Development of the Korean Medicine Core Outcome Set for Facial Palsy: herbal medicine treatment of patients with facial palsy in primary clinics.

Introduction: Facial palsy (FP) significantly affects the quality of life of patients and poses a treatment challenge in primary healthcare settings. This study aimed to develop a Korean medicine (KM) core outcome set (COS) for FP, with a focus on evaluating the effectiveness of herbal medicine (HM) treatments in KM primary clinics. Methods: Outcomes and effect modifiers related to FP treatments were initially identified through related review articles. Subsequently, experts in the field took part in three rounds of modified Delphi consensus exercises to refine and prioritize these outcomes and effect modifiers. Additionally, primary KM clinicians were involved in a Delphi consensus round to assess the suitability and feasibility of the proposed COS in real-world clinical settings. Results: The initial review of related literature identified 44 relevant studies, resulting in an initial selection of 23 outcomes and 10 effect modifiers. The expert consensus process refined these to 8 key outcomes and 6 effect modifiers, which established the foundation of the COS-FP-KM. Subsequently, primary KM clinicians confirmed the practicality and applicability of the COS, endorsing its suitability for use in KM primary clinics. Conclusion: The COS-FP-KM establishes a standardized approach for assessing HM treatment effectiveness in FP patients in KM primary clinics. The COS-FP-KM encourages consistent outcome reporting and enhances patient care quality. Future work should aim to integrate broader stakeholder perspectives to refine and validate the COS further.

Targeted Tick-Borne Disease Recognition: Assessing Risk for Improved Public Health.

Tick-borne diseases (TBDs) pose a rapidly growing threat to public health. The incidence of TBDs is on the rise, necessitating a comprehensive understanding of the risk factors beyond demographic considerations. This brief report combines a preliminary review of the literature with geographical case mapping to identify the various factors influencing TBD risk. The report highlights the vulnerability of outdoor workers, the importance of outdoor activities, and the role of education in adopting preventive behaviors. Pet ownership and interactions with animals are also associated with an increased risk. The state of Illinois is used as a case study for this report, revealing regional variations in TBD incidence, and linking them to agricultural practices, forested areas, and park accessibility. These findings inform recommendations for targeted prevention strategies, emphasizing the need for detailed geographical data to enhance public health efforts in curbing TBD incidence and risk.

Exploring the Role of Guanylate-Binding Protein-2 in Activated Microglia-Mediated Neuroinflammation and Neuronal Damage.

Neuron damage by microglia, which act as macrophage cells in the brain, can result in various brain diseases. However, the function of pro-inflammatory or anti-inflammatory microglia in the neurons remains controversial. Guanylate-binding protein-2 (GBP2) is expressed and activated in the microglia in the early phase of the inflammatory response and plays an important role in controlling immune responses. In this study, we evaluated whether GBP2 initially reduces the immune response induced by microglia, and whether microglia induce pro-inflammatory functions in neurons via GBP2 expression. In lipopolysaccharide (LPS)-stimulated microglia, we assessed the expression of GBP2 and how it affects neurons via activated microglia. The biological functions of microglia due to the downregulation of the GBP2 gene were examined using short hairpin RNA (shRNA)-RNA-GBP2. Downregulated GBP2 affected the function of mitochondria in the microglia and showed reduced neuronal damage when compared to the control group in the co-culture system. Furthermore, this protein was observed to be highly expressed in the brains of dementia mice. Our results are the first to report that the downregulation of GBP2 in activated microglia has an anti-inflammatory function. This study suggests that the GBP2 gene can be used as a therapeutic target biomarker for inflammation-related neurodegenerative diseases.

Dualistic Effects of PRKAR1A as a Potential Anticancer Target in Cancer Cells and Cancer-Derived Stem Cells.

