No-ozone cold plasma induces apoptosis in human neuroblastoma cell line via increased intracellular reactive oxygen species (ROS).

BACKGROUND: This study aimed to evaluate the effect of argon-based No-ozone Cold Plasma (NCP) on neuroblastoma cancer cell apoptosis. METHODS: Experiments were performed with SK-N-SH and HS 68. Cell cultures were treated with NCP for 1, 3, and 5 min. NCP was applied using three different strategies: direct NCP application to cell cultures, to only media, and to only cells. Evaluation of cell viability and the level of the reactive oxygen species (ROS) was performed. N-acetyl-L-cysteine (NAC) was also used to antagonize intracellular ROS. Cleaved caspase 3, PARP, aquaporin (AQP) 3 and 8 were detected. RESULTS: NCP induced a gradual decrease in the SK-N-SH cell viability. In contrast, the viability of HS 68 cells did not change. SK-N-SH cells viability was reduced the most when the only media-NCP application strategy was employed. Intracellular ROS levels were significantly increased with time. Cleaved caspase 3 and PARP were increased at 6 h after NCP application. SK-N-SH cells remained viable with NAC after NCP application. AQP 3 and 8 were over-expressed in SK-N-SH cells. CONCLUSION: These findings demonstrate the anti-cancer effect of NCP on neuroblastoma cells. NCP enhanced the selective apoptosis of neuroblastoma cells due to the increased intracellular ROS.

Improving quality of life for a patient with fibromyalgia and their caregiver: A protocol for the application of the integrative medical service model.

OBJECTIVES: Patients with incurable diseases experience difficulty carrying out activities of daily living and rely on caregivers. Caregivers of patients with fibromyalgia (FM) are unable to understand the extent of the patients' suffering because the pain sites are invisible. To address this problem, this study will apply an integrative healthcare service model to a single FM case to manage pain and enhance the quality of life and, subsequently, gather feedback from different sources regarding the treatment. This paper presents the study protocol. METHODS: We will conduct an observational study to gather quantitative and qualitative feedback from various perspectives regarding the application of an integrative healthcare service program for FM patients developed in Korea for an FM patient-caregiver pair. The program will comprise eight 100-minute weekly sessions, during which integrative services that combine Western and Oriental medicines (Korean traditional medicine) will be provided to enhance pain management and quality of life. The feedback collected after each session will be reflected in the next session' content. RESULTS: The results will comprise the feedback from the patient and caregiver in accordance with revisions made to the program. CONCLUSIONS: The results will provide basic data for optimizing an integrative healthcare service system in Korea for patients suffering from chronic pain owing to diseases such as FM.

Effect of Muscle Energy Technique on Hamstring Flexibility: Systematic Review and Meta-Analysis.

Since 2005, there have been no systematic reviews on the effects of multiple manual therapies, including muscle energy technique (MET), on the hamstrings. Therefore, this systematic review aimed to provide clinical evidence for the effectiveness of the MET on hamstring flexibility. We queried 10 electronic databases (PubMed, EMBASE, The Cochrane Library, KISS, NDSL, KMBASE, KISTI, RISS, Dbpia, and OASIS) up to the end of March 2022. This study only included randomized controlled trials (RCTs) investigating the use of MET for the hamstring. The literature was organized using Endnote. Literature screening and data extraction were conducted by two researchers independently. The methodological quality of the included RCTs was evaluated using the Cochrane risk-of-bias tool 1.0, and the meta-analysis was performed using RevMan 5.4. In total, 949 patients from 19 RCTs were selected according to the inclusion criteria. During active knee extension tests, the efficacy between MET and other manipulations did not significantly differ. For sit and reach tests, MET groups had higher flexibility compared to stretching (MD = 1.69, 95% CI: 0.66 to 2.73, p = 0.001) and no treatment (MD = 2.02, 95% CI: 0.70 to 3.33, p = 0.003) groups. No significant differences were observed in the occurrence of adverse reactions. Overall, we found that MET is more efficacious for improving hamstring flexibility compared to stretching and having no treatment during sit and reach tests because it combines isometric contraction with stretching. Owing to clinical heterogeneity, uncertain risk of bias, and the small number of included studies, further high-quality studies should assess the effectiveness of MET.

The efficacy, effectiveness, and safety of Kyung-ok-ko: A narrative review.

