Functional neural substrates of Parkinson's disease and potential underpinnings of acute responses to acupuncture stimulation.

Parkinson's disease is a heterogenous neurodegenerative disorder with a wide variety of motor and non-motor symptoms. This study used resting-state fMRI to identify the neural substrates of PD and explore the acute neural response to acupuncture stimulation in 74 participants (50 patients with PD and 24 healthy controls). All participants with PD were evaluated for the severity of symptoms using the Unified Parkinson's Disease Rating Scale and Balance Master. The z-transformed fractional amplitude of low-frequency fluctuation analysis showed significant differences between the PD and healthy controls in the cerebellar regions, which are thought to play a crucial role in PD pathology. Subsequently, seed-based functional connectivity of the cerebellum with the frontal, parietal, and limbic regions was identified as a potential diagnostic marker for PD. In addition, spontaneous neural activity in the precentral gyrus and thalamus was significantly associated with the severity of PD symptoms. Neural activity in the precentral gyrus, precuneus, and superior temporal gyrus showed a significant correlation with Balance Master indicators. Finally, acupuncture stimulation at GB34 significantly reduced the activity of the occipital regions in patients with PD, but this effect was not observed in healthy controls. The mixed-effects analysis revealed an interaction effects between group and acupuncture stimulation, suggesting that the modulatory effects of acupuncture could differ depending on disease status. Therefore, this study suggests the neural substrates of PD and potential underpinnings of acute neural response to acupuncture stimulation.

Traditional herbal medicine Oryeongsan for heart failure: A systematic review and meta-analysis.

Background and objective: Heart failure (HF) is associated with high mortality and hospitalization rates, and its prevalence increases with age. As congestion is the most common cause of hospitalization for HF, diuretics are the most prescribed drugs. However, these agents have side effects due to electrolyte imbalance. In Asian countries, Oryeongsan (ORS) and its variants are used to manage fluid imbalances, including HF congestion. Therefore, ORS is considered a complementary treatment to overcome the limitations of diuretics. This review aimed to elucidate the safety and effectiveness of ORS combined with conventional Western medicine (CWM) for HF. Materials and methods: A literature search was conducted using the PubMed, Embase, CENTRAL, Scopus, CiNii, CNKI, and ScienceON databases to retrieve relevant studies published up to July 2024. Two independent investigators were involved in the data collection and analysis. Randomized controlled trials (RCTs) that evaluated the effects of ORS and its variants in combination with CWM as treatments for HF were selected. The outcome measures included left ventricular ejection fraction (LVEF), total effective rate (TER), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), 6-min Walk Test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHF-Q), serum brain natriuretic peptide (BNP) level, serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, 24-h urine volume, Lee's score, and New York Heart Association (NYHA) grade I ratio for effectiveness; and incidence of adverse events (AEs) for safety. The methodological quality of the included RCTs was assessed using the Cochrane's Risk of Bias tool. Results: Fifty-nine RCTs that comprised 5069 participants and compared CWM combined with ORS and its variants (treatment group) to CWM alone or CWM plus placebo (control group) were included. Based on the meta-analysis, LVEF was found to significantly improve (mean difference: 6.36, 95 % confidence interval: 5.11 to 7.61, P < 0.00001) in the treatment group. TER, LVEDD, LVESD, 6MWT, MLHF-Q, serum BNP and NT-proBNP levels, 24-h urine volume, Lee's score, and NYHA grade I ratio were also significantly improved in the treatment group compared with the control group with CWM alone. LVEF and TER were improved without significance in the treatment group compared with the control group with CWM plus placebo. The incidence of AEs did not significantly differ between the two groups. Conclusions: Combining CWM with ORS or its variants was more effective than CWM alone in managing HF and could serve as a relatively safe treatment for HF. Further studies are required to validate the findings of the present study.

