Coptisine induces autophagic cell death through down-regulation of PI3K/Akt/mTOR signaling pathway and up-regulation of ROS-mediated mitochondrial dysfunction in hepatocellular carcinoma Hep3B cells.

Coptisine is isoquinoline alkaloid derived from Coptidis Rhizoma and is known to have potential anti-cancer activity toward various carcinomas. Targeting autophagy is one of the main approaches for cancer therapy, but whether the anti-cancer efficacy of coptisine involves autophagy is still unclear. Therefore, this study investigated the effect of coptisine on autophagy in hepatocellular carcinoma (HCC) Hep3B cells, and identified the underlying mechanism. Our results showed that coptisine increased cytotoxicity and autophagic vacuoles in a concentration-dependent manner. Furthermore, the expressions of light chain 3 (LC3)-I/II, Beclin-1 and autophagy genes were markedly increased by coptisine, while the expression of p62 decreased. In addition, we found that pretreatment with bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, markedly reduced coptisine-mediated autophagic cell death, but 3-methyladenine, an inhibitor for autophagosome formation did not. Moreover, our results showed that although coptisine up-regulated AMP-activated protein kinase (AMPK) that partially induced LC3-I/II, coptisine-mediated AMPK signaling did not directly regulate autophagic cell death. Additionally, we found that coptisine suppressed the phosphorylation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), and this effect was notably enhanced by PI3K inhibitor LY294002. Meanwhile, coptisine significantly increased both the production of mitochondrial reactive oxygen species (ROS) and the recruitment of mitophagy-regulated proteins to mitochondria. Furthermore, N-acetylcysteine, a potential ROS scavenger, substantially suppressed the expression of mitophagy-regulated proteins and LC3 puncta by coptisine. Overall, our results demonstrate that coptisine-mediated autophagic cell death was regulated by PI3K/Akt/mTOR signaling and mitochondrial ROS production associated with mitochondrial dysfunction. Taken together, these findings suggest that coptisine exerts its anti-cancer effects through induction of autophagy in HCC Hep3B cells.

Loganin Inhibits Lipopolysaccharide-Induced Inflammation and Oxidative Response through the Activation of the Nrf2/HO-1 Signaling Pathway in RAW264.7 Macrophages.

Inflammation caused by the excessive secretion of inflammatory mediators in abnormally activated macrophages promotes many diseases along with oxidative stress. Loganin, a major iridoid glycoside isolated from Cornus officinalis, has recently been reported to exhibit anti-inflammatory and antioxidant effects, whereas the underlying mechanism has not yet been fully clarified. Therefore, the aim of the present study is to investigate the effect of loganin on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Our results indicated that loganin treatment markedly attenuated the LPS-mediated phagocytic activity and release of nitric oxide (NO) and prostaglandin E2, which was associated with decreased the expression of inducible NO synthase and cyclooxygenase-2. In addition, loganin suppressed the expression and their extracellular secretion of LPS-induced pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1ß. Furthermore, loganin abolished reactive oxygen species (ROS) generation, and promoted the activation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in LPS-stimulated macrophages. However, zinc protoporphyrin, a selective HO-1 inhibitor, reversed the loganin-mediated suppression of pro-inflammatory cytokines in LPS-treated macrophages. In conclusion, our findings suggest that the upregulation of the Nrf2/HO-1 signaling pathway is concerned at least in the protective effect of loganin against LPS-mediated inflammatory and oxidative stress, and that loganin can be a potential functional agent to prevent inflammatory and oxidative damage.

Effectiveness and safety of herbal medicine for cancer-related fatigue in lung cancer survivors: A systematic review and meta-analysis.

