Uncoupling the BMP receptor antagonist function from the WNT agonist function of R-spondin 2 using the inhibitory peptide dendrimer RWd.

Signaling by bone morphogenetic proteins (BMPs) plays pivotal roles in embryogenesis, adult tissue homeostasis, and disease. Recent studies revealed that the well-established WNT agonist R-spondin 2 (RSPO2) is also a BMP receptor (BMP receptor type 1A) antagonist, with roles in early Xenopus embryogenesis and human acute myeloid leukemia (AML). To uncouple the BMP antagonist function from the WNT agonist function and to promote development of AML therapeutics, here we identified a 10-mer peptide (RW) derived from the thrombospondin 1 domain of RSPO2, which specifically prevents binding between RSPO2 and BMP receptor type 1A without altering WNT signaling. We also show that a corresponding RW dendrimer (RWd) exhibiting improved half-life relieves inhibition of BMP receptor signaling by RSPO2 in human AML cells, reduces cell growth, and induces differentiation. Moreover, microinjection of RWd in Xenopus embryos ventralizes the dorsoventral embryonic patterning by upregulating BMP signaling without affecting WNT signaling. Our study corroborates the function of RSPO2 as a BMP receptor antagonist and provides a proof of concept for pharmacologically uncoupling BMP antagonist from WNT agonist functions of RSPO2 using the inhibitor peptide RWd with enhanced target selectivity and limited side effects.

Head formation requires Dishevelled degradation that is mediated by March2 in concert with Dapper1.

Dishevelled (Dvl/Dsh) is a key scaffold protein that propagates Wnt signaling essential for embryogenesis and homeostasis. However, whether the antagonism of Wnt signaling that is necessary for vertebrate head formation can be achieved through regulation of Dsh protein stability is unclear. Here, we show that membrane-associated RING-CH2 (March2), a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by regulating the turnover of Dsh protein via ubiquitin-mediated lysosomal degradation in the prospective head region of Xenopus We further found that March2 acquires regional and functional specificities for head formation from the Dsh-interacting protein Dapper1 (Dpr1). Dpr1 stabilizes the interaction between March2 and Dsh in order to mediate ubiquitylation and the subsequent degradation of Dsh protein only in the dorso-animal region of Xenopus embryo. These results suggest that March2 restricts cytosolic pools of Dsh protein and reduces the need for Wnt signaling in precise vertebrate head development.

Illnesses Encountered During Medical Volunteering in Takeo Province, Cambodia.

Background and Objectives: Medical volunteering seeks to meet the clinical needs of underserved areas, but has been criticized for difficulties in addressing local health issues and resultant lack of sustainability. Our team has visited rural Cambodia annually since 2012. This study reports the illnesses encountered during the recent mission and share our experiences to improve the efficiency of medical volunteering. Materials and Methods: Infrastructure, such as public electricity or water, was unavailable, hence most medical care and records were hand-performed. We categorized (1) primary diagnoses (chief complaints) by duration of symptoms, and (2) primary and secondary diagnoses (illnesses that were not related to the chief complaint) by severity of illness since patients commonly reported multiple symptoms. Blood pressure and anthropometric values were also checked and analyzed. Results: We encountered 317 adult and 141 pediatric patients. Among adults, 61.3% had persistent chronic (>6 month) symptoms of their chief complaints. The commonest diagnoses of chronic symptoms were musculoarthritis (31.5%) and gastroesophageal reflux disease and/or gastritis (21.7%). Hypertension and/or cardiac problems were relatively common among males (13.6%). The most common diagnosis among the severest cases (specialized or intensive care recommended) was cardiac problems (14.8%), often with abnormalities in sonography or electrocardiogram. For children, the overwhelming majority of diagnoses were related to acute symptoms and low severity, and approximately half were cases of the common cold. Commonly prescribed drugs were antacids or mucosal protectors (31.3%), Non-steroidal anti-inflammatory drugs (NSAIDs) or other painkillers (27.6%), and antiparasites (17.7%) in adults, and NSAIDs (44.7%) and antiparasites (23.2%) in children. Among adults, 32.7% were diagnosed with hypertension, and body mass index (p = 0.003) and age (p < 0.001) were both correlated with hypertension and its grade. Conclusion: Our study offers practical help to volunteer health workers planning to visit Southeast Asia.