Combination therapy of acupuncture and herbal medicine for heart failure: A systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) is characterized by functional or structural dysfunction of the heart, resulting in impaired blood ejection or ventricular filling. Conventional Western Medicine (CWM) remains the mainstay of treatment for HF; however, the occurrence of adverse events (AEs) necessitates the exploration of alternative treatments. Herbal medicine and acupuncture are adjunctive therapies for HF and have shown potential for improving heart function. This systematic review and meta-analysis aimed to assess the effectiveness and safety of acupuncture and herbal medicine in treating HF. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Citation Information by National Institute of Informatics, KoreaMed, Research Information Sharing Service, and DBpia were searched for randomized controlled trials (RCTs) evaluating the effects of acupuncture and herbal medicine along with CWM as adjunctive treatments for HF, published from inception to May 31, 2024. Treatment effectiveness was determined by evaluating the left ventricular ejection fraction as the primary metric, along with the measurement of the total effective rate, brain natriuretic peptide level, N-terminal prohormone of brain natriuretic peptide level, left ventricular end-diastolic volume, and left ventricular end-systolic volume; the administration of the Minnesota Living with Heart Failure Questionnaire; and the conduct of a 6-minute walk test. Treatment safety was evaluated based on the incidence of AEs. The methodological quality of all included RCTs was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager, version 5.4.1. RESULTS: Of the 133 publications identified, 8 RCTs met the inclusion criteria. The meta-analysis showed significant improvements in left ventricular ejection fraction, brain natriuretic peptide levels, N-terminal prohormone of brain natriuretic peptide levels, left ventricular end-systolic volume, left ventricular end-diastolic volume, and 6-minute walk test results. Additionally, significant differences were observed in the total effective rate and Minnesota Living with Heart Failure Questionnaire responses. No significant medication-related AEs occurred in the intervention group. Conversely, 7 control patients developed well-known AEs associated with CWM. CONCLUSION: Acupuncture combined with herbal medicine and CWM is more effective than CWM alone, indicating a safe treatment approach. Consequently, the proactive administration of acupuncture alongside herbal medicine to patients with HF can be undertaken without concerns regarding AEs.

The usefulness of quantitative 99mTc-HMPAO WBC SPECT/CT for predicting lower extremity amputation in diabetic foot infection.

We investigated the usefulness of quantitative 99mTc-white blood cell (WBC) single photon emission computed tomography (SPECT)/computed tomography (CT) for predicting lower extremity amputation in diabetic foot infection (DFI). A total of 93 feet of 83 consecutive patients with DFI who underwent WBC SPECT/CT for treatment planning were retrospectively analysed. The clinical and SPECT/CT parameters were collected along with the measurements of the maximum standardized uptake value (SUVmax) at DFI. Statistical logistic regression analysis was performed to explore the predictors of LEA and receiver operating characteristic (ROC) curve was analysed to assess the predictive value of SPECT/CT. The independent predictors of amputation were previous amputation (OR 11.9), numbers of SPECT/CT lesions (OR 2.1), and SUVmax of DFI; either continuous SUVmax (1-increase) (OR 1.3) or categorical SUVmax > 1.1 (OR 21.6). However, the conventional SPECT/CT interpretation failed to predict amputation. In ROC analysis, the SUVmax yielded a fair predictor (area under the curve (AUC) 0.782) of amputation. The model developed from these independent predictors yielded an excellent performance for predicting amputation (AUC 0.873). Quantitative WBC SPECT/CT can provide new information useful for predicting the outcomes and guiding treatment for patients with DFI.

Prognostic Value of Radiomic Analysis Using Pre- and Post-Treatment 18F-FDG-PET/CT in Patients with Laryngeal Cancer and Hypopharyngeal Cancer.

BACKGROUND: The prognostic value of conducting 18F-FDG PET/CT imaging has yielded different results in patients with laryngeal cancer and hypopharyngeal cancer, but these results are controversial, and there is a lack of dedicated studies on each type of cancer. This study aimed to evaluate whether combining radiomic analysis of pre- and post-treatment 18F-FDG PET/CT imaging features and clinical parameters has additional prognostic value in patients with laryngeal cancer and hypopharyngeal cancer. METHODS: From 2008 to 2016, data on patients diagnosed with cancer of the larynx and hypopharynx were retrospectively collected. The patients underwent pre- and post-treatment 18F-FDG PET/CT imaging. The values of ΔPre-Post PET were measured from the texture features. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most predictive features to formulate a Rad-score for both progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curve analysis and Cox regression were employed to assess PFS and OS. Then, the concordance index (C-index) and calibration plot were used to evaluate the performance of the radiomics nomogram. RESULTS: Study data were collected for a total of 91 patients. The mean follow-up period was 71.5 mo. (8.4-147.3). The Rad-score was formulated based on the texture parameters and was significantly associated with both PFS (p = 0.024) and OS (p = 0.009). When predicting PFS, only the Rad-score demonstrated a significant association (HR 2.1509, 95% CI [1.100-4.207], p = 0.025). On the other hand, age (HR 1.116, 95% CI [1.041-1.197], p = 0.002) and Rad-score (HR 33.885, 95% CI [2.891-397.175], p = 0.005) exhibited associations with OS. The Rad-score value showed good discrimination when it was combined with clinical parameters in both PFS (C-index 0.802-0.889) and OS (C-index 0.860-0.958). The calibration plots also showed a good agreement between the observed and predicted survival probabilities. CONCLUSIONS: Combining clinical parameters with radiomics analysis of pre- and post-treatment 18F-FDG PET/CT parameters in patients with laryngeal cancer and hypopharyngeal cancer might have additional prognostic value.

