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Acupuncture treatment can be defined as a medical procedure with an acupuncture needle at acupoints. Establishing suitable control settings is essential, based on the target elements of the acupuncture therapy. In order to properly design a clinical trial or an experiment, a control group must be established. Here, we overview the significance of the control group and its limitations in acupuncture research. Clinical trials have employed a variety of study designs and controls for acupuncture treatment in order to compare the effects of actual treatments with control groups that include no treatment or treatment as usual, sham acupuncture at true acupoints, real acupuncture at non-acupoints, and sham acupuncture at non-acupoints. In order to determine the point-specificity of acupuncture, real acupuncture at non-acupoints should be taken into consideration, whereas sham acupuncture at the same true acupoints should be used to determine the needling-specific effect of acupuncture. It is crucial to choose the optimum control for acupuncture treatments depending on the study's main goal and to interpret the results in accordance with the research design.

BackgroundWhen patients continue to experience cough despite conventional treatment, East Asian traditional medicine (EATM) including herbal medicine and/or acupuncture has been frequently used. Previous systematic reviews of EATM treatment for chronic cough have been conducted mainly on herbal medicine, targeting patients with conditions that cause cough. In clinical practice, EATM interventions are not limited to herbal medicine, and considering that chronic cough is often caused by two or more conditions or unspecific causes, a comprehensive investigation is clinically relevant. We examined the current research status of EATM for chronic cough.MethodsBased on Arksey and O'Malley's scoping review methodological framework, a total of six English, Chinese, Korean, and Japanese electronic databases were searched on August 2022. Any clinical studies on EATM targeting chronic cough patients (regardless of their cause) were included.ResultsAmong 474 included studies, the study designs were mainly randomized controlled trials (72.4%), and the population was evenly distributed between children and adults. The cause of cough was not reported in most studies (56.1%). The common cause of cough was upper airway cough syndrome and post-respiratory infection (9.5%, each), followed by mixed cause (7.6%), nonspecific cause (5.9%), and gastroesophageal reflux disease (4.0%). EATM was conducted for a mean of 19.1 days, and herbal medicine was the most common (80.6%). Conventional medication was frequently used as a control (81.2%). For outcomes, the total effective rate was the most frequently utilized (94.3%), followed by cough severity (53.8%). EATM treatment showed positive outcomes in most studies.ConclusionsIn future EATM studies, it is necessary to either specify the cause of chronic cough or to report that the study was targeting nonspecific chronic cough. In addition, high-quality studies assessing the efficacy of EATM with placebo control treatment should be conducted, using validated evaluation tools.

Klebsiella pneumoniae is an uncommon cause of septic arthritis in adults. However, late detection can cause serious complications, including joint destruction and immobility. The purpose of this study was to report a case of successfully treated septic arthritis of the hip joint (SAHJ) caused by K. pneumoniae. A 49-year-old female patient presented to our hospital with fever and progressive severe pain in the right hip area. Although there was no abnormality on plain radiographs, ultrasonography revealed diffuse swelling of the right hip joint. Under ultrasonography guidance, the hip joint fluid was aspirated, and Gram staining and culturing were performed. The patient’s pain was significantly reduced after the joint aspiration. The Gram staining and culturing revealed gram-negative bacilli, which were subsequently identified as K. pneumoniae. According to the results, systemic intravenous antibiotic (ceftriaxone) was administered without complications, and the patient was discharged on oral antibiotic (ciprofloxacin). Clinical cases of septic arthritis of the knee or sacroiliac joint have been occasionally reported in adults, but cases of SAHJ are rare. Moreover, K. pneumonia-induced SAHJ has not been reported to date. Therefore, we report this very rare case and its successful treatment.

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.

Background: Gyejibokryeong-hwan (GBH), a herbal mixture that is widely used for climacteric syndrome, is studied for its efficacy; however, no study evaluated the GBH indication, which is a blood-stasis pattern based on traditional Chinese medicine theory. Methods: This was a randomized, double-blinded, placebo-controlled clinical pilot trial. Fifty subjects with climacteric syndrome were recruited and randomly assigned to GBH group or placebo group. Subjects were administered GBH or placebo granules for 4 weeks followed by 4 weeks of observation period. For the primary outcome, the Menopause Rating Scale (MRS) was evaluated. For the secondary outcomes, quality of life, degrees of abdominal resistance and tenderness, blood-stasis pattern questionnaire and degree of upward movement of Qi were evaluated. Results: After 4-week intervention, the mean change of total MRS score significantly decreased in the GBH group compared to the placebo group (p = 0.037). The quality of life related to physical health (p = 0.008) and blood-stasis pattern (p = 0.018) significantly improved in the GBH group but not in the placebo group. Conclusion: Our findings provide evidence of the feasibility of recruiting subjects with GBH indications and show that GBH may have clinical efficacy for the treatment of menopausal symptoms, especially urogenital symptoms, without any significant adverse events. Trial registration: This trial was registered at Clinical Research Information Service (CRIS identifier: KCT0002040).

Abstract Background To evaluate safety of acupuncture treatment by Korean Medicine Doctors (KMDs), a prospective, practice-based survey on adverse events (AEs) associated with acupuncture was conducted. Methods From July 2016 to October 2017, KMDs were invited to participate in an online survey. Frequency was calculated as the number of AEs per 10,000 treatments; severity was assessed with the Common Terminology Criteria for Adverse Events Grading (Severity) Scale; and causality was evaluated using the World Health Organisation-Uppsala Monitoring Centre system for standardised case causality assessment. Associations between AE occurrence and KMDs’ type of practice/clinical experience and patient age/gender/current medication(s) were analysed. Results Data on 37,490 acupuncture treatments were collected from 222 KMDs. At least one AE was reported from 4,518 acupuncture treatments, giving a frequency rate of 1,205 per 10,000 acupuncture treatments; this increased to 4,768 treatments when administrative problems related to defective devices or medical negligence were added, for a rate of 1,272 per 10,000 acupuncture treatments. Commonly reported AEs were bleeding, needle site pain, and bruising. Approximately 72.9% of AEs/administrative problems were assessed as they certainly occurred by acupuncture treatment in causality assessment. Most AEs/administrative problems were considered mild in severity and two life-threatening AEs were resolved with no sequelae. Compared to males, female patients were more likely to experience AEs and KMDs’ clinical experience was not associated with reported AE occurrence. Conclusions Although acupuncture-associated AEs occur commonly, they are largely transient and mild. Acupuncture performed by qualified KMDs may serve as a reliable medical treatment with acceptable safety profiles.

Abstract Background Insomnia is one of the most frequent symptoms in people with cancer. Electroacupuncture has been widely used in people with cancer or insomnia. We explored the feasibility and preliminary effectiveness of electroacupuncture for cancer-related insomnia. Methods People with cancer and insomnia disorder were randomly allocated to electroacupuncture, sham-electroacupuncture, or usual care groups. Participants received either 10 sessions of electroacupuncture at real acupoints, sham-electroacupuncture at non-acupoints, or usual care in each group for 4 weeks. We calculated the recruitment, adherence, and completion rates of participants. The Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), sleep diary and actigraphy-derived sleep parameters, Functional Assessment of Cancer Therapy-Fatigue (FACT-F), Montreal Cognitive Assessment (MoCA), and salivary levels of cortisol and melatonin were evaluated as outcome measures. Results Twenty-two participants were enrolled (8, 6, and 8 respectively in the electroacupuncture, sham-electroacupuncture, and usual care groups) and 20 participants completed the trials (8, 4, and 8 respectively). The recruitment, adherence, and completion rates were 78.57% (22/28), 95.45% (21/22), and 90.91% (20/22), respectively. Most of the participants had previously received conventional treatment for insomnia, but few had received Korean medicine treatment, without any demographic or clinical differences between groups. In the electroacupuncture group, there was a statistically significant reduction of 10.13 (mean) ± 8.15 (standard deviation) and 5 ± 3.70 points in mean ISI and PSQI scores at 4 weeks post-treatment (P = .0098 and .0066), compared with sham-electroacupuncture (2.06 ± 7.15 and 1.61 ± 4.34; P = .4796 and .3632) and usual care (3.25 ± 2.60 and 1.38 ± 2.13; P = .0096 and .1112). Although there was no significant difference in ISI score between groups at 4 weeks post-treatment, the electroacupuncture group continued to improve significantly at 4 weeks’ follow-up, showing borderline and significant differences compared to the sham-electroacupuncture and usual care (P = .0614 and .0015). The FACT-F scores in electroacupuncture group showed a significant improvement compared with the sham-electroacupuncture group (P = .0305). No electroacupuncture-related adverse events were reported. Conclusions Electroacupuncture might be feasible for cancer-related insomnia, despite slow participant recruitment. Additional trials with adequately powered sample sizes and a substantial change to the recruitment procedure are needed. Trial registration Clinical Research Information Service, KCT0002162 . Submitted 27 October 2016, Registered 2 December 2016 - Retrospectively registered (The first participant enrolment: 28 November 2016),

