Shizhe Deng

Background: The Xingnao Kaiqiao acupuncture protocol is a well-established technique in traditional Chinese medicine, widely used for neurological rehabilitation, particularly in patients with post-stroke aphasia. However, the central neural mechanisms underlying both single-acupoint and multi-acupoint needling within this protocol remain largely unclear. This study aims to use magnetoencephalography (MEG) to compare the cerebral magnetic signals evoked by verum and sham acupuncture of the Xingnao Kaiqiao protocol in healthy adults, and to explore the central mechanisms associated with language task states. Methods: This is a single-blind, randomized, sham-controlled trial. A total of 40 healthy, right-handed volunteers aged 18–45 years will be recruited and randomly allocated in a 1:1 ratio to either the verum acupuncture (VA) group or the sham acupuncture (SA) group. The VA group will receive needling at the standard Xingnao Kaiqiao acupoints, following the protocol’s established manipulation techniques. The SA group will receive superficial needling at non-acupoints located 1 cun lateral to each corresponding verum acupoint, without any manipulation. MEG data will be acquired during resting state, acupuncture state (single-acupoint and multi-acupoint sequences), and language task state (picture naming and language repetition tasks). Structural MRI data will be collected for source localization. The primary outcome will be changes in MEG signals before and after acupuncture. The secondary outcome will be the Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS). Discussion: This study will use MEG to explore the central effects of Xingnao Kaiqiao acupuncture at both single-acupoint and multi-acupoint levels. It may add to current understanding of how acupuncture affects brain networks related to language processing. The findings may provide a neuroimaging basis for further research on the mechanisms of this classical acupuncture technique. Clinical trial registration: International Traditional Medicine Clinical Trial Registry ( https://itmctr.ccebtcm.org.cn/ ) ITMCTR2026000214. This study was registered on 14th January 2026.

Copper (Cu) is a vital trace element required for sustaining life and is involved in numerous critical metabolic processes within the body. Cuproptosis, a newly recognized type of Cu-dependent cell death, is mechanistically distinct from apoptosis, autophagy, pyroptosis, and ferroptosis. It is characterized by abnormal Cu accumulation and aberrant interactions with key enzymes of the tricarboxylic acid (TCA) cycle, which lead to protein aggregation, loss of iron–sulfur cluster proteins, and proteotoxic stress, ultimately leading to cell death. Recent studies have revealed that Cu dyshomeostasis and cuproptosis are intricately linked to the pathological progression of several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), Wilson’s disease (WD), and Menkes disease (MD). In this review, we systematically elucidate the systemic Cu metabolism, the molecular mechanisms of cuproptosis, and its intricate interplay with different neurodegenerative disorders. We also examined the relationship between cuproptosis and other types of cell death. Finally, we discuss therapeutic strategies targeting cuproptosis and Cu dyshomeostasis to combat neurodegenerative diseases and propose potential directions for future research.

Background: Despite being a significant modifiable risk factor for stroke, high alcohol use (HAU) lacks dedicated in-depth research on its attributable stroke burden. Using data from the Global Burden of Disease Study 2021 (GBD 2021), we assessed the spatiotemporal burden of stroke attributable to HAU to facilitate evidence-based policymaking and resource allocation. Methods: Our analysis focused on disability-adjusted life years (DALYs), deaths, and the age-standardized rates (ASRs) spanning from 1990 to 2021, with projections up to 2036 using Bayesian age-period-cohort (BAPC) models. Subgroup analyses were conducted on the basis of sex, age group, geographical region, and stroke subtype. Results: Globally, HAU-attributable stroke DALYs and deaths increased from 1990 to 2021, whereas the age-standardized DALY rate (ASDR) and the age-standardized mortality rate (ASMR) displayed decreasing patterns, with these trends projected to persist over the next decade. Compared with females and younger populations, males and the individuals aged 60 years and above consistently bore the majority of the disease burden. Notably, among the age groups under 35 years, there were significant upward trajectories in both DALY rates and mortality rates. In 2021, Vietnam recorded the highest ASDR [378.5 (95% UI: 84.09 to 688.25) per 100,000] and ASMR [16.22 (95% UI: 4.02 to 29.11) per 100,000], whereas the substantial disease burden in China positioned East Asia as the highest-burden GBD region. Driven by factors such as economic transitions, the middle- and low-middle socio-demographic index (SDI) regions, notably Southeast Asia, experienced the most pronounced upward trends in the ASRs. Intracerebral hemorrhage (ICH) was further confirmed as the predominant HAU-related stroke subtype. Conclusions: This study reveals the distribution characteristics and temporal trends of HAU-associated stroke burden among various regions and populations, underscoring the need for evidence-based interventions tailored to specific geographic and demographic contexts.

