Metabolic impairments associated with type 2 diabetes mellitus and the potential effects of exercise therapy: An exploratory randomized trial based on untargeted metabolomics.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common condition that is characterized by metabolic impairments. Exercise therapy has proven effective in improving the physiological and psychological states of patients with T2DM; however, the influence of different exercise modalities on metabolic profiles is not fully understood. This study first aimed to investigate the metabolic changes associated with T2DM among patients and then to evaluate the potential physiological effects of different exercise modalities (Tai Chi and brisk walking) on their metabolic profiles. METHODS: This study included 20 T2DM patients and 11 healthy subjects. Patients were randomly allocated to either the Tai Chi or walking group to perform Dijia simplified 24-form Tai Chi or brisk walking (80-100 m/min), with 90 minutes each time, three times per week for 12 weeks, for a total of 36 sessions. The healthy group maintained daily living habits without intervention. Glycemic tests were conducted at the baseline and after 12 weeks. Serum and urine samples were collected for untargeted metabolomic analyses at baseline and 12 weeks to examine the differential metabolic profiles between T2DM and healthy subjects, and the metabolic alterations of T2DM patients before and after exercise therapy. RESULTS: Compared to the healthy group, T2DM patients exhibited metabolic disturbances in carbohydrates (fructose, mannose, galactose, glycolysis/gluconeogenesis), lipids (inositol phosphate), and amino acids (arginine, proline, cysteine, methionine, valine, leucine, and isoleucine) metabolism, including 20 differential metabolites in the serum and six in the urine. After exercise, the glycemic results showed insignificant changes. However, patients who practiced Tai Chi showed significant improvements in their post-treatment metabolic profiles compared to baseline, with nine serum and six urine metabolites, including branch-chained amino acids (BCAAs); while those in the walking group had significantly altered nine serum and four urine metabolites concerning steroid hormone biosynthesis and arachidonic acid metabolism compared to baseline. CONCLUSION: T2DM patients displayed impaired carbohydrate, lipid, and amino acid metabolism, and exercise therapy improved their metabolic health. Different modalities may act through different pathways. Tai Chi may improve disrupted BCAAs metabolism, whereas brisk walking mainly regulates steroid hormone biosynthesis and arachidonic acid metabolism.

Genetic evidence suggests a genetic association between major depressive disorder and reduced cortical gray matter volume: A Mendelian randomization study and mediation analysis.

BACKGROUND: Several studies have suggested an association between major depressive disorder (MDD) and abnormal brain structure. However, it is unclear whether MDD affects cortical gray matter volume, a common indicator of cognitive function. We aimed to determine whether MDD was associated with decreased cortical gray matter volume (GMV) through a Mendelian randomization (MR) study. METHODS: We obtained summary genetic data from a study conducted by the Psychiatric Genomics Consortium, which recruited a total of 480,359 participants (135,458 cases and 344,901 controls). Genetic tools-single nucleotide polymorphisms (SNPs)-of MDD were extracted from the study and their effects on gray matter volumes of the cortex and total brain were evaluated in a large cohort from the UK Biobank (n = 8427). The effects of the SNPs were pooled using inverse variance weighted (IVW) analysis and further tested in several sensitivity analyses. We tested whether C-reactive protein (CRP) levels and interleukin-6 signaling were the mediators of the effects using a multivariate MR model. RESULTS: Thirty-three SNPs were identified and adopted as genetic tools for predicting MDD. IVW analysis showed that MDD was associated with lower overall GMV (beta value -0.106, 95%CI -0.188 to -0.023, p = 0.011) in the frontal pole (left frontal pole, -0.152, 95%CI -0.177 to -0.127, p = 0.013; right frontal pole, -0.133, 95%CI -0.253 to -0.013, p = 0.028). Multivariate and mediation analysis showed that interleukin-6 was an important mediator of GMV reduction. Reverse causality analysis found no evidence that total GMV affected the risk of MDD, but showed that increased left precuneus cortex volume and left posterior cingulate cortex volume were associated with increased risk of MDD. LIMITATIONS: Potential pleiotropic effects and overestimation of real-world effects. Key assumptions for MR analysis may not be satisfactorily met. CONCLUSION: MDD was associated with a reduced GMV, and interleukin-6 might be a mediator of GMV reduction.

