Determination of the Combined Effects of Asian Herbal Medicine with Calcium and/or Vitamin D Supplements on Bone Mineral Density in Primary Osteoporosis: A Systematic Review and Meta-Analysis.

Our review of 52 RCTs from 5 databases suggests a tendency for notable improvement in BMD when combining herbal medicine with supplements (calcium and vitamin D variants) compared to supplement monotherapy in primary osteoporosis. However, caution is needed in interpreting results due to substantial heterogeneity among included studies. PURPOSE: To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. METHODS: We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. RESULTS: In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095 g/cm2 (lumbar) and 0.625 ± 0.090 g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08 g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06-0.10, p < 0.001, I2 = 97%) and 0.06 g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04-0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. CONCLUSION: Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future.

Lactobacillus Casei-fermented Amomum Xanthioides Mitigates non-alcoholic fatty liver disease in a high-fat diet mice model.

Non-alcoholic fatty liver disease (NAFLD) is a substantial global health issue owing to its high prevalence and the lack of effective therapies. Fermentation of medicinal herbs has always been considered a feasible strategy for enhancing efficacy in treating various ailments. This study aimed to investigate the potential benefits of the Lactobacillus casei-fermented Amomum xanthioides (LAX) on NAFLD in a high-fat diet model. HFD-fed C57BL6/j mice were administered with 200 mg/kg of LAX or unfermented Amomum xanthioides (AX) or 100 mg/kg of metformin for 6 weeks from the 4th week. The 10-week HFD-induced alterations of hepatic lipid accumulation and hepatic inflammation were significantly attenuated by LAX dominantly (more than AX or metformin), which evidenced by pathohistological findings, lipid contents, inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 6 and IL-1ß, oxidative parameters such as reactive oxygen species (ROS) and malondialdehyde (MDA), and molecular changes reversely between lipogenic proteins such as glycerol-3-phosphate acyltransferase (GPAM) and sterol regulatory element-binding protein (SREBP)- 1, and lipolytic proteins including peroxisome proliferator-activated receptor (PPAR-α) and AMP-activated kinase (AMPK)-α in the liver tissues. In addition, the abnormal serum lipid parameters (triglyceride, total cholesterol and LDL-cholesterol) notably ameliorated by LAX. In conclusion, these findings support the potential of LAX as a promising plant-derived remedy for NAFLD.

Mapping of systematic reviews on traditional medicine across health conditions: a protocol for a systematic map.

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

Acupuncture for patients with insomnia and predictors of treatment response: a chart review.

BACKGROUND: Acupuncture is a potentially effective non-pharmacological treatment for insomnia. OBJECTIVE: We observed the responses of patients with insomnia to acupuncture in routine clinical practice. In addition, we explored patient characteristics that might affect the treatment response to acupuncture for insomnia. METHODS: Medical records of patients with insomnia in a Korean medicine clinic with baseline Insomnia Severity Index (ISI) scores ⩾8 and Pittsburgh Sleep Quality Index (PSQI) scores ⩾5 were reviewed. Acupuncture was applied at ST43, GB41, ST41, SI5, HT3, KI10, HT7 and ST3, for 1-2 months. The ISI and PSQI were measured monthly to assess insomnia severity. The effect of acupuncture over time was analyzed using a multilevel linear model for repeated measures. In addition, logistic regression was used to explore predictors of treatment response. RESULTS: A total of 91 patients with insomnia aged 59.2 ± 12.5 years (mean ± standard deviation (SD)) (90.1% female) were included in the analysis. After the acupuncture treatment, ISI scores were significantly reduced by -3.75 (95% confidence interval (CI) = -4.99, -2.50) and -4.69 (95% CI = -6.22, -3.16) after the first and second month, respectively. The PSQI global scores also improved, and sleep duration showed a tendency to increase by 0.35 h (95% CI = -0.17, 0.86) after acupuncture treatment. Three cases of mild fatigue were reported. In addition, higher baseline pain/discomfort predicted a greater likelihood of response after acupuncture treatment (odds ratio (OR) = 1.66, 95% CI = 1.10, 2.60). CONCLUSION: In a real-world setting, the insomnia of outpatients in a clinic was slightly alleviated after acupuncture treatment. These findings require validation by randomized controlled trials.

