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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).

Background: This study aimed to investigate whether placebo control is differently disclosed in drug and non-drug randomised clinical trial (RCT) participant information leaflets (PILs) and how this might affect participant blinding and direction of study outcomes. Methods: PILs were obtained from trials registered in the International Standard Randomised Controlled Trial Number database via email. Placebo descriptions in PILs were categorised as Full Disclosure (FD), Partial Disclosure (PD), or Missing Information (MI). Associations between intervention type (drug or non-drug)/placebo disclosure (FD or PD/MI) and participant blinding success/trial outcome direction (positive or non-positive) were examined using a two-sided Fisher's exact test. Results: Of 116 collected PILs, 56 % were for drug trials and 44 % were for non-drug trials. Among them, 88 PILs had the corresponding publications available and 68 reports specified primary outcomes. Drug trials were more likely to fully disclose placebo information than non-drug trials (92.3 % vs. 74.5 %, p < 0.05). However, the success rate of blinding was only reported in 3 out of 88 trial publications (3.4 %), precluding further analysis. Furthermore, there was no significant association between the direction of trial results and the type of intervention or placebo disclosure. Conclusion: Our study findings suggest that drug and non-drug RCTs might differ in the way they reveal placebo control information. Further research is warranted to understand what leads to more common PD of placebo information in non-drug trials than drug trials and to determine the optimal placebo control disclosure in specific trial context.

Abstract Background The B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors. Methods In this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo. Results ITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues. Conclusions Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT), which is to be used with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when real and sham acupuncture needles are used in a study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist in the reporting of sham acupuncture procedures and related components.

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

Abstract Objective The description of controls is important in acupuncture clinical trials to interpret its effectiveness without fallacy. This paper aims to evaluate the reporting quality of acupuncture studies on the characteristics of sham needles. Study design and setting Using a checklist developed from previously published reporting guidelines, the distribution of reported items and changes of reporting rates over time were investigated. Two-way ANOVA and linear regression were conducted. Results Original articles of RCTs of any design involving sham needles as controls were eligible for assessment. 117 trials from three 2-year time periods between 2009 and 2018 were included. Seven items out of 25 were reported in more than 50% of the studies. While significant differences of reporting scores among categories were observed, there were no significant differences among time periods; no significant improvement was observed over time. Conclusions Low reporting qualities of sham needles used in acupuncture studies may influence how researchers understand the effectiveness of acupuncture. This study evaluated previous publications from 2009 to 2018 and found that reporting qualities on sham needles did not improve over time. Further studies are required to validate the items used in this study to endorse better reporting of controls in acupuncture trials.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when both real and sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting of sham acupuncture procedures and the related components.

BackgroundObesity is a public health issue worldwide. Conversational agents (CAs), also frequently called chatbots, are computer programs that simulate dialogue between people. Owing to better accessibility, cost-effectiveness, personalization, and compassionate patient-centered treatments, CAs are expected to have the potential to provide sustainable lifestyle counseling for weight management. ObjectiveThis systematic review aimed to critically summarize and evaluate clinical studies on the effectiveness and feasibility of CAs with unconstrained natural language input for weight management. MethodsPubMed, Embase, the Cochrane Library (CENTRAL), PsycINFO, and ACM Digital Library were searched up to December 2022. Studies were included if CAs were used for weight management and had a capability for unconstrained natural language input. No restrictions were imposed on study design, language, or publication type. The quality of the included studies was assessed using the Cochrane risk-of-bias assessment tool or the Critical Appraisal Skills Programme checklist. The extracted data from the included studies were tabulated and narratively summarized as substantial heterogeneity was expected. ResultsIn total, 8 studies met the eligibility criteria: 3 (38%) randomized controlled trials and 5 (62%) uncontrolled before-and-after studies. The CAs in the included studies were aimed at behavior changes through education, advice on food choices, or counseling via psychological approaches. Of the included studies, only 38% (3/8) reported a substantial weight loss outcome (1.3-2.4 kg decrease at 12-15 weeks of CA use). The overall quality of the included studies was judged as low. ConclusionsThe findings of this systematic review suggest that CAs with unconstrained natural language input can be used as a feasible interpersonal weight management intervention by promoting engagement in psychiatric intervention-based conversations simulating treatments by health care professionals, but currently there is a paucity of evidence. Well-designed rigorous randomized controlled trials with larger sample sizes, longer treatment duration, and follow-up focusing on CAs’ acceptability, efficacy, and safety are warranted.