The efficacy and safety of oral microecological agents as add-on therapy for atopic dermatitis: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Atopic dermatitis (AD) is a common skin disease that is hard to completely cure in a short time. Guidelines recommend the use of topical corticosteroids (TCS) as first-line anti-inflammatory therapy for AD, but long-term use has significant side effects. Microecological agents (MA), including probiotics, prebiotics and synbiotics, have been widely reported as a potential adjunctive therapy of AD, but whether MA can contribute to AD treatment is currently controversial. Therefore, we conducted a systematic review and meta-analysis to investigate whether MA as an add-on therapy for AD has synergistic and attenuated effects and to further understand the role of MA in clinical interventions for AD. METHODS: We systematically searched Medline, Embase, Web of Science, Cochrane Library and PsycINFO databases up to Apr 11, 2023, and bibliographies were also manually searched, for potentially relevant studies regarding MA as additional therapy of AD. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The primary outcomes (SCORAD scores and the number of adverse events) and the secondary outcomes (pruritus scores, the quality of life and the frequency of TCS) were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. R (V4.4.3) software was used for data synthesis. The certainty of the evidence was evaluated with the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system. We also performed a trial sequential analysis to assess the reliability of the evidence. RESULTS: A total of 21 studies, including 1230 individuals, were identified, 20 of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that compared with controls, oral MA as an add-on therapy was associated with significantly lower SCORAD scores (MD = -5.30, 95% CI -8.50, -1.55, p < 0.01, I2  = 81%). However, adverse events, pruritus scores, quality of life, and frequency of TCS use showed no significant difference in this meta-analysis study (p > 0.05). CONCLUSIONS: This meta-analysis showed that MA plus TCS could be an effective and safe treatment for patients with AD to relieve relevant symptoms, which might be used as an add-on therapy in the treatment of AD. However, due to the limited number of studies, results should be interpreted with caution. Further studies with a larger sample size are needed to explore the optimal protocol of MA plus TCS.

The conscious processing of emotion in depression disorder: a meta-analysis of neuroimaging studies.

Background: Depression is generally accompanied by a disturbed conscious processing of emotion, which manifests as a negative bias to facial/voice emotion information and a decreased accuracy in emotion recognition tasks. Several studies have proved that abnormal brain activation was responsible for the deficit function of conscious emotion recognition in depression. However, the altered brain activation related to the conscious processing of emotion in depression was incongruent among studies. Therefore, we conducted an activation likelihood estimation (ALE) analysis to better understand the underlying neurophysiological mechanism of conscious processing of emotion in depression. Method: Electronic databases were searched using the search terms "depression," "emotion recognition," and "neuroimaging" from inceptions to April 10th, 2023. We retrieved trials which explored the neuro-responses of depressive patients to explicit emotion recognition tasks. Two investigators independently performed literature selection, data extraction, and risk of bias assessment. The spatial consistency of brain activation in conscious facial expressions recognition was calculated using ALE. The robustness of the results was examined by Jackknife sensitivity analysis. Results: We retrieved 11,365 articles in total, 28 of which were included. In the overall analysis, we found increased activity in the middle temporal gyrus, superior temporal gyrus, parahippocampal gyrus, and cuneus, and decreased activity in the superior temporal gyrus, inferior parietal lobule, insula, and superior frontal gyrus. In response to positive stimuli, depressive patients showed hyperactivity in the medial frontal gyrus, middle temporal gyrus, and insula (uncorrected p < 0.001). When receiving negative stimuli, a higher activation was found in the precentral gyrus, middle frontal gyrus, precuneus, and superior temporal gyrus (uncorrected p < 0.001). Conclusion: Among depressive patients, a broad spectrum of brain areas was involved in a deficit of conscious emotion processing. The activation of brain regions was different in response to positive or negative stimuli. Due to potential clinical heterogeneity, the findings should be treated with caution. Systematic review registration: https://inplasy.com/inplasy-2022-11-0057/, identifier: 2022110057.

The effect and safety of constraint-induced movement therapy for post-stroke motor dysfunction: a meta-analysis and trial sequential analysis.

Background: Due to motor function insufficiency, patients with post-stroke motor dysfunction (PSMD) have limitations in performing an activity, feel restricted during social participation, and feel impaired in their quality of life. Constraint-induced movement therapy (CIMT) is a neurorehabilitation technique, but its effectiveness on PSMD after stroke still remains controversial. Objective: This meta-analysis and trial sequential analysis (TSA) aimed to comprehensively evaluate the effect and safety of CIMT for PSMD. Methods: Four electronic databases were searched from their inception to 1 January 2023 to identify randomized controlled trials (RCTs) investigating the effectiveness of CIMT for PSMD. Two reviewers independently extracted the data and assessed the risk of bias and reporting quality. The primary outcome was a motor activity log for the amount of use (MAL-AOU) and the quality of movement (MAL-QOM). RevMan 5.4, Statistical Package for Social Sciences (SPSS) 25.0, and STATA 13.0 software were used for statistical analysis. The certainty of the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. We also performed the TSA to assess the reliability of the evidence. Results: A total of 44 eligible RCTs were included. Our results showed that CIMT combined with conventional rehabilitation (CR) was superior to CR in improving MAL-AOU and MAL-QOM scores. The results of TSA indicated that the above evidence was reliable. Subgroup analysis demonstrated that CIMT (≥6 h per day or duration ≤ 20 days) combined with CR was more effective than CR. Meanwhile, both CIMT and modified CIMT (mCIMT) combined with CR were more efficient than CR at all stages of stroke. No severe CIMT-related adverse events occurred. Conclusion: CIMT may be an optional and safe rehabilitation therapy to improve PSMD. However, due to limited studies, the optimal protocol of CIMT for PSMD was undetermined, and more RCTs are required for further exploration. Clinical trial registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=143490, identifier: CRD42019143490.