Background: To investigate the efficacy of acupuncture in improving motor dysfunction after ischemic stroke (IS) and to investigate the effect of acupuncture on corticospinal tract (CST) remodeling using diffusion tensor imaging. Methods: Published literature on the effect of acupuncture on CST remodeling after IS using diffusion tensor imaging in the form of randomized controlled trials (RCTs) were systematically retrieved and screened from Cochrane Library, Web of Science, PubMed, Embase, CNKI, CBM, VIP, and Wanfang databases from inception to December 2022. The methodological quality of the included studies was critically and independently evaluated by 2 reviewers using the Cochrane Risk of Bias Assessment Tool for RCTs. The correlated data were extracted using the pre-designed form, and all analyses were performed using Reviewer Manager version 5.4. Results: Eleven eligible RCTs involving 459 patients were eventually included. The combined evidence results showed that the acupuncture group significantly improved patients’ National Institute of Health stroke scale, Fugl-Meyer Assessment Scale, and Barthel index compared with conventional medical treatment. The acupuncture group significantly promoted remodeling of the CST, as reflected by an increase in fractional anisotropy (FA) throughout the CST [MD = 0.04, 95% CI (0.02, 0.07), P = .001], and in addition, subgroup analysis showed that the acupuncture group significantly improved FA in the infarct area compared with conventional medical treatment at around 4 weeks [MD = 0.04, 95% CI (0.02, 0.06), P = .0002] and FA of the affected cerebral peduncle [MD = 0.03, 95% CI (0.00, 0.07), P = .02]. Also, compared with conventional medical treatment, the acupuncture group significantly increased average diffusion coefficient of the affected cerebral peduncle [MD = −0.21, 95% CI (−0.28, −0.13), P < .00001]. Conclusion: The results of the meta-analysis suggest that acupuncture therapy can improve the clinical manifestations of motor dysfunction in patients after IS and advance a possibly beneficial effect on CST remodeling. However, due to the number and quality of eligible studies, these findings need to be further validated in more standardized, rigorous, high-quality clinical trials.

Introduction: According to several studies, a specific dietary pattern can reduce the risk of dementia and cognitive impairment. However, the robustness of these results has not been tested. The study intends to investigate the association between nutrition intake and cognitive impairment in middle-aged and older adults (≥45-years) and provide reliable, evidence-based references for healthcare decision-makers, researchers, and policymakers. Review question: Are the dietary characteristics of community-dwelling adults (≥45-years) associated with the occurrence of cognitive impairment? Objectives: The primary objective of this protocol is to synthesize the longitudinal observational evidence on the relationship between nutrition intake patterns and the incidence of cognitive impairment in middle-aged and older adults (≥45-years), and to provide detailed dietary recommendations for the prevention of cognitive impairment in this population. Methods and analysis: Cohort studies conducted among adults (≥45-years) will be included. The following electronic databases will be searched for relevant records published by July 2023, with a restriction on language to English: Pubmed, Medline, Embase, Web of science, Cochrane Library. The studies will be selected, the data will be extracted, and the bias risk will be assessed by two independent investigators. The Meta-analysis of Observational Studies in Epidemiology guidelines will be followed to summarize observational studies, and the protocol will adhere to the recommendations from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. Endnote X9 will be used to manage data screening. We will use Review Manager 5.4 and Stata 16.0 to conduct data analysis, and a random-effects model will be applied to pool clinically homogenous studies. The results will be presented based on the form of nutrition intake. For assessing publication bias, Egger’s test and visual inspection of funnel plots will be utilized. Ethics and dissemination: As this study does not involve primary data, ethical approval is not required. The final report will be published in a peer-reviewed journal. Prospero registration number: A registration number of DOI 10.17605/OSF.IO/NAKC3 was assigned to it on October 15, 2022 on Prospero.