Kyung-ok-ko (KOK), a traditional medicinal formula in East Asia, has been recently studied across various fields. However, comprehensive reviews of clinical applications of KOK targeting clinical and experimental studies are lacking. Therefore, the application of KOK is being limited to the range of tonic medicines. To overcome this limitation, we aim to investigate the effectiveness, mechanism, and safety of KOK to obtain evidence regarding its effects in clinical applications. We searched for clinical and experimental articles in 11 databases (PubMed, Cochrane Library, Excerpta Medica dataBASE, China National Knowledge Infrastructure, Google Scholar, Research Information Sharing Service, Oriental Medicine Advanced Searching Integrated System, Koreanstudies Information Service System, Korean Medical Database, DBpia, and ScienceON). We selected 54 studies based on the inclusion criteria. Three clinical studies used KOK for a consumptive disease and health promotion. Fifty-one experimental studies reported the antioxidant activity, neuroprotective activity, anticancer effect, anti-inflammatory activity, immunological activity, growth promotion, impacts on cardiovascular system diseases, gastrointestinal system diseases, respiratory system diseases, and metabolic bone disease, hepatoprotective function, and antifatigue function of KOK, which were considered effective and safe in consumptive, chronic, metabolic, inflammatory, and immune diseases. We identified the effectiveness of KOK in the treatment of a wide range of diseases. However, further clinical studies are warranted in the future.

Comparison of Concordance between Chuna Manual Therapy Diagnostic Methods (Palpation, X-ray, Artificial Intelligence Program) in Lumbar Spine: An Exploratory, Cross-Sectional Clinical Study.

Before Chuna manual therapy (CMT), a manual therapy applied in Korean medicine, CMT spinal diagnosis using palpation or X-ray is performed. However, studies on the inter-rater concordance of CMT diagnostic methods, concordance among diagnostic methods, and standard CMT diagnostic methods are scarce. Moreover, no clinical studies have used artificial intelligence (AI) programs for X-ray image-based CMT diagnosis. Therefore, this study sought a feasible and standard CMT spinal diagnostic method and explored the clinical applicability of the CMT-AI program. One hundred participants were recruited, and the concordance within and among different diagnostic modalities was analyzed by dividing them into manual diagnosis (MD), X-ray image-based diagnosis (XRD) by experts and non-experts, and XRD using a CMT-AI program by non-experts. Regarding intra-group concordance, XRD by experts showed the highest concordance (used as a gold standard when comparing inter-group concordance), followed by XRD using the AI program, XRD by non-experts, and then MD. Comparing diagnostic results between the groups, concordance with the gold standard was the highest for XRD using the AI program, followed by XRD by non-experts, and MD. Therefore, XRD is a more reasonable CMT diagnostic method than MD. Furthermore, the clinical applicability of the CMT-AI program is high.

An Observational Study Using Ultrasound to Assess Allowable Needle Insertion Range of Acupoint CV12.

BACKGROUND: Abdominal organ injuries are a rarely reported complication when deep acupuncture needling is applied to the abdomen. In order to ascertain the allowable needle insertion range (ANIR) of the abdomen region, we selected acupoint CV12, which is commonly used for treating gastric disease, and ANIR was measured with an ultrasound device. METHOD: Eighty-five healthy volunteers were recruited, of which 83 cases of ultrasound images were obtained. To investigate the prediction factor of ANIR, we also measured several anthropometric factors. RESULTS: The average ANIR was 25.3 ± 10.2; generally, the ANIRs of females were thicker than those of males; and the liver was observed in 62.7% subjects' ultrasound images. The non-observed group showed thicker ANIR and higher BMI than the liver-observed group. CONCLUSION: There are reliable variables that make it possible to predict the ANIR. It is advised to refer to anthropometric factors in needling acupoint CV12 to avoid complications with the acupuncture treatment. However, individual differences are not negligible when applying deep needling. Thus, if the risk is not judged before or during the procedure, practitioners could consider the patient's ANIR on CV12 when applying acupuncture by examining the individual anatomical structures using ultrasound and considering internal organ positions to prevent adverse events due to acupuncture.

Introduction to methodology for the development of an integrative medical service model.

