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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).

Objective: Sham acupuncture has been used as a control in acupuncture efficacy trials. However, questions have been raised about whether it is a physiologically inert placebo. We aimed to understand global research trends and provide guidance for future research by conducting a bibliometric analysis of sham acupuncture studies. Methods: Journal articles published to date related to sham acupuncture were retrieved from Web of Science on May 29, 2023. The publication year, country, keyword, author, and organization of the studies were analyzed using the available bibliometric information. Using VOSviewer software, the co-occurrence of keywords in sham acupuncture studies was visualized as a network map by cluster analysis and overlay analysis according to the publication year. Results: A total of 3428 studies were included in the analysis. Studies on sham acupuncture have been steadily increasing since 1991, with most of the studies conducted in China (1514 studies, 44.17 %), followed by the United States (789 studies, 23.02 %) and South Korea (277 studies, 8.08 %). The keywords of sham acupuncture research were classified into four clusters: evidence synthesis, pain clinical research, mechanism research, and acupressure research. Keyword analysis according to the publication year showed that evidence synthesis on sham acupuncture was recently focused on psychiatric conditions including depression and insomnia through systematic reviews, and clinical and mechanism studies on sham acupuncture were mostly conducted relatively in the past. Conclusion: This bibliometric analysis provides a comprehensive overview of the development and global trends of sham acupuncture research to date, suggesting directions for future research.

Introduction Traditional medicine (TM) is an important part of healthcare either as the main healthcare system or as a complement to conventional medicine. The effectiveness of TM has been assessed in clinical trials that have been synthesised into thousands of systematic reviews (SRs). This study is commissioned by the World Health Organization (WHO) and is aimed at providing a systematic map of SRs of TM interventions across health conditions, as well as identifying gaps in the research literature in order to prioritise future primary research.Methods and analysis This is the protocol for a systematic map of SRs reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will search 17 electronic databases to identify SRs of TM. The literature search covers the last 5 years, from January 2018 to December 2022. At least two independent reviewers will perform the database search, screening of eligible SRs, data extraction and quality assessments using the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR 2). The characteristics and extent of SRs will be analysed according to disease classification, and type of TM intervention, and visualised by means of (interactive) graphical maps.Ethics and dissemination Ethical approval is not required as this is a systematic map of published studies. The findings of the study will be disseminated through online-available maps, presentations and scientific publications.PROSPERO registration number CRD42023416355.

Objective: To investigate the current evidence on traditional medicine in managing bruxism and its clinical efficacy. Methods: A search was conducted in nine databases to identify potential eligible articles published from the date of inception until August 3, 2022. All clinical studies that used traditional medicine of any type in treating bruxism were eligible for inclusion. Two authors performed data extraction and quality assessments independently. Retrieved data were tabulated and discussed narratively. Results: A total of 16 clinical studies were included in this scoping review. Of the 16 studies, three studies were randomized controlled trials, one was a case–control study, 10 were case series, and two were case reports. Our review identified studies of interventions based on herbal medicine and acupuncture-related therapies. Most studies reported positive results, but the overall quality of the included studies was typically fair to poor. Conclusions: This study is the first scoping review on traditional medicine for bruxism despite the limited evidence. More research on traditional medicine in bruxism management should be conducted for better clarification and application in daily practice.

Abstract Kimchi is a Korean traditional fermented food which is one of the most popular ethnic fermented foods in Korea and consumed daily. The purpose of this review was to systematically evaluate all prospective clinical studies of kimchi and to estimate the effectiveness of kimchi for health in general. Three English databases, four Korean databases, and two clinical trial registries were searched until November 7, 2022. Two independent reviewers extracted and tabulated the data. The outcomes of this review were any health-related outcomes that studied on kimchi or kimchi-derived probiotics. Eleven randomized controlled trials (RCTs) were included in this review, with 638 participants enrolled in total and 608 participants completing the trials. Most of the included RCTs examined serum lipid profiles and clinical parameters and found that kimchi interventions showed decrease in serum lipids, cholesterols and body fats. Kimchi interventions may be safe and effective treatment option for the treatment of general health, obesity, and irritable bowel syndrome, regardless of the lack of adequate trials. In the future, research that can verify the conflicting results on the health benefits of kimchi should be conducted rigorously to provide the scientific basis for the benefits of kimchi.