The Impact of Early Acupuncture on Bell's Palsy Recurrence: Real-World Evidence from Korea.

Evidence-based treatment for Bell's palsy includes the administration of steroids within 3 days of symptom onset. Additionally, a few studies have suggested the importance of combining early acupuncture treatment in the acute phase of Bell's palsy with steroids. This study aimed to observe the impact of early acupuncture for Bell's palsy using real-world health insurance data in Korea. This retrospective study extracted data from 45,986 adult patients with Bell's palsy who received steroids between 2015 and 2017 with a follow-up period of at least 3 years until 2020 from the Korea National Health Insurance database. They were divided into the early acupuncture group (n = 28,267) and the comparison group (n = 17,719) based on the presence of an acupuncture treatment code within 7 days of diagnosis. The impact of early acupuncture on the likelihood of Bell's palsy recurrence was evaluated using multivariate logistic regression. The patients in the early acupuncture group had a lower likelihood of recurrence (odds ratio: 0.81, 95% confidence interval: 0.69-0.95). This study observed a beneficial impact of early acupuncture on Bell's palsy using real-world health insurance data in Korea. Further research is required to confirm these findings.

Acupuncture for Attenuating Frontal Lobe α Band Asymmetry Induced by Anger: a pilot study.

Objectives: Previous studies have shown that anger can lead to frontal lobe α (8-13 Hz) band asymmetry (FAA) in electroencephalogram (EEG), in accordance with motivational direction. This pilot study aimed to investigate the impact of acupuncture on FAA elicited by anger. Methods: Thirty-four right-handed participants scoring above 75 points on the Novaco Anger Scale were included. Baseline EEG signals were recorded for eight minutes using a 32-channel cap under comfortable conditions. Anger was induced through a nine-minute sequence of Articulated Thoughts in Simulated Situations (ATSS) task. Following that, participants received acupuncture at GB20 and GB21 for 10 minutes. Fast Fourier transform was employed for frequency analysis, and repeated measure ANOVA was conducted for statistical analysis. Results: The results revealed that participants exhibited significantly higher FAA (p = 0.026), particularly in the left hemisphere, after the ATSS task sequence compared to the baseline. During acupuncture treatment, the greater left-sided FAA was significantly reduced (p = 0.027) and reversed. Upon the cessation of acupuncture, FAA returned to a value between the baseline and the anger-evoked stage (p = 0.046). Conclusion: The EEG results of this study revealed that anger stimulation induced an increase in left-sided FAA, which was effectively alleviated by acupuncture. This led to an immediate restoration of FAA asymmetry induced by anger. These findings suggest the potential of acupuncture as a treatment option for reducing FAA associated with anger.

Bangpungtongsung-san for patients with major depressive disorder: study protocol for a randomized controlled phase II clinical trial.

BACKGROUND: Bangpungtongsung-san (BTS) is a representative herbal medicine that has been widely used for patients with obesity in east Asian countries. Various preclinical studies have demonstrated the anti-depressive effect of BTS granules in various animal models of depression. This phase II trial aimed to explore the efficacy and safety of BTS in human patients with depression. METHODS: A total of 126 patients diagnosed with major depressive disorder and who are not underweight (body mass index ≥ 18.5 kg/m2) will be enrolled in this study. Eligible participants will be randomly allocated into three groups: the high-dose BTS, low-dose BTS, and placebo groups in a 1:1:1 ratio. BTS or placebo granules will be orally administered twice a day for 8 weeks. The BTS and placebo granules will be made to have identical color, scent, and shape, and participants and investigators will be blinded to the allocation. The primary efficacy endpoint is the change from baseline of the 17-item Hamilton Depression Rating Scale total score at 8 weeks. The superiority of the high- and low-dose BTS granules to the placebo granules will be tested. DISCUSSION: The results of this clinical trial will provide evidence on the efficacy and safety of BTS for patients with major depressive disorder. This study will be conducted in accordance with ethical and regulatory guidelines, and the results will be submitted and published in international peer-reviewed journals. TRIAL REGISTRATION: CRIS registration Number: KCT0007571; registered on 2022/07/26 ( https://cris.nih.go.kr/cris/search/detailSearch.do/23192 ).

