OBJECTIVE: To explore the efficacy of acupuncture based on "gut-brain axis" combined with sensory integration training in children with autism spectrum disorder (autism) and its effect on gastrointestinal symptoms. METHODS: A total of 96 children with autism were randomized into an observation group and a control group, 48 cases in each group, with 3 cases dropped out. Children in the control group received sensory integration training. On the basis of the treatment in the control group, children in the observation group received acupuncture therapy based on "gut-brain axis", and the point selection of scalp acupuncture was forehead five needles, i.e. bilateral Touwei (ST8), Toulinqi (GB15), Shenting (GV24) and Sishencong (EX-HN1), the point selection of body acupuncture was Zhongshu (GV7) and bilateral Tianshu (ST25), Pishu (BL20), Xinshu (BL15), Zusanli (ST36), Hegu (LI4), Taichong (LR3). Acupuncture was delivered once every other day, 3 times a week. Both groups were treated for 12 weeks. Before and after treatment, the scores of autism behavior checklist (ABC), childhood autism rating scale (CARS), autism treatment evaluation checklist (ATEC) and gastrointestinal TCM symptoms, as well as the relative abundance of intestinal flora were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the ABC and CARS scores were decreased compared with those before treatment in the two groups (P<0.001, P<0.05), and the ABC and CARS scores in the observation group were lower than those in the control group (P<0.01). After treatment, the item scores of language, sensory perception, sociability, behavior, and the total score of ATEC in the observation group were decreased compared with those before treatment (P<0.001, P<0.01), the item scores of language, sociability, behavior, and the total score of ATEC in the control group were decreased compared with those before treatment (P<0.01, P<0.001, P<0.05); the each-item and total scores in the observation group were lower than those in the control group (P<0.05). After treatment, the scores of loose stool, stomach duct pain, stomach duct stuffiness, decreased appetite, and the total scores of gastrointestinal TCM symptoms were reduced compared with those before treatment in the two groups (P<0.001), and the above scores in the observation group were lower than those in the control group (P<0.001). After treatment, the relative abundance of Escherichia coli and Enterococcus was decreased compared with that before treatment in the two groups (P<0.001), and the above relative abundance in the observation group was lower than that in the control group (P<0.001); the relative abundance of Bifidobacterium and Lactobacillus was increased compared with that before treatment in the two groups (P<0.001), and the above relative abundance in the observation group was higher than that in the control group (P<0.001). The total effective rate was 88.9% (40/45) in the observation group, which was higher than 66.7% (30/45) in the control group (P<0.05). CONCLUSION On the basis of sensory integration training, acupuncture based on "gut-brain axis" can improve the behavioral status and gastrointestinal symptoms, and correct the imbalance of intestinal flora in children with autism.
Humans ; Acupuncture Therapy ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child, Preschool ; Child ; Acupuncture Points ; Treatment Outcome ; Brain-Gut Axis ; Gastrointestinal Diseases/physiopathology*

In recent years, the ongoing development of transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) has demonstrated significant potential in the treatment and rehabilitation of various brain diseases. In particular, the combined application of TES and TMS has shown considerable clinical value due to their potential synergistic effects. This paper first systematically reviews the mechanisms underlying TES and TMS, highlighting their respective advantages and limitations. Subsequently, the potential mechanisms of transcranial electromagnetic combined stimulation are explored, with a particular focus on three combined stimulation protocols: Repetitive TMS (rTMS) with transcranial direct current stimulation (tDCS), rTMS with transcranial alternating current stimulation (tACS), and theta burst TMS (TBS) with tACS, as well as their clinical applications in brain diseases. Finally, the paper analyzes the key challenges in transcranial electromagnetic combined stimulation research and outlines its future development directions. The aim of this paper is to provide a reference for the optimization and application of transcranial electromagnetic combined stimulation schemes in the treatment and rehabilitation of brain diseases.
Humans ; Transcranial Magnetic Stimulation/methods* ; Transcranial Direct Current Stimulation/methods* ; Brain Diseases/therapy*

