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.

Structural and functional changes of anterior cingulate cortex subregions in migraine without aura: relationships with pain sensation and pain emotion.

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine.

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.

Corrigendum: Circulating exosomal microRNA profiles in migraine patients receiving acupuncture treatment: a placebo-controlled clinical trial.

[This corrects the article DOI: 10.3389/fnmol.2022.1098766.].

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.

Manual acupuncture as prophylaxis for migraine without aura: study protocol for a multi-center, randomized, single-blinded trial.

BACKGROUND: Migraine is a highly prevalent neurological disorder. It is the third most prevalent disorder and the seventh highest cause of disability worldwide. Acupuncture may be a viable prophylactic treatment option for frequent or uncontrolled migraine. Clinical studies comparing acupuncture and placebo acupuncture have not reached a consistent conclusion in confirming whether acupuncture is effective in migraine prophylaxis. The effect of acupuncture mainly depends on acupoints and needles operation. We found that the design of the placebo acupuncture in previous studies included shallow needling at sham acupoints, non-penetrating needling at sham acupoints, and needling at inactive acupuncture points to achieve the inert effect of control group, but the non-penetrating needling at true acupoints was ignored. This randomized controlled trial aims to use true acupoints for non-penetrating acupuncture as control to evaluate the efficacy of manual acupuncture for the prophylaxis of migraine without aura (MWoA). METHODS/DESIGN: This is a single-blinded, randomized, controlled, prospective, multi-center trial with two parallel treatment groups. A total of 198 eligible patients with MWoA will be randomly divided into two groups (1:1 allocation ratio). The intervention group will receive manual acupuncture and the control group will receive placebo acupuncture (non-penetrating). Patients will receive three acupuncture treatment sessions per week for 4 consecutive weeks. All patients will then receive a 12-week follow-up. DISCUSSION: In this study, we are evaluating the efficacy and safety of manual acupuncture in the prophylaxis of MWoA. The placebo control is using non-penetrating needling verum acupoints. It is essential to determine an appropriate control method to ensure the methodological quality of a randomized controlled trial. TRIAL REGISTRATION: The trial has been registered in the Chinese Clinical Trial Registry (approval no. ChiCTR2000032308 ) in April 2020.

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.

Circulating exosomal microRNA profiles in migraine patients receiving acupuncture treatment: A placebo-controlled clinical trial.

Background: Acupuncture has a long history of being used in Chinese medicine for the treatment of migraine. However, molecular biomarkers for diagnosis and prognosis of migraine and its treatment are lacking. This study aimed to explore whether acupuncture could regulate differentially expressed exosomal miRNAs between patients with migraine without aura (MWoA) and healthy controls (HCs) and to identify diagnostic biomarkers that helped differentiate MWoA patients from HCs and identify prognostic biomarkers that helped to predict the effect of acupuncture. Methods: Here, we isolated serum exosomes from patients with MWoA and HCs before and after true and sham acupuncture treatment. Then, small RNA sequencing and bioinformatics analysis were performed to screen out key miRNAs specifically responding to acupuncture treatment. Pearson's correlation analysis was used to evaluate the correlation between miRNAs and clinical phenotypes. Finally, we applied a machine learning method to identify diagnostic biomarkers of MWoA patients and identify prognostic biomarkers that helped to predict the effect of acupuncture. Results: Small RNA sequencing identified 68 upregulated and 104 downregulated miRNAs in MWoA patients compared to those in HCs. Further, we identified eight upregulated and four downregulated miRNAs in migraine patients after true acupuncture treatment (trAMWoA), but not in the sham acupuncture treatment (shAMWoA) or HC group. Among them, has-miR-378a-5p was positively correlated with time unable to work, study, or do housework due to migraine (p < 0.05), whereas has-miR-605-3p was negatively correlated with the restrictive subscale of the migraine-specific quality of life questionnaire (MSQ) (p < 0.05). We then evaluated the diagnostic and prognostic potential of these 12 miRNAs in patients with MWoA. The combination of serum levels of exosomal has-miR-369-5p, has-miR-145-5p, and has-miR-5,010-3p could serve as diagnostic and prognostic biomarkers for MWoA patients following acupuncture treatment. Conclusion: This is the first study on the serum exosomal miRNA profiles of migraineurs before and after acupuncture treatment. Our results improve our understanding of the molecular functions of miRNAs in MWoA. More importantly, they expand our view of evaluating the clinical outcomes of migraine patients treated with acupuncture, using exosomal RNA markers. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000034417, July 2020.