Background: The purpose of this article was to present a valid and reliable theoretical framework and method for the development of an integrated medical service model for the four major diseases. Methods: Methodologies for each process were presented based on three theoretical frameworks. The three theories were the double diamond process model, the Donabedian model, and the International Classification of Functioning, Disability, and Health model. Based on this, in the process of problem finding, a literature review, service user questionnaire, and interview methods were applied. For problem definition and solution, expert focus group interview and expert Delphi methods were applied. The subjects of the study were mainly selected from experts for each disease and users of medical services. For literature review, systematic literature review and subject range literature review were conducted, and for analysis, a meta-analysis was carried out. In the case of focus group interview and Delphi, the validity and reliability of domain derivation and sub-items were analyzed by applying the qualitative analysis method. Results: To develop an integrative medical service model, a theoretical framework and a systematic methodology were needed, and case studies were performed to prove its validity and reliability. This showed that the development of a medical service model needs to follow a scientific procedure. Conclusions: By introducing methodological approaches and procedures for the development of an integrated medical service model for the four major diseases, the researchers provided basic information on model development.

Comparison of concordance between chuna manual therapy diagnosis methods (palpation, X-ray, artificial intelligence program) in lumbar spine: An exploratory, cross-sectional, prospective observational study protocol.

INTRODUCTION: Chuna manual therapy (CMT) is a type of manual medicine practiced by Korean medical doctors in South Korea. Spinal diagnosis in CMT uses a system that applies manual diagnostic and X-ray tests to detect specific vertebral malpositions, based on the relative alignment across vertebral bodies. Recently, artificial intelligence (AI) programs have been developed to assist in the radiological diagnosis of CMT using X-ray images. Nevertheless, a few clinical studies have reported on the concordance between diagnosticians, diagnostics methodologies, and the use of AI programs for diagnosing CMT. At present, the evidence to support CMT diagnosis is insufficient. This study thus aims to overcome such limitations by collecting and comparing CMT diagnostic data from experts and non-experts through manual diagnosis, X-ray test, and images obtained using an AI program. The study aims to search for CMT diagnosis methods with more outstanding rationality and consistency and to explore the potential use of AI-based CMT diagnosis programs. METHODS/DESIGN: This study will be conducted as an exploratory, cross-sectional, prospective observational study that will recruit 100 non-specialist subjects. Each subject will submit a signed consent after the screening test and undergo L-spine standing AP & lateral X-ray imaging. Manual CMT diagnosis will be performed by 3 CMT experts according to the standard operation procedure (SOP). The X-ray images of the 100 subjects will subsequently be used to make the CMT radiological diagnoses according to the same SOP by the CMT expert group (n = 3) and CMT non-expert group (n = 3). Among the subjects, those in the non-expert group will receive another CMT radiological diagnosis with spinal data obtained using the AI program, approximately 1 month from after initial diagnosis.Based on the collected diagnostic data, within- and between-group concordance levels will be assessed for each diagnostic method. The verified level of concordance will be used to test the potential use of CMT diagnostic method and CMT AI programs with high levels of rationality and consistency. ETHICS AND DISSEMINATION: This trial has received complete ethical approval from the Wonkwang University Korean Medicine Hospital (IRB 2021-8). We intend to submit the results of the trial to a peer-reviewed journal and/or conferences. TRIAL REGISTRATION: https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&search_page=M&pageSize=10&page=undefined&seq=20613&status=5&seq_group=20613, Identifier: KCT0006707.

Altered thalamic gray matter volume in firefighters with heavy alcohol use.

BACKGROUND: Alcohol, a known addictive substance, affects the structural properties of the brain. In this study, we explored associations between alcohol use and gray matter properties among firefighters, who are often exposed to significant occupational stress. METHODS: Gray matter volume (GMV) was evaluated using voxel-based morphometry in 287 male firefighters (mean age: 48.8 ± 7.7 years). Firefighters were classified into 32 never-drinkers, 162 non-heavy alcohol users, and 93 heavy alcohol users according to their alcohol consumption. GMV was compared between groups, and the correlations between GMV and alcohol use were investigated. A voxel-wise height threshold of p < 0.001 (uncorrected) was used, with small volume correction applied on cluster level. RESULTS: Heavy alcohol users had lower GMV in the bilateral thalamus than non-heavy alcohol users or never-drinkers. Heavy alcohol users also showed lower GMV in the left insula, compared to other groups. The higher the alcohol consumption among firefighters, the lower the GMV of the right thalamus. CONCLUSIONS: The results of this study show that heavy alcohol use has an association with lower GMV in several core regions, including the thalamus. When considering the impact of these brain regions on cognitive and behavioral control, our findings suggest a need for concern about heavy alcohol use among firefighters.