The integration of innovative medical technologies and interdisciplinary collaboration could improve the treatment of cancer, a globally prevalent and often deadly disease. Despite recent advancements, current cancer therapies fail to specifically address recurrence and target cancer stem cells (CSCs), which contribute to relapse. In this study, we utilized three types of cancer cells, from which three types of CSCs were further derived, to conduct a proteomic analysis. Additionally, shared cell surface biomarkers were identified as potential targets for a comprehensive treatment strategy. The selected biomarkers were evaluated through short hairpin RNA treatment, which revealed contrasting functions in cancer cells and CSCs. Knockdown of the identified proteins revealed that they regulate the epithelial-mesenchymal transition (EMT) and stemness via the ERK signaling pathway. Resistance to anticancer agents was consequently reduced, ultimately enhancing the overall anticancer effects of the treatment. Additionally, the significance of these biomarkers in clinical patient outcomes was confirmed using bioinformatics. Our study suggests a novel cancer treatment strategy that addresses the limitations of current anticancer therapies.

Variations of oxidative potential of PM2.5 in a medium-sized residential city in South Korea measured using three different chemical assays.

Although it is evident that PM2.5 has serious adverse health effects, there is no consensus on what the biologically effective dose is. In this study, the intrinsic oxidative potential (OPm) and the extrinsic oxidative potential (OPv) of PM2.5 were measured using three chemical assays including dithiothreitol (DTT), ascorbic acid (AA), and reduced glutathione (GSH), along with chemical compositions of PM2.5 in South Korea. Among the three chemical assays, only OPmAA showed a statistically significant correlation with PM2.5 while OPmGSH and OPmDTT were not correlated with PM2.5 mass concentration. When the samples were categorized by PM2.5 mass concentrations, the variations in the proportion of Ni, As, Mn, Cd, Pb, and Se to PM2.5 mass closely coincided with changes in OPm across all three assays, suggesting a potential association between these elements and PM2.5 OP. Multiple linear regression analysis identified the significant PM components affecting the variability in extrinsic OPv. OPvAA was determined to be significantly influenced by EC, K+, and Ba while OC and Al were common significant factors for OPvGSH and OPvDTT. It was also found that primary OC was an important variable for OPvDTT while secondary OC significantly affected the variability of OPvGSH.

Understanding Habitats and Environmental Conditions of White-Tailed Deer Population Density and Public Health Data to Aid in Assessing Human Tick-Borne Disease Risk.

The extent of tick-borne diseases (TBDs) in the United States is largely unknown and underreported. Equitable diagnostic and treatment options may vary by geographic location. Triangulating multi-modal data sources informed by a One Health approach provides robust proxies for human TBD risk. Using data from the Indiana Department of Natural Resources collected from hunters during the white-tailed deer (Odocoileus virginianus) hunting season and other sources, we employ a mixed-methods approach based on thematic mapping and mixed effects modelling to determine if deer population density aligns with official disease data at the county level from (1) positive canine serological reports for, anaplasmosis, and Lyme Disease (LD); (2) positive human cases of ehrlichiosis, anaplasmosis, LD, and Spotted Fever rickettsioses; and (3) tick infectivity. We propose the need for multimodal data analysis using a variety of potential proxies to better estimate disease risk and inform public health policy and practice. We find similar spatial distributions between deer population density and human and canine TBDs in northeastern and southern Indiana, which are rural and mixed geographic areas. Overall, LD is more prevalent in the northwest, central-western, and southeastern counties, while ehrlichiosis is more common in the southern counties. These findings hold true across humans, canines, and deer.

The clinical effects of Gyejibongnyeong-Hwan (Gui Zhi Fu Ling Wan) on patients with hyperlipidemia: A study protocol for a multicenter, double-blind, two-armed parallel, investigator-initiated, exploratory randomized controlled trial.