Objective To explore the effects of Shuanglu Tongnao Formula on neuroinflammation in ischemic stroke (IS) rats via the P2X purinoceptor 7 receptor (P2X7R)/NLR family pyrin domain-containing 3 (NLRP3) pathway. Methods The rats were divided into five groups: the IS group, control group, Shuanglu Tongnao Formula group, P2X7R inhibitor brilliant blue G (BBG) group, and Shuanglu Tongnao Formula combined with P2X7R activator adenosine triphosphate (ATP) group, with 18 rats in each group. Except for the control group, rats in all other groups were used to construct an IS model using the suture method. After successful modeling, the drug was given once a day for 2 weeks. Neurological function scores and cerebral infarction volume ratios were measured in rats. Pathological examination of the ischemic penumbra brain tissue was performed. Immunofluorescence staining was used to quantify the proportions of microglia co-expressing both inducible nitric oxide synthase (iNOS) and ionized calcium-binding adapter molecule 1 (Iba1), as well as arginase 1 (Arg1) and Iba1, in the ischemic penumbra brain tissue. ELISA was used to detect tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukin 6 (IL-6) and IL-10 in the ischemic penumbra brain tissue. Western blotting was used to measure P2X7R, NLRP3, and IL-1β proteins in the ischemic penumbra brain tissue. Results Compared with the control group, the IS group showed disordered neuronal arrangement, nuclear condensation, and obvious infiltration of inflammatory cells in the ischemic penumbra; significantly elevated neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with reduced proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. Compared with the IS group, the Zhuang medicine Shuanglu Tongnao Formula and BBG groups demonstrated alleviated brain tissue damage; reduced neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with increased proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. ATP reversed the effects of Zhuang medicine Shuanglu Tongnao Formula on microglial polarization and neuroinflammation in IS rats. Conclusion Zhuang medicine Shuanglu Tongnao Formula may promote the transformation of microglia from M1 type to M2 type by inhibiting the P2X7R/NLRP3 pathway, thereby improving neuroinflammation in IS rats.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology* ; Rats ; Ischemic Stroke/pathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Interleukin-10/metabolism* ; Brain Ischemia/drug therapy* ; Microglia/metabolism*

Ultrasound has emerged as a non-invasive neural modulation technique. Its mechanisms of action in the brain involve mechanical, cavitation, and thermal effects, which modulate neural activity by activating mechanosensitive ion channels, enhancing cell permeability, and improving blood circulation. The ultrasound-piezo-electric systems, based on the coupling between ultrasound and piezoelectric materials, can generate wireless electrical stimulation to promote neural repair, significantly improving therapeutic outcomes for neurodegenerative diseases and showing potential as a replacement for traditional invasive deep brain stimulation techniques. The ultrasound-responsive piezoelectric drug delivery system combines mechano-electrical conversion capability of piezoelectric materials with the non-invasive penetration advantage of ultrasound. This system achieves synergistic therapeutic effects for neurodegenerative diseases through on-demand drug release and wireless electrical stimulation in deep brain regions. It can effectively overcome the blood-brain barrier limitation, enabling precisely targeted drug delivery to specific brain regions. Simultaneously, it generates electrical stimulation in deep brain areas to exert synergistic neuroreparative effects. Together, these capabilities provide a more precise, efficient, and safe solution for treating neurodegenerative diseases. This review summarizes the neural regulatory mechanisms, technical advantages, and research progress of the ultrasound-responsive piezoelectric drug delivery systems for neurodegenerative disease therapy, aiming to offer novel insights for the field.
Humans ; Neurodegenerative Diseases/drug therapy* ; Drug Delivery Systems/methods* ; Blood-Brain Barrier ; Ultrasonic Waves ; Brain ; Ultrasonic Therapy ; Deep Brain Stimulation/methods*