Abstract Cancer‐related fatigue (CRF) is one of the most common chronic symptoms experienced by cancer patients. As moxibustion is a popular traditional therapy for managing fatigue, it can be an alternative strategy to treat CRF as well. Therefore, we rigorously designed a full‐scale, multicenter, assessor‐blinded, randomized controlled trial to evaluate the efficacy and safety of moxibustion treatment for CRF. Ninety‐six subjects suffering from CRF were recruited and randomly assigned to moxibustion group, sham moxibustion group, or usual care group. Both the moxibustion group and the sham group received moxibustion treatment for 8 weeks and the usual care group did not. Brief fatigue inventory (BFI) score and Functional Assessment of Cancer Therapy‐Fatigue score were used to assess CRF at baseline and weeks 5, 9, and 13. Questionnaires for the assessment of cognitive impairment, quality of life, and Cold–Heat and Deficiency–Excess patterns were also evaluated. BFI scores significantly decreased in moxibustion group compared to the usual care group (mean difference of −1.92, p

Background: The first treatment option for major depressive disorder (MDD) is antidepressants, however, there is substantial demand for alternative therapies due to its low compliance and remission rates. This study was aimed to explore the effectiveness, safety, and feasibility of electroacupuncture plus moxibustion therapy for MDD. Methods: Thirty adults with MDD were randomly assigned to the treatment group (TG) or control group (CG). The TG was treated with electroacupuncture plus moxibustion, and the CG received sham interventions at non-acupoints for 8 weeks. The primary outcome measure was the intergroup difference of the mean change of total score of the Hamilton rating scale for depression (HRSD) between baseline and week 9. Secondary outcome measures were Beck's depression inventory, insomnia severity index, the state-trait anxiety inventory, the EuroQol-5 dimension index, the measure yourself medical outcome profile version 2, and frontal alpha asymmetry measured by electroencephalography. Adverse events (AEs) were monitored for safety assessment. Results: The primary outcome measure was not significantly different between the two groups (p=0.2641), although the scores of HRSD in both groups improved significantly after treatment. No significant difference was identified between groups in secondary outcome measures. The incidence of AE was not significantly different between the two groups (p=0.1067). Conclusion: A clinical trial using electroacupuncture plus moxibustion for MDD seems feasible. However, further studies with the larger size, adopting ideal controls are warranted to provide a confirmative conclusion to the efficacy and safety of electroacupuncture plus moxibustion for MDD. Trial registration: The protocol was registered at Korean Clinical Trial Registry (CRIS-KCT0001810)

This study aimed to compare the cost-effectiveness of manual therapy and usual care for patients with chronic neck pain. A cost-utility analysis alongside a pragmatic randomized controlled trial was conducted in five South Korean hospitals. Data were procured from surveys and nationally representative data. Participants were 108 patients aged between 19 and 60 years, with chronic neck pain persisting for at least 3 months and a pain intensity score of ≥5 on the numerical rating scale in the last 3 days. The study was conducted for 1 year, including 5 weeks of intervention and additional observational periods. Participants were divided into a manual therapy (Chuna) group and a usual care group, and quality-adjusted life-years, costs, and the incremental cost-effectiveness ratio were calculated. The quality-adjusted life-years of the manual therapy group were 0.024 higher than that of the usual care group. From the societal perspective, manual therapy incurred a lower cost—at $2,131—and was, therefore, the more cost-effective intervention. From a healthcare system perspective, the cost of manual therapy was higher, with an incremental cost-effectiveness ratio amount of $11,217. Manual therapy is more cost-effective for non-specific chronic neck pain management from both a healthcare system and societal perspective.

Background: Cancer-related cognitive impairment (CRCI) is a significant problem for cancer patients, as the number of cancer survivors experiencing cognitive impairments is increasing in the absence of standard treatment. There have been attempts to improve the cognitive function of patients with cancer using acupuncture; however, no studies have been conducted using electroacupuncture. Thus, we designed a preliminary study to investigate the feasibility of a clinical trial using electroacupuncture in CRCI patients. Methods: We conducted a single-arm, pilot, clinical trial to investigate the feasibility of a study protocol for further large-scale clinical trials of electroacupuncture in CRCI patients. All participants were treated with electroacupuncture twice a week for 30 minutes at a time, for 8 weeks on acupoints GV20, GV24, EX-HN1, and GB20, HT7, PC6, and KI3. Both subjective and objective outcomes of cognitive function, quality of life (QoL), and psychological factors were measured in all participants at baseline, week 4, 8, and 12. For safety assessment, vital signs, laboratory examinations, and adverse events (AEs) were observed throughout the trial. Results: A total of 12 participants were enrolled at Daejeon and Dunsan Korean Medicine Hospital of Daejeon University from 21 April 2017 to 31 January 2018. After 8 weeks of treatment, electroacupuncture significantly improved both subjective and objective cognitive outcomes, including the perceived cognitive impairments scale of the Functional Assessment of Cancer Therapy-Cognitive Function, QoL scale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire-C30, Korean version of Montreal Cognitive Assessment, Boston Naming Test, Seoul Verbal Learning Test, and Rey Complex Figure Test. During the entire trial period, 19 AEs were observed, with no serious AEs. Additionally, it was found that all feasibility outcomes, including recruitment, completion, and adherence rates, achieved successful results as the ratio exceeded 0.8. Conclusion: Our study results revealed that electroacupuncture improved cognitive complaints in cancer patients, and we expect electroacupuncture to be a safe and effective management therapy for CRCI patients. These feasibility trial results will be used as preliminary data for future randomized controlled clinical trials. Trial registration number: Korean Clinical Trial Registry (KCT0002168).

Introduction: Gastroesophageal reflux-induced chronic cough (GERC) is one of the most common etiologies of chronic cough. Despite the growing prevalence and interest in GERC, no effective treatment is currently available. In our study, we used a combination of herbal medicines, Ojeok-san (OJS) plus Saengmaek-san (SMS), for the treatment of GERC.Methods: We conducted a pilot, randomized, placebo-controlled, parallel-arm, single-center clinical trial to assess the feasibility of our study protocol, as our study is the first herbal medicine trial for GERC. All enrolled participants were randomly assigned to either the intervention or placebo group in a 1:1 ratio and were administered trial drugs three times a day for 6 weeks, with an evaluation visit performed every 2 weeks for their efficacy and safety assessment until the follow-up visit (week 8). We evaluated the severity and frequency of cough, cough-specific quality of life, airway hypersensitivity, and reflux-related gastrointestinal symptoms, as well as pattern identification, to investigate the complex mechanisms of reflux cough syndrome.Results: A total of 30 participants were enrolled, and 25 completed the study at Kyung Hee University Korean Medicine Hospital from 26 December 2018 to 31 May 2021. OJS plus SMS significantly improved the cough diary score (CDS), cough visual analog scale, Korean version of the Leicester Cough Questionnaire, Hull Airway Reflux Questionnaire, and Gastrointestinal Symptom Rating Scale after the treatment compared to the baseline. Notably, OJS plus SMS showed significant efficacy in the daytime and total CDS compared with the placebo. Only one adverse event was observed during the trial, and no serious adverse events occurred. Additionally, we achieved successful results in feasibility outcomes by exceeding the ratio of 80%.Conclusion: We confirmed the feasibility of our trial design and demonstrated the potential of OJS plus SMS in relieving the severity of cough and GI symptoms in GERC patients with safe and successful feasibility results. We anticipate that our study results will be used as the basis for further large-scale, well-designed, confirmatory trials to evaluate the safety and efficacy of OJS plus SMS in GERC.Clinical Trial Registration: [https://cris.nih.go.kr], identifier WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003115].