The efficacy and safety of high-dose nonsedating antihistamines in chronic spontaneous urticaria: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Standard doses of second-generation H1-antihistamines (sgAHs) as first-line treatment are not always effective in treating chronic spontaneous urticaria (CSU), and hence an increase in the dose of sgAHs is recommended. However, literature evaluating the efficacy and safety of this treatment remains inconclusive, highlighting the need for a systematic review and meta-analysis. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of high-dose sgAHs compared with standard-dose sgAHs in treating CSU. METHODS: A systematic literature search of double-blind, randomized controlled trials (RCT) utilizing multiple doses of sgAHs was performed by searching the electronic databases Medline, Embase, PsycInfo, Cochrane databases, and Web of Science. Bibliographies were also manually searched. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The response rate, the number of adverse events, somnolence, and withdrawal due to adverse events were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. RevMan (V5.3) software was used for data synthesis. RESULTS: A total of 13 studies were identified, seven of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that high-dose sgAHs was associated with a significantly higher response rate than standard-dose (RR 1.13, 95% CI 1.02 to 1.26; P = 0.02). Conversely, high doses of sgAHs were associated with significantly higher somnolence rates than standard dose (RD 0.05, 95% CI 0.01 to 0.09; P = 0.02). There was no significant difference in adverse events or withdrawal due to adverse events between standard- and high-dose treatments. CONCLUSIONS: Our analyses showed that a high dose of sgAHs (up to two times the standard dose) might be more effective than a standard dose in CSU treatment. High-dose and standard-dose sgAHs showed similar adverse events, except for somnolence, where incidence was found to be dose-dependent in some studies. However, given the limited number of studies, our meta-analysis results should be interpreted with caution.

Acupuncture for carpal tunnel syndrome: A systematic review and meta-analysis of randomized controlled trials.

Background: The evidence for the effectiveness of acupuncture for patients with carpal tunnel syndrome (CTS) is insufficient. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness of acupuncture on CTS through a comprehensive literature search. Methods: English and Chinese databases were searched from their inceptions until 27 October 2022 to collect randomized controlled trials (RCTs) that investigated the effect of acupuncture on CTS. Two reviewers independently selected studies that met the eligibility criteria, extracted the required data, assessed the risk of bias using version 2 of the Cochrane risk-of-bias tool for randomized trials (ROB 2), and evaluated the quality of reporting for acupuncture interventions using the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The primary outcomes were symptom severity and functional status, while secondary outcomes included pain intensity, responder rate, and electrophysiological parameters. Review Manager software (version 5.4.1) was used for data analysis. The certainty of the evidence was rated with GRADEpro (version 3.6) software. Results: We included 16 RCTs with a total of 1,025 subjects. The overall risk of bias was rated as low in one RCT, some concerns in 14, and high in one. Compared with night splints, acupuncture alone was more effective in relieving pain, but there were no differences in symptom severity and functional status. Acupuncture alone had no advantage over medicine in improving symptom severity and electrophysiological parameters. As an adjunctive treatment, acupuncture might benefit CTS in terms of symptom severity, functional status, pain intensity, and electrophysiological parameters, and it was superior to medicine in improving the above outcomes. Few acupuncture-related adverse events were reported. The above evidence had a low or very low degree of certainty. Conclusion: Acupuncture as an adjunctive treatment may be effective for patients with CTS. Additionally, more rigorous studies with objective outcomes are needed to investigate the effect of acupuncture in contrast with sham acupuncture or other active treatments. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=329925, identifier CRD42022329925.

Attention bias modification for depression: A systematic review and meta-analysis.