The effectiveness of Kami Guibi-tang for cognitive impairment patients: A retrospective chart review.

Background: and Purpose: The number of patients with cognitive impairment is increasing worldwide. Therapeutic drugs that slow disease progression are being developed; however, further research is required. This study investigated the effects of Kami Guibi-tang on patients with various types of cognitive decline. Methods: This study was a single-center, retrospective chart review of patients who visited KyungHee University Hospital at Gangdong from January 2015 to March 2022. The study included participants who took Kami Guibi-tang for more than 90 days and were assessed on the Korean version Mini-Mental State Examination (MMSE-K) scores before and after treatment. Participants who received other liquid herbal medicines during the treatment were excluded. The outcome of interest was changed scores in MMSE-K and Short form of Geriatric Depression Scale (S-GDS). Results: A total of 31 participants were included. The total MMSE-K score significantly increased with time and showed a significant increase at 3 and 9 months compared with baseline. Among the MMSE-K subscores, the orientation subscore showed a significant increase at three months compared with baseline, and the attention and calculation subscore showed a significant increase with time. In addition, four participants with vascular dementia showed a significant increase in the total MMSE-K score over time and a significant increase after 9 months compared with baseline. The S-GDS score in 31 participants showed a significant decrease with time and at all time points compared with baseline. Conclusions: Kami Guibi-tang may improve cognitive function in patients with cognitive decline.

Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review.

PURPOSE: There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe combination and whether such regimens have differences in safety. We compared the lipid-modifying efficacy and safety of 5 mg rosuvastatin/10 mg ezetimibe to those of 20 mg rosuvastatin. MATERIALS AND METHODS: A literature search was conducted using the PubMed, EMBASE, Cochrane, Web of Sciences, and SCOPUS databases up to December 2021. Human studies investigating the two aforementioned regimens with a randomized controlled design were selected. Outcome variables included the percentage reduction in LDL-C and other lipid parameters and rates of composite adverse events (AEs), including muscle-related symptoms. A random-effects meta-analysis was performed after heterogeneity testing between studies. RESULTS: Seven studies were included in this meta-analysis. The percentage LDL-C reduction did not differ between the combination and monotherapy groups [standardized mean difference (SMD) 0.08; 95% confidence interval (CI) -0.09 to 0.26; p=0.35]. The risk of composite AEs (odds ratio 0.50; 95% CI 0.15 to 1.72; p=0.27) of the combination was not different compared to the monotherapy group. The percentage of total cholesterol reduction was greater in the combination group (SMD 0.22; p=0.02), whereas that of triglyceride reduction and high-density lipoprotein cholesterol elevation did not differ between the two groups. CONCLUSION: This meta-analysis showed that 5 mg rosuvastatin/10 mg ezetimibe had largely comparable lipid-modifying efficacy and tolerability as 20 mg rosuvastatin.

Prediction of Neoadjuvant Chemoradiotherapy Response in Rectal Cancer Patients Using Harmonized Radiomics of Multcenter 18F-FDG-PET Image.

We developed machine and deep learning models to predict chemoradiotherapy in rectal cancer using 18F-FDG PET images and harmonized image features extracted from 18F-FDG PET/CT images. Patients diagnosed with pathologic T-stage III rectal cancer with a tumor size > 2 cm were treated with neoadjuvant chemoradiotherapy. Patients with rectal cancer were divided into an internal dataset (n = 116) and an external dataset obtained from a separate institution (n = 40), which were used in the model. AUC was calculated to select image features associated with radiochemotherapy response. In the external test, the machine-learning signature extracted from 18F-FDG PET image features achieved the highest accuracy and AUC value of 0.875 and 0.896. The harmonized first-order radiomics model had a higher efficiency with accuracy and an AUC of 0.771 than the second-order model in the external test. The deep learning model using the balanced dataset showed an accuracy of 0.867 in the internal test but an accuracy of 0.557 in the external test. Deep-learning models using 18F-FDG PET images must be harmonized to demonstrate reproducibility with external data. Harmonized 18F-FDG PET image features as an element of machine learning could help predict chemoradiotherapy responses in external tests with reproducibility.