BackgroundHigh relapse rates remain a clinical challenge in the management of breast cancer (BC), with distant recurrence being a major driver of patient deterioration. To optimize the surveillance regimen for distant recurrence after neoadjuvant chemotherapy (NAC), we conducted a comprehensive analysis using bioinformatics and machine learning approaches.Materials and methodsMicroarray data were retrieved from the GEO database, and differential expression analysis was performed with the R package ‘Limma’. We used the Metascape tool for enrichment analyses, and ‘WGCNA’ was utilized to establish co-expression networks, selecting the soft threshold power with the ‘pickSoftThreshold’ algorithm. We integrated ten machine learning algorithms and 101 algorithm combinations to identify key genes associated with distant recurrence in BC. Unsupervised clustering was performed with the R package ‘ConsensusCluster Plus’. To further screen the key gene signature of residual cancer burden (RCB), multiple knockdown studies were analyzed with the Genetic Perturbation Similarity Analysis (GPSA) database. Single-cell RNA sequencing (scRNA-seq) analysis was conducted through the Tumour Immune Single-cell Hub (TISCH) database, and the XSum algorithm was used to screen candidate small molecule drugs based on the Connectivity Map (CMAP) database. Molecular docking processes were conducted using Schrodinger software. GMT files containing gene sets associated with metabolism and senescence were obtained from GSEA MutSigDB database. The GSVA score for each gene set across diverse samples was computed using the ssGSEA function implemented in the GSVA package.ResultsOur analysis, which combined Limma, WGCNA, and machine learning approaches, identified 16 RCB-relevant gene signatures influencing distant recurrence-free survival (DRFS) in BC patients following NAC. We then screened GATA3 as the key gene signature of high RCB index using GPSA analysis. A novel molecular subtyping scheme was developed to divide patients into two clusters (C1 and C2) with different distant recurrence risks. This molecular subtyping scheme was found to be closely associated with tumor metabolism and cellular senescence. Patients in cluster C2 had a poorer DRFS than those in cluster C1 (HR: 4.04; 95% CI: 2.60–6.29; log-rank test p < 0.0001). High GATA3 expression, high levels of resting mast cell infiltration, and a high proportion of estrogen receptor (ER)-positive patients contributed to better DRFS in cluster C1. We established a nomogram based on the N stage, RCB class, and molecular subtyping. The ROC curve for 5-year DRFS showed excellent predictive value (AUC=0.91, 95% CI: 0.95–0.86), with a C-index of 0.85 (95% CI: 0.81–0.90). Entinostat was identified as a potential small molecule compound to reverse high RCB after NAC. We also provided a comprehensive review of the EDCs exposures that potentially impact the effectiveness of NAC among BC patients.ConclusionThis study established a molecular classification scheme associated with tumor metabolism and cancer cell senescence to predict RCB and DRFS in BC patients after NAC. Furthermore, GATA3 was identified and validated as a key gene associated with BC recurrence.

BackgroundThis study aimed to explore individual prevalence of respiratory symptoms and to describe the Korean population's treatment approaches, preventive health behaviors, and mental health conditions during the pandemic.MethodsWe analyzed responses from an online nationwide survey, conducted between February 2021 to May 2021, about people's experiences during the pandemic. Statistical analysis was also performed to see if there were any significant differences in treatment and prevention strategies between different groups of respondents (between those had respiratory symptoms, compared with those who did not, and between those tested positive for COVID-19, compared with those who did not).ResultsA total of 2,177 survey respondents completed the survey and, of these, only 142 had experienced symptoms. The most frequently reported respiratory infections related symptoms were runny or blocked nose (47.6%), cough (45.5%), fever (44.1%), sore throat (42.0%), and fatigue (30.1%). More than half of the respondents (53.1%) used complementary and alternative medicine (CAM) approaches as means of preventive measures. In terms of preventive behaviors, the more emphasized behaviors were mask-wearing (58.9%) and hand-washing after coming home (42.7%). The majority of the respondents (64.9%) did not show signs of mental health issues.ConclusionIn South Korea, conventional medicine was mainly used for COVID-19 treatment whereas CAM was commonly used as preventive measures. COVID-19 was also found to have less impact on the general population's mental health. The findings of this study may shed light on how the pandemic impacted the general population.

Background: Since the beginning of the Coronavirus disease 2019 (COVID-19) pandemic, various complementary and alternative medicines (CAMs) have been used in clinical practice. In this overview, we summarized the evidence for CAM interventions in the treatment of COVID-19 patients. Methods: For this overview, PubMed, Embase and Cochrane Library were searched from inception to October 2021. Systematic reviews (SRs) on the effectiveness and safety of CAM interventions for COVID-19 patients were located, and the MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) was used to evaluate the reporting quality of the included SRs. Keywords including COVID-19 and CAM interventions were used for locating SRs. For evidence mapping, we created a two-dimensional bubble plot that included the width and strength of the evidence for each CAM intervention and specific outcome. Results: In this overview, we identified 24 SRs (21 for Traditional Chinese Medicine (TCM) medications, two for vitamin D and one for home-based activity). From the included SRs, TCM herbal medications were reported to show good results in decreasing the rate of disease progression (relative risk (RR) 0.30, 95% confidence intervals (CI) [0.20, 0.44]), time to the resolution of fever (standard mean difference (SMD) -0.98, 95% CI [-1.78, -0.17]) and rate of progression to severe COVID-19 cases (RR 0.34, 95% CI [0.18, 0.65]), but the evidence for other interventions did not show effectiveness with certainty. Gastric disturbance was a major adverse event of TCM medications. Conclusion: There is evidence that TCM medications are effective in the symptom management of COVID-19 patients. However, evidence for the effectiveness of most CAM interventions still needs evaluation.

Background: Few studies investigated the prescription patterns of traditional Korean medicine (TKM) therapies for PCOS in clinical practice. The purpose of this study was to identify the common symptoms, herbal prescription patterns and types of adjunctive treatment for treating polycystic ovary syndrome (PCOS) in major traditional Korean medicine (TKM) hospitals. Methods: A retrospective chart review of PCOS patients was used for the study. The study involved the analysis of medical records (ICD-10, polycystic ovary syndrome: E28.2) from four TKM-based university hospitals in South Korea. Results: A total of 120 PCOS patients were analyzed. We found that PCOS patients had a wide range of symptoms, including menstrual irregularity, oligomenorrhea, amenorrhea, acne, infertility, and metrorrhagia. The most commonly prescribed prescriptions for PCOS treatment were Chokyung-san (Tiaojing-san), Gamiguibi-tang (Jiawei Guipi-tang), and Changbudodam-tang (Cangfu Daotan-tang). In addition, patients were most often treated with adjunctive acupuncture and moxibustion. Conclusion: Our study presents the major gynecological herbal prescriptions and other adjunctive therapies used for the treatment of PCOS in TKM-based hospitals. However, further pharmacological investigations and effective clinical trials should be developed to ensure the objectivity of efficacy assessments.