BACKGROUND: Hyperlipidemia, the most common form of dyslipidemia, is associated with an increased risk of atherosclerotic cardiovascular diseases. There is a constant demand for therapeutic agents with relatively few side effects that can be administered from the initial stage of hyperlipidemia, herbal medicines derived from natural products can be considered candidates for treating dyslipidemia. This study aims to explore the feasibility, preliminary effectiveness, and safety of Gyejibongnyeong-Hwan (GBH) in patients with hyperlipidemia. METHODS: This was a 2-armed, parallel, multicenter, and exploratory randomized controlled trial on dyslipidemia. We will recruit 90 patients aged 20 to 65 years with hyperlipidemia between November 2021 and December 2022. Eligible participants will be randomly assigned to receive GBH or placebo granules for 8 weeks and followed up for 4 weeks after 4 weeks of lifestyle modification. The primary outcome is the percentage changes in low-density lipoprotein cholesterol from baseline to week 8. The secondary outcomes are percentage changes in other blood lipid parameters, blood glucose parameters, and blood stasis scores. As an exploratory outcome measure, metabolite analysis will be conducted to observe changes in metabolic patterns. DISCUSSION: This is the first randomized controlled trial to explore the clinical effect and safety of GBH compared to placebo control in patients with hyperlipidemia, thereby potentially facilitating better management of hyperlipidemia. The results of this pilot study could form a foundation for future large-scale confirmatory clinical trials. ETHICS AND DISSEMINATION: This study was permitted by the Ministry of Food and Drug Safety on investigational new drug application on August 12, 2021 and approved by the Institutional Review Board of Kyung Hee University, Seoul, Republic of Korea (KOMCIRB202110012001) on November 26, 2021. The results will be published in a peer-reviewed journal and disseminated electronically and in print.

A Study on the Interoperability Technology of Digital Identification Based on WACI Protocol with Multiparty Distributed Signature.

In digital identity authentication, credentials are typically stored in a digital wallet and authenticated through a single key-based signature and public key verification. However, ensuring compatibility between systems and credentials can be challenging and the existing architecture can create a single point of failure, which can hinder system stability and prevent data interchange. To address this problem, we propose a multiparty distributed signature structure using FROST, a Schnorr signature-based threshold signature algorithm, applied to the WACI protocol framework for credential interaction. This approach eliminates a single point of failure and secures the signer's anonymity. Additionally, by following standard interoperability protocol procedures, we can ensure interoperability during the exchange of digital wallets and credentials. This paper presents a method that combines a multiparty distributed signature algorithm and an interoperability protocol, and discusses the implementation results.

Korean medicine treatment for premature ovarian failure: Three case reports.

INTRODUCTION: Premature ovarian failure (POF) is defined as amenorrhea lasting for more than 4 months before 40 years of age, which is accompanied by a serum follicle-stimulating hormone (FSH) concentration above 40 mlU/mL. POF can cause a series of symptoms associated with low estrogen levels, such as hot flushes, excessive sweating, and infertility. This study aimed to report three cases of POF that were treated successfully with Korean medicine. CASE REPRESENTATION: Three patients with POF were selected for inclusion in this study. The treatment regimen consisted of herbal medicines, electroacupuncture, moxibustion, and Hominis placental pharmacopuncture. The basic treatment period was 3 months, and follow-up was performed after menstrual recovery. Following treatment, all three patients resumed menstruation without any adverse events. One patient also conceived successfully. CONCLUSIONS: These case reports suggest that Korean medicine could be effective for treating POF. Further preclinical and clinical studies are needed to investigate the mechanism of action of herbal medicines and acupuncture in improving menstruation and FSH levels.

Development of the Korean Medicine Core Outcome Set for Primary Dysmenorrhea (COS-PD-KM) for Herbal Medicine Treatment of Primary Dysmenorrhea in Primary Clinics.

The aim of this study was to develop a Korean medicine (KM) core outcome set (COS) for primary dysmenorrhea to evaluate the effectiveness of herbal medicine (HM) in treating primary dysmenorrhea in patients visiting KM primary clinics. Previously reported outcomes were identified through a literature review to define outcomes and effect modifiers (EMs) for the questionnaire. Experts were invited to conduct modified Delphi consensus exercises, and primary care clinicians were invited to conduct Delphi consensus exercises to evaluate suitability and feasibility. Finally, an additional round of a modified Delphi exercise was conducted with experts to obtain a final agreement on the COS. Seventeen outcomes and 15 EMs were included from a literature review, and one effect modifier was suggested by the experts (Phase 1). In Phase 2, after the modified Delphi consensus exercises by experts, 10 outcomes and 11 EMs were included in the COS. The clinicians all agreed on the feasibility of COS (Phase 3). Finally, 10 outcomes and 6 EMs were included in the COS-PD-KM after the final modified Delphi consensus exercise (Phase 4). The effectiveness of HM used in primary clinics could be evaluated with this COS in patients with primary dysmenorrhea. Further studies that involve more relevant stakeholder groups, such as patient representatives and gynecological experts, are needed.