Neural plasticity promotes the reorganization of language networks and is an essential recovery mechanism for poststroke aphasia (PSA). Neuroplasticity may be a pivotal bridge to elucidate the potential recovery mechanisms of acupuncture for aphasia. Therefore, understanding the neuroplasticity mechanism of acupuncture in PSA is crucial. However, the underlying therapeutic mechanism of neuroplasticity in PSA after acupuncture needs to be explored. Excitotoxicity after brain injury affects the activity of neurotransmitters and disrupts the transmission of normal neuron information. Thus, a helpful strategy of acupuncture might be to improve PSA by affecting the availability of these neurotransmitters and glutamate receptors at synapses. In addition, the regulation of neuroplasticity by acupuncture may also be related to the regulation of astrocytes. Considering the guiding significance of acupuncture for clinical treatment, it is necessary to carry out further study about the influence of acupuncture on the recovery of aphasia after stroke. This study summarizes the current research on the neural mechanism of acupuncture in treating PSA. It seeks to elucidate the potential effect of acupuncture on the recovery of PSA from the perspective of synaptic plasticity and integrity of gray and white matter.

Acupuncture therapy is widely used in the clinic, and its therapeutic effects have been proven by numerous studies. The dose–effect relationship of acupuncture is a fundamental aspect of the acupuncture research system. Recent studies found that different acupuncture dosages altered study results directly, indicating the importance of screening the optimal stimulation dosage. However, the system for studying the acupuncture dose–effect relationship is still in its infancy, and the methodology of the system needs to be improved. This review aimed to define the factors impacting acupuncture “dosage” and “effect,” and to improve the methodological system for research on the dose–effect relationship of acupuncture. By summarizing the current findings of acupuncture dose–effect studies, we discussed the vital acupuncture parameters and methodological problems that influence the relationship between acupuncture dosage and its effects. These factors consist of specific influencing factors (acupoint selection, acupuncture manipulation parameters, de qi response) and nonspecific influencing factors (comparison selection, blinding procedure, patient expectancy). Our perspectives offer suggestions for the design of acupuncture dosage–effect trials. Further studies need to be conducted to establish the methodological system and provide systematic evidence of the acupuncture dose–effect relationship. Graphical http://links.lww.com/AHM/A37

Background. Aphasia is a common symptom in stroke patients, presenting with the impairment of spontaneous speech, repetition, naming, auditory comprehension, reading, and writing function. Multiple rehabilitation methods have been suggested for the recovery of poststroke aphasia, including medication treatment, behavioral therapy, and stimulation approach. Acupuncture has been proven to have a beneficial effect on improving speech functions in repetition, oral speech, reading, comprehension, and writing ability. Neuroimaging technology provides a visualized way to explore cerebral neural activity, which helps reveal the therapeutic effect of acupuncture therapy. In this systematic review, we aim to reveal and summarize the neuroimaging mechanism of acupuncture therapy on poststroke aphasia to provide the foundation for further study. Methods. Seven electronic databases were searched including PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, the Wanfang databases, and the Chinese Scientific Journal Database. After screening the studies according to the inclusion and exclusion criteria, we summarized the neuroimaging mechanism of acupuncture on poststroke aphasia, as well as the utilization of acupuncture therapy and the methodological characteristics. Result. After searching, 885 articles were retrieved. After removing the literature studies, animal studies, and case reports, 16 studies were included in the final analysis. For the acupuncture type, 10 studies used manual acupuncture and 5 studies used electroacupuncture, while body acupuncture (10 studies), scalp acupuncture (7 studies), and tongue acupuncture (8 studies) were applied for poststroke aphasia patients. Based on blood oxygen level-dependent (BOLD) and diffusion tensor imaging (DTI) technologies, 4 neuroimaging analysis methods were used including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), seed-based analysis, and independent component analysis (ICA). Two studies reported the instant acupuncture effect, and 14 studies reported the constant acupunctures effect on poststroke aphasia patients. 5 studies analyzed the correlation between the neuroimaging outcomes and the clinical language scales. Conclusion. In this systematic review, we found that the mechanism of acupunctures effect might be associated with the activation and functional connectivity of language-related brain areas, such as brain areas around Brocas area and Wernickes area in the left inferior temporal gyrus, supramarginal gyrus, middle frontal gyrus, and inferior frontal gyrus. However, these studies were still in the preliminary stage. Multicenter randomized controlled trials (RCT) with large sample sizes were needed to verify current evidence, as well as to explore deeply the neuroimaging mechanisms of acupunctures effects.