Effect of an herbal medicine, Chunghyul-dan, on prevention of recurrence in patients with ischemic stroke: A retrospective cohort study.

Research indicates that Chunghyul-dan (CHD), a herbal medicine, has an inhibitory effect on stroke recurrence in small vessel disease. Recent studies have suggested that CHD might also act on large arteries. This study aimed to verify the preventive effect of CHD on strokes of all the Trial of Org 10172 in Acute Stroke Treatment (TOAST) causative classifications. We retrospectively analyzed 2 years of medical records of patients with ischemic stroke treated with CHD, 600 mg once daily, in combination with antiplatelet or anticoagulant agents. The prevalence of stroke recurrence in 2 years was analyzed. Stroke recurrence was defined as new neurological symptoms with corresponding brain imaging results. Nine of the 202 patients (4.46%) had recurrent ischemic stroke. Four occurred within 180 days, 3 between 180 and 365 days, and 2 between 365 and 730 days. All had only 1 recurrence. The recurrence rates were 1.12%, 5%, and 5.48% for small vessel occlusion, cardioembolism, and large vessel atherosclerosis, respectively. There were no adverse effects. These results suggest that CHD could inhibit ischemic stroke recurrence of all TOAST causative categories. A randomized controlled trial is needed to confirm this hypothesis.

Effect of Kami Guibi-tang (KGT) in elderly subjects with insomnia: a study protocol from a single center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The incidence of insomnia increases with age and is related to cognitive function in older adults; therefore, it is important to manage it actively. In this study, we report a protocol for the evaluation of the efficacy and safety of Kami Guibi-tang (KGT), a herbal prescription that has been widely used in East Asia for insomnia, forgetfulness, and depression, in older adults with insomnia. METHODS: In this single-center, double-blind, randomized controlled trial, 60 older adults with insomnia and subjective cognitive decline will be recruited and randomly assigned to the KGT or placebo group. The KGT group will take KGT granules thrice a day for 12 weeks, whereas the control group will take placebo granules in the same manner. Participants will be assessed for sleep, cognitive function, quality of life, and depression using the Pittsburgh Sleep Quality Index-Korean (PSQI-K), Insomnia Severity Index-Korean (ISI-K), Seoul Neuropsychological Screening Battery-Dement (SNSB-D), 36-item MOS Short Form Survey (SF-36) and Short version of the Geriatric Depression Scale (S-GDS) before and at the end of administration of the investigational product. The PSQI-K, ISI-K, and SF-36 will be further assessed 12 weeks after the end of medication to determine whether the effects on sleep and quality of life are sustained. The PSQI-K total score difference between the two groups at 12 and 24 weeks will be the primary outcome; all other endpoints will be secondary. Safety will be assessed by performing blood tests and electrocardiograms before taking the investigational drug, 6 weeks after taking the drug, and 12 weeks after taking the drug; any adverse events will be observed throughout the study. DISCUSSION: The protocol will provide a detailed process for a clinical trial to evaluate the efficacy and safety of KGT in elderly patients with insomnia. We will also investigate if changes in cognitive function correlated with improvements in insomnia. TRIAL REGISTRATION: This trial was registered at CRIS (Clinical Research Information Service) on April 27, 2023 (KCT0008391, version 2.0).  https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24811&search_page=L .

Development and External Validation of 18F-FDG PET-Based Radiomic Model for Predicting Pathologic Complete Response after Neoadjuvant Chemotherapy in Breast Cancer.