Objectives: Ganglion cysts require a sustainable treatment that suppresses their frequent recurrence. This study aimed to explore the clinical effects of Scolopendra pharmacopuncture (SP) and electroacupuncture on ganglion cysts.Methods: We retrospectively reviewed the patient records and follow-up reports for 20 patients with wrist ganglion cysts who received SP and electroacupuncture from April 2016 to March 2017. The cyst diameter, recurrence, visual analog scale (VAS) scores for pain, the Korean version of the disabilities of arm, shoulder, and hand (K-DASH) score, and the Korean version of the patientrated wrist evaluation (K-PRWE) score before and after treatment were noted.Results: After treatment, the cyst diameter decreased significantly from 13.61 ± 6.41 mm to 5.15 ± 6.18 mm (p < 0.001), and VAS score for pain decreased from 1.31 ± 1.77 to 0.41 ± 0.33 (p = 0.021). Further, the K-DASH score decreased significantly from 8.97 ± 12.66 to 2.21 ± 7.39 (p = 0.016), and score for the function subscale of K-PRWE decreased from 11.37 ± 4.48 to 9.1 ± 3.67 (p = 0.046). No recurrences were reported from the followed-up patients. Any complication related to SP or electroacupuncture was not observed, except mild rash, itching, and swelling at the injection site in four patients.Conclusion: Combination of SP and electroacupuncture may be effective in treating ganglion cysts; further prospective studies with large population are needed to clarify the effect of SP and electroacupuncture.

Abstract Background Muscle soreness after exercise, called delayed-onset muscle soreness (DOMS), may cause significant changes in muscle function and may increase the risk of sports injuries. Therefore, various therapeutic strategies have been studied to help recovery after exercise. Jakyakgamcho-tang (JGT) is a widely prescribed herbal medicine to treat muscle pain and cramps in traditional Eastern medicine. The aim of this study is to evaluate the effect of JGT for reducing pain and improving muscle damage after exercise. Methods This study is a randomized, double-blind, placebo-controlled, crossover design clinical trial. A total of 30 healthy male adults will be recruited. Subjects who voluntarily wish to participate in this study will be hospitalized for 4 days. On the first day, the subjects will perform a standardized treadmill exercise for 1 h to induce DOMS. After the exercise, the subjects will take either JGT or a placebo for 3 days. After a more than 1 week wash-out period, the subjects will repeat the same process with the other drug. Pain intensity, calf circumference, and pain threshold will be measured as outcome measures. Blood tests and blood pressure will be measured as safety assessments. In addition, blood tests for muscle damage and inflammation markers, such as creatine kinase, interleukin-6, and C-reactive protein, will be analyzed. Discussion This will be the first trial to assess the effect of JGT on exercise-induced muscle soreness. Our findings will provide valuable data to determine the clinical effects of JGT on DOMS. Trial registration Clinical Research Information Sevice, KCT0003457. Registered on 29 January 2019.

Abstract Background Gastroesophageal reflux disease (GERD) is a major cause of chronic cough. GERD-induced chronic cough is difficult to diagnose because some patients do not complain of any gastrointestinal (GI) reflux symptoms. Although chronic cough due to GERD is highly prevalent, no effective treatment is currently available, especially for GERD-related cough without GI symptoms. Because the herbal medicines Ojeok-san and Saengmaek-san can effectively treat GERD and cough, we aim to evaluate the efficacy and safety of a combination of these components for relieving chronic cough due to GERD. Methods/design This is a study protocol of a randomized, double-blind, placebo-controlled, single-center pilot trial. After a 1-week run-in period, a total of 30 patients with GERD-induced chronic cough will be randomly allocated to an intervention group (n = 15) or a placebo group (n = 15). Participants will receive 5.76 g of Ojeok-san plus Saengmaek-san or a placebo three times per day for 6 weeks. The primary outcome measures, which are the frequency and severity of cough, will be recorded using a cough diary. The secondary outcome measures will include a cough visual analogue scale, the Leicester Cough Questionnaire (Korean version), the Gastrointestinal Symptom Rating Scale, the Hull Airway Reflux (hypersensitivity) Questionnaire, the Pattern Identification for Chronic Cough Questionnaire, the Pattern Identification for Gastroesophageal Reflux Disease, and safety testing. Adverse events will also be reported. Discussion This will be the first clinical trial to explore the use of herbal medicines for GERD-related chronic cough, including patients without GI reflux symptoms. This study will provide useful evidence regarding the efficacy and safety of Ojeok-san plus Saengmaek-san treatment. In addition, this trial will offer a scientific basis for the combination of herbal medicines. This study will also provide important data for conducting a larger-scale clinical trial on GERD-induced chronic cough. Trial registration This trial has been registered with Clinical Research Information Service (CRIS) of South Korea (http://cris.nih.go.kr; registration number KCT0003115). Registered August 28, 2018.

Abstract Background Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive abilities and memory leading to dementia. Electroacupuncture (EA) is a complementary alternative medicine approach, applying an electrical current to acupuncture points. In clinical and animal studies, EA causes cognitive improvements in AD and vascular dementia. However, EA-induced changes in cognition and microglia-mediated amyloid β (Aβ) degradation have not been determined yet in AD animals. Therefore, this study investigated the EA-induced molecular mechanisms causing cognitive improvement and anti-inflammatory activity in five familial mutation (5XFAD) mice, an animal model of AD. Methods 5XFAD mice were bilaterally treated with EA at the Taegye (KI3) acupoints three times per week for 2 weeks. To evaluate the effects of EA treatment on cognitive functions, novel object recognition and Y-maze tests were performed with non-Tg, 5XFAD (Tg), and EA-treated 5XFAD (Tg + KI3) mice. To examine the molecular mechanisms underlying EA effects, western blots, immunohistochemistry, and micro-positron emission tomography scans were performed. Furthermore, we studied synapse ultrastructures with transmission electron microscopy and used electrophysiology to investigate EA effects on synaptic plasticity in 5XFAD mice. Results EA treatment significantly improved working memory and synaptic plasticity, alleviated neuroinflammation, and reduced ultrastructural degradation of synapses via upregulation of synaptophysin and postsynaptic density-95 protein in 5XFAD mice. Furthermore, microglia-mediated Aβ deposition was reduced after EA treatment and coincided with a reduction in amyloid precursor protein. Conclusions Our findings demonstrate that EA treatment ameliorates cognitive impairment via inhibition of synaptic degeneration and neuroinflammation in a mouse model of AD.

Objectives: Emerging studies found the potential effects of acupuncture for treating chronic pain and mental disorders, namely, depressive and anxiety disorders. Acupuncture is widely used for treating culture-related anger syndrome, Hwa-byung. This pilot trial aimed to investigate the feasibility of a clinical trial testing acupuncture for the psychosomatic symptoms of Hwa-byung.Methods: A total of 26 patients with Hwa-byung planned to be randomly assigned to the acupuncture or sham acupuncture groups. About 10 treatment sessions were applied over 4 weeks. The 100-mm visual analog scale was used to measure the six major Hwa-byung symptoms: stuffiness in the chest, heat sensations, pushing-up in the chest, feeling a mass in the throat, feelings of unfairness, and hard feelings. The criteria for assessing the success of this pilot trial were defined as improvement in three or more of the six Hwa-byung symptoms after treatment, with an effect size >0.2.Results: A total of 15 patients were finally included and randomly assigned to the acupuncture group (n = 7) or the sham acupuncture group (n = 8). After 10 treatment sessions, the Cohen's d effect sizes for acupuncture compared to sham acupuncture were >0.2 for each one of the six major Hwa-byung symptoms, which met our a priori criteria for success. Also, the effect size for the somatic symptoms of “stuffiness in the chest” was 0.81 (95% CI −0.40, 2.20), referring to a large effect size.Conclusions: Our results suggest that acupuncture treatment would be regarded as an acceptable intervention for a full-scale study of psychosomatic symptoms in patients with Hwa-byung.Trial Registration:cris.nih.go.kr, identifier: KCT0001732.

