Efficacy of repetitive transcranial magnetic stimulation with different application parameters for post-stroke cognitive impairment: a systematic review.

Background: Cognitive impairment is a prevalent consequence of stroke, seriously affecting recovery and quality of life while imposing substantial burdens on both patients' families and society. Repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for post-stroke cognitive impairment (PSCI). However, the a lack of standardized and explicit guidelines regarding rTMS application parameters. Therefore, this study systematically evaluated the efficacy of various parameters of rTMS in treating PSCI and explored its potential mechanism. Methods: We conducted a comprehensive search across seven scientific databases, namely China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), China Science and Technology Journal Database (VIP), Web of Science, PubMed, Embase, and Cochrane Library, to identify randomized controlled trials (RCTs) investigating the efficacy of rTMS for PSCI. The search encompassed the period from database creation until July 28, 2023. To evaluate the risk of bias in included studies, we employed the Cochrane recommended risk of bias assessment tool. Furthermore, we extracted relevant clinical application parameters associated with rTMS and performed comparative analyses to assess their therapeutic effects under different parameter settings. Results: The present study included 45 RCTs involving a total of 3,066 patients with PSCI. Both high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) demonstrated safety and efficacy, yet failed to exhibit significant differentiation in terms of cognitive improvement. Furthermore, intermittent theta burst stimulation (iTBS), although yielding positive results, did not surpass traditional rTMS in effectiveness. Combining HF-rTMS with LF-rTMS resulted in superior efficacy compared to single rTMS intervention. Moreover, the combination of rTMS with other cognitive therapies exhibited potential for enhanced benefits among patients. Conclusion: rTMS can effectively and safely enhance cognitive function, improve quality of life, and enhance activities of daily living in patients with PSCI. Furthermore, the combination of rTMS with other conventional rehabilitation methods can yield additional positive effects. However, due to insufficient evidence, an optimal parameter protocol for rTMS can not be currently recommended. Future research should prioritize orthogonal experimental design methods that incorporate multiple parameters and levels to determine the optimal parameter protocol for rTMS in PSCI.

Effect of acupuncture therapy for postoperative gastrointestinal dysfunction in gastric and colorectal cancers: an umbrella review.

Background: Gastrointestinal dysfunction is a prevalent postoperative complication in patients undergoing surgery for gastric cancer and colorectal cancer. Acupuncture holds promise as a great potential therapeutic intervention. The efficacy of acupuncture therapy for postoperative gastrointestinal dysfunction has been assessed in some studies, however, the variability in results and study quality influences practical clinical application. Therefore, it is necessary to summarize and analyze the published clinical research data in this field. Objective: This study aimed to synthesize evidence from systematic reviews and meta-analyses in order to assess the efficacy of acupuncture therapy for postoperative gastrointestinal dysfunction in patients with gastric and colorectal cancer. Design: Umbrella review of systematic reviews and meta-analyses. Methods: We searched China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), China Science and Technology Journal Database (VIP), Chinese biomedical literature service system (SinoMed), PubMed, Embase, Cochrane Library, and Web of Science for all systematic review/meta-analysis of acupuncture for postoperative gastrointestinal dysfunction in gastric and colorectal cancers. From the establishment of the database to July 8, 2023. Two independent reviewers conducted literature extraction and evaluation. The quality of included studies was assessed using The preferred reporting items for systematic reviews and meta-analysis statements 2020 (PRISMA2020), the quality of the methods was assessed using a measuring tool to assess systematic reviews 2 (AMSTAR 2), and the level of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). The statistical analysis was conducted using RevMan 5.4, and the effect size was expressed as Odds Ratio (OR), Mean Difference (MD), and 95% confidence interval (CI) based on the extracted data type (test level α= 0.05). The heterogeneity was assessed using the I 2 statistic and Q-test (χ2). The outcome indicators such as time to first defecation and time to first flatus were utilized as endpoints to assess the efficacy of different acupuncture therapies. Results: A total of six systematic reviews/meta-analyses were included in this study, involving 12 different acupuncture therapies. PRISMA 2020 indicated that the studies all scored between 13-20.5. There were deficiencies in protocol and registration, assessment of the quality of evidence for outcome indicators, risk of bias, and declaration of conflict of interest. The AMSTAR 2 evaluations showed that five studies were very low quality and one was low quality. The level of evidence for various acupuncture interventions varied from very low to moderate.For patients with gastrointestinal dysfunction after gastric cancer surgery, ear acupressure [MD=-11.92, 95% (-14.39,-9.44), P<0.00001], moxibustion [MD=-19.16, 95% (-23.00,-16.22), P<0.00001], warm needling [MD=-12.81, 95% (-17.61,-8.01), P<0.00001], acupoint application [MD=-6.40, 95% (-10.26,-2.54), P=0.001], manual acupuncture [MD=-18.32, 95% (-26.31,-10.39), P<0.00001] and transcutaneous electrical acupoint stimulation (TEAS) [MD=-5.17, 95% (-9.59,-0.74), P=0.02] could promote the recovery of gastrointestinal function after surgery.For postoperative colorectal cancer patients, electroacupuncture [MD=-15.17, 95% (-28.81,-1.54), P<0.05], manual acupuncture [MD=-20.51, 95% (-39.19,-1.84), P<0.05], warm needling [MD=-18.55, 95% (-23.86,-13.24), P<0.05], ear acupressure [MD=-5.38, 95% (-9.80,-0.97), P<0.05], acupoint application [MD=-26.30, 95% (-32.81,-19.79), P<0.05], ear acupressure+acupressure [MD=-9.67, 95% (-13.58,-5.76), P<0.05], ear acupressure+manual acupuncture [MD=-18.70, 95% (-21.01,-16.39), P<0.05], ear acupressure+moxibustion [MD=-22.90, 95% (-30.10,-15.70), P<0.05], moxibustion+acupressure [MD=-14.77, 95% (-20.59,-8.95), P<0.05] improved postoperative gastrointestinal function. In addition, the efficacy of acupressure [MD=-12.00, 95% (-31.60,7.60), P>0.05] needed to be further demonstrated. Conclusion: Acupuncture therapy has a positive therapeutic impact on postoperative gastrointestinal dysfunction in gastric and colorectal cancers, but this finding should still be taken with caution.