[Revealing the mechanisms underlying the therapeutic effects of acupuncture on migraine using neuroimaging: a narrative review].

Migraine is a neurological disorder characterized by attacks of moderate or severe headache and various neurological symptoms. Acupuncture, as a commonly used non-pharmacological therapy, has the advantage of obvious therapeutic effect and few side effects in the prevention and treatment of migraine. But the underlying mechanism of acupuncture on migraine remains unclear. Recently, advances in neuroimaging technology have helped to objectively assess the effect of acupuncture on treating migraine and offered new opportunities to explore the central mechanism of acupuncture on treating migraine. In order to better understand the current status of neuroimaging studies on the therapeutic mechanism of acupuncture on migraine and shed light on future research, this review aims to overview the neuroimaging studies in recent 10 years from two aspects: (1) Central mechanism of acupuncture on treating acute migraine attack; (2) Central mechanism of acupuncture on preventing migraine attack.

Tai Chi for Improving Chronic Primary Musculoskeletal Pain: Protocol for a Systematic Review.

Background. Chronic primary musculoskeletal pain (CPMP) is a major health problem that has physical and psychological impacts as well as an associated economic burden. Currently, pharmacological treatment remains unsatisfactory because of side effects and potential misuse. Therefore, nonpharmacological approaches for pain are being actively explored, and Tai Chi has attracted increased attention as a therapy for pain. Although clinical trials have shown that Tai Chi may be effective in treating CPMP, no systematic review has clarified its effectiveness and safety. The objective of this systematic review is to assess the effect and safety of Tai Chi for patients suffering from CPMP. Methods and Analysis. We will search relevant electronic databases from inception to May 31, 2021: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, the Wanfang database, the Chongqing VIP database, and China Biology Medicine Disc. Studies comparing the use of Tai Chi with other managements for CPMP patients will be included. Our review will include studies that measured change in pain intensity as the primary outcome using patient-reported ratings (visual analog scale or numerical rating scale). Hospital Anxiety and Depression Scale scores, SF-36 Health Survey scores, Pittsburgh Sleep Quality Index scores, and adverse effects will be explored as secondary outcomes. The risk of bias and the reporting quality of included studies will be evaluated using the Cochrane Collaboration risk-of-bias assessment method. The data will be analyzed using RevMan v5.3 software. Study Registration. This study protocol was registered on PROSPERO. The registration number for this protocol is CRD42020165048.

Revealing the Neural Mechanism Underlying the Effects of Acupuncture on Migraine: A Systematic Review.

