Repetitive transcranial magnetic stimulation impacts the executive function of patients with vascular cognitive impairment: a systematic review and meta-analysis.

Objective: Executive dysfunction is a core symptom of vascular cognitive impairment (VCI), which seriously affects patients' prognosis. This paper aims to investigate the effectiveness of rTMS on executive function in VCI. Methods: The databases selected for this study included Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal Database (VIP), and China Biology Medicine Disc (CBM). The screening times were conducted from the time of library construction until August 23, 2023. The inclusion criteria for this meta-analysis were randomized controlled trials (RCTs) on rTMS for VCI, which include executive function scores. The primary metrics were executive subscale scores of the Cognitive Comprehensive Scale and total scores of the Executive Specificity Scale. The secondary metrics were subscale scores of the Executive Specificity Scale. The quality of each eligible study was assessed using the Cochrane Risk of Bias tool. Meta-analysis and bias analysis were performed using Stata (version 16.0) and RevMan (version 5.3). Results: A total of 20 high-quality clinical RCTs with 1,049 samples were included in this paper. The findings from the primary outcomes revealed that within the rTMS group, there were significantly higher scores observed for the executive sub-item on the cognitive composite scale (SMD = 0.93, 95% CI = 0.77-1.08, p < 0.00001, I 2 = 14%) and the total score on the executive specific scale (SMD = 0.69, 95% CI = 0.44-0.94, p < 0.00001, I 2 = 0%) compared to the control group. As for the secondary outcome measures, as shown by the Trail Making Test-A (time) (MD = -35.75, 95% CI = -68.37 to -3.12, p = 0.03, I 2 = 55%), the Stroop-C card (time) (SMD = -0.46, 95% CI = -0.86 to -0.06, p = 0.02, I 2 = 0%) and the Stroop-C card (correct number) (SMD = 0.49, 95% CI = 0.04-0.94, p = 0.03, I 2 = 0%), the experimental group shorts time and enhances accuracy of executive task in comparison to the control group. Subgroup analysis of the main outcome demonstrated that intermittent theta burst stimulation (iTBS), higher frequency, lower intensity, longer duration, and combined comprehensive therapy exhibited superior efficacy. Conclusion: rTMS is effective in the treatment of the executive function of VCI. The present study has some limitations, so multi-center, large-sample, objective indicators and parameters are needed to further explore in the future.Systematic review registration:https://www.crd.york.ac.uk/prospero/, CRD42023459669.

Comparative Analysis of Short-Term and Long-Term Clinical Efficacy of Mesenchymal Stem Cells from Different Sources in Knee Osteoarthritis: A Network Meta-Analysis.