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, referring to a diffuse brain dysfunction caused by sepsis in the absence of direct central nervous system (CNS) infection. SAE occurs in up to 70% of patients with sepsis. Globally, the annual incidence of sepsis ranges from 30.0 to 48.9 million cases, resulting in approximately 11 million deaths per year, which accounts for 20% of all global mortalities. SAE is identified as an independent risk factor contributing to the increased mortality rate among these patients. Early diagnosis of SAE and related cerebral protection interventions hold significant clinical importance. Currently, the main indicators of brain function for sepsis patients include Glasgow coma score (GCS), confusion assessment method for the intensive care unit (CAM-ICU), electroencephalogram (EEG), brain CT or magnetic resonance imaging (MRI) and other related imaging changes, which have the problems of low sensitivity, poor specificity, and non-objective evaluation of the results of the diagnosis of SAE. This article focuses on the latest progress in the pathogenesis of SAE and systematically reviews potential biomarkers related to the onset of SAE from multiple aspects, including inflammatory markers, endothelial and neuronal injury markers, and metabolic markers. This will provide new insights for the clinical diagnosis and treatment of SAE.
Humans ; Sepsis-Associated Encephalopathy/therapy* ; Biomarkers ; Sepsis/complications* ; Magnetic Resonance Imaging ; Electroencephalography ; Brain Diseases/etiology*

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

The bone-touching acupuncture method, as one of the five-body acupuncture techniques, is widely used and highly effective in the treatment of brain diseases, though its theoretical foundation has been lacking. This paper explores the close connection between bones and the brain in both physiological and pathological states, as described in traditional Chinese medicine (TCM) classics, and explains the "bone-brain axis" concept within the framework of TCM. It summarizes the effects and characteristics of the five-body acupuncture techniques, traces the origins and modern applications of the bone-touching acupuncture method, and discusses its theoretical basis for treating brain diseases. The aim is to provide a reference for future clinical and mechanistic research on bone-touching acupuncture in brain disease treatment and to offer new perspectives and approaches for acupuncture treatment of brain diseases.
Humans ; Acupuncture Therapy/methods* ; Brain/physiopathology* ; Brain Diseases/physiopathology* ; Bone and Bones/physiopathology* ; Medicine, Chinese Traditional/methods*

OBJECTIVE: To investigate the effect of hyperbaric oxygen (HBO) on paroxysmal sympathetic hyperexcitation (PSH) after brain injury. METHODS: A multicenter retrospective study was conducted. Fifty-six patients with PSH who received HBO treatment from four hospitals in Henan Province from January 2021 to September 2023 were selected as the HBO group, and 36 patients with PSH who did not receive HBO treatment from Zhengzhou People's Hospital from May 2018 to December 2020 were selected as the control group. PSH assessment measure (PSH-AM) score [clinical feature scale (CFS) score+diagnostic likelihood tool (DLT) score] and Glasgow coma scale (GCS) were compared before and after HBO treatment, and between HBO group and control group to evaluate the effect of HBO treatment on prognosis of PSH patients. RESULTS: There were no statistically significant differences in age, gender, PSH etiology, GCS score, time from onset to occurrence of PSH, CFS score, CFS+DLT score and frequency of PSH episodes between the two groups, indicating comparability. The duration of HBO treatment ranged from 3 to 11 days for 56 patients receiving HBO treatment, and the duration of HBO treatment ranged from 3 to 5 courses. Compared with before treatment, after HBO treatment, PSH symptoms in HBO patients were significantly relieved (body temperature increase: 14.29% vs. 64.29%, heart rate increase: 25.00% vs. 98.21%, shortness of breath: 14.29% vs. 76.79%, blood pressure increase: 8.93% vs. 85.71%, sweating: 10.71% vs. 85.71%, muscle tone increased: 19.64% vs. 75.00%, all P < 0.05), CFS+DLT score decreased significantly (16.90±4.81 vs. 22.12±3.12, P < 0.01), GCS score improved (12.31±5.34 vs. 5.95±2.18, P < 0.01). After 30 days of hospitalization, compared with the control group, PSH symptoms in the HBO group were improved (body temperature increase: 14.29% vs. 19.44%, heart rate increase: 19.64% vs. 25.00%, shortness of breath: 10.71% vs. 27.78%, blood pressure increase: 7.14% vs. 22.22%, sweating: 8.93% vs. 25.00%, muscle tone increased: 19.64% vs. 38.89%, all P < 0.05 except body temperature increase), CFS+DLT score decreased (16.90±3.81 vs. 19.98±4.89, P < 0.05), GCS score increased (14.12±4.12 vs. 12.31±4.14, P < 0.01), the length of intensive care unit (ICU) stay was shortened (days: 18.01±5.67 vs. 24.93±8.33, P < 0.01). CONCLUSIONS HBO treatment can significantly relieve the symptoms of patients with PSH after brain injury and provide a new idea for the treatment of PSH patients.
Humans ; Hyperbaric Oxygenation/methods* ; Retrospective Studies ; Brain Injuries/therapy* ; Female ; Male ; Prognosis ; Glasgow Coma Scale ; Autonomic Nervous System Diseases/etiology*