Sham acupuncture should have two distinct features: first, it must be morphologically similar to verum acupuncture for blinding purposes, and second, it must not exert physiologically expected effects of verum acupuncture. While several types of sham acupuncture are currently used, there are on-going debates on which sham acupuncture can meet the criteria for being an appropriate control intervention in acupuncture research. In view of this situation, it is unreasonable to regard the use of sham acupuncture in acupuncture research as the same as the use of placebo drugs in drug research. Given the current research evidence that sham acupuncture can exert not only the originally expected non-specific effects but also sham acupuncture-specific effects, it would be misleading to simply regard sham acupuncture as the same as placebo. Therefore, researchers should be cautious when using the term sham acupuncture in clinical investigations.

Abstract Background Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease that affects 1–3% of adults worldwide. Currently, it is not possible to completely cure AD; therefore, alternative treatments need to be developed to meet the patients’ needs. Here, based on our previous pilot study, we conducted the first confirmatory randomized controlled trial to evaluate the effect of acupuncture in patients with mild to moderate AD. Methods A randomized, participant- and assessor-blinded, sham-controlled trial was designed with an intervention period twice-weekly for 4 weeks and a 4-week follow-up. We equally allocated 36 participants to the verum acupuncture (VA) and sham acupuncture (SA) groups. The main outcome measure was the change in SCORing Atopic Dermatitis index (SCORAD) score before and after treatment. Results A total of 36 participants, aged 19 to 38 years, were enrolled, and 35 were included in the intention-to-treat analyses. The mean change in total SCORAD score differed significantly among the two groups at 4 weeks after randomization (P

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.

SCF (Supply Chain Finance), as an emerging technology-driven financial optimization approach, has grown quickly worldwide with the development of information technology. China is one noteworthy country influenced by SCF development; its traditional financial market structure dominated by banks is undergoing change. The E-commerce-centered SCF has evolved into the representative capital provider in the new financial “Blue Ocean” market. For capturing competitiveness, Chinese JD (Jingdong) SCF practice backed to JD E-commerce is a typical example involving business model innovations, but with few previous related studies on this aspect. Therefore, to fill the research gap, this paper introduces a hybrid theoretical analysis of the BMC (Business Model Canvas) considering a three-layer strategic innovation structure and financial analysis regarding a modified competitive advantages-gaining model to comprehensively explore the recent innovative development and transformation of JD SCF business based on the perspective of competitive advantages. This study identifies JD SCF’s two times of business model innovations that benefit from its sustainable development; verifies that “cost”, “differentiation”, and “focused strategy” are three means for JD SCF practice gaining competitiveness at different development stages and simultaneously emphasizes that the latter two are influenced by business model innovation. The mixed analysis work in this paper may contribute both theoretical and practical implications.

This review examined recently published (July 2014 to June 2017), randomized controlled trials (RCTs) which investigated the safety and effectiveness of combined Korean medicine/complementary alternative medicine (CAM) and Western medicine, to indicate the direction for integrative medical practice. The Korean Medicine Convergence Research Information Center evidence-based medicine database (KMCRIC EBM DB) was used to retrieve relevant RCTs indexed in the last 3 years. Study design, country, sample size, disease/condition with the Korean Standard Classification of Diseases code, interventions, direction of outcomes, and adverse events were extracted and summarized. A total of 93 RCTs were included in this review. Acupuncture/moxibustion was the most commonly used intervention (n = 47; 51%), and 19% (n = 18) of the studies treated musculoskeletal disorders, followed by circulatory disorders (n = 16; 17%), and mental and behavioral disorders (n = 9; 10%). Integrative treatment was reported as more effective than monotherapy in approximately 83% of these studies. Adverse events were poorly reported in most studies. This review suggests that integrative treatments are feasible, effective, and safe for various diseases/conditions, based on the evidence from recently published RCTs. Future studies on integrative healthcare are warranted.