Background: Joint articular injection of mesenchymal stem cells (MSCs) has emerged as a novel treatment approach for osteoarthritis (OA). However, the effectiveness of MSCs derived from different sources in treating OA patients remains unclear. Therefore, this study aimed to explore the differences between the effectiveness and safety of different sources of MSCs. Materials and Methods: For inclusion consideration, we searched trial registries and published databases, including PubMed, Cochrane Library, Embase, and Web of Science databases. Revman (V5.3), STATA (V16.0), and R (V4.0) were utilized for conducting data analysis, while the Cochrane Risk of Bias Tool was employed for assessing the quality of the studies. We derived outcome measures at 6 and 12 months based on the duration of study follow-up, including visual analog scale (VAS) score, WOMAC score, WOMAC pain, WOMAC Functional Limitation, and WOMAC stiffness. The evaluation time for short-term effectiveness is set at 6 months, while 12 months is utilized as the longest follow-up time for most studies to assess long-term effectiveness. Results: The evaluation of literature quality showed that the included studies had excellent methodological quality. A meta-analysis revealed that different sources of MSCs improved knee function and pain more effectively among patients suffering from knee OA (KOA) than controls. The results of the network meta-analysis showed the following: short-term functional improvement (the indexes were evaluated after 6 months of follow-up) (WOMAC total score: bone marrow-derived MSC (BMMSC) vs. adipose-derived MSC (ADMSC) (mean difference (MD) = -20.12, 95% confidence interval (CI) -125.24 to 42.88), umbilical cord-derived MSC (UCMSC) (MD = -7.81, 95% CI -158.13 to 74.99); WOMAC stiffness: BMMSC vs. ADMSC (MD = -0.51, 95% CI -7.27 to 4.29), UCMSC (MD = -0.75, 95% CI -9.74 to 6.63); WOMAC functional limitation: BMMSC vs. ADMSC (MD = -12.22, 95% CI -35.05 to 18.86), UCMSC (MD = -9.31, 95% CI -44.26 to 35.27)). Long-term functional improvement (the indexes were evaluated after 12 months of follow-up) (WOMAC total: BMMSC vs. ADMSC (MD = -176.77, 95% CI -757.1 to 378.25), UCMSC (MD = -181.55, 95% CI -937.83 to 541.13); WOMAC stiffness: BMMSC vs. ADMSC (MD = -0.5, 95% CI -26.05 to 18.61), UCMSC (MD = -1.03, 95% CI -30.44 to 21.69); WOMAC functional limitation: BMMSC vs. ADMSC (MD = -5.18, 95% CI -316.72 to 177.1), UCMSC (MD = -8.33, 95% CI -358.78 to 218.76)). Short-term pain relief (the indexes were evaluated after 6 months of follow-up) (VAS score: UCMSC vs. BMMSC (MD = -10.92, 95% CI -31.79 to 12.03), ADMSC (MD = -14.02, 95% CI -36.01 to 9.81), PLMSC (MD = -17.09, 95% CI -46.31 to 13.17); WOMAC pain relief: BMMSC vs. ADMSC (MD = -11.42, 95% CI -39.52 to 11.77), UCMSC (MD = -6.73, 95% CI -47.36 to 29.15)). Long-term pain relief (the indexes were evaluated after 12 months of follow-up) (VAS score: BMMSC vs. UCMSC (MD = -4.33, 95% CI -36.81 to 27.08), ADMSC (MD = -11.43, 95% CI -37.5 to 13.42); WOMAC pain relief: UCMSC vs. ADMSC (MD = 0.23, 95% CI -37.87 to 38.11), BMMSC (MD = 5.89, 95% CI -25.39 to 51.41)). According to the GRADE scoring system, WOMAC, VAS, and AE scores were of low quality. Conclusion: Meta-analysis suggests MSCs can effectively treat KOA by improving pain and knee function compared to control groups. In terms of functional improvement in KOA patients, both short-term (6-month follow-up) and long-term (12-month follow-up) results indicated that while the differences between most treatments were not statistically significant, bone marrow-derived MSCs may have some advantages over other sources of MSCs. Additionally, BM-MSCs and UC-MSCs may offer certain benefits over ADMSCs in terms of pain relief for KOA patients, although the variances between most studies were not statistically significant. Therefore, this study suggests that BM-MSCs may present clinical advantages over other sources of MSCs.

The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis.

OBJECTIVE: To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple injections. METHODS: One hundred twenty patients with grade I-III knee osteoarthritis were randomly assigned to three groups: PRP1 group, who received a single injection of platelet-rich plasma; PRP3 group, who received three PRP injections one week apart; PRP5 group, who received five PRP injections one week apart. The patients' conditions were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index-VA3.1 version (WOMAC-VA3.1) at baseline and 6, 12, 24, and 52 weeks 52 weeks follow up. RESULTS: Out of the total participants, 106 patients (30 males and 76 females) completed the study. The primary outcome measure, WOMAC pain score, registered significant improvements across all groups when compared to pre-treatment levels. However, the application of 3 and 5 injections of platelet-rich plasma was substantially more effective than that of a single injection in reducing knee pain and stiffness, as well as enhancing physical function in patients with knee osteoarthritis. No statistically discernable difference was observed between PRP3 and PRP5 at all follow-up intervals, and there was no discernable difference between 3 and 5 PRP injections either. Mild side effects occurred in all three groups. CONCLUSIONS: The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. Furthermore, no significant difference was observed in the efficacy of three or five injections. Therefore, we recommend using three injections of PRP in the treatment of patients with knee osteoarthritis of grade I-III.

Impact of autologous platelet-rich plasma therapy vs. hyaluronic acid on synovial fluid biomarkers in knee osteoarthritis: a randomized controlled clinical trial.