Background: The acupotomy is an acupuncture device recently used to stimulate lumbar vertebrae such as transverse processes (TPs) and facet joints (FJs). However, there are many organs, nerves, and blood vessels, which can lead to side effects if the needle misses the treatment target. Therefore, information regarding appropriate insertion depths, which is currently lacking, could facilitate its safe use. We retrospectively investigated the depth from the skin to the TP and FJ of the lumbar vertebrae, using magnetic resonance imaging (MRI). Methods: This retrospective chart review was conducted at a single medical centre in Korea. From 55,129 patient records, 158 subjects were selected. Perpendicular depth from the skin to the left and right TPs and FJs was measured using T1-weighted sagittal plane MRI. Depth differences between the left and right sides were evaluated using the paired t-test and analysis of covariance (body mass index [BMI] as a covariate). The influence of BMI on depth at each location was evaluated by simple linear regression analysis. Results: The mean age was 43.2 years and mean BMI was 23.6 kg/m2. The depth from skin to the TPs or FJs was unaffected by age, sex, or side. Mean depths (cm) were as follows: (TPs) L1 = 4.5, L2 = 4.9, L3 = 5.3, L4 = 5.7, L5 = 5.9; (FJs) L12 = 3.8, L23 = 4.0, L34 = 4.4, L45 = 4.6, L5S1 = 4.6. Depth was highly correlated with BMI at each location. Conclusion: The depth of TPs and FJs adjusted for BMI can safely and effectively be used for treatment via various invasive interventions, including acupotomy treatment, in the lumbar region.

Background: Danggwijagyaksan (DJS) has been one of the most widely used herbal medicines for gynecological disorders in traditional East Asian medicine. Several clinical studies about DJS have shown improvement in menopausal symptoms. This pilot study aimed to evaluate the efficacy, safety and feasibility of DJS for treating climacteric syndrome with a blood-deficiency-dominant pattern. Methods: This was a randomized, double-blind, placebo-controlled pilot trial. A group of 45-to 60-year-old women with climacteric syndrome were registered for the trial. The participants received treatment over a 4-week period and were then followed for 4 weeks. The primary outcome measure was the mean change in the Menopause Rating Scale (MRS). Secondary outcome measures included the World Health Organization Quality of Life-BREF (WHOQOL-BREF), the Blood-Deficiency Scoring System (BDSS), lean body mass, and serum hormone levels, including follicle-stimulating hormone (FSH) and estradiol (E2) levels. Results: The MRS and BDSS scores decreased significantly in both groups, but the differences between two groups were not significant. The WHOQOL-BREF scores increased in the control group. No statistically meaningful differences in serum hormone levels or lean body mass were observed in both groups. There were no serious adverse events, and the laboratory tests were within the normal range. The recruitment rate, completion rate and medication adherence rate were over 90% in both groups, indicating high feasibility. Conclusions: DJS showed clinical effectiveness in the treatment of climacteric syndrome with a blood-deficiency-dominant pattern. Additionally, DJS was shown to be safe and feasible for a large-scale study to confirm the efficacy of the treatment. Trial registration: Clinical Research Information Service (CRIS, https://cris.nih.go.kr): KCT0002387.

Background: The first treatment option for major depressive disorder (MDD) is antidepressants, however, there is substantial demand for alternative therapies due to its low compliance and remission rates. This study was aimed to explore the effectiveness, safety, and feasibility of electroacupuncture plus moxibustion therapy for MDD. Methods: Thirty adults with MDD were randomly assigned to the treatment group (TG) or control group (CG). The TG was treated with electroacupuncture plus moxibustion, and the CG received sham interventions at non-acupoints for 8 weeks. The primary outcome measure was the intergroup difference of the mean change of total score of the Hamilton rating scale for depression (HRSD) between baseline and week 9. Secondary outcome measures were Beck's depression inventory, insomnia severity index, the state-trait anxiety inventory, the EuroQol-5 dimension index, the measure yourself medical outcome profile version 2, and frontal alpha asymmetry measured by electroencephalography. Adverse events (AEs) were monitored for safety assessment. Results: The primary outcome measure was not significantly different between the two groups (p=0.2641), although the scores of HRSD in both groups improved significantly after treatment. No significant difference was identified between groups in secondary outcome measures. The incidence of AE was not significantly different between the two groups (p=0.1067). Conclusion: A clinical trial using electroacupuncture plus moxibustion for MDD seems feasible. However, further studies with the larger size, adopting ideal controls are warranted to provide a confirmative conclusion to the efficacy and safety of electroacupuncture plus moxibustion for MDD.

Long-term sequelae refer to persistent symptoms or signs for >6 months after SARS-CoV-2 infection. The most common symptoms of sequelae are fatigue and neuropsychiatric symptoms (concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression). However, approved treatments have not been fully established. Herbal medicines are administered for 12 weeks to patients who continuously complain of fatigue or cognitive dysfunction for >4 weeks that only occurred after COVID-19 diagnoses. Based on the Korean Medicine syndrome differentiation diagnosis, patients with fatigue will be administered Bojungikgi-tang or Kyungok-go, whereas those with cognitive dysfunction will be administered Cheonwangbosim-dan. Results could support evidence that herbal medicines may mitigate fatigue and cognitive dysfunction caused by COVID-19. Furthermore, by investigating the effects of herbal medicines on changes in metabolite and immune response due to COVID-19, which may be responsible for sequelae, the potential of herbal medicines as one of the therapeutic interventions for post-acute sequelae of SARS-CoV-2 infection can be evaluated. Therefore, the effects of herbal medicine on fatigue and cognitive dysfunction sequelae due to COVID-19 will be elucidated in this study to provide an insight into the preparation of medical management for the post-acute sequelae of SARS-CoV-2 infection.

This study evaluated the efficacy and safety of Banha-sasim-tang (BST) in patients with functional dyspepsia (FD). BST (Banxia-xiexin-tang in traditional Chinese medicine and Hange-shashin-to in Kampo medicine) is traditionally prescribed for the treatment of dyspepsia with epigastric stiffness and gastric fullness in China, Japan, and Korea. Patients with FD were randomly administered an oral dose (10 g) of BST syrup or placebo, twice a day for 4 weeks. The primary outcome was the symptom checklist part of the Nepean dyspepsia index (NDI). The secondary outcomes were the quality of life (QoL) part of the NDI, functional dyspepsia-related QoL (FD-QoL), and visual analog scale (VAS). A total of 60 patients with FD were screened, and 50 were randomized into BST group (n = 25) and placebo group (n = 25). Two patients in the placebo group withdrew before the start of the treatment. Administration of BST syrup resulted in improvement in the symptom-related NDI score in the BST group compared with that in the control group; however, the difference was not significant. BST syrup significantly improved “fullness after eating” index of NDI at follow-up time point (2.88 ± 2.65 vs 4.78 ± 2.69, p = 0.0081). In the total score of the QoL section of the NDI and FD-QoL scales, there was no significant improvement in the BST group compared to that in the placebo group. With regard to improvement in overall FD symptoms, the VAS scale showed improvement in both groups, but the difference was not significant. Interestingly, follow-up investigation showed a significantly beneficial effect of BST on FD symptoms, when compared to placebo. Significant improvement observed in VAS score (39.60 ± 22.29 vs 52.17 ± 20.55, p = 0.048). This indicated that the effect of BST lasted even after the completion of the medication regimen. Overall, our data suggest that while BST showed no significant improvement in the symptom-related NDI score and the QoL related scores in NDI and FD-QoL after 4 weeks of treatment, it effectively improved the VAS score and fullness after eating-related symptoms in the follow-up visit.Clinical Trial Registration:https://cris.nih.go.kr; Identifier KCT 0002013

Background: Cognitive impairment is an age-dependent chronic disorder that exponentially worsens with age; however, its treatment is mostly symptomatic. Moxibustion is widely accepted in East Asia as a treatment for cognitive impairment. This systematic review aimed to verify the efficacy and underlying mechanism of moxibustion in treating cognitive impairment. Methods: Sixteen trials involving 324 animals obtained from MEDLINE (PubMed), EMBASE, the Cochrane library, the Chinese National Knowledge Infrastructure, Wan-Fang, Cqvip, the Korean Studies Information Service System, and the Oriental Medicine Advanced Searching Integrated System met the inclusion criteria. We extracted the results of behavioral tests and immunohistochemical biomarkers from the included articles and evaluated the risk of bias and reporting quality. Results: The moxibustion group showed significantly decreased escape latency, increased crossing times, and prolonged dwelling times in the Morris water maze test. There was a significantly enhanced latency period and reduced error time in the step-down test and nerve behavior score. The effects of moxibustion were found to be mediated by suppression of oxidative stress and apoptosis, modulation of inflammation and Aβ genesis activation of vascular endothelial growth factor, and adjustment of metabolites in the tricarboxylic acid cycle and fatty acid metabolism. Conclusion: Our results demonstrated the therapeutic efficacy of moxibustion on cognitive impairment and suggested the putative mechanism. However, considering the small number of included studies, high bias risk, low reporting quality, and the limitations of animal experimentation, our results need to be confirmed by more detailed studies.