Modulatory effects of acupuncture on raphe nucleus-related brain circuits in patients with chronic neck pain: A randomized neuroimaging trial.

OBJECTIVE: Acupuncture has shown promise in treating neck pain. Clinical trials have shown mixed results, possibly due to heterogeneous methodologies and the lack of knowledge regarding underlying brain circuit mechanism of action. In this study, we investigated the specific contribution of the serotonergic system in treating neck pain, and the specific brain circuits involved. METHODS: A total of 99 patients with chronic neck pain (CNP) were randomized to receive true acupuncture (TA) or sham acupuncture (SA) 3 times weekly for 4 weeks. Patients with CNP in each group were assessed for primary outcomes by measuring the Visual Analog Scale (VAS) and the duration of each attack; secondary outcomes were measured using the Neck Disability Index (NDI), Northwick Park Neck Pain Questionnaire (NPQ), McGill Pain Questionnaire (MPQ), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and the 12-item Short Form Quality Life Scale (SF-12); levels of functional circuits connectivity were assessed using resting-state functional magnetic resonance imaging in the dorsal (DR) and median (MR) raphe nucleus, before and after undergoing acupuncture. RESULTS: Patients receiving TA showed more extensive symptom improvement compared with SA. Regarding the primary outcomes, changes observed in the TA group were as follows: VAS = 16.9 mm (p < 0.001) and the duration of each attack = 4.30 h (p < 0.001); changes in the SA group: VAS = 5.41 mm (p = 0.138) and the duration of each attack = 2.06 h (p = 0.058). Regarding the secondary outcomes, changes in the TA group: NDI = 7.99 (p < 0.001), NPQ = 10.82 (p < 0.001), MPQ = 4.23 (p < 0.001), SAS = 5.82 (p < 0.001), SDS = 3.67 (p = 0.003), and SF-12 = 3.04 (p < 0.001); changes in the SA group: NDI = 2.97 (p = 0.138), NPQ = 5.24 (p = 0.035) and MPQ = 2.90 (p = 0.039), SAS = 1.48 (p = 0.433), SDS = 2.39 (p = 0.244), and SF-12 = 2.19 (p = 0.038). The modulatory effect of TA exhibited increased functional connectivity (FC) between the DR and thalamus, between the MR and parahippocampal gyrus, amygdala, and insula, with decreased FC between the DR and lingual gyrus and middle frontal gyrus, between the MR and middle frontal gyrus. Furthermore, changes in the DR-related circuit were specifically associated with the intensity and duration of pain, and the MR-related circuit was correlated with the quality of life with CNP. CONCLUSION: These results demonstrated the effectiveness of TA in treating neck pain and suggested that it regulates CNP by reconfiguring the function of the raphe nucleus-related serotonergic system.

Effects of transcutaneous neuromuscular electrical stimulation on post-stroke dysphagia: a systematic review and meta-analysis.