Background: Depression is a mental health disorder characterized by affective, somatic, and cognitive symptoms. Attention bias modification (ABM) has been widely used to treat depression. However, the results seem inconsistent. We conducted a systematic review and meta-analysis to investigate the efficacy of ABM for depression and to explore the optimal protocol of ABM. Methods: Seven databases were systematically searched from their inceptions to 5 October 2022 to include randomized controlled trials (RCTs) of ABM for depression. Two independent reviewers selected the eligible articles, extracted data, and evaluated the risk of bias using version 2 of the Cochrane risk-of-bias tool (ROB 2.0) for randomized trials. The primary outcome was the evaluation of depressive symptoms using widely accepted and validated scales. The secondary outcomes included rumination and attentional control. Meta-analysis was conducted by using RevMan (version 5.4) and Stata (version 12.0). Subgroup analyses and meta-regressions were performed to identify the source of heterogeneity. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: A total of 19 trials involving 20 datasets (1,262 participants) were included. The overall risk of bias in one study was rated as low risk of bias, three studies were considered as high, and the remaining studies were some concerns. Compared with attention control training (ACT), ABM had a greater effect in the improvement of depression (SMD = -0.48, 95% CI -0.80 to -0.17, I2 = 82%) and rumination (MD = -3.46, 95% CI -6.06 to -0.87, I2 = 0%). No significant differences were observed in the attentional control outcome between ABM and ACT (MD = 3.07, 95% CI -0.52 to 6.65, I 2 = 0%). Subgroup analysis demonstrated that adults exhibited a greater decrease in depression scores than adolescents. ABM using the dot-probe task, training target stimulus presented by face, and training directions by left-right were associated with better antidepressant effects. ABM training delivered in the laboratory tended to yield a better effect than those conducted at home. Sensitivity analysis indicated that the results were robust. The certainty of the evidence for all outcomes was low or very low, and publication bias may exist. Conclusion: Due to high heterogeneity and limited studies, not enough current evidence supported that ABM could be an effective intervention to relieve depressive symptoms. More rigorous RCTs are required to verify the benefits and to explore the optimal protocol of ABM training for depression.Systematic Review Registration: [PROSPERO], identifier [No. CRD42021279163].

Prevalence and risk factors of cognitive impairment in Chinese patients with hypertension: a systematic review and meta-analysis.

Background: Cognitive impairment is prevalent in Chinese patients with hypertension; however, current evidence on prevalence and risk factors is required to be synthesized. Objectives: This systematic review and meta-analysis aimed to evaluate the prevalence and risk factors of cognitive impairment in Chinese patients with hypertension. Methods: Two reviewers independently searched PubMed, Web of Science, Embase, The Cochrane Library, CNKI, CBM, the Wanfang database, and the VIP database from their inception to 7 June 2023. The gray literature and the reference lists of the included studies were also retrieved manually. Moreover, we also independently performed the eligibility screening, data extraction, and data synthesis. The primary outcome was the prevalence of cognitive impairment in Chinese patients with hypertension, and the secondary outcomes were the risk factors for cognitive impairment in patients with hypertension. R (version 4.0.3) was used for data synthesis. Results: In total, 82 studies involving 53,623 patients with hypertension were included in this meta-analysis. The pooled prevalence of cognitive impairment in patients with hypertension was 37.6% (95% CI: 33.2-42.2%). A total of 12 risk factors, including advanced age (r = -0.34, 95% CI: -0.45, -0.21), female sex (OR = 1.15, 95% CI: 1.01-1.32), BMI > 24 Kg/m2 (OR = 1.76, 95% CI: 1.04-3.00), lower educational level (OR = 2.01, 95% CI: 1.10-3.67), single status (OR = 1.63, 95% CI: 1.32-2.02), complications with diabetes (OR = 1.44, 95% CI: 1.14-1.80), coronary heart disease (OR = 1.49, 95% CI: 1.12-1.97), higher stage of hypertension [stage 3 vs. stage 1, OR = 3.08, 95% CI: 1.82-5.22; stage 2 vs. stage 1, OR = 1.83, 95% CI: 1.29-2.60], no regular physical activity (OR = 0.40, 95% CI: 0.21-0.77), higher levels of systolic blood pressure (r = -0.25, 95% CI: -0.42, -0.08), Hcy (r = -0.39, 95% CI: -0.63, -0.09), and IL-6 (r = -0.26, 95% CI: -0.48, -0.02) were detected. Conclusion: Cognitive impairment is prevalent in Chinese patients with hypertension, and the increased prevalence was associated with several demographic characteristics, complicated disease, no regular physical activity, worse hypertension status (higher stages and SBP), and high levels of biomarkers. Therefore, more attention should be paid to the early identification and treatment of patients with hypertension who are at high risk for cognitive impairment in clinical practice. In addition, relevant risk factors should be controlled to reduce the incidence of cognitive impairment. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO, identifier [CRD42023410437].