Approximately half of lung cancer patients (LCP) receiving chemotherapy are experiencing cancer-related fatigue (CRF). In East Asia, herbal medicines (HMs) have been used as tonics due to their anti-fatigue effect. This systematic review evaluated the effectiveness and safety of HMs for CRF in LCP. We comprehensively searched 12 electronic medical databases to search randomized controlled trials (RCTs) and quasi-RCTs investigating HMs for CRF in LCP, published up to September 2019. The primary outcome was the fatigue severity. Secondary outcomes included patients' quality of life (QOL), activities of daily life (ADL), and incidence of adverse events. Cochrane's risk of bias tool assessed the methodological quality of included RCTs. The risk ratio or mean difference was estimated with 95% confidence intervals by performing a meta-analysis. Twelve RCTs with 861 participants were included. Compared to conventional medicine alone, HM combined with conventional medicine significantly improved fatigue level, QOL, and ADL. As monotherapy, HM significantly improved ADL compared with megestrol. No serious HM-related adverse events were reported. Limited evidence suggests that HM could be effective and safe for CRF in LCP. However, further high-quality RCTs are needed to confirm these findings owing to the small number and low methodological quality of the included studies.

Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK.

Mori Ramulus, the dried twigs of Morus alba L., has been attracting attention for its potent antioxidant activity, but its role in muscle cells has not yet been elucidated. The purpose of this study was to evaluate the protective effect of aqueous extracts of Mori Ramulus (AEMR) against oxidative stress caused by hydrogen peroxide (H2O2) in C2C12 mouse myoblasts, and in dexamethasone (DEX)-induced muscle atrophied models. Our results showed that AEMR rescued H2O2-induced cell viability loss and the collapse of the mitochondria membrane potential. AEMR was also able to activate AMP-activated protein kinase (AMPK) in H2O2-treated C2C12 cells, whereas compound C, a pharmacological inhibitor of AMPK, blocked the protective effects of AEMR. In addition, H2O2-triggered DNA damage was markedly attenuated in the presence of AEMR, which was associated with the inhibition of reactive oxygen species (ROS) generation. Further studies showed that AEMR inhibited cytochrome c release from mitochondria into the cytoplasm, and Bcl-2 suppression and Bax activation induced by H2O2. Furthermore, AEMR diminished H2O2-induced activation of caspase-3, which was associated with the ability of AEMR to block the degradation of poly (ADP-ribose) polymerase, thereby attenuating H2O2-induced apoptosis. However, compound C greatly abolished the protective effect of AEMR against H2O2-induced C2C12 cell apoptosis, including the restoration of mitochondrial dysfunction. Taken together, these results demonstrate that AEMR could protect C2C12 myoblasts from oxidative damage by maintaining mitochondrial function while eliminating ROS, at least with activation of the AMPK signaling pathway. In addition, oral administration of AEMR alleviated gastrocnemius and soleus muscle loss in DEX-induced muscle atrophied rats. Our findings support that AEMR might be a promising therapeutic candidate for treating oxidative stress-mediated myoblast injury and muscle atrophy.

Analysis of the Use of Korean Medicine Treatments among Children and Adolescents in South Korea: Analysis of Nationally Representative Sample.

Korean medicine (KM) is pivotal within South Korea's healthcare system. This study aimed to investigate the current use and determinants associated with KM among children and adolescents through an analysis of the 2019 Korea Health Panel Annual Data. Subjects were divided into two groups: the integrative medicine (IM) group, utilizing both KM and conventional medicine (CM) (n = 163), and the CM-only group (n = 1843) for the year 2019. Differences in various factors between the IM and CM groups were investigated using the chi-square test or t-tests. Moreover, binomial logistic regression was employed to ascertain factors influencing the choice of KM over exclusive CM utilization. The IM group had a higher mean age (p = 0.011) and annual household income (p < 0.001) compared to the CM group. The regression analysis indicated a significant association between the use of both KM and CM and being an adolescent (p = 0.011), residing in Seoul/Gyeonggi/Incheon (p = 0.017), living in Daejeon/Chungcheong/Sejong (p = 0.001), and belonging to the first income percentile (p = 0.002). Significant differences were observed in the KM usage patterns between the groups of children and adolescents. These insights could contribute to the development of strategies for the optimal allocation of medical resources within South Korea's distinctive medical framework.

Factors associated with the use of pharmacopuncture in addition to acupuncture in South Korea: An analysis of a nationally representative panel.