The aim of our retrospective study is to develop and externally validate an 18F-FDG PET-derived radiomics model for predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. A total of 87 breast cancer patients underwent curative surgery after NAC at Soonchunhyang University Seoul Hospital and were randomly assigned to a training cohort and an internal validation cohort. Radiomic features were extracted from pretreatment PET images. A radiomic-score model was generated using the LASSO method. A combination model incorporating significant clinical variables was constructed. These models were externally validated in a separate cohort of 28 patients from Soonchunhyang University Buscheon Hospital. The model performances were assessed using area under the receiver operating characteristic (AUC). Seven radiomic features were selected to calculate the radiomic-score. Among clinical variables, human epidermal growth factor receptor 2 status was an independent predictor of pCR. The radiomic-score model achieved good discriminability, with AUCs of 0.963, 0.731, and 0.729 for the training, internal validation, and external validation cohorts, respectively. The combination model showed improved predictive performance compared to the radiomic-score model alone, with AUCs of 0.993, 0.772, and 0.906 in three cohorts, respectively. The 18F-FDG PET-derived radiomic-based model is useful for predicting pCR after NAC in breast cancer.

Oncologic Outcomes in Nipple-sparing Mastectomy with Immediate Reconstruction and Total Mastectomy with Immediate Reconstruction in Women with Breast Cancer: A Machine-Learning Analysis.

BACKGROUND: This study used a single-institution cohort, the Severance dataset, validated the results by using the surveillance, epidemiology, and end results (SEER) database, adjusted with propensity-score matching (PSM), and analyzed by using a machine learning method. To determine whether the 5-year, disease-free survival (DFS) and overall survival (OS) of patients undergoing nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) are not inferior to those of women treated with total mastectomy/skin-sparing mastectomy (TM/SSM). METHODS: The Severance dataset enrolled 611 patients with early, invasive breast cancer from 2010 to 2017. The SEER dataset contained data for 485,245 patients undergoing TM and 14,770 patients undergoing NSM between 2000 and 2018. All patients underwent mastectomy and IBR. Intraoperative, frozen-section biopsy for the retro-areolar tissue was performed in the NSM group. The SEER dataset was extracted by using operation types, including TM/SSM and NSM. The primary outcome was DFS for the Severance dataset and OS for the SEER dataset. PSM analysis was applied. Survival outcomes were analyzed by using the Kaplan-Meier method and Cox proportional hazard (Cox PH) regression model. We implemented XGBSE to predict mortality with high accuracy and evaluated model prediction performance using a concordance index. The final model inspected the impact of relevant predictors on the model output using shapley additive explanation (SHAP) values. RESULTS: In the Severance dataset, 151 patients underwent NSM with IBR and 460 patients underwent TM/SSM with IBR. No significant differences were found between the groups. In multivariate analysis, NSM was not associated with reduced oncologic outcomes. The same results were observed in PSM analysis. In the SEER dataset, according to the SHAP values, the individual feature contribution suggested that AJCC stage ranks first. Analyses from the two datasets confirmed no impact on survival outcomes from the two surgical methods. CONCLUSIONS: NSM with IBR is a safe and feasible procedure in terms of oncologic outcomes. Analysis using machine learning methods can be successfully applied to identify significant risk factors for oncologic outcomes.

A randomized trial of genotype-guided perindopril use.

OBJECTIVE: Cough caused by angiotensin-converting enzyme inhibitors (ACEIs) limits their clinical application and cardiovascular benefits. This randomized trial investigated whether genotype-guided perindopril use could reduce drug-related cough in 20 to 79-year-old individuals with hypertension. METHODS: After screening 120 patients and randomization, 68 were assigned to genotyping ( n  = 41) and control ( n  = 27) groups. NELL1 p.Arg382Trp (rs8176786) and intron (rs10766756) genotype information was used to subdivide the genotyping group into high-risk and low-risk subgroups with at least one or no risk alleles for ACEI-related cough, respectively. The high-risk subgroup received candesartan (8 mg/day) for 6 weeks, whereas the low-risk subgroup received perindopril (4 mg/day). The control group, which was not genotyped, received perindopril (4 mg/day). The primary outcome variables were cough and moderate/severe cough; the secondary outcome variable was any adverse event. RESULTS: During the 6-week period, the risk of cough was lower in the genotyping group than in the control group [five (12.2%) and nine (33.3%) participants, respectively; hazard ratio: 0.25; log-rank P  = 0.017]. The moderate/severe cough risk was also lower in the genotyping group [one (2.4%) and five (18.5%) participants, respectively; hazard ratio: 0.12; log-rank P  = 0.025]. Differences in cough (hazard ratio: 0.56; log-rank P  = 0.32) and moderate/severe cough risk (hazard ratio: 0.26; log-rank P  = 0.19) between the low-risk and control groups were not significant. The risk of total adverse events was similar between any two groups. CONCLUSION: Cough risk was lower during genotype-guided treatment than during conventional treatment. These results support the utility of NELL1 variant data in clinical decision making to personalize renin-angiotensin system blocker therapy use. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT05535595 (retrospectively registered at September 7, 2022).