Lifestyle intervention Tai Chi for adult patients with type 2 diabetes mellitus: a PRIO-harms based overview of 17 systematic reviews.

Objective: To systematically summarize current evidence and determine the clinical effectiveness and safety of Tai Chi for type 2 diabetes mellitus (T2DM) in adults by conducting an overview of systematic reviews (SRs). Methods: A systematic search encompassing five electronic databases was conducted until July 30, 2023, to identify relevant systematic reviews (SRs) based on randomized controlled trials (RCTs) concerning Tai Chi for T2DM. The methodological quality of the included SRs was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) and the Risk of Bias in Systematic Reviews (ROBIS) tool. The Preferred Reporting Items for Overview of Systematic Review (PRIO-harms) checklist was used to promote a more balanced reporting of benefits and harms in this overview. Corrected covered area (CCA) was used to calculate the degree of overlapping primary studies. Primary outcome measures were glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG), while secondary outcomes encompassed health-related quality measures. The GRADE (Grades of Recommendations, Assessment, Development, and Evaluation) framework was utilized to assess the quality of evidence for the outcome measures. Results: A total of 17 eligible SRs were included in this overview. One SR reported negative conclusions, while the remaining 16 reported positive ones on different outcomes. A total of 4 SRs reported adverse events, either absent or minor. Most of the SRs exhibited critically low quality (15/17) and a high risk of bias (14/17), as indicated by AMSTAR2 and ROBIS, respectively. The CCA was 12.14%, indicating a high degree of primary study overlapping. Evidence from 135 results for 24 outcomes concerning Tai Chi for T2DM was evaluated using the GRADE approach, most of which were rated very low. Conclusion: Tai Chi shows promise as a potentially effective and safe lifestyle intervention for adults with T2DM, particularly in improving HbA1c, FBG, BMI, and overall quality of life (QoL). However, these results should be cautiously interpreted due to methodological flaws observed in the current SRs and the low quality of the SRs based on GRADE. Furthermore, there is a compelling need for additional well-designed, high-quality RCTs and SRs to establish robust and conclusive evidence regarding the efficacy of Tai Chi for managing T2DM in the future. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42019140988.

The effectiveness and safety of repetitive transcranial magnetic stimulation on spasticity after upper motor neuron injury: A systematic review and meta-analysis.

To systematically evaluate the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) on spasticity after upper motor neuron (UMN) injury. Eight electronic databases were searched from inception to August 6, 2022. Randomized controlled trials (RCTs) investigating the effectiveness and safety of rTMS on spasticity after UMN injury were retrieved. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Review Manager 5.3 and Stata 14.0 software were used to synthesize data. The certainty of the evidence was appraised with the Grade of Recommendation, Assessment, Development and Evaluation tool. Forty-two studies with a total of 2,108 patients were included. The results of meta-analysis revealed that, compared with control group, rTMS could significantly decrease scores of the Modified Ashworth Scale (MAS) in patients with UMN injury. The subgroup analysis discovered that rTMS effectively decreased the MAS scores in patients with stroke. Meanwhile, rTMS treatment > 10 sessions has better effect and rTMS could decrease the MAS scores of upper limb. Thirty-three patients complained of twitching facial muscles, headache and dizziness, etc. In summary, rTMS could be recommended as an effective and safe therapy to relieve spasticity in patients with UMN injury. However, due to high heterogeneity and limited RCTs, this conclusion should be treated with caution.

The effect and safety of Tai Chi on bone health in postmenopausal women: A meta-analysis and trial sequential analysis.