Background: Integrative herbal medicine has been reported to have beneficial effects in the treatment of coronavirus disease 2019 (COVID-19).Aim: To compile up-to-date evidence of the benefits and risks of herbal medicine for the treatment of COVID-19 symptoms.Methods: Eleven databases, including PubMed, Cochrane Register of Controlled Trials (CENTRAL), Embase, Allied and Complementary Medicine Database (AMED), Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chinese Science and Technique Journals Database (VIP), Research Information Service System (RISS), Korean Medical database (KMBase), Korean Association of Medical Journal database (KoreaMed), and OASIS database, were searched from 15 June, 2020, until 28 March 2022. Randomized controlled trials (RCTs), published in any language, reporting the efficacy and safety outcomes of herbal medicine in patients of all ages with a PCR-confirmed diagnosis of COVID-19 were included in this analysis. Data extraction and quality assessments were performed independently.Results: Random-effects meta-analyses showed evidence of favorable effects of treatment with herbal medicine when added to standard treatment, versus standard treatment alone, on the total effective rate (p = 0.0001), time to remission from fever (p < 0.00001), rate of remission from coughing (p < 0.0001), fatigue (p = 0.02), sputum production (p = 0.004), improvement of manifestations observed on chest computed tomography scans (p < 0.00001), incidence of progression to severe COVID-19 (p = 0.003), all-cause mortality (p = 0.003), time to a negative COVID-19 coronavirus test (p < 0.0001), and duration of hospital stay (p = 0.0003). There was no evidence of a difference between herbal medicine added to standard treatment, versus standard treatment alone, on the rate of remission from symptoms such as a fever, sore throat, nasal congestion and discharge, diarrhea, dry throat, chills, and the rate of conversion to a negative COVID-19 coronavirus test. Meta-analysis showed no evidence of a significant difference in adverse events between the two groups. There was an unclear risk of bias across the RCTs included in this analysis, indicating that most studies had methodological limitations.Conclusion: Current evidence suggests that herbal medicine added to standard treatment has potential benefits in the treatment of COVID-19 symptoms but the certainty of evidence was low.

BackgroundTraditional, Complementary and Integrative Medicine (TCIM) has been reported to use for symptom management of coronavirus disease 2019 (COVID-19). The objective of this review was to identify the overall usage prevalence of TCIM interventions for COVID-19.MethodsSurveys on the general population and observational studies on the COVID-19 patient chart review were located in the search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases in September 2021. Observational studies, such as cross-sectional studies, surveys, cohort studies and hospital-based patient case reviews, published in any language, reporting the usage of TCIM in the patients with COVID-19 or the general population during the COVID-19 pandemic were included in this review. Data screening and extraction were performed independently by two reviewers. The reporting quality of the included studies was assessed with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement. To conduct a meta-analysis of the usage prevalence of various TCIM interventions, the effect size of the proportion for each intervention was calculated with the inverse variance method. The main outcome was usage prevalence of TCIM interventions among patients with COVID-19 or the general population during the COVID-19 pandemic.ResultsA total of 62 studies were included in this review. The overall TCIM usage prevalence was estimated to be 0.64 (95% CI 0.54–0.73). The overall prevalence did not differ between the population-based survey (0.65, 95% CI 0.48–0.81) and the hospital-based patient case review (0.63, 95% CI 0.52–0.73). Statistical heterogeneity and comparatively low quality in reporting were observed, which should be cautiously considered when interpreting the results.ConclusionVarious TCIM interventions were reported to be used with comparatively high frequency. Future international collaborative research might overcome the main limitation of this study, i.e., the heterogeneity of the included data.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278452, identifier: CRD42021278452.

We are grateful for the relevant comments by Hu et al. [...]

Background and Objectives: Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder characterized by inattention, hyperactivity, and impulsivity. However, it is uncertain whether the use of acupuncture (AT) in children with ADHD is supported by the current evidence. This review aims to provide updated evidence of the effectiveness of acupuncture in children with ADHD. Methods: Nine databases were searched from their inception to 28 July 2022. Two authors independently screened potentially eligible studies. The quality assessment of the selected studies was performed using Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). The characteristics of the included studies were presented in a tabular form, and a meta-analysis was performed on the treatment effects of AT on ADHD symptoms. Results: Fourteen studies involving 1185 patients evaluating the efficacy of AT for ADHD treatment were included in this review. Compared to conventional medicine alone, the meta-analysis indicated that AT as an add-on to conventional medicine has a positive effect on improving conduct problems, learning problems, hyperactivity–impulsivity, and hyperactivity symptoms in ADHD patients. Similarly, AT alone was found to improve learning problems, hyperactivity–impulsivity, and hyperactivity symptoms in ADHD patients and exhibited better total treatment efficacy than conventional medicine alone. No major adverse events were reported. The risk of bias of the included studies was generally concerning. Conclusions: Evidence on the effectiveness of AT for ADHD patients is currently too limited to provide recommendations for its usage. More studies with the proper methodology are needed for the validation of AT interventions in treating children with ADHD.