Association of Hearing Loss With Anatomical and Functional Connectivity in Patients With Mild Cognitive Impairment.

Importance: Hearing loss is the most important modifiable risk factor for cognitive impairment; however, the association of hearing loss with anatomical and functional connectivity is not fully understood. This association may be elucidated by evaluating the findings of newer imaging technologies. Objectives: To evaluate the association of hearing loss with anatomical and functional connectivity in patients with mild cognitive impairment (MCI) by using multimodal imaging technology. Design, Setting, and Participants: This was a prospective cross-sectional study of patients with MCI under the care of a neurology clinic at the Soonchunhyang University Bucheon Hospital (Republic of Korea) from April to September 2021. Data were analyzed from April 1 to June 30, 2022. Main Outcomes and Measures: Pure tone averages (PTA) and word recognition scores were used to measure hearing acuity. Magnetic resonance imaging (MRI) and positron emission tomography scans of the brain were used to assess functional and anatomical connectivity. Results of diffusion MRI, voxel- and surface-based morphometric imaging, and global brain amyloid standardized uptake ratio were analyzed. Neuroimaging parameters of patients with MCI plus hearing loss were compared with those of patients with MCI and no hearing loss. Correlation analyses among neuroimaging parameters, PTA, and word recognition scores were performed. Results: Of 48 patients with MCI, 30 (62.5%) had hearing loss (PTA >25 dB) and 18 (37.5%) did not (PTA ≤25 dB). Median (IQR) age was 73.5 (69.0-78.0) years in the group with hearing loss and 75.0 (65.0-78.0) years in the group with normal hearing; there were 20 (66.7%) and 14 (77.8%) women in each group, respectively. The group with MCI plus hearing loss demonstrated decreased functional connectivity between the bilateral insular and anterior divisions of the cingulate cortex, and decreased fractional anisotropy in the bilateral fornix, corpus callosum forceps major and tapetum, left parahippocampal cingulum, and left superior thalamic radiation. Fractional anisotropy in the corpus callosum forceps major and bilateral parahippocampal cingulum negatively correlated with the severity of hearing loss shown by PTA testing. The 2 groups were not significantly different in global ß-amyloid uptake, gray matter volume, and cortical thickness. Conclusion and Relevance: The findings of this prospective cross-sectional study suggest that alterations in the salience network may contribute to the neural basis of cognitive impairment associated with hearing loss in patients who are on the Alzheimer disease continuum.

Vision for tobacco endgame in Korea: suggestions for countries with endgame aspirations.

Tobacco endgame is a focal point of discussion at both national and international levels. We aimed to describe efforts related to achieving the tobacco endgame in the Republic of Korea, an exemplar of a country with endgame aspirations, and compare them with the efforts of other nations. We reviewed the tobacco endgame efforts of three nations considered tobacco control leaders: New Zealand (NZ), Australia and Finland. The efforts/attempts of each country were described using an endgame strategy category. The tobacco control leaders had explicit goals to achieve a smoking prevalence of <5% before a target date and had legislation and research centres for tobacco control and/or endgame. NZ is implementing a mixture of conventional and innovative endgame interventions; the others use incremental conventional approaches. In Korea, there has been an attempt to ban the sale and manufacture of combustible cigarettes. The attempt led to the filing of a petition, and a survey of adults showed 70% supported the legislation banning tobacco. The Korean government mentioned a tobacco endgame in a 2019 plan, yet a target and an end date were absent. The 2019 plan in Korea included incremental FCTC strategies. Practices in the leading countries show that legislation and research are key to ending the tobacco epidemic. The MPOWER measures must be strengthened, endgame objectives must be set and bold strategies must be adopted. Key endgame policies include those with evidence of effectiveness, such as retailer reductions.

A Comparative Study on the Neuroprotective Effect of Geopung-Chunghyuldan on In Vitro Oxygen-Glucose Deprivation and In Vivo Permanent Middle Cerebral Artery Occlusion Models.

