Menopausal Hormone Therapy and Osteoarthritis Risk: Retrospective Population-Based Study in South Korea.

OBJECTIVES: This study aimed to investigate the risk of osteoarthritis associated with menopausal hormone therapy (MHT). METHODS: This population-based retrospective cohort study used a database of Korean health insurance claims (2007-2020). Females aged ≥ 40 who initiated menopause-related healthcare visits between 2011 and 2014 were identified. The MHT group comprised females aged ≥ 40 who initiated MHT for ≥ 6 months during this period. The non-MHT group comprised females aged ≥ 40 who attended menopause-related healthcare visits but did not receive MHT. To account for potential confounding factors, the two groups were matched at a 1:1 ratio using propensity score matching. RESULTS: A cohort of 453,040 postmenopausal females aged ≥ 40 years was identified, with 26,354 assigned to either the MHT or non-MHT group after propensity matching. The median age was 49 years, and the median follow-up was 8.2 years. The Cox proportional hazards model demonstrated an elevated risk of osteoarthritis with MHT (hazard ratio [HR], 1.154; 95% confidence interval [CI], 1.117-1.193) for knee (HR, 1.148; 95% CI, 1.102-1.195) and other arthritis (HR, 1.205; 95% CI, 1.151-1.261), although not statistically significant for hip arthritis. Tibolone (HR, 1.211; 95% CI, 1.161-1.263), estrogen-progestogen therapy (EPT) (HR, 1.092; 95% CI, 1.048-1.137), and estrogen therapy (ET) (HR, 1.235; 95% CI, 1.148-1.329) were associated with a higher risk of osteoarthritis compared to non-MHT users. CONCLUSIONS: MHT was associated with an increased risk of osteoarthritis, consistently observed across tibolone, EPT, and ET, particularly affecting joints other than the hip, with a trend toward an elevated risk of hip osteoarthritis.

Glucose-dependent insulinotropic polypeptide (GIP) alleviates ferroptosis in aging-induced brain damage through the Epac/Rap1 signaling pathway.

Glucose-dependent insulinotropic polypeptide (GIP), a 42-aminoacid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, promoting neuronal proliferation, maintaining physiological homeostasis, and inhibiting cell death, all of which play a crucial role in the context of neurodegenerative diseases. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell model, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the Epac/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for the pathogenesis of ferroptosis in neurodegenerative diseases and aging. [BMB Reports 2024; 57(9): 417-423].

A humanized ACE2 mouse model recapitulating age- and sex-dependent immunopathogenesis of COVID-19.

In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments.

Brown garlic: A nutritionally improved garlic with therapeutic value in asthma treatment via modulation of S-nitrosothiols.

Nitric Oxide (NO) regulates important physiological functions. Garlic (Allium sativum) is an important food component consumed fresh and processed for thousands of years. It has high L-arginine, which contributes to the NO system in the body. Both garlic and NO impact important physiological processes. Here we produced brown garlic, with significantly higher nutritional and therapeutic value compared to fresh and black garlic. Lower exhaled NO was recorded in asthmatic mice fed with brown garlic but with higher blood SNOs and no change in eNOS and iNOS expression. Lung biopsy showed reduced eosinophil accumulation in asthmatic mice fed with brown garlic. Real-time PCR and Western blot analyses indicated high expression of antioxidant genes but reduced interleukin genes, IL-4, IL-5, IL-6, IL-13, IL1ß, and TNF-α brown garlic-fed asthmatic mice as compared to that in fresh and black garlic-fed asthmatic mice. This study provides the first comprehensive and conclusive insight into the nutritional benefits of brown garlic and its therapeutic value for the treatment of asthma in animals.

Activity in the dorsal hippocampus-mPFC circuit modulates stress-coping strategies during inescapable stress.

