Exploring Traditional Medicine Diagnostic Classification for Parkinson's Disease Using Hierarchical Clustering.

INTRODUCTION: Personalized diagnosis and therapy for Parkinson's disease (PD) are needed due to the clinical heterogeneity of PD. Syndrome differentiation (SD) in traditional medicine (TM) is a diagnostic method for customized therapy that comprehensively analyzes various symptoms and systemic syndromes. However, research identifying PD classification based on SD is limited. METHODS: Ten electronic databases were systematically searched from inception to August 10, 2021. Clinical indicators, including 380 symptoms, 98 TM signs, and herbal medicine for PD diagnosed with SD, were extracted from 197 articles; frequency statistics on clinical indicators were conducted to classify several subtypes using hierarchical clustering. RESULTS: Four distinct cluster groups were identified, each characterized by significant cluster-specific clinical indicators with 95% confidence intervals of distribution. Subtype 2 had the most severe progression, longest progressive duration, and highest association with greater late-stage PD-associated motor symptoms, including postural instability and gait disturbance. The action properties of the herbal formula and original SD presented in the data sources for subtype 2 were associated with Yin deficiency syndrome. DISCUSSION/CONCLUSION: Hierarchical clustering analysis distinguished various symptoms and TM signs among patients with PD. These newly identified PD subtypes may optimize the diagnosis and treatment with TM and facilitate prognosis prediction. Our findings serve as a cornerstone for evidence-based guidelines for TM diagnosis and treatment.Eine personalisierte Diagnose und Therapie des Morbus Parkinson (MP) ist angesichts der ausgeprägten klinischen Heterogenität des MP unerlässlich. Die Syndromdifferenzierung (SD) ist in der traditionellen Medizin (TM) eine diagnostische Methode für eine maßgeschneiderte Therapie, bei der verschiedene Symptome und systemische Syndrome umfassend analysiert werden. Es liegen jedoch nur begrenzt Forschungsergebnisse in Bezug auf eine SD-basierte Klassifikation des MP vor.Zehn elektronische Datenbanken wurden systematisch durchsucht, von der Einrichtung bis zum 10. August 2021. Klinische Indikatoren einschließlich von 380 Symptomen, 98 TM-Zeichen sowie pflanzlichen Heilmitteln für mittels SD diagnostiziertem MP wurden aus 197 Artikeln extrahiert, und Häufigkeitsstatistiken der klinischen Indikatoren wurden erstellt, um mittels hierarchischem Clustering eine Reihe von Subtypen zu klassifizieren.Vier verschiedene Cluster-Gruppen wurden identifiziert, die jeweils durch signifikante, Cluster-spezifische klinische Indikatoren mit 95% Konfidenzintervall der Verteilung gekennzeichnet waren. Subtyp 2 hatte den schwersten Verlauf, die längste Progressionsdauer und die stärkste Assoziation mit einem höheren Ausmaß von motorischen Symptomen des MP im Spätstadium, darunter Haltungsinstabilität und Gangstörungen. Die Wirkungseigenschaften der pflanzlichen Formulierung sowie die ursprüngliche SD, die in den Datenquellen für Subtyp 2 genannt wurden, waren mit Yin-Mangel-Syndrom assoziiert.Die hierarchische Clustering-Analyse hob verschiedene Symptome und TM-Zeichen bei Patienten mit MP hervor. Die neu identifizierten MP-Subtypen könnten die Diagnose und Behandlung mittels TM optimieren und zur Prognoseerstellung beitragen. Unsere Ergebnisse sind ein Fundament für eine evidenzbasierte Leitlinie für die TM-Diagnostik und -Therapie.

Feasibility of Applying the OMOP Common Data Model to Traditional Eastern Asian Medicine Dataset.

To evaluate the feasibility of applying the Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) to databases of traditional East Asian medicine (TEAM), we composed a TEAM dataset and transformed it to the OMOP CDM. We found that some important TEAM information entities could not be transformed to the OMOP CDM (version 6.0) data fields. We suggest to develop data fields and guideline for transforming TEAM data to the OMOP CDM.

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.

Weight Control Registry Using Korean Medicine: A Protocol for a Prospective Registry Study.

Lifestyle and physical characteristics affect body weight, and understanding these factors improves the precision of weight loss treatment. Many obese patients in Korea are receiving Korean medicine (KM) treatment, including herbal medicine and acupuncture, for weight loss. However, the real-world data (RWD) are insufficient in terms of being longitudinal and diverse. Weight Control Registry using KM is a prospective registry study that enrolls patients receiving KM treatment for weight loss and collects RWD from multiple clinics. The patients who are eligible for this study are aged 19-65 years, receive KM weight loss treatment, understand the study objectives, and consent voluntarily. Clinical data of patient characteristics and KM treatment patterns will be regularly collected until 2026. The longitudinal accumulation of various RWD will establish a high-quality study database for KM weight loss treatment. With this study, we expect to contribute to understanding the current trend of weight loss treatment with KM and solve further questions regarding this treatment.