Pharmacopuncture is a widely used Korean medicine treatment, but its usage patterns and associated factors remain unclear. This study aimed to explore factors related to the use of pharmacopuncture alongside acupuncture and investigate the associated medical cost burden in South Korea. We analyzed the 2019 Korea Health Panel Annual Data, focusing on adult outpatients who received acupuncture alone or both acupuncture and pharmacopuncture (PA). We employed individual-level and visit-level approaches, using chi-square tests, t-tests, and binary logistic regression for analysis. Among 1280 patients, 10% were PA users. Logistic regression showed that PA use was significantly associated with being aged 30 to 49 (odd ratio [OR] = 2.531; P = .009), having an education level of elementary school or lower (OR = 2.571; P = .011), and being in the 2nd (OR = 1.914; P = .041) or 3rd income percentile (OR = 1.925; P = .020). Of 13,101 medical visits, 5.80% involved PA, with PA visits incurring significantly higher costs than acupuncture only visits (KRW 4438.33 vs 14,700.16; P < .001). Arthritis, shoulder disorders, and other joint conditions were more prevalent among PA visits (P < .001). This study reveals socioeconomic factors influencing pharmacopuncture use and highlights potential health inequalities in its access in South Korea. The higher costs associated with PA visits suggest a need for considering its inclusion in health insurance coverage. Future research should focus on the effectiveness, cost-effectiveness, and standardization of pharmacopuncture to address unmet healthcare needs and inform policy decisions.

Effectiveness of mind-body medicine for Hwa-Byung (a Korean cultural diagnosis of suppressed anger): A systematic review of interventional studies.

OBJECTIVE: This systematic review analysed the effectiveness of mind-body modalities (MBMs) in Hwa-byung (HB). METHODS: Ten electronic databases were searched. Intervention studies using MBMs for individuals with HB, published up to July 2023, were included. The methodological quality of the included studies was assessed using the Cochrane RoB and ROBINS-I tools. Meta-analysis of continuous variables was presented as mean differences (MDs) and their 95% confidence intervals (CIs). RESULTS: Nine studies including five randomized controlled clinical trials, were included. The MBM types were meditation, relaxation, biofield therapy, art therapy, and forest-based MBM, and comprehensive HB programs. Most studies used an MBM group, with 5-6 sessions delivered during an average of 4-5 weeks. As a result of the meta-analysis, art therapy showed a statistically significantly better effect on improving the Hwa-Byung Scale (HB-S) score compared to the waitlist control (MD = -7.74; 95% CI = -9.81 to -5.66). In the before-and-after comparison, MBMs were frequently reported to have significant benefits for improving the HB-S total score (7/7, 100%), depressive mood (4/5, 80%), and state anxiety (6/8, 75%). Some methodological flaws were identified in the included studies, including the reliability of diagnosis, non-implementation of assessor blinding, and inappropriate control groups. CONCLUSIONS: This review identified potentially promising MBMs that were not previously recommended in the current HB clinical practice guidelines. In the future, high-quality clinical studies that include the use of standardized HB diagnostic criteria, homogeneous interventions, appropriate control groups, standard assessment tools such as the HB-S, and assessor blinding are needed.

Effectiveness and safety of East Asian herbal medicine for menopausal insomnia: a systematic review and meta-analysis.

Background: Menopausal insomnia significantly impacts the quality of life in women. East Asian herbal medicines (EAHMs) have been traditionally used in Asian countries, but their efficacy and safety require systematic evaluation. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of EAHM for treating menopausal insomnia. Methods: A comprehensive literature search was conducted across 10 electronic databases from inception until 19 July 2023. Randomized controlled trials (RCTs) investigating EAHM for menopausal insomnia were included. Two reviewers independently screened studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. The primary outcome was sleep quality, insomnia severity, and sleep architecture. Secondary outcomes included total effective rate (TER), menopausal symptoms, and adverse effects. Meta-analysis was conducted using a random-effects model, and the results were calculated as mean differences (MDs) or risk ratios (RRs) and their 95% confidence intervals (CIs). Also, the certainty of evidence was assessed using the GRADE approach. Results: A total of 70 RCTs involving 6,035 participants met the inclusion criteria. The most frequently used EAHMs were modified Suan Zao Ren Tang, and the most frequently used herbal component was Zizyphus jujuba Miller var. spinosa Hu ex H. F. Chou [Rhamnaceae; Zizyphi Semen]. Compared with sedative-hypnotics, EAHM significantly improved sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI) (MD -2.18, 95% CI -2.56 to -1.80), and reduced menopausal symptoms, as assessed by the Kupperman Index (MD -4.92, 95% CI -6.03 to -3.80). Similar results were seen when EAHM was added to sedative-hypnotics. When EAHM was additionally used in sedative-hypnotics, similar benefits were shown for PSQI (MD -2.46, 95% CI -3.09 to -1.82) and the Kupperman Index (MD -4.64, 95% CI -5.07 to -4.21). EAHM was generally safer than sedative-hypnotics, with significantly fewer adverse reactions (RR 0.15, 95% CI 0.07-0.34). However, the certainty of evidence was moderate to low. Conclusion: EAHMs, alone or with sedative-hypnotics, may be effective and safe for improving sleep quality and managing menopausal symptoms. Future studies should include diverse populations, rigorous methodologies, and explore mechanisms of action to confirm these findings. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?], identifier [CRD42023446708].