The dry port can smooth the movement of cargo and eliminate capacity pressure, natural restriction and externalities faced by seaports. A network of dry ports also can reduce the amount of pollution emitted from logistics activities by allowing the increasing share of environmentally friendly modes of transport. The paper suggests a green routing model for dry port selection to increases the percentage of using rail or inland waterway transportation in the journey through dry port, instead of road transportation. This model reduces the amount of emission from logistics activities, such as carbon dioxide (CO2), nitric oxides (NOx) and particulate matter (PM) with the minimum cost, considering both the emission charge and the shipping charge. A case study is conducted for Samsung Thai Nguyen factory in the North of Vietnam to validate the model application. The results indicate that the smallest total cost route saves up to 51% of CO2 and 36.5% of PM emission exhausted than unimodal road transportation. The research provides a useful guideline for new green transport policies of public agents as well as decision-making processes in private companies. Keywords: Dry Port, Green Route, Emission charges, Transportation Charges, Vietnam

A boom in e-commerce in Korea has sparked off high daily-volume demand for small-sized home delivery services, which poses a great challenge to distribution networks, especially in urban areas where traffic congestion, accessibility, and pollution are serious problems. In addition, security issues for people who live in small townhouses and detached houses without security systems and guards have received increasing attention from the government and society. Thus, the introduction of a new alternative for home delivery services, unmanned parcel lockers, is urgent for residents living in these areas. This paper examines and compares potential socio-economic impacts in terms of costs and benefits when such lockers are installed at selected locations in residential areas. The results show that this policy is worthy of adoption, with several undeniable benefits to local communities. In addition, sensitivity analyses estimate the economic performance of this project at different social discount rates, and they check the sensitivity of economic performance based on variations in the variables. The value of travel time savings was identified as a critical and dominating factor directly affecting economic performance.

Flexible metal for Electronic Skin Amorphous alloys have never been such a viable approach for flexible electronics because now their excellent properties are not compromised by the structure and morphology. A collaborative team of scientists led by Prof Sanghun Jeon from Korea Advanced Institute of Science and Technology optimize the performance of a Fe33Zr67 metal alloy for multifunctional skin-like sensors. One critical step is that they understand and control the deposition condition to avoid the porous structure and obtain uniform amorphous alloy films. As a result, the Fe33Zr67 metal alloy possesses higher strength, lower Young's modulus and can be made into pressure sensors, temperature sensors and photosensors when integrated with In-Zn-O thin film transistors. This highly versatile and high performance alloy can be used in many scenarios, such as medical, healthcare and wearable electronics.

Fracture healing is related to osteogenic differentiation and mineralization. Recently, due to the unwanted side effects and clinical limitations of existing treatments, various natural product-based chemical studies have been actively conducted. Albiflorin is a major ingredient in Paeonia lactiflora, and this study investigated its ability to promote osteogenic differentiation and fracture healing. To demonstrate the effects of albiflorin on osteoblast differentiation and calcified nodules, alizarin red S staining and von Kossa staining were used in MC3T3-E1 cells. In addition, BMP-2/Smad and Wnt/β-catenin mechanisms known as osteoblast differentiation mechanisms were analyzed through RT-PCR and western blot. To investigate the effects of albiflorin on fracture healing, fractures were induced using a chainsaw in the femur of Sprague Dawley rats, and then albiflorin was intraperitoneally administered. After 1, 2, and 3 weeks, bone microstructure was analyzed using micro-CT. In addition, histological analysis was performed by staining the fractured tissue, and the expression of osteogenic markers in serum was measured. The results demonstrated that albiflorin promoted osteoblastogenesis and the expression of RUNX2 by activating BMP-2/Smad and Wnt/β-catenin signaling in MC3T3-E1 cells. In addition, albiflorin upregulated the expression of various osteogenic genes, such as alkaline phosphatase, OCN, bone sialoprotein, OPN, and OSN. In the femur fracture model, micro-CT analysis showed that albiflorin played a positive role in the formation of callus in the early stage of fracture recovery, and histological examination proved to induce the expression of osteogenic genes in femur tissue. In addition, the expression of bone-related genes in serum was also increased. This suggests that albiflorin promotes osteogenesis, bone calcification and bone formation, thereby promoting the healing of fractures in rats.