Background: Tai Chi may be a promising exercise to prevent and control bone loss in postmenopausal women. This meta-analysis and trial sequential analysis aimed to evaluate the effect and safety of Tai Chi on bone health in postmenopausal women. Method: Seven databases were searched from their inceptions to 11 May 2022 to collect randomized controlled trials (RCTs) investigating the effect and safety of Tai Chi on bone health in postmenopausal women. Two independent reviewers identified the eligible studies, extracted data, and assessed the risk of bias of included studies using the revised Cochrane risk-of-bias tool for randomized trials. The primary outcome was the bone mineral density (BMD), and secondary outcomes included bone turnover markers and calcaneus quantitative ultrasound. Subgroup analyses were conducted based on the duration of Tai Chi. Sensitivity analyses and publication bias assessment were performed. RevMan software (version 5.4.1) and R software (version 3.6.1) were used for data synthesis. The certainty of evidence was rated with the Grading of recommendations assessment, development, and evaluation (GRADE) system. We also performed the trial sequential analysis to evaluate the reliability of the evidence. Results: A total of 25 reports involving 24 studies were included. Four studies were considered as high overall risk of bias, and the rest were some concerns. Among included studies, there were three comparisons including Tai Chi vs. non-intervention, Tai Chi vs. other exercises, and Tai Chi plus nutraceutical vs. nutraceutical. Compared with non-intervention, Tai Chi was more effective to improve BMD of lumbar spine (MD = 0.04, 95% CI 0.02 to 0.07, I 2 = 0%, low certainty), femoral neck (MD = 0.04, 95% CI 0.02 to 0.06, I 2 = 0%, low certainty), and trochanter (MD = 0.02, 95% CI 0.00 to 0.03, I 2 = 0%, very low certainty), but there was no significant difference in increasing the BMD of Ward's triangle (MD = 0.02, 95% CI -0.01 to 0.04, I 2 = 0%, very low certainty). Trial sequential analysis showed that the effect of Tai Chi vs. non-intervention on the BMD of lumbar spine and femoral neck was reliable, but the effect on the BMD of trochanter and Ward's triangle needed further verification. The subgroup analyses suggested that Tai Chi training for over 6 months had greater improvement in BMD of the lumbar spine, femoral neck, and trochanter than non-intervention. No significant differences were observed in the above outcomes of Tai Chi vs. other exercises, and Tai Chi plus nutraceutical vs. nutraceutical. There was insufficient evidence to support the effect of Tai Chi on bone turnover markers and calcaneus quantitative ultrasound. Few Tai Chi relevant adverse events occurred. Conclusion: Tai Chi may be an optional and safe exercise for improving BMD loss in postmenopausal women, and practicing Tai Chi for more than 6 months may yield greater benefits. However, more rigorously designed RCTs are required to verify the benefits and to explore the optimal protocol of Tai Chi exercise for bone health. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309148, identifier: CRD42022309148.

Effectiveness and safety of acupuncture for post-stroke spasticity: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to comprehensively evaluate the effectiveness and safety of acupuncture for post-stroke spasticity. Methods: Nine electronic databases were searched from their inception to 6 June 2022, to identify randomized-controlled trials (RCTs) that investigated the effectiveness and safety of acupuncture for post-stroke spasticity. Two reviewers independently screened the studies, extracted the data, assessed the risk of bias. The reporting quality of interventions in controlled trials of acupuncture was evaluated using Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The RevMan 5.4 and R 4.2.0 software were used for statistical analysis. Results: A total of 88 eligible studies were included, involving 6,431 individuals. The pooled data demonstrated that acupuncture combined with conventional rehabilitation (CR) was superior to CR in reducing the Modified Ashworth Scale (MAS) score (standardized mean difference [SMD] = -0.73; 95% CI = -0.83 to -0.63; I 2 = 65%; low certainty of evidence). The favorable results were also observed in comparisons of acupuncture vs. CR (SMD = -0.22, 95% CI = -0.36 to -0.07; I 2 = 49%; moderate certainty of evidence). Subgroup analysis showed that acupuncture treatment with a frequency of once or twice a day was more effective than CR. In addition, the antispasmodic effect of acupuncture treatment increased with more sessions. Four studies explicitly reported slight acupuncture-related adverse events. Conclusion: Acupuncture could be recommended as adjuvant therapy for spasticity after stroke. However, due to the high risk of bias and heterogeneity of the included studies, the effectiveness of acupuncture for post-stroke spasticity remains to be confirmed.

Clinical practice guidelines and expert consensus statements on rehabilitation for patients with COVID-19: protocol for a systematic review.

INTRODUCTION: COVID-19 is a highly infectious disease, characterised by respiratory, physical and psychological dysfunctions. Rehabilitation could effectively alleviate the symptoms and promote recovery of the physical and mental health of patients with COVID-19. Recently, rehabilitation medical institutions have issued clinical practice guidelines (CPGs) and expert consensus statements involving recommendations for rehabilitation assessments and rehabilitation therapies for COVID-19. This systematic review aims to assess the methodological quality and reporting quality of the guidance documents, evaluate the heterogeneity of the recommendations and summarise the recommendations with respect to rehabilitation assessments and rehabilitation therapies for COVID-19 to provide a quick reference for front-line clinicians, therapists and patients as well as reasonable suggestions for future guidelines. METHODS AND ANALYSIS: The electronic databases including PubMed, Embase, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Wanfang Database and China National Knowledge Infrastructure (CNKI) and websites of governments or organisations (eg, National Guideline Clearinghouse, Guidelines International Network, National Institute for Health and Clinical Excellence, Scottish Intercollegiate Guidelines Network and WHO) will be searched for eligible CPGs and expert consensus statements from inception to August 2022. CPGs and expert consensus statements published in Chinese or English and presenting recommendations for modern functional rehabilitation techniques and/or traditional Chinese medicine rehabilitation techniques for COVID-19 will be included. Reviews, interpretations, old versions of CPGs and expert consensus statements and those for the management of other diseases during the pandemic will be excluded. Two reviewers will independently review each article, extract data, appraise the methodological quality following the Appraisal of Guidelines for Research & Evaluation II tool and assess the reporting quality with the Reporting Items for Practice Guidelines in Healthcare statement. The Measurement Scale of Rate of Agreement will be used to evaluate the heterogeneity of the recommendations in different CPGs and expert consensus statements. Agreement between reviewers will be calculated using the intraclass correlation coefficient. We will also summarise the recommendations for rehabilitation in patients with COVID-19. The results will be narratively described and presented as tables or figures. ETHICS AND DISSEMINATION: Ethics approval is not needed for this systematic review because information from published documents will be used. The findings will be submitted for publication in a peer-reviewed journal and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PROSPERO REGISTRATION NUMBER: CRD42020190761.