Geopung-Chunghyuldan (GCD), which is a mixture of Chunghyuldan (CD), Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, is used to treat ischemic stroke in traditional Korean medicine. This study aimed to investigate the effects of GCD and CD on ischemic brain damage using in vitro and in vivo stroke models, as well as to elucidate the synergistic effects of GCD against ischemic insult. To study the effect of GCD in an in vitro ischemia model, SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD). Cell death after 16 h of OGD exposure was measured using the MTT assay and live/dead cell counting methods. An in vivo ischemia mice model was established through permanent middle cerebral artery occlusion (pMCAO). To determine the neuroprotective effect of GCD, it was orally administered immediately and 2 h after pMCAO. The infarct volume was measured through 2,3,5-triphenyltetrazolium chloride staining at 24 h after pMCAO. Compared with the control group, GCD treatment significantly reduced OGD-induced cell death in SH-SY5Y cells; however, CD treatment did not show a significant protective effect. In the pMCAO model, compared with the control group, treatment with GCD and CD significantly and mildly reduced the infarct volume, respectively. Our findings indicate that compared with CD, GCD may allow a more enhanced neuroprotective effect in acute ischemic stroke, indicating a potential synergistic neuroprotective effect. The possibility of GCD as a novel alternative choice for the prevention and treatment of ischemic stroke is suggested.

A Systematic Review of In Vivo Studies of the Efficacy of Herbal Medicines for Anti-Aging in the Last Five Years.

BACKGROUND: The world's population is rapidly aging, and attention to and research on the increase in life expectancy and age-related diseases are needed. This study aimed to review the in vivo studies on the anti-aging effects of herbal medicines. METHODS: In vivo studies of single or complex herbal medicines for anti-aging that were published in the last five years were included in this review. The following databases were used: PubMed, Scopus, ScienceDirect, Web of Science and EMBASE. RESULTS: A total of 41 studies were considered eligible for the review. The articles were classified into body organs and functions, experimental country, herbal medicine, extraction method, administration route, dosage, duration, animal model, aging-induced method, sex, number of animals per group, and outcomes and mechanisms A single herbal extract was used in a total of 21 studies including Alpinia oxyphylla Miq., Acanthopanax senticosus and Lyceum barbarum, and a multi-compound herbal prescription was used in a total of 20 studies, including Modified Qiongyu paste, Wuzi Yanzong recipe, etc. Each herbal medicine had anti-aging effects on learning and memory, cognition, emotion, internal organs, gastrointestinal tracts, sexual functions, musculoskeletal function and so on. The common mechanisms of action were antioxidant and anti-inflammatory, and various effects and mechanisms for each organ and function were identified. CONCLUSIONS: Herbal medicine exhibited beneficial effects on anti-aging in various parts of the body and its function. Further investigation of the appropriate herbal medicine prescriptions and their components is recommended.

Efficacy of Artemisia annua Linné in improving cognitive impairment in a chronic cerebral hypoperfusion-induced vascular dementia animal model.

BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Currently, no FDA-approved drugs are available for the treatment of VaD. Artemisia annua Linné (AA) is known to have antioxidant properties, but its effects and mechanisms of action on cognitive impairment are still unknown. PURPOSE: In this study, the improvement in cognitive impairment by AA in terms of protection against oxidative stress, neuroinflammation, and preservation of the integrity of the neurovascular unit (NVU) was assessed in an animal model of VaD with bilateral common carotid artery occlusion (BCCAO). METHODS: Eight-week-old male Wistar rats were allowed to adapt for four weeks, and BCCAO was induced at 12 weeks of age. The rats were randomly assigned into four groups, with seven rats in each group: sham group without BCCAO, VaD group that received oral administration of distilled water after BCCAO surgery, and two AA groups that received oral administration of 150 mg/kg or 750 mg/kg AA after BCCAO surgery for 8 weeks. Nine weeks after BCCAO surgery, the cognitive function of the rats was evaluated and accumulated oxidative stress was assessed by immunohistochemistry, immunofluorescence, and western blotting. Damage to the components of the NVU was evaluated, and sirtuin (Sirt) 1 and 2 expression and nuclear factor-erythrocyte 2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) activation were investigated to assess the reduction in cell signaling and antioxidant pathways. RESULTS: BCCAO-induced cerebral perfusion decreased memory function and induced neuroinflammation and oxidative stress. But AA treatment mitigated cognitive impairment and reduced neuroinflammation and oxidative stress caused by chronic cerebral hypoperfusion. AA extracts activated the Nrf2/Keap1/activating antioxidant response elements pathway and maintained Sirt 1 and 2, subsequently leading to the maintenance of neurons, improved construct of microvessels, increased platelet-derived growth factor receptor beta, and platelet-endothelial cell adhesion molecule-1 associated with the blood-brain barrier integrity. CONCLUSION: AA is effective in alleviating BCCAO-induced cognitive decline and its administration may be a useful therapeutic approach for VaD.