The effect of autogenous tooth bone graft material without organic matter and type I collagen treatment on bone regeneration.

OBJECTIVES: The aim of this study is to examine the effect of particulate autogenous tooth graft removed with organic matter and type I collagen addition on bone regeneration and to validate the possibility of useful allograft material for jaw defects. MATERIAL AND METHODS: Autogenous tooth bone maker (Korean Dental Solution® KOREA) made particulate autogenous tooth not including organic matter. We used to the developed tooth grafts for experiment. Cell adhesion test with hemacytometer and energy dispersive X-ray spectroscopy (Supra40 VP®, Carl Zeiss, Germany) analysis about the particulate autogenous tooth and type I collagen were performed. Rabbits were divided into three groups: bone graft with organic matter (OM) removing particulate autogenous tooth group, bone graft with OM removing particulate autogenous tooth and type I collagen group, and a control group. Bone grafting was performed in rabbit's calvaria. The rabbits were sacrificed at different interval at 1, 2, 4, and 6 weeks after bone grafting for the histopathologic observation and observed the effect of bone regeneration by SEM, H-E & Masson stains, osteocalcin IHC staining. RESULT: In vitro cytopathological study showed affinity for cells, cell attachment pattern, and cell proliferation in the order of control group, OM-removed and collagen-treated group, OM-removed particulate autogenous tooth group. The results of the degree of mineralization were opposite to those of the previous cell experimental results, and the OM-removed group, OM-removed group and collagen-treated group were relatively higher than the control group. Histopathologic analysis showed that vascularization and neonatal bone formation were higher in particulate autogenous tooth group with removing OM and with addition of collagen than control group and group of OM removed only. Immunohistochemical analysis showed that osteocalcin (OSC) expression was not observed in the control group, but at 4 weeks groups, OSC expression was observed the OM removed and OM-removed-collagen-treated particulate autogenous tooth, and the degree of expression was somewhat stronger in group of the OM removed and collagen additionally treated particulate autogenous tooth. CONCLUSION: Particles that do not contain organic matter, the saint tooth, was responsible for sufficient bone graft material through the role of space maintenance and bone conduction, and further improved bone formation ability through additional collagen treatment. Therefore, research on various extracellular substrates and autologous bone grafting materials is necessary, and through this, it is possible to lay the foundation for a new type of autologous bone grafting material with excellent academic and technical utility.

Application of a Drone Magnetometer System to Military Mine Detection in the Demilitarized Zone.

We propose a magnetometer system fitted on an unmanned aerial vehicle (UAV, or drone) and a data-processing method for detecting metal antipersonnel landmines (M16) in the demilitarized zone (DMZ) in Korea, which is an undeveloped natural environment. The performance of the laser altimeter was improved so that the drone could fly at a low and stable altitude, even in a natural environment with dust and bushes, and a magnetometer was installed on a pendulum to minimize the effects of magnetic noise and vibration from the drone. At a flight altitude of 1 m, the criterion for M16 is 5 nT. Simple low-pass filtering eliminates magnetic swing noise due to pendulum motion, and the moving average method eliminates changes related to the heading of the magnetometer. Magnetic exploration was conducted in an actual mine-removal area near the DMZ in Korea, with nine magnetic anomalies of more than 5 nT detected and a variety of metallic substances found within a 1-m radius of each detection site. The proposed UAV-based landmine detection system is expected to reduce risk to detection personnel and shorten the landmine-detection period by providing accurate scientific information about the detection area prior to military landmine-detection efforts.

Surgical Treatment of Medication-Related Osteonecrosis of the Jaw: A Retrospective Study.

The purpose of this study was to confirm the success rate of surgical treatment of medication-related osteonecrosis of the jaw (MRONJ) in patients at a single institution (Association of Oral and Maxillofacial Surgery (AAOMS) stages 1, 2, or 3), and to identify the factors that influence treatment outcomes. As a result of analyzing the outcomes of treatment, surgical "success" was achieved in 93.97% (109) of cases, and "failure" was observed at 6.03% (7) cases. Analysis of patient factors that potentially affect treatment outcomes showed that zoledronate dose (p = 0.005) and the IV (intravenous) injection of drugs (p = 0.044) had significant negative impacts.