The association between paralytic side and health-related quality of life in facial palsy: a cross-sectional study of the Korea National Health and Nutrition Examination Survey (2008-2012).

BACKGROUND: Facial palsy is known to have correlations with low level of quality of life. However, little is known about the association between preference based health-related quality of life (HRQoL) and paralytic side of facial palsy. METHODS: This study used Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012) data, only when the facial palsy examination had been included in the survey contents. Hierarchical regression analyses were used to obtain optimal regression coefficients in the association between paralytic side of the facial palsy and HRQoL measured by EuroQoL-5 Dimension (EQ-5D). We also analyzed the association between the deteriorated domains of EQ-5D and facial palsy in both subgroups by using multiple logistic regression models. RESULTS: We included the data of 28,106 participants aged ≥19 years who were examined as facial palsy according to House-Brackmann score and completed EQ-5D questionnaire in KNHANES 2008-2012. The mean EQ-5D score was significantly low and percentages of deteriorated numbers in its domains were significantly high in facial palsy group. CONCLUSIONS: These results show that, after adjusting for confounding variables, left facial palsy is associated with impaired HRQoL compared with right-sided palsy. Among the domains of EQ-5D, only 'self-care' domain was directly affected by the disease in left facial palsy patients. These findings could be used in developing model and conducting analyses of economic evaluation about facial palsy interventions.

Efficacy and safety of acupuncture for functional constipation: a randomised, sham-controlled pilot trial.

BACKGROUND: The prevalence of functional constipation (FC) is 3-27%, and FC has been reported to cause discomfort in daily life and various complications. The treatment for FC depends on laxatives, and thus, effective and non-toxic alternative treatments are needed. METHODS: We conducted a randomised, sham-controlled parallel-design, pilot trial. Participants with FC were randomly assigned to either the real acupuncture (RA) or sham acupuncture (SA) group. The RA consisted of eight fixed acupuncture points (bilateral ST25, ST27, BL52 and BL25) and four additional points targeted to the individual based on Traditional Korean medicine (TKM). SA consisted of shallow acupuncture insertion at 12 non-acupuncture points. Twelve sessions were provided over 4 weeks. The outcome measures were weekly defecation frequency (DF), spontaneous complete bowel movement (SCBM), Bristol stool scale (BSS) score and constipation assessment scale (CAS) score. The participants were followed for 4 weeks after the treatment. RESULTS: Thirty participants were enrolled (15:15). The mean DF were 5.86 ± 5.62, 5.43 ± 3.39 and 5.79 ± 3.64 in the RA group and 3.73 ± 1.62, 5.00 ± 1.77 and 5.40 ± 1.96 in the SA group at weeks 1, 5, and 9, respectively. The increases in weekly SCBMs were 2.50 ± 3.86 and 2.71 ± 4.01 with RA and 2.33 ± 2.74 and 1.93 ± 2.25 with SA at weeks 5 and 9, respectively (mean difference [MD] 0.78). The BSS scores were 0.57 ± 1.72 and 1.09 ± 1.30 with RA and 0.15 ± 1.06 and 0.14 ± 0.88 with SA at weeks 5 and 9, respectively (MD 0.95). The CAS score changes were - 3.21 ± 2.91 and - 3.50 ± 3.98 with RA and - 2.67 + ±2.82 and - 2.87 ± 2.95 with SA at weeks 5 and 9, respectively. Greater improvements were observed in subgroup analysis of participants with hard stool. The numbers of participants who developed adverse events (AEs) were equal in both groups (four in each group), and the AEs were not directly related to the intervention. CONCLUSIONS: This clinical trial shows feasibility with minor modifications to the primary outcome measure and comparator. Acupuncture showed clinically meaningful improvements in terms of SCBMs occurring more than 3 times per week and in these improvements being maintained for 4 weeks after treatment completion. As this is a pilot trial, future studies are warranted to confirm the efficacy and safety. TRIAL REGISTRATION: KCT0000926 (Registered on 14 November 2013).

PLD1 regulates Xenopus convergent extension movements by mediating Frizzled7 endocytosis for Wnt/PCP signal activation.