Background: Stroke is a major health issue worldwide. Since Chinese herbal medicine is widely used for the treatment of stroke, there is a need to evaluate its efficacy as an alternative treatment option. The aim of this paper is to carry out an overview of Chinese herbal medicine for the treatment of stroke by summarizing and evaluating all existing Cochrane reviews. Methods: The Cochrane Database of Systematic Reviews was searched from its inception date to August 2019 using “stroke” and “herbal medicine” or “traditional medicine” as search terms. For the methodological quality assessment of the Cochrane reviews, the Assessment of Multiple Systematic Reviews (AMSTAR) tool was used. Results: Eight Cochrane reviews that evaluated the efficacy of herbal medicine for the treatment of stroke were included in this overview. There were 71 randomized controlled trials, with 5770 patients in total. The AMSTAR scores of the Cochrane reviews included in this study ranged from 9 to 11 with a mean score of 10. Three reviews met all the 11-item criteria of the AMSTAR. All reviews presented potential efficacy of herbal medicine for stroke treatment in terms of improvement of neurological deficit. Conclusions: This overview reveals the potential efficacy of herbal medicines for the treatment of stroke in terms of neurological deficit improvement. However, due to the high risk of bias in the reviews’ studies, an affirmative conclusion for the recommendation of herbal medicine for clinical practice could not be drawn. Keywords: Chinese herbal medicine, Stroke, Overview, Cochrane reviews

Background Attention deficit hyperactivity disorder (ADHD) patients often use complementary and alternative medicine to treat symptoms, and acupuncture is one option. This systematic review aims to assess whether acupuncture is an effective treatment for attention deficit hyperactivity disorder (ADHD). Methods We will search nine databases from their inception: PubMed, AMED, CINAHL, EMBASE, the Cochrane Central Register of Controlled Trials, RISS, KoreaMed, KISS, and the China National Knowledge Infrastructure database. Two investigators will independently review the selected studies, extract the data, and analyze them. The Cochrane Risk of Bias Assessment Tool will be used to assess the risk of bias. Discussion Because this is a systematic review, no ethical approval is needed. The systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to support health policy and practice. Trial registration number Reviewregistry1345.

Background: This study aimed to obtain the symptom, prescription and therapeutic patterns for the treatment of patients with menopausal syndrome in major Korean medicine (KM) hospitals. Methods: We used a retrospective chart review of climacteric disorder and postmenopausal syndrome patients by examining medical records (ICD-10, menopausal and female climacteric states: N95.1, Menopausal and perimenopausal disorder, unspecified: N95.9) from eight university KM hospitals in South Korea. Results: The main symptoms of 1,682 patients with menopausal disorders visiting 8 college-affiliated oriental medicine hospitals were hot flush, hyperhidrosis, fatigue, insomnia, and chest tightness. Guipi-tang (decoction), Siwu Guipi-tang (decoction), Qingxin Lianzi-yin (decoction), Jiawei Xiaoyao-san (powder) and Guipi Wendan-tang (decoction) were the most commonly prescribed herbal medicines for menopausal disorders. Patients were most often treated with a combination of herbal medicine and acupuncture. Conclusion: Our study shows that the current prescribed herbal medicines were used for treating menopausal disorders in Korean medicine hospitals. However, the objectivity of the efficacy assessment should be studied further.

Breast cancer (BC) is the most common cancer in women and is a serious threat to women’s health. Cancer-related fatigue (CRF) is a distressing symptom in BC patients during and after chemotherapy or radiation therapy that severely affects quality of life (QoL). AT is widely used for fatigue management. However, the effect of AT on CRF is still uncertain. This study aimed to evaluate the efficacy and safety of AT in the management of CRF in patients with BC. Eleven databases were searched through June 2022. Two researchers independently performed the database search, study selection, data extraction, and risk of bias assessment. Study selection was performed based on predefined Participants, Intervention, Comparators, Outcomes, Study design (PICOS) criteria, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed when reporting the results. A meta-analysis was performed according to the Cochrane systematic review method using RevMan 5.3. A total of 12 studies including a total of 1084 participants were included. The results showed that AT had a beneficial effect compared with sham AT (n = 256, SMD = −0.26, 95% CI [−0.51, −0.01], p = 0.04, I2 = 0%) and a long-term effect on fatigue score (n = 209, MD = −0.32, 95% CI [–0.59, −0.04], p = 0.02, I2 = 0%). Meta-analysis showed that AT had a beneficial effect compared with usual care (UC) on fatigue scores (n = 238, SMD = −0.39, 95% CI [−0.66 to −0.12], p = 0.005, I2 = 0%). Of the 12 articles, 3 articles were judged as having a low risk of bias in all domains and hence were of high quality. No serious adverse effects were identified. AT is an effective and safe treatment for CRF, and AT is more effective than sham AT or UC or wait-list control (WLC). Nevertheless, the methodological quality of most of these studies was low, and the included studies/sample sizes were small, so the ability to derive decisive implications was limited. Further research is needed to confirm these findings.

Background: Nocturnal crying is a common condition in which children intermittently or continuously cry and fuss during the night, at certain times or throughout the night. It is a common pediatric sleep disturbance for which medical assistance is highly sought by parents, and one of the non-pharmacologic treatments for nocturnal crying is pediatric acupuncture. This review aimed to review the literature about the effectiveness and safety of pediatric acupuncture for nocturnal crying.Methods: Literature searches were performed on PubMed, the Cochrane Controlled Register of Trials (CENTRAL), Allied and Complementary Medicine Database (AMED), Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chinese Science and Technique Journals Database (VIP), OASIS, the Research Information Service System (RISS), and National Digital Science Library (NDSL) from the available date of inception until December 28, 2020. Two review authors independently screened the titles and abstracts of all relevant articles from the search to select eligible articles. All variants of clinical studies on acupuncture treatment for nocturnal crying, including case reports and case studies, were eligible. Data were independently extracted by two review authors using a standard data extraction form. Retrieved data are presented in a tabular form and narratively discussed.Results: We included 12 studies (10 case series and two case reports) with a total sample size of 2,324 children recruited from the hospital outpatient department. All of the included studies were conducted in mainland China and administered acupuncture as the sole intervention. For the primary outcome, the total efficacy rate of acupuncture treatment for nocturnal crying was reported as 100% in 9 studies, 95% in one study, 94% in another study, and 86% in the remaining study. For the secondary outcome, one study reported a 14% recurrence rate, whereas another study reported an 11% recurrence rate after treatment. There were no follow-ups in most of the studies. None of the studies reported possible adverse events. Most children recovered after one treatment. Generally, the acupoints that were most frequently selected were acupoints EM30 and PC9.Conclusions: This comprehensive review suggested that pediatric acupuncture may be an effective treatment for nocturnal crying, which could be worth investigating further.