Development of the Korean Medicine Core Outcome Set for Stroke Sequelae: Herbal Medicine Treatment of Elderly Patients With Stroke Sequelae in Primary Clinics.

Objectives: We developed a Korean medicine core outcome set for stroke sequelae (COS-SS-KM) to evaluate the effectiveness and safety of herbal medicine (HM) for stroke sequelae, especially for elderly stroke patients in primary clinics. Methods: We identified previously reported outcomes from a literature review and defined the list of outcomes and effect modifiers for the core outcome set (COS) questionnaire. Three rounds of modified Delphi consensus exercises with experts were conducted online for suitability assessment, and one round of a modified Delphi consensus exercise with primary clinicians was conducted for feasibility assessment. Results: The review identified 17 outcomes and 16 effect modifiers; moreover, six outcomes and one effect modifier were suggested by the experts. The final COS comprised 8 outcomes and 12 effect modifiers for history taking, and experts listed 13 major symptoms of stroke sequelae for symptom assessment. The clinicians agreed on the feasibility of the COS. Conclusion: This COS will help primary care researchers assess the effectiveness of pharmacotherapy, including HM, for elderly patients with stroke sequelae. Future studies should focus on reflecting the opinions of all stakeholders.

Efficacy and safety of acupuncture on oligomenorrhea due to polycystic ovary syndrome: An international multicenter, pilot randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common disorders of reproductive endocrinology affecting women of reproductive age. Our study aims to explore the feasibility of a full-scale trial to evaluate the efficacy and safety of acupuncture for PCOS. METHODS: This study is a two-armed, parallel, multi-country, multi-center, pilot randomized controlled trial (RCT) for PCOS with oligomenorrhea. We will recruit 60 women aged 20 to 40 years with oligomenorrhea due to PCOS. The participants will be randomly assigned to acupuncture and control groups. The acupuncture group will undergo a total of 40 sessions for 16 weeks with usual care. The control group will be managed with usual care (regular meals, sufficient sleep, and appropriate exercise) only. The primary clinical outcome is mean change in menstrual frequency from baseline to 16 weeks and 32 weeks (follow-up) after the start of the trial. The secondary outcomes are menstrual period, levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total testosterone, LH/FSH ratio, antral follicle count and ovarian volume, body mass index, waist hip ratio, acne severity, and health-related quality of life questionnaire scores at 16 and 32 weeks after the start of the trial. DISCUSSION: This is the first protocol for multi-country, multi-center RCTs for PCOS in Korea and China. The control group in this study will be subjected to usual care (regular meals, enough sleep, and appropriate exercise). The results of this study will provide evidence for future clinical decisions and guidelines.This trial has been registered at ClinicalTrials.gov (Identifier: NCT04509817).

Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells.

Breast cancer in women is one of the most common life-threatening malignancies. Despite of the development for the improved treatment, there are still many limitations to overcome. Among them, cancer stem cells (CSCs) are well known for tumor formation, development, cellular heterogeneity, and cancer recurrence. Therefore, to completely cure breast cancer, treatment of both cancer and CSC is required. To selectively target CSCs, we generated a liposome-based smart nano complex using CEACAM 6 (CD66c) antibody (Ab), a novel cell-surface biomarker of breast-derived CSCs (BCSCs) discovered in our previous research. Selective and increased cellular uptake was observed in BCSCs treated with CD66c Ab-conjugated rhodamine-labeled liposomes (CDRHOL) depending on the expression level of CD66c. CD66c Ab-conjugated doxorubicin (DOX)-loaded liposomes (CDDOXL) selectively showed increased cell killing effects in BCSCs with high CD66c expression levels. In an in vivo animal study, CDRHOL showed enhanced accumulation in xenografted BCSC tumors with low delivery into non-target organs. Moreover, mice treated with CDDOXL have assessed the decreased induction ability of immune response by low expression levels of pro-inflammatory cytokines and reduced liver toxicity by histopathological analysis. Finally, the improved antitumor effect of CDDOXL was evaluated in a metastatic BCSC mouse model via systemic administration. Collectively, our study is the first to demonstrate that a multi-functional nano complex using a novel surface biomarker of BCSC may be a more effective therapeutic agent for the treatment of cancer and CSCs.