Phospholipase D (PLD) is involved in the regulation of receptor-associated signaling, cell movement, cell adhesion and endocytosis. However, its physiological role in vertebrate development remains poorly understood. In this study, we show that PLD1 is required for the convergent extension (CE) movements during Xenopus gastrulation by activating Wnt/PCP signaling. Xenopus PLD1 protein is specifically enriched in the dorsal region of Xenopus gastrula embryo and loss or gain-of-function of PLD1 induce defects in gastrulation and CE movements. These defective phenotypes are due to impaired regulation of Wnt/PCP signaling pathway. Biochemical and imaging analysis using Xenopus tissues reveal that PLD1 is required for Fz7 receptor endocytosis upon Wnt11 stimulation. Moreover, we show that Fz7 endocytosis depends on dynamin and regulation of GAP activity of dynamin by PLD1 via its PX domain is crucial for this process. Taken together, our results suggest that PLD1 acts as a new positive mediator of Wnt/PCP signaling by promoting Wnt11-induced Fz7 endocytosis for precise regulation of Xenopus CE movements.

Moxibustion for cancer-related fatigue: study protocol for a randomized controlled trial.

BACKGROUND: Cancer-related fatigue is one of the most common symptoms experienced by cancer patients, and it diminishes their quality of life. However, there is currently no confirmed standard treatment for cancer-related fatigue, and thus, many patients who suffer cancer-related fatigue seek complementary and alternative medicines such as moxibustion. Moxibustion is one of the most popular therapies in traditional Korean medicine used to manage fatigue. Recent studies have also demonstrated that moxibustion is effective for treating chronic fatigue. However, there is insufficient evidence supporting the effect of moxibustion against cancer-related fatigue. The aim of this study is to assess the efficacy and safety of moxibustion treatment for cancer-related fatigue. METHODS/DESIGN: A multi-center, three-armed parallel, randomized controlled trial will be conducted. Ninety-six patients with cancer-related fatigue will be recruited from three clinical research centers. They will be randomly allocated to one of three groups in a 1:1:1 ratio. The moxibustion group will receive moxibustion treatment at CV8, CV12, LI4 and ST36. The sham moxibustion group will receive sham moxibustion at non-acupoints. Both the moxibustion and sham moxibustion groups will receive 30-min treatments twice a week for 8 weeks. The usual care group will not receive moxibustion treatment. All participants will be educated via a brochure on how to manage cancer-related fatigue in daily life. The outcome measurements will be evaluated at baseline, week 5, week 9, and week 13 by assessors who are blinded to the group allocation. The primary outcome measure will be the mean change in the average scores of the Brief Fatigue Inventory before and after treatments between groups. The secondary outcome measures will be the mean difference in changes from baseline of the Brief Fatigue Inventory, functional assessments of cancer therapy-fatigue, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 scores, and Montreal Cognitive Assessment scores between groups. Safety will be assessed by monitoring adverse events at each visit. DISCUSSION: The results of this study will provide evidence to confirm whether moxibustion can be used as a therapeutic option for treating cancer-related fatigue. TRIAL REGISTRATION: Clinical Research Information Service KCT0002170 . Registered 16 December 2016.

Current utilization and influencing factors of complementary and alternative medicine among children with neuropsychiatric disease: a cross-sectional survey in Korea.

BACKGROUND: Complementary and alternative medicine (CAM) is widespread but has various utilization rates according to country and the condition of patients. Generally, CAM is more frequently used in diseases that have no clear treatment method in conventional medicine. Therefore, a high utilization rate of CAM can be assumed in pediatric neurological diseases, but few studies have investigated the utilization of CAM in children with neuropsychiatric diseases. In particular, studies regarding the current use of CAM are scarce. METHODS: We conducted a survey of the parents or caregivers of patients who visited the pediatric rehabilitation clinic, pediatric neurology clinic, or pediatric psychiatry clinic at one university hospital from April to July 2011. We analyzed the factors that affect the utilization of CAM and other rehabilitation therapies. RESULTS: Among the 578 patients recruited, 258 patients have ever received CAM (51.5%), and the current CAM utilization rate was 19.0% (110 patients). Two hundred patients (34.6%) were currently receiving only other rehabilitation therapies, and 268 patients (46.4%) were currently receiving no type of therapy. The rate of current CAM usage was significantly high in epilepsy patients. The ORs of 1-6-year-old and 7-12-year-old children compared with 13-19-year-old children were 3.14 (95 % CI 1.31-7.53) and 3.34 (95% CI 1.64-6.79), respectively, and the OR of the group with longer disease duration (≥48 months) compared with the group with shorter disease duration was 3.36 (95% CI 1.71-6.59). Only the age and disease duration showed statistically significant differences between the patients who were administered CAM and those who received other rehabilitation therapies (p < 0.0001). CONCLUSIONS: CAM is preferred by patients under 13 years of age compared with patients aged 13-19 years, whereas other rehabilitation therapies are preferred by patients aged 1-6 years, followed by those aged 6-12 years and then by those aged 13-19 years. The patient's age and disease duration are the major factors influencing CAM use. Future studies should specify particular diseases, rather than combining all types of neuropsychiatric diseases, and include the socio-economic status of the parents.