In South Korea, car insurance that includes medical coverage of traditional Korean medicine (TKM) has increased exponentially. Clinical practice guidelines (CPG) for traffic injuries were established in 2016. We aimed to revise and update de novo CPG and distribute the adapted CPG to TKM practitioners and patients. Clinical key questions from previous CPG were identified and updated regarding the grade of recommendation and level of evidence using additional evidence from the literature obtained through a systematic search and the use of the Grading of Recommendations Assessment, Development, and Evaluation methodology. The dissemination and implementation of the updated CPG were conducted at the CPG Center of Korean Medicine. Ultimately, 25 recommendations based on 13 clinical key questions were developed: 2 for diagnosis, 22 for TKM treatments, and 1 for prognosis. After recognition by professional societies and certification by the CPG Center of Korean Medicine, leaflets, card news, and infographics for TKM doctors in South Korea were produced and distributed. These are the only TKM CPG for patients who have experienced traffic injuries. They are expected to contribute to standardized and evidence-based treatment using TKM and similar interventions. Moreover, disseminating the adapted CPG will promote treatment reliability and strengthen insurance coverage.

Background: Dry eye syndrome is the most common complication of refractive surgery. Acupuncture is widely used for the treatment of ophthalmologic diseases, but to date, few have explored the effects of acupuncture for the treatment of this condition following refractive surgery. The objective of this study is to assess the feasibility of a study design for evaluating the effectiveness of acupuncture treatment along with usual care compared with usual care only for dry eye syndrome after refractive surgery. Methods: A total of 18 patients with dry eye syndrome occurring after refractive surgery participated in this study. For 4 weeks, the acupuncture plus usual care and usual care only groups received treatment three times a week. A series of assessments, namely the ocular surface disease index (OSDI), visual analog scale for ocular discomfort, quality of life, tear film break-up time, Schirmer 1 test, and fluorescein-stained corneal-surface photography, along with other general assessments were carried out. Results: Although preliminary, changes in OSDI from the baseline values were significantly different between the two groups at week 5 (p = 0.0003). There was a significant difference in the trends of OSDI changes between the acupuncture plus usual care and the usual care only groups (p = 0.0039). No serious adverse events were reported during the study. Conclusion: Four weeks of acupuncture treatment in addition to usual care is a feasible treatment for dry eye syndrome after refractive surgery. A full-scale randomized controlled trial is needed to confirm the clinical effectiveness of acupuncture.

Abstract 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.

Abstract Background Low back pain (LBP) is common, with a lifetime prevalence of 80%, and as such it places substantial social and economic burden on individuals and society. Chuna manual therapy (CMT) combines aspects of physiology, biodynamics of spine and joint motion, and basic theory of movement dynamics. This study aimed to test the comparative effectiveness and safety of CMT for non-acute LBP. Methods A three-arm, multicenter, pragmatic, randomized controlled pilot trial was conducted from 28 March 2016 to 19 September 2016, at four medical institutions. A total of 60 patients were randomly allocated to the CMT group (n = 20), usual care (UC) group (n = 20), or combined treatment (CMT + UC) group (n = 20), and received the relevant treatments for 6 weeks. The primary outcome was a numeric rating scale (NRS) representation of LBP intensity, while secondary outcomes included NRS of leg pain, Oswestry disability index (ODI), Patient Global Impression of Change (PGIC), the EuroQol-5 dimensions (EQ-5D), lumbar range of motion, and safety. Results A total of 60 patients were included in the intention-to-treat analysis and 55 patients (CMT, 18; UC, 18; CMT + UC, 19) were included in the per-protocol analysis (drop-out rate 5.3%). Over the treatment period there were significant differences in the NRS score for LBP (CMT mean − 3.28 (95% CI − 4.08, − 2.47); UC − 1.95 (− 2.82, − 1.08); CMT + UC − 1.75 (− 2.70, − 0.80), P

Abstract Background This study aims to assess the efficacy and safety of geonchildan, a Korean traditional herbal medicine, for patients with active rheumatoid arthritis (RA) and evaluate the feasibility of a large-scale confirmatory clinical trial. Methods/design This is a randomized, double-blind, placebo-controlled, parallel two-arm pilot trial in Seoul, Korea. Altogether, 30 patients diagnosed with RA for at least 3 months and with a Disease Activity Score for 28 joints (DAS28) ≥ 3.2 will be enrolled. Participants are randomly assigned to one of two groups, the experimental group or the placebo group, in a 1:1 ratio and will make four scheduled visits. The participants will be administered geonchildan or a placebo three times per day for 12 weeks. The change in DAS28 will be examined as the primary efficacy outcome. The secondary efficacy outcomes include the proportion of patients achieving ACR20, ACR50, ACR70, and EULAR responses; the DAS28 sub-items; the consumption of medication; Korean Health Assessment Questionnaire scores; inflammatory parameters; and the Korean medical diagnostic pattern indicator. Adverse events and laboratory test results will be recorded to evaluate safety. The process, resources used, and management of the study will also be assessed to determine the feasibility of a large-scale trial. Discussion This is the first clinical trial to explore the efficacy and safety of geonchildan in patients with active RA. If the superiority of geonchildan versus the placebo is demonstrated and the study design is feasible, this study could form the foundation for a large-scale clinical trial. The results will be published in a peer-reviewed journal. Trial registration Clinical Research Information Service, KCT0001943. Registered on 14 June 2016.

Background: This study aims to review the current quantity and quality of case reports and case series published by clinical doctors who worked in local Korean medicine clinics. Methods: Seven electronic databases, one in English and six in Korean, were searched for case studies authored by clinically-based Korean Medicine doctors (KMDs) and published in academic journals between January 2000 and December 2018. The following data were extracted: the number of cases per article, authorship order, types of academic journals, the number of articles published in the domestic or international academic journals by publication year, citation counts, and classification of diseases. We assessed the quality of the reports based on 28 items from the CAse REport (CARE) checklist. Results: A total of 266 case reports or case series met the inclusion criteria. There were 125 articles (47.0%) in which all authors consist of who worked in Korean medicine clinics. The overall increase in the number of published articles by year showed a sharp increase after 2010. Articles were focused primarily on Korean medicine therapeutic and diagnostic approaches. The most commonly reported cases were diseases of the skin (346 or 40.9%). Overall, the quality of the reports was acceptable (75.3%) but several items such as diagnostic challenges, patient perspective, informed consent, intervention adherence and tolerability, and adverse events were substantially underreported. Conclusions: To improve disease diagnosis and treatment, KMDs in clinical practice should be encouraged to report and publish case studies, using the CARE checklist to ensure quality.

Studies have reported that mild adverse events (AEs) are common after manual therapy and that there is a risk of serious injury. We aimed to assess the safety of Chuna manipulation therapy (CMT), a traditional manual Korean therapy, by analysing AEs in patients who underwent this treatment. Patients who received at least one session of CMT between December 2009 and March 2019 at 14 Korean medicine hospitals were included. Electronic patient charts and internal audit data obtained from situation report logs were retrospectively analysed. All data were reviewed by two researchers. The inter-rater agreement was assessed using the Cohen’s kappa coefficient, and reliability analysis among hospitals was assessed using Cronbach’s Alpha coefficient. In total, 2,682,258 CMT procedures were performed in 289,953 patients during the study period. There were 50 AEs, including worsened pain (n = 29), rib fracture (n = 11), falls during treatment (n = 6), chest pain (n = 2), dizziness (n = 1), and unpleasant feeling (n = 1). The incidence of mild to moderate AEs was 1.83 (95% confidence interval [CI] 1.36–2.39) per 100,000 treatment sessions, and that of severe AEs was 0.04 (95% CI 0.00–0.16) per 100,000 treatment sessions. Thus, AEs of any level of severity were very rare after CMT. Moreover, there were no instances of carotid artery dissection or spinal cord injury, which are the most severe AEs associated with manual therapy in other countries.