Background: Migraine is a chronic neurological disorder characterized by attacks of moderate or severe headache and various neurological symptoms. Migraine is typically treated by pharmacological or non-pharmacological therapies to relieve pain or prevent migraine attacks. Pharmacological therapies show limited efficacy in relieving headache and are often accompanied by adverse effects, while the benefits of acupuncture, a non-pharmacological therapy, have been well-documented in both the treatment and prevention of acute migraine attacks. However, the underlying mechanism of the effect of acupuncture on relieving migraine remains unclear. Recent advances in neuroimaging technology have offered new opportunities to explore the underlying neural mechanism of acupuncture in treating migraine. To pave the way for future research, this review provides an overview neuroimaging studies on the use of acupuncture for migraine in the last 10 years. Methods: Using search terms about acupuncture, neuroimaging and migraine, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure from January 2009 to June 2020 for neuroimaging studies that examined the effect of acupuncture in migraine. All published randomized and non-randomized controlled neuroimaging studies were included. We summarized the proposed neural mechanism underlying acupuncture analgesia in acute migraine, and the proposed neural mechanism underlying the sustained effect of acupuncture in migraine prophylaxis. Results: A total of 619 articles were retrieved. After removing reviews, meta-analyses, animal studies and etc., 15 articles were eligible and included in this review. The methods used were positron emission computed tomography (PET-CT; n = 2 studies), magnetic resonance spectroscopy (n = 1), and functional magnetic resonance imaging (fMRI; n = 12). The analyses used included the regional homogeneity (ReHo) method (n = 3), amplitude of low frequency (ALFF) method (n = 2), independent component analysis (ICA; n = 3), seed-based analysis (SBA; n = 1), both ICA and SBA (n = 1), Pearson's correlation to calculate functional connectivity (FC) between brain regions (n = 1), and a machine learning method (n = 1). Five studies focused on the instant effect of acupuncture, and the research objects were those with acute migraine (n = 2) and migraine in the interictal phase (n = 3). Ten studies focused on the lasting effect of acupuncture, and all the studies selected migraine patients in the interictal phase. This review included five task-based studies and 10 resting-state studies. None of the studies conducted a correlation analysis between functional brain changes and instant clinical efficacy. For studies that performed a correlation analysis between functional brain changes and sustained clinical efficacy, the prophylactic effect of acupuncture on migraine might be through regulation of the visual network, default mode network (DMN), sensory motor network, frontoparietal network (FPN), limbic system, and/or descending pain modulatory system (DPMS). Conclusion: The neural mechanism underlying the immediate effect of acupuncture analgesia remains unclear, and the neural mechanism of sustained acupuncture treatment for migraine might be related to the regulation of pain-related brain networks. The experimental design of neuroimaging studies that examined the effect of acupuncture in migraine also have some shortcomings, and it is necessary to standardize and optimize the experimental design. Multi-center neuroimaging studies are needed to provide a better insight into the neural mechanism underlying the effect of acupuncture on migraine. Multi-modality neuroimaging studies that integrate multiple data analysis methods are required for cross-validation of the neuroimaging results. In addition, applying machine learning methods in neuroimaging studies can help to predict acupuncture efficacy and screen for migraineurs for whom acupuncture treatment would be suitable.

Comparison of Effects and Brain-Gut Regulatory Mechanisms of Acupuncture and Flunarizine for Migraine: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: As a central nervous system disease, migraine often coexists with gastrointestinal disorders, which suggests a disruption of brain-gut regulation. Clinical studies have confirmed that acupuncture and flunarizine not only alleviate migraine attacks but also substantially inhibit accompanying gastrointestinal symptoms. However, it is still not clear how acupuncture and flunarizine regulate the interactions of brain, gut, and microbiome. Therefore, this study will combine neuroimaging technology and gut microbiota detection technology to explore and compare the effects and brain-gut modulating mechanisms of acupuncture and flunarizine for migraine. METHODS: This randomized clinical trial will recruit 66 patients with migraine without aura. Participants will be randomly assigned in a 1 : 1 ratio to an acupuncture group or a control group. The acupuncture treatment strategy is based on experience from our previous study and consensus meetings with clinical experts. Patients will receive 12 sessions of manual acupuncture treatment (once every other day to a total of three times per week, followed by a 2-day break). Flunarizine will be administered at a dose of 5 mg daily in the control group. Participants in both groups will receive treatment for a period of 4 weeks. The primary outcome is the change in frequency of migraine attacks, and the secondary outcomes include the changes in migraine days (days on which migraine attacks occurred), average migraine severity, gastrointestinal symptoms, psychiatric symptoms, and quality of life. Fresh stool samples will be collected, and 16S ribosomal RNA gene sequencing analysis will be used for gut microbiota. Magnetic resonance imaging will be applied to detect between-group changes in brain function. The abovementioned indicators will be collected at baseline, after a 4-week intervention, and at the 12-week follow-up. Discussions. From the perspective of brain-gut regulatory mechanisms, we will combine brain neuroimaging and gut microbiological data to partially reveal the similarities and differences of acupuncture and flunarizine on the treatment of migraine. The trial is registered with ChiCTR2000034417.