[Research progress of effect of Tai Chi on cognitive function in the elderly based on neuroelectrophysiological techniques and brain imaging techniques].

With the increasing prominence of population aging, the cognitive decline of the elderly has gradually become a hotspot of clinical research. As a traditional rehabilitation exercise, Tai Chi has been proved to have a positive effect on improving cognitive function and delaying cognitive decline in the elderly. However, the related brain function mechanism is still unclear. In this paper, we collected studies which observed the changes of Tai Chi on brain regions related to cognitive function in the elderly using magnetic resonance imaging (MRI), electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS). We summarized relevant studies from perspective of structural and functional changes in the brain. The results showed that Tai Chi may delay and improve cognitive decline in the elderly by reshaping the structure and function of brain regions related to cognitive function such as memory, attention and execution. The effect of Tai Chi for cognitive function may be associated with positive regulation of cardiovascular function, emotion and meditation level of the elderly. In addition, the improvement of cognitive function further enhances the balance of the elderly. We also found that practice time, frequency and intensity of Tai Chi could be factors influencing the improvement of cognitive function and brain function in the elderly.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats.

OBJECTIVE: To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs). METHODS: Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta. RESULTS: EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects. CONCLUSION: EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

Effect of Exercise on Breast Cancer: A Systematic Review and Meta-analysis of Animal Experiments.

Objective: Exercise is reported to be beneficial for breast cancer. However, the results seem inconsistent. We conducted this systematic review and meta-analysis of animal experimental studies to fully understand the effect of exercise on breast cancer in animal model. Methods: We searched databases from inception to April 2022 and manually searched related references to retrieve eligible studies. We screened eligible studies and extracted related data. We assessed the risk of bias and reporting quality using the SYstematic Review Centre for Laboratory animal Experimentation Risk of Bias tool and the Animal Research: Reporting of In Vivo Experiments guidelines 2.0, respectively. We summarized the study characteristics and findings of included studies and conducted meta-analysis with RevMan software. Subgroup analysis and sensitivity analysis were also performed. Results: We identified 537 potential literatures and included 47 articles for analysis. According to the results of risk of bias assessment, only selective outcome reporting was in low risk of bias. Items of sequence generation, random outcome assessment, and incomplete outcome data were rated as high risk of bias. Most of other items were rated unclear risk of bias. In reporting quality assessment, all included articles reported grouping method and experimental procedures. However, no study provided information of the study protocol registration. Meta-analysis showed that, compared with sedentary lifestyle, exercise reduced more tumor weight (MD = -0.76, 95%CI -0.88 to -0.63, p = 0.85, I 2 = 0%) and tumor number per animal (MD = -0.61, 95%CI -0.91 to -0.31, p = 0.34, I 2 = 8%). Exercise decreased more tumor incidence than sedentary lifestyle both in motorized wheel/high-intensity (OR = 0.22, 95%CI 0.11 to 0.46, p = 0.09, I 2 = 41%) and free wheel/low-intensity treadmill running (OR = 0.45, 95%CI 0.14 to 1.44, p = 0.04, I 2 = 60%). Sensitivity analysis showed that the results were robust. Conclusion: Exercise could reduce tumor weight, number of tumors per animal, and incidence of tumor in breast cancer model of mice and rats. However, the risk of bias items and reporting guidelines in preclinical studies should be concerned. Future research should consider standards of conducting and reporting preclinical studies and choose suitable exercise protocol for higher quality evidence of exercise for breast cancer.

Establishing a Regulatory Science System for Supervising the Application of Artificial Intelligence for Traditional Chinese Medicine: A Methodological Framework.