With the globalization of trade and the rapid development of the world economy, the problem of air pollution emissions produced by shipping is becoming more serious. The exhaust gas emitted by ships has become a significant source of air pollution in ocean and coastal areas. In recent years, governments have paid more attention to shipping emissions as a major source of environmental problems. Establishing ship emission inventories plays an important role in formulating ship emission control measures and regulations. This study aimed to propose a framework for calculating ship air pollutant emissions by comprehensively considering processes and methods officially used in developed countries such as the US and those in the EU, as well as South Korean circumstances and available data sets. The framework was divided into three sections: defining the inventory, data collection and analysis of the data, and ship air pollutant emission estimation. The results of this study provided a standard for South Korean domestic port emission inventories. A case study focused on the Gwangyang and Yeosu Ports, one of the leading port areas in South Korea, using adaptive data collection and emission-calculation processes. This study can be used as guidelines when the Ministry of Oceans and Fisheries (MOF) or the Ministry of Environment (MOE) adopts a standard process in South Korea in the near future. Subsequently, it is necessary to establish a national port emission management system to respond to world environmental changes.

As a result of the rapid growth of international trade, atmospheric pollution from transportation has been more topical than ever, especially in dense hub port-cities. The shipping industry should pay more attention corresponding to its contribution to local atmospheric pollution. This paper supports the application of data collected from the vessel tracking service system with a bottom-up approach to generate a comprehensive 2019 local ship emission inventory at Port of Incheon. The calculated emission inventory presented the dominance of CO2 emission and the considerable contribution of NOx and SOx emissions, the significant contribution of auxiliary engines during the hotelling at berth during the year of 2019. Then, based on calculated emission inventory, this study suggested and simulated applicable green policies in the practice: (1) local emission control area realization, (2) vessel speed reduction program, (3) application of cold ironing, and (4) establishment of a national integrated emission platform. The combination of the three first policies could help reduce the significant volume of emitted CO (29%), NOx (30%), SOx (93%), PM10 and PM2.5 (64%), VOC (28%), NH3 (30%), and CO2 (30%).

Background: Clinical research in acupuncture has been criticized for not reflecting real-world practice in terms of diagnosis and intervention. This study aimed to collect data on the principles of diagnosis and selection of acupoints from Korean medicine doctors (KMDs) and analyze the patterns and priorities in decision-making. Methods: The study design was based on the data of an actual patient with functional dyspepsia (FD) (according to Rome III criteria) to create simulated patients, and a KMD specialized in gastrointestinal disorders was allocated to collect the clinical information as objectively as possible. Sixty-nine KMDs were recruited to diagnose a simulated patient based on the actual patient's clinical information, in a manner similar to that performed in their clinics. Results: After the diagnostic procedures were completed, the pattern identification, selected acupoints, reasons for choosing them, and importance of symptoms for deciding their diagnoses were documented. The information needed was clearly distinguishable from those routinely asked in western medicine, and information regarding fecal status, abdominal examination, appetite status, pulse diagnosis, and tongue diagnosis were listed as vital. The doctors identified the patient's pattern as “spleen-stomach weakness”, “liver qi depression”, or “food accumulation or phlegm-fluid retention”. The most frequently selected acupoints were CV12, LI4, LR3, ST36, and PC6. Conclusion: There are common acupoints across different patterns, but pattern-specific acupoints were also recommended. These results can provide useful information to design clinical research and education for better clinical performance in acupuncture that reflects real-world practice.