As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.
Humans ; Microglia/physiology* ; Central Nervous System ; Neurodegenerative Diseases/therapy* ; Brain/physiology* ; Homeostasis

Objective: To observe the effects of transcranial direct current stimulation (tDCS) on nerve injury markers and prognosis in patients with acute severe carbon monoxide poisoning (ASCOP) . Methods: In May 2021, 103 ASCOP patients were treated in the emergency department of Harrison International Peace Hospital of Hebei Medical University from November 2020 to January 2021. The patients were divided into two groups according to whether they received tDCS treatment. The control group (50 cases) were given oxygen therapy (hyperbaric oxygen and oxygen inhalation) , reducing cranial pressure, improving brain circulation and cell metabolism, removing oxygen free radicals and symptomatic support, and the observation group (53 cases) was treated with 2 weeks of tDCS intensive treatment on the basis of conventional treatment. All patients underwent at least 24 h bispectral index (BIS) monitoring, BIS value was recorded at the hour and the 24 h mean value was calculated. Neuron-specific enolase (NSE) and serum S100B calcium-binding protein (S100B) were detected after admission, 3 d, 7 d and discharge. Follow-up for 60 days, the incidence and time of onset of delayed encephalopathy (DEACMP) with acute carbon monoxide poisoning in the two groups were recorded. Results: The NSE and S100B proteins of ASCOP patients were significantly increased at admission, but there was no significant difference between the two groups (P=0.711, 0.326) . The NSE and S100B proteins were further increased at 3 and 7 days after admission. The increase in the observation group was slower than that in the control group, and the difference was statistically significant (P(3 d)=0.045, 0.032, P(7 d)=0.021, 0.000) ; After 14 days, it gradually decreased, but the observation group decreased rapidly compared with the control group, with a statistically significant difference (P=0.009, 0.025) . The 60 day follow-up results showed that the incidence of DEACMP in the observation group was 18.87% (10/53) , compared with 38.00% (19/50) in the control group (P=0.048) ; The time of DEACMP in the observation group[ (16.79±5.28) d] was later than that in the control group[ (22.30±5.42) d], and the difference was statistically significant (P=0.013) . Conclusion: The early administration of tDCS in ASCOP patients can prevent the production of NSE and S100B proteins, which are markers of nerve damage. and can improve the incidence and time of DEACMP.
Humans ; Biomarkers ; Brain Diseases/therapy* ; Carbon Monoxide Poisoning/therapy* ; Oxygen ; Phosphopyruvate Hydratase ; Prognosis ; S100 Calcium Binding Protein beta Subunit ; Transcranial Direct Current Stimulation