Cancer patients have a 2 times higher prevalence of insomnia than healthy populations and cancer-related insomnia has received minimal attention while insomnia can aggravate the rehabilitation of cancer patients. Cheonwangbosimdan is a Korean herbal medicine generally used to relieve sleep deprivation, however, few studies presented the effects of Cheonwangbosimdan on cancer-related insomnia. The purpose of study is to examine the feasibility of Cheonwangbosimdan treatments for cancer patients. Twenty-two participants were allocated into a Cheonwangbosimdan or cognitive-behavioral therapy for insomnia (CBT-I) control group by equal number. The intervention group took Cheonwangbosimdan liquid once in a day and attend visits once a week for 4 weeks. The CBT-I group underwent individualized behavioral therapy 4 times in 4 weeks. The primary outcome is changes in the Insomnia Severity Index (ISI) from baseline to the end of the trial. Responses to the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Zung Self-Rating Anxiety Scale (SAS), Brief Fatigue Inventory (BFI), Euroqol-5 Dimensions-5 Levels (EQ-5D-5L), and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) were secondary outcomes used to evaluate the quality of sleep. Outcomes were measured at a follow-up visit (visit 5) in the fifth week of the trial. There is no difference between 2 groups, but both groups showed tendency to alleviate cancer insomnia symptoms. SAS-K showed significant difference between the 2 groups (P < .001), as treatment group score was highly lowered than control group score. The study can contribute to more attentive care for insomnia in cancer patients.

PURPOSE:Low back pain (LBP) is a common ailment in most developed countries. Because most cases of LBP are known as 'non-specific', it has been challenging to develop experimental pain models of LBP which reproduce patients' clinical pain. In addition, previous models have limited applicability in a steady-pain-state neuroimaging environment. Thus, this study aims to devise a low back pain model with a simple methodology to induce experimental LBP, which has similar pain properties to patients' clinical pain, and to apply the model in a steady-pain-state neuroimaging study. METHODS:Our low back extension (LBE) pain model was tested on 217 LBP patients outside the magnetic resonance imaging (MRI) scanner to determine the reproducibility of endogenous pain and the similarity to their own clinical pain (STUDY1), and applied in a steady-pain-state functional MRI study (47 LBP patients and 23 healthy controls) to determine its applicability (induced head motions and brain functional connectivity changes; STUDY2). RESULTS:By the LBE pain model, 68.2% of the LBP patients reported increased LBP with high similarity of sensations to their own clinical pain (STUDY1), and the head motions were statistically similar to and correlated with those in resting state (STUDY2). Furthermore, the LBE model altered brain functional connectivity by decreasing the default-mode and the sensorimotor networks, and increasing the salience network, which was significantly associated with the intensity of the induced pain. Conversely, the healthy controls showed increased somatosensory network (but not of the cognitive pain processing). CONCLUSION:Our investigations suggest that our LBE pain model, which increased LBP with high similarity to the LBP patients' own pain sensation and induced patient-specific brain responses with acceptable head motion, could be applied to neuroimaging studies investigating brain responses to different levels of endogenous LBP.

The underlying mechanism of pain reduction by acupuncture is still unclear, because acupuncture treatment involves multidimensional factors. In this study, we investigated the differential influence of acupuncture components on brain functional connectivity and on pain reduction. We used a specific form of sham acupuncture (phantom acupuncture; PHNT), which only has a needling-credibility (a belief that they were treated with real acupuncture needles), while real acupuncture (REAL) has a somatosensory needling stimulation, as well as a needling-credibility. Forty-three patients with low back pain were randomized into the REAL group (n = 25) and the PHNT group (n = 18). They underwent two pain steady-state fMRI runs implemented by a low back extension (LBE) pain model (lifting the low back using air-cuff inflation) before and after REAL or PHNT stimulation. Subjective pain ratings, perceived throughout the LBE runs due to the posture, were reported (LBEpain). The regions of interest (ROI) were (1) the main nodes of the default mode network (DMN) – the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), (2) the main nodes of the salience network (SN) – the anterior/posterior insular cortices (a/pINS), and (3) the low back-specific region of sensorimotor network (SMN), S1back. Significant reductions in LBEpain were observed in both groups (REAL = −1.02 ± 1.53, PHNT = −1.26 ± 2.20). In REAL group, decreased LBEpain was positively correlated with decreased functional connectivity between the mPFC and pINS (r = 0.58, P < 0.05). Reduced LBEpain in PHNT was negatively correlated with increased PCC–aINS connectivity (r = −0.48, P < 0.05) and tended toward positive correlation with decreased S1back–pINS connectivity (r = 0.44, P = 0.07). Our findings might suggest different brain mechanisms of observed pain reduction; REAL seems to involve detachment of the self from the sensory aspect of pain, while PHNT does to shift attention to self and disengages physical pain processing hubs. This exploratory study proposes a sham methodology to dissociate the influence of different acupuncture components in acupuncture research. Further studies need to be followed with more elaborated hypothesis, study design, and analysis considering various cognitive/affective factors for better understanding of brain mechanisms of pain reduction regarding the different acupuncture aspects.

Abstract Background Although pain after back surgery is known to be difficult to control, various treatment options are available to patients and physicians. A protocol for a confirmatory randomized controlled trial (RCT) on pain and function after back surgery was designed based on the results of a pilot trial. The aim of this study is to compare the effectiveness and safety of electroacupuncture (EA) with usual care (UC) versus UC alone on pain control and functional improvement after back surgery. Methods/design This study is a multi-center, randomized, assessor-blinded trial with an active control conducted in conjunction with a cost-effectiveness analysis and qualitative research. Participants with non-acute low back pain with or without leg pain after back surgery who have a Visual Analogue Scale (VAS) pain intensity score ≥ 50 mm will be randomly assigned to either the EA with UC group (n = 54) or the UC group (n = 54). Following randomization, participants in both groups will receive the same UC treatment twice a week for a four-week treatment period. Participants assigned to the EA with UC group will additionally receive EA twice a week for the same four-week period. The primary outcome measure will be assessed using a VAS pain intensity score for low back pain. The secondary outcomes will include the Oswestry Disability Index, EuroQol 5-Dimension score, and drug intake. The primary and secondary outcomes will be measured at one, four, and eight weeks post randomization. Discussion The results of this study will provide evidence of the effectiveness and cost-effectiveness of EA in managing postoperative pain following back surgery. In addition, the qualitative research results will help improve the quality of integrative medical interventions. Trial registration Clinical Research Information Service (CRIS), Republic of Korea, KCT0001939 . Registered on 8 June 2016.

Abstract Background This study aims to explore the safety, efficacy, and feasibility of Danggwijagyaksan (DJS) for alleviating climacteric syndrome in peri- and postmenopausal women with a blood-deficiency dominant pattern. Methods/design This is a randomized, double-blind, placebo-controlled pilot clinical trial. A total of 34 women with climacteric syndrome who have signed informed consent forms will be registered in this study. Placebo or DJS will be randomly assigned to the participants in an equal proportion. The participants will visit the clinical trial center every 2 weeks and receive placebo or DJS granules. The treatment period is 4 weeks and the administration frequency is three times daily. Data will be collected from the participants at baseline, at week 5, and at week 9 after random allocation. The primary outcome measure will be the mean change in the Menopause Rating Scale from baseline to week 5. Secondary outcome measures will include the World Health Organization Quality of Life-BREF (WHOQOL-BREF) score, the Blood Deficiency Scoring System score, lean body mass, and blood tests, including serum follicle-stimulating hormone and estradiol concentration. To assess the safety of DJS, a laboratory test will be conducted before and after treatment and the participants will be asked about any occurrence of adverse events every visit. The recruitment rate, completion rate, and medication adherence will also be calculated, to assess feasibility. Discussion The findings of this study will provide the basis for a full-scale randomized controlled trial to confirm the safety and efficacy of DJS for the treatment of climacteric syndrome in peri- and postmenopausal women. Trial registration Clinical Research Information Service (CRIS), Republic of Korea, KCT0002387 . Registered on 25 July 2017.