Background: Dysphagia is one of the common complications after stroke. It is closely related to lung infection and malnutrition. Neuromuscular electrical stimulation (NMES) is widely used in the treatment of post-stroke dysphagia, but the evidence-based medical evidence of NMES is limited. Therefore, this study aimed to evaluate the clinical efficacy of NMES in patients with post-stroke dysphagia by systematic review and meta-analysis. Methods: We searched the CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, and Web of Science databases for all randomized controlled trials (RCTs) of NMES in the treatment of post-stroke dysphagia from the establishment of the database to 9 June 2022. The risk of bias assessment tool recommended by Cochrane and the GRADE method was used to assess the risk of bias and the quality of evidence. RevMan 5.3 was used for statistical analysis. Sensitivity and subgroup analyses were performed to evaluate the intervention effect more specifically. Results: A total of 46 RCTs and 3,346 patients with post-stroke dysphagia were included in this study. Our meta-analysis showed that NMES combined with routine swallowing therapy (ST) could effectively improve swallowing function in Penetration-Aspiration Scale (MD = -0.63, 95% CI [-1.15, -0.12], P = 0.01), Functional Oral Intake Scale (MD = 1.32, 95% CI [0.81, 1.83], P < 0.00001), Functional Dysphagia Scale (MD = - 8.81, 95% CI [-16.48, -1.15], P = 0.02), the Standardized Swallowing Assessment (MD = -6.39, 95% CI [-6.56, -6.22], P < 0.00001), the Videofluoroscopic Swallow Study (MD = 1.42, 95% CI [1.28, 1.57], P < 0.00001) and the Water swallow test (MD = -0.78, 95% CI [-0.84, -0.73], P < 0.00001). Furthermore, it could improve the quality of life (MD = 11.90, 95% CI [11.10, 12.70], P < 0.00001), increase the upward movement distance of hyoid bone (MD = 2.84, 95% CI [2.28, 3.40], P < 0.00001) and the forward movement distance of hyoid bone (MD = 4.28, 95% CI [3.93, 4.64], P < 0.00001), reduce the rate of complications (OR = 0.37, 95%CI [0.24, 0.57], P < 0.00001). Subgroup analyses showed that NMES+ST was more effective at 25 Hz, 7 mA or 0-15 mA, and at courses ( ≤ 4 weeks). Moreover, patients with an onset of fewer than 20 days and those older than 60 years appear to have more positive effects after treatment. Conclusion: NMES combined with ST could effectively increase the forward and upward movement distance of the hyoid bone, improve the quality of life, reduce the rate of complications, and improve the swallowing function of patients with post-stroke dysphagia. However, its safety needs to be further confirmed. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022368416.

Acupuncture and moxibustion in patients with cancer-related insomnia: A systematic review and network meta-analysis.

Objectives: Cancer-related insomnia (CRI) is one of the most common and serious symptoms in patients with cancer. Acupuncture and moxibustion have been widely applied in the treatment of CRI. Nevertheless, the comparative efficacy and safety of different acupuncture and moxibustion techniques remain unclear. This study aimed to evaluate and compare the efficacy and safety of different acupuncture and moxibustion techniques in the treatment of CRI. Methods: Eight medical databases were comprehensively searched for relevant randomized controlled trials (RCTs) as of June 2022. Two independent reviewers assessed the risk of bias and conducted the research selection, data extraction, and quality assessment of the included RCTs. A network meta-analysis (NMA) was performed using frequency models, combining all available direct and indirect evidence from RCTs. The Pittsburgh Sleep Quality Index (PSQI) was set as the primary outcome, and adverse events and effective rates were set as the secondary outcomes. The efficacy rate was calculated as the ratio of patients with insomnia symptom relief to the total number of patients. Results: Thirty-one RCTs with 3,046 participants were included, including 16 acupuncture- and moxibustion-related therapies. Transcutaneous electrical acupoint stimulation [surface under the cumulative ranking curve (SUCRA) 85.7%] and acupuncture and moxibustion (SUCRA 79.1%) were more effective than Western medicine, routine care, and placebo-sham acupuncture. Furthermore, Western medicine showed significantly better effects than placebo-sham acupuncture. In the NMA, the acupuncture and moxibustion treatments with the best therapeutic effects for CRI were transcutaneous electrical acupoint stimulation (SUCRA 85.7%), acupuncture and moxibustion (SUCRA 79.1%), auricular acupuncture (SUCRA 62.9%), routine care combined with intradermal needling (SUCRA 55.0%), and intradermal needling alone (SUCRA 53.3%). No serious acupuncture- or moxibustion-related adverse events were reported in the included studies. Conclusion: Acupuncture and moxibustion are effective and relatively safe in treating CRI. The relatively conservative recommended order of acupuncture- and moxibustion-related therapies for CRI is as follows: transcutaneous electrical acupoint stimulation, acupuncture and moxibustion, and auricular acupuncture. However, the methodological quality of the included studies was generally poor, and further high-quality RCTs are needed to strengthen the evidence base.

Transcutaneous electrical acupoint stimulation for immunologic function after surgery in patients with gastrointestinal tumor: a meta-analysis.