Acute effects of Amomum villosum Lour. fruit extract on postprandial glycemia and insulin secretion: A single-blind, placebo-controlled, crossover study in healthy subjects.

BACKGROUND: Amomum villosum Lour., (Zingiberaceae) an herbaceous plant in the ginger family, has been used to treat various diseases. In a single-blind, randomized, crossover study, we assessed the postprandial blood insulin and blood glucose responses in healthy subjects (n = 40) after the Amomum villosum water extract (AVE) (5 g/person) or a placebo (5 g/person) consumption. METHODS: During each treatment course, the healthy subject consumed a regular late afternoon meal, followed by fasting for 12 h, and arrived at the clinical study center the next morning. Blood insulin and blood glucose levels were assessed at 0, 30, 60, 90, and 120 min after AVE consumption. Between each treatment, the subjects accomplished one week of a washout period. RESULTS: The AVE intake demonstrated a significant (67.26%) decline in postprandial blood glucose AUC0-120 min (incremental area under the curve from 0 to 120 min) versus the placebo (P = 0.011). Furthermore, AVE reduced postprandial blood insulin AUC0-120 min by 59.95% compared to the placebo group (P < 0.003), supporting the blood glucose results. CONCLUSION: This study revealed that AVE consumption significantly reduced postprandial insulin and glucose levels in healthy individuals, due in part to inhibition of α-glucosidase, and glucose transport.

A systematic review and meta-analysis of the efficacy of acupuncture and electroacupuncture against chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in 68.1% of patients within the first month of undergoing chemotherapy; however, standardized treatment for CIPN has not been established yet. The efficacy of acupuncture, a widely used treatment for CIPN in South Korea, has not been studied sufficiently. This study aimed to review the studies that evaluated the efficacy of acupuncture or electroacupuncture (EA) in treating CIPN. METHODS: A literature search was performed on relevant international databases - MEDLINE, Embase, the Allied and Complementary Medicine Databases, and China National Knowledge Infrastructure - as well as Korean databases - the National Digital Science Library, Oriental Medicine Advanced Searching Integrated System, DBpia, and Korean Studies Information Service System. Randomized controlled trials (RCTs) that aimed to treat CIPN symptoms with acupuncture or EA and set not only a control group with a conventional pharmacological treatment or injection, but also a placebo control or sham-acupuncture group, were included. Meta-analysis was conducted to elucidate the efficacy of acupuncture/EA on the basis of symptom score. RESULTS: Of the 13 studies included in the literature review, 12 RCTs compared acupuncture and pharmacological treatments. There were 3 EA RCTs, but only 1 RCT compared EA and sham-EA. A total of 832 participants were included in these studies. Five RCTs showed that acupuncture was more effective than pharmacological treatment in terms of efficacy rate. Regarding the risk of bias summary, the quality of included studies was poor. Only 1 study compared the efficacy of EA and sham EA; therefore, the specific efficacy of acupuncture could not be elucidated. CONCLUSION: Acupuncture is safe, but the symptom-alleviating effect on CIPN can hardly be determined because of methodological deficiencies of the included studies. In terms of the clinical efficacy rate, acupuncture was more effective than conventional pharmacological treatments. PROSPERO REGISTRATION NUMBER: CRD42018111509.

Whitlockite Granules on Bone Regeneration in Defect of Rat Calvaria.

Whitlockite (WH; Ca18Mg2(HPO4)2(PO4)12) is a calcium phosphate based ceramic that contains magnesium ions. As the second most abundant mineral in living bone, WH occupies 25-35 wt % of the inorganic portion of human bone. Compared to hydroxyapatite (HAp, Ca10(PO4)6(OH)2), WH possesses better mechanical properties, faster resorbability, and promotion behavior on the osteogenesis. In this article, we introduced a fabrication method of interconnected porous WH granules through vacuum filtration, followed by sintering treatment based on the thermal stability of WH synthesized using the tri-solvent system. This study presents a histological, radiological, and immunohistochemical evaluation of the bone healing potential of these WH granules in a 5 mm diameter calvarial bone defect in rats. The histological evaluation shows no inflammation or foreign body reaction in the WH group. The WH group displays newly formed bone at the same thickness as the original bone. On the contrary, bone formation is not observed in the nontreated (NT) group. Besides, immunohistochemistry (IHC) confirmed that WH granules promoted bone regeneration with the significantly higher expression of bone morphogenetic proteins-2 (BMP-2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) compared to the NT group without the addition of exogenous cells or growth factors. These results suggest that WH has excellent potential for application in bone tissue regeneration.