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.

Acupotomy treatment for finger joint contracture after immobilization: Case report.

INTRODUCTION: Contractures frequently occur in the finger joints after immobilization. This report describes the effect of acupotomy treatment in patients with joint contracture due to immobilization of the finger joints. PATIENT CONCERNS AND CLINICAL FINDINGS: Case 1 was of a 39-year-old male patient who had flexion limitation of the left thumb and difficulty in grasping. Case 2 was of a 41-year-old female patient who had flexion limitation of the right index finger and difficulty in typing. Stiffness occurred after tendon repair surgery and cast immobilization in both cases. In Case 1, the patient had limited flexion movement of the first metacarpophalangeal and interphalangeal joints after 5 weeks of immobilization of the left thumb in a cast. In Case 2, the patient had limited flexion movement after 3 weeks of immobilization of the second proximal interphalangeal joint of the left hand in a cast. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: We diagnosed both patients with finger joint contracture due to immobilization. Conservative treatment for approximately 4 weeks did not lead to improvement in either patient. Acupotomy is the key treatment for improving movement in Korean Medicine. Therefore, acupotomy was performed, and joint stiffness markedly improved without adverse events. Both patients reported that the daily use of the damaged fingers became comfortable. CONCLUSION: We found that acupotomy may be effective for finger joint contracture due to improper immobilization. We suggest it as a simple and safe treatment for joint contracture.

Gait Disturbance Improvement and Cerebral Cortex Rearrangement by Acupuncture in Parkinson's Disease: A Pilot Assessor-Blinded, Randomized, Controlled, Parallel-Group Trial.

BACKGROUND: Parkinson's disease (PD) leads to impaired mobility and limited independence. OBJECTIVE: We investigated the effects of acupuncture on gait disturbance and analyzed hemodynamic changes caused by acupuncture in the cerebral cortex of patients with PD. METHODS: Participants (n = 26) with gait disturbance due to PD were randomly assigned to the intervention (acupuncture twice a week for 4 weeks + conventional therapy) or control (conventional therapy) groups. We analyzed gait parameters using the GAITRite system and hemodynamic responses in the cerebral cortices using functional near-infrared spectroscopy, Unified Parkinson's Disease Rating Scale (UPDRS) scores, neurotransmitter levels, as well as the immediate effects of acupuncture in patients with PD. RESULTS: The participants tended to walk with hypometric gait (high cadence, short steps) overground. After acupuncture treatment, those in the intervention group showed a significant reduction in cadence and the UPDRS scores involving "walking and balance" compared with those in the control group (P = .004 and P = .020, respectively); the stride, swing, and single support times were significantly increased (P = .006, P = .001, and P = .001, respectively). Oxyhemoglobin levels in the intervention group while walking on a treadmill were significantly increased in the prefrontal and supplementary motor areas. The oxyhemoglobin levels in the prefrontal cortex and swing time revealed significant positive correlations. CONCLUSIONS: Our findings indicated that acupuncture tended to improve hypometric gait and rearranged activation of the cerebral cortex. Thus, acupuncture may be a useful complementary treatment for gait disturbance, including hypometric gait, in patients with PD. Trial Registration Number. Clinical Research Information Service (KCT0002603), https://cris.nih.go.kr/cris/index.jsp.

Beta wave enhancement neurofeedback improves cognitive functions in patients with mild cognitive impairment: A preliminary pilot study.

BACKGROUND: Mild cognitive impairment (MCI) is a symptom characterizing cognitive decline and a transitional state between normal aging and dementia; however, there is no definitive diagnosis and treatment for MCI. Neurofeedback (NF), which is a training mechanism that employs operant conditioning to regulate brain activity, has been increasingly investigated concerning its beneficial effects for dementia and MCI. METHODS: This study investigated cognitive improvement and hemodynamic changes in the prefrontal cortex (PFC) following NF training in patients with MCI. Five patients with MCI received NF training for enhanced beta band activity in the dorsolateral PFC-16 sessions for 8 weeks-with each session divided into 9 5-minute trials. The primary outcome measure was a cognitive assessment tool: the Korean version of the Montreal Cognitive Assessment. The secondary outcome measures were the Central Nervous System Vital Signs for neurocognitive testing, hemodynamic changes using functional near-infrared spectroscopy in the PFC during a working-memory task, and Beck Depression Inventory scores. RESULTS: After completing the training, patients' cognitive function significantly improved in domains such as composite memory, cognitive flexibility, complex attention, reaction time, and executive function. Increased electroencephalogram beta power was observed over NF training sessions (Spearman rank correlation test: r = 0.746, P = .001). The threshold value for gaining positive feedback from pre-NF baseline on beta power significantly increased (Spearman rank correlation test: r = 0.805, P = .001). Hemodynamic response in PFC changed after NF training, and individual differences were identified. Specifically, hypoactivation of the hemodynamic response by emotional distraction recovered following NF training. CONCLUSION: We suggest that patients' cognitive processing efficiency was improved by the NF training. These beneficial results suggest that NF training may have potential therapeutic applications to prevent the progression from MCI to dementia. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (KCT0003433).