Objective: Observe the effects of platelet-rich plasma (PRP) therapy on inflammatory cytokines in the synovial fluid of the knee joint of patients with KOA, and explore the effects of PRP intra-articular injection on the inflammation of the knee joint environment and the possible mechanism of action. Methods: Seventy patients were randomized to undergo three blinded weekly intra-articular injections of PRP or hyaluronic acid (HA). The concentrations of inflammatory cytokines, including interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, IL-8, IL-17A, IL-17F, IL-4, IL-5, and IL-10, in the synovial fluid were evaluated before the intervention and 1 month after the third injection. The Western Ontario and McMaster University (WOMAC) and visual analog scale (VAS) scores were used to assess pain and functional status of the knee joints in both groups before the intervention, immediately post-intervention, and 1, 3, 6, and 12 months after the intervention. Results: Baseline characteristics were similar in both groups with no statistical difference. The IL-6, IL-1ß, TNF-α, IL-17A, and IL-10 levels in the synovial fluid of the observation group decreased significantly after, vs. before, the intervention (p < 0.05), whereas the IL-8, IL-17F, and IL-4 levels decreased (p > 0.05) and IL-5 levels increased (p > 0.05). There was no statistically significant difference between inflammatory cytokine levels in the synovial fluid of the samples from the control group before and after the intervention (p > 0.05). There were no statistically significant differences between the two groups immediately after intervention (p > 0.05). At 1, 3, 6, and 12 months after intervention, the WOMAC and VAS scores were significantly better in the observation group than in the control group (p < 0.05). Conclusion: Platelet plasma therapy can reduce the concentrations of inflammatory cytokines IL-6, IL-1ß, TNF-α, IL-17A, and IL-10 in the synovial fluid of KOA patients, reduce the expression levels of IL-8, IL-17F, and IL-4, clear the pro-inflammatory factors, improve the inflammatory environment of the affected knee joint, and alleviate pain caused by inflammation. Thus, alleviating pain and improving knee function in patients with KOA.

Application of vagus nerve stimulation on the rehabilitation of upper limb dysfunction after stroke: a systematic review and meta-analysis.

Objective: This study aimed to elucidate the efficacy, safety, and long-term implications of vagus nerve stimulation (VNS) as a viable therapeutic option for patients with upper limb dysfunction following a stroke. Methods: Data from the following libraries were searched from inception to December 2022: PubMed, Wanfang, Scopus, China Science and Technology Journal Database, Embase, Web of Science, China Biology Medicine Disc, Cochrane Library, and China National Knowledge Infrastructure. Outcomes included indicators of upper limb motor function, indicators of prognosis, and indicators of safety (incidence of adverse events [AEs] and serious AEs [SAEs]). Two of the authors extracted the data independently. A third researcher arbitrated when disputes occurred. The quality of each eligible study was evaluated using the Cochrane Risk of Bias tool. Meta-analysis and bias analysis were performed using Stata (version 16.0) and RevMan (version 5.3). Results: Ten trials (VNS combined with rehabilitation group vs. no or sham VNS combined with rehabilitation group) with 335 patients were included in the meta-analysis. Regarding upper extremity motor function, based on Fugl-Meyer assessment scores, VNS combined with other treatment options had immediate (mean difference [MD] = 2.82, 95% confidence interval [CI] = 1.78-3.91, I2 = 62%, p < 0.00001) and long-term (day-30 MD = 4.20, 95% CI = 2.90-5.50, p < 0.00001; day-90 MD = 3.27, 95% CI = 1.67-4.87, p < 0.00001) beneficial effects compared with that of the control treatment. Subgroup analyses showed that transcutaneous VNS (MD = 2.87, 95% CI = 1.78-3.91, I2 = 62%, p < 0.00001) may be superior to invasive VNS (MD = 3.56, 95% CI = 1.99-5.13, I2 = 77%, p < 0.0001) and that VNS combined with integrated treatment (MD = 2.87, 95% CI = 1.78-3.91, I2 = 62%, p < 0.00001) is superior to VNS combined with upper extremity training alone (MD = 2.24, 95% CI = 0.55-3.93, I2 = 48%, p = 0.009). Moreover, lower frequency VNS (20 Hz) (MD = 3.39, 95% CI = 2.06-4.73, I2 = 65%, p < 0.00001) may be superior to higher frequency VNS (25 Hz or 30 Hz) (MD = 2.29, 95% CI = 0.27-4.32, I2 = 58%, p = 0,03). Regarding prognosis, the VNS group outperformed the control group in the activities of daily living (standardized MD = 1.50, 95% CI = 1.10-1.90, I2 = 0%, p < 0.00001) and depression reduction. In contrast, quality of life did not improve (p = 0.51). Safety was not significantly different between the experimental and control groups (AE p = 0.25; SAE p = 0.26). Conclusion: VNS is an effective and safe treatment for upper extremity motor dysfunction after a stroke. For the functional restoration of the upper extremities, noninvasive integrated therapy and lower-frequency VNS may be more effective. In the future, further high-quality studies with larger study populations, more comprehensive indicators, and thorough data are required to advance the clinical application of VNS. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023399820.