Background: There are numerous reports worldwide on the use of complementary therapy for female infertility. This paper presents an overview of the available systematic reviews (SRs) on the outcomes of complementary therapy for female infertility. Methods: Electronic databases, including Pubmed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Google scholar, and six Korean medical databases (KoreaMed, KMBASE, OASIS, NDSL, KCI, and RISS) will be searched from their date of inception. Eligible SRs will be independently selected by two authors, according to the defined inclusion criteria. Methodological quality of the final selected SRs will then be evaluated using the ‘Assessment of multiple systematic reviews 2 (AMSTAR2)’. Finally, we will report on the characteristics and outcomes of efficacy and safety of each individual SR. Discussion: This overview will apprise the overall quality and evidence of the outcomes of SRs of complementary therapy for female infertility. Keywords: Complementary therapy, Infertility, Overview, Systematic review

The immunosuppressive state in the tumor microenvironment (TME) of breast cancer makes it difficult to treat with immunotherapy. Oncolytic viruses not only lyse tumor cells but also reshape the TME. Therefore, they can play a multi-mechanism synergistic effect with immunotherapy. In this study, an oncolytic adenovirus Ad5F11bSP-Rantes was constructed and used as a vector to express the chemokine Rantes. The objective of this study was to test the dual mechanisms of the oncolytic effect mediated by virus replication and the enhanced anticancer immune response mediated by Rantes chemotaxis of immune cells. It was found that Ad5F11bSP-Rantes has strong infectivity and effective killing activity against breast cancer cells. In the established triple negative breast cancer (TNBC) xenograft model in NCG mice whose immune system was humanized with human peripheral blood mononuclear cells (PBMCs), Ad5F11bSP-Rantes achieved 88.33% tumor inhibition rate. Rantes expression was high in mouse blood, a large number of CD3+ lymphocytes infiltrated in tumor tissues and E-cadherin was up-regulated in cancer cells, suggesting that Ad5F11bSP-Rantes altered the TME and induced a reversal of cancer cell epithelial–mesenchymal transition (EMT). In conclusion, oncolytic adenovirus can exert the oncolytic effect and the chemotactic effect of immune cells and realize the synergy of multiple anticancer effects. This strategy creates a candidate treatment for the optimization of breast cancer, especially TNBC, combination therapy.

Although acupuncture (AT) is used in the treatment of CRF, the evidence from different systematic reviews (SRs) of AT has not yet been comprehensively evaluated. Moxibustion, which is a treatment method that is well established within Traditional East Asian Medicine, applies the heat of burning herbs towards or onto special points on the skin. Commonly, the herb Artemisia vulgaris, is used. It has been used for palliative cancer care, as well as for CRF. The aim of this overview was to evaluate the efficacy of AT and moxibustion in the management of CRF. Eleven databases were searched through for studies that were published from their dates of inception to February 2022. The study selection, the data extraction, and the assessment were performed independently by two researchers. The methodological and report quality were assessed by using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool. The evidence quality was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Fifteen SRs on AT (n = 10) and moxibustion (n = 5) treatments for CRF were included, and they include 169 randomized controlled trials and 14,392 participants. All of the SRs that were evaluated by the AMASTAR-2 had more than one deficiency, and so all of the SRs were rated as either low or critically low. For the GRADE, 18 outcomes were rated as very-low-quality evidence, 13 as low-quality evidence, 3 as moderate-quality evidence, and 0 as high-quality evidence. Most of the SRs reached the potential benefits of AT for CRF. No serious adverse effects were identified. In conclusion, the evidence suggests that, despite the advantages of AT in terms of the improvement in and the safety of the treatment of CRF, the methodological quality of most of these studies is low, which limits our ability to draw definitive meanings. Further research of high quality is needed in order to confirm these findings.

Background: To date, the coronavirus disease 2019 (COVID-19) pandemic remains ongoing and continues to affect millions of people worldwide. In the effort of fighting this pandemic, there has been an increasing interest in the potential of traditional, complementary, and integrative medicines (TCIMs) in engaging COVID-19. This study presents a bibliometric analysis of the research trends of TCIMs for COVID-19. Methods: Six databases were searched on July 15, 2021, to retrieve all the citations on TCIM-focused randomized controlled trials (RCTs) available on COVID-19. Only RCTs that mentioned at least one TCIMs for the treatment and/or management or COVID-19 were eligible. Data such as number and countries of trials conducted, publication journal, research focus, study design, and sample size were extracted for analysis. Results: The resulting 56 articles were authored by 553 unique authors, and included 28 English articles, 19 Chinese articles with English abstracts, and 9 Chinese articles without English abstract. Analyses had shown that China was the dominant country with TCIM related RCT publications, followed by India and the United States. The included articles were published across 24 English journals and 22 Chinese journals with a wide range of impact factors from 0.220 to 56.272. The most commonly studied TCIM modalities included Chinese herbal decoction (n=12) and Chinese patent medicine (n=16). In terms of study designs, TCIM interventions were integrated with standard medicine across the trials with most trials having a small to medium sample size and open-labeled. Conclusion: This bibliometric analysis of RCTs demonstrated the research trends and characteristics of TCIM utilized in COVID-19 research. Although there are still many research gaps and limitations for pandemic research, the publication of TCIM-focused RCTs is anticipated to show a continuously increasing trend.