Inhibitory effects of Euphorbia supina on Propionibacterium acnes-induced skin inflammation in vitro and in vivo.

BACKGROUND: Euphorbia supina (ES) plant has been used as treatment for inflammatory conditions. The antibacterial effect and the anti-inflammatory mechanism of ES for Propionibacterium (P.) acnes-induced inflammation in THP-1 cells and acne animal model remain unclear. Therefore, the objective of the present study was to determine the antibacterial and anti-inflammatory activities of ES against P. acnes, the etiologic agent of skin inflammation. METHOD: The antibacterial activities of ES were tested with disc diffusion and broth dilution methods. Cytotoxicity of ES at different doses was evaluated by the MTT assay. THP-1 cells were stimulated by heat-killed P. acnes in the presence of ES. The pro-inflammatory cytokines and mRNA levels were measured by ELISA and real-time-PCR. MAPK expression was analyzed by Western blot. The living P. acnes was intradermally injected into the ear of BLBC/c mice. Subsequently, chemical composition of ES was analyzed by liquids chromatography-mass spectrometry (LC-MS). RESULT: ES had stronger antibacterial activity against P. acnes and inhibitory activity on lipase. ES had no significant cytotoxicity on THP-1 cells. ES suppressed the mRNA levels and production of IL-8, TNF-a, IL-1ß in vitro. ES inhibited the expression levels of pro-inflammatory cytokines and the MAPK signaling pathway. Ear thickness and inflammatory cells were markedly reduced by ES treatment. Protocatechuic acid, gallic acid, quercetin, and kaempferol were detected by LC-MS analysis in ES. CONCLUSIONS: Our results demonstrate antibacterial and anti-inflammatory activities of ES extract against P. acnes. It is suggested that ES extract might be used to treatment anti-inflammatory skin disease.

Antioxidant Activity of Royal Jelly Hydrolysates Obtained by Enzymatic Treatment.

Recently, research on the processing of raw functional materials with the aim of improving various physiological activities has been conducted. In this study, we investigated the antioxidant activity of royal jelly (RJ) hydrolysates obtained from three commercial proteases. Enzyme-treated royal jelly (ERJ), in which the RJ hydrolysates were converted into easy-to-absorb shorter chain monomers through the removal of two known allergen proteins, showed no difference in the content of (E)-10-hydroxydec-2-enoicacid (10-HDA) or the freshness parameter and showed a significant increase in total free amino acid content. The antioxidant activity of ERJ was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and chemical assays. The ERJ showed about 80% DPPH-radical scavenging activity at same concentration of ascorbic acid. The antioxidant effect of ERJ was confirmed to be due to reduction of intracellular reactive oxidative species (ROS) and nitric oxide (NO) production in LPS-treated macrophages. Moreover, ERJ significantly increased the activity of the antioxidant enzyme superoxide dismutase (SOD) and the level of the antioxidant glutathione (GSH) in a dose-dependent manner. Interestingly, these antioxidant activities of ERJ were stronger than those of non-treated RJ. These findings indicate that ERJ has high potential as an antioxidant agent for use in human and animal diets.

Chrysanthemum indicum Inhibits Adipogenesis and Activates the AMPK Pathway in High-Fat-Diet-Induced Obese Mice.

Chrysanthemum indicum (CI) is widely distributed in China and many parts of the tropical world, and has been reported to have antibacterial, antiviral, anti-oxidant and immunomodulatory effects, but no information is available on its effects on high fat diet (HFD)-induced obesity. This was undertaken to investigate the mechanism responsible for the effect of ethyl acetate fraction of CI (CIEA) on adipogenesis, in vitro and in vivo models of obesity. In the in vitro study, differentiating 3T3-L1 cells were treated with media to initiate differentiation (MDI) in the presence or absence of CIEA with different concentrations, and in the in vivo study, C57BL/6 mice were fed with HFD and administered CIEA daily for six weeks. Garcinia cambogia (GC) was used as the positive control, and was administered in the same manner as CIEA. Results showed CIEA reduced HFD-induced body weight gain, epididymal white adipose tissue (eWAT), and liver weight. In addition, CIEA significantly decreased serum lipid profiles, including total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLc) and increased high density lipoprotein cholesterol (HDLc) levels. Furthermore, CIEA also reduced leptin levels and increased adiponectin levels in serum, and significantly decreased peroxisome proliferator-activated receptor [Formula: see text] (PPAR[Formula: see text]) and CCAAT/enhancer-binding protein (C/EPBs) levels, but increased PPAR[Formula: see text] level and the phosphorylation of AMP-activated protein kinase (AMPK) in eWATs and in the liver tissues of HFD fed obese mice. Taken together, these results indicate CIEA might be beneficial for preventing obesity.