Anatomical connectivity and lesion-deficit studies have shown that the dorsal and ventral hippocampi contribute to cognitive and emotional processes, respectively. However, the role of the dorsal hippocampus (dHP) in emotional or stress-related behaviors remains unclear. Here, we showed that neuronal activity in the dHP affects stress-coping behaviors in mice via excitatory projections to the medial prefrontal cortex (mPFC). The antidepressant ketamine rapidly induced c-Fos expression in both the dorsal and ventral hippocampi. The suppression of GABAergic transmission in the dHP-induced molecular changes similar to those induced by ketamine administration, including eukaryotic elongation factor 2 (eEF2) dephosphorylation, brain-derived neurotrophic factor (BDNF) elevation, and extracellular signal-regulated kinase (ERK) phosphorylation. These synaptic and molecular changes in the dHP induced a reduction in the immobility time of the mice in the tail-suspension and forced swim tests without affecting anxiety-related behavior. Conversely, pharmacological and chemogenetic potentiation of inhibitory neurotransmission in the dHP CA1 region induced passive coping behaviors during the tests. Transneuronal tracing and electrophysiology revealed monosynaptic excitatory connections between dHP CA1 neurons and mPFC neurons. Optogenetic stimulation of dHP CA1 neurons in freely behaving mice produced c-Fos induction and spike firing in the mPFC neurons. Chemogenetic activation of the dHP-recipient mPFC neurons reversed the passive coping behaviors induced by suppression of dHP CA1 neuronal activity. Collectively, these results indicate that neuronal activity in the dHP modulates stress-coping strategies to inescapable stress and contributes to the antidepressant effects of ketamine via the dHP-mPFC circuit.

Raepenol™ Cream, a Complex of Natural Compounds, Promotes Wound Healing and Relieves Pruritus In Vivo.

BACKGROUND/AIM: Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial. MATERIALS AND METHODS: This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response. RESULTS: Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears. CONCLUSION: Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments.

Protective Effects of Imatinib on a DSS-induced Colitis Model Through Regulation of Apoptosis and Inflammation.

BACKGROUND/AIM: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and a multifactorial etiology. While imatinib has demonstrated efficacy in the treatment of immune-related diseases, its potential effects in IBD treatment remain underexplored. MATERIALS AND METHODS: This study aimed to investigate the therapeutic effects of imatinib in colitis treatment. A dextran sulfate sodium (DSS)-induced colitis model was used to mimic IBD in mice. Imatinib was administered orally to mice simultaneously with DSS treatment. The effects of imatinib on DSS-induced colitis were evaluated by analyzing colitis-related pathology, including the disease activity index (DAI), histological lesions, inflammatory markers, and tight junction integrity. Additionally, western blot analysis and quantitative real-time polymerase chain reaction were used to assess inflammatory markers, tight-junction proteins, and cell death. RESULTS: In the DSS-induced colitis model, imatinib treatment exerted protective effects by attenuating weight loss, restoring colon length, reducing spleen weight, and improving the DAI score and histological lesions. Additionally, imatinib reduced the level of proinflammatory cytokines, including TNF-α, IL-6, and IL-1ß. Furthermore, imatinib treatment restored tight-junction integrity and decreased the expression of apoptosis marker proteins. CONCLUSION: Overall, imatinib treatment significantly alleviated the symptoms of DSS-induced colitis by influencing the expression of proinflammatory cytokines, tight junction proteins, and apoptotic markers in mice. These findings highlight imatinib as a potential therapeutic candidate for IBD.

Silibinin Mitigates Vanadium-induced Lung Injury via the TLR4/MAPK/NF-κB Pathway in Mice.