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Abstract Background Functional dyspepsia (FD) refers to the presence of one or more gastrointestinal symptoms including postprandial fullness, epigastric pain, burning, and early satiety without an organic explanation for chronic symptoms. FD causes considerable discomfort in patients and affects their everyday activity and productivity. Because most conventional treatments have limited efficacy, numerous patients seek alternatives such as herbal medicines. In this proposed study, we will conduct a clinical trial of an herbal drug, Banha-sasim-tang (BST). Furthermore, participants will be limited to those classified as having an excess pattern by using an instrument of pattern identification for FD to determine the efficacy of BST in a specific subset of patients. Methods This randomized, blinded, parallel-group clinical trial of BST versus placebo will consist of 4 weeks of oral administration of BST or placebo and a 4-week follow-up period. The Korean version of the symptom-based questionnaire of the Nepean Dyspepsia Index (NDI-K) will be used as the primary outcome measure. Secondary outcome measures will include the quality-of-life (QoL) evaluation from the NDI-K, the FD-related QoL (FD-QoL) scale, assessment of gastric myoelectrical dysrhythmias (GMA), and a Visual Analog Scale (VAS) analysis. Discussion The results of this trial are expected to provide relevant evidence demonstrating that BST can be used as an effective treatment in a specific subset of FD subjects. Trial registration KCT 0002013 . Registered at Clinical Research Information Service in the Republic of Korea on 18 August 2016.

Although Electroacupuncture (EA) has been reported to be potentially effective for cognitive disorders, there is limited information about which domains of cognitive function can be improved by EA treatment. Sixty patients with MCI were randomly assigned (1:1:1) to groups to receive 24 sessions over 12 weeks of EA, sham EA, or usual care. In the EA group, electric stimulation was applied at bilateral PC6 and HT7. Various cognitive tests included in the Seoul Neuropsychological Screening Battery II (SNSB-II) were performed at baseline and post-treatment to explore effects of EA on five cognitive domains: attention, language, visuospatial function, memory, and frontal/executive function. Among 60 randomized participants (63.7 ± 7.1 years, 89.7% females), 45 (75%) completed the study. Of the five cognitive function domains of SNSB-II, the T score of visuospatial function showed a tendency to be higher in the EA group than in the usual care group at post-treatment assessment (mean difference: 10.16 (95% CI, 1.14, 19.18), Cohen’s d = 0.72, p = 0.0283). According to the results of this pilot study, the estimated effect size of EA on the visuospatial function of MCI patients compared to usual care was medium. Large-scale clinical trials are needed to confirm effects of EA on cognitive functions.

This study aimed to investigate the feasibility of a combined treatment of bee venom acupuncture (BVA) and non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of non-specific chronic neck pain (NCNP). Patients with NCNP for ≥3 months were randomly allocated to a BVA, NSAIDs, or combined group (1:1:1), receiving 6 sessions of BVA, loxoprofen (180 mg daily), or a combination, respectively, for 3 weeks. Recruitment, adherence, and completion rates were calculated to assess feasibility. Bothersomeness, pain, disability, quality of life, depressive status, treatment credibility, and adverse events were assessed. In total, 60 participants were enrolled, and 54 completed the trial. Recruitment, adherence, and completion rates were 100%, 95%, and 90%, respectively. Bothersomeness, pain, disability, and depressive symptoms significantly improved in all groups after treatment (p < 0.05). The combined group showed continuous improvement during the follow-up period (p < 0.05). Quality of life was significantly improved (p < 0.05), and treatment credibility was maintained in the BVA and combined groups. No serious adverse events were reported. Combined treatment of BVA and NSAIDs are feasible for the treatment of NCNP, showing high persistence of the effect, credibility, and safety. Additional trials with longer follow-up are needed to confirm this effect.

Cheonwangbosim-dan (CWBSD) is a traditional Korean herb formula that has been widely prescribed for insomnia patients with a heart-yin deficiency (HYD) pattern. Several studies have reported that heart function and insomnia are interrelated, and few have explored associations between insomnia, oral microbiota, and tongue diagnosis. This study aimed to evaluate the effects of CWBSD on primary insomnia, tongue diagnosis, and oral microbiota. At baseline, 56 patients with primary insomnia were assigned to two groups, a HYD group and a non-HYD (NHYD) group and they took CWBSD for 6 weeks. During the study, Pittsburgh Sleep Quality Indices (PSQIs) and Insomnia Severity Indices (ISIs) decreased significantly in both groups. However, the PSQI reduction observed in the HYD group was greater than in the NHYD group and sleep times increased only in the HYD group. As sleep quality improved, the amount of tongue coating increased at the posterior tongue, where heart function appears. At baseline, the HYD and NHYD group had a specific oral microbiota (Veillonella at genus level), but no significant change was observed after taking CWBSD. Additionally, subjects were divided into two oral microbiota types (“orotypes”). The genera Prevotella, Veillonella, or Neisseria were abundant in each orotype. The reduction in PSQI in orotype 1 during the 6-week treatment period was greater than in orotype 2. In conclusion, this study shows that CWBSD could be used to treat primary insomnia in patients with a HYD pattern as determined using tongue diagnosis and oral microbiota distributional patterns.

Abstract Background Radial pressure pulse wave (RPPW) examination has been a key diagnostic component of traditional Chinese medicine. The objective of this study was to investigate the changes in RPPW along with various hemodynamic variables after acupuncture stimulation and to examine the validity of pulse diagnosis as a modern diagnostic tool. Methods We conducted acupuncture stimulation at both ST36 acupuncture points in 25 healthy volunteers. We simultaneously assessed the RPPW by pulse tonometry; heart rate variability (HRV) by electrocardiogram; photoplethysmogram (PPG) signals, respiration rate, peripheral blood flow velocity and arterial depth by ultrasonography; and cardiac output by impedance cardiography, before, during and after a session of acupuncture stimulation. Results We observed consistent patterns of increased spectral energy at low frequency (

Introduction: This study aims to investigate the effects of acupuncture stimulation on the radial artery’s pressure pulse wave, along with various hemodynamic parameters, and to explore the possible underlying mechanism of pulse diagnosis in healthy participants in their twenties. Methods and analysis: This study is a prospective, si

Acupuncture therapy (AT) is a non-pharmacological method of treatment that has been applied to various neurological diseases. However, studies on its longitudinal effect on the neural mechanisms of patients with mild cognitive impairment (MCI) for treatment purposes are still lacking in the literature. In this clinical study, we assess the longitudinal effects of ATs on MCI patients using two methods: (i) Montreal Cognitive Assessment test (MoCA-K, Korean version), and (ii) the hemodynamic response (HR) analyses using functional near-infrared spectroscopy (fNIRS). fNIRS signals of a working memory (WM) task were acquired from the prefrontal cortex. Twelve elderly MCI patients and 12 healthy people were recruited as target and healthy control (HC) groups, respectively. Each group went through an fNIRS scanning procedure three times: The initial data were obtained without any ATs, and subsequently a total of 24 AT sessions were conducted for MCI patients (i.e., MCI-0: the data prior to ATs, MCI-1: after 12 sessions of ATs for 6 weeks, MCI-2: another 12 sessions of ATs for 6 weeks). The mean HR responses of all MCI-0–2 cases were lower than those of HCs. To compare the effects of AT on MCI patients, MoCA-K results, temporal HR data, and spatial activation patterns (i.e., t-maps) were examined. In addition, analyses of functional connectivity (FC) and graph theory upon WM tasks were conducted. With ATs, (i) the averaged MoCA-K test scores were improved (MCI-1, p = 0.002; MCI-2, p = 2.9e–4); (ii) the mean HR response of WM tasks was increased (p < 0.001); and (iii) the t-maps of MCI-1 and MCI-2 were enhanced. Furthermore, an increased FC in the prefrontal cortex in both MCI-1/MCI-2 cases in comparison to MCI-0 was obtained (p < 0.01), and an increasing trend in the graph theory parameters was observed. All these findings reveal that ATs have a positive impact on improving the cognitive function of MCI patients. In conclusion, ATs can be used as a therapeutic tool for MCI patients as a non-pharmacological method (Clinical trial registration number: KCT 0002451 https://cris.nih.go.kr/cris/en/).