BackgroundPeer review is widely used in academic fields to assess a manuscript's significance and to improve its quality for publication. This scoping review will assess existing peer review guidelines and/or checklists intended for reviewers of biomedical journals and provide an overview on the review guidelines.MethodsPubMed, Embase, and Allied and Complementary Medicine (AMED) databases were searched for review guidelines from the date of inception until February 19, 2021. There was no date restriction nor article type restriction. In addition to the database search, websites of journal publishers and non-publishers were additionally hand-searched.ResultsOf 14,633 database publication records and 24 website records, 65 publications and 14 websites met inclusion criteria for the review (78 records in total). From the included records, a total of 1,811 checklist items were identified. The items related to Methods, Results, and Discussion were found to be the highly discussed in reviewer guidelines.ConclusionThis review identified existing literature on peer review guidelines and provided an overview of the current state of peer review guides. Review guidelines were varying by journals and publishers. This calls for more research to determine the need to use uniform review standards for transparent and standardized peer review.Protocol registrationThe protocol for this study has been registered at Research Registry (www.researchregistry.com): reviewregistry881.

Background: Medical observation period is a period of 14 days after any exposure to coronavirus disease 2019 (COVID-19) occurred. This review aimed to summarize and analyze the herbs and herbal formulae recommended by available guidelines. Methods: A total of 14 sources were searched for potential guidelines that provide herbal medicine treatment for the medical observation period of COVID-19. We summarized and analyzed the recommended herbal formulae and performed a network analysis to identify the relationship between herbs. Results: We found 9 guidelines that provide herbal formula for medical observation based on clinical manifestation. There are 12 herbal formulae with a total of 53 herbs recommended by the guidelines. The result of our network analysis showed that the herb Citri Reticulatae Pericarpium (Chen Pi) strongly paired with the herb Glycyrrhizae Radix et Rhizoma (Gan Cao). Conclusion: This review briefly summarized the usage of herbal medicine for the medical observation period of COVID-19 and may serve as a reference for future studies. More research is needed in the future to provide evidence on the usage of herbal medicine in various phases of COVID-10.

Background: Coronavirus disease 2019 (COVID-19) is pandemic and has caused illness to many people worldwide. This review aimed to summarize and analyze the herbal formulae provided by the guidelines for their pattern identifications (PIs) and compositions of herbs to treat patients with COVID-19. Methods: We searched 7 data sources for eligible traditional medicine guidelines up to March 6, 2020 and found a total of 28 traditional medicine guidelines that provide treatment measures for COVID-19. Results: Of the 28 guidelines, there were 26 government-issued Chinese guidelines and 2 Korean guidelines. After standardizing the terminology of the PIs and herbal formulae, there were 8 PIs and 23 herbal formulae for the mild stage, 11 PIs and 31 herbal formulae for the moderate stage, 8 PIs and 21 herbal formulae for the severe stage, and 6 PIs and 23 herbal formulae for the recovery stage in the Chinese guidelines. In the Korean guidelines, there were 4 PIs and 15 herbal formulae for the mild stage, 3 PIs and 3 herbal formulae for the severe stage, and 2 PIs and 2 herbal formulae for the recovery stage. In the frequency analysis of herbs, Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum, Ephedrae Herba, and Gypsum Fibrosum were found to be the herbs with the high frequency of usage in the Chinese guidelines. Conclusion: This review can be used as guidance for the traditional medicine treatment of COVID-19. Clinical evidence is needed in the future to evaluate the efficacy of traditional medicine.

Background and Objectives: This review aimed to provide an updated review of evidence regarding the effects of aromatherapy in relieving symptoms of burn injuries, focusing on pain and physiological distress. Materials and Methods: Fifteen databases (including five English databases, four Korean medical databases, and four Iranian databases) and trial registries were searched for studies published between their dates of inception and July 2021. Two review authors individually performed study selection, data extraction, and risk of bias assessment, and any discrepancies were solved by a third review author. Results: Eight RCTs met our inclusion criteria and were analyzed in this updated systematic review. Our meta-analyses revealed that inhaled aromatherapy plus routine care showed beneficial effects in relieving pain after dressing, as compared to placebo plus routine care (p < 0.00001) and routine care alone (p = 0.02). Additionally, inhaled aromatherapy plus routine care (p < 0.00001) and aromatherapy massage plus routine care (p < 0.0001) also showed superior effects in calming anxiety, as compared to routine care alone. None of the included studies reported on AEs. Overall, the risk of bias across the studies was concerning. Conclusions: This updated review and synthesis of the studies had brought a more detailed understanding of the potential application of aromatherapy for easing the pain and anxiety of burn patients.