R-Spondin 2 governs Xenopus left-right body axis formation by establishing an FGF signaling gradient.

Establishment of the left-right (LR, sinistral, dextral) body axis in many vertebrate embryos relies on cilia-driven leftward fluid flow within an LR organizer (LRO). A cardinal question is how leftward flow triggers symmetry breakage. The chemosensation model posits that ciliary flow enriches a signaling molecule on the left side of the LRO that promotes sinistral cell fate. However, the nature of this sinistralizing signal has remained elusive. In the Xenopus LRO, we identified the stem cell growth factor R-Spondin 2 (Rspo2) as a symmetrically expressed, sinistralizing signal. As predicted for a flow-mediated signal, Rspo2 operates downstream of leftward flow but upstream of the asymmetrically expressed gene dand5. Unexpectedly, in LR patterning, Rspo2 acts as an FGF receptor antagonist: Rspo2 via its TSP1 domain binds Fgfr4 and promotes its membrane clearance by Znrf3-mediated endocytosis. Concordantly, we find that at flow-stage, FGF signaling is dextralizing and forms a gradient across the LRO, high on the dextral- and low on the sinistral side. Rspo2 gain- and loss-of function equalize this FGF signaling gradient and sinistralize and dextralize development, respectively. We propose that leftward flow of Rspo2 produces an FGF signaling gradient that governs LR-symmetry breakage.

ß-Arrestin 1 mediates non-canonical Wnt pathway to regulate convergent extension movements.

ß-Arrestins are multifaceted proteins that play critical roles in termination of G protein-coupled receptor (GPCR) signaling by inducing its desensitization and internalization as well as in facilitation of many intracellular signaling pathways. Here, we examine using Xenopus embryos whether ß-arrestin 1 might act as a mediator of ß-catenin-independent Wnt (non-canonical) signaling. Xenopus ß-arrestin 1 (xßarr1) is expressed in the tissues undergoing extensive cell rearrangements in early development. Gain- and loss-of-function analyses of xßarr1 revealed that it regulates convergent extension (CE) movements of mesodermal tissue with no effect on cell fate specification. In addition, rescue experiments showed that xßarr1 controls CE movements downstream of Wnt11/Fz7 signal and via activation of RhoA and JNK. In line with this, xßarr1 associated with key Wnt components including Ryk, Fz, and Dishevelled. Furthermore, we found that xßarr1 could recover CE movements inhibited by xßarr2 knockdown or its endocytosis defective mutant. Overall, these results suggest that ß-arrestin 1 and 2 share interchangeable endocytic activity to regulate CE movements downstream of the non-canonical Wnt pathway.

ROTACs leverage signaling-incompetent R-spondin for targeted protein degradation.

Proteolysis-targeting chimeras (PROTACs) are an emerging technology for therapeutic intervention, but options to target cell surface proteins and receptors remain limited. Here we introduce ROTACs, bispecific WNT- and BMP-signaling-disabled R-spondin (RSPO) chimeras, which leverage the specificity of these stem cell growth factors for ZNRF3/RNF43 E3 transmembrane ligases, to target degradation of transmembrane proteins. As a proof-of-concept, we targeted the immune checkpoint protein, programmed death ligand 1 (PD-L1), a prominent cancer therapeutic target, with a bispecific RSPO2 chimera, R2PD1. The R2PD1 chimeric protein binds to PD-L1 and at picomolar concentration induces its lysosomal degradation. In three melanoma cell lines, R2PD1 induced between 50 and 90% PD-L1 protein degradation. PD-L1 degradation was strictly dependent on ZNRF3/RNF43. Moreover, R2PD1 reactivates cytotoxic T cells and inhibits tumor cell proliferation more potently than Atezolizumab. We suggest that signaling-disabled ROTACs represent a paradigm to target cell surface proteins for degradation in a range of applications.