There is no consensus on whether transcutaneous acupoint electrical stimulation can be used to improve the immune function of postoperative patients with gastrointestinal tumors. This meta-analysis aims to evaluate the effects of transcutaneous electrical acupoint stimulation (TEAS) on postoperative immune function of patients with gastrointestinal tumor and provide evidence-based basis for clinical evaluation. The method used in this study is to systematically searched English databases including PubMed, Cochrane Library (CENTRAL), Excerpta Medica Database (EMbase), Web of Science and Chinese databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data, VIP database and China Biomedical Literature Database (SinoMed). Relevant registration platform named Chinese Clinical Trial Registry (ChiCTR) was also searched. Manual search and document tracking are also performed. The aforementioned databases were retrieved for transcutaneous electrical acupoint stimulation for immunologic function after surgery in patients with gastrointestinal tumor randomized controlled trials (RCTs) from inception to 1 November 2022. Meta-analysis was conducted by RevMan5.4.1 software, and the evidence quality was evaluated using Cochrane risk bias evaluation form. In this study, a total of 18 trials with 1618 participants were analyzed. Only two studies were shown to be low risk. The results showed that there were significant differences in cellular immune and inflammatory factors and receptors, such as CD3+, CD4+, CD4+/CD8+, NK, IL-6, TNF-α, sIL-2 R, IL-2 and CRP, had significant effects (P < 0.05) after TEAS intervention on gastrointestinal tumor; however, CD8+ (P = 0.07) and IL-10 (P = 0.26) did not. Judging from the current evidence, TEAS was found to improve the immune function of patients with gastrointestinal tumors after surgery and reduce the level of inflammatory response, worthy of clinical promotion and use.

Abnormal Dynamics of Functional Connectivity Density Associated With Chronic Neck Pain.

Background: Chronic neck pain (CNP) is highly prevalent and complicated, associated with limited movement, and accompanied by shoulder pain and other clinical manifestations such as dizziness, anxiety, and insomnia. Brain structural and functional abnormalities often occur in patients with CNP. However, knowledge of the brain's functional organization and temporal dynamics in CNP patients is limited. Dynamic functional connectivity density (dFCD) can reflect the ability of brain areas or voxels to integrate information, and could become neuroimaging markers for objectively reflecting pain to a certain extent. Therefore, this study compared the dFCD between CNP patients and healthy controls (HCs) and investigated potential associations of the abnormal density variability in dynamic functional connectivity with pain characteristics in CNP patients. Methods: Resting functional magnetic resonance imaging was performed for 89 CNP patients and 57 HCs. After preprocessing resting-state fMRI images by the Data Processing and Analysis of Brain Imaging toolbox, the sliding window method was applied to investigate dFCD changes in CNP patients and HCs using the DynamicBC toolbox. Then we quantified dFCD variability using their standard deviation. Based on the pain-associated factors collected from the case report form of CNP patients, the mean dFCD variability values of each dFCD from region of interest were extracted to calculate Pearson's correlation coefficient to study the potential correlation between dFCD abnormal variability and pain. Results: Compared with HCs, the dFCD values of the anterior cingulate cortex, occipital lobe, temporal lobe, and cerebellum were statistically different in patients with CNP. Subsequent correlation analysis showed that the variable dFCD in the related brain region was correlative with the course of the disease and clinical symptoms, such as pain and depression, in patients with CNP. Conclusion: Dynamic functional alterations were observed in the brain regions of CNP patients, and the dFCD of these brain regions could become neuroimaging markers for objectively reflecting pain to a certain extent. This suggests that chronic pain may cause changes in pain processing and emotional feedback and highlights the link between dynamic neural communication in brain regions and disease conditions, deepening our understanding of chronic pain diseases, and guiding clinical practice.

The Comparative Efficacy of Multiple Acupuncture for Alzheimer's Disease: A Bayesian Network Meta-Analysis.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Numerous cases have illustrated that the acupuncture method could improve AD patients' cognitive function and daily living ability. However, the optimal acupuncture treatments remain controversial. Therefore, we aimed to conduct a systematic review to compare the efficacy of multiple acupuncture therapies for AD and identify the optimal acupuncture intervention for delaying AD progression. Methods: To select potentially concerned randomized controlled trials (RCTs), we searched four English databases, four Chinese databases, and additional sources from 1 May 2021. Two independent reviewers conducted study screening, data extraction, and methodological quality assessment. The primary outcome was global cognitive function improvement. Pairwise and Bayesian network meta-analyses were performed using STATA v15.0 and ADDIS v1.16.8. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to assess the quality of evidence. Results: This study included 34 RCTs with 2,071 participants. Regarding global cognitive function improvement, the pairwise meta-analysis confirmed that electronic acupuncture (EA) plus conventional medicine (CM) and manual acupuncture (MA) plus CM were statistically significantly different from CM, and EA plus CM was ranked as the best combination in the network meta-analysis. In terms of response rate, MA outperformed CM statistically significantly; warm acupuncture (WA) was ranked as the best in the network meta-analysis. Regarding activity of daily living improvement, EA plus CM, MA plus CM, and fire acupuncture plus CM, MA, and scalp acupuncture were statistically significantly different from CM, and EA plus CM was ranked as the best combination in the network meta-analysis. However, the evidences were ranked as low to critically low. Conclusions: Acupuncture, as a monotherapy or an adjuvant therapy, may have a beneficial effect on efficacy for AD. EA plus CM may be the optimal acupuncture therapy for AD and should be administered to AD patients. It may aid and support patient, operative, and societal decision-making. Due to the dearth of high-quality evidence, additional high-quality studies should be conducted to ensure these findings in the future. This study is registered with PROSPERO (CRD42021252305).