This review aims to evaluate the effectiveness of acupressure as a treatment method for osteoarthritis. Fourteen electronic databases were searched from the date of inception until 16 March 2021, for eligible studies. Studies comparing acupressure with sham acupuncture, no intervention or conventional intervention were eligible for inclusion. The risk of bias of the included studies was assessed using the Cochrane Collaboration’s Risk of Bias Assessment tool Version 2.0. A total of eight trials were included in this review, focusing on the seven trials investigating knee osteoarthritis. The risk of bias is judged as low in only two trials and concerning in the remaining six trials. The meta-analysis showed that acupressure has equivalent effects in reducing pain (p = 0.12), relieving stiffness (p = 0.38), and improving physical function (p = 0.12), as compared to sham acupressure. Pooled results also showed similar results where acupressure has an equivalent effect in reducing pain (p = 0.09), and relieving stiffness (p = 0.68), but showed a favorable effect in improving physical function of joints (MD –6.30, CI 95%: −11.69 to −0.92, p = 0.02), as compared to no intervention. For acupressure complementing conventional intervention, pooled results showed superior effects for easing pain compared to conventional intervention alone (MD −3.72, 95% CI: −4.84 to −2.61, p < 0.00001). Overall, the studies included in this review have concerning quality and suffer from small sample sizes, and the findings of this review should be interpreted with caution. More clinical trials with proper methodology are needed to confirm the effectiveness of acupressure for osteoarthritis.

This study aimed to describe and assess the current evidence in systematic reviews on cupping therapy for various conditions. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure, and six Korean databases for systematic reviews of trials on cupping treatments for any condition published prior to March 2021. We used a bubble plot to graphically display the clinical topics, the number of articles, the number of participants in the total population, confidence, and effectiveness. Thirteen systematic reviews that met the inclusion criteria were included in the evidence map, and 16 bubbles were created. The findings from six reviews showed potential benefits of cupping for conditions such as low back pain, ankylosing spondylitis, knee osteoarthritis, neck pain, herpes zoster, migraine, plaque psoriasis, and chronic urticaria. Cupping has been applied in a variety of clinical areas, and systematic reviews in a few of these areas have demonstrated statistically significant benefits. The evidence map provides a visual overview of cupping research volume and findings. Evidence mapping can facilitate the transfer of knowledge from researchers to policymakers and promote research on musculoskeletal pain (such as low back pain, neck pain, and knee osteoarthritis) and skin disease (plaque psoriasis).

This review aimed to investigate the efficacy of integrative medicine (herbal medicine combined with drug therapy) in the treatment of Behcet’s disease (BD). Eleven databases were searched from their inception to 7 December 2020, for randomized control trials (RCTs) that reported the effects of integrative medicine in treating BD. The risk of bias was assessed using seven domain criteria from the Cochrane Collaboration tool. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the quality of evidence. The direction of the effect is also shown in the form of an albatross plot. Sixteen trials met the inclusion criteria and were analyzed. The overall risk of bias was determined to be uncertain. The meta-analysis showed a superior response rate with herbal medicine plus drug therapy (relative risk (RR) 1.19, 95% confidence interval (CI) 1.13 to 1.25, n = 1034, p < 0.00001, I2 = 0%, low certainty of evidence (CoE)) compared to drug therapy. Integrative medicine also lowered the recurrence rate after 2 months of follow-up (RR 0.27, 95% CI 0.09 to 0.76, n = 120, p = 0.01, I2 = 0%, low CoE). The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and skin lesions were also significantly improved using integrative medicine, but equivalent effects were seen for oral ulcers, genital ulcers, and eye inflammation. Minor adverse events were reported in both groups. Our findings suggest that herbal medicine combined with drug therapy is more effective for the treatment of BD than drug therapy alone. Although the type of drug therapy used varied across the studies, integrative medicine was shown to improve the total response rate, skin lesions, the ESR, and the CRP level. However, the overall risk of bias of the studies was concerning, and the CoE was low. Information on adverse events (AEs) was also insufficient. In addition, the number of studies included for data synthesis for most outcomes was small. Future studies with rigorous RCTs may help establish the efficacy of integrative medicine in the treatment of BD.

Hypertension has been a crucial public health challenge among adults. This study aimed to develop a novel method for non-contact prediction of hypertension using facial characteristics such as facial features and facial color. The data of 1099 subjects (376 men and 723 women) analyzed in this study were obtained from the Korean Constitutional Multicenter Study of Korean medicine Data Center (KDC) at the Korea Institute of Oriental Medicine (KIOM). Facial images were collected and facial variables were extracted using image processing techniques. Analysis of covariance (ANCOVA) and Least Absolute Shrinkage and Selection Operator (LASSO) were performed to compare and identify the facial characteristic variables between the hypertension group and normal group. We found that the most distinct facial feature differences between hypertension patients and normal individuals were facial shape and nose shape for men in addition to eye shape and nose shape for women. In terms of facial colors, cheek color in men, as well as forehead and nose color in women, were the most distinct facial colors between the hypertension groups and normal individuals. Looking at the AUC value, the prediction power for women is better than men. In conclusion, we managed to explore and identify the facial characteristics variables related to hypertension. This study may provide new evidence in the validity of predicting hypertension using facial characteristics.

This study aims to investigate the association between hypertension and facial complexion and determine whether facial complexion is a predictor for hypertension. Using the Commission internationale de l’éclairage L*a*b* (CIELAB) color space, the facial complexion variables of 1099 subjects were extracted in three regions (forehead, cheek, and nose) and the total face. Logistic regression was performed to analyze the association between hypertension and individual color variables. Four variable selection methods were also used to assess the association between hypertension and combined complexion variables and to compare the predictive powers of the models. The a* (green-red) complexion variables were identified as strong predictors in all facial regions in the crude analysis for both genders. However, this association in men disappeared, and L* (lightness) variables in women became the strongest predictors after adjusting for age and body mass index. Among the four prediction models based on combined complexion variables, the Bayesian approach obtained the best predictive in men. In women, models using three different methods but not the stepwise Akaike information criterion (AIC) obtained similar AUC values between 0.82 and 0.83. The use of combined facial complexion variables slightly improved the predictive power of hypertension in all four of the models compared with the use of individual variables.