Machine learning for the prediction of cognitive impairment in older adults.

Objective: The purpose of this study was to develop and validate a predictive model of cognitive impairment in older adults based on a novel machine learning (ML) algorithm. Methods: The complete data of 2,226 participants aged 60-80 years were extracted from the 2011-2014 National Health and Nutrition Examination Survey database. Cognitive abilities were assessed using a composite cognitive functioning score (Z-score) calculated using a correlation test among the Consortium to Establish a Registry for Alzheimer's Disease Word Learning and Delayed Recall tests, Animal Fluency Test, and the Digit Symbol Substitution Test. Thirteen demographic characteristics and risk factors associated with cognitive impairment were considered: age, sex, race, body mass index (BMI), drink, smoke, direct HDL-cholesterol level, stroke history, dietary inflammatory index (DII), glycated hemoglobin (HbA1c), Patient Health Questionnaire-9 (PHQ-9) score, sleep duration, and albumin level. Feature selection is performed using the Boruta algorithm. Model building is performed using ten-fold cross-validation, machine learning (ML) algorithms such as generalized linear model (GLM), random forest (RF), support vector machine (SVM), artificial neural network (ANN), and stochastic gradient boosting (SGB). The performance of these models was evaluated in terms of discriminatory power and clinical application. Results: The study ultimately included 2,226 older adults for analysis, of whom 384 (17.25%) had cognitive impairment. After random assignment, 1,559 and 667 older adults were included in the training and test sets, respectively. A total of 10 variables such as age, race, BMI, direct HDL-cholesterol level, stroke history, DII, HbA1c, PHQ-9 score, sleep duration, and albumin level were selected to construct the model. GLM, RF, SVM, ANN, and SGB were established to obtain the area under the working characteristic curve of the test set subjects 0.779, 0.754, 0.726, 0.776, and 0.754. Among all models, the GLM model had the best predictive performance in terms of discriminatory power and clinical application. Conclusions: ML models can be a reliable tool to predict the occurrence of cognitive impairment in older adults. This study used machine learning methods to develop and validate a well performing risk prediction model for the development of cognitive impairment in the elderly.

Associations between dietary and blood inflammatory indices and their effects on cognitive function in elderly Americans.

Objective: To determine the correlations between dietary and blood inflammation indices in elderly Americans and their effects on cognitive function. Methods: This research extracted data from the 2011-2014 National Health and Nutrition Examination Survey for 2,479 patients who were ≥60 years old. Cognitive function was assessed as a composite cognitive function score (Z-score) calculated from the results of the Consortium to Establish a Registry for Alzheimer's Disease Word Learning and Delayed Recall tests, the Animal Fluency test, and the Digit Symbol Substitution Test. We used a dietary inflammatory index (DII) calculated from 28 food components to represent the dietary inflammation profile. Blood inflammation indicators included the white blood cell count (WBC), neutrophil count (NE), lymphocyte count (Lym), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), neutrophil-albumin ratio (NAR), systemic immune-inflammation index [SII, calculated as (peripheral platelet count) × NE/Lym], and systemic inflammatory response index [SIRI, calculated as (monocyte count) × NE/Lym]. WBC, NE, Lym, NLR, PLR, NAR, SII, SIRI, and DII were initially treated as continuous variables. For logistic regression, WBC, NE, Lym, NLR, PLR, NAR, SII, and SIRI were divided into quartile groups, and DII was divided into tertile groups. Results: After adjusting for covariates, WBC, NE, NLR, NAR, SII, SIRI, and DII scores were markedly higher in the cognitively impaired group than in the normal group (p < 0.05). DII was negatively correlated with the Z-score when combined with WBC, NE, and NAR (p < 0.05). After adjusting for all covariates, DII was positively correlated with SII in people with cognitive impairment (p < 0.05). Higher DII with NLR, NAR, SII, and SIRI all increased the risk of cognitive impairment (p < 0.05). Conclusion: DII was positively correlated with blood inflammation indicators, and higher DII and blood inflammation indicators increased the risk of developing cognitive impairment.