In this study, we reported a methodological framework for the development of a guideline for establishing a regulatory science system for supervising the application of artificial intelligence for traditional Chinese medicine (TCM). It introduced all of the key steps for developing the guideline as follows: the composition of the guideline expert groups, summary steps, agency, purpose, targeted population, writing, publishing, updating, dissemination, dynamic monitoring, and evaluation. The guideline will provide the basis for national authorities to effectively regulate artificial intelligence technology and enrich the supervisory system for TCM, and it will be of great significance to TCM.

Low-rank sparse feature selection with incomplete labels for Alzheimer's disease progression prediction.

BACKGROUND: How to predict the cognitive performance of Alzheimer's disease (AD) and identify the informative neuroimaging markers is essential for timely treatment and possible delay of the disease. However, incomplete labeled samples and noises in neuroimaging data pose challenges to building reliable and robust prediction models. In this paper, we present a model named Low-rank Sparse Feature Selection with Incomplete Labels (LSFSIL) for predicting cognitive performance and identifying informative neuroimaging markers with MRI data and incomplete cognitive scores. METHOD: We propose a sparse matrix decomposition method to decompose the incomplete cognitive score matrix into two parts for recovering missing scores and utilizing incomplete labeled data. The former is the recovered cognitive score matrix without missing values. To make the recovered scores close to the real ones, a manifold regularizer is devised to fit the label distribution for capturing the label correlations locally. The latter is a ℓ1-norm regularized matrix which represents the associated errors. Next, a low-rank regression model that regards the recovered matrix as the target is developed to increase the robustness to noises and outliers. Besides, ℓ2,1-norm is introduced into the objective function as a sparse regularization to identify the important features. RESULTS: Experimental results demonstrate that LSFSIL achieves higher performance and outperforms several state-of-the-art feature selection approaches. Moreover, the neuroimaging markers selected by LSFSIL are consistent with the previous AD studies. CONCLUSIONS: LSFSIL is effective in informative neuroimaging marker identification for cognitive performance prediction with incomplete labeled data.

A Systematic Review and Meta-Analysis of the Prevalence and Risk Factors of Depression in Type 2 Diabetes Patients in China.

Background: The prevalence of type 2 diabetes mellitus (T2DM) is increasing in China. Depression in patients with T2DM interferes with blood glucose management, leads to poor treatment outcomes, and has a high risk of dementia and cardiovascular event. We conducted this systematic review and meta-analysis to evaluate the prevalence of depression in patients with T2DM in China and explore potential risk factors associated with depression in T2DM. Methods: We conducted a literature search in MEDLINE/PubMed, EMBASE, the Cochrane Library, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), the Chinese Science and Technology Periodical Database (VIP), and the Wanfang Database from their inception to February 25, 2022 to include population-based, cross-sectional surveys that investigated the prevalence of depression in Chinese T2DM patients and studied possible risk factors. Gray literature and reference lists were also manually searched. We used the Agency for Healthcare Research and Quality methodology checklist to assess the risk of bias in the included studies. Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The primary outcome was the pooled prevalence of depression in Chinese T2DM patients, and the secondary outcomes included potential risk factors for depression in T2DM patients. R (version 3.6.1) and Stata (version 12.0) software were used for data synthesis. Results: We included 48 reports that identified 108,678 subjects. Among the included reports, 4 were rated as low risk of bias, 40 moderate risks of bias, and 4 high risks of bias. The prevalence of depression in T2DM patients in China was 25.9% (95% CI 20.6%-31.6%). The prevalence of depression was higher in women (OR = 1.36, 95% CI 1.19-1.54), subjects ≥60 years (OR = 1.56, 95% CI 1.14-2.14), with a primary school or lower education (vs. middle or high school education (OR = 1.49, 95% CI 1.16 - 1.92); vs. college degree or higher education (OR = 1.84, 95% CI 1.16 - 2.92), with a duration of T2DM ≥ 10 years (OR = 1.68, 95% CI 1.11-2.54), with complications (OR = 1.90, 95% CI 1.53-2.36), insulin users (OR = 1.46, 95% CI 1.09-1.96) and individuals living alone (OR = 2.26, 95% CI 1.71-2.98). T2DM patients with current alcohol use had a lower prevalence of depression (OR = 0.70, 95% CI 0.58-0.86). Prevalence varied from 0.8 to 52.6% according to different instruments used to detect depression. Conclusion: The prevalence of depression in T2DM patients is remarkable in China. Potential risk factors of depression in T2DM patients included women, age ≥ 60 years, low educational level, complications, duration of diabetes ≥ 10 years, insulin use, and living alone. High-quality epidemiological investigations on the prevalence of depression in Chinese T2DM patients are needed to better understand the status of depression in T2DM. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182979.