Optimal Method of Electrical Stimulation for the Treatment of Upper Limb Dysfunction After Stroke: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The obstacle of limb motor caused by stroke, especially the decline of motor function of upper limbs, can directly affect the activities of daily living of stroke patients with hemiplegia. Based on long-term clinical practice, the treatment effect of electrical stimulation methods for stroke limb dysfunction has been widely recognized and supported by authoritative guidelines and systematic reviews. However, which electrical stimulation method is the optimum in the treatment of stroke limb dysfunction is still a controversial issue. OBJECTIVE: In this paper, we adopted Network Meta-Analysis (NMA) to rank the priorities of various electrical stimulation methods, so as to select the optimal electrical stimulation method and discuss its rationality in guiding clinical practice. METHODS: We carried out a systematic review by searching a total of 6806 studies from 8 databases and 2 clinical trial registries, and finally screened out 34 studies for further investigation. Then, pairwise meta-analysis and Bayesian network meta-analysis were employed to evaluate the effectiveness and ranking of various interventions. The primary outcome measure was Fugl-Meyer Assessment Upper Extremity (FMA-UE), and the secondary outcome measures were Modified Barthel Index (MBI) and Modified Ashworth Scale (MAS). Finally, the risk of bias, publication bias and sensitivity of the Randomized Controlled Trials (RCTs) were evaluated. RESULTS: On the basis of comprehensive rehabilitation treatment (RT), the Functional Electrical Stimulation (FES) was superior than other electrical stimulation methods in improving both FMA-UE and MBI. Meanwhile, the results indicated that the Transcutaneous Electrical Acupoint Stimulation (TEAS) was the only electrical stimulation method that showed treatment advantages in reducing MAS. CONCLUSION: The study showed that FES had the optimal overall rehabilitation effect on upper limb dysfunction of stroke patients based on the comprehensive RT, while the treatment effect of TEAS on upper limb spasticity after stroke was the most significant.

High-Intensity Interval Training and Moderate-Intensity Continuous Training Attenuate Oxidative Damage and Promote Myokine Response in the Skeletal Muscle of ApoE KO Mice on High-Fat Diet.

The purpose of this study was to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the skeletal muscle in Apolipoprotein E knockout (ApoE KO) and wild-type (WT) C57BL/6J mice. ApoE KO mice fed with a high-fat diet were randomly allocated into: Control group without exercise (ApoE-/- CON), HIIT group (ApoE-/- HIIT), and MICT group (ApoE-/- MICT). Exercise endurance, blood lipid profile, muscle antioxidative capacity, and myokine production were measured after six weeks of interventions. ApoE-/- CON mice exhibited hyperlipidemia and increased oxidative stress, compared to the WT mice. HIIT and MICT reduced blood lipid levels, ROS production, and protein carbonyl content in the skeletal muscle, while it enhanced the GSH generation and potently promoted mRNA expression of genes involved in the production of irisin and BAIBA. Moreover, ApoE-/- HIIT mice had significantly lower plasma HDL-C content, mRNA expression of MyHC-IIx and Vegfa165 in EDL, and ROS level; but remarkably higher mRNA expression of Hadha in the skeletal muscle than those of ApoE-/- MICT mice. These results demonstrated that both exercise programs were effective for the ApoE KO mice by attenuating the oxidative damage and promoting the myokines response and production. In particular, HIIT was more beneficial to reduce the ROS level in the skeletal muscle.

Optimal Acupuncture Methods for Nonspecific Low Back Pain: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Nonspecific low back pain (NLBP) is a common disabling disease that cannot be attributed to a specific, recognizable pathology. The use of acupuncture for NLBP is supported by several guidelines and systematic reviews. However, the efficacy of different acupuncture methods for NLBP management is still debated. This study ranked the effectiveness of acupuncture methods using network meta-analysis to screen out the optimal acupuncture methods and expound the current controversies for their effective application in health policies as well as guiding clinical operations. METHODS: The following databases were searched for relevant randomized controlled trials (RCTs) from inception to December 20, 2020: China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, WANFANG Database, Chinese biomedical literature service system, PubMed, Web of Science, Embase, and Cochrane Library. Relevant registration platforms, including the International Standard Randomised Controlled Trial Number Register (ISRCTN) and Chinese Clinical Trial Registry (ChiCTR), were also searched. Manual retrieval and tracking of references was also performed. Pairwise meta-analysis and Bayesian network meta-analysis using Revman and ADDIS, respectively, were performed and standardized mean differences examined. The primary outcome was visual analog scale (VAS) score and the secondary outcome was Oswestry Disability Index (ODI) score. Safety was defined as the incidence of adverse events. RESULTS: A total of 30 trials with 3196 participants were analyzed; 16.67% of which showed a high risk of bias. The results indicated that fire acupuncture plus manual acupuncture, auricular needling, and electroacupuncture plus warm acupuncture were most effective in reducing VAS score. The most effective interventions for reducing ODI score were manual acupuncture plus conventional medicines, followed by moxibustion and manual acupuncture plus moxibustion. Manual acupuncture plus moxibustion was dominant in the cluster ranking. Acupuncture showed a lower incidence of adverse events (7.70%) than other interventions (conventional medicines, routine care, and placebo; 12.24%). CONCLUSION: We found that manual acupuncture plus moxibustion is the most effective way to reduce NLBP pain and disability. Acupuncture is safer than other interventions. However, more direct comparative evidence from high-quality, large-sample, multicenter RCTs is needed to validate these findings.