Literature review on the interdisciplinary biomarkers of multi-target and multi-time herbal medicine therapy to modulate peripheral systems in cognitive impairment.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease characterized by the deposition of amyloid-beta (Aß) peptide and neurofibrillary tangles in the brain. The approved drug for AD has certain limitations such as a short period of cognitive improvement effect; moreover, the development of drug for AD therapeutic single target for Aß clearance in brain ended in failure. Therefore, diagnosis and treatment of AD using a multi-target strategy according to the modulation of the peripheral system, which is not only limited to the brain, is needed. Traditional herbal medicines can be beneficial for AD based on a holistic theory and personalized treatment according to the time-order progression of AD. This literature review aimed to investigate the effectiveness of herbal medicine therapy based on syndrome differentiation, a unique theory of traditional diagnosis based on the holistic system, for multi-target and multi-time treatment of mild cognitive impairment or AD stage. Possible interdisciplinary biomarkers including transcriptomic and neuroimaging studies by herbal medicine therapy for AD were investigated. In addition, the mechanism by which herbal medicines affect the central nervous system in connection with the peripheral system in an animal model of cognitive impairment was reviewed. Herbal medicine may be a promising therapy for the prevention and treatment of AD through a multi-target and multi-time strategy. This review would contribute to the development of interdisciplinary biomarkers and understanding of the mechanisms of action of herbal medicine in AD.

Effectiveness of Sopoongsan for chronic upper body pruritus in patients with atopic or seborrheic dermatitis: A pilot study protocol for a randomized, double-blind, placebo-controlled, parallel trial.

INTRODUCTION: Chronic pruritus persists for > 6 weeks and is known to decrease patients' quality of life. Due to the complex pathological mechanism of chronic pruritus, there is still a lack of satisfactory therapeutic agents; therefore, complementary therapies are required to improve itching symptoms. In the Republic of Korea, Sopoongsan, an herbal formula, has been used to treat itching, dizziness, and skin paralysis. To our knowledge, this is the first study to evaluate whether Sopoongsan improves chronic pruritus and to identify Sopoongsan-related changes in the immune response in patients with chronic upper body pruritus. METHODS: A randomized, double-blind, placebo-controlled parallel trial will be conducted to assess 20 patients with chronic upper body pruritus for 3 months who have been diagnosed with allergic atopic dermatitis or seborrheic dermatitis. The patients will be randomly allocated to either the placebo-control (n = 10) or treatment (n = 10) group. The total study period will be 8 weeks (i.e., administration of Sopoongsan or placebo drugs for 4 wk and follow-up for 4 wk). Participants will be allowed to receive external treatment, except for antipruritic medications administered orally, throughout the study period. The primary outcome measure will be the numeric rating scale results for itching, whereas the secondary outcome measures will be questionnaire survey (Dermatological Life Quality Index and Epworth Sleepiness Scale) findings and the immune response index, including interferon gamma, interleukin-4, immunoglobulin E, thymic stromal lymphopoietic protein, and histamine, to investigate the biological mechanisms underlying chronic pruritus. DISCUSSION AND CONCLUSIONS: We expect that the results of this study will provide important clinical evidence regarding the effectiveness of Sopoongsan on itching symptoms, quality of life, sleep disturbance, and changes in the immune response. The findings will help elucidate the mechanism underlying the therapeutic effect of Sopoongsan for chronic pruritus and lay the foundation for further studies in this area.

Deep autoencoder-powered pattern identification of sleep disturbance using multi-site cross-sectional survey data.