The Modernization of Oriental Music Therapy: Five-Element Music Therapy Combined with Artificial Intelligence.

In recent years, music has been regarded as a promising non-pharmacological intervention for a number of physical and mental conditions. Five-elements music therapy-based on the five-element theory-is a unique non-pharmacological therapy of East Asian traditional medicine. It has the potential to effectively provide individualized music therapy to individuals with illness. However, one limitation of this music therapy is that the classification of the five elements and its application is mainly based on subjective judgment. The development of artificial intelligence (AI) has enabled the acoustic analysis of multi-factor sound sources. This can develop five-element music therapy. Here, we discussed the challenges proposed by the future combination of five-element music therapy and AI. Further, we hypothesized that AI may promote its use in the medical field.

Use of Herbal Decoction and Pharmacopuncture in Individuals with Chronic Disease: findings from a nationally representative panel.

Objectives: This study analyzed the Korea Health Panel Annual Data 2019 to investigate factors related to the use of non-insured Korean medicine (KM) treatment in individuals with chronic diseases. The non-insured KM treatments of interest were herbal decoction (HD) and pharmacopuncture (PA). Methods: Among adults aged 19 or older, 6,159 individuals with chronic diseases who received outpatient KM treatment at least once in 2019 were included. They were divided into three groups according to the KM treatment used (1) basic insured KM non-pharmacological treatment (BT) group (n = 629); (2) HD group (n = 256); (3) PA group (n = 184). Logistic regression analysis was used to explore factors associated with favoring HD or PA use over BT. Potentially relevant candidate factors were classified using the Andersen Behavior Model. Results: Compared to BT, the 1st to 3rd quartiles of income compared to the 4th quartile (odds ratio 1.50 to 2.06 for HD; 2.03 to 2.83 for PA), health insurance subscribers compared to medical aid (odds ratio 2.51; 13.43), and presence of musculoskeletal diseases (odds ratio 1.66; 1.91) were significantly positively associated with HD and PA use. Moreover, the presence of cardiovascular disease (odds ratio 1.46) and neuropsychiatric disease (odds ratio 1.97) were also significantly positively associated with HD use. Conclusion: The presence of some chronic diseases, especially musculoskeletal diseases, was significantly positively associated with HD and PA use, while low economic status was significantly negatively associated with HD and PA use, indicating the potential existence of unmet medical needs in this population. Since chronic diseases impose a considerable health burden, the results of this study can be used for reference for future health insurance coverage policies in South Korea.

Delphi study for developing a checklist of adverse events associated with acupotomy.