Acupuncture for Chronic Fatigue Syndrome: An Overview of Systematic Reviews.

OBJECTIVE: To evaluate the quality of the existing studies and summarize evidence of important outcomes of meta-analyses/systematic reviews (MAs/SRs) of CFS. METHODS: Potentially eligible studies were searched in the following electronic databases from inception to 1 September, 2019: Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed and Cochrane Library. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. The methodological quality of the literature was evaluated by A Measure Tool to Assess Systematic Reviews-2 (AMSTAR-2) and the quality of the report was assessed by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The intra-class correlation coefficient was used to assess the consistency of the reviewers, with an overall intraclass correlation coefficient score of 0.967. RESULTS: Ten MAs/SRs were included. The overall conclusions were that acupuncture had good safety and efficacy in the treatment of CFS, but some of these results were contradictory. The GRADE indicated that out of the 17 outcomes, high-quality evidence was provided in 0 (0%), moderate in 3 (17.65%), low in 10 (58.82%), and very low in 4 (23.53%). The results of AMSTAR-2 showed that the methodological quality of all included studies was critically low. The PRISMA statement revealed that 8 articles (80%) were in line with 20 of the 27-item checklist, and 2 articles (20%) matched with 10-19 of the 27 items. CONCLUSION: We found that acupuncture on treating CFS has the advantage for efficacy and safety, but the quality of SRs/MAs of acupuncture for CFS need to be improved.

Dynamic alterations of amplitude of low-frequency fluctuations in patients with chronic neck pain.

Background: The pathogenesis of neck pain in the brain, which is the fourth most common cause of disability, remains unclear. Furthermore, little is known about the characteristics of dynamic local functional brain activity in cervical pain. Objective: The present study aimed to investigate the changes of local brain activity caused by chronic neck pain and the factors leading to neck pain. Methods: Using the amplitude of low-frequency fluctuations (ALFF) method combined with sliding window approach, we compared local brain activity that was measured by the functional magnetic resonance imaging (fMRI) of 107 patients with chronic neck pain (CNP) with that of 57 healthy control participants. Five pathogenic factors were selected for correlation analysis. Results: The group comparison results of dynamic amplitude of low-frequency fluctuation (dALFF) variability showed that patients with CNP exhibited decreased dALFF variability in the left inferior temporal gyrus, the middle temporal gyrus, the angular gyrus, the inferior parietal marginal angular gyrus, and the middle occipital gyrus. The abnormal dALFF variability of the left inferior temporal gyrus was negatively correlated with the average daily working hours of patients with neck pain. Conclusions: The findings indicated that the brain regions of patients with CNP responsible for audition, vision, memory, and emotion were subjected to temporal variability of abnormal regional brain activity. Moreover, the dALFF variability in the left inferior temporal gyrus might be a risk factor for neck pain.This study revealed the brain dysfunction of patients with CNP from the perspective of dynamic local brain activity, and highlighted the important role of dALFF variability in understanding the neural mechanism of CNP.

Mindfulness and Cyberbullying Among Chinese Adolescents: The Mediating Roles of Perceived Social Support and Empathy.

INTRODUCTION: Previous studies have shown that mindfulness is associated with fewer cyberbullying behaviors in adolescents. The present study investigated the ways in which mindfulness is related to cyberbullying in Chinese adolescents by considering the role of empathy and perceived social support. METHODS: A total of 1,390 Chinese high school students were recruited for this study. Adolescents' self-reports of mindfulness, cyberbullying, empathy, and perceived social support were used in the analyses. RESULTS: The results showed our model fitted the data well [χ2/df = 2.413, CFI = 0.968, TLI = 0.958, RMSEA (90% CI) = 0.059 (0.040-0.078)], and revealed empathy and perceived social support partially mediate the relationship between mindfulness and cyberbullying. CONCLUSION: The results of this study indicate adolescents' mindfulness plays a crucial role on the likelihood of cyberbullying as well as empathy and perceived social support. Improving the mindfulness skills of adolescents should be considered by teachers and parents seeking to decrease cyberbullying.

[Normativity of overview report of the systematic review of acupuncture and moxibustion at home and abroad based on PRIO-harms scale].