Pattern identification (PI) is a diagnostic method used in Traditional East Asian medicine (TEAM) to select appropriate and personalized acupuncture points and herbal medicines for individual patients. Developing a reproducible PI model using clinical information is important as it would reflect the actual clinical setting and improve the effectiveness of TEAM treatment. In this paper, we suggest a novel deep learning-based PI model with feature extraction using a deep autoencoder and k-means clustering through a cross-sectional study of sleep disturbance patient data. The data were obtained from an anonymous electronic survey in the Republic of Korea Army (ROKA) members from August 16, 2021, to September 20, 2021. The survey instrument consisted of six sections: demographics, medical history, military duty, sleep-related assessments (Pittsburgh sleep quality index (PSQI), Berlin questionnaire, and sleeping environment), diet/nutrition-related assessments [dietary habit survey questionnaire and nutrition quotient (NQ)], and gastrointestinal-related assessments [gastrointestinal symptom rating scale (GSRS) and Bristol stool scale]. Principal component analysis (PCA) and a deep autoencoder were used to extract features, which were then clustered using the k-means clustering method. The Calinski-Harabasz index, silhouette coefficient, and within-cluster sum of squares were used for internal cluster validation and the final PSQI, Berlin questionnaire, GSRS, and NQ scores were used for external cluster validation. One-way analysis of variance followed by the Tukey test and chi-squared test were used for between-cluster comparisons. Among 4,869 survey responders, 2,579 patients with sleep disturbances were obtained after filtering using a PSQI score of >5. When comparing clustering performance using raw data and extracted features by PCA and the deep autoencoder, the best feature extraction method for clustering was the deep autoencoder (16 nodes for the first and third hidden layers, and two nodes for the second hidden layer). Our model could cluster three different PI types because the optimal number of clusters was determined to be three via the elbow method. After external cluster validation, three PI types were differentiated by changes in sleep quality, dietary habits, and concomitant gastrointestinal symptoms. This model may be applied to the development of artificial intelligence-based clinical decision support systems through electronic medical records and clinical trial protocols for evaluating the effectiveness of TEAM treatment.

Efficacy and safety of Gyejibokryeong-hwan (GBH) in major depressive disorder: study protocol for multicentre randomised controlled trial.

BACKGROUND: Gyejibokryeong-hwan (GBH) is an herbal medicine composed of five herbs. It has been widely used to treat gynaecological diseases in traditional East Asian medicine. Recent animal studies suggest antidepressant effects of GBH. In this trial, we explore the efficacy and safety of GBH in patients with major depressive disorder and to identify the optimal dose for the next phase III trial. METHODS: This trial will enrol 126 patients diagnosed with major depressive disorder and not treated with antidepressants. Participants will be randomised to receive a high or a low dose of GBH or placebo granules. The study drugs will be administered three times a day, for 8 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) will be used to measure the severity of depressive symptoms at weeks 2, 4, 6, 8, and 12. The primary efficacy endpoint is the change from baseline in HDRS-17 total score post-treatment at week 8. Analysis of covariance will be based on the baseline HDRS-17 total score and site as the covariates. Safety assessment will be based on the frequency of adverse events. The severity and causality of the study drug will be assessed. DISCUSSION: This study is designed to evaluate the efficacy and safety of GBH granules compared with placebo in patients with major depressive disorder. TRIAL REGISTRATION: Clinical Research Information Service KCT0004417 . Registered on November 1, 2019 (prospective registration).

Trichosanthis Semen Suppresses Lipopolysaccharide-Induced Neuroinflammation by Regulating the NF-κB Signaling Pathway and HO-1 Expression in Microglia.

Neuroinflammation, which is mediated by microglia that release various inflammatory cytokines, is a typical feature of neurodegenerative diseases (NDDs), such as Alzheimer's disease and Parkinson's disease. Hence, alleviating neuroinflammation by downregulating pro-inflammatory action, and upregulating anti-inflammatory action of microglia is an efficient therapeutic target for NDDs. In this study, we evaluated whether trichosanthis semen (TS), a dried ripe seed of Trichosanthes kirilowii Maximowicz, reduces lipopolysaccharide (LPS)-induced neuroinflammation by regulating microglial responses in vitro and in vivo. Our results presented that TS reduced the release of pro-inflammatory mediators, such as nitric oxide (NO), inducible NO synthase, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 via inhibition of the nuclear factor kappa B (NF-κB) signaling pathway in LPS-treated BV2 microglial cells. Moreover, TS induced anti-inflammatory mediators, such as interleukin-10, found in inflammatory zone 1, and chitinase 3-like 3 by the upregulation of heme oxygenase 1 (HO-1). We further confirmed that TS administration suppressed microglial activation, but enhanced HO-1 expression in LPS-injected mice. These results suggest that TS has anti-neuroinflammatory effects via inhibition of NF-κB signaling through the activation of HO-1, and that TS may be a therapeutical candidate for NDDs treatment.