Pain is a kind of complex physiological and psychological symptom, which makes the person debilitated and uncomfortable. Some persistent pain is unbearable for the patients, reducing the quality of life and bringing considerable pressure to the individuals and society. Pain killers seem to be effective in analgesia for patients, but their safety and addiction are crucial issues. From the theory of traditional Chinese medicine (TCM), the blocked meridian is the main cause of pain, and effective acupuncture can play a positive analgesic effect. Acupuncture that can date back thousands of years is one of the ancient medical practices in China. Its safety and effectiveness are respected. Based on its superior safety and inferior side effects, it has been gradually recognized as a therapeutic intervention method for complementary medicine, which is also generally used to treat multiple pain diseases. It is shown by modern medical studies that neurotransmitters are the material basis for the acupuncture effect, and the effect of acupuncture analgesia is related to changes in neurotransmitters. However, the specific mechanism has not been elucidated. This review aims to comprehensively discuss the historical evolution of acupuncture analgesia, clinical research of acupuncture analgesia, comparison of acupuncture and drug therapy, the neurotransmitter mechanism of acupuncture analgesia, the effect of acupuncture manipulation on analgesia, and bibliometric analysis of acupuncture treatment for pain, to explore the superiority and related mechanism of acupuncture analgesia from different aspects, and to provide a more effective treatment for alleviating patients’ pain.

Recent experiments have demonstrated that different needling manipulations may induce variable effects via diverse physiological mechanisms. A previous study indicated that needling at Fengchi (GB 20) improved cerebral blood flow in patients with vertigo induced by posterior circulation ischemia (PCI). In this study, we aim to explore the quantity-effect relationship and the physiological mechanisms underlying different acupuncture manipulations in PCI patients with vertigo. We propose a pragmatic randomized and controlled trial. All participants, outcome assessors, and statisticians will be blinded. A total of 144 eligible participants will be randomized into one of four treatment groups receiving acupuncture at Fengchi (GB 20) with different one-minute manipulation parameters. Group 1 will receive twirling at a frequency of 60 times per minute toward the contralateral outer canthus at a depth of 0.5 to 0.8 cun. Group 2 will receive twirling at a frequency of 60 times per minute toward the Adam’s apple at a depth of 0.5 to 0.8 cun. Group 3 will receive twirling at a frequency of 120 times per minute toward the contralateral outer canthus at a depth of 0.5 to 0.8 cun. Group 4 will receive twirling at a frequency of120 times per minute toward the Adam’s apple at a depth of 0.5 to 0.8 cun. Additional points will be added based on individualized pattern diagnoses. The participants will receive 14 acupuncture sessions over 3 to 4 weeks. The subjects will be assessed at two time points: baseline and post-treatment. The primary outcome measurements will include subjective measurements (Vertebrobasilar System Ischemic Neurological Impairment Scale, UCLA Dizziness Questionnaire, Activities of Daily Living Scale, and Psychological and Social Adaptation Scale) and objective measurements (Transcranial Doppler, carotid ultrasonography and changes in cerebral oxygenation) to reduce bias arising from the placebo effect. We will use metabolomics to investigate the mechanisms underlying the different manipulation parameters. This trial aims to explore the quantity-effect relationship between different acupuncture manipulations and their clinical effects. The results from this study may help explain the contradictory results found in acupuncture studies that practice different manipulations. Chinese Clinical Trial Registry: ChiCTR-RTRCC-12002675 (registered on 14 November 2012).