OBJECTIVE: To evaluate and compare the normativity of overview report of systematic review (Overviews) of acupuncture and moxibustion at home and abroad so as to further improve the report quality of Overviews of acupuncture and moxibustion in China and provide reliable evidences. METHODS: The articles relevant with Overviews of acupuncture and moxibustion at home and abroad were retrieved by computer from the databases of CNKI, VIP, Wanfang, China BioMedical Literature database (SinoMed), PubMed, Embase and Conchrane Library, dated from the time of establishment to February 12, 2019. The preferred reporting items for Overviews (PRIO-harms) was adopted to evaluate their normativity and make the comparison of the articles between China and foreign countries. RESULTS: A total of 13 articles of Overviews of acupuncture and moxibustion were included, 9 articles of them were of Chinese version and the rest were of English version. The results of PRIO-harms indicated that the proportions of the item numbers related to adequate, partial and inadequate adherence of Chinese version were 3.7%, 63.8% and 32.5%, and those of English version were 12.0%, 57.4% and 30.6% respectively. The reports on the item 10 "additional search for primary studies", the item 12 "data items" and the item 26 "Dual/(co-)authorship" were inadequate adherence by 100% in the articles of both Chinese and English version. CONCLUSION: The overall information of English article report is better than Chinese one, but the reports of either Chinese or English articles are not so satisfactory. It is suggested that the Overviews report should be in reference to the specification in PRIO-harms and the Chinese researchers should study the advantages of English article report and improve the normalization and report quality so as to obtain the high-quality evidences in evidence-based medicine.

Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity.

INTRODUCTION: Skeletal muscle is the major producing and metabolizing site of lactic acid. A family of monocarboxylate transporter (MCT) proteins, especially MCT1 and MCT4, are involved in the lactate-pyruvate exchange and metabolism. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal coordinator of antioxidant response and energy metabolism, and has been reported to associate with the physiological functions of the skeletal muscle. METHODS: In this study, C57BL/6 J mice were administrated with an Nrf2 activator, sulforaphane (SFN) before taking incremental treadmill exercise to exhaustion under hypoxia; then the effects of SFN on exercise endurance and molecular/biochemical makers of the skeletal muscle were evaluated. RESULTS: The results indicated that SFN pretreatment enhanced the exercise endurance under hypoxia. SFN not only increased the expressions of antioxidant genes and activity of antioxidant enzymes, but also significantly increased the mRNA and protein levels of MCT1 and CD147, but not MCT4. Moreover, the expressions of LDH-B and LDH activity of converting lactate into pyruvate, as well as citrate synthase activity were significantly higher, whereas the LDH activity of converting pyruvate into lactate and blood lactate level were remarkably lower in the SFN-exercise mice than those of the phosphate-buffered saline-exercise group. Furthermore, Atf3Δzip2 (the alternatively spliced isoform of activating transcription factor-3) mRNA was increased by the exercise and further potentiated by SFN. CONCLUSION: These results show, for the first time, that SFN increases MCT1 expression in the skeletal muscle under acute hypoxic exercise and suggest that Nrf2 activation is a promising strategy to enhance exercise performance under hypoxia.

The Role of MicroRNAs in the Pathogenesis of Diabetic Nephropathy.

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients; it is also an important cause of renal dysfunction, renal fibrosis, and end-stage renal disease. Unfortunately, the pathogenesis of DN is complex and has not yet been fully elucidated; hence, the pathogenesis of DN to determine effective treatments of crucial importance is deeply explored. Early DN research focuses on hemodynamic changes and metabolic disorders, and recent studies have shown the regulatory role of microRNAs (miRNAs) in genes, which may be a new diagnostic marker and therapeutic target for diabetic nephropathy. In this review, we summarize the recent advances in the clinical value and molecular mechanisms of miRNAs in DN, providing new ideas for the diagnosis and treatment of DN.

Hypoxia preconditioning promotes endurance exercise capacity of mice by activating skeletal muscle Nrf2.