Background: As it is predicted that large-scale viral diseases will occur more frequently in the future, there are voices that Korean Medicine (KM) community need to discuss the role of KM and what to prepare to play a significant part of national disease control system in the post-Coronavirus Disease 2019 (COVID-19) era. Methods: This paper summarizes the edited highlights of an online video meeting by Google meet on 23 April 2020, organized by the Korean Medicine Convergence Research Information Center. Six speakers who are experts in respiratory medicine, cardiology and neurology, gastroenterology, and neuropsychiatry presented what KM community should prepare for the future acute infectious disease outbreaks by learning from experiences of KM teleconsultation center for COVID-19. Results: Unlike in the past infectious disease outbreaks, KM community has played a bigger part in COVID-19 pandemic in spite of regulatory challenges via activities of KM teleconsultation centers. Telemedicine in pandemic could be more actively utilized in light of the present KM teleconsultation center’s achievements. Data from KM teleconsultation centers would be useful to establish an evidence-base for effectiveness and safety of KM treatments if they are properly collected and analyzed. It might be beneficial to adopt an integrative medicine approach in response to acute viral infectious diseases in the future but the inclusion of KM in the national disease control system is required. Conclusion: The present online discussion suggested possible directions of clinical research in KM for the post-COVID-19 era.

Background: Experiencing difficulties and challenges though COVID-19 pandemic, there are voices that it needs to be discussed to seek direction of basic research and college education of Korean Medicine (KM) so that KM community can play a significant role in the future infectious disease outbreaks. Methods: This paper summarizes the edited highlights of an online video meeting by Google meet on May 19, 2020, organized by the Korean Medicine Convergence Research Information Center. Five researchers specialized in immunology, microbiology, virology, preventive medicine, and herbology, respectively, presented what KM community should prepare for the future acute infectious disease outbreaks by learning from the previous research on antiviral effect of herbs for coronavirus and the experiences of the present COVID-19 pandemic. Results: There are a lot of herbs or natural products with potential anti-coronavirus effects reported from in vitro experiments and despite criticism, many clinical trials on traditional herbal medicine for COVID-19 are being conducted. In addition to establishing research evidence, KM community should train and produce public health professionals among Korean Medicine Doctors (KMDs) and official participation in public healthcare system should be ensured in terms of regulation and policy. Newly developed KM treatments can be interpreted by the KM theories and also should be allowed by regulations for KMDs to utilize them. Conclusion: The present online discussion suggested directions of basic research for acute viral infections diseases utilizing KM and how to enforce relevant education and regulations in the post-COVID-19 era.

Abstract Background While full disclosure of information on placebo control in participant information leaflets (PILs) in a clinical trial is ethically required during informed consent, there have been concerning voices such complete disclosures may increase unnecessary nocebo responses, breach double-blind designs, and/or affect direction of trial outcomes. Taking an example of acupuncture studies, we aimed to examine what participants are told about placebo controls in randomized, placebo-controlled trials, and how it may affect blinding and trial outcomes. Methods Authors of published randomized, placebo-controlled trials of acupuncture were identified from PubMed search and invited to provide PILs for their trials. The collected PILs were subjected to content analysis and categorized based on degree of information disclosure on placebo. Blinding index (BI) as a chance-corrected measurement of blinding was calculated and its association with different information disclosure was examined. The impact of different information disclosure from PILs on primary outcomes was estimated using a random effects model. Results In 65 collected PILs, approximately 57% of trials fully informed the participants of placebo control, i.e. full disclosure, while the rest gave deceitful or no information on placebo, i.e. no disclosure. Placebo groups in the studies with no disclosure tended to make more opposite guesses on the type of received intervention than those with disclosure, which may reflect wishful thinking (BI −0.21 vs. −0.16; p = 0.38). In outcome analysis, studies with no disclosure significantly favored acupuncture than those with full disclosure (standardized mean difference − 0.43 vs. −0.12; p = 0.03), probably due to enhanced expectations. Conclusions How participants are told about placebos can be another potential factor that may influence participant blinding and study outcomes by possibly modulating patient expectation. As we have few empirical findings on this issue, future studies are needed to determine whether the present findings are relevant to other medical disciplines and at the same time a routine practice of fully disclosing placebo information in PILs calls for reevaluation.