Carthami Semen Pharmacopuncture Combined with Electroacupuncture on Carpal Tunnel Syndrome: A Retrospective Case Series Study.

While carpal tunnel syndrome (CTS) is the most common entrapment neuropathy affecting the wrist, resulting in substantial physical, psychological, and economic effects, there is no gold standard therapy for CTS. In this case series study, we aimed to report CTS patients treated with Carthami Semen Pharmacopuncture (CSP) and electroacupuncture (EA) showing improvements in their symptoms, and the combinatorial effects of CSP and EA. We collected medical records of CTS outpatients who received CSP and EA at Chuk-u Acupuncture & Moxibustion Korean Medicine Clinic from August 2017 to September 2018. The outcome measures were the visual analog scale (VAS) for pain, paresthesia, the Korean version of the Boston carpal tunnel questionnaire (K-BCTQ) score, and changes in nocturnal pain, Tinel sign, and Phalen's test. We included patient satisfaction at the completion of all treatments. 17 patients were included for this case series study. After treatment, VAS for pain decreased significantly from 50.41 ± 16.19 to 9.59 ± 9.46, VAS for paresthesia also decreased significantly from 63.50 ± 11.49 to 14.75 ± 12.97, and K-BCTQ symptom severity scale decreased from 2.48 ± 0.68 to 1.89 ± 0.70 (all p < 0.001). Nocturnal pain, Tinel signs, and Phalen's test showed improvements after all the treatments. All the patients reported favorable overall satisfaction with the treatments, and 69.23% wanted future pharmacopuncture treatments if CTS recurred. No complications were detected. The combination of CSP and EA could be an effective and safe option in treating CTS.

Polycystin-1 Enhances Stemmness Potential of Umbilical Cord Blood-Derived Mesenchymal Stem Cells.

Polycystic Kidney Disease (PKD) is a disorder that affects the kidneys and other organs, and its major forms are encoded by polycystin-1 (PC1) and polycystin-2 (PC2), as PKD1 and PKD2. It is located sandwiched inside and outside cell membranes and interacts with other cells. This protein is most active in kidney cells before birth, and PC1 and PC2 work together to help regulate cell proliferation, cell migration, and interactions with other cells. The molecular relationship and the function between PKD1 and cancer is well known, such as increased or decreased cell proliferation and promoting or suppressing cell migration depending on the cancer cell type specifically. However, its function in stem cells has not been revealed. Therefore, in this study, we investigated the biological function of PC1 and umbilical cord blood-derived mesenchymal stem cell (UCB-MSC). Furthermore, we assessed how it affects cell migration, proliferation, and the viability of cells when expressed in the PKD1 gene. In addition, we confirmed in an ex vivo artificial tooth model generated by the three-dimension printing technique that the ability to differentiate into osteocytes improved according to the expression level of the stemness markers when PKD1 was expressed. This study is the first report to examine the biological function of PKD1 in UCB-MSC. This gene may be capable of enhancing differentiation ability and maintaining long-term stemness for the therapeutic use of stem cells.

The Effect of Annexin A1 as a Potential New Therapeutic Target on Neuronal Damage by Activated Microglia.

Brain disease is known to cause irrevocable and fatal loss of biological function once damaged. One of various causes of its development is damage to neuron cells caused by hyperactivated microglia, which function as immune cells in brain. Among the genes expressed in microglia stimulated by various antigens, annexin A1 (ANXA1) is expressed in the early phase of the inflammatory response and plays an important role in controlling the immune response. In this study, we assessed whether ANXA1 can be a therapeutic target gene for the initial reduction of the immune response induced by microglia to minimize neuronal damage. To address this, mouse-origin microglial cells were stimulated to mimic an immune response by lipopolysaccharide (LPS) treatment. The LPS treatment caused activation of ANXA1 gene and expression of inflammatory cytokines. To assess the biological function in microglia by the downregulation of ANXA1 gene, cells were treated with short hairpin RNA-ANXA1. Downregulated ANXA1 affected the function of mitochondria in the microglia and showed reduced neuronal damage when compared to the control group in the co-culture system. Taken together, our results showed that ANXA1 could be used as a potential therapeutic target for inflammation-related neurodegenerative diseases.