Patients with Behçet’s disease often use complementary and alternative medicine for treating their symptoms, and herbal medicine is one of the options. This systematic review provides updated clinical evidence of the effectiveness of herbal medicine for the treatment of Behçet’s disease (BD). We searched eleven electronic databases from inception to March 2020. All randomized controlled trials (RCTs) or quasi-RCTs of BD treatment with herbal medicine decoctions were included. We used the Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias and the grading of recommendations assessment, development and evaluation (GRADE) approach to assess the certainty of evidence (CoE). Albatross plot was also used to present the direction of effect observed. Eight studies were included. The risk of bias was unclear or low. The methodological quality was low or very low. Seven RCTs showed significant effects of herbal medicine on the total response rate (Risk ratio, RR 1.26, 95% CI 1.09 to 1.45, seven studies, very low CoE). Four RCTs showed favorable effects of herbal medicine on the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level compared with drug therapy. Herbal medicine favorably affected the ESR (MD −5.56, 95% CI −9.99 to −1.12, p = 0.01, I2 = 96%, five studies, very low CoE). However, herbal medicine did not have a superior effect on CRP. Two RCTs reported that herbal medicine significantly decreased the recurrence rate after three months of follow-up (RR 0.23, 95% CI 0.09 to 0.63, two studies, low CoE). Our findings suggest that herbal medicine is effective in treating BD. However, the included studies had a poor methodological quality and some limitations. Well-designed clinical trials with large sample sizes are needed.

Fennel is used as an alternative treatment for primary dysmenorrhea. This review aims to evaluate the effectiveness and safety of fennel for reducing pain in primary dysmenorrhea. Twenty databases, including English, Korean, Chinese, Japanese, Iranian, and Spanish databases, were searched from inception to 20 October 2020. All randomized controlled trials (RCTs) investigating the effectiveness of fennel for treating primary dysmenorrhea were considered. Two reviewers conducted the data extraction and risk of bias assessment independently. Any discrepancies were resolved through discussion with a third reviewer. A total of 12 studies were included in this review. The pooled results of seven trials showed that the effect of fennel is similar to that of conventional drug therapies in alleviating pain (n = 502, standardized mean difference (SMD): 0.07, 95% confidence interval(CI): −0.08 to 0.21, p < 0.37, I2 = 0%). In comparison with placebo, fennel was seen to have favorable effects on reducing pain in primary dysmenorrhea (n = 468, SMD: −3.27, 95% CI: −5.28 to −1.26, p = 0.001, I2 = 98%). Only three studies assessed adverse events (AEs), and one study reported minor AEs. Although the risk of bias for all the included studies was moderate, potential publication bias was observed due to the presence of a greater number of small studies with favorable effects. This systematic review concludes that fennel is as effective as conventional drug therapies in alleviating pain in primary dysmenorrhea. More studies that include more diverse populations and robust evidence of fennel’s effects will be needed in future research endeavors.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. Methods: Twelve databases were searched through 12 May 2020. Randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of herbal medicines for the treatment of COVID-19 were eligible. The study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool was used for the assessment of the risk of bias in all included RCTs. Mean differences (MDs), risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and the effect sizes of the studies were pooled. Results: Seven RCTs with a total of 855 patients were included. All included trials compared the combined therapy of herbal medicine with Western medicine to Western medicine alone. The combined therapy significantly improved the total effective rate (RR 1.23, 95% CI 1.13 to 1.34, p < 0.001), cough symptom disappearance rate (RR 1.45, 95% CI 1.12 to 1.89, p = 0.005), and sputum production symptom disappearance rate (RR 1.73, 95% CI 1.19 to 2.50, p = 0.004). Beneficial effects of the combined therapy were also seen in TCM syndrome score of cough (MD −1.18, 95% CI −1.34 to −1.03, p < 0.001), fever (MD −0.62, 95% CI −0.79 to −0.45, p < 0.001), dry and sore throat (MD −0.83, 95% CI −1.45 to −0.20, p = 0.009), and fatigue (MD −0.60, 95% CI −1.04 to −0.17, p = 0.007). The overall risk of bias of the included studies was unclear. No serious adverse events were reported. Conclusion: Significant effects of the combined therapy of herbal medicine with Western medicine were found, and revealed the potential role of herbal medicine in treating COVID-19. More high-quality RCTs are needed to further validate the effectiveness and adverse events of herbal medicine in the treatment of COVID-19.

MicroRNAs are small RNA molecules that play a major role in the post-transcriptional regulation of genes and influence the development, differentiation, proliferation, and apoptosis of cells and the development and progression of tumors. The epithelial–mesenchymal transition is a process by which epithelial cells morphologically transform into cells with a mesenchymal phenotype. The epithelial–mesenchymal transition plays a highly important role in tumor invasion and metastasis. Increasing evidence indicates that microRNAs are tightly associated with epithelial–mesenchymal transition regulation in tumor cells. In breast cancer, various microRNA molecules have been identified as epithelial–mesenchymal transition inducers or inhibitors, which, through different mechanisms and signaling pathways, participate in the regulation of breast cancer invasion and metastasis among various biological behaviors. The epithelial–mesenchymal transition–related microRNAs in breast cancer provide valuable molecules for researching cell invasion and metastasis, and they also provide candidate targets that may be significant for the targeted therapy of breast cancer.