Ultrasensitive Electrical Detection of Hemagglutinin for Point-of-Care Detection of Influenza Virus Based on a CMP-NANA Probe and Top-Down Processed Silicon Nanowire Field-Effect Transistors.

Rather than the internal genome nucleic acids, the biomolecules on the surface of the influenza virus itself should be detected for a more exact and rapid point-of-care yes/no decision for influenza virus-induced infectious diseases. This work demonstrates the ultrasensitive electrical detection of the HA1 domain of hemagglutinin (HA), a representative viral surface protein of the influenza virus, using the top-down complementary metal oxide semiconductor (CMOS) processed silicon nanowire (SiNW) field-effect transistor (FET) configuration. Cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-NANA) was employed as a probe that specifically binds both to the aldehyde self-aligned monolayer on the SiNWs and to HA1 simultaneously. CMP-NANA was serially combined with two kinds of linkers, namely 3-aminopropyltriethoxysilane and glutaraldehyde. The surface functionalization used was verified using the purification of glutathione S-transferase-tagged HA1, contact angle measurement, enzyme-linked immunosorbent assay test, and isoelectric focusing analysis. The proposed functionalized SiNW FET showed high sensitivities of the threshold voltage shift (ΔVT) ~51 mV/pH and the ΔVT = 112 mV (63 mV/decade) with an ultralow detectable range of 1 fM of target protein HA1.

Effect of Samryungbaekchul-san Combined with Otilonium Bromide on Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Randomized Controlled Trial.

Conventional and herbal drugs are frequently used together to treat many disorders. Samryungbaekchul-san (SRS, a herbal formula) and otilonium bromide (OB, an antispasmodic agent) are widely used to treat diarrhea-predominant irritable bowel syndrome (D-IBS) in Eastern Asian countries. However, there have been no studies on the co-administration of SRS and OB. Therefore, we aimed to preliminarily assess the feasibility of SRS combined with OB for D-IBS treatment in a pilot double-blind, four-arm, parallel-group, randomized controlled trial (RCT), including 80 patients diagnosed with D-IBS according to the Rome III criteria. The patients were randomly assigned to four treatment groups and were administered drugs for eight weeks after a two-week preparatory period. Follow-up was conducted four weeks after the administration period. The primary outcome was evaluated by using a global D-IBS symptom improvement score; no statistically significant difference was observed between the groups. However, multiple logistic regression analysis of primary outcome scores shows that SRS significantly improved D-IBS symptoms (p < 0.05). For secondary outcomes, better results were observed in the SRS + OB group, in terms of symptoms, including abdominal pain, discomfort, frequency of abdominal pain, and stool form than in OB alone or placebo groups (p < 0.05). In conclusion, the co-administration of SRS and OB might be an effective and safe strategy for the treatment of D-IBS. Large-scale RCTs are warranted to further confirm and clarify these findings.

Protocol for a systematic review and meta-analysis of the efficacy of acupuncture and electroacupuncture against chemotherapy-induced peripheral neuropathy.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in approximately 30% to 40% of patients who receive chemotherapy; however, standardized treatment for CIPN has not yet been developed. Acupuncture is widely used to treat CIPN in Korea, but its efficacy has not been investigated. The purpose of this study is to review the current literature on the efficacy of acupuncture and electroacupuncture (EA) in treating CIPN. MATERIALS AND METHODS: We will perform a literature review using the relevant databases, including MEDLINE, Embase, the Allied and Complementary Medicine Databases (AMED), and China National Knowledge Infrastructure (CNKI), as well as Korean databases, including the National Digital Science Library (NDSL), Oriental Medicine Advanced Searching Integrated System (OASIS), DBpia, and Korean studies Information Service System (KISS). Randomized controlled trials describing treatment of CIPN symptoms with acupuncture or EA will be included. The primary outcomes will be scores on a visual analog scale and a numeric rating scale for neuropathic pain. We will also assess the risk of bias by evaluating the available studies using the tools of the Cochrane Collaboration and carry out a meta-analysis. ETHICS AND DISSEMINATION: Ethical approvals and patient consent are not necessary because the meta-analysis will be based on published research. We will submit our meta-analysis to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42018111509.