Regulation and status of herbal medicine clinical trials in Korea: a narrative review.

BACKGROUND: Herbal medicine has been used frequently in Korean medicine. We aimed to summarize the relevant regulations for herbal medicine clinical trials and to analyze their current status in the Republic of Korea. METHODS: We searched for legislation to find regulations on herbal medicine clinical trials. Additionally, the websites of the Korean Ministry of Food and Drug Safety (KMFDS) and Clinical Research Information Service (CRIS) were searched to investigate the current status of them. RESULTS: To conduct herbal medicine clinical trials for new drugs or previously approved drugs outside of indications, investigational new drug (IND) approval should be obtained from the KMFDS. For clinical trials of herbal medicines that have been used for more than 3 years with 200 cases at the clinical trial institution, nonclinical data can be exempted from IND approval. Total 95 and 108 herbal medicine clinical trials from the KMFDS and CRIS websites were analyzed. The number of clinical trials showed an increasing trend each year, as did KMFDS-regulated clinical trials. Recently, three clinical trials targeting new herbal formulations frequently used in Korean medicine institutions have been approved based on relevant regulations. CONCLUSION: We confirmed that herbal medicine clinical trials are managed through strict regulations, which can ensure the safe and effective use of herbal medicine. Despite strict regulations, attempts to accumulate evidence through clinical trials for herbal medicine are increasing. High-quality clinical trials should be conducted to develop new drugs that reflect the clinical setting using relevant regulations, evaluate the efficacy and safety of the drugs, and strengthen insurance coverage.

A Password Meter without Password Exposure.

To meet password selection criteria of a server, a user occasionally needs to provide multiple choices of password candidates to an on-line password meter, but such user-chosen candidates tend to be derived from the user's previous passwords-the meter may have a high chance to acquire information about a user's passwords employed for various purposes. A third party password metering service may worsen this threat. In this paper, we first explore a new on-line password meter concept that does not necessitate the exposure of user's passwords for evaluating user-chosen password candidates in the server side. Our basic idea is straightforward; to adapt fully homomorphic encryption (FHE) schemes to build such a system but its performance achievement is greatly challenging. Optimization techniques are necessary for performance achievement in practice. We employ various performance enhancement techniques and implement the NIST (National Institute of Standards and Technology) metering method as seminal work in this field. Our experiment results demonstrate that the running time of the proposed meter is around 60 s in a conventional desktop server, expecting better performance in high-end hardware, with an FHE scheme in HElib library where parameters support at least 80-bit security. We believe the proposed method can be further explored and used for a password metering in case that password secrecy is very important-the user's password candidates should not be exposed to the meter and also an internal mechanism of password metering should not be disclosed to users and any other third parties.

Biological Functions and Identification of Novel Biomarker Expressed on the Surface of Breast Cancer-Derived Cancer Stem Cells via Proteomic Analysis.

Breast cancer is one of the most common life-threatening malignancies and the top cause of cancer deaths in women. Although many conventional therapies exist for its treatment, breast cancer still has many handicaps to overcome. Cancer stem cells (CSCs) are a well-known cause of tumor recurrences due to the ability of CSCs for self-renewal and differentiation into cell subpopulations, similar to stem cells. To fully treat breast cancer, a strategy for the treatment of both cancer cells and CSCs is required. However, current strategies for the eradication of CSCs are non-specific and have low efficacy. Therefore, surface biomarkers to selectively treat CSCs need to be developed. Here, 34 out of 641 surface biomarkers on CSCs were identified by proteomic analysis between the human breast adenocarcinoma cell line MCF-7 and MCF-7-derived CSCs. Among them, carcinoembryonic antigen-related cell adhesion molecules 6 (CEACAM6 or CD66c), a member of the CEA family, was selected as a novel biomarker on the CSC surface. This biomarker was then experimentally validated and evaluated for use as a CSC-specific marker. Its biological effects were assessed by treating breast cancer stem cells (BCSCs) with short hairpin (sh)-RNA under oxidative cellular conditions. This study is the first to evaluate the biological function of CD66c as a novel biomarker on the surface of CSCs. This marker is available as a moiety for use in the development of targeted therapeutic agents against CSCs.