Objective(s): MicroRNAs (miRNAs) are small non-coding RNAs that function in all biological processes. Recent findings suggest that exosomes, which are small vesicles abundantly secreted by various cell types, can transport miRNAs to target cells. Here, we elucidated the effect of miRNA-loaded exosomes on lipopolysaccharide (LPS)-induced inflammation in H9c2 cardiomyocytes.Materials and Methods: Exosomes were isolated from mesenchymal stem cells (MSC) and loaded with miR-412-5p. Additionally, the effect of the miR-412-5p-loaded exosomes on LPS-induced inflammation in H9c2 cardiomyocytes was evaluated by assessing the levels of nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2). The expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inflammatory cytokines, and mitogen-activated protein kinase (MAPK) signaling factors was evaluated using reverse transcription-quantitative PCR and western blotting.Results: miR-412-5p-loaded exosomes inhibited LPS-induced secretion of inflammatory mediators (NO, PGE2, and ROS), pro-inflammatory cytokines (IL-1β and IL-6), and COX-2 and iNOS expression. Additionally, miR-412-5p-loaded exosomes significantly decreased the expression of MAPK signaling molecules, including p-extracellular signal-regulated kinase (ERK), p-p38, and p-Jun kinase (JNK), in H9c2 cardiomyocytes.Conclusion: These findings showed that miR-412-5p-loaded exosomes ameliorated LPS-induced inflammation in H9c2 cardiomyocytes by inhibiting COX-2 and iNOS expression, inflammatory mediators, and pro-inflammatory cytokines via the MAPK pathway. The findings indicate that miR-412-5p-loaded exosomes may be effective for the prevention of myocardial injury.

Current evidence on the effectiveness and safety of Chuna manipulative therapy (CMT) for managing non-acute lower back pain (LBP) is insufficient. We investigated the comparative effectiveness and safety of CMT, a Korean style of manipulation, plus usual care (UC) compared to UC alone for non-acute LBP. We conducted a parallel, two-armed, multi-centered, assessor blinded, pragmatic, randomized controlled trial at four major Korean medical hospitals. Overall, 194 patients were randomly allocated to either CMT plus UC (n = 97) or UC alone (n = 97), for six weeks of treatment and six months follow-up. The primary outcome was measured using the numerical rating scale (NRS) of LBP intensity at 7 weeks. Secondary outcomes included NRS of leg pain, Oswestry Disability Index (ODI) for functional disability, patient global impression of change (PGIC) scale, and safety. A total of 194 patients were included in the intention-to-treat analysis, and 174 patients provided complete data for the primary outcome. At 7 weeks, clinically significant differences between groups were observed in the NRS of LBP (CMT + UC: −3.02 ± 1.72, UC: −1.36 ± 1.75, p < 0.001), ODI scores (CMT + UC: −5.65 ± 4.29, UC: −3.72 ± 4.63, p = 0.003), NRS of leg pain (CMT + UC: −2.00 ± 2.33, UC: −0.44 ± 1.86, p < 0.0001), and PGIC (CMT + UC: −0.28 ± 0.85, UC: 0.01 ± 0.66, p = 0.0119). Mild to moderate safety concerns were reported in 21 subjects. CMT plus UC showed higher effectiveness compared to UC alone in patients with non-acute LBP in reducing LBP and leg pain and in improving function with good safety results using a powered sample size and including mid-term follow-up.

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).

INTRODUCTION:Low back pain (LBP) is a globally prevalent disorder with high social significance. Invasive surgical procedures are increasingly being used to treat LBP despite a lack of solid evidence supporting their long-term benefits. This nationwide retrospective cohort study investigated the association between acupuncture treatment and lumbar surgery rate in patients with LBP. METHODS:Using the National Health Insurance Service Sample Cohort Database for 2002-2013, we identified newly diagnosed LBP patients in Korea between 2004 and 2010 and divided them into an acupuncture group and control group according to whether or not they received acupuncture. Propensity scores based on age, sex, income, and Charlson Comorbidity Index were matched between the two study groups. The lumbar surgery rate in the two years following the first visit (control group) or the first acupuncture session (acupuncture group) was calculated. In addition to the overall analysis, stratified analyses were also conducted in different age, sex, and income strata. Sensitivity analyses were further performed using varying definitions of acupuncture treatment. RESULTS:After matching, 130,089 subjects were included in each study group. The lumbar surgery rate was significantly lower in the acupuncture group than in the control group (hazard ratio [HR] 0.633, 95% confidence interval [CI] 0.576-0.696). Decrease in HR was consistently observed in the acupuncture group for all age strata, except for patients in their 20s (HR 1.031, 95% CI 0.804-1.323). HR for lumbar surgery tended to be further reduced in the older age groups upon acupuncture treatment, with no apparent sex-related differences. Lowered HR in the acupuncture group was continuously observed across all income groups; the higher income group showed a tendency of greater decrease. Sensitivity analyses showed that the number of acupuncture sessions had no major impact on the likelihood of lumbar surgery, but also that more intensive acupuncture treatment was associated with further reduction in lumbar surgery rates. CONCLUSION:The present results found that administration of acupuncture treatment is associated with lower lumbar surgery rates for LBP patients in Korea. Prospective studies are warranted in the future to further investigate the effect of acupuncture treatment on lumbar surgery incidence.

With increase of spine surgeries, failed back surgery syndrome (FBSS) prevalence is also rising. While complementary and alternative medicine (CAM) is commonly used for low back pain (LBP), there are no studies reporting use of integrative Korean medicine in FBSS patients.Patients with pain continuing after back surgery or recurring within 1 year and visual analogue scale (VAS) of LBP or leg pain of ≥6 (total n = 120) were recruited at 2 hospital sites from November 2011 to September 2014. Weekly sessions of integrative Korean medicine treatment were conducted for 16 weeks (herbal medicine, acupuncture/electroacupuncture, pharmacopuncture/bee venom pharmacopuncture, and Chuna manual therapy) with additional follow-ups at 24 weeks and 1 year. Outcome measures included VAS of LBP and leg pain (primary outcome), Oswestry Disability Index (ODI), Short-Form 36 (SF-36), medical use, and patient global impression of change (PGIC).VAS of LBP and leg pain improved at 6 months (LBP from 6.1±2.0 at baseline to 2.9±2.3; and leg pain from 5.4±2.6 to 2.4±2.5, respectively). Eighty patients (66.7%) showed improvement of 50% or more in main pain of LBP or leg pain from baseline. Disability and quality of life also improved at 6 months (ODI from 41.3±12.3 at baseline to 23.6±13.6; and SF-36 from 42.8±14.5 to 62.7±16.8). At 1 year follow-up, conventional medical management use decreased, improvement in pain and disability was maintained, and 79.2% reported improvement of PGIC.Despite limitations as an observational study, integrative Korean medicine treatment showed positive results in pain, function, and quality of life of FBSS patients.

Bee venom acupuncture (BVA) is an effective treatment for chronic low back pain (CLBP) through the pharmacological effects of bee venom and the simultaneous stimulation of acupoints. However, evidence of its efficacy and safety in humans remains unclear. Using a double-blind, randomized study, 54 patients with non-specific CLBP were assigned to the BVA and sham groups. All participants underwent six sessions of real or sham BVA for 3 weeks, in addition to administration of 180 mg of loxonin per day. The primary outcome, that is, “bothersomeness” derived from back pain, was assessed using the visual analog scale. Secondary outcomes included pain intensity, dysfunction related to back pain (Oswestry Disability Index), quality of life (EuroQol 5-Dimension), and depressive mood (Beck’s depression inventory). Outcomes were evaluated every week during the treatment period and followed up at weeks 4, 8, and 12. After 3 weeks of the treatment, significant improvements were observed in the bothersomeness, pain intensity, and functional status in the BVA group compared with the sham group. Although minimal adverse events were observed in both groups, subsequent recovery was achieved without treatment. Consequently, our results suggest that it can be used along with conventional pharmacological therapies for the treatment of CLBP.