BACKGROUND: Acupotomy, a more invasive procedure than acupuncture, involves the use of a thicker needle with an integrated knife at the tip, necessitating safety research. We aimed to define relevant adverse events (AEs) and create a standardized form of the ACUPOtomy-related AEs CHECKlist (ACUPOCHECK). METHODS: Before conducting the Delphi process, a systematic review and pilot prospective study were conducted to gather information on previously reported AEs. Using these data, pilot versions of the ACUPOCHECK and Delphi questionnaires were developed. The Delphi questionnaire involved selecting types of AE for inclusion, establishing separate criteria for acupotomy-related AEs, and achieving a consensus on AE assessment. Thirteen Korean doctors with experience in acupotomy or AE research were recruited to participate in each Delphi round. Consensus was considered to have been reached if the critical value for the content validity ratio met or exceeded 0.538. RESULTS: The final ACUPOCHECK was developed using four rounds of the Delphi method and one face-to-face consensus meeting. It included 12 local AEs (pain, hemorrhage, bruise, hematoma, edema, pruritus, rash, infection, nerve damage, dysesthesia, movement impairment, and pneumothorax) and 14 systemic AEs (disease aggravation, needle fatigue, sleepiness, procedural nausea, procedural vomiting, procedural headache, procedural dizziness, sweating, procedural shock, syncope, dyspnea, procedural pain, sleep disorder, and postprocedural infection). Separate criteria were established for pain, hemorrhage and bruising: pain was defined as pain that occurrs during daily activities and persists for longer than 72 h, hemorrhage as bleeding that continues for ≥ 3 min despite pressure application, and bruising as having a bruise with a diameter of ≥ 3 cm. Open-ended descriptions were allowed for AEs not covered by the checklist, and severity and causality were assessed using the Common Terminology Criteria for Adverse Events and modified World Health Organization-Uppsala Monitoring Center criteria. CONCLUSION: ACUPOCHECK provides a standardization framework that can help research on traditional practices as well as new tools and techniques that are more invasive and may cause more severe AEs. Subsequent studies will use ACUPOCHECK to develop rational safety guidelines for acupotomy techniques. Please cite this article as: Jun H, Lee H, Yoon SH, Kwon CY, Jeon D, Lee JH, Leem J. Delphi study for developing a checklist of adverse events associated with acupotomy. J Integr Med. 2024; Epub ahead of print.

Safety of herbal decoctions: A scoping review of clinical studies in South Korea focusing on liver and kidney functions.

ETHNOPHARMACOLOGICAL RELEVANCE: Approximately 27% of individuals seeking Korean medicine (KM) services in South Korea are prescribed herbal decoctions. The South Korean government has considered the validity of providing National Health Insurance coverage for herbal decoctions. Therefore, it is important to investigate their safety. AIM OF THE STUDY: To investigate the safety of herbal decoctions commonly prescribed by KM doctors and to assess their effects on liver and kidney function by comprehensively analyzing Korean clinical studies in a scoping review. MATERIALS AND METHODS: The Arksey and O'Malley framework and modified methods were applied in this scoping review. A comprehensive search of seven electronic health databases was conducted, and relevant clinical studies published between 2000 and 2022 were identified. Subsequently, only clinical studies reporting the results of liver and/or renal function tests in patient prescribed herbal decoctions by KM doctors were included. The characteristics of the included clinical studies and the reported proportion of each liver and/or renal function indicator were analyzed. Meta-analyses of the effects of herbal decoction on liver and/or renal function reported in prospective cohort studies were also performed. RESULTS: Fifty-nine clinical studies were included in this review. The proportion of prospective cohort studies markedly decreased in the 2010s compared to the 2000s, while there was no noticeable change in the number of relevant clinical studies. Herbal decoctions were prescribed for less than one month in most included studies. Abnormal changes in liver or renal function indicators were identified in a small number of studies (3.70% and 7.69%, respectively). In a meta-analysis of 15 prospective cohort studies, no statistically significant changes in four liver function indices and two renal function indices were observed before and after the prescription of herbal decoctions. CONCLUSIONS: Qualitative and quantitative analyses demonstrated favorable safety profiles for herbal decoctions. This scoping review includes the gaps noted between clinical application and research regarding the safety profiles of herbal decoctions. These findings could be used as evidence to support the inclusion of herbal decoction prescriptions in the National Health Insurance coverage in South Korea.

Adverse events of herbal decoction: A systematic review and meta-analysis over past 10 years.