Efficacy of Kami Guibi-tang as an Add-On Therapy to Acetylcholinesterase Inhibitor for Cognitive Function in Mild Alzheimer's Disease: A Pilot Study.

Background: Kami Guibi-tang (KGT), a traditional Korean herbal medicine is mainly used to treat insomnia and nervousness. Acetylcholinesterase inhibitors (AChEIs) are the main treatments for mild Alzheimer's disease (AD), a degenerative brain disease. However, currently no drug can fundamentally treat AD or reverse the advanced cognitive decline. This clinical study explored the efficacy and safety of adding KGT to AChEI for cognitive function in mild AD. Methods: This was a pilot study for a larger randomized, double-blind, placebo-controlled trial. Participants between 55-90 years diagnosed with mild AD were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea. They were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary outcome was treatment efficacy, as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D). Changes in SNSB subscores were assessed as secondary outcomes. Safety parameters, including adverse events and abnormalities in blood tests, electrocardiograms, and brain magnetic resonance imaging were also monitored. Results: Between March 2018 and November 2020, seven participants each in the KGT group and the placebo group completed the 24-week trial. There were no significant changes in SNSB-D total or subindex scores for either group (p = 0.69 and 0.63, respectively), and no significant differences were observed between them (p=0.71). No adverse events related to KGT were reported. We also compared and analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment (aMCI) using protocol of this study. The aMCI group showed a significant improvement in the total SNSB-D score, especially in the memory domain, compared to the mild AD group (p = 0.04 and 0.02, respectively). The Korean Mini-Mental State Exam and Korean Instrumental Activities of Daily Living scores also significantly improved in the aMCI group (p = 0.01 and 0.02, respectively). Conclusions: Compared to placebo, adding KGT to AChEI did not significantly improve cognitive function in SNSB in patients with mild AD. We suggest that KGT would have a positive effect on patients with early stages of cognitive impairment such as aMCI. The findings could assist design larger, longer-term clinical trials of KGT use in elderly patients with mild AD. This study was registered in the Korean Clinical Trial Registry on December 26, 2017, with the CRIS approval number KCT0002904.

Effectiveness and Therapeutic Mechanism of Pharmacopuncture for Pain in Parkinson's Disease: A Study Protocol for a Pilot Pragmatic Randomized, Assessor-Blinded, Usual Care-Controlled, Three-Arm Parallel Trial.

Pain in Parkinson's disease (PD) represents a complex phenotype known to decrease quality of life. This pragmatic randomized, controlled clinical trial evaluated the efficacy of pharmacopuncture (PA) for improving pain symptoms and investigated the corresponding therapeutic mechanisms in patients with PD. Ninety patients with PD-related pain were randomly allocated to receive either PA, manual acupuncture, or usual care in a 1:1:1 ratio; sixty healthy controls were included for comparative analysis of brain imaging data. Over 12 weeks, study treatment provided 2 days per week for 8 weeks with a follow-up period of 4 weeks. The primary outcome measure was the King's Parkinson's Disease Pain Scale score for assessing improvement in PD-related pain, including a sub-analysis to investigate the pattern of changes in pain according to a PD-related pain mechanism-based classification. Secondary outcome measures included a numerical rating scale-based assessment of the intensity and location of pain and changes in pain-associated symptoms, such as depression, anxiety, and sleep disorders. Exploratory outcome measures included structural and functional brain patterns on magnetic resonance imaging, blood molecular signature changes, gait analysis, facial expression and movement assessment in response to emotional stimuli, and a traditional Korean medicine syndrome differentiation questionnaire. The trial findings provided important clinical evidence for the effectiveness of PA in the management of PD-related pain and its associated symptoms, and helped elucidate the mechanism of its therapeutic effect on PD-related pain.