of patients with normalised tympanometry (p=0.03). CONCLUSIONS: Despite some indications of potential symptom improvement, the evidence regarding the effectiveness and efficacy of HMs for OME is of poor quality and therefore inconclusive. PROTOCOL REGISTRATION NUMBER: CRD42013005430.