BACKGROUND: Herbal decoctions (HDs) are the oldest and most common herbal medicine formulations. Different HDs exist, and some consumers are concerned that they may become contaminated during manufacturing. Therefore, the need for a safety assessment of HDs has been raised. This study aimed to investigate the adverse events (AEs) associated with HDs by comprehensively analyzing randomized controlled trials (RCTs) using systematic reviews and meta-analyses. METHODS: A systematic search was conducted on PubMed, Embase, and the Cochrane Library for articles published up to November 2022. The included RCTs compared HDs with other treatments published between 2013 and 2022, and the risk of bias was assessed using RevMan 5.4. Meta-analyses of the number of AEs associated with HDs reported in the included RCTs were also performed. RESULTS: The systematic review included 26 RCTs, and the meta-analysis included 17 RCTs that reported AEs. The meta-analysis comparing HDs with active controls showed that both the number of AEs (14 studies; risk ratio (RR)= 0.50 cases, 95 % confidence interval (CI) [0.29, 0.88]; I2 = 42 %) and the number of patients who complained of AEs (seven studies; RR=0.51 patients, 95 % CI [0.28, 0.94]; I2 =9 %) were fewer in the HDs group than in the active control groups. CONCLUSION: This study showed that HDs are safer than other conventional medications based on the results of qualitative and quantitative syntheses of RCTs.

The effect of sham acupuncture can differ depending on the points needled in knee osteoarthritis: A systematic review and network meta-analysis.

Objective: In sham acupuncture-controlled acupuncture clinical trials, although sham acupuncture techniques are different from those of verum acupuncture, the same acupuncture points are often used for verum and sham acupuncture, raising the question of whether sham acupuncture is an appropriate placebo. We aimed to examine the effects of sham and verum acupuncture according to the points needled (same or different between verum and sham acupuncture) in knee osteoarthritis. Methods: Ten databases were searched to find randomized controlled clinical trials (RCTs) assessing the effects of verum acupuncture with sham acupuncture or waiting lists on knee osteoarthritis. Sham acupuncture was classified as using the same acupuncture points as those in verum acupuncture (SATV) or using sham points (SATS). A frequentist network meta-analysis (NMA) was conducted, and the certainty of evidence was evaluated. Results: A total of 10 RCTs involving 1628 participants were included. Verum acupuncture was significantly superior to SATS but not different from SATV in terms of pain reduction. Additionally, SATV was significantly superior to the waiting list. For physical function, no difference were found between verum acupuncture, SATV, and SATS. The certainty of evidence was low to moderate. Conclusion: For knee osteoarthritis, the pain reduction effect of acupuncture may differ according to the needling points of sham acupuncture, and the control group should be established according to the specific aim of the study design and treatment mechanism.

Research status of east Asian traditional medicine treatment for chronic cough: A scoping review.

BACKGROUND: When 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. METHODS: Based 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. RESULTS: Among 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. CONCLUSIONS: In 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.

An evidence map on traditional medicine across health outcomes.

Background: Traditional medicine (TM) plays a significant role in healthcare either as part of the primary healthcare system or as an adjunct to conventional medicine. This study aimed to map systematic reviews (SRs) of TM modalities across health conditions and identify gaps in the research literature to facilitate priority setting in future TM research. Methods: We searched 17 databases from January 2018 to December 2022. Reviewers in pairs independently performed the database search, screened each record for inclusion, extracted data, and performed quality assessments using the AMSTAR 2 - A Measurement Tool to Assess systematic Reviews. To be included in this evidence map, the studies had to be SRs of clinical studies that evaluated the effectiveness of a TM modalities. The included SRs were analyzed according to TM modality, ICD-11 disease classification, and health outcomes, and visualized using graphical plots. Results: We retrieved 241,509 records. After excluding duplicate records, 181,616 titles and abstracts were screened and 20,856 records were selected for full-text assessment, of which 18,137 records were further excluded. The final 2719 included SRs were primarily in adults (2591) with only 128 SRs in the pediatric population. The most commonly evaluated health conditions were diseases of the digestive system, circulatory system, and genitourinary system, with herbal medicine (n = 1867) and acupuncture (n = 471) being the most investigated TM modalities in treating these illnesses. Based on AMSTAR 2 criteria, the methodology quality of the included SRs is considerably low. Conclusion: This evidence map provides a comprehensive overview of the extent and nature of the available research onTM modalities across health conditions. It provides an initial step towards characterizing the global evidence base and outlining gaps in the existing evidence. We regard this study as laying the basis for future research of TM modalities. Registration: The protocol of this map is registered in PROSPERO (CRD42023416355).