Effectiveness of Response Inhibition Training and Its Long-Term Effects in Healthy Adults: A Systematic Review and Meta-Analysis.

Objective: This study aims to evaluate the effectiveness and long-term effects of response inhibition training as a therapeutic approach in healthy adults. Methods: The PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database (VIP) were searched for studies. Data on the improvement of Cognitive function and its long-term effect were extracted by two authors independently. The pooled data were meta-analyzed using a random-effects model, and the quality of each eligible study was assessed by The Cochrane Collaboration's tool. Results: Nine articles were included. 1 of the articles included 2 trials, so 10 eligible trials (response inhibition training group vs. control group) were identified. A total of 490 patients were included. Response inhibition training has beneficial effects on improving cognitive function in healthy adults compared to control treatment (SMD, -0.93; 95% CI, -1.56 to -0.30; Z = 2.88, P = 0.004), the subgroup analysis results showed that either GNG training alone (SMD, -2.27; 95% CI, -3.33 to -1.21; Z = 4.18, P < 0.0001) or the combination of both SST and GNG significantly improved cognitive function in healthy adults (SMD, -0.94; 95% CI, -1.33 to -0.56; Z = 4.80, P < 0.0001), whereas SST training alone did not have such an effect (SMD, -0.15; 95% CI, -0.76 to 0.47; Z = 0.47, P = 0.64). But its long-term effects are not significant (SMD, -0.29; 95% CI, -0.68 to 0.10; Z = 1.45, P = 0.15). The subgroup analysis results showed that neither GNG training alone (SMD, -0.25; 95% CI, -0.75 to 0.24; Z = 0.99, P = 0.32) nor SST training alone (SMD, 0.03; 95% CI, -0.42 to 0.48; Z = 0.14, P = 0.89) could improve the cognitive function of healthy adults in the long term. In contrast, the combination of both training (SMD, -0.95; 95% CI, -1.46 to -0.45; Z = 3.68, P = 0.0002) can have long-term effects on the improvement of cognitive function in healthy adults. Conclusion: The findings of our study indicate that response inhibition training can improve the cognitive function of healthy adults and that more RCTs need to be conducted to validate their usefulness in clinical cases.

[Effect of acupuncture at " three points of ilioumbar" on lumbar function and pain in patients with iliopsoas muscle strain].

OBJECTIVE: To compare the clinical effect of acupuncture at "three points of iliolumbar" combined with celecoxib and celecoxib alone in the treatment of iliopsoas muscle strain. METHODS: A total of 60 patients with iliopsoas muscle strain were randomly divided into an observation group and a control group, 30 patients in each group. Celecoxib was given orally to both groups, 200 mg once a day for 3 days. On the basis of the above drugs, acupuncture was applied at Yaoda (Extra), Wushu (GB 27), Qiayao (Extra) in the observation group, once a day for 3 days. The Japanese Orthopaedic Association (JOA) score and visual analogue scale (VAS) score were observed and compared before and after treatment, and the content of 5-hydroxytryptamine (5-HT) in serum was detected by enzyme-linked immunosorbent assay (ELISA) before and after treatment in the two groups. RESULTS: After treatment, the JOA scores in the two groups were increased (both P<0.05), and the VAS scores and 5-HT contents were decreased (all P<0.05). The increase of JOA score in the observation group was greater than that in the control group (P<0.05), and the decrease of VAS score and 5-HT content in the observation group was greater than that in the control group (both P<0.05). CONCLUSION: Acupuncture at "three points of ilioumbar" combined with celecoxib in the treatment of iliopsoas muscle strain can improve lumbar function, relieve pain and reduce 5-HT content in serum, which is better than celecoxib alone.