Acupuncture for Radiation-Induced Xerostomia in Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Radiation-induced xerostomia is one of the most common symptoms experienced by cancer patients. The aim of our study is to evaluate the preventive and therapeutic effect of acupuncture for radiation-induced xerostomia in cancer patients. METHODS: Eight databases were searched for all published randomized clinical trials (RCTs) on acupuncture for radiation-induced xerostomia in cancer patients up to December 31, 2019. Manual searching included other conference abstracts and reference lists. Meta-analysis was conducted using Revman V.5.3, and risks of bias for included studies was assessed following the Cochrane Handbook. RESULTS: Eight clinical trials (725 participants) were analyzed, and 3 were included in a meta-analysis. All included trials had a high risk of bias, such as selection, performance, and detection bias. Analysis indicated favorable effects of acupuncture regarding the improvement of xerostomia symptoms (MD -3.05, P = 0.02, 95% CI -5.58 to -0.52), compared with sham acupuncture. There were no significant differences between real acupuncture and sham acupuncture regarding the stimulated salivary flow rate (MD 0.37, P = 0.08, 95% CI -0.05 to 0.79) and unstimulated salivary flow rate (MD 0.09, P = 0.12, 95% CI -0.02 to 0.21), which were whole salivary flow rate. Compared with no acupuncture (standard oral care, usual care, or no treatment), acupuncture produced a significant improvement in patient-reported xerostomia, without causing serious adverse effects. However, a Grading of Recommended Assessments analysis revealed that the quality of all acupuncture outcome measures was low. CONCLUSION: The present meta-analysis and systematic review suggests that acupuncture is effective at improving xerostomia symptoms in cancer patients but not at objective salivary flow measurements. The evidence is still limited due to the low quality of the published studies.

Acupuncture versus Various Control Treatments in the Treatment of Migraine: A Review of Randomized Controlled Trials from the Past 10 Years.

BACKGROUND: Migraine is defined as a recurrent headache of moderate to severe intensity that seriously affects the quality of life. Recent clinical trials have confirmed that acupuncture is effective in treating migraine. We aimed to review the effectiveness of acupuncture in the treatment of migraine by comparing treatment and various control groups in accordance with the newly published guidelines for systematic reviews. MATERIALS AND METHODS: The following databases were searched for relevant articles published from January 1, 2010 to December 31, 2019: Embase, PubMed, Medline, Cochrane Library, and four Chinese databases. The present review included randomized controlled trials in which acupuncture was the sole treatment or an adjunctive treatment for migraine. Two researchers independently conducted the study selection, data extraction, and quality assessment processes. Disagreements between reviewers were solved by discussion and data reanalysis. The quality of each included study was evaluated using the Cochrane Collaboration risk-of-bias assessment method and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist. RESULTS: Forty-nine studies were analyzed and ranked based on the latest STRICTA and Cochrane Collaboration risk-of-bias assessment standards. The analysis revealed that acupuncture reduced headache frequency compared with no treatment (mean difference [MD] = -1.80, P < 0.00001, 95% confidence interval [CI] -2.34 to -1.26) and western medicine (MD = -1.75, P = 0.003, 95% CI -2.91 to -0.58). Headache frequency did not significantly differ between patients who received real acupuncture versus those who received sham acupuncture (MD = -0.64, P = 0.24, 95% CI -1.70 to 0.42). CONCLUSION: The present review evaluated the current research on the use of acupuncture for migraine, compared with various control treatments. The evidence for the effectiveness of acupuncture in controlling migraine is still limited due to the low quality of the published studies.

Effect of regulating gut microbiota using probiotics on functional changes in the brain: protocol for a systematic review.

INTRODUCTION: There is a growing number of randomised controlled trials (RCTs) that focus on functional changes in the brain detected by functional MRI (fMRI) and gut microbiota composition changes after using probiotics.However, the effect of probiotics on functional changes in the brain through gut microbiota remains controversial in existing RCTs. Furthermore, to our knowledge, there is no systematic review to evaluate the effect of probiotics on functional changes in the brain through gut microbiota. Therefore, we aim to summarise literatures evaluating the potential association between probiotics, gut microbiota and functional changes in the brain to elucidate whether probiotics influence gut microbiota and affect functional changes in the brain through gut microbiota. METHODS AND ANALYSIS: China National Knowledge Infrastructure, Wanfang Data, VIP Databases (the Chongqing VIP Chinese Science and Technology Periodical Database), SinoMed, PubMed, Web of Science, MEDLINE (The National Library of Medicine), EMBASE (Excerpt Medica Database), Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov will be searched until July 2019. The Grey Literature in Europe (OpenSIGLE) database and Google search engine will also be used. The reference lists of each included study will be reviewed to determine whether there are any further relevant studies. RCTs using probiotics compared with a placebo/control will be included. We will use risk of bias assessment and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of evidence. The results of the systematic review will be synthesised narratively in the domains of the three primary outcome measures: (1) Increased/decreased activity in brain regions or altered functional connectivity (FC) of brain detected by fMRI and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (2) Changes in composition and diversity of the gut microbiota and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (3) Increased/decreased activity in brain regions or altered FC of brain detected by fMRI and the changes in composition or diversity of the gut microbiota after administration of probiotics. ETHICS AND DISSEMINATION: The results will be disseminated through a peer-reviewed publication. As no private and confidential patient data will be included in the reporting, there are no ethical considerations associated with this protocol. PROSPERO REGISTRATION NUMBER: CRD42019145114.