Implementation strategy for introducing a clinical skills examination to the Korean Oriental Medicine Licensing Examination: a mixed-method modified Delphi study

PURPOSE: This study investigated the validity of introducing a clinical skills examination (CSE) to the Korean Oriental Medicine Licensing Examination through a mixed-method modified Delphi study METHODS: A 3-round Delphi study was conducted between September and November 2022. The expert panel comprised 21 oriental medicine education experts who were officially recommended by relevant institutions and organizations. The questionnaires included potential content for the CSE and a detailed implementation strategy. Subcommittees were formed to discuss concerns around the introduction of the CSE, which were collected as open-ended questions. In this study, a 66.7% or greater agreement rate was defined as achieving a consensus. RESULTS: The expert panel's evaluation of the proposed clinical presentations and basic clinical skills suggested their priorities. Of the 10 items investigated for building a detailed implementation strategy for the introduction of the CSE to the Korean Oriental Medicine Licensing Examination, a consensus was achieved on 9. However, the agreement rate on the timing of the introduction of the CSE was low. Concerns around 4 clinical topics were discussed in the subcommittees, and potential solutions were proposed. CONCLUSION: This study offers preliminary data and raises some concerns that can be used as a reference while discussing the introduction of the CSE to the Korean Oriental Medicine Licensing Examination.

Electroacupuncture for Cancer-Related Cognitive Impairment: A Clinical Feasibility Study.

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

Comparative Effectiveness of Collaborative Treatment with Korean and Western Medicine for Low Back Pain: A Prospective Cohort Study.

In Korea, low back pain is the ailment that is most frequently treated using collaborative care regimens that include aspects of Western and traditional Korean medicine. As part of a national pilot project on the collaboration between Western and Korean medicine, we aimed to investigate the clinical effectiveness of collaborative treatment and compare it with treatment methods that involved only Korean or Western Medicine practices for patients with low back pain. This nationwide, multicenter, prospective, observational, and comparative study spanned 8 weeks, during which patients with low back pain were evaluated at three time points (at baseline, 4 weeks, and 8 weeks). The primary outcome was low back pain-related disability measured by the Oswestry Disability Index, while the secondary outcomes included severity of low back pain (as on a numeric rating scale) and quality of life (as per a 5-level EuroQol-5 dimensions questionnaire). We analyzed 150 patients (including 129 per-protocol cases) and found that the Oswestry Disability Index and 5-level EuroQol-5 dimensions showed statistically significant differences over time between the collaborative treatment group and the sole treatment group after adjusting for sex, income level, and age. Conversely, the numeric rating and EuroQol-visual analog scales showed no significant between-group differences over time. Based on our findings, we believe that collaborative treatment that includes parallelly administered aspects of Western and Korean medicine can benefit patients with low back pain by facilitating functional improvements and lead to a better quality of life.

RSPO2 inhibits BMP signaling to promote self-renewal in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a rapidly progressing cancer, for which chemotherapy remains standard treatment and additional therapeutic targets are requisite. Here, we show that AML cells secrete the stem cell growth factor R-spondin 2 (RSPO2) to promote their self-renewal and prevent cell differentiation. Although RSPO2 is a well-known WNT agonist, we reveal that it maintains AML self-renewal WNT independently, by inhibiting BMP receptor signaling. Autocrine RSPO2 signaling is also required to prevent differentiation and to promote self-renewal in normal hematopoietic stem cells as well as primary AML cells. Comprehensive datamining reveals that RSPO2 expression is elevated in patients with AML of poor prognosis. Consistently, inhibiting RSPO2 prolongs survival in AML mouse xenograft models. Our study indicates that in AML, RSPO2 acts as an autocrine BMP antagonist to promote cancer cell renewal and may serve as a marker for poor prognosis.

R-spondins are BMP receptor antagonists in Xenopus early embryonic development.

BMP signaling plays key roles in development, stem cells, adult tissue homeostasis, and disease. How BMP receptors are extracellularly modulated and in which physiological context, is therefore of prime importance. R-spondins (RSPOs) are a small family of secreted proteins that co-activate WNT signaling and function as potent stem cell effectors and oncogenes. Evidence is mounting that RSPOs act WNT-independently but how and in which physiological processes remains enigmatic. Here we show that RSPO2 and RSPO3 also act as BMP antagonists. RSPO2 is a high affinity ligand for the type I BMP receptor BMPR1A/ALK3, and it engages ZNRF3 to trigger internalization and degradation of BMPR1A. In early Xenopus embryos, Rspo2 is a negative feedback inhibitor in the BMP4 synexpression group and regulates dorsoventral axis formation. We conclude that R-spondins are bifunctional ligands, which activate WNT- and inhibit BMP signaling via ZNRF3, with implications for development and cancer.