Acupuncture for Psychosomatic Symptoms of Hwa-byung, an Anger Syndrome: A Feasibility Randomized Controlled Trial.

Objectives: Emerging studies found the potential effects of acupuncture for treating chronic pain and mental disorders, namely, depressive and anxiety disorders. Acupuncture is widely used for treating culture-related anger syndrome, Hwa-byung. This pilot trial aimed to investigate the feasibility of a clinical trial testing acupuncture for the psychosomatic symptoms of Hwa-byung. Methods: A total of 26 patients with Hwa-byung planned to be randomly assigned to the acupuncture or sham acupuncture groups. About 10 treatment sessions were applied over 4 weeks. The 100-mm visual analog scale was used to measure the six major Hwa-byung symptoms: stuffiness in the chest, heat sensations, pushing-up in the chest, feeling a mass in the throat, feelings of unfairness, and hard feelings. The criteria for assessing the success of this pilot trial were defined as improvement in three or more of the six Hwa-byung symptoms after treatment, with an effect size >0.2. Results: A total of 15 patients were finally included and randomly assigned to the acupuncture group (n = 7) or the sham acupuncture group (n = 8). After 10 treatment sessions, the Cohen's d effect sizes for acupuncture compared to sham acupuncture were >0.2 for each one of the six major Hwa-byung symptoms, which met our a priori criteria for success. Also, the effect size for the somatic symptoms of "stuffiness in the chest" was 0.81 (95% CI -0.40, 2.20), referring to a large effect size. Conclusions: Our results suggest that acupuncture treatment would be regarded as an acceptable intervention for a full-scale study of psychosomatic symptoms in patients with Hwa-byung. Trial Registration: cris.nih.go.kr, identifier: KCT0001732.

Correction: Choi et al. Feasibility and Effect of Electroacupuncture on Cognitive Function Domains in Patients with Mild Cognitive Impairment: A Pilot Exploratory Randomized Controlled Trial. Brain Sci. 2021, 11, 756.

The authors wish to make the following correction to [...].

Herbal Medicine for Patients with Cognitive Impairment: An Observational Study.

PURPOSE: The potential effects of herbal medicine for patients with cognitive disorders have been reported in various human and animal studies. This study aimed to explore the effect of herbal medicine treatment according to the Korean Medicine (KM) pattern identification for patients with mild cognitive impairment and early dementia. PATIENTS AND METHODS: Twenty patients with mild cognitive impairment or mild dementia who planned to receive herbal medicine treatment were enrolled. Herbal formulae were prescribed based on the KM pattern for 12-24 weeks. Seoul Neuropsychological Screening Battery II (SNSB-II) and Montreal Cognitive Assessment (MoCA) were assessed at the baseline, after 12 weeks, and after 24 weeks (Trial registration: cris.nih.go.kr, KCT0004799). RESULTS: Herbal medicine products, including Yukmijihwang-tang, Samhwangsasim-tang, Palmul-tang, Banhasasim-tang, and Yukgunja-tang, were prescribed to the patients. Among the SNSB-II five cognitive function domains, the T scores for language, visuospatial function, memory, and frontal/executive function increased over time. The MoCA score also improved following the treatment (mean difference 4.23 [95% CI: 2.60, 5.86], p < 0.0001 at 12-week follow-up compared to the baseline). Considering the KM pattern scores, phlegm-dampness and fire-heat scores tended to improve after the treatment. No serious adverse events related to the intervention were reported. CONCLUSION: The potential effect of herbal medicine formulae products on improving cognitive functions in patients with cognitive impairment was observed. Further research is needed to objectify the KM pattern identification process and evaluate the KM pattern-related signs and symptoms.

Cinnamomum verum-derived O-methoxycinnamaldehyde prevents lipopolysaccharide-induced depressive-like behavior in mice via NFAT mRNA stability in T lymphocytes.