BACKGROUND/AIM: Silibinin, has been investigated for its potential benefits and mechanisms in addressing vanadium pentoxide (V2O5)-induced pulmonary inflammation. This study explored the anti-inflammatory activity of silibinin and elucidate the mechanisms by which it operates in a mouse model of vanadium-induced lung injury. MATERIALS AND METHODS: Eight-week-old male BALB/c mice were exposed to V2O5 to induce lung injury. Mice were pretreated with silibinin at doses of 50 mg/kg and 100 mg/kg. Histological analyses were performed to assess cell viability and infiltration of inflammatory cells. The expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) and activation of the MAPK and NF-[Formula: see text]B signaling pathways, as well as the NLRP3 inflammasome, were evaluated using real-time PCR, western blot analysis, and immunohistochemistry. Whole blood analysis was conducted to measure white blood cell counts. RESULTS: Silibinin treatment significantly improved cell viability, reduced inflammatory cell infiltration, and decreased the expression of pro-inflammatory cytokines in V2O5-induced lung injury. It also notably suppressed the activation of the MAPK and NF-[Formula: see text]B signaling pathways, along with a marked reduction in NLRP3 inflammasome expression levels in lung tissues. Additionally, silibinin-treated groups exhibited a significant decrease in white blood cell counts, including neutrophils, lymphocytes, and eosinophils. CONCLUSION: These findings underscore the potent anti-inflammatory effects of silibinin in mice with V2O5-induced lung inflammation, highlighting its therapeutic potential. The study not only confirms the efficacy of silibinin in mitigating inflammatory responses but also provides a foundational understanding of its role in modulating key inflammatory pathways, paving the way for future therapeutic strategies against pulmonary inflammation induced by environmental pollutants.

A machine learning-based electronic nose system using numerous low-cost gas sensors for real-time alcoholic beverage classification.

This study introduces numerous low-cost gas sensors and a real-time alcoholic beverage classification system based on machine learning. Dogs possess a superior sense of smell compared to humans due to having 30 times more olfactory receptors and three times more olfactory receptor types than humans. Thus, in odor classification, the number of olfactory receptors is a more influential factor than the number of receptor types. From this perspective, this study proposes a system that utilizes distinctive data patterns resulting from heterogeneous responses among numerous low-cost homogeneous MOS-based sensors with poor gas selectivity. To evaluate the performance of the proposed system, learning data were gathered using three alcoholic beverage groups including different aged whiskeys, Korean soju with 99% same compositions, and white wines made from the Sauvignon blanc variety, sourced from various countries. The electronic nose system was developed to classify alcoholic samples measured using 30 gas sensors in real time. The samples were injected into a gas chamber for 60 seconds, followed by a 60-second injection of clean air. After preprocessing the time-series data into four distinct datasets, the data were analyzed using a machine learning algorithm, and the classification results were compared. The results showed a high classification accuracy of over 99%, and it was observed that classification performance varied depending on data preprocessing. As the number of gas sensors increased, the prediction accuracy improved, reaching up to 99.83 ± 0.21%. These experimental results indicated that the proposed electronic nose system's classification performance was comparable to that of commercial electronic nose systems. Additionally, the implementation of an alcoholic beverage classification system based on a pretrained LDA model demonstrated the feasibility of real-time classification using the proposed system.

COVID-19 and Neurodevelopmental Delays in Early Childhood: A Longitudinal Analysis of Developmental Outcomes in Korean Children.

This study employed a longitudinal analysis to evaluate the association between the coronavirus disease 2019 pandemic and neurodevelopment by analyzing over 1.8 million children from the Korean Developmental Screening Test for Infants and Children included in South Korea's National Health Screening Program. We compared the developmental outcomes in five age groups-9-17 months, 18-29 months, 30-41 months, 42-53 months, and 54-65 months-between the pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Significant increases in potential developmental delays were observed during the pandemic in communication, cognitive, social interaction, self-care, and fine motor skills across most age groups. All five age groups experienced notable disruptions in communication and fine motor skills. Children from socioeconomically disadvantaged backgrounds faced higher risks across all domains. These findings highlight the need for targeted interventions and continuous monitoring to support the developmental needs of children affected by pandemic-related disruptions.

