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 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.

Role of optical coherence tomography in depression detection: a protocol of systematic review and meta-analysis.

INTRODUCTION: Optical coherence tomography (OCT) is a non-invasive approach for detecting changes in the retinal layers, which may also reflect changes in brain structure and function. As one of the leading causes of disability worldwide, depression has been associated with alteration of brain neuroplasticity. However, the role of OCT measurements in detecting depression remains unknown. This study aims to employ a systematic review and meta-analysis approach to explore ocular biomarkers measured by OCT for detecting depression. METHODS AND ANALYSIS: We will search studies describing the relationship between OCT and depression across seven electronic databases, and retrieve articles published from database inception to date. We will also manually search grey literature and reference lists included in the retrieved studies. Two independent reviewers will screen studies, extract data and assess risk of bias. Target outcomes will include peripapillary retinal nerve fibre layer thickness, macular ganglion cell complex thickness and macular volume, as well as other related indicators. Next, we will conduct subgroup analysis and meta-regression to explore study heterogeneity, then perform sensitivity analysis to investigate the robustness of the synthesised results. Meta-analysis will be performed using Review Manager (V.5.4.1) and STATA (V.12.0), and the certainty of evidence will be graded according to the Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: Ethics approval is not necessary because the data used in this systematic review and meta-analysis will be extracted from published studies. Study results will be disseminated by publishing our findings in a peer-reviewed journal.

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.

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].

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.

[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.

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.

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.

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.

Extracorporeal Shock Wave Therapy on Spasticity After Upper Motor Neuron Injury: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study was to evaluate the effectiveness and safety of extracorporeal shock wave therapy on spasticity after upper motor neuron injury. DESIGN: Eight electronic databases were searched systematically from their inception to August 3, 2021, to provide robust evidence for the efficacy of extracorporeal shock wave therapy for spasticity and range of motion after upper motor neuron injury. Study screening, data extraction, risk of bias assessment, and evaluation of the certainty of evidence were performed independently by two independent reviewers. Data analysis was conducted using RevMan 5.3.5 and R 3.6.1 software. RESULTS: Forty-two studies with 1973 patients who met the eligibility criteria were selected from articles published from 2010 to 2021, of which 34 were included in the meta-analysis. A comparison intervention revealed that extracorporeal shock wave therapy significantly decreased the Modified Ashworth Scale score and increased the passive range of motion of a joint. Regarding the safety of extracorporeal shock wave therapy, slightly adverse effects, such as skin injury, bone distortion, muscle numbness, pain, petechiae, and weakness, were reported in five studies. CONCLUSIONS: Extracorporeal shock wave therapy may be an effective and safe treatment for spasticity after upper motor neuron injury. However, because of poor methodological qualities of the included studies and high heterogeneity, this conclusion warrants further investigation. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the impact of extracorporeal shock wave therapy on spasticity after upper motor neuron injury; (2) Describe the factors that affect the efficacy of extracorporeal shock wave therapy on spasticity; and (3) Discuss the mechanism of action of extracorporeal shock wave therapy on spasticity. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Acupuncture for tension-type headache: a systematic review and meta-analysis of randomized controlled trials.

Background: Tension-type headache (TTH) is the most common neurologic disease worldwide. Acupuncture is commonly applied to treat TTH, but evidence of acupuncture for TTH is contradictory based on previous meta-analyses. Therefore, we conducted this systematic review and meta-analysis to update the evidence of acupuncture for TTH and aimed to provide a valuable reference for clinical application. Methods: We searched 9 electronic databases from their inceptions to July 1, 2022 for randomized controlled trials (RCTs) of acupuncture for TTH. We also manually searched reference lists and relevant websites, and the experts in this field were consulted for possible eligible studies. Two independent reviewers conducted literature screening, data extraction, and risk of bias assessment. The revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias of included studies. Subgroup analyses were carried out based on frequency of acupuncture, total sessions, treatment duration, needle retention, types of acupuncture and categories of medication. Data synthesis was performed using Review Manager 5.3 and Stata 16. The Grading of Recommendations Assessment, Development and Evaluation Approach (GRADE) was used to evaluate the certainty of evidence of each outcome. Meanwhile, the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) was used to assess the reporting quality of interventions in clinical trials of acupuncture. Results: 30 RCTs involving 2,742 participants were included. According to ROB 2, 4 studies were considered as low risk, and the rest studies were some concerns. After treatment, compared with sham acupuncture, acupuncture had greater effect in improvement of responder rate [3 RCTs, RR = 1.30, 95%CI (1.13, 1.50), I2 = 2%, moderate certainty] and headache frequency [5 RCTs, SMD = -0.85, 95%CI (-1.58, -0.12), I2 = 94%, very low certainty]. In contrast to medication, acupuncture was more effective to reduce pain intensity [9 RCTs, SMD = -0.62, 95%CI (-0.86, -0.38), I2 = 63%, low certainty]. Adverse events were evaluated in 16 trials, and no serious event associated with acupuncture occurred. Conclusions: Acupuncture may be an effective and safe treatment for TTH patients. Due to low or very low certainty of evidence and high heterogeneity, more rigorous RCTs are needed to verify the effect and safety of acupuncture in the management of TTH.