Abstract Background Not many studies have investigated individual sensitivity to acupuncture. To explore the intrinsic factors related to individual responses to acupuncture, we reviewed published pre-clinical studies using responder analysis on pain. Methods We searched the PubMed and EMBASE databases to June 2015. We included pre-clinical reports describing responders and non-responders to anti-nociceptive and analgesic effects of acupuncture in animal study. We identified the potential intrinsic factors which might be related with the response to acupuncture. Results Totally, 216 potentially relevant articles were retrieved and 14 studies met our inclusion criteria. Rat (n = 1348) and rabbit (n = 56) were used, and only electroacupuncture (EA) was applied as an intervention. Results showed that high levels of cholecystokinin-8 and receptors were associated with poor responsiveness to EA. Endogenous opioids including β-endorphin and met-enkephalin, descending inhibitory norepinephrine and serotonin system, and hypothalamic 5′-AMP-activated protein kinase seemed to be associated with high-level responses. Spinal levels of neurotransmitters and pro-inflammatory cytokines were also differentially expressed depending on the EA sensitiveness. In the central nervous system, hypothalamus, periaqueductal grey, pituitary gland, and spinal cord were suggested to be involved in the EA responsiveness. Identified individual variations did not seem to be accidental, as the responsiveness to EA was replicated over time. However, methodological issues such as reproducibility, cut-off criteria, and clinical relevance need to be further elaborated. Conclusion Our study suggests that the identification of the biological factors differentiating responders from non-responders is necessary and it may aid in understanding how acupuncture modulates pain.

Background: Acupuncture has been reported to have significant effects, not only in alleviating impaired motor function, but also rescuing dopaminergic neuron deficits in rodent models of Parkinson's disease (PD). However, a systemic analysis of these beneficial effects has yet to be performed.Objective: To evaluate the neuroprotective effect of acupuncture in animal models of PD.Methods: A literature search of the PubMed, MEDLINE, EMBASE, China National Knowledge Infrastructure, Research Information Service System, and Japan Society of Acupuncture and Moxibustion databases was performed to retrieve studies that investigated the effects of acupuncture on PD. The quality of each included study was evaluated using the 10-item checklist modified from the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies. RevMan version 5.3 (Foundation for Statistical Computing, Vienna, Austria) was used for meta-analysis.Results: The 42 studies included scored between 2 and 7 points, with a mean score of 4.6. Outcome measures included tyrosine hydroxylase (TH) level and dopamine content. Meta-analysis results revealed statistically significant effects of acupuncture for increasing both TH levels (33.97 [95% CI 33.15–34.79]; p < 0.00001) and dopamine content (4.23 [95% CI 3.53–4.92]; p < 0.00001) compared with that observed in PD control groups. In addition, motor dysfunctions exhibited by model PD animals were also mitigated by acupuncture treatment.Conclusions: Although there were limitations in the number and quality of the included studies, results of this analysis suggest that acupuncture exerts a protective effect on dopaminergic neurons in rodent models of PD.