Mahaenggamseok-tang, a herbal medicine, for lower respiratory tract infections in pediatric patients: A protocol for systematic review and meta-analysis.

BACKGROUND: The aim of this study is to assess the clinical evidence for or against Mahaenggamseok-tang (MHGT) as a treatment for lower respiratory tract infections (LRTIs) in pediatric patients. METHOD: This systematic review will include randomized clinical trials (RCTs) of MHGT, as a treatment for LRTIs, compared with other therapies such as placebo and western medicine. The search terms will be selected according to the medical subject heading. We will search the following databases for systematic reviews from 2000 to Feb 2020: 5 English databases (The Cochrane Database of Systematic reviews, MEDLINE, Excerpta Medica dataBASE, Allied and Complementary Medicine Database, and Cumulative Index to Nursing and Allied Health Literature), 1 Chinese database, 5 Korean databases (Oriental Medicine Advanced Searching Integrated System, DataBase Periodical Information Academic (DBPIA), Research Information Service System, Korean Studies Information Service System, and National Digital Science Library), and 1 Japanese database (J-Stage). All RCTs of decoctions or alternate forms of MHGT will be included. We will search for all parallel or crossover RCTs without language restrictions. The methodological quality of the RCTs will be assessed using Cochrane risk of bias. Furthermore, the studies will be limited to those performed in children under 16 years of age. RESULTS AND CONCLUSIONS: Our systematic review and meta-analysis will provide evidence for MHGT as a treatment for LRTI. The findings can help practitioners and patients recognize more effective and safer therapeutic methods. PROSPERO REGISTRATION NUMBER: CRD42020165698.

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

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

Moxibustion as an adjunct for lower urinary tract symptoms associated with benign prostate enlargement: A randomized controlled pilot trial.

BACKGROUND: Benign prostatic enlargement (BPE) causes discomfort in daily life, including lower urinary tract symptoms (LUTSs) caused by the enlarged prostate, and requires long-term management as a chronic, irreversible disease. To improve LUTS, certain complementary therapies have been used with or without doctors' directions. Conventional treatments and complementary therapies tend to be combined unsystematically, depending on patient preference; thus, research for safe and efficient combination therapy is warranted. METHODS: Twenty-nine participants were randomly assigned to an integrative group (IG, n = 15) or a conventional group (CG, n = 14). The IG received moxibustion (twice weekly for 4 weeks, at the acupuncture points SP6, LR3, and CV4) and conventional medication for 4 weeks, followed by conventional medication alone for 8 weeks. The CG received conventional medication alone for 12 weeks. The outcome measures were International Prostate Symptom Score (IPSS), patient's global impression of changes (PGIC), maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), and frequency-volume chart. RESULTS: Total IPSS (IG, -2.4 ±â€Š4.2; CG, 0.9 ±â€Š4.0; P = .039), PGIC-A (IG, 3.5 ±â€Š1.0; CG, 2.2 ±â€Š1.0; P = .001), and PGIC-B (IG, 3.5 ±â€Š0.1; CG, 4.7 ±â€Š0.6; P = .004) were significantly improved in the IG compared with the CG, 4 weeks after baseline. Among the IPSS items, incomplete emptying (IG, -0.6 ±â€Š0.7; CG, 0.4 ±â€Š1.2; P = .019), straining (IG, -0.6 ±â€Š0.8; CG, 0.2 ±â€Š1.2; P = .046), and nocturia (IG, -0.8 ±â€Š1.4; CG, 0.1 ±â€Š1.0; P = .045) showed significant differences. The Qmax and PVR volume did not differ significantly at 12 weeks after the baseline. CONCLUSION: Moxibustion can be considered an adjunct therapy to improve LUTS in BPE patients. A full-sized randomized controlled trial would be feasible with comparator modifications and an extended study period. The study design should include a placebo group and narrow the eligibility to subjects who do not respond well to conventional treatments.

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

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