Anti-inflammatory effect of Euphorbia supina extract in dextran sulfate sodium-induced colitis mice.

The aim of this study is to examine the anti-inflammatory effect of Euphorbia supina (ES) ethanol extract in dextran sulfate sodium (DSS)-induced experimental colitis model. ES was per orally administered at different doses of 4 or 20 mg/kg body weight with 5% DSS in drinking water for 7 days. Twenty mg/kg of ES administration regulated body weight decrease, recovered colon length shortening, and increased disease activity index score and myeloperoxidase level in DSS-induced colitis. Histological features showed that 20 mg/kg of ES administration suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, ES suppressed the expressions of COX-2, iNOS, NF-kB, IkBα, pIkBα in colon tissue. These findings demonstrated a possible effect of amelioration of ulcerative colitis and could be clinically applied.

Triticum aestivum sprout-derived polysaccharide exerts hepatoprotective effects against ethanol-induced liver damage by enhancing the antioxidant system in mice.

Triticum aestivum sprout-derived polysaccharide (TASP) has anti-diabetic properties, but no information is available in regards to its protective effect against ethanol-induced hepatic injury. This study aimed to investigate the mechanism behind the protective role of TASP against ethanol-induced liver injury in vivo. Male C57BL/6 mice were administered ethanol with or without TASP for 10 consecutive days by oral gavage. Silymarin was administered in the same manner as a positive control. TASP reduced ethanol-induced hepatic lipid accumulation and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. TASP also prevented glutathione (GSH) depletion and increased the superoxide dismutase (SOD) in liver tissue. In addition, TASP significantly inhibited ethanol-induced cytochrome P450 2E1 (CYP2E1) activation, and upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and downregulated NADPH oxidase genes in ethanol fed mice. Furthermore, the upregulation of Nrf2 was found to be regulated by a phosphatidylinositol 3-kinase (PI3K)/Akt pathway. TASP also attenuated hepatic injury by modulation of caspase-3 and apoptosis-associated mitochondrial proteins including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) in liver tissues of mice. The study demonstrated that TASP treatment protects against ethanol-induced hepatic injury via multiple pathways by inhibiting steatosis and improving antioxidant marker levels during hepatic injury. Such properties provide a basis for therapeutic agents against alcohol-induced liver injury.

Inhibitory effect on TNF-α-induced IL-8 secretion in HT-29 cell line by glyceroglycolipids from the leaves of Ficus microcarpa.

Bioassay-guided fractionation based on the anti-inflammatory activity of a methanol extract of Ficus microcarpa leaves led to the isolation of seven galactolipids: 2(S)-3-O-octadeca-9Z,12Z,15Z-trienoylglyceryl-O-ß-D-galactopyranoside (1), (2S)-2,3-O-dioctadeca-9Z,12Z,15Z-trienoylglyceryl-O-ß-D-galactopyranoside (2), (2S)-2,3-O-dioctadeca-9Z,12Z-dienoylglyceryl-O-ß-D-galactopyranoside (3), (2S)-3-O-octadeca-9Z,12Z,15Z-trienoylglyceryl-6'-O-(α-D-galactopyranosyl)-ß-D-galactopyranoside (4), (2S)-2,3-O-dioctadeca-9Z,12Z,15Z-trienoylglyceryl-6'-O-(α-D-galactopyranosyl)-ß-D-galactopyranoside (5), gingerglycolipid B (6), and (2S)-2,3-O-dioctadeca-9Z,12Z-dienoylglyceryl-6'-O-(α-D-galactopyranosyl)-ß-D-galactopyranoside (7). Their chemical structures were elucidated by mass, 1D-, and 2D-NMR spectroscopic methods as well as chemical methods. The antiinflammatory effect of these compounds on TNF-α induced IL-8 secretion in the HT-29 cell line was evaluated. All above galactolipids showed significant inhibition ranging 40% at a concentration of 50 µM. The results suggest that galactolipids from the leaves of F. microcarpa may be used as potent anti-inflammatory agents.