Objective: Itch is an unpleasant sensation associated with an urge to scratch and is a major health care issue associated with atopic dermatitis (AD). Contagious itch, i.e., subjective feelings of itchiness induced by watching others’ scratching behavior, is common in patients with AD. Using electroencephalography, we examined alpha (8–13 Hz) oscillations in sensorimotor areas associated with the desire to scratch in patients with AD. Methods: Thirty-six patients with AD and 34 healthy controls (HCs) participated in this study. They evaluated their itch levels after watching short videos of a model scratching or tapping parts of his body. Neural oscillations were recorded from nine electrodes, including those placed over sensorimotor areas. Time–frequency analysis was used to compare mu rhythm suppression over the sensorimotor areas in response to these videos between patients with AD and HCs. Results: The behavioral test showed that the visual stimuli induced increased feelings of itchiness in patients with AD relative to HCs under the tapping and scratching conditions. The time–frequency analysis revealed that mu rhythm suppression in response to scratching images was significantly prominent in patients with AD, but not in HCs. Conclusion: Patients with AD exhibited increased susceptibility to contagious itch. This phenomenon might be related to enhanced mu rhythm suppression in sensorimotor areas of the brain in these patients. Our findings provide new insight into the neurophysiological basis of itch sensations in patients with AD.

Antibody–drug conjugate (ADC) linkers play an important role in determining the safety and efficacy of ADC. The Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linker is a newly developed linker in the form of a di-aryl sulfate structure consisting of phenolic payload and self-immolative group (SIG). In this study, using two bioanalytical approaches (namely “bottom-up” and “middle-up” approaches) via the liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method, in vitro and in vivo linker stability experiments were conducted for the OHPAS linker. For comparison, the valine-citrulline-p-aminobenzyloxycarbonyl (VC-PABC) linker was also evaluated under the same experimental conditions. In addition, the catabolite identification experiments at the subunit intact protein level were simultaneously performed to evaluate the catabolic fate of ADCs. As a result, the OHPAS linker was stable in the in vitro mouse/human plasma as well as in vivo pharmacokinetic studies in mice, whereas the VC-PABC linker was relatively unstable in mice in vitro and in vivo. This is because the VC-PABC linker was sensitive to a hydrolytic enzyme called carboxylesterase 1c (Ces1c) in mouse plasma. In conclusion, the OHPAS linker appears to be a good linker for ADC, and further experiments would be warranted to demonstrate the efficacy and toxicity related to the OHPAS linker.

Previous studies have suggested that acupuncture is effective for ameliorating itch intensity. However, factors associated with the antipruritic effects of acupuncture have yet to be clarified. In a randomized, sham-controlled, crossover trial, we investigated the antipruritic effects of acupuncture against histamine-induced itch in healthy volunteers. Autonomic changes using heart rate variability (HRV) and brain connectivity using functional magnetic resonance imaging (fMRI) were also assessed to identify physiological factors associated with the acupuncture response. Acupuncture significantly reduced itch intensity and skin blood perfusion as assessed by laser Doppler perfusion imaging compared to sham control, indicating the antipruritic effects of acupuncture. In responder and non-responder analysis, the power of normalized high frequency (HF norm) was significantly higher, while the power of normalized low frequency (LF norm) and LF/HF ratio were significantly lower in responders compared to non-responders, suggesting the acupuncture response involved parasympathetic activation. In fMRI analysis, the putamen and the posterior part of the midcingulate cortex (pMCC) were positively connected to itch and negatively correlated with itch intensity in responders. These results suggest that parasympathetic activity and functional connectivity of the putamen and pMCC could be associated with antipruritic response to acupuncture.