Corrigendum: Pre-transplant crossmatch-negative donor-specific anti-HLA antibody predicts acute antibody-mediated rejection but not long-term outcomes in kidney transplantation: an analysis of the Korean Organ Transplantation Registry.

[This corrects the article DOI: 10.3389/fimmu.2024.1420351.].

Corrigendum: Effects of exercise treatment on functional outcome parameters in mid-portion Achilles tendinopathy: a systematic review.

[This corrects the article DOI: 10.3389/fspor.2023.1144484.].

Universal health coverage saves more lives among severely ill COVID-19 patients: A difference-in-differences analysis of individual patient data in South Korea.

BACKGROUND: Universal health coverage (UHC) ensures affordability of a variety of essential health services for the general population. Although UHC could mitigate the harmful effects of coronavirus disease 2019 (COVID-19) on patients and their socioeconomic position, the debate on UHC's scope and ability to improve health outcomes is ongoing. This study aimed to identify the impact of UHC policy withdrawal on the health outcomes of South Korea's severely ill COVID-19 patients. METHODS: We used a propensity score matching (PSM) and difference-in-differences combined model. This study's subjects were 44,552 hospitalized COVID-19 patients contributing towards health insurance claims data, COVID-19 notifications and vaccination data extracted from the National Health Information Database and the Korea Disease Control and Prevention Agency from 1 December 2020 to 30 April 2022. After PSM, 2460 patients were included. This study's exposures were severity of illness and UHC policy change. The primary outcome was the case fatality rate (CFR) for COVID-19, which was defined as death within 30 days of a COVID-19 diagnosis. There were four secondary outcomes, including time interval between diagnosis and hospitalization (days), length of stay (days), total medical expenses (USD) and the time interval between diagnosis and death (days). RESULTS: After the UHC policy's withdrawal, the severely ill patients' CFR increased to 284 per 1000 patients [95% confidence interval (CI) 229.1-338.4], hospitalization days decreased to 9.61 days (95% CI -11.20 to -8.03) and total medical expenses decreased to 5702.73 USD (95% CI -7128.41 to -4202.01) compared with those who were not severely ill. CONCLUSIONS: During the pandemic, UHC may have saved the lives of severely ill COVID-19 patients; therefore, expanding services and financial coverage could be a crucial strategy during public health crises.

The effects of gaze stability exercises on balance, gait ability, and fall efficacy in patients with chronic stroke: A 2-week follow-up from a randomized controlled trial.

BACKGROUND: This study aimed to examine the effect of gaze stability exercises on balance, gait ability, and fall efficacy in patients with chronic stroke, as well as to investigate whether any observed effects were maintained 2 weeks later. METHODS: In this experiment, 30 chronic stroke patients were selected. The patients were randomly divided into 3 groups (10 patients in each group). All patients in the 3 groups performed basic neurodevelopmental treatment. Group 1 performed balance exercises accompanied by gaze stability exercises. Group 2 performed gaze stability exercises, and group 3 performed balance exercises. Each exercise program for 40 minutes 3 times a week for 4 weeks. After the intervention period, the patient's balance, gait ability, and fall efficacy were measured again. In order to know whether the training effect is maintained, a 2-week follow-up test was conducted after the training. RESULTS: The results of this study showed that there was a significant improve in balance (overall stability index, limit of stability test, and Berg Balance Scale), gait ability (gait velocity, cadence, step time and step length, Timed Up and Go [TUG] test), and fall efficacy over the different time within the 3 groups. The effect was observed to be maintained in follow-up tests after 2 weeks. In the comparison among 3 groups, the overall stability index, limit of stability test in the balance test and the gait velocity, cadence, step time, step length and Timed Up and Go test in the gait test all showed statistically significant differences, and the other items did not have significant differences. In most of the assessments, group 1 that used balance exercise combined with gaze stability exercise showed a better improvement than the other 2 groups. CONCLUSION: As a result, for stroke patients, gaze stability exercise is an effective arbitration method to improve balance and gait ability and fall efficacy. With balance exercise combined with gaze stability exercise, a greater effect can be seen than with gaze stability exercise or balance exercise alone. Thus, this combination exercise program can be recommended as effective.