BACKGROUND: Depressive-like behaviors are related to inflammatory immune activation. Cinnamomum verum (CV) has anti-inflammatory effects, but the molecular mechanisms underlying the antidepressant effects after immunological activation still remain elusive. PURPOSE: The aim of the present study was to investigate the effect of CV in improving depressive-like behavior and explore its underlying mechanism in T lymphocytes. METHODS: Mice were randomly divided into Control, LPS, LPS plus fluoxetine, LPS plus CV, and LPS plus MCA groups. Behavior was evaluated using forced swimming test (FST) and tail suspension test (TST). The experimental group mice were exposed to LPS to induce depressive-like behavior. Cell viability was measured upon treating splenic T lymphocytes and Jurkat T cells with CV. Cytokine activity was measured using ELISA and RT-qPCR. The components of CV were analyzed by HPLC. NFAT expression was evaluated by western blotting, immunofluorescence, and luciferase assay. To verify the half-life of NFAT mRNA, Jurkat cells were treated with actinomycin D for 1.5, 3, and 4.5 h. RESULTS: CV effectively prevents inflammation-induced depressive-like behaviors. CV dose-dependently decreased protein and mRNA levels of TNFα and IL-2. Inhibition of TNFα and IL-2 production involves an MCA-mediated decrease in NFAT mRNA level, rather than inhibition of nuclear translocation. This mechanism was independent of NFAT transcription inducer p38 MAPK; it can be attributed to the promotion of NFAT mRNA decay. CONCLUSION: Overall, MCA might be an alternative or adjuvant to existing NFAT-targeting immunosuppressants for clinical prophylaxis or therapy in the context of inflammation-induced depressive disorder or other T-cell-associated inflammatory disorders.

A Pilot Study of Whether the Cold-Heat Syndrome Type is Associated with Treatment Response and Immune Status in Patients with Non-Small Cell Lung Cancer.

The cold-heat syndrome type (ZHENG) is one of the essential elements of syndrome differentiation in East Asian Medicine. This pilot study aimed to explore the characteristics of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) based on the cold-heat syndrome type. Twenty NSCLC patients treated with ICI monotherapy were included in the study and completed the cold-heat syndrome differentiation questionnaire. Demographic and clinical characteristics of the included patients were obtained through electronic medical records. Additionally, blood samples of 10 patients were analyzed with cytokine level and immune profiling. Patients were divided into two groups of cold type (n = 9) and non-cold type (n = 11), according to the cold symptoms questionnaire's cutoff point. No significant difference between the two groups was observed in clinical response to ICIs (p=0.668). Progression-free survival (PFS) seemed to be longer in patients with non-cold type than cold type (p=0.332). In patients with adenocarcinoma, the non-cold type showed longer PFS than the cold type (p=0.036). Also, there were more patients with PD-L1 negative in the cold type compared to the non-cold type (p=0.050). In immune profiling, the proportion of effector memory CD8 T-cells was higher in patients with cold type than with non-cold type (p=0.015), and the proportion of terminal effector CD8 T-cells was lower in patients with cold type than with non-cold type (p=0.005). This pilot study has shown the potential for differences in prognosis and immune status between patients with cold and non-cold types. Hopefully, it provides essential information and insight into NSCLC patients' characteristics from the perspective of syndrome differentiation. Further large-scale observational studies and intervention studies are required.

Feasibility and Effect of Electroacupuncture on Cognitive Function Domains in Patients with Mild Cognitive Impairment: A Pilot Exploratory Randomized Controlled Trial.

Although Electroacupuncture (EA) has been reported to be potentially effective for cognitive disorders, there is limited information about which domains of cognitive function can be improved by EA treatment. Sixty patients with MCI were randomly assigned (1:1:1) to groups to receive 24 sessions over 12 weeks of EA, sham EA, or usual care. In the EA group, electric stimulation was applied at bilateral PC6 and HT7. Various cognitive tests included in the Seoul Neuropsychological Screening Battery II (SNSB-II) were performed at baseline and post-treatment to explore effects of EA on five cognitive domains: attention, language, visuospatial function, memory, and frontal/executive function. Among 60 randomized participants (63.7 ± 7.1 years, 89.7% females), 45 (75%) completed the study. Of the five cognitive function domains of SNSB-II, the T score of visuospatial function showed a tendency to be higher in the EA group than in the usual care group at post-treatment assessment (mean difference: 10.16 (95% CI, 1.14, 19.18), Cohen's d = 0.72, p = 0.0283). According to the results of this pilot study, the estimated effect size of EA on the visuospatial function of MCI patients compared to usual care was medium. Large-scale clinical trials are needed to confirm effects of EA on cognitive functions.