BACKGROUND:Recently, porous acupuncture (PA), which is anodized to increase its surface area for higher stimulation intensity, was developed and showed significantly improved therapeutic effects with more comfort as compared with original acupuncture (OA) in vivo. However, the impact of PA on the change of local blood flow as well as its efficacy and acceptability has not yet been confirmed in a clinical trial. In a randomized, controlled crossover clinical trial, we investigated the effects of PA on the change in local blood flow using laser Doppler perfusion imaging and considered the sensation of pain intensity and discomfort severity using a visual analogue scale (VAS) to explore its physiological impact and the possibility of PA in clinical use. METHODS:Twenty-one healthy participants were randomly treated with PA or OA on one side of Zusanli (ST36) and each participant served as his or her own control. Baseline local blood flow and galvanic skin response (GSR) were obtained for 5 min and acupuncture interventions were subsequently performed. Next, local blood flow and GSR were subsequently obtained for 10 min after insertion, 10 min after manipulation, and 5 min after the withdrawal of acupuncture. At the end of the experiment, participants were asked to indicate the sensation of pain intensity at each session of insertion, retention, manipulation, and withdrawal as well as the overall pain intensity and discomfort severity. RESULTS:PA significantly increased the local blood flow as compared with OA and there was no significant difference in GSR between patients treated with PA versus OA in each phase of insertion and manipulation. No significant difference in pain intensity or discomfort severity was found during manipulation, retention, or withdrawal of acupuncture. CONCLUSIONS:These results indicate that PA increases local blood flow, which can be closely related to the observed enhanced performance, without any associated discomfort or pain, suggesting its applicability in clinical practice.

BACKGROUND AND OBJECTIVE:Trial registration is widely endorsed as it is considered not only to enhance transparency and quality of reporting but also to help safeguard against outcome reporting bias and probably spin, known as specific reporting that could distort the interpretation of results thus mislead readers. We planned to investigate the current registration status of recently published randomized controlled trials (RCTs) of acupuncture, outcome reporting bias in the prospectively registered trials, and the association between trial registration and presence of spin and methodological factors in acupuncture RCTs. METHODS:Acupuncture RCTs published in English in recent 5 years (January 2013 to December 2017) were searched in PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Trial registration records identified in the publications and trial registries were classified into prospectively registered, retrospectively registered, or unregistered. Primary outcomes were identified and the direction of the results was judged as statistically significant (positive) or statistically nonsignificant (negative). We compared registered and published primary outcomes to assess outcome reporting bias and assessed whether discrepancies favored statistically significant outcomes. Frequency and strategies of spin in published reports with statistically nonsignificant results for primary outcomes were then identified. We also analyzed whether the trial registration status was associated with spin and quality of methodological factors. RESULTS:Of the 322 included RCTs, 41.9% (n = 135) were prospectively registered. Among 64 studies that were prospectively registered and specified primary outcomes, 25 trials had the discrepancies between the registered and published primary outcomes and 60% of them (15 trials) favored the statistically significant findings. Among 169 studies that specified primary outcomes, trial registration status was not associated with the direction of results, i.e., statistically significant or not. Spin was identified in 56.4% out of 78 studies with statistically nonsignificant primary outcomes and claiming efficacy with no consideration of statistically nonsignificant primary outcomes was the most common strategy for spin. Trial registration status was not statistically different between studies with and without spin. CONCLUSION:While trial registration seemed to have improved over time, primary outcomes in registered records and publications were often inconsistent, tending to favor statistically significant findings and spin was common in studies with statistically nonsignificant primary outcomes. Journal editors and researchers in this field should be alerted to still prevalent reporting bias and spin.

Parkinson's disease (PD) is caused by the selective loss of dopaminergic neurons in the substantia nigra (SN) and the depletion of striatal dopamine (DA). Acupuncture, as an alternative therapy for PD, has beneficial effects in both PD patients and PD animal models, although the underlying mechanisms therein remain uncertain. The present study investigated whether acupuncture treatment affected dopamine neurotransmission in a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found that acupuncture treatment at acupoint GB34 improved motor function with accompanying dopaminergic neuron protection against MPTP but did not restore striatal dopamine depletion. Instead, acupuncture treatment increased dopamine release that in turn, may lead to the enhancement of dopamine availability in the synaptic cleft. Moreover, acupuncture treatment mitigated MPTP-induced abnormal postsynaptic changes, suggesting that acupuncture treatment may increase postsynaptic dopamine neurotransmission and facilitate the normalization of basal ganglia activity. These results suggest that the acupuncture-induced enhancement of synaptic dopamine availability may play a critical role in motor function improvement against MPTP.