Elite endurance athletes are used to train under hypoxic/high-altitude conditions, which can elicit certain stress responses in skeletal muscle and helps to improve their physical performance. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular redox homeostasis and metabolism in skeletal muscle, playing important roles in adaptation to various stresses. In this study, Nrf2 knockout (KO) and wild-type (WT) mice were preconditioned to 48 h of hypoxia exposure (11.2% oxygen), and the effects of hypoxia preconditioning (HP) on exercise capacity and exercise-induced changes of antioxidant status, energetic metabolism, and mitochondrial adaptation in skeletal muscle were evaluated. Nrf2 knockout (KO) and wild-type (WT) mice were exposed to normoxia or hypoxia for 48 h before taking incremental treadmill exercise to exhaustion under hypoxia. The skeletal muscles were collected immediately after the incremental treadmill exercise to evaluate the impacts of HP and Nrf2 on the exercise-induced changes. The results indicate the absence of Nrf2 did not affect exercise capacity, although the mRNA expression of certain muscular genes involved in antioxidant, glycogen and fatty acid catabolism was decreased in Nrf2 KO mice. However, 48-h HP enhanced exercise capacity in WT mice but not in Nrf2 KO mice, and the exercise capacity of WT mice was significantly higher than that of Nrf2 KO mice. These findings suggest HP promotes exercise capacity of mice with the participation of the Nrf2 signal in skeletal muscle.NEW & NOTEWORTHY Hypoxia preconditioning (HP) activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signal, which was involved in HP-elicited adaptation responses to hypoxia, oxidative, and metabolic stresses in skeletal muscle. On the other hand, Nrf2 deficiency abolished the enhanced exercise capacity after the 48-h HP. Our results indicate that Nrf2 plays an essential role in the exercise capacity-enhancing effect of HP, possibly by modulating muscular antioxidative responses, the mRNA expression of muscular genes involved in glycogen and fatty acid metabolism, as well as mitochondrial biogenesis, and through the cross talk with AMPK and hypoxia-inducible factor-1α signaling.

[Literature quality analysis of RCTs regarding acupuncture for chronic neck pain].

The internationally-accepted Consolidated Standards for Reporting of Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) were applied to evaluate the literature quality of randomized controlled trials (RCTs) regarding acupuncture for chronic neck pain in past 10 years. The literature of RCTs regarding acupuncture for chronic neck pain was searched by computer; the English literature was searched in PubMed and EMbase, while the Chinese literature was searched in CNKI, Wanfang database, VIP database and China Biomedical Literature Database. The literature published from January 2008 to January 2018 was searched. As a result, 29 Chinese articles and 10 English articles were included. According to CONSORT, among Chinese articles, 28 articles (96.6%) described baseline data, 23 articles (79.3%) described randomization, 0 articles (0.0%) described allocation concealment, 3 articles (10.3%) described blind method; among English articles, 6 articles (60.0%) described baseline data, 8 articles (80.0%) described randomization, 8 articles (80.0%) described allocation concealment, and 7 articles (70.0%) described blind method. According to STRICTA, among Chinese articles, 8 articles (27.6%) described needle instrument selection, 18 articles (62.1%) described needle depth, 24 articles (82.8%) described needling sensation, and 0 articles (0.0%) described acupuncturist' qualifications; among English articles, 5 articles (50.0%) described needle instrument selection, 8 articles (80.0%) described needle depth, 3 articles (30.0%) described needling sensation, and 4 articles (40.0%) described acupuncturist' qualifications. In conclusion, the reporting of acupuncture details in Chinese literature is superior to that in English literature, while the reporting of trial design in English literature is slightly superior to that in Chinese literature. Moreover, both Chinese and English literature need to further improve clinical trial design to improve the reporting quality of clinical evidence based on CONSORT and STRICTA.

Effects of acute hypoxia exposure with different durations on activation of Nrf2-ARE pathway in mouse skeletal muscle.

BACKGROUND: Hypoxia training enhances the endurance capacity of athletes. This response may in part be attributed to the hypoxia-induced increase in antioxidant capacity in skeletal muscles. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor which regulates the expression of genes via binding to the antioxidant-response element (ARE) of these genes, plays a crucial role in stimulating the body's defense system and potentially responds to hypoxia. Meanwhile, hypoxia-inducible factor-1α (HIF-1α) is an important player in protecting cells from hypoxic stress. The purpose of this study was to investigate the effects of acute hypoxia exposure with different durations on the activation of Nrf2-ARE pathway and a possible regulatory role of HIF-1α in these responses. METHODS: C57BL/6J mice were allocated into the non-hypoxia 0-hour, 6-hour, 24-hour, and 48-hour hypoxic exposure (11.2% oxygen) groups. The quadriceps femoris was collected immediately after hypoxia. Further, to investigate the possible role of HIF-1α, C2C12 myoblasts with HIF-1α knockdown by small interfering RNA (siRNA) and the inducible HIF-1α transgenic mice were employed. RESULTS: The results showed that 48-hour hypoxia exposure up-regulated protein expression of Nrf2, Nrf2/ARE binding activity and the transcription of antioxidative genes containing ARE (Sod1 and others) in mouse skeletal muscle. Moreover, HIF-1α siRNA group of C2C12 myoblasts showed a remarkable inhibition of Nrf2 protein expression and nuclear accumulation in hypoxia exposure for 72 hours compared with that in siRNA-Control group of the cells. In addition, HIF-1α transgenic mice gave higher Nrf2 protein expression, Nrf2/ARE binding activity and expressions of Nrf2-mediated antioxidative genes in their skeletal muscle, compared with those in the wild-type mice. CONCLUSIONS: The findings suggested that the acute hypoxia exposure could trigger the activation of Nrf2-ARE pathway, with longer duration associated with higher responses, and HIF-1α expression might be involved in promoting the Nrf2-mediated antioxidant responses in skeletal muscle.