Research Trends of Pharmacopuncture: a bibliometric analysis using VOSviewer (2007-2023).

Objectives: Pharmacopuncture is considered a unique new type of acupuncture in Korean medicine (KM). This study was performed to investigate the research trends regarding pharmacopuncture through a bibliometric analysis using VOSviewer. Methods: The Web of Science Core Collection was searched for this study. The search terms were pharmacopuncture and pharmaco-puncture. The search was conducted on May 23, 2023, and 185 studies retrieved up to this date were included. Software VOSviewer version 1.6.19 was used to perform the bibliometric analysis. After data clearing, keyword co-occurrence and cooperation pattern analyses were performed. Results: The number of studies on pharmacopuncture have gradually increased since the mid-2000s, with the most published in 2020 (46 studies). The quality of the studies has also steadily increased, and recently, several randomized controlled trials of pharmacopuncture have been conducted. Moreover, this treatment has been investigated in the context of KM clinical practice guideline development in Korea. The scope of pharmacopuncture studies to date seems to be limited to musculoskeletal pain and bee venom pharmacopuncture. The researchers from Jaseng Medical Foundation have been the core researchers in the field of pharmacopuncture in Korea. They collaborated with researchers from universities or government-funded research institutes. However, small-scale research teams from KM clinics and university researchers were also identified as independent clusters. Conclusion: Pharmacopuncture research has grown both quantitatively and qualitatively, but the scope needs to be further expanded. There is also a gap between the use of pharmacopuncture by KM doctors in clinical settings and pharmacopuncture research. Based on these findings, some suggestions for future studies in this field are discussed. Furthermore, these findings may be used as data to expand and globalize pharmacopuncture research in the future.

Research and Public Interest in Mindfulness in the COVID-19 and Post-COVID-19 Era: A Bibliometric and Google Trends Analysis.

Public and research interest in mindfulness has been growing, and the Coronavirus disease 2019 (COVID-19) pandemic seems to have accelerated this growth. This study was conducted to investigate the public and research interest in mindfulness in the context of COVID-19. The term 'Mindfulness' was searched in Google Trends, and data were collected from December 2004 to November 2022. The relationship between the relative search volume (RSV) of 'Mindfulness' and that of related topics was analyzed, and 'Top related topics and queries' for the search term 'Mindfulness' were investigated. For bibliometric analysis, a search was conducted in the Web of Science database. Keyword co-occurrence analysis was conducted, and a two-dimensional keyword map was constructed using VOSviewer software. Overall, the RSV of 'Mindfulness' increased slightly. The RSVs of 'Mindfulness' and 'Antidepressants' showed an overall significant positive correlation (r = 0.485) but a statistically significant negative correlation during the COVID-19 era (-0.470). Articles on mindfulness in the context of COVID-19 were closely related to depression, anxiety, stress, and mental health. Four clusters of articles were identified, including 'mindfulness', 'COVID-19', 'anxiety and depression', and 'mental health'. These findings may provide insights into potential areas of interest and identify ongoing trends in this field.

The Impact of SARS-CoV-2 Infection on Heart Rate Variability: A Systematic Review of Observational Studies with Control Groups.

Autonomic nervous system (ANS) dysfunction can arise after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and heart rate variability (HRV) tests can assess its integrity. This review investigated the relationship between the impact of SARS-CoV-2 infection on HRV parameters. Comprehensive searches were conducted in four electronic databases. Observational studies with a control group reporting the direct impact of SARS-CoV-2 infection on the HRV parameters in July 2022 were included. A total of 17 observational studies were included in this review. The square root of the mean squared differences of successive NN intervals (RMSSD) was the most frequently investigated. Some studies found that decreases in RMSSD and high frequency (HF) power were associated with SARS-CoV-2 infection or the poor prognosis of COVID-19. Also, decreases in RMSSD and increases in the normalized unit of HF power were related to death in critically ill COVID-19 patients. The findings showed that SARS-CoV-2 infection, and the severity and prognosis of COVID-19, are likely to be reflected in some HRV-related parameters. However, the considerable heterogeneity of the included studies was highlighted. The methodological quality of the included observational studies was not optimal. The findings suggest rigorous and accurate measurements of HRV parameters are highly needed on this topic.