The role of short-chain fatty acids in inflammatory skin diseases.

Short-chain fatty acids (SCFAs) are metabolites of gut microbes that can modulate the host inflammatory response, and contribute to health and homeostasis. Since the introduction of the gut-skin axis concept, the link between SCFAs and inflammatory skin diseases has attracted considerable attention. In this review, we have summarized the literature on the role of SCFAs in skin inflammation, and the correlation between SCFAs and inflammatory skin diseases, especially atopic dermatitis, urticaria, and psoriasis. Studies show that SCFAs are signaling factors in the gut-skin axis and can alleviate skin inflammation. The information presented in this review provides new insights into the molecular mechanisms driving gut-skin axis regulation, along with possible pathways that can be targeted for the treatment and prevention of inflammatory skin diseases.

Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats.

OBJECTIVE: To investigate whether the antihypertensive mechanism of electroacupuncture (EA) is associated with attenuating phenotype transformation of vascular smooth muscle cells (VSMCs) via phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways. METHODS: Eight Wistar-ktoyo (WKY) rats were set as normal blood pressure group (normal group). A total of 32 spontaneous hypertensive rats (SHRs) were randomly divided into 4 groups using random number tables: a model group, an EA group, an EA+PI3K antagonist group (EA+P group), and an EA+p38 MAPK agonist+extracellular signal-regulated kinase (ERK) agonist group (EA+M group) (n=8/group). SHRs in EA group, EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks, while rats in the normal and model groups were bundled in same condition. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of each rat was measured at 0 week and the 4th week. After 4-week intervention, thoracic aorta was collected for hematoxylin-eosin (HE) staining, immunohistochemistry [the contractile markers α-smooth muscle actin (α-SMA) and calponin and the synthetic marker osteopontin (OPN)] and Western blot [α-SMA, calponin, OPN, PI3K, phosphorylated-Akt (p-Akt), Akt, p-p42/44 ERK, total p42/44 ERK, p-p38 MAPK and total p38 MAPK]. RESULTS: EA significantly reduced SBP, DBP and MAP (P<0.01). HE staining showed that the wall thickness of thoracic aorta in EA group was significantly decreased (P<0.01). From results of immunohistochemistry and Western blot, EA increased the expression of α-SMA and calponin, and decreased the expression of OPN (P<0.01). In addition, the expression of PI3K and p-Akt increased (P<0.01), while the expression of p-p42/44 ERK and p-p38 MAPK decreased in EA group (P<0.01). However, these effects were reversed by PI3K antagonist, p38 MAPK agonist and ERK agonist. CONCLUSIONS: EA was an effective treatment for BP management. The antihypertensive effect of EA may be related with inhibition of phenotypic transformation of VSMCs, in which the activation of PI3K/Akt and the repression of MAPK pathway were involved.

The effects of acupuncture therapy in migraine: An activation likelihood estimation meta-analysis.

Background: Previous functional magnetic resonance imaging studies indicated that acupuncture could activate the brain regions in patients with migraine. However, these studies showed inconsistent results. This activation likelihood estimation (ALE) meta-analysis aimed to investigate the consistent activated change of brain regions between pre- and post-acupuncture treatment in migraineurs. Methods: We conducted a literature search in PubMed, Embase, Web of Science, the Cochrane Library, the China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, the Wanfang Database, and the Chinese Biomedical Literature Database from their inception to 18 August, 2022, to obtain articles assessing the functional magnetic resonance imaging changes of acupuncture for migraine. Two investigators independently performed literature selection, data extraction, and quality assessment. The methodological quality was assessed with a modified version of the checklist. The reporting quality of interventions among included studies was evaluated by the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Our meta-analysis was conducted according to the GingerALE software. The Jackknife sensitivity analysis was used to assess the robustness of the results. Results: 14 articles were finally included according to the eligible criteria. Regarding the immediate effect of acupuncture on migraine, the ALE meta-analysis demonstrated that the deactivation regions were mainly located in the superior frontal gyrus, and middle frontal gyrus (uncorrected P < 0.001). The ALE meta-analysis of the cumulative effect showed that the activation regions were the thalamus, superior frontal gyrus, posterior lobe of the cerebellum, insula, middle frontal gyrus, precentral gyrus, anterior cingulate, and the deactivation brain regions were located in the transverse temporal gyrus, postcentral gyrus, superior temporal gyrus, anterior cingulate, parahippocampal gyrus, inferior parietal lobule, and inferior occipital gyrus (uncorrected P < 0.001). Conclusion: Acupuncture could activate multiple brain areas related with the regulation of pain conduction, processing, emotion, cognition, and other brain regions in patients with migraine. In the future, the combination of multiple imaging technologies could be a new approach to deeply investigate the central mechanism of acupuncture for migraine.