Additive effect of bFGF and selenium on expansion and paracrine action of human amniotic fluid-derived mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cell-derived conditioned medium (MSC-CM) has emerged as a promising cell-free tool for restoring degenerative diseases and treating traumatic injuries. The present study describes the effect of selenium as a reactive oxygen species (ROS) scavenger and its additive effect with basic fibroblast growth factor (bFGF) on in vitro expansion of amniotic fluid (AF)-MSCs and the paracrine actions of AF-MSC-CM as well as the associated cellular and molecular mechanisms. METHODS: In this study, we obtained CM from human AF-MSCs cultured with selenium. The stemness of selenium-treated AF-MSCs was evaluated by cell growth and differentiation potential. Human fibroblasts were treated with AF-MSC-CM and analyzed for cell signaling changes. For in vivo wound healing assay, ICR mice with a full-thickness skin wound were used. RESULTS: Selenium played a critical role in in vitro expansion of AF-MSCs through activation of the AKT-ERK1/2, Smad2, and Stat3 signaling pathways along with inactivation of GSK3ß. When administered together with bFGF, it showed remarkable effect in inhibiting ROS accumulation and preserving their multipotency. Proliferation and migration of human dermal fibroblasts and in vivo wound healing were improved in the CMs derived from AF-MSCs exposed to selenium and bFGF, which was caused by the Smad2, AKT-MEK1/2-ERK, and NFκB signaling triggered by the paracrine factors of AF-MSCs, such as TGF-ß, VEGF, and IL-6. Our results suggest the following: (a) supplementation of selenium in AF-MSC culture contributes to in vitro expansion and preservation of multipotency, (b) ROS accumulation causes progressive losses in proliferative and differentiation potential, (c) the separate activities of bFGF and selenium in MSCs exert an additive effect when used together, and (d) the additive combination improves the therapeutic effects of AF-MSC-derived CMs on tissue repair and regeneration. CONCLUSION: Antioxidants, such as selenium, should be considered as an essential supplement for eliciting the paracrine effects of MSC-CMs.

Effect of herbal extract granules combined with otilonium bromide on irritable bowel syndrome with diarrhoea: a study protocol for a randomised controlled trial.

INTRODUCTION: Irritable bowel syndrome (IBS), known as a functional and organic gastrointestinal disorder, is a collection of symptoms that occur together and generally include pain or discomfort in the abdomen and changes in bowel movement patterns. Due to the limitations of conventional treatments, alternative IBS treatments are used by many patients worldwide. Samryungbaekchulsan (SRS), a herbal formula, has long been used for alleviating diarrhoea-predominant IBS (D-IBS) in traditional Korean medicine. Otilonium bromide (OB) is an antimuscarinic compound used to relieve spasmodic pain in the gut, especially in IBS. Although herbal formulae and Western drugs are commonly coadministered for various diseases in Korea, few clinical studies have been conducted regarding the synergic effects of these treatments for any disease, including D-IBS. METHODS AND ANALYSIS: This trial is a randomised, double-blinded, placebo-controlled, double-dummy, four-arm, parallel study. After a 2-week preparation period, 80 patients with D-IBS will be randomly assigned to one of four treatment groups consisting of SRS (water extract granules, 5 g/pack, three times a day) with OB (tablet form, one capsule three times a day) or their placebos, with treatment lasting for 8 weeks. Post-treatment follow-up will be conducted 4 weeks after the end of treatment. The primary outcome is the finding obtained using the Subject's Global Assessment of Relief method. The secondary outcomes are the severity of symptoms related to D-IBS, determined using a 10-point scale, and the change in symptoms. ETHICS AND DISSEMINATION: This trial has full ethical approval of the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS15MISV0033) and the Korean Ministry of Food and Drug Safety (30769). The results of the study will be disseminated through a peer-reviewed journal and/or conference presentations. TRIAL PROTOCOL VERSION: IS15MISV0033 version 4.0 (25 July 2016). TRIAL REGISTRATION NUMBER: KCT0001621 (approval date: 10 August 2015).