[Reporting quality of randomized controlled trials of acupuncture for cancer pain].

Based on the internationally-recognized Consolidated Standards for Reporting of Trials (CONSORT) statement and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA), the reported quality of randomized controlled trials (RCTs) of acupuncture for cancer pain during last 10 years were evaluated. The RCTs of acupuncture for cancer pain were searched by computer. The English databases included PubMed and EMbase while the Chinese databases included CNKI, Wanfang, VIP and SinoMed. The publication date of the literature was from March 2009 to March 2019. As a result, 22 Chinese RCTs and 13 English RCTs were included. According to the CONSORT statement, among the Chinese studies, 1 RCT reported primary and secondary outcomes, 8 RCTs reported randomization, none of RCTs reported allocation concealment and blind method, and 4 RCTs reported baseline data; among the English studies, 8 RCTs reported primary and secondary outcomes, 8 RCTs reported randomization, 6 RCTs reported described allocation concealment, 7 RCTs reported blind method, and 13 RCTs reported baseline data. According to the STRICTA statement, among the Chinese studies, 17 RCTs reported the name of acupoints, 6 RCTs reported depth of insertion, 17 RCTs reported acupuncture response sought, and none of RCTs reported the qualifications of acupuncturists; among the English studies, 12 RCTs reported the name of acupoints, 7 RCTs reported depth of insertion, 8 RCTs reported acupuncture response sought, and 7 RCTs reported the qualifications of acupuncturists. The Chinese RCTs have more detailed description of acupuncture intervention and theory, but not enough attention is paid to methodological description such as randomization, blindness, data analysis. On the other hand, the English RCTs have better description of methodology, but the description of theory and details of acupuncture is relatively weak. It is concluded that more efforts were needed to further improve the clinical trial design according to the CONSORT statement and STRICTA statement to improve the quality of clinical evidence.

Acupuncture for patients with cancer-induced xerostomia: a systematic review protocol.

INTRODUCTION: Xerostomia is a common symptom in patients with cancer. Currently available methods to manage xerostomia include stringent oral hygiene using fluoride agents and antimicrobials, saliva substitutes and sialagogic agents, but side effects such as headache, dizziness and sweating can occur with these therapies. Clinical trials have shown that acupuncture may be effective in treating xerostomia. The objective of this systematic review is to assess the effectiveness and safety of acupuncture treatment for xerostomia caused by cancer. METHODS AND ANALYSIS: This systematic review will incorporate articles identified by electronically searching the following databases: PubMed, MEDLINE, the Cochrane Library, AMED, EMbase, WorldSciNet, Nature, Science Online, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, the Wanfang Database and China Biology Medicine Disc from inception to 1 December 2019. Other sources including conference proceedings and reference lists of identified publications and existing systematic reviews will also be searched. Two reviewers will independently search the databases, perform data extraction and assess the quality of studies. Data will be synthesised using either a fixed-effects model or a random-effects model, according to heterogeneity testing. Patient-reported change in the Visual Analogue Scale or the Xerostomia Inventory will be assessed as the primary outcome. Saliva collection, whole saliva production and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 will be evaluated as secondary outcomes. RevMan V. 5.3 will be employed for data analysis. The results will be expressed as risk ratios for dichotomous data and mean differences for continuous data. ETHICS AND DISSEMINATION: This protocol will not evaluate individual patient information or affect patient rights and therefore does not require ethical approval. Results from this review will be disseminated through peer-reviewed journals and conference reports. TRIAL REGISTRATION NUMBER: CRD42019129069.

[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.