Testing reliability and validity of the Korean version of Debriefing Assessment for Simulation in Healthcare (K-DASH).

BACKGROUND: Use of the Debriefing Assessment for Simulation in Healthcare (DASH©) would be beneficial for novice debriefers with less or no formal training in debriefing. However, the DASH translated into Korean and tested for psychometrics is not yet available. Thus, this study was to develop a Korean version of the DASH student version (SV) and test its reliability and validity among baccalaureate nursing students in Korea. METHODS: The participants were 99 baccalaureate nursing students. Content validity using content validity index (CVI), construct validity using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and internal consistency using Cronbach's alpha coefficient were assessed. RESULTS: Both Item-CVIs and Scale-CVI were acceptable. EFA supported the unidimensional latent structure of Korean DASH-SV and results of CFA indicated 6 items converged within the extracted factor, significantly contributing to the factor (p ≤ .05). Items were internally consistent (Cronbach's α = 0.82). CONCLUSION: The Korean version of the DASH-SV is arguably a valid and reliable measure of instructor behaviors that could improve faculty debriefing and student learning in the long term.

Effects of sensorimotor training on functional and pain outcomes in achilles tendinopathy: a systematic review.

Background: Considering the neuromuscular alterations in Achilles tendinopathy (AT), sensorimotor training (SMT) might be beneficial to restore the neuromuscular capacity of the muscle-tendon complex and thereby improve patients' functions and alleviate symptoms. However, there is still a lack of knowledge concerning the effects of SMT on improving functional (e.g., strength) and pain outcomes in this population. Thus, the purpose of this study was to synthesize current evidence to analyze the efficacy of SMT in people with AT. Methods: A systematic electronic search was performed in PubMed, Web of Science, and Cochrane Central Register of Controlled Trials from inception to December 2023. Studies applying SMT in people with AT investigating functional or clinical pain outcomes were considered. Protocols had to incorporate balance, stabilization, proprioception, or vibration training. Patients with insertional or mid-portion AT (≥18 years age) diagnosed with clinical or sonographic evaluation were included. Results: The search yielded 823 records. A total of three randomized controlled trials were considered eligible for the analysis. Each trial used a different SMT protocol: balance training, balance with stabilization training, or whole-body vibration training (WBVT) with other co-interventions. Most functional and pain parameters improved compared to baseline. The first study reported a decrease in pain and an increase in performance (i.e., countermovement jump height) and endurance (i.e., number of heel-raises) by 12-week use of a balance training in addition to isometric, concentric/eccentric, and eccentric exercises. The second study evaluated the four weeks effect of SMT (balance and stabilization training plus eccentric exercises) in addition to passive physiotherapy (deep frictions, ice, ultrasound), resulting in an increased plantarflexion peak torque and reduced pain levels. The third study investigating WBVT reported at 12 weeks an increase in flexibility and a decrease in tendon pain. Discussion: SMT in addition to other co-interventions (i.e., eccentric, isometric, concentric/eccentric training, physiotherapy) showed improvements in strength, performance, muscle flexibility, and alleviated clinical outcomes of pain. SMT might therefore be useful as part of a multimodal treatment strategy protocol in patients suffering from AT. However, due to the small number of studies included and the diversity of SMT protocols, the current evidence is weak; its additional effectiveness should be evaluated. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=467698, Identifier CRD42023467698.

Comparisons of clinical outcomes between hypertensive and normotensive living kidney donors: a prospective, multicenter nationwide cohort study.

Background: Living kidney donors with hypertension are potential candidates for solving the donor shortages in renal transplantation. However, the safety of donors with hypertension after nephrectomy has not been sufficiently confirmed. Methods: A total of 642 hypertensive and 4,848 normotensive living kidney donors who were enrolled in the Korean Organ Transplantation Registry between May 2014 and December 2020 were included in this study. The study endpoints were a decreased estimated glomerular filtration rate (eGFR) and proteinuria. Results: In the entire cohort, donors with hypertension had a lower eGFR before nephrectomy in comparison to normotensive donors which remained lower after kidney transplantation. The incidence of proteinuria in hypertensive donors increased during follow-up. In propensity score-matched analysis, the risk of eGFR being <60 mL/min/1.73 m2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.50-1.19) or <45 mL/min/1.73 m2 (HR, 0.50; 95% CI, 0.06-4.03) was not significantly increased in donors with hypertension. However, hypertensive donors were found to have a significantly higher risk of proteinuria than normotensive donors (HR, 2.28; 95% CI, 1.05-4.94). Similar findings were also observed in the analysis of the entire cohort, indicating that hypertensive donors had a significantly higher risk of proteinuria (adjusted HR, 1.77; 95% CI, 1.10-2.85), without a substantial increase in the risk of decreased renal function. Conclusion: The risk of proteinuria after donation was substantially increased in donors with hypertension. These findings underscore the need for careful monitoring of proteinuria in hypertensive donors following donation.

Impact of Blood Pressure on Allograft Function and Survival in Kidney Transplant Recipients.

The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP <110; 110-119; 120-129; 130-139; and ≥140 mmHg. SBP trajectories were classified into decreasing, stable, and increasing groups. Primary outcome was composite kidney outcome of ≥50% decrease in eGFR or death-censored graft loss. Compared with the 110-119 mmHg group, both the lowest (adjusted hazard ratio [aHR], 2.43) and the highest SBP (aHR, 2.25) were associated with a higher risk of composite kidney outcome. In time-varying model, also the lowest (aHR, 3.02) and the highest SBP (aHR, 3.60) were associated with a higher risk. In the trajectory model, an increasing SBP trajectory was associated with a higher risk than a stable SBP trajectory (aHR, 2.26). This associations were consistent in the validation set. In conclusion, SBP ≥140 mmHg and an increasing SBP trajectory were associated with a higher risk of allograft dysfunction and failure in KT patients.

The Effectiveness of Overground Robot Exoskeleton Gait Training on Gait Outcomes, Balance, and Motor Function in Patients with Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study aimed to investigate the effects of overground robot exoskeleton gait training on gait outcomes, balance, and motor function in patients with stroke. METHODS: Following the PRISMA guidelines, literature searches were performed in the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, Ovid-LWW, and RISS databases. A total of 504 articles were identified, of which 19 were included for analysis after application of the inclusion and exclusion criteria. The included literature was qualitatively evaluated using the PEDro scale, while the Egger's regression, funnel plot, and trim-and-fill methods were applied to assess and adjust for publication bias. RESULTS: The averaged PEDro score was 6.21 points, indicating a high level of methodological quality. In the analysis based on dependent variables, higher effect sizes were observed in the following ascending order: gait speed (g = 0.26), motor function (g = 0.21), gait ability (g = 0.18), Timed Up and Go Test (g = -0.15), gait endurance (g = 0.11), and Berg Balance Scale (g = 0.05). Subgroup analyses further revealed significant differences in Asian populations (g = 0.26), sessions lasting longer than 30 min (g = 0.37), training frequency of three times per week or less (g = 0.38), and training duration of four weeks or less (g = 0.25). Overall, the results of this study indicate that overground robot exoskeleton gait training is effective at improving gait speed in patients with stroke, particularly when the sessions exceed 30 min, are conducted three times or less per week, and last for four weeks or less. CONCLUSION: our results suggest that training is an effective intervention for patients with stroke, provided that appropriate goal-setting and intensity